RPEP-03573 · 2018This review consolidates evidence on how neuropeptides — signaling molecules released by nerves in the airways — contribute to asthma, COPD, and cystic fibrosis. The nervous system doesn't just control breathing; it actively drives disease processes like excessive mucus production, airway smooth muscle contraction, and inflammation through peptides like substance P, CGRP, VIP, and others.
The authors highlight that mucus hypersecretion is a shared feature across all three diseases, and neuropeptides play a central but underappreciated role in driving it. They also identify several less-studied neuropeptides that deserve more research attention as potential therapeutic targets.
Atanasova, Kalina R; Reznikov, Leah R · Review
RPEP-03576 · 2018GHRH (Growth Hormone-Releasing Hormone) antagonists exert protective effects against inflammation and cancer through p53-mediated pathways. P53 — a tumor suppressor protein frequently mutated in cancers — functions not only to regulate cell cycle, senescence, and apoptosis, but also to suppress inflammation across multiple human tissues. GHRH antagonistic analogs have been developed with clinical applications spanning benign prostatic hyperplasia, breast, prostate and lung cancers, diabetes, and neurodegenerative diseases, with their beneficial effects mediated at least partly through p53 activation.
Barabutis, Nektarios; Schally, Andrew V; Siejka, Agnieszka ·
RPEP-03579 · 2018RTD-1 (rhesus theta-defensin 1) was rapidly and potently fungicidal against both drug-sensitive and multidrug-resistant C. albicans strains. It killed fungi by permeabilizing cell membranes, triggering ATP release and intracellular reactive oxygen species (ROS) accumulation. Compared to histatin 5 (a well-characterized human antifungal peptide), RTD-1 killed C. albicans at more than 200-fold lower concentrations and much more rapidly.
Critically, RTD-1 was completely resistant to Candida proteases for 2 hours under conditions that rapidly and completely destroyed histatin 5 — a major advantage for therapeutic development. Testing of 14 natural theta-defensin isoforms revealed that some were more active than amphotericin B and/or caspofungin against fluconazole-resistant organisms, including the multidrug-resistant Candida auris — a pathogen the CDC considers an urgent threat.
Basso, Virginia; Garcia, Angie; Tran, Dat Q; Schaal, Justin B; Tran, Patti; Ngole, Diana; Aqeel, Younus; Tongaonkar, Prasad; Ouellette, André J; Selsted, Michael E · In Vitro
RPEP-03586 · 2018Across four cardiovascular outcome trials (ELIXA, LEADER, SUSTAIN 6, and EXSCEL), GLP-1 receptor agonists produced a significant 10% relative risk reduction in the composite of cardiovascular death, non-fatal heart attack, and non-fatal stroke (HR 0.90, 95% CI 0.82–0.99, p=0.033).
Cardiovascular mortality was reduced by 13% (HR 0.87, 95% CI 0.79–0.96, p=0.007) and all-cause mortality by 12% (HR 0.88, 95% CI 0.81–0.95, p=0.002). No significant effects were found for individual endpoints of heart attack, stroke, unstable angina hospitalization, or heart failure hospitalization when analyzed separately.
Bethel, M Angelyn; Patel, Rishi A; Merrill, Peter; Lokhnygina, Yuliya; Buse, John B; Mentz, Robert J; Pagidipati, Neha J; Chan, Juliana C; Gustavson, Stephanie M; Iqbal, Nayyar; Maggioni, Aldo P; Öhman, Peter; Poulter, Neil R; Ramachandran, Ambady; Zinman, Bernard; Hernandez, Adrian F; Holman, Rury R ·
RPEP-03587 · 2018Although obese patients with acute heart failure had lower NT-proBNP levels than non-obese patients (inverse correlation, p<0.001 across BMI classes), the peptide biomarker's ability to predict death at 180 days was not affected by obesity. NT-proBNP remained a reliable prognostic indicator for long-term mortality regardless of BMI class, with no significant interaction between BMI and NT-proBNP for 180-day mortality (interaction p=0.24).
However, for the combined endpoint of 30-day death or heart failure rehospitalization, there was a significant BMI-NT-proBNP interaction (p=0.02), suggesting the relationship between NT-proBNP and short-term outcomes may differ by weight category.
Bhatt, Ankeet S; Cooper, Lauren B; Ambrosy, Andrew P; Clare, Robert M; Coles, Adrian; Joyce, Emer; Krishnamoorthy, Arun; Butler, Javed; Felker, G Michael; Ezekowitz, Justin A; Armstrong, Paul W; Hernandez, Adrian F; O'Connor, Christopher M; Mentz, Robert J · Clinical Substudy
RPEP-03590 · 2018In a 60-day double-blind, placebo-controlled trial of 54 overweight subjects, a polyphenol supplement combining hibiscus and lemon verbena extracts increased the appetite-suppressing hormone GLP-1 (glucagon-like peptide-1) and decreased the hunger-promoting hormone ghrelin. Participants also showed improvements in body measurements, reduced blood pressure and heart rate, and reported a more positive overall health perception. The authors propose that these effects may be mediated through AMPK (AMP-activated protein kinase) activation, which influences energy metabolism and fat management.
Boix-Castejón, Marina; Herranz-López, María; Pérez Gago, Alberto; Olivares-Vicente, Mariló; Caturla, Nuria; Roche, Enrique; Micol, Vicente · Randomized Controlled Trial
RPEP-03598 · 2018The tripartite peptide vaccine (AntpMAPMUC1tet) combined with CpG adjuvant produced enhanced antigen-specific immune responses in mice compared to the vaccine alone. Specifically, it increased interferon-gamma (IFN-γ) and IL-4 T cell responses and induced a Th1-biased immune profile characterized by a higher ratio of IgG2a to IgG1 antibodies.
Importantly, vaccination generated long-term MUC1-specific antibody and T cell responses, and mice vaccinated with this construct showed delayed growth of MUC1-positive tumors. The cell-penetrating peptide component successfully delivered the branched multiple antigen peptides to antigen-presenting cells.
Brooks, Nicole; Hsu, Jennifer; Esparon, Sandra; Pouniotis, Dodie; Pietersz, Geoffrey A ·
RPEP-03602 · 2018The PEG-prodrug system used protease-cleavable peptide linkers (LVPR, LDPR, and LVPRLVPR) to release therapeutic peptides at controlled rates. Taspoglutide release could be tuned over more than one order of magnitude, providing stable serum levels from approximately 0.08 to 3 μmol/L for about 20 hours.
Amylin and pramlintide levels were maintained at approximately 20 nmol/L and remained stable for at least 24 hours. Critically, the PEG attachment protected the peptides from degradation: after 24 hours in serum, less than 2% of taspoglutide within the prodrug was degraded. The researchers suggest that combining this technology with other formulation strategies could enable once-monthly administration.
Böttger, Roland; Knappe, Daniel; Hoffmann, Ralf ·
RPEP-03603 · 2018SS-31 treatment conferred comprehensive protection against hind limb ischemia-reperfusion injury through multiple mechanisms:
- Reduced oxidative stress: lowered malondialdehyde levels and increased SOD and catalase activities and protein levels
- Protected mitochondria: preserved cellular ATP content and mitochondrial membrane potential, reduced cytosolic cytochrome c release
- Suppressed inflammation: prevented IR-induced increases in TNF-α and IL-1β
- Blocked apoptosis: maintained cleaved caspase-3 at very low levels
- Preserved tissue integrity: prevented histological deterioration seen in vehicle controls
Both pre-ischemia and post-ischemia SS-31 administration were effective, with pre-treatment showing mildly superior protection.
Cai, Jing; Jiang, Yu; Zhang, Meng; Zhao, Hongting; Li, Huihui; Li, Kuanyu; Zhang, Xin; Qiao, Tong ·
RPEP-03607 · 2018MK-0677 produced a 1.76-fold increase in geometric mean IGF-1 levels (95% CI 1.48–2.10; p < 0.001) in hemodialysis patients, compared to only a 1.07-fold change with placebo (95% CI 0.89–1.27; p = 0.718). After adjusting for baseline IGF-1, MK-0677 produced a 65% greater increase in IGF-1 compared to placebo (ratio of geometric means 1.65; 95% CI 1.33–2.04; p < 0.001).
No serious adverse effects were attributed to MK-0677 during the 3-month study period. This is the first study of MK-0677 in dialysis patients and demonstrates that the drug's ability to increase IGF-1 — previously shown in healthy subjects — is preserved in this critically ill population.
Campbell, Garland A; Patrie, James T; Gaylinn, Bruce D; Thorner, Michael O; Bolton, Warren K ·
RPEP-03618 · 2018The S. aureus Pmt ABC transporter defends bacteria from killing by important human AMPs and from elimination by human neutrophils. Pmt contributes to virulence during skin infection in an AMP-dependent manner — when AMP activity was removed from the experimental system, the virulence advantage of Pmt was eliminated. This provides the first direct in vivo evidence that antimicrobial peptide resistance per se is important during bacterial infection, not just in laboratory conditions.
Cheung, Gordon Y C; Fisher, Emilie L; McCausland, Joshua W; Choi, Justin; Collins, John W M; Dickey, Seth W; Otto, Michael ·
RPEP-03621 · 2018NK1R protein was localized by immunofluorescence to the surface of some intracardiac neurons and smooth muscle cells of coronary vessels. Quantitative RT-PCR showed NK1R mRNA was present in all four heart chambers, with the highest levels in the left atrium.
Laser capture microdissection revealed NK1R mRNA in some intracardiac neurons but not in cardiomyocytes or coronary smooth muscle cells, suggesting post-transcriptional regulation in smooth muscle cells.
In long-term diabetes (53 weeks post-induction), NK1R mRNA was significantly downregulated in the right atrium and upregulated in the right ventricle, indicating chamber-specific dysregulation of neuropeptide receptor expression in diabetic cardiomyopathy.
Chottova Dvorakova, Magdalena; Mistrova, Eliska; Paddenberg, Renate; Kummer, Wolfgang; Slavikova, Jana ·
RPEP-03622 · 2018Non-mulberry silk fibroin (NMSF)-based nanofibrous dressings functionalized with LL-37 antimicrobial peptide and growth factors significantly outperformed mulberry silk (Bombyx mori), PVA, and control dressings for diabetic wound healing (P<0.01 at 14 days).
NMSF dressings demonstrated faster granulation tissue development, angiogenesis (blood vessel formation), and re-epithelialization. Gene expression analysis showed higher matrix metalloproteinase activity and collagen protein expression, indicating enhanced tissue remodeling. At 4 weeks, NMSF-treated wounds showed organized extracellular matrix deposition (collagen types I and III, elastin, reticulin) and higher wound breaking strength compared to all other groups. The non-mulberry silk's inherent RGD cell-binding motifs enhanced cell-material interactions.
Chouhan, Dimple; Janani, G; Chakraborty, Bijayashree; Nandi, Samit K; Mandal, Biman B ·
RPEP-03623 · 2018Using an isolated perfused rat colon, the researchers found that luminal and especially vascular infusion of acetate and butyrate significantly increased GLP-1 secretion, with a smaller effect on PYY secretion (but only after intracellular cAMP was enhanced). Propionate had no effect on either hormone.
Critically, the study showed this effect does NOT work through the FFAR2 and FFAR3 fatty acid receptors, as widely assumed. A specific FFAR2/FFAR3 agonist (CFMB/AR420626) had no effect on GLP-1 output, and a FFAR3 antagonist didn't block the SCFA-induced response. Instead, blocking voltage-gated calcium channels (nifedipine), opening KATP channels (diazoxide), or inhibiting ATP synthesis (2,4-DNP) completely abolished the responses — indicating SCFAs are metabolized as an energy source by colonocytes, and it's this metabolic process that drives GLP-1 secretion.
Christiansen, Charlotte Bayer; Gabe, Maria Buur Nordskov; Svendsen, Berit; Dragsted, Lars Ove; Rosenkilde, Mette Marie; Holst, Jens Juul · Animal
RPEP-03625 · 2018Microinfusion of NPS into the basolateral amygdala (BLA) one hour after predator-scent stress exposure completely abolished the extreme behavioral response in a rat PTSD model. This single treatment restored decreased hippocampal expression of BDNF and, unexpectedly, NPY-Y1 receptor (NPY-Y1R) — though it did not affect decreased NPY expression itself.
Critically, administering both an NPY-Y1R antagonist and an NPS receptor antagonist together had an additive effect that completely prevented NPS's anxiolytic effects and disrupted NPY-Y1R expression. This reveals that NPS acts through both its own receptor and the NPY-Y1R system, and that crosstalk between these two neuropeptide pathways is necessary for the stress-protective effect.
Cohen, Hagit; Vainer, Ella; Zeev, Kaplan; Zohar, Joseph; Mathé, Aleksander A ·
RPEP-03626 · 2018Using solid-phase peptide synthesis and chemoselective ligations, researchers constructed a series of targeted immune system engagers (ISErs) bearing different numbers and combinations of: two cancer-targeting 'binder' peptides (targeting ephrin A2 and integrin α3 receptors) and one immune-stimulating 'effector' peptide (targeting formyl peptide receptors). The study demonstrated that multivalency and receptor density significantly influence avidity effects — binding strength increased with more binding moieties. Both cancer cell binding and immune cell stimulation activities were characterized across the constructs.
Conibear, Anne C; Pötgens, André J G; Thewes, Karine; Altdorf, Claudia; Hilzendeger, Clarissa; Becker, Christian F W ·
RPEP-03630 · 2018BUF2-magnetite nanobioconjugates demonstrated cell-penetrating ability in both bacterial and mammalian cells, with intracellular uptake confirmed in THP-1 human monocyte cells for the first time. The conjugates were biocompatible and did not cause significant cell toxicity. However, the conjugation to nanoparticles abolished BUF2's native antimicrobial activity, indicating that direct surface attachment constrains the peptide's functional conformation.
Cuellar, Monica; Cifuentes, Javier; Perez, Jessica; Suarez-Arnedo, Alejandra; Serna, Julian A; Groot, Helena; Muñoz-Camargo, Carolina; Cruz, Juan C ·
RPEP-03633 · 2018In a 90-day double-blind, placebo-controlled trial of 120 subjects, daily oral supplementation with a liquid nutraceutical containing hydrolyzed fish collagen peptides, vitamins, antioxidants, and other ingredients produced a 40% increase in skin elasticity (p < .0001) versus placebo. Histological analysis of skin biopsies showed reduced solar elastosis and improved collagen fiber organization. Joint pain decreased by 43% and joint mobility improved by 39%. Self-perception questionnaires confirmed subjects felt more hydrated and elastic skin.
Czajka, Anna; Kania, Ewa M; Genovese, Licia; Corbo, Andrea; Merone, Giovanni; Luci, Cecilia; Sibilla, Sara ·
RPEP-03634 · 2018Adolescent VPA rats showed lower OXT mRNA levels, fewer oxytocin-immunoreactive (OXT-ir) cells in the hypothalamus, and reduced oxytocin concentrations in cerebrospinal fluid compared to controls. The oxytocin deficit was already present in neonatal VPA rats, with fewer OXT-ir cells in the supraoptic nucleus.
Acute intranasal oxytocin administration restored social preference in adolescent VPA rats, demonstrating immediate therapeutic potential.
Critically, early postnatal oxytocin treatment produced long-term effects: social impairments and repetitive behaviors were ameliorated through adolescence, and this behavioral improvement was accompanied by an increase in OXT-ir cells in the brain. This suggests early oxytocin intervention may have a developmental window of opportunity with lasting therapeutic benefits.
Dai, Yu-Chuan; Zhang, Hong-Feng; Schön, Michael; Böckers, Tobias M; Han, Song-Ping; Han, Ji-Sheng; Zhang, Rong ·
RPEP-03636 · 2018Paradoxically, BALB/c mice (the Leishmania-susceptible strain) showed significantly higher expression of all tested antimicrobial peptide genes (mBD-1, mBD-2, mBD-3, mBD-4, mBD-6, and CRAMP) compared to C57BL/6 mice (the resistant strain). Despite this higher AMP expression, BALB/c mice still developed cutaneous leishmaniasis.
The cytokine profiles confirmed expected immune responses: susceptible BALB/c mice had elevated IL-10 (anti-inflammatory) and reduced IL-12, while resistant C57BL/6 mice showed the opposite pattern. This demonstrates that elevated antimicrobial peptide expression alone cannot overcome Leishmania infection when the broader immune response is skewed toward susceptibility.
Daneshvar, Hamid; Tavakoli Kareshk, Amir; Sharifi, Iraj; Keyhani, Alireza; Tavakoli Oliaee, Razieh; Asadi, Arash ·
RPEP-03639 · 2018Antibiotic-peptide conjugates (APCs) combine known antibiotics with antimicrobial, cell-penetrating, or membrane-active peptides via chemical linkers. The strategy targets multiple bacterial resistance mechanisms simultaneously: efflux pump activation (which reduces intracellular antibiotic concentrations), target site protection proteins, and mutations in DNA/topoisomerase genes that alter binding sites.
The conjugation approach aims to produce synergistic antibacterial activity while mitigating individual limitations — improving cellular penetration of antibiotics while reducing the serum instability, cytotoxicity, hemolysis, and salt sensitivity that limit standalone antimicrobial peptides.
David, Akinwale Ajayi; Park, Shang Eun; Parang, Keykavous; Tiwari, Rakesh Kumar ·
RPEP-03645 · 2018Cell penetrating peptides (CPPs) are short peptide sequences that can cross cell membranes — a feat that most therapeutic molecules cannot accomplish. This review classifies CPPs into categories based on their origin and properties, describes their uptake mechanisms (direct penetration vs. endocytosis), and catalogs their biomedical applications as delivery vehicles for nucleic acids, proteins, siRNA, drugs, and nanoparticles.
The key insight is that CPPs can carry virtually any type of therapeutic cargo across cell membranes, making them one of the most versatile drug delivery tools in biomedical research.
Derakhshankhah, Hossein; Jafari, Samira · Review
RPEP-03652 · 2018Sodium phenylbutyrate (PBA) boosted the production of beta-defensins (pBD-1, pBD-3) and other host defense peptides in porcine intestinal cells through two independent mechanisms: TLR2/TLR4-mediated activation of the NF-κB inflammatory pathway, and histone modification (HDAC inhibition and histone H3 phosphorylation). Critically, PBA increased defensin production without triggering an excessive inflammatory response.
The study also identified that p38-MAPK and EGFR signaling pathways are involved in regulating this defensin induction. This dual mechanism — immune receptor activation plus epigenetic modification — suggests that dietary compounds could be used to boost the body's natural antimicrobial peptide defenses in the gut.
Dou, Xiujing; Han, Junlan; Ma, Qiuyuan; Cheng, Baojing; Shan, Anshan; Gao, Nan; Yang, Yu · In Vitro
RPEP-03659 · 2018Researchers developed and validated a lab assay (SCiMetPep) that predicts how quickly peptide drugs break down at the subcutaneous injection site — a major factor in how much drug actually reaches the bloodstream. Using tissue from humans, rats, and minipigs, the assay measured degradation rates and identified the specific enzymatic breakdown products for insulin, lixisenatide, exenatide, liraglutide, and semaglutide.
The in vitro results matched published in vivo data well. When applied to a series of structurally related peptides, injection-site metabolic stability correlated with bioavailability — confirming that what happens to a peptide right at the injection site is a major determinant of how much drug your body actually absorbs. The assay can identify which parts of a peptide are vulnerable to breakdown, guiding chemists to design more stable versions.
Esposito, Simone; de Leonibus, Maria Lucia; Ingenito, Raffaele; Bianchi, Elisabetta; Orsatti, Laura; Monteagudo, Edith · Method Development / Validation Study
RPEP-03661 · 2018Metformin inhibited rat pituitary tumor cell growth through AMPK activation and suppression of the mTOR-p70S6 kinase pathway. Crucially, metformin maintained its ability to activate AMPK and inhibit cell growth even in cells treated with forskolin (an adenylyl cyclase activator) and in cells overexpressing the GHRH receptor stimulated with GHRH. This demonstrates that adenylyl cyclase over-activation — a hallmark of some pituitary tumors — does not prevent metformin from working, contradicting concerns that hyperactive cAMP signaling might negate AMPK-based therapies.
Faggi, Lara; Giustina, Andrea; Tulipano, Giovanni ·
RPEP-03664 · 2018In 34 alcohol-dependent individuals receiving baclofen 30 mg/day vs. placebo for one week in a double-blind crossover:
Outpatient phase (1 week of treatment):
- Acyl-ghrelin significantly increased (P=0.01)
- Leptin significantly increased (P=0.01)
- Amylin significantly increased (P=0.004)
- GLP-1 significantly increased (P=0.02)
Laboratory experiment (alcohol cue-reactivity + self-administration):
- Significant drug × time-point interactions for amylin (P=0.001) and insulin (P=0.03)
- Trend-level interactions for GLP-1 (P=0.06) and ACTH (P=0.10)
- No significant effect on alcohol drinking behavior (P≥0.05)
Prolactin, TSH, growth hormone, cortisol, and ACTH were also measured but showed less consistent changes.
Farokhnia, Mehdi; Sheskier, Mikela B; Lee, Mary R; Le, April N; Singley, Erick; Bouhlal, Sofia; Ton, Timmy; Zhao, Zhen; Leggio, Lorenzo ·
RPEP-03672 · 2018This review evaluated all non-insulin drugs studied as add-on therapies for type 1 diabetes, including pramlintide (an amylin analog), GLP-1 receptor agonists, DPP-4 inhibitors, SGLT1/SGLT2 inhibitors, metformin, sulfonylureas, and thiazolidinediones. The bottom line: none provided dramatic improvement. Average HbA1c reductions were a modest 0.2-0.5% (2-6 mmol/mol) across all drug classes.
At the time of publication, SGLT inhibitors were considered the most promising avenue for further development in type 1 diabetes. The authors identified obese type 1 patients, those with residual beta-cell function, and hypoglycemia-prone patients as subgroups most likely to benefit from adjunct therapy.
Frandsen, Christian Seerup; Dejgaard, Thomas Fremming; Madsbad, Sten; Holst, Jens Juul · Review
RPEP-03675 · 2018The stapled peptide EHBI2, designed to mimic the H-helix of the EGFR kinase domain, successfully disrupted the asymmetric kinase dimer interface required for EGFR activation. Peptide stapling notably enhanced cell permeation compared to the unconstrained version.
In cell-based assays, EHBI2 significantly reduced EGFR phosphorylation (the marker of EGFR activation) and phosphorylation of the downstream signaling substrate Akt, confirming disruption of the entire EGFR signaling cascade. This is the first H-helix-based compound targeting the asymmetric dimer interface of the EGFR kinase domain that can successfully inhibit EGFR activation and signaling.
Fulton, Melody D; Hanold, Laura E; Ruan, Zheng; Patel, Sneha; Beedle, Aaron M; Kannan, Natarajan; Kennedy, Eileen J ·
RPEP-03676 · 2018Pramlintide (an amylin analog peptide) significantly suppressed meal-stimulated glucagon responses in type 1 diabetes patients after 3–4 weeks of treatment. The glucagon area under the curve dropped by 63% (1,988 to 737 pg/mL/min, p<0.001), and the post-meal glucose rise dropped dramatically (11,963 to 2,493 mg/dL/min, p<0.01).
In contrast, liraglutide (a GLP-1 receptor agonist) had no effect on either glucagon or glucose responses during mixed-meal testing in type 1 diabetes — a striking failure for a drug that effectively suppresses glucagon in type 2 diabetes.
Galderisi, Alfonso; Sherr, Jennifer; VanName, Michelle; Carria, Lori; Zgorski, Melinda; Tichy, Eileen; Weyman, Kate; Cengiz, Eda; Weinzimer, Stuart; Tamborlane, William · Clinical Trial
RPEP-03691 · 2018The new assay achieved detection limits of 50-200 pg/mL for banned peptidic drugs under 2 kilodaltons, covering:
• Gonadotropin releasing hormone (GnRH) and its analogs
• Growth hormone secretagogues (GHS)
• Growth hormone releasing peptides (GHRPs)
• Desmopressin (a vasopressin analog)
The 'dilute-and-inject' strategy eliminated complex sample preparation while maintaining high sensitivity and specificity. The method combined two-dimensional liquid chromatography, DMSO-assisted electrospray ionization, and high-resolution mass spectrometric detection. A tailored reporter template facilitated rapid data review, enabling high-throughput screening.
Görgens, Christian; Guddat, Sven; Thomas, Andreas; Thevis, Mario ·
RPEP-03692 · 2018In a crossover trial comparing three lunch meals (control, avocado-inclusive, avocado-added):
- The avocado-added meal decreased the 3-hour GLP-1 AUC compared to control (P = 0.03)
- PYY3-36 and GIP showed negative associations with hunger, desire to eat, and 'how much could you eat' (all P < 0.001)
- PYY3-36 and GIP showed positive associations with fullness, satisfaction, and composite appetite score (all P < 0.001)
- GLP-1 was negatively associated with hunger and positively associated with satisfaction and composite score (all P < 0.05)
- Ghrelin (the hunger hormone) results were not highlighted as significant
Haddad, Ella; Wien, Michelle; Oda, Keiji; Sabaté, Joan ·
RPEP-03693 · 2018In a mouse melanoma model, gp100 peptide vaccine formulated in incomplete Freund's adjuvant (IFA) induced antigen-specific T cells that forcibly redirected other anti-CTLA-4-induced T cells away from the tumor to the vaccination site. This inflammatory trap was driven by a vicious cycle: T cells at the injection site recruited inflammatory monocytes via IFN-γ, which in turn attracted more T cells through CXCR3, ICAM-1, and CCL2 signaling — all dependent on the persistent IFA depot.
In contrast, non-persistent vaccine formulations — dendritic cell vaccines, viral vector vaccines, or water-soluble peptide formulations — synergized powerfully with both anti-CTLA-4 and anti-PD-L1 checkpoint blockade. These combinations achieved complete tumor regression, even in tumors that were primarily resistant to dual checkpoint blockade alone.
Hailemichael, Yared; Woods, Amber; Fu, Tihui; He, Qiuming; Nielsen, Michael C; Hasan, Farah; Roszik, Jason; Xiao, Zhilan; Vianden, Christina; Khong, Hiep; Singh, Manisha; Sharma, Meenu; Faak, Faisal; Moore, Derek; Dai, Zhimin; Anthony, Scott M; Schluns, Kimberly S; Sharma, Padmanee; Engelhard, Victor H; Overwijk, Willem W · Animal Study
RPEP-03697 · 2018Once-weekly GLP-1 receptor agonists effectively lower HbA1c and body weight in type 2 diabetes with a low risk of hypoglycemia. Semaglutide showed the greatest reductions in both HbA1c and body weight in head-to-head comparisons with exenatide ER and dulaglutide. Exenatide ER and dulaglutide demonstrated similar or superior efficacy to oral antidiabetic drugs. All once-weekly GLP-1 RAs were effective as both monotherapy and add-on therapy to various background medications including insulin. Gastrointestinal side effects (nausea, vomiting, diarrhea) were the most common adverse events.
Handelsman, Yehuda; Wyne, Kathleen; Cannon, Anthony; Shannon, Michael; Schneider, Doron ·
RPEP-03704 · 2018A strong correlation was found between maximum cortisol levels measured by the GHRP-2 test and the insulin tolerance test (r = 0.777, P < 0.001). In male subjects without functional adenoma (n = 104), the GHRP-2 test achieved high sensitivity (95%) and specificity (85%) for diagnosing adrenocortical insufficiency.
The results support using the GHRP-2 test as a substitute for the insulin tolerance test when evaluating HPA axis function in male patients free of functional pituitary adenomas. However, the test's performance was affected by sex and the presence of functional adenomas, limiting its applicability in those subgroups.
Hayakawa, Tomoaki; Kitamura, Tetsuhiro; Tamada, Daisuke; Mukai, Kosuke; Hayashi, Reiko; Takahara, Mitsuyoshi; Otsuki, Michio; Shimomura, Iichiro ·
RPEP-03705 · 2018A cell-penetrating peptide made of 16 histidine residues (H16) was successfully used to modify liposomes, creating a delivery system that enters cells and naturally targets lysosomes. The H16-modified liposomes (H16-Lipo) were internalized by human fibrosarcoma cells via multiple endocytosis pathways and localized specifically to intracellular lysosomes.
As proof of concept, the H16-Lipo delivered alpha-galactosidase A (GLA) — a lysosomal enzyme — to the lysosomes of GLA-knockdown cells and improved their proliferation. This demonstrates the system's potential for treating lysosomal storage diseases, where patients lack specific lysosomal enzymes.
Hayashi, Taiki; Shinagawa, Matsumi; Kawano, Tsuyoshi; Iwasaki, Takashi · In Vitro
RPEP-03708 · 2018The primary composite outcome of cardiovascular death, myocardial infarction, or stroke occurred in 338 patients (7%) in the albiglutide group at a rate of 4.6 events per 100 person-years, compared to 428 patients (9%) in the placebo group at 5.9 events per 100 person-years. This yielded a hazard ratio of 0.78 (95% CI: 0.68–0.90), demonstrating superiority of albiglutide over placebo (p=0.0006 for superiority, p<0.0001 for non-inferiority).
Safety outcomes were reassuring: acute pancreatitis occurred in 10 albiglutide vs. 7 placebo patients, pancreatic cancer in 6 vs. 5 patients, and medullary thyroid carcinoma in zero patients in both groups. Treatment-related deaths were rare (2 in albiglutide, 3 in placebo).
Hernandez, Adrian F; Green, Jennifer B; Janmohamed, Salim; D'Agostino, Ralph B; Granger, Christopher B; Jones, Nigel P; Leiter, Lawrence A; Rosenberg, Anne E; Sigmon, Kristina N; Somerville, Matthew C; Thorpe, Karl M; McMurray, John J V; Del Prato, Stefano ·
RPEP-03709 · 2018In this systematic review of 32 animal studies, angiotensin IV (Ang IV) improved cognitive performance in 7 of 11 studies in normal animals and 8 of 9 studies in cognitively impaired models. Ang IV and its analogs (including dihexa and Nle1-Ang IV) enhanced spatial working memory, passive avoidance, and object recognition. Angiotensin-(1-7) benefited memory in 2 of 3 studies and showed anti-dementia properties. The peptides were most effective when delivered directly into the brain (intracerebroventricularly) close to the time of learning or memory testing.
Ho, Jean K; Nation, Daniel A ·
RPEP-03726 · 2018Systematic screening of the 10 most frequently falsified peptide drugs from three suspected illegal internet pharmacies revealed:
Purity: ranged between 5% and 75% for cysteine-containing peptides — meaning up to 95% of some products were impurities rather than the intended drug
Elemental impurities:
- Multiple samples contained arsenic (As) at concentrations up to 10x the ICH toxicity limit for parenteral (injectable) drugs
- All arsenic was present in the more toxic inorganic form (confirmed by speciation analysis)
- One sample was contaminated with lead (Pb)
Other concerns: high variation in drug amount per unit, significant peptide-related impurities, and the presence of residual solvents from manufacturing
The study also flagged the inherent danger of some products being doping peptides or preclinical drugs not approved for human use.
Janvier, Steven; Cheyns, Karlien; Canfyn, Michaël; Goscinny, Séverine; De Spiegeleer, Bart; Vanhee, Celine; Deconinck, Eric ·
RPEP-03732 · 2018New single-cell molecular tools have revealed that gut sensory cells (enteroendocrine cells) are far more complex than previously thought. Key discoveries include: individual gut sensor cells can express both ghrelin and cholecystokinin — opposing appetite hormones — simultaneously, challenging the old 'one cell, one hormone' model. These cells are also capable of multimodal sensing and form direct synapses with nerves, providing a fast neural pathway for gut-to-brain signaling alongside slower hormonal communication.
The evolutionary perspective reveals that gut sensory epithelial cells are among the most ancient cell types, present even in Trichoplax, one of the first multicellular organisms.
Kaelberer, Melanie M; Bohórquez, Diego V · Review
RPEP-03733 · 2018A peptide vaccine targeting folate receptor alpha (FR) was safe and elicited or augmented immune responses in more than 90% of breast and ovarian cancer patients in a phase I trial. The vaccine used HLA-class II epitopes designed for broad population coverage regardless of HLA genotype. FR-specific T cell responses developed slowly (median 5 months to peak) but persisted for at least 12 months after vaccination. All patients tolerated the vaccine well, with no serious safety concerns.
Kalli, Kimberly R; Block, Matthew S; Kasi, Pashtoon M; Erskine, Courtney L; Hobday, Timothy J; Dietz, Allan; Padley, Douglas; Gustafson, Michael P; Shreeder, Barath; Puglisi-Knutson, Danell; Visscher, Dan W; Mangskau, Toni K; Wilson, Glynn; Knutson, Keith L ·
RPEP-03737 · 2018This review proposes BPC157, a cytoprotective peptide isolated from gastric juices, as a potential therapeutic agent for cancer cachexia. The authors present preclinical evidence that BPC157 may rescue from cancer cachexia through its explored modes of action, positioning it as a candidate for clinical trials.
Kang, Eun A; Han, Young-Min; An, Jeong Min; Park, Yong Jin; Sikiric, Predrag; Kim, Deok Hwan; Kwon, Kwang An; Kim, Yoon Jae; Yang, Donghwa; Tchah, Hann; Hahm, Ki Baik ·
RPEP-03740 · 2018Researchers used peptide stapling — a chemical technique that locks a peptide into a helical shape — on shortened versions of orexin-A to try to maintain their biological activity. The stapled peptides did activate orexin receptors, proving that the receptors can accommodate and respond to rigidly helical peptides. However, all stapled variants had reduced potency compared to the unmodified truncated peptide.
Stapling near the C-terminus (the business end of the peptide) completely killed activity. Central and N-terminal stapling positions kept the peptides active but weaker, likely because the rigid helix locked the peptide into a shape that wasn't quite optimal for receptor binding.
Karhu, Lasse; Weisell, Janne; Turunen, Pauli M; Leino, Teppo O; Pätsi, Henri; Xhaard, Henri; Kukkonen, Jyrki P; Wallén, Erik A A · In Vitro Study
RPEP-03742 · 2018Across 17 RCTs with 466 participants with neurodevelopmental disorders, intranasal oxytocin showed:
- Emotion recognition: no significant effect (Hedges' g = 0.08 — essentially zero)
- Empathy: moderate but non-significant effect (Hedges' g = 0.49)
- Theory of mind: small, significant effect (Hedges' g = 0.21)
Meta-regression found that none of the moderating variables — diagnosis type, participant age, oxytocin dose, or frequency of administration — predicted treatment response. This uniformly modest-to-null result across different conditions and dosing approaches suggests a fundamental limitation rather than a design problem that could be solved with optimization.
Keech, Britney; Crowe, Simon; Hocking, Darren R ·
RPEP-03747 · 2018Gastrin family peptides — specifically a modified CCK fragment called (pGlu-Gln)-CCK-8 and gastrin-17 — directly stimulate insulin secretion from pancreatic beta cells and promote beta-cell growth and survival. In cell studies, both peptides increased insulin release and boosted beta-cell proliferation while protecting against toxic damage. In live mice, (pGlu-Gln)-CCK-8 improved glucose disposal, enhanced insulin release, and reduced appetite.
The study also revealed that diabetes changes how CCK and gastrin are expressed in pancreatic islets: in diabetic mice, CCK shifted toward glucagon-producing alpha cells while gastrin shifted toward insulin-producing beta cells, suggesting these peptide systems actively adapt during disease.
Khan, Dawood; Vasu, Srividya; Moffett, R Charlotte; Irwin, Nigel; Flatt, Peter R · Preclinical Study (Cell + Animal)
RPEP-03748 · 2018While most manufactured bioactive peptides show negligible toxicity, some naturally occurring peptides and enzymes can induce significant toxicity. The review identifies six main safety concerns with biologically active peptides: intestinal wall disruption, erythrocyte and lymphocyte toxicity, free radical production, enzyme-mediated tissue damage, immune-mediated tissue damage, and direct cytotoxicity.
The authors advocate for systematic safety evaluation — particularly using in silico (computational) methods — before peptides are used in food production or pharmaceutical applications. They emphasize that both immunogenicity (immune reactions against the peptide itself) and direct toxicity need assessment, as the growing use of peptides across food, cosmetics, and medicine demands standardized safety protocols.
Khan, Fazlullah; Niaz, Kamal; Abdollahi, Mohammad · Review
RPEP-03750 · 2018Compared to placebo, low-molecular-weight collagen peptide (LMWCP) supplementation at 1,000 mg/day for 12 weeks showed:
- Significantly higher skin hydration at both 6 weeks and 12 weeks
- Significantly improved visual wrinkle assessment score at 12 weeks
- Three out of three skin wrinkling parameters significantly improved at 12 weeks
- Two out of three skin elasticity parameters significantly improved versus placebo at 12 weeks
- One elasticity parameter improved within the LMWCP group from baseline
- Zero adverse events reported throughout the study
The collagen peptides contained >15% Gly-X-Y tripeptide content including 3% Gly-Pro-Hyp, which are the bioactive sequences thought to stimulate skin collagen production.
Kim, Do-Un; Chung, Hee-Chul; Choi, Jia; Sakai, Yasuo; Lee, Boo-Yong ·
RPEP-03751 · 2018The engineering process involved several innovations:
1. Reduced non-specific cell binding by lowering HSPG-binding activity of the parent antibody
2. Added tumor specificity by fusing a cyclic peptide recognizing EpCAM (a tumor-associated marker) to the antibody's light chain
3. Engineered endosomal escape motifs into both the heavy chain (VH) and light chain (VL) variable domains
4. The final construct, epCT65, effectively localized to the cytosol of only EpCAM-expressing tumor cells
5. Achieved approximately 2-fold improved endosomal escape efficiency compared to constructs with escape motifs in either VH or VL alone
6. Maintained full IgG format, preserving stability and potential for clinical development
Kim, Ji-Sun; Park, Jae-Yeong; Shin, Seung-Min; Park, Seong-Wook; Jun, Sei-Yong; Hong, Jin-Sun; Choi, Dong-Ki; Kim, Yong-Sung ·
RPEP-03754 · 2018Long-pulsed 1064-nm Nd:YAG laser treatment significantly reduced erythema (redness) and increased dermal collagen production in LL-37-induced rosacea-like skin lesions. Laser-treated mice showed significantly higher mRNA levels of type I collagen, TGF-β (a growth factor that promotes tissue repair), and MMP-1 (an enzyme that breaks down damaged collagen) compared to untreated mice.
These results suggest the laser works by triggering MMP-mediated collagen remodeling — essentially clearing out disorganized connective tissue and replacing it with healthy new collagen, which addresses the dermal damage underlying rosacea rather than just treating surface symptoms.
Kim, Miri; Kim, Jongsic; Jeong, Seo-Won; Jo, Hyunmu; Park, Hyun Jeong ·
RPEP-03755 · 2018Researchers created bifunctional hybrid peptides by combining a mitochondrial targeting sequence (MTS) with the cell-penetrating peptide sC18. Not all MTS sequences were equally effective — careful selection was critical. The CPP sC18 served a dual role, driving both cellular uptake and sub-organelle entry into the mitochondrial matrix.
When conjugated to the cancer drug chlorambucil, the optimized hybrid peptide enhanced intracellular drug delivery, demonstrating its potential as a mitochondria-targeted drug carrier for cancer and other mitochondrial diseases.
Klimpel, Annika; Neundorf, Ines ·
RPEP-03756 · 2018Four 11-amino acid self-assembling peptide (P11-SAP) hydrogels were compared for their scaffold properties and effects on periodontal cells.
Single-component P11-SAP systems demonstrated:
- ~30% higher porosity than complementary systems
- Almost 2-fold higher protein adsorption
- 1.7-fold increase in cell adhesion and cellular growth versus complementary systems
- Significantly enhanced osteogenic (bone-forming) differentiation of human calvarial osteoblasts compared to standard culture surfaces
All four hydrogels were cytocompatible, with cell responses similar to standard culture surfaces. The differences in properties were directly attributable to amino acid composition, demonstrating rational design capability.
Koch, Franziska; Wolff, Anne; Mathes, Stephanie; Pieles, Uwe; Saxer, Sina S; Kreikemeyer, Bernd; Peters, Kirsten ·