RPEP-14527 · 2025In mice at simulated 4,000 m altitude, bovine collagen peptide (BCP) supplementation for 5 days produced an 8-fold increase in rotarod (balance/endurance) performance compared to controls (p<0.05).
In human volunteers exercising under hypobaric hypoxic conditions, BCP supplementation significantly improved blood oxygen saturation (SpO2) and physical performance metrics (p<0.001 for key measures). In vitro assays confirmed significant antioxidant activity. The peptide was characterized as rich in glycine, proline, and glutamic acid with confirmed peptide structure via FT-IR spectroscopy.
Zhang, Rui; Fu, Zi-Xian; Xiong, Jun-Bin; Guo, Wei-Hong; Shi, Wen-Pu; Jia, Bin; Shi, Jun-Ling; Yin, Da-Chuan ·
RPEP-14529 · 2025Among 17 GLP-1 receptor agonists across 137 trials (310 treatment arms, 56,683 patients), retatrutide 12 mg weekly produced the largest weight reduction (mean -26.56%, 95% CI: -43.89% to -3.01%). Tirzepatide 15 mg weekly was consistently effective across all populations: -22.76% in non-diabetic overweight/obese patients, -11.09% in Caucasian T2D patients, and -4.97% in Asian T2D patients.
Higher baseline body weight predicted better weight loss outcomes, while higher baseline HbA1c predicted better glycemic improvements. For HbA1c reduction, tirzepatide 10 mg and oral orforglipron 10 mg were the most effective agents. The analysis also revealed marked differences in weight loss efficacy between diabetic and non-diabetic populations and between ethnic groups.
Zhang, Shaolong; Yu, Boran; Xu, Jiamin; Jin, Siyao; Li, Yanming; Bing, Hao; Li, Jueyu; Ma, Xiangyu; Zhang, Xianhua; Zhao, Libo ·
RPEP-14531 · 2025Hunger-promoting AgRP neurons release NPY to decrease cAMP in hypothalamic MC4R neurons, while satiety-promoting POMC neurons release αMSH to increase cAMP. Each release event is all-or-none, stochastic, and affects multiple neurons within an approximately 100 µm diameter region.
The peptides compete: NPY signaling is blunted by high αMSH in the fed state, and αMSH signaling is blunted by high NPY in the fasted state. Eating resolves this competition by simultaneously boosting αMSH and suppressing NPY, sustaining elevated cAMP throughout a meal. This elevated cAMP progressively potentiates excitatory feeding-related synaptic inputs with each bite, gradually promoting satiation over many minutes.
Zhang, Stephen X; Kim, Angela; Madara, Joseph C; Zhu, Paula K; Christenson, Lauren F; Lutas, Andrew; Kalugin, Peter N; Sunkavalli, Praneel S; Jin, Yihan; Pal, Akash; Tian, Lin; Lowell, Bradford B; Andermann, Mark L ·
RPEP-14535 · 2025This review examines drugs that can prevent alcohol relapse in patients with alcohol-associated liver disease (ALD). Established medications like naltrexone and acamprosate reduce relapse in general alcohol use disorder but have limited data specifically in liver disease patients. Baclofen is the only drug tested in randomized trials in patients with cirrhosis, showing early benefit but mixed results in later studies.
Notably, emerging peptide-based therapies show early promise: GLP-1 receptor agonists, FGF21 (fibroblast growth factor-21) analogs, and psilocybin are all showing early signals for reducing alcohol use. Despite guideline support, these medications remain dramatically underused due to stigma, lack of provider training, and fragmented care.
Zhang, Wei; Hwang, Soo Young; Luther, Jay · Review
RPEP-14536 · 2025Researchers built a point-of-care electrochemical biosensor using cobalt nanoparticles embedded in nitrogen-doped hollow carbon nanostructures to detect exendin-4, a peptide drug used for type 2 diabetes. The best-performing sensor (Co3O4@HNCNs) detected exendin-4 at concentrations as low as 0.46 picomolar — an extremely sensitive threshold.
The sensor worked across a detection range of 1.0 to 90.0 pM with a sensitivity of 0.60 μA/pM. When tested on real human blood serum and urine samples, it achieved recovery rates of 96–104%, demonstrating practical accuracy for clinical use.
Zhang, Wei; Natarajan, Bharathi; Kannan, Palanisamy; Medlín, Rostislav; Nicolai, Laurent Christophe; Procházka, Michal; Minar, Jan; Subramanian, Palaniappan · In Vitro
RPEP-14539 · 2025The peptide FFRKSKEK (derived from the human LL-37 host defense peptide) showed high broad-spectrum antibacterial efficiency (>99%) against five clinically isolated methicillin-resistant bacteria — S. aureus, E. coli, S. epidermidis, E. cancerogenus, and P. aeruginosa — with just 15 minutes of ultrasound irradiation.
Critically, the peptide had negligible toxicity to mammalian cells and low self-antibacterial activity (meaning it only kills effectively when activated by ultrasound, providing a built-in safety mechanism). Molecular dynamics simulations revealed that ultrasound amplifies the peptide's membrane-penetrating ability through piezoelectric polarization of the diphenylalanine sequence, which also generates reactive oxygen species and disrupts bacterial electron transport chains. In a goat model of intervertebral infection — one of the most difficult infection sites to treat — the sonosensitive peptide produced better outcomes than vancomycin.
Zhang, Xiaoguang; Feng, Xiaobo; Ma, Liang; Lei, Jie; Li, Gaocai; Zhang, Weifeng; Liang, Huaizhen; Tong, Bide; Wu, Di; Yang, Cao; Tan, Lei ·
RPEP-14540 · 2025The M12-C peptide vaccine candidate showed multiple advantages: shortened vaccination schedule, enhanced antibody levels, and improved survival against both vaccine-type and non-vaccine-type streptococcal strains. M12-C antiserum demonstrated opsonization and killing of multiple non-vaccine strains (M1, M3, M6, M18). All three vaccine candidates induced Th1-type responses with IFN-γ secretion and increased effector memory T cells.
Zhang, Xiaolan; Ma, Yue; Na, Rige; Hou, Wenli; Hanski, Emanuel; Zhou, Qin ·
RPEP-14548 · 2025This is a trial protocol rather than a results paper. The study introduces a novel combination of individualized neoantigen peptide vaccines with critical lesion radiotherapy (CLERT) for stage IV cancer patients across multiple tumor types.
Key design features include a randomized 1:1 allocation with placebo control (rare in neoantigen trials), a crossover design allowing placebo patients to switch to the vaccine arm upon progression, and a basket-trial framework that leverages shared neoantigens across cancer types. The primary endpoints are progression-free survival and objective response rate.
Zhang, Yan; Hu, Ye-Fan; Ma, Lingyu; Wu, Yifei; Chao, Dandan; Chen, Xian; Xu, Zhiyuan; Su, Xiaoping; Dai, Wei; Huang, Jiandong; Fu, Pingfu; Kong, Feng-Ming Spring ·
RPEP-14554 · 2025Electroacupuncture at ST36 significantly increased gastric emptying rate, restored stomach slow-wave rhythms, and improved smooth muscle architecture in diabetic gastroparesis rats. The treatment reduced inflammatory infiltration and increased expression of nNOS, C-kit, and SCF — markers of healthy stomach nerve and muscle function.
The mechanism was mapped to a specific neural circuit: electroacupuncture activated vagal targets (ChAT and α7nAChR) at the stimulation site, sending signals through spinal segments L4-L6 to the nucleus tractus solitarius (NTS) in the brainstem, which then regulated gastrointestinal peptides (gastrin, motilin, and vasoactive intestinal peptide) and restored interstitial cells of Cajal function via vagal efferent pathways.
Critically, subdiaphragmatic vagotomy completely abolished the electroacupuncture-induced improvements in gastric motility and ICC recovery, confirming the vagus nerve is indispensable to this therapeutic effect.
Zhang, You; Tang, Yi-Wen; Zhou, Jin; Wei, Yan-Rong; Peng, Yu-Ting; Yan, Zi; Yue, Zeng-Hui ·
RPEP-14555 · 2025Combination therapy (nimodipine + statins) achieved 90% overall response rate versus 68% with nimodipine alone (p<0.05). After 7 days, the combination group had significantly lower endothelin-1 levels, higher CGRP levels, lower VEGF levels, higher peroxiredoxin 2 levels, and slower mean cerebral artery blood flow velocity (indicating less vasospasm). Adverse reactions occurred in only 6% of the combination group versus 20% with nimodipine alone (p<0.05).
Zhang, Yu; Ma, Feifan; Gan, Ning; Xu, Zhijie; Jiao, Yang; Zhang, Jiancang ·
RPEP-14557 · 2025Casein and whey hydrolysates reduced IBS symptoms (diarrhea, anxiety, visceral hypersensitivity), improved gut barrier proteins (ZO-1, claudin-1, occludin), decreased pro-inflammatory cytokines (IL-6, IL-1β, TNF-α), increased IL-10, reduced mast cell activation and PGE2 production, and reshaped gut microbiota. Three novel COX2-inhibitory peptides identified: RGPF (IC50 0.36 mM), FPK (IC50 0.64 mM), NPW (IC50 1.10 mM).
Zhang, Yu; Lin, Zhiqing; Yao, Qi; He, Jian; Feng, Haotian; Zhang, Wenyi; Liu, Zhigang; Yuan, Tian; Liu, Xuebo; Ding, Long ·
RPEP-14568 · 2025GLP-1 receptor agonists activated CaMKK2-AMPK signaling in the brain, which reduced BACE1-mediated cleavage of amyloid precursor protein and lowered amyloid-beta generation. Plasma GLP-1 levels were found to be decreased in Alzheimer's model mice and negatively correlated with amyloid-beta load in human patients with AD.
In microglia (the brain's immune cells), GLP-1RAs increased AMPK activity, which inhibited neuroinflammation and promoted the clearance of amyloid-beta through phagocytosis. The combined effects led to reduced amyloid plaque formation and improved memory deficits in transgenic Alzheimer's mice.
Zhang, Yun; Chen, Huaqiu; Feng, Yijia; Liu, Mingjing; Lu, Zhi; Hu, Bolang; Chen, Lifen; Zhang, Yang; Liu, Jiawen; Cai, Fang; Zhao, Yifan; Pan, Wenhao; Liao, Xinxin; Pan, Sipei; Bestard-Lorigados, Isabel; Wu, Yili; Song, Weihong ·
RPEP-14580 · 2025Liraglutide (a GLP-1 receptor agonist) outperformed metformin across multiple endpoints in women with PCOS and obesity. Compared to metformin, liraglutide produced greater improvements in glucose metabolism, lipid metabolism, BMI, leptin levels, and reproductive hormone levels (FSH, E2, LH) — all statistically significant (p<0.05).
Critically, liraglutide reduced methylation of the leptin promoter in ovarian granulosa cells more than metformin. The liraglutide group also had higher rates of menstrual cycle restoration, normal ovulation, and natural pregnancy compared to the metformin group.
Zhao, Hongli; Guo, Yanying · Retrospective Cohort
RPEP-14586 · 2025In the SURMOUNT-CN trial post hoc analysis (n=169), tirzepatide 10 mg reduced predicted 10-year T2D risk from 5.3% to 1.2%, and 15 mg from 4.9% to 1.0%, compared to placebo (5.8% to 4.5%) at week 52. The LS mean risk reductions versus placebo were -3.2% (95% CI: -4.2% to -2.2%) for 10 mg and -3.4% (95% CI: -4.4% to -2.4%) for 15 mg. Significantly greater reductions were observed across all subgroups regardless of baseline BMI status or prediabetes status.
Zhao, Lin; Tao, Feng; Cheng, Zhifeng; Lu, Yibing; Liu, Ming; Chen, Hong; Zhang, Min; Yang, Yang; Song, Xiang; Sun, Yuzi; Ma, Xiao; Si, Si; Zhang, Hanxi; Li, Xiaoying ·
RPEP-14591 · 2025The generative framework outperformed most existing computational models for designing antimicrobial peptides with specific activity against target bacteria. Key components and results:
- A conditional Variational Autoencoder (cVAE) was pretrained to generate AMPs with editable physicochemical properties (charge, hydrophobicity, etc.)
- A conditional diffusion model learned hidden representations of AMPs for targeting specific pathogens
- MIC (minimum inhibitory concentration) predictors were built for specific bacterial strains
- Systematic screening identified two 'star' AMP candidates for E. coli and two for S. aureus, each showing excellent antibacterial activity, low hemolysis, and favorable toxicity profiles
- The framework allows 'programmable' peptide design — specifying desired properties and target pathogen as inputs
Zhao, Weizhong; Hou, Kaijieyi; Tang, Chang; Shen, Yiting; Liu, Jinlin; Hu, Xiaohua ·
RPEP-14603 · 2025DiPGLa-H, a tandem-repeat variant of the frog-derived antimicrobial peptide PGLa, achieved a therapeutic index of 35.94 — meaning it kills bacteria at concentrations far below those that harm host cells. It was effective against E. coli, Staphylococcus aureus, and Acinetobacter baumannii, and disrupted biofilms formed by multiple pathogenic species.
In mouse peritoneal inflammation models, DiPGLa-H improved survival rates by 31–38% and reduced bacterial burdens in key organs by 100-fold to 1,000-fold. The peptide works by disrupting both inner and outer bacterial membranes, causing cell shrinkage, vesiculation, and intracellular content leakage.
A DAMP4 fusion protein strategy combined with non-chromatographic purification achieved high-purity biosynthesis with yields of 21.2 mg/mL, enabling cost-effective large-scale production.
Zheng, Liangjun; Zafir, Muhammad; Zhang, Ziqian; Ma, Yadong; Yang, Fengyi; Wang, Xiaokun; Xue, Xuemei; Wang, Chen; Li, Ping; Liu, Pilong; El-Gohary, Fatma A; Zhao, Xin; Xue, Huping ·
RPEP-14604 · 2025GLP-1 receptor agonists affect bone metabolism through multiple mechanisms relevant to both osteoarthritis and osteoporosis. These include anti-inflammatory effects, modulation of chondrocyte matrix metabolism (protecting cartilage), analgesic properties, promotion of bone formation, inhibition of bone resorption, and reduced fracture incidence. The review synthesizes evidence suggesting GLP-1RAs could serve as a dual-purpose therapeutic for these commonly co-occurring conditions.
Zheng, Meiqi; Zhao, Jingjing; Wang, Yuxuan; Cui, Zifan; Qiao, Zihong; Wu, Hongzhuo; Shi, Chenxia; Wang, Xiaofeng ·
RPEP-14610 · 2025The linear peptide composed of four (D-Trp)-(D-Arg)-(D-Lys) repeating units demonstrated robust antimicrobial activity against multidrug-resistant bacteria including MRSA and Klebsiella pneumoniae, with high stability and improved biocompatibility compared to typical antimicrobial peptides.
Critically, the peptide showed low potential for resistance development and the ability to alleviate existing resistance, restoring antibiotic sensitivity in resistant bacteria. This was attributed to its multiple simultaneous mechanisms: membrane targeting, non-membrane lysis through DNA binding, reactive oxygen species accumulation, ATP depletion, and metabolic interference. In vivo, the peptide showed therapeutic efficacy in both MRSA and K. pneumoniae pneumonia mouse models, as well as in a lipopolysaccharide-induced lung injury model.
Zhong, Chao; He, Yongtao; Zou, Jing; Gao, Luyang; Wang, Jiahui; Zhu, Jingyi; Xue, Wenjing; Gou, Sanhu; Zhang, Yun; Liu, Hui; Ni, Jingman ·
RPEP-14611 · 2025Liraglutide (a GLP-1 receptor agonist) protected human blood vessel cells from high-glucose-induced aging and dysfunction through a specific molecular pathway: SIRT1-mediated deacetylation of p53 and p65. At 1 μM concentration over 72 hours, liraglutide reduced cellular senescence markers, lowered reactive oxygen species (ROS) and oxidative stress, upregulated antioxidant defenses, and promoted new blood vessel formation and cell migration (all p<0.05).
Critically, when SIRT1 was knocked down, liraglutide's protective effects were diminished; when SIRT1 was overexpressed, the effects were enhanced. This establishes SIRT1 as the key mediator — liraglutide protects blood vessels by activating the same longevity-associated protein that caloric restriction and exercise stimulate.
Zhong, Weili; Yang, Ying; Wang, Yanru · In Vitro
RPEP-14612 · 2025Seven retrospective cohort studies involving 5,066,681 patients were analyzed. The pooled analysis found a significantly increased colorectal cancer risk in GLP-1 RA users compared to the reference population (RR 2.31; 95% CI: 1.82-2.93; I² = 36%; p < 0.0001).
However, when GLP-1 RA users were compared specifically to users of other diabetes drugs, the colorectal cancer incidence was not significantly different (OR 1.73; 95% CI: 0.21-14.18; p = 0.61; I² = 100%). The extremely wide confidence interval and 100% heterogeneity in this comparison indicate the data is highly inconsistent. Quality assessment showed low-to-moderate risk of bias across studies.
Zhong, Ying; Wu, Tingting; Khan, Najeeb Ullah ·
RPEP-14615 · 2025From over 68 million non-redundant gene sequences obtained through ultra-deep metagenomic sequencing of grassland plant phyllosphere microbiomes, researchers identified 885,396 potential antimicrobial peptides (AMPs). Of these, 99.76% were previously uncharacterized.
The researchers reconstructed hundreds of near-complete bacterial genomes, with 32.61% representing unclassified species. Of the biosynthetic gene clusters (BGCs) found in these genomes, 91.97% were also previously unknown.
Host plant family significantly influenced microbial biosynthetic capacity. Pseudomonas genomes associated with grasses (Poaceae) contained an average of 28 BGCs, significantly more than those associated with daisy-family plants (Asteraceae, mean = 14.76, p = 0.033).
Critically, all 13 AMPs synthesized via solid-phase peptide synthesis demonstrated real antimicrobial activity, each inhibiting at least one tested bacterial strain.
Zhou, Hongzhang; Gao, Yu; Wu, Baiyila; Xu, Gang; Tian, Limei; Sun, Yunlei; Yang, Fuyu; Ni, Kuikui ·
RPEP-14623 · 2025This review examines how unimolecular polypharmacology — designing single molecules that hit multiple receptors simultaneously — has transformed obesity and diabetes treatment. Blockbuster drugs like tirzepatide (GLP-1/GIP dual agonist) and retatrutide (GLP-1/GIP/glucagon triple agonist) have achieved unprecedented weight loss and blood sugar control, surpassing what single-receptor agonists can do.
Tirzepatide in particular has demonstrated remarkable effectiveness for weight loss, glycemic control, and additional cardiovascular and kidney benefits. However, the review also addresses ongoing challenges: gastrointestinal side effects, patient compliance (particularly with injections), and the problem of weight rebound when treatment stops.
Zhou, Qingtong; Li, Guanyi; Hang, Kaini; Li, Jie; Yang, Dehua; Wang, Ming-Wei · Review
RPEP-14628 · 2025The FFFGHK peptide self-assembled into an injectable, biodegradable, anti-swelling supramolecular hydrogel that demonstrated multiple therapeutic effects:
In vitro: eliminated reactive oxygen species (ROS), inhibited inflammatory responses, rescued cell apoptosis, accelerated neuron adhesion and proliferation, and promoted differentiation of neural stem cells into neurons.
In vivo (rats with SCI): significantly enhanced recovery of autonomous motor functions and signal transduction, and promoted neuronal regeneration at the injury site. The single-component design — combining the self-assembling phenylalanine (FFF) motif with the bioactive GHK tripeptide — created a material that serves simultaneously as a structural scaffold and a therapeutic agent.
Zhou, Xiaolin; Guo, Yanqiu; Gao, Zhan; Lv, Gan; Wang, Xiangyang; Zhang, Mengpei; Zhou, Yunlong ·
RPEP-14631 · 2025The lead candidate UTG-4, a stapled triple agonist targeting GLP-1R/GIPR/GCGR, demonstrated enhanced efficacy over semaglutide (GLP-1R monoagonist) and tirzepatide (GLP-1R/GIPR dual agonist) in obese mice across multiple endpoints: weight loss, food intake suppression, glucose tolerance, and liver health. In Apoe knockout mice (a model of atherosclerosis), UTG-4 showed remarkable anti-atherosclerotic effects. Mechanistically, UTG-4 alleviated endothelial-to-mesenchymal transition in human aortic endothelial cells — a key process driving atherosclerosis progression. The peptide achieved balanced bioactivity across all three receptor targets comparable to their native ligands, with improved pharmacokinetic properties.
Zhou, Yaqi; Tu, Longfang; Wang, Xueying; Xu, Jiean; Xu, Shujing; Ning, Xiao; Xiong, Xiaochun; Zheng, Nan ·
RPEP-14635 · 2025Larimicin78-102 demonstrated broad-spectrum antibacterial activity against common aquatic pathogens including Vibrio fluvialis, Pseudomonas fluorescens, and Pseudomonas putida, plus anti-biofilm activity against all three. The peptide killed bacteria by disrupting both outer and inner cell membranes, causing ATP leakage and intracellular reactive oxygen species (ROS) accumulation.
In vivo, Larimicin78-102 raised survival of V. fluvialis-infected large yellow croaker to 95%. The peptide also modulated the immune response: it reduced pro-inflammatory cytokines TNF-α and IL-1β while upregulating the anti-inflammatory factor IL-4. It boosted innate immune gene expression (piscidin, hepcidin, lysozyme) and enhanced lysozyme enzymatic activity. The peptide showed good thermal stability, cation tolerance, and no cytotoxicity or hemolytic activity.
Zhou, Zhenzhen; Chen, Fangyi; Hao, Hua; Wang, Ke-Jian ·
RPEP-14639 · 2025MASH and T2DM share a bidirectional feedback loop: impaired hepatic insulin signaling (from fatty liver) worsens blood glucose control, while chronic hyperglycemia and insulin resistance further drive liver inflammation and fibrosis. Key cellular players include hepatocytes, Kupffer cells (liver macrophages), hepatic stellate cells (which produce scar tissue), and pancreatic β-cells.
Emerging therapies targeting multiple pathways simultaneously show the most promise: GLP-1 receptor agonists and dual incretin agents address both metabolic and liver inflammation, while PPAR modulators, thyroid hormone receptor beta agonists (like resmetirom), FXR agonists, and FGF analogues target distinct but overlapping mechanisms. Non-coding RNAs were identified as important regulators of lipid metabolism and inflammation in both diseases.
Zhu, Bo ·
RPEP-14643 · 2025From the FAERS database (Q2 2018 to Q1 2025), 149 adverse event reports linked CGRP antagonists to Raynaud's phenomenon across 7 drugs:
- Erenumab had the most reports
- Fremanezumab showed the strongest adverse event signal across all four statistical methods
- Drug-gene network analysis identified key molecular nodes: AKT1, EGFR, ERBB2 for rimegepant
- KEGG pathway analysis revealed PI3K signaling as the most likely mechanism for small molecule CGRP antagonists (rimegepant, atogepant, ubrogepant) inducing Raynaud's
- The PI3K/AKT pathway connects CGRP blockade to vascular dysfunction
The authors recommend regular monitoring for Raynaud's in patients receiving CGRP antagonists, particularly those with underlying vascular dysfunction.
Zhu, Haibin; Ma, Minghua; Tian, Weiwei; Wu, Tingting; Wang, Yan; Huo, Yan; Liao, Xiaolan ·
RPEP-14655 · 2025Six unique peptides derived from yellow mealworm larvae (Tenebrio molitor) simultaneously inhibited two key diabetes-related enzymes: α-glucosidase (which breaks down carbohydrates into sugar) and DPP-IV (which degrades the GLP-1 hormone). The peptides — designated DK-7, WK-6, GR-7, FK-8, SK-6, and DK-8 — also enhanced glucose uptake in insulin-resistant liver cells (HepG2).
Molecular docking revealed how the peptides bind to both enzymes through hydrogen bonds and hydrophobic interactions at specific active site residues, establishing a dual-target inhibition mechanism from a single food-derived peptide source.
Zhu, Yuying; Zhou, Enning; Tang, Yingran; Li, Qiangqiang; Wu, Liming · In Vitro
RPEP-14656 · 2025Researchers discovered the neural circuit that drives hedonic eating — consuming palatable food purely for pleasure, not hunger. A specific pathway from the peri-locus ceruleus to VTA dopamine neurons controls this behavior: these neurons encode how tasty food is and drive continued consumption.
Critically for the GLP-1 drug field, semaglutide initially suppressed these dopamine neurons during food consumption, but mice developed tolerance — recovering both their palatable food appetite and dopamine neuron activity during repeated semaglutide treatment. When researchers artificially inhibited these dopamine neurons during eating, the tolerance was reversed. This reveals that the dopamine pleasure system actively fights against semaglutide's appetite-suppressing effects.
Zhu, Zhenggang; Gong, Rong; Rodriguez, Vicente; Quach, Kathleen T; Chen, Xinyu; Sternson, Scott M · Basic Research (Mouse Neuroscience)
RPEP-14657 · 2025Across 15 RCTs with 11,179 patients, zavegepant 10 mg nasal inhalation significantly outperformed placebo for pain freedom at 2 hours (RR = 1.54, 95% CI: 1.28-1.82) and most bothersome symptom freedom at 2 hours. However, zavegepant did not demonstrate significant superiority over oral CGRP receptor antagonists in either efficacy or long-term symptom relief. On safety, zavegepant 10 mg had more adverse events than placebo but was not inferior to oral gepants.
Zhu, Zixiang; Tang, Yanbing; Li, Longyuan; Ni, Hanyu; Liu, Meirong; Chen, Zhouqing; Wang, Zhong ·
RPEP-14659 · 2025In a double-blind randomized trial of 731 patients with heart failure with preserved ejection fraction (HFpEF) and obesity, tirzepatide (up to 15 mg weekly) produced comprehensive improvements across every clinical measure over a median of 104 weeks.
Compared to placebo, tirzepatide reduced the combined risk of cardiovascular death or worsening heart failure events by 33–59% (hazard ratios 0.41–0.67 depending on analysis). At 52 weeks, tirzepatide improved the Kansas City Cardiomyopathy Questionnaire score by 6.9 points, increased 6-minute walk distance by 18.4 meters, improved quality of life (EQ-5D-5L), improved NYHA functional class, enhanced patient-reported well-being, and reduced heart failure medication burden. The hierarchical composite win ratio was 1.63, meaning tirzepatide patients were 63% more likely to have a better outcome than placebo patients.
Zile, Michael R; Borlaug, Barry A; Kramer, Christopher M; Baum, Seth J; Litwin, Sheldon E; Menon, Venu; Ou, Yang; Weerakkody, Govinda J; Hurt, Karla C; Kanu, Chisom; Murakami, Masahiro; Packer, Milton · Rct
RPEP-14661 · 2025A 68-year-old male with BMI 31.2 and HbA1c 5.9% was treated with tirzepatide. Results:
- Total weight loss: 28.7 lbs (BMI dropped from 31.2 to 26.8)
- Skeletal muscle mass loss: 9.9 lbs (34% of total weight loss)
- Both body weight and muscle mass decreased by approximately 15% from baseline
- HbA1c normalized from 5.9% to 5.3%
The proportional nature of the muscle loss — roughly matching the percentage of total weight lost — suggests muscle wasn't being disproportionately targeted. However, losing a third of all weight as muscle is still clinically significant, particularly in an older patient at risk for sarcopenia.
Zinn, Jessica; Poretsky, Leonid ·
RPEP-14668 · 2025Pretreatment with a 100:1 CBD:THC ratio (100 mg/kg CBD, 1 mg/kg THC) administered intraperitoneally rescued CGRP-induced light aversion in CD1 mice. The cannabinoid combination also rescued increased resting time in darkness, decreased zone transitions, and partially rescued decreased rearing behavior caused by centrally administered CGRP.
Importantly, the automated squint assay showed that CBD:THC pretreatment partially rescued CGRP-induced spontaneous pain. An open field assay confirmed that the CGRP effects were migraine-specific (light aversion) rather than general anxiety, strengthening the specificity of both the migraine model and the cannabinoid rescue effect.
Zorrilla, Erik; Duong, Thomas L; Piña, Cassandra L; Russo, Andrew F ·
RPEP-14671 · 2025Molecular dynamics simulations revealed how tirzepatide activates both the GLP-1 and GIP receptors. The receptor activation involves a closure-to-open transition in the extracellular domain and movement of transmembrane helices — similar to how simpler class A receptors activate. Tirzepatide's conserved residues bind similarly to both receptors, but mutations in non-conserved residues create a biased binding pattern: C-terminal mutations weaken binding to GLP-1R, while N-terminal mutations strengthen binding to GIPR. This explains tirzepatide's dual-agonist profile at the molecular level.
Zou, Xuejun; He, Yu; Gao, Ya; Wang, Jian; Zhang, John Z H · Computational
RPEP-14673 · 2025Incretin mimetics, including GLP-1 and GIP receptor agonists, have achieved first-line treatment status for type 2 diabetes and obesity due to high efficacy and positive impact on comorbidities such as sleep apnea and heart failure. Multiple agents are available with varying durations of action, dosing frequencies, and delivery devices. Patients require education on proper administration, expected side effects, and nutrition considerations. Future developments include dual- and triple-mechanism agents and new oral formulations in a rapidly developing therapeutic pipeline.
Zupec, Jason; Munger, Rebecca; Scaletta, Alice; Quinn, Diane H ·
RPEP-14674 · 2025Fasting oxyntomodulin (OXM) levels were significantly higher in obese individuals compared to overweight and healthy controls (p < 0.0001). OXM levels positively correlated with visceral fat mass and volume in the obese group.
Logistic regression showed that higher OXM was significantly associated with increased risk of obesity and insulin resistance, particularly in more advanced stages of weight gain. The findings suggest OXM could serve as a measurable indicator of visceral adiposity and early metabolic dysfunction.
Zwierz, Mateusz; Buczyńska, Angelika; Kościuszko, Maria; Sobieska, Katarzyna; Adamska, Agnieszka; Siewko, Katarzyna; Krętowski, Adam Jacek; Popławska-Kita, Anna · Cross Sectional
RPEP-14680 · 2025Systematic variant screening of PYY3-36 identified key amino acids responsible for Y2 receptor selectivity, potency, and stability. Combined with fatty diacid derivatization (attaching a fatty acid chain for albumin binding and extended half-life), this produced highly selective, long-acting Y2 receptor agonists.
In preclinical models:
- The analogs improved glucose metabolism in diabetic db/db mice
- Combined with a long-acting GLP-1 receptor agonist, they showed superior blood glucose lowering in diabetic ZSF1 rats compared to GLP-1 alone
- The combination also produced greater body weight loss than GLP-1 alone in a high-fat diet-induced mouse obesity model
One analog, PYY1875, has progressed into clinical trials for obesity, validating the drug development approach.
Østergaard, Søren; Jessen, Carsten; Paulsson, Johan F; Kasimova, Marina A; Conde-Frieboes, Kilian W; Straarup, Ellen Marie; Skyggebjerg, Rikke Bjerring; Ynddal, Lars; Sanfridson, Annika; Wulff, Birgitte S; Chambers, Adam P ·
RPEP-14683 · 2025No significant association between GLP-1RA therapy and suicidality across integrated meta-analytic evidence. Methodological limitations: heterogeneous definitions, inconsistent reporting, small event numbers. Ongoing surveillance recommended.
Ștefănescu, Cristina; Bratu, Elena Alexandra; Pelin, Ana Maria; Boroi, Denisa; Crecan-Suciu, Bianca Daniela; Ștefănescu, Victorița ·
RPEP-14688 · 2026Among 1,002 post-weight loss body contouring patients, complication rates did not differ significantly by weight loss method across all procedure types (panniculectomy, brachioplasty, thighplasty, breast surgery). Weight loss methods included bariatric surgery (67.9%), lifestyle modification (14.3%), combination therapy (10.1%), and GLP-1 pharmacotherapy alone (7.8%).
BMI at the time of surgery and diabetes were identified as independent predictors of increased postoperative complications, regardless of how the weight was lost. Each procedure type showed its own expected complication patterns, but the method of weight loss was not a factor.
Abbott, Erin N; Giannas, Emmanuel; Dorjsuren, Nomongo; King, Daniella; Li, Ruoying; Christopher, Adrienne; Gergoudis, Franklin; Gabriel, Allen; Perdikis, Galen; Assi, Patrick ·
RPEP-14690 · 2026Across six observational studies with 4,831,654 patients, pooled odds ratios showed no statistically significant increase in NAION with semaglutide versus non-GLP-1 RA comparators (OR=2.44; 95% CI 0.59–10.15; very low certainty). When compared specifically to SGLT2 inhibitors, the pooled OR was 0.72 (95% CI 0.38–1.35).
In adjusted time-to-event analyses, the pooled hazard ratio was 1.63 (95% CI 0.88–2.39; low certainty), but this estimate was fragile — removing one influential study shifted it to 1.92 (95% CI 1.03–2.81). By indication, the signal differed: type 2 diabetes patients showed a pooled aHR of 1.70 (95% CI 1.10–2.64; low certainty), while obesity/overweight patients showed no increased risk (aHR 0.47; 95% CI 0.19–1.13; moderate certainty).
Abdelaal, Abdelaziz; Serhan, Hashem Abu; Alsaadi, Mustafa; Yaldo, Luke; Gaier, Eric D; Elhusseiny, Abdelrahman M ·
RPEP-14694 · 2026In aluminum chloride-induced Alzheimer's model rats, liraglutide (0.3 mg/kg twice daily, subcutaneous) significantly ameliorated anxiety, depression-like behaviors, and memory function deficits compared to untreated aluminum-exposed rats.
Liraglutide therapy preserved brain histopathological structure and demonstrated antioxidant and anti-apoptotic properties. Most notably, liraglutide decreased hippocampal levels of oxidized LDL (oxLDL), lysophosphatidic acid (LPA), LPA receptor 1 (LPAR1), and β-secretase 1 (BACE1) compared to the aluminum chloride group. This oxLDL/LPA/LPAR1/BACE1 pathway represents a novel mechanism for liraglutide's neuroprotective effects, reported for the first time in this study.
Abo El-Magd, Nada F; Ramadan, Nehal M; Eraky, Salma M ·
RPEP-14699 · 2026A 59-year-old woman with type 2 diabetes and gastroparesis developed EDKA after initiating dulaglutide:
- She had discontinued SGLT-2 inhibitors one month before the event
- EDKA developed shortly after starting dulaglutide
- Presentation: nausea, vomiting, abdominal pain, modestly elevated glucose
- Laboratory findings confirmed EDKA (metabolic acidosis with ketones despite near-normal blood sugar)
- Successfully treated with intravenous insulin and fluid resuscitation
- Dulaglutide was discontinued, with no recurrence on follow-up
This case challenges the assumption that EDKA is primarily an SGLT-2 inhibitor complication and suggests GLP-1 RAs can trigger it in susceptible patients.
Adrejiya, Parth; Alhujaily, Ensaf; Abubaker, Mohammad; Dorenbush, Chelsae; Khouzam, Rami ·
RPEP-14700 · 2026A 45-year-old woman with metastatic carotid body tumor showed an excellent initial response to 177Lu-DOTATATE peptide receptor radionuclide therapy (PRRT). After disease progression with widespread metastases and spinal cord compression at multiple levels leaving her wheelchair-bound, rechallenge PRRT again produced an exceptional treatment response. This case demonstrates that retreatment with peptide-targeted radiation can be effective in somatostatin receptor-expressing paragangliomas.
Aggarwal, Piyush; Satapathy, Swayamjeet; Sarungbam, Bidya; Sood, Ashwani; Kumar, Rajender; Goyal, Shikha; Mittal, Bhagwant Rai ·
RPEP-14701 · 2026The review categorizes long COVID cardiovascular biomarkers into established and emerging groups. Established markers include cardiac troponins (heart muscle damage), natriuretic peptides BNP/NT-proBNP (heart stress and failure), D-dimer (clotting), and inflammatory markers like C-reactive protein and interleukin-6.
Emerging biomarkers with clinical potential include growth differentiation factor-15 (GDF-15, a stress-responsive peptide), galectin-3 (fibrosis and inflammation), von Willebrand factor (endothelial damage), endothelin-1 (a vasoconstrictor peptide indicating vascular dysfunction), and circulating microRNAs. The review emphasizes that no single biomarker is sufficient — combinations and longitudinal monitoring will be needed for effective clinical use in long COVID cardiovascular management.
Aguiar, Carlos Eduardo Oliveira; Costa, Juan Marcos Caram; Oliveira, Marina Maria Gomes Leite; Lopes, Caio Ferraz; Lima, Pedro Henrique Melo; Dietrich, Victoria Cenci; Grenfell, Rafaella Fortini Queiroz; de Melo, Fabrício Freire ·
RPEP-14703 · 2026The review identifies several key mechanisms:
1. Platelets and megakaryocytes are active synthesizers of host defense peptides, not passive carriers — representing a paradigm shift in understanding platelet biology.
2. Different peptides have distinct effects: LL-37 activates platelets via the glycoprotein VI (GPVI) receptor, while defensins stabilize fibrin clots through amyloid-like interactions.
3. HDPs function as concentration-dependent molecular switches — at lower levels they promote physiological repair, while at higher levels (during infection) they can drive pathological thromboinflammation.
4. The review proposes "adaptive thrombopoiesis" — a concept where systemic peptide surges during infection act as danger signals that reprogram newly formed platelets for enhanced immune function.
Aguilar-Ruiz, Sergio Roberto; Sánchez-Peña, Francisco Javier; Rodríguez-Magadán, Héctor Maximino; Domínguez-Martínez, Miguel Angel; Bernardino-Hernández, Héctor Ulises; Aquino-Domínguez, Alba Soledad ·
RPEP-14704 · 2026Researchers created PEGylated PLGA nanoparticles loaded with oxytocin (OT-NP-PEG) that successfully delivered the peptide from the nose directly to the brain in mice. The nanoparticles were 93–116 nm in diameter with sustained release (>42% at 24 hours, 58% at 72 hours) and showed greater diffusion through simulated nasal mucus than non-PEGylated versions.
Using radioactively labeled oxytocin ([14C] OT), the team demonstrated rapid brain uptake — particularly in the olfactory bulb and frontal cortex — with reduced accumulation in the blood and liver compared to free oxytocin. Mice treated with intranasal OT-NP-PEG showed increased self-grooming, confirming the oxytocin remained biologically active after delivery.
Ahmad, Naveed; Han, Shunping; Utami, Rifka; Baker, Rafal; Helal, Dina; Li, Zhuoni; Tricklebank, Mark; Paloyelis, Yannis; Wang, Julie; Petrinovic, Marija M; Bansal, Sukhi; Al-Jamal, Khuloud T · Animal Study
RPEP-14707 · 2026Researchers created hydrogels from peptide-polymer conjugates — short phenylalanine-histidine peptides linked to polyethylene glycol (PEG) chains. These conjugates self-assemble into beta-sheet nanofibers at acidic pH, forming cross-links that hold the hydrogel together.
Adding metal ions (cobalt, nickel, copper, or zinc) dramatically improved the hydrogel's mechanical properties. Metal coordination produced orders-of-magnitude higher network stability, expanded the range of stress the gel could withstand without breaking, and improved the gel's ability to recover after deformation. Each metal ion produced different effects depending on its coordination geometry, giving researchers a tunable toolkit for engineering gel properties.
The assembly was enthalpy-driven at low concentrations, but at high concentrations, chain stretching created an entropic penalty that limited network connectivity.
Ahmadi, Mostafa; Wittek, Kamila; Rieger, Hanna Sophie; Thomas, Marius; Hartmann, Lars; Besenius, Pol; Seiffert, Sebastian · Laboratory Study
RPEP-14708 · 2026The review synthesizes preclinical and limited clinical evidence showing that GLP-1 receptor agonists may address nicotine dependence through two mechanisms:
1. **Reduced nicotine cravings**: GLP-1 RAs modulate central reward pathways (mesolimbic dopamine system) that underlie nicotine's addictive properties, potentially reducing cravings and nicotine intake.
2. **Weight gain prevention**: The well-established appetite-suppressing and weight-loss effects of GLP-1 RAs could counteract the metabolic changes that follow nicotine withdrawal (increased caloric intake, reduced energy expenditure).
This dual mechanism could improve quit success rates while eliminating one of the primary psychological barriers to smoking cessation.
Ahmed, Ghazi Uddin; Zehra, Eiman; Rasheed, Sana; Akhtar, Syed Owais; Raza, Ahmed Asad; Mujaddadi, Khunsha; Samadi, Abedin ·
RPEP-14716 · 2026The review presents evidence that vitamin D stimulates the production of antimicrobial peptides (AMPs) across multiple cell types involved in viral defense:
- Natural killer cells, monocytes, neutrophils, and respiratory tract epithelial cells all produce AMPs in response to vitamin D signaling
- These AMPs exhibit broad-spectrum activity against viruses, bacteria, and fungi
- Beyond direct antimicrobial activity, AMPs serve as chemotactic agents (attracting immune cells) and promote cytokine and chemokine production (amplifying the immune response)
- AMPs are evolutionarily conserved and part of the innate immune system, making them effective against both known and novel pathogens
- Vitamin D appears to reduce viral survival and replication specifically through AMP induction
Akimbekov, Nuraly S; Digel, Ilya; Tastambek, Kuanysh; Rodriguez-Raecke, Rea; Kistaubayeva, Aida S; Sakhanova, Svetlana K; Wu, Xia; Razzaque, Mohammed S ·
RPEP-14720 · 2026GLP-1 receptor agonist users with diabetes had significantly higher total healthcare expenditures ($22,029) compared to non-users ($15,165). Use of GLP-1 RAs increased from 4.3% in 2016 to 10.6% in 2020 — roughly 1 in 13 adults with diabetes.
After adjusting for age, sex, race, obesity, physical activity, and other conditions, GLP-1 RA use was independently associated with significantly higher total, payer, and out-of-pocket expenditures (all p ≤ 0.001). The economic burden fell on both insurance systems and patients themselves.
Akpan, Nsima; Zhou, Bo; Rasu, Rafia S; Sambamoorthi, Usha · Cross Sectional