RPEP-10604 · 2025Across 61 studies (20,680 patients) evaluating 16 pharmacologic treatments for episodic migraine prevention:
- No high-certainty evidence favored any one treatment over another for effectiveness
- CGRP monoclonal antibodies probably resulted in fewer treatment discontinuations due to adverse events compared to topiramate (risk difference -16.2%, 95% CI: -18.4% to -12.8%; moderate-certainty evidence)
- CGRP-mAbs may result in less migraine-related disability and improved quality of life compared to gepants (low-certainty evidence)
- For most other comparisons, evidence was of low certainty, uncertain, or absent
- Only 19 of 61 studies had low risk of bias
Damen, Johanna A A; Yang, Bada; Idema, Demy L; Vernooij, Robin W M; Huis In 't Veld, Linde; Kusters, Mike; Spijker, Rene; van der Braak, Kim; Heus, Pauline; Jenniskens, Kevin; Hooft, Lotty ·
RPEP-10605 · 2025Among 40 Pseudomonas aeruginosa isolates (from India and Australia):
• 65% were resistant to polymyxin B; 80% to colistin
• Polymyxin B MICs ranged from 0.5 to 512 µg/mL, with 22.5% being highly resistant (MIC ≥256 µg/mL)
• Polymyxin B and colistin MICs were strongly correlated (Spearman's R ≥0.6, p≤0.001)
• LL-37 (human cathelicidin) showed moderate correlation with polymyxin B, colistin, and Mel4
• Mel4 (synthetic AMP) showed weaker correlations with polymyxins
• SNP analysis identified nalC (E153Q/D) and mipB (V469M, G441S) variants as associated with MICs to all antimicrobials
• Strains with MICs 64-512 µg/mL were significantly more likely to harbor these variants (p<0.05)
Damtie, Meseret Alem; Vijay, Ajay Kumar; Willcox, Mark Duncan Perry ·
RPEP-10608 · 2025Dual-modified lipid nanoparticles functionalized with RVG29 peptide (for BBB penetration) and mannose (for astrocyte targeting) delivered circHIPK2 siRNA to the brain with high specificity. The 134 nm nanoparticles showed good stability and biosafety. CircHIPK2 silencing markedly suppressed astrocyte activation, reducing GFAP and IL-1β expression (p<0.0001 in vivo). Neurobehavioral testing showed significantly improved righting reflex, negative geotaxis, and spatial learning/memory in treated neonatal mice with hypoxic-ischemic brain damage.
Dang, Yinxia; Shen, Fuhui; Wang, Shengxia; Zhang, Yating; Lu, Xia; Qin, Dongyuan; Feng, Dan; Song, Yanjun; Cheng, Zihuan; Ma, Ruicong; Wang, Fan ·
RPEP-10614 · 2025GLP-1RAs have established benefits in type 2 diabetes, body weight management, and cardiovascular risk protection. Beyond these, growing evidence supports organ-protective effects in multiple systems:
- Renal: GLP-1RAs show kidney-protective effects that may slow chronic kidney disease progression
- Hepatic: Benefits in non-alcoholic fatty liver disease/metabolic dysfunction-associated steatotic liver disease
- Respiratory: Emerging evidence for lung-protective effects
- Neurological: Potential neuroprotective benefits in neurodegenerative diseases
The review explores both weight-dependent and weight-independent mechanisms underlying these multi-organ benefits, suggesting that GLP-1 receptor signaling has direct protective effects on tissues throughout the body.
Daniels, Samuel; Karlsson, Cecilia; Schrauwen, Patrick; Parker, Victoria E R ·
RPEP-10615 · 2025A 69-year-old female with morbid obesity (starting BMI 47, weight 241 lb) lost 90 lb (over 30% of body weight) over 65 weeks of semaglutide treatment. This weight loss exceeded the average reduction reported in previous large-scale studies. The patient experienced no side effects. Additionally, her hypertension resolved and her glucose levels normalized during treatment.
Danish, Sidra; Dogra, Vallabh; Rauf, Uzma; Saghir, Maryam; Aslam, Nadia ·
RPEP-10617 · 2025In 11 healthy adults, whey protein-glucose coingestion (25WG) produced the lowest glucose excursions compared to glucose alone (25G or 50G). Key peptide hormone responses: glucagon increased ~3-fold with 25WG (suppressed with glucose alone), GIP was significantly higher with 25WG versus both 25G and 50G, GLP-1 was similar across conditions, and insulin was higher for 25WG versus 25G.
Critically, despite greater insulin secretion, whole-body glucose disposal (Rd) was not enhanced. Endogenous glucose production was less suppressed with 25WG (~50%) versus 25G (~70%) or 50G (~80%). The net glycemic benefit stemmed from reduced early-phase (30-60 min) glucose absorption from the gut — a novel mechanistic finding.
Dao, Giang M; Shaw, Chistopher S; Betik, Andrew C; Kuriel, Vicky; Bruce, Clinton R; Kowalski, Greg M ·
RPEP-10620 · 2025Two bola-amphiphilic peptides, L2 (Ac-KLIIIK-NH₂) and L5 (Ac-KIIILK-NH₂), which differ only in the position of a single leucine residue, form morphologically distinct nanostructures — nanosheets and nanotubes, respectively. Cryo-EM helical reconstruction of the L5 nanotube at near-atomic resolution revealed steric zipper interfaces characteristic of cross-β amyloid fibrils, rather than the simple amphiphilic packing previously assumed. Like amyloid structures, these assemblies were highly sensitive to conservative amino acid substitutions, meaning tiny sequence changes dramatically altered the resulting nanostructure.
Das, Abhinaba; Gnewou, Ordy; Zuo, Xiaobing; Wang, Fengbin; Conticello, Vincent P ·
RPEP-10621 · 2025Systematic modification of substituents on benzyl groups attached to short amphipathic peptides produced measurable changes in fibril formation, molecular packing, and immune responses.
Both the position and the electronic nature (electron-donating vs. withdrawing) of substituents at the para-position of benzyl rings, as well as the chain length connecting the backbone to the aromatic moiety, influenced self-assembly behavior and immunogenicity. The effects were observed both in vitro and in vivo, demonstrating that principles from organic chemistry substituent effects translate directly to peptide nanomaterial design.
Das, Anirban; Pramanik, Ushasi; Brown, Elise M; Liu, Chih-Yun; Gong, Huan; Fascetti, Jonathan; Gibson, Mark; Stealey, Samuel; Zustiak, Silviya P; Berkland, Cory; Jackrel, Meredith E; White, Mark A; Rudra, Jai S ·
RPEP-10625 · 2025This review examines how peptide-functionalized nanoparticles and nanoscaffolds are being developed to treat degenerative retinal diseases like diabetic retinopathy, age-related macular degeneration (AMD), and retinitis pigmentosa. Key approaches include RGD-modified nanoparticles for receptor-mediated targeting of retinal cells, self-assembling peptide hydrogels that mimic the extracellular matrix to support retinal regeneration, and PEGylated nanostructures that cross the blood-retinal barrier while avoiding immune reactions. Preclinical animal studies have shown promising results for targeted drug delivery, neuroprotection, and stem cell-based regeneration, but scalability, long-term safety, and non-invasive delivery methods remain major challenges.
Dashti, Razieh; Safaei, Fariba; Sadeghian, Golfam; Hosseini, Seyyed Abed; Salimibani, Milad · Review
RPEP-10638 · 2025Researchers developed a new method for "stapling" peptides — chemically locking them into their active helical shape — that works on unprotected peptides using natural amino acid residues (lysine and cysteine). The technique, called FlICk (Fluorescent Isoindole Crosslink), uses a three-component reaction that is rapid, mild, and highly selective. A key bonus: the staple itself is fluorescent, emitting blue-green light that allows researchers to directly image the peptide inside cells without needing to attach a separate fluorescent tag. A FlICk-stapled peptide showed cytotoxicity with an IC50 of 5.10 μM, matching the potency of a conventional olefin-stapled version.
Dayanara, Naysilla L; Froelich, Juliette; Roome, Pascale; Perrin, David M · In Vitro
RPEP-10641 · 2025Peptide receptor radionuclide therapy (PRRT) remains a potential treatment option for medullary thyroid carcinoma, particularly for patients with RET-negative recurrent or metastatic disease who have limited systemic therapy options. However, its clinical utility in the RET inhibitor era is uncertain. Highly selective RET inhibitors have proven efficacy with low toxicity for RET-mutated MTC, and multikinase inhibitors are available but limited by resistance and side effects. PRRT's role is now most relevant for the subset of patients who cannot benefit from RET-targeted therapy.
de Andrade, Fernanda Accioly; Bulzico, Daniel; Corbo, Rossana; Vaisman, Fernanda ·
RPEP-10647 · 2025Constipation in diabetes has a multifactorial etiology involving structural changes in gastrointestinal tract wall tissues and functional abnormalities secondary to chronic hyperglycemia. GLP-1 receptor agonists — peptide-based medications critical for glycemic control and cardiovascular/renal risk reduction in type 2 diabetes — are identified as an additional cause of constipation.
Diagnosis is typically clinical, as validated methods for assessing colonic transit are invasive and limited to specialized centers. Treatment follows a stepwise approach: dietary modification and physical activity first, followed by laxatives, and finally newer agents or mechanical methods for refractory cases.
De Fano, Michelantonio; Baluganti, Sara; Manco, Marcello; Porcellati, Francesca; Fanelli, Carmine G; Bassotti, Gabrio ·
RPEP-10649 · 2025Using top-down peptidomics on milk samples from four farms, the researchers identified 2,213 peptides total, with 19 matching known bioactive sequences. Key bioactivities included DPP-IV inhibition (relevant to type 2 diabetes management), ACE inhibition (relevant to blood pressure control), antioxidant activity, enhanced calcium uptake, and antimicrobial effects.
Specific DPP-IV-inhibitory peptides such as LDQWLCEKL and VGINYWLAHK were identified, along with ACE-inhibitory peptides YLGY and FFVAPFPEVFGK. Antimicrobial peptides SDIPNPIGSENSEK and VLNENLLR showed broad-spectrum activity against harmful microorganisms. Additional peptides with osteoanabolic, antianxiety, and immunomodulatory properties were also detected.
De Fazio, Rosario; Di Francesco, Antonella; Di Ciccio, Pierluigi Aldo; Cunsolo, Vincenzo; Britti, Domenico; Lomagistro, Carmine; Roncada, Paola; Piras, Cristian ·
RPEP-10662 · 2025Among 243 patients across nine Belgian headache clinics: 86.0% reported worsening migraine during the mandatory 3-month treatment holiday, with 59.4% deteriorating within the first month. Only 3.0% improved and 11.0% experienced no change. For 5.9%, worsening extended beyond the 3-month holiday, delaying treatment resumption.
Anxiety about the holiday was reported by 45.0% of patients, with 18.6% experiencing very high anxiety levels. A significant association was found between anxiety and migraine deterioration (p=0.012). Despite the negative impact, 49.1% found the holiday useful for confirming treatment need, and 22.6% found it very useful.
De Praeter, Ruben; Tuerlinckx, Evelien; Schoenen, Jean; Boon, Elizabet; Sava, Simona Liliana; Debruyne, Frederik; Delmotte, Koen; De Pauw, Adinda; Van Dycke, Annelies; Van Humbeeck, Cindy; Versijpt, Jan ·
RPEP-10663 · 2025Of 2,940 consecutive acute coronary syndrome patients in the START-ANTIPLATELET registry, 807 (27.4%) met the SELECT trial eligibility criteria for semaglutide at 60 days post-discharge: age ≥45, BMI ≥27, history of MI/stroke/peripheral artery disease, and no diabetes.
At one-year follow-up, the SELECT-eligible group had significantly lower rates of major adverse cardiovascular events (MACE: 4.6% vs. 8.2%, p=0.004) and net adverse clinical events (NACE: 3.6% vs. 7.6%, p<0.001) compared to ineligible patients. This paradoxically lower event rate in the eligible group suggests that the SELECT criteria may identify a population with a different risk profile than the broader ACS population.
De Sio, Vincenzo; Gragnano, Felice; Capolongo, Antonio; Guarnaccia, Natale; Maddaluna, Pasquale; Acerbo, Vincenzo; Galli, Mattia; Berteotti, Martina; Sperlongano, Simona; Cesaro, Arturo; Moscarella, Elisabetta; Pelliccia, Francesco; Patti, Giuseppe; Antonucci, Emilia; Cirillo, Plinio; Pignatelli, Pasquale; Palareti, Gualtiero; Pengo, Vittorio; Gresele, Paolo; Marcucci, Rossella; Calabrò, Paolo ·
RPEP-10664 · 2025Palmitoylated LL37 antimicrobial peptide encapsulated in PLGA nanoparticles showed enhanced stability and controlled release. Microfluidic fabrication produced superior nanoparticles compared to nanoprecipitation — smaller (102.3 nm vs 189.3 nm), more uniform, more stable, and with prolonged peptide release. The loaded nanoparticles enhanced keratinocyte uptake and significantly accelerated fibroblast-mediated wound closure. Proteomic analysis of the nanoparticle protein corona showed enrichment in coagulation, inflammation modulation, and extracellular matrix remodeling proteins.
De Soricellis, Chiara; Laigle, Chloé; Spinelli, Lucio; Monti, Maria Chiara; Amante, Chiara; Russo, Paola; Aquino, Rita Patrizia; Rousselle, Patricia; Lollo, Giovanna; Del Gaudio, Pasquale ·
RPEP-10672 · 2025Eight triazolium-based peptoids with polyproline I (PPI) helical structures were tested against bacterial and eukaryotic membrane models. Calcein leakage experiments (measuring membrane disruption) showed excellent correlation with both antibacterial activity against Gram-positive and Gram-negative bacteria and selectivity (low toxicity to human red blood cells).
CD spectroscopy confirmed the designed PPI helical fold. Fluorescence assays quantitatively measured membrane association and showed the peptoids localize at the membrane interface. Solid-state NMR spectroscopy revealed significant reduction in lipid order parameters in the presence of peptoids, indicating membrane destabilization. These converging biophysical findings establish that the peptoids share the membrane-mediated mechanism of action of their natural antimicrobial peptide templates.
De, Kathakali; Guerinot, Cassandra; Charbonnel, Nicolas; Faure, Allison; Josse, Jérôme; Aisenbrey, Christopher; Faure, Sophie; Bechinger, Burkhard ·
RPEP-10675 · 2025Two thymine-conjugated nucleopeptides formed hydrogels in water at neutral pH via antiparallel β-sheet structures with π-π stacking and H-bonding. Antimicrobial activity against MDR clinical isolates: MRSA (MIC 15.92-16.86 μM), K. pneumoniae (MIC 8.8-50 μM), P. aeruginosa (active), plus standard B. subtilis and E. coli. Biocompatibility was excellent: IC50 values of 0.5-1.1 mM on HEK-293 cells (30-70× higher than MIC values). In vitro wound healing assays confirmed no disruption of cell or mitochondrial membranes. Nanostructural characterization showed nanofibrillar networks by TEM.
Deb, Swapnendu; Gupta, Shalini; Bose, Supratim; Mondal, Tanushree; Mondal, Biplab; Banerjee, Arindam ·
RPEP-10678 · 2025The computationally designed multi-epitope vaccine incorporating NY-ESO-1 and MAGE-C2 antigens demonstrated favorable properties across multiple simulation analyses. The vaccine construct showed satisfactory allergenicity profiles, strong antigenicity, and good physicochemical properties.
Molecular docking and dynamics simulations confirmed stable interactions with TLR2 and TLR4 immune receptors. In silico immune simulation predicted significant increases in helper T cells, cytotoxic T cells, interferon-gamma, and interleukin-2 after repeated vaccine exposure — all key components of an anti-tumor immune response. The inclusion of BCSP31, RpfB adjuvants, and PADRE helper epitope enhanced the overall immunogenicity of the construct.
Dehghankhold, Mahvash; Nezafat, Navid; Farahmandnejad, Mitra; Abolmaali, Samira Sadat; Tamaddon, Ali Mohammad ·
RPEP-10680 · 2025**Injectable semaglutide (n=129):**
- 6 months: -10.4 kg weight, -3.9 kg/m² BMI, -1.9% HbA1c
- 12 months: -9.3 kg weight, -3.4 kg/m² BMI, -1.5% HbA1c
- 24 months: -15.9 kg weight, -5.8 kg/m² BMI, -1.5% HbA1c
**Oral semaglutide (n=46):**
- 6 months: -6.7 kg weight, -2.6 kg/m² BMI, -1.5% HbA1c
- 12 months: -10.7 kg weight, -3.9 kg/m² BMI, -0.8% HbA1c
Notably, weight loss was maintained and even continued to increase through 24 months with injectable semaglutide — contradicting concerns about weight plateau or regain during extended treatment. The oral formulation showed comparable effectiveness to injectable at 12 months despite initial slower weight loss.
Del Prete, Michela; Gavazzi, Lidia; Disoteo, Olga Eugenia; Vignati, Federico; Di Sacco, Gianleone; Muratori, Fabrizio ·
RPEP-10681 · 2025The study established the first population reference range for endogenous TB4 concentration in racehorse blood. TB4 levels were not significantly affected by gender, age, or horse breed. A critical pre-analytical finding was that TB4 concentrations increase significantly and rapidly in plasma stored at 4°C without cell separation, due to cell lysis releasing intracellular TB4.
Most significantly, the researchers demonstrated that administration of a commercially available TB4 product to a horse resulted in detectable non-natural synthesis impurities in equine plasma, providing a reliable marker for doping detection.
Delcourt, Vivian; Garcia, Patrice; Chabot, Benjamin; Aber, Nina; Pescher, Mylène; Cacault, Marie; Scholtes, Priscilla; Loup, Benoit; Barnabé, Agnès; Popot, Marie-Agnès; Bailly-Chouriberry, Ludovic ·
RPEP-10685 · 2025In a rotenone-induced Parkinson's disease rat model, tirzepatide (50 and 100 nmol/kg, subcutaneous) demonstrated multiple neuroprotective effects:
- Prevented rotenone-induced motor deficits
- Significantly inhibited proinflammatory cytokines TNF-α and IL-6
- Upregulated striatal dopamine levels
- Alleviated oxidative stress
- Reduced alpha-synuclein aggregation
- Effects were dose-dependent, with 100 nmol/kg more effective than 50 nmol/kg
- Neuroprotection was comparable to the GLP-1 agonist exendin-4 (8 μg/kg), supporting the potential benefit of dual GLP-1/GIP receptor activation
Delvadia, Prashant; Dhote, Vipin; Mandloi, Avinash Singh; Soni, Ritu; Shah, Jigna ·
RPEP-10687 · 2025BPC-157 significantly protected the liver, kidneys, and lungs from damage caused by ischemia-reperfusion injury in the lower extremities of rats. In the group that received BPC-157 before the procedure, kidney tissue showed markedly less vacuolization, tubular dilation, and cell shedding. Lung tissue had reduced edema and congestion, and liver tissue showed less sinusoidal dilation, necrosis, and immune cell infiltration.
Biochemical markers backed up the tissue findings: antioxidant activity (measured by TAS) was significantly higher in all three organs of BPC-157-treated rats, while oxidative stress markers (TOS and OSI) were lower. The antioxidant enzyme PON-1 was also elevated in the treatment group.
Demirtaş, Hüseyin; Özer, Abdullah; Yıldırım, Alperen Kutay; Dursun, Ali Doğan; Sezen, Şaban Cem; Arslan, Mustafa · Animal Study
RPEP-10689 · 2025Vaccine-induced T cell responses against multiple MC38 tumor neoantigens were immunogenic (generated strong T cell responses) but failed to regress established tumors or prevent tumor engraftment prophylactically. However, these same T cells showed robust killing of cells that were externally loaded with neoantigen peptide. Tumor-cell killing was rescued when target peptide-MHC complexes were saturated on the cell surface. This demonstrates that the level of neoantigen protein expression and MHC-I presentation — not just immunogenicity — determines whether a neoantigen can serve as an effective vaccine target.
Deng, Li; Walsh, Scott R; Nguyen, Andrew; Inkol, Jordon M; Westerveld, Michael J; Chen, Lan; El-Sayes, Nader; Mossman, Karen L; Workenhe, Samuel T; Wan, Yonghong ·
RPEP-10692 · 2025GLP-1 receptor agonists exhibit immunoregulatory effects beyond their well-established metabolic benefits. The review synthesizes evidence showing that GLP-1R signaling affects multiple immune cell types, modulating both innate and adaptive immune responses.
The therapeutic potential of GLP-1RAs is evaluated across seven autoimmune and autoinflammatory conditions: psoriasis, inflammatory bowel diseases, rheumatoid arthritis, asthma, multiple sclerosis, Sjögren's syndrome, and systemic lupus erythematosus. Evidence comes from in vitro studies, preclinical animal models, and clinical observations in patients taking GLP-1RAs for metabolic indications who showed improvements in co-existing autoimmune conditions.
Deng, Sihui; Chen, Zeyu; Shi, Yuling ·
RPEP-10698 · 2025In this large comparative effectiveness study of 21,790 veterans with type 2 diabetes, liraglutide, semaglutide, and dulaglutide showed no significant differences in kidney failure or cardiovascular outcomes. Kidney failure hazard ratios were similar across all comparisons (e.g., liraglutide vs semaglutide HR 0.93, 95% CI 0.60–1.44), and the composite cardiovascular-kidney-metabolic outcome and major adverse cardiovascular events were also comparable.
The most notable finding involved all-cause mortality. Liraglutide was associated with a 31% lower hazard of death compared to dulaglutide in intent-to-treat analysis (HR 0.69, 95% CI 0.58–0.83) and a 50% lower hazard in per-protocol analysis (HR 0.50, 95% CI 0.31–0.82). Liraglutide also showed a trend toward lower mortality versus semaglutide (HR 0.83, 95% CI 0.69–0.99), though this lost statistical significance in per-protocol models. For gastrointestinal side effects, dulaglutide was associated with lower risk of gallstones (HR 0.72) and acute cholecystitis (HR 0.62) compared to semaglutide.
Derington, Catherine G; Sarwal, Amara; Wei, Guo; Hartsell, Sydney E; Throolin, Michael; Singh, Ravinder; Nevers, McKenna R; Zhang, Chong; Katkam, Niharika; Takyi, Augustine; Chakravartula, Akhil R; Babu, Poorvika; Deshmukh, Vikrant G; Boucher, Robert E; Drakos, Stavros G; Greene, Tom; Shen, Jincheng; Beddhu, Srinivasan ·
RPEP-10701 · 2025A 55-year-old woman with chronic kidney disease, type 2 diabetes with neuropathy, peripheral vascular disease, and prior pancreatitis developed severe gastrointestinal symptoms consistent with the temporal relationship of GLP-1 receptor agonist dose titration. The case was complicated by sepsis physiology, gastrointestinal bleeding, hemodynamic instability, and metabolic derangement, requiring multidisciplinary management including endocrinology, gastroenterology, and cardiology.
DesRochers, Peter; Kaiser, Linus; Lee, Seoyoon; Perchetti, Garrett A; Lazarescu, Roxana ·
RPEP-10703 · 2025Twenty-four participants with diabetic peripheral neuropathy treated with GLP-1 receptor agonists showed significant improvement in clinical neuropathy scores (TNS improved from 3.7 to 2.3, p=0.005) and nerve conduction (sural nerve amplitude improved from 11.9 to 14.2 μV, p=0.013) after 3 months. Axonal excitability testing revealed improvements consistent with enhanced Na+/K+-ATPase pump function and Na+ permeability, supported by mathematical modeling. Three GLP-1RAs were used: semaglutide, dulaglutide, and exenatide.
Dhanapalaratnam, Roshan; Issar, Tushar; Poynten, Ann M; Milner, Kerry-Lee; Kwai, Natalie C G; Krishnan, Arun V ·
RPEP-10706 · 2025Among 6,424,228 T2DM adults, GLP-1RA use was associated with significantly lower suicide attempt risk (aHR: 0.63; 95% CI: 0.47-0.85). Cannabis use disorder (CUD) dramatically elevated risk (aHR: 5.50; 95% CI: 4.39-6.89). Among CUD patients using GLP-1RAs, the elevated risk persisted (aHR: 5.75; 95% CI: 3.42-9.69) with no protective GLP-1RA effect (aHR: 1.00; 95% CI: 0.37-2.69 for GLP-1RA effect within CUD group).
Dhruva, Yesh; Messias, Erick; Lin, Ping-I ·
RPEP-10707 · 2025Positive 99mTc-PYP grading was significantly associated with increased left ventricular mass (β=111.21, p=0.009) and greater interventricular septal thickness (β=0.48, p=0.003) in hereditary ATTR patients. Nuclear scan positivity also correlated with log-transformed BNP (β=1.99, p=0.002) in hereditary patients and log-transformed troponin (β=1.68, p=0.007) in wild-type ATTR patients.
The quantitative heart-to-contralateral lung ratio from nuclear imaging did not correlate with BNP or troponin but was significantly associated with LV mass (β=134.52, p=0.001) and septal thickness (β=0.46, p=0.002) in hereditary patients. These genotype-dependent differences support a stratified diagnostic approach.
Di Giovanni, Bennett; Gustafson, Dakota; Arivalagan, Priya; Adamson, Mitchell B; Vishram-Nielsen, Julie; Delgado, Diego ·
RPEP-10708 · 2025Using a Markov decision model, researchers compared three weight loss strategies for morbidly obese patients with end-stage kidney disease who need to reach BMI ≤35 to qualify for kidney transplant. At 5 years, sleeve gastrectomy got the most patients to transplant (14.74%), followed by dual GLP-1/GIP receptor agonists like tirzepatide (9.06%), and single GLP-1 agonists (4.83%).
Sleeve gastrectomy produced faster weight loss, with 27.49% of patients reaching the BMI target by 6 months. Surgery also showed a survival advantage, especially in patients starting at higher BMIs.
However, dual GLP-1/GIP agonists still got a substantial number of patients to transplant and represent a viable non-surgical alternative, particularly for patients who cannot undergo or prefer to avoid surgery.
Di Napoli, Marissa; Rouhi, Armaun D; Baimas-George, Maria; Dumon, Kristoffel; Castle, Rose; Kennealey, Peter; Nydam, Trevor; Choudhury, Rashikh · Modeling Study
RPEP-10714 · 2025The lateral septum serves as a neural relay center integrating homeostatic (nutritional need-driven) and hedonic (pleasure-driven) feeding circuits. GLP-1 receptors are present in the LS, and their activation within this region modulates food intake. The extensive neural connections between the LS and other brain regions involved in feeding behavior position it as a critical node where GLP-1 signaling may influence eating through multiple pathways simultaneously.
Dib, Tatiana; Covarrubias, María José; Escobar, Angélica; Renard, Georgina M; Bravo, Javier A; Sotomayor-Zárate, Ramón ·
RPEP-10715 · 2025The review highlights several key peptide-related signaling pathways influenced by gut microbiota:
- GLP-1: Activation of brainstem NTS by GLP-1 influences mood, cognition, and gastrointestinal motility
- Prolactin-releasing peptide (PrRP): Binds to PrRPR to suppress food intake and regulate stress, cardiovascular reactions, and circadian rhythms
- GPR119: Suppresses appetite with potential applications in type 2 diabetes and obesity treatment
- SCFAs interact with GPCRs, TLRs, and PPARs to influence inflammatory reactions, gut motility, hormone secretion, and neurochemical signaling
- Olfactory receptor OR51E1 influences blood pressure and vascular reactivity
- Butyrate binding to NF-κB and PPARγ regulates inflammation and prevents oxidized LDL uptake, reducing cardiovascular disease risk
Dicks, Leon M T ·
RPEP-10717 · 2025Branching cell-penetrating peptides (penetratin and penetramax) into dimer and trimer structures significantly increased their ability to enhance transepithelial permeation of insulin and other cargo molecules across Caco-2 cell monolayers. The enhancement correlated with the degree of branching — trimers outperformed dimers, which outperformed linear forms. The mechanism involved immediate and reversible effects on cell monolayer integrity and cytoskeletal alterations, consistent with paracellular transport. In vivo pharmacokinetic studies in rats confirmed that dimeric penetramax enhanced intestinal insulin delivery compared to linear penetramax.
Diedrichsen, Ragna Guldsmed; Mishra, Narendra Kumar; Fredholt, Freja; Heade, Joanne; Sørensen, Kasper Kildegaard; Jensen, Knud Jørgen; Nielsen, Hanne Mørck ·
RPEP-10727 · 2025Using three computational platforms (ADMETlab, OECD QSAR toolbox, and VEGA HUB), 82 peptide sequences from seven bee antimicrobial peptides (abaecin, apamin, apisimin, apidaecin, defensin, hymenoptaecin, and melittin) were profiled against 81 descriptors.
Key findings across all seven BAMPs:
- Met drug-likeness rules from Lipinski, Pfizer, and GSK
- Predicted favorable cell permeability, high water solubility, and oral bioavailability
- No blood-brain barrier penetration predicted
- Non-substrates of p-glycoprotein
- No cytochrome P450 enzyme inhibition (no drug-drug interaction risk)
- Free of respiratory toxicity, hepatotoxicity, carcinogenicity, and mutagenicity
- No toxicophore or PAINS (pan-assay interference) alerts
- Predicted antibacterial, antifungal, and antiviral activity
- Non-toxic to gonadal receptors, stress receptors, PPAR-γ, mitochondrial membrane receptors, and p53
Dinata, Roy; Arati, Chettri; Saeed, Ahmed-Laskar; Manikandan, Bose; Abinash, Giri; Pori, Buragohain; Bidanchi, Rema Momin; Roy, Vikas Kumar; Gurusubramanian, Guruswami ·
RPEP-10743 · 2025In a retrospective cohort of 774,968 adults with T2DM, GLP-1 receptor agonist initiation was associated with significantly reduced mental health-related healthcare utilization compared to DPP-4 inhibitor initiation:
- Office visits for depression: IRR 0.87 (95% CI 0.82–0.92) — 13% reduction
- Office visits for anxiety: IRR 0.85 (95% CI 0.81–0.90) — 15% reduction
- Outpatient hospital visits for depression: IRR 0.96 (95% CI 0.95–0.98) — 4% reduction
No significant changes were observed for emergency department or inpatient visits. Reductions were more pronounced with semaglutide, liraglutide, and dulaglutide specifically.
Do, Duy; Lee, Tiffany; Inneh, Angela; Patel, Urvashi ·
RPEP-10747 · 2025Among 108,019 new users of migraine preventive medications, the 12-month unadjusted risk of new-onset hypertension was essentially identical across treatment groups: erenumab 9.34%, other anti-CGRP mAbs 9.42%, standard oral preventives 9.09%, and onabotulinumtoxinA 9.10%.
At 36 months, adjusted relative risks for acute myocardial infarction and stroke showed no significant differences: erenumab vs. other mAbs — MI: RR 1.02 (95% CI 0.45–1.59), stroke: RR 0.90 (0.56–1.25); erenumab vs. onabotulinumtoxinA — MI: RR 0.87 (0.19–1.55), stroke: RR 0.97 (0.42–1.52). No elevated cardiovascular risk was identified for erenumab.
Dodick, David W; Tepper, Stewart J; Ailani, Jessica; Khodavirdi, Ani C; Pannacciulli, Nico; Fu, Alan; Kent, Shia T; Gill, Karminder; Urman, Robert; Oh, Sam S ·
RPEP-10751 · 2025Hydrogen sulfide levels were reduced by 81% in human HFpEF patients and were similarly depleted in two rodent models of cardiometabolic HFpEF. This depletion was linked to reduced CSE enzyme expression and activity alongside increased SQR expression.
Genetic knockout of CSE in endothelial cells worsened HFpEF features including elevated E/e' ratio and left ventricular end-diastolic pressure, impaired aortic vasorelaxation, and increased mortality. Pharmacological H₂S supplementation restored bioavailability, improved diastolic function, and reduced cardiac fibrosis. Combining the H₂S donor DATS with the GLP-1/glucagon receptor agonist survodutide synergistically reduced obesity, improved diastolic function and exercise capacity, and decreased oxidative stress and cardiac fibrosis in ZSF1 obese rats.
Doiron, Jake E; Elbatreek, Mahmoud H; Xia, Huijing; Yu, Xiaoman; Gehred, Natalie D; Gromova, Tatiana; Chen, Jingshu; Driver, Ian H; Muraoka, Naoto; Jensen, Martin; Shambhu, Smitha; Tang, W H Wilson; LaPenna, Kyle B; Sharp, Thomas E; Goodchild, Traci T; Xian, Ming; Xu, Shi; Quiriarte, Heather; Allerton, Timothy D; Zagouras, Alexia; Wilcox, Jennifer; Shah, Sanjiv J; Pfeilschifter, Josef; Beck, Karl-Friedrich; Vondriska, Thomas M; Li, Zhen; Lefer, David J ·
RPEP-10758 · 2025In 3,250 acute ischemic stroke patients followed for 12 months, 702 (21.6%) experienced major disability or death. Patients in the highest quartile of plasma NPY had significantly worse outcomes:
- Primary composite (death + major disability): OR 1.56 (95% CI: 1.19-2.04) vs lowest quartile
- Per standard deviation increase in log-NPY: OR 1.18 (1.07-1.30) for primary outcome
- Per SD increase for major disability alone: OR 1.28 (1.15-1.42)
Adding NPY to conventional risk factors improved prediction: category-free net reclassification index 8.82% (P=0.040) and integrated discrimination improvement 0.38% (P=0.011).
Dong, Wenjing; Lu, Yaling; Long, Jiayi; Peng, Yanbo; Ju, Zhong; Xu, Tan; Zhang, Yonghong; Zhai, Guojie; Zhong, Chongke ·
RPEP-10759 · 2025Researchers achieved high-yield production of the marine antimicrobial peptide Spgillcin177-189 using a multicopy yeast expression system in Pichia pastoris. The multicopy strategy yielded 126.1 mg/L — 2.75 times more than single-copy strains. The recombinant peptide showed potent activity against multiple foodborne pathogens (MIC range 5.25–84 μg/mL), effective bactericidal and anti-biofilm activity against S. aureus and V. parahaemolyticus, good heat stability, and no significant cytotoxicity or hemolysis.
The peptide works by targeting bacterial cell membranes via hydrogen bonding with surface components, disrupting membrane integrity and causing cell death.
Dong, Xianxian; Liao, Huiliang; Zhang, Chang; Chen, Fangyi; Peng, Hui; Hong, Xiao; Hao, Hua; Xiong, Ming; Ma, Jiahao; Wang, Ke-Jian · In Vitro
RPEP-10760 · 2025A 39-year-old male on semaglutide (1.7 mg/week) following transoral outlet reduction surgery presented with severe bilateral lower extremity weakness, loss of reflexes, and sensory impairment. Laboratory testing revealed thiamine and vitamin E deficiencies. MRI showed cauda equina nerve root enhancement without structural abnormalities. He was diagnosed with lumbosacral polyradiculopathy due to micronutrient deficiencies.
Symptoms developed over 3 months and worsened after semaglutide dose increase. Treatment included semaglutide discontinuation, thiamine and vitamin E supplementation, and inpatient rehabilitation. Motor and sensory symptoms improved over the following month.
Donigan, Emma C; Ingersent, Elizabeth; Wanberg, Erik J; Jegen, Dominika A; Passmore, Rachael ·
RPEP-10764 · 2025The review synthesizes evidence supporting the paradox:
- GIP receptor agonism (tirzepatide): Activating both GIP and GLP-1 receptors produces greater weight loss and metabolic improvement than GLP-1 alone — demonstrated in clinical trials leading to tirzepatide's approval
- GIP receptor antagonism (maridebart cafraglutide/MariTide): Blocking GIP while activating GLP-1 also enhances weight loss — demonstrated in early clinical data
- The paradox is supported by: human genetic evidence (GIPR loss-of-function variants associated with lower BMI), rodent genetic knockout models, and preclinical pharmacology in rodents and non-human primates
- The review highlights where early preclinical findings successfully predicted clinical efficacy and where the translation was less straightforward
Douros, Jonathan D; Mowery, Stephanie A; Knerr, Patrick J ·
RPEP-10765 · 2025Gut peptide hormones directly influence taste perception through multiple mechanisms: they regulate taste receptor expression and function in taste buds and the gastrointestinal tract. GLP-1, leptin, ghrelin, and CCK each modulate specific aspects of taste sensitivity at both peripheral (tongue) and central (brain reward circuitry) levels. Metabolic conditions like obesity and diabetes — characterized by hormonal resistance (leptin, insulin) and neurotransmitter dysregulation — contribute to altered taste preferences and compulsive eating behaviors. The review establishes a gut-brain-taste axis integrating peripheral gustatory signals with central homeostatic and hedonic mechanisms.
Doval-Caballero, Jose Luis Eduardo; Ferreira-Hermosillo, Aldo; Eugenio-Ponce, Genesis Dinora; García-Sáenz, Manuel Ramon; Ibarra-Salce, Raúl; Tenorio-Rojo, Andrea Patricia; Luna-Avila, Eduardo Salif; Gete-Palacios, Paulo César; Pérez-Hernández, Fernando; Rojas-Milán, Eduardo; López-Cruz, Luis Angel; Méndez-Hernández, César Alejandro ·
RPEP-10766 · 2025Analysis of 38 T-cell epitopes and 144 non-epitopes revealed that immunogenic peptides have strong amino acid preferences at central positions p4-p8, while non-epitopes do not.
Molecular dynamics simulations (100 ns) of representative epitope and non-epitope complexes with TCR-peptide-HLA showed:
- The immunogenic epitope formed a more stable complex with greater flexibility, supporting an induced-fit recognition mechanism
- It established a broader and longer-lasting network of hydrogen bonds and π interactions across positions p4-p8
- The non-epitope engaged the TCR at only two positions, explaining its inability to trigger a full immune response
These findings identify the peptide's central region as the primary driver of TCR engagement and immunogenicity.
Doytchinova, Irini; Sotirov, Stanislav; Dimitrov, Ivan ·
RPEP-10767 · 2025This review examines three emerging therapeutic classes for substance use disorders: GLP-1 receptor agonists, dopamine D3 receptor antagonists, and corticotropin-releasing factor (CRF) antagonists. GLP-1 receptor agonists (like semaglutide and liraglutide) show promise in reducing alcohol and substance use by modulating the brain's reward circuitry — preclinical studies demonstrate reduced drug-seeking behavior, and early clinical observations are encouraging. CRF antagonists target the stress and relapse pathways, while D3R antagonists specifically modulate reward processing. Together, these three approaches address different stages and mechanisms of addiction: reward, stress, and relapse.
Draghmeh, Khaled; Fuehrlein, Brian · Review
RPEP-10782 · 2025Fish-derived collagen peptides combined with calcium and vitamin D3 significantly improved skin hydration by 23% and skin elasticity by 8.52% in menopausal women after six months. Collagen alone improved elasticity by 12.23%. All active supplement groups (calcium+D3, collagen, and the combination) significantly reduced hair shedding compared to placebo.
However, none of the supplement combinations produced significant changes in bone turnover markers (P1NP, BAP, osteocalcin) or body composition over the six-month period. Safety markers (creatinine, ALT, AST) remained normal across all groups.
Duangjai, Acharaporn; Srivilai, Jukkarin; Nangola, Sawitree; Amornlerdpison, Doungporn · Rct
RPEP-10787 · 2025Among 1,131 patients with obesity who completed at least one year of semaglutide therapy combined with the Individualized Virtual Integrative Medicine (IVIM) protocol, the average weight loss was 19.5% of total body weight at 52 weeks. Nearly half (47.8%) lost 20% or more of their body weight, and 99.2% lost at least 5%. Weight loss followed a consistent trajectory of approximately 0.739 pounds per week (p < 0.0001). Patients who continued to 68 weeks lost an average of 21.8% of their body weight.
At milestone timepoints: 12 weeks saw 6.5% weight loss (14.9 lbs), 24 weeks 12.6% (28.6 lbs), 36 weeks 16.4% (36.8 lbs), and 52 weeks 19.5% (45.95 lbs).
Duncan, Jessica; Lee Stevens, Patrick; Bigby, Emily; Floyd, Courtney; Malina, Josh; Nickens, Jennifer; Lambert, Amber; Kantor, Taylor · Retrospective Cohort
RPEP-10788 · 2025Among 29,516 patients with type 2 diabetes and atherosclerotic cardiovascular disease who started once-weekly GLP-1 receptor agonists, those who remained persistent with therapy had significantly lower cardiovascular risks compared to non-persistent patients:
- 2-point MACE (major adverse cardiovascular events): HR 0.696 (95% CI: 0.626–0.774), representing a ~30% risk reduction
- Stroke: HR 0.668 (95% CI: 0.573–0.777), representing a ~33% risk reduction
- Myocardial infarction (heart attack): HR 0.710 (95% CI: 0.621–0.813), representing a ~29% risk reduction
All associations were statistically significant (p < 0.001). Persistent patients were followed for an average of 418 days, while non-persistent patients were followed for 741 days.
Dunn, Tyler J; Zhu, Yong; Gronroos, Noelle N; Xie, Lin; Sargent, Andrew; Gamble, Cory; Billings, Liana K ·
RPEP-10791 · 2025Peptides derived from Torreya grandis nuts improved multiple metabolic markers in mice fed a high-fat diet. The supplementation reduced body weight, total cholesterol, triglycerides, and LDL while increasing HDL. Lipid droplet accumulation in the liver, muscles, and blood vessels was markedly reduced in the high-peptide group.
The peptides also favorably shifted gut microbiota composition, increasing beneficial Akkermansia and Parabacteroides while decreasing Firmicutes, which boosted short-chain fatty acid production. Proteome analysis identified a vicilin-like antimicrobial peptide, and transcriptome analysis showed lipid regulation via the PPAR-α pathway. Molecular docking identified 4 potential lipid II inhibitory peptides.
Durrani, Rabia; Yutian, Sun; Bowen, Hou; Ullah, Hammad; Durand, Erwann; Meiyun, Yang; Yiyang, Long; Delavault, André; Yasir, Muhammad; Weiwei, Huan; Fei, Gao; Lili, Song · Animal
RPEP-10792 · 2025NT-proBNP point-of-care testing showed excellent agreement with laboratory standards:
- Passing-Bablok analysis: slope = 1.08 (CI 0.97–1.19), intercept = 18.22 (CI -41.6 to 4.5) — indicating equivalent results
- Intraclass correlation coefficient (ICC) = 0.97
- POCT correctly classified 92% of cases against COMPERA 2.0 4-risk-strata thresholds
BNP point-of-care testing was less reliable:
- Passing-Bablok showed non-equivalence (slope = 1.24, CI 1.11–1.31)
- POCT correctly classified only 86% of cases
- BNP identified fewer high-risk patients than NT-proBNP
- BNP and NT-proBNP risk status agreed at only 57% of visits (p < 0.0009)
NT-proBNP in posted (mailed) blood samples showed good agreement with immediately processed samples. Exercise did not have a clinically significant effect on either NT-proBNP or BNP results.
Durrington, Charlotte; Battersby, Christian; Holt, Laura; Fairman, Alexandra; Strickland, Scarlett; Salisbury, Thomas; Turton, Helena A; Watson, Lisa; Smith, Ian; Roman, Stefan; Ablott, Jenna; Hitchcock, Felicity; Roddis, Chloe; Oakes, Eleanor; Wilshaw, Heather; Woodrow, Iain; Armstrong, Iain; Charalampopoulos, Athanasios; Elliot, Charlie A; Hameed, Abdul; Hamilton, Neil; Hurdman, Judith A; Lawrie, Allan; Middleton, Jennifer T; Zafar, Hamza; Rothman, Alex M K; Condliffe, Robin; Lewis, Robert A; Kiely, David G; Thompson, A A Roger ·