RPEP-10370 · 2025Papain hydrolysis of winged bean seed protein produced ACE-inhibitory fractions. Three key subfractions were identified: F-12-12 (87.8% ACE inhibition, pI 10.0), F-16-6 (77.3% inhibition, pI 6.8), and F-16-2 (50.1% inhibition, pI 3.6). Sequencing identified 11 peptides via database search and 4 via de novo sequencing, totaling 15 unique ACE-inhibitory peptides. All were oligopeptides of 4-15 amino acid residues with molecular weights of 489.9-1656.7 Da (all <2 kDa).
Chay, Shyan Yea; Brishti, Fatema Hossain; Auwal, Shehu Muhammad; Abdul Kari, Zulhisyam; Roslan, Nurdiyana Aqilah; Wong, Clement Kiing Fook; Saari, Nazamid ·
RPEP-10372 · 2025The peptide nanofiber-nanoceramic composite passed all ISO 10993 biocompatibility evaluations conducted by IFDA laboratories. Specific results included: non-cytotoxic with no significant reduction in cell viability, acceptable hemolytic activity in blood compatibility testing, no evidence of DNA damage in genotoxicity assays, no irritation or sensitization reactions, and no adverse clinical signs, weight changes, or organ pathologies in systemic toxicity studies in mice.
In the bone regeneration study in rabbits, the material demonstrated complete and osteoinductive bone formation over one month. The self-assembling peptide nanofibers (15-20 nm) contribute osteogenic, angiogenic, and immunomodulatory properties while mimicking extracellular matrix architecture. The spherical nanohydroxyapatite (30-45 nm) and tricalcium phosphate provide the mineral component with optimized particle size, morphology, and pH stability for vascularized bone formation.
Chegeni, Solmaz; Tavakol, Hani; Rezayat, Seyed Mahdi; Tavakol, Shima ·
RPEP-10379 · 2025The composite hydrogel (EW/OKGM@GHK-Cu, or GEK) combined oxidized konjac glucomannan and egg white proteins cross-linked via Schiff base chemistry, loaded with the bioactive copper peptide GHK-Cu. The hydrogel demonstrated self-healing capability, meaning it could repair itself after damage.
The GEK dressing exhibited multiple therapeutic properties: antibacterial activity, anti-inflammatory effects, hemostatic function through tissue adhesion, and promotion of neovascularization (new blood vessel formation). These combined properties made it effective for skin regeneration in infected wound models, positioning it as a comprehensive wound management solution derived entirely from natural food sources.
Chen, Han; Yang, Pu; Xue, Ping; Li, Songjie; Dan, Xin; Li, Yang; Lei, Lanjie; Fan, Xing ·
RPEP-10382 · 2025Across six GLP-1 receptor agonists (exenatide, liraglutide, lixisenatide, dulaglutide, semaglutide, and tirzepatide), 19 distinct neurological adverse event signals were identified from 28,953 reports in the FAERS database spanning 2005–2024.
The most notable signals included dizziness, tremor, dysgeusia (taste distortion), lethargy, taste disorder, presyncope (near-fainting), parosmia (smell distortion), allodynia (pain from normally non-painful touch), and hypoglycemic unconsciousness.
Time-to-onset analysis showed a median latency of 32 days (IQR 7–122 days), with 45.28% of neurological events occurring within the first 30 days of treatment initiation. These signals were confirmed across multiple statistical methods including reporting odds ratios, proportional reporting ratios, information components, and empirical Bayes geometric means.
Chen, He; Liu, Sixing; Gao, Shuai; Shi, Hangyu; Yan, Yan; Xu, Yixing; Fang, Jiufei; Wang, Weiming; Chen, Huan; Liu, Zhishun ·
RPEP-10395 · 2025The review identifies and characterizes 10 antimicrobial neuropeptides with dual immune functions:
1. PACAP — anti-inflammatory, neuroprotective
2. VIP — immunosuppressive, anti-inflammatory
3. α-MSH — anti-inflammatory, antimicrobial
4. Ghrelin — anti-inflammatory, metabolic regulation
5. Adrenomedullin — vasodilatory, antimicrobial
6. NPY — immune cell modulation
7. Urocortin II — stress response, immunomodulation
8. CGRP — neurogenic inflammation, vasodilation
9. Substance P — pro-inflammatory, antimicrobial
10. Catestatin — antimicrobial, immune modulation
These neuropeptides share structural similarities with traditional antimicrobial peptides and are directly involved in innate immunity. Their specific receptors represent therapeutic targets for immune-related diseases.
Chen, Kaiqi; Wu, Xiaojun; Li, Xiaoke; Pan, Haoxuan; Zhang, Wenhui; Shang, Jinxi; Di, Yinuo; Liu, Ruonan; Zheng, Zhaodi; Hou, Xitan ·
RPEP-10401 · 2025In this RCT of 55 dementia patients, the experimental group receiving oral rehabilitation showed significantly lower histatin-5 (HTN-5) levels at 3 months (β=-0.08, effect size=0.72), improved salivary flow rate at 6 months (β=0.89, ES=0.89), and better oral health quality of life at 6 months (β=6.99, ES=1.31) compared to controls. Changes in salivary flow rate (β=4.03), HTN-5 level (β=-0.78), and beta-defensin 2 level (β=-0.91) at 3 months all predicted improved quality of life at 6 months (all p<0.05).
Chen, Ming-An; Yang, Yuan-Han; Liu, Ching-Kuan; Matsuo, Koichiro; Hsu, Chih-Cheng; Lin, Ying-Chu; Huang, Hsiao-Ling ·
RPEP-10403 · 2025The researchers built a two-step nanoparticle platform using flash nanocomplexation (FNC) technology. Liraglutide was first encapsulated in nanoparticles formed by tannic acid and aluminum ions held together by coordination and hydrogen bonding. These particles were then coated with positively charged hydroxypropyl trimethylammonium chloride chitosan (HTCC) to boost skin penetration.
The resulting nanoparticles demonstrated superior transdermal penetration compared to unformulated liraglutide, produced durable blood-sugar-lowering effects, and showed long-acting therapeutic efficacy against obesity in a mouse model.
Chen, Nipeng; Zeng, Zhipeng; Chen, Haolin; Liu, Hong; Zhang, Zhihui; Ke, Fangfang; Ji, Xiaoyu; Liu, Lixin; Zhang, Zhen; Chen, Yongming · Animal Study
RPEP-10404 · 2025In db/db diabetic mice treated with liraglutide (200 µg/kg/day for 6 weeks), multiple kidney-protective effects were observed:
- Improved renal function and reduced kidney fibrosis
- Upregulated antioxidant enzymes (T-SOD, GSH-Px, GSH)
- Reduced oxidative damage markers (8-OHDG, MDA, LPO, 4-HNE, 12-Lox, NOX4)
- Decreased iron deposition via reduced TfR1 (iron import) and increased FPN1 (iron export)
- Inhibited ferroptosis through activation of the Fsp1-CoQ10-NAD(P)H pathway
In vitro experiments confirmed that liraglutide protected cells from high glucose-induced viability decline and lipid peroxidation through the same pathway.
Chen, Qi; Song, Ji-Xian; Zhang, Zhi; An, Ji-Ren; Gou, Yu-Jing; Tan, Miao; Zhao, Yashuo ·
RPEP-10409 · 2025CPPCGM, a deep learning framework using protein language models, achieved state-of-the-art performance in both identifying and generating cell-penetrating peptides. The classifier achieved Matthews correlation coefficient scores of 0.876, 0.923, and 0.664 across three benchmark datasets — significantly outperforming existing methods.
The generator component (similar to a generative adversarial network) successfully created novel CPP sequences not present in training data, with qualitative and quantitative evaluation confirming their CPP-like properties. The tool is publicly available on GitHub.
Chen, Qiufen; Zhang, Yuewei; Gao, Jiali; Zhang, Jun ·
RPEP-10410 · 2025Vasostatin-2, a bioactive peptide cleaved from chromogranin A, prevents artery re-narrowing after coronary stent placement. Patients with coronary restenosis had significantly lower serum vasostatin-2 levels than those without (p<0.001). In mice, recombinant vasostatin-2 inhibited neointimal hyperplasia after arterial injury by binding to ACE2, activating the NR1D1/Gas1 pathway, promoting smooth muscle cell death, and preventing their excessive proliferation. Mutant vasostatin-2 that couldn't bind ACE2 lost its protective effect.
Chen, Qiujing; Liu, Jingmeng; Madonna, Rosalinda; Li, Feifei; Chen, Shuai; Li, Leying; Wu, Xinrui; Maimati, Yipaerguli; Ding, Fenghua; Wang, Xiaoqun; Shen, Ying; Zhang, Ruiyan; Shen, Weifeng; Dai, Yang; Lu, Lin; De Caterina, Raffaele ·
RPEP-10414 · 2025A bacteria-based biohybrid system (P/L@EcN) combining the probiotic E. coli Nissle 1917 with nanoparticles loaded with the anticancer peptide ruxotemitide (LTX-315) successfully suppressed tumor growth in a mouse breast cancer model. The system achieved enhanced tumor accumulation and penetration, triggered cancer cell death through pyroptosis (caspase-1-dependent), remodeled the tumor immune environment by boosting M1 macrophages and reducing immune-suppressive MDSCs, and showed no systemic toxicity.
Chen, Shiyi; Ouyang, Xunping; Wei, Xue; He, Gang; Xian, Yiwen; Zhang, Chong; Wu, Decheng · Animal
RPEP-10425 · 2025Liraglutide (200 μg/kg/day for 8 weeks) improved glucose metabolism, cardiac remodeling, and heart function while reducing lipid peroxidation and ferroptosis in Goto-Kakizaki diabetic rats. The drug upregulated ferroptosis-related protective proteins including NRF2 (both cytoplasmic and nuclear forms), GPX4, and FTH-1.
In cell culture, high glucose triggered lipid reactive oxygen species production, reduced mitochondrial mass, and lowered ferroptosis-protective proteins — effects that were reversed by liraglutide treatment. Silencing NRF2 with siRNA abolished liraglutide's protective effects, confirming NRF2 as the key mediator of its anti-ferroptotic action.
Chen, Xuepin; Wang, Tianying; Gao, Yan; Wang, Guo An; Guan, Jun; Dai, Hongyan ·
RPEP-10435 · 2025This systematic review of 11 studies (7 preclinical, 4 human) found consistent signals that GLP-1 receptor agonists may protect cartilage, reduce inflammation, and relieve pain in osteoarthritis. Preclinical studies showed favorable chondroprotective and immunomodulatory effects with a dose-dependent response, primarily through inhibition of the NF-κB inflammatory pathway. The limited human studies supported these findings.
GLP-1 agonists were assessed for structural effects (cartilage protection), immunomodulation, analgesia, and molecular pathway effects in osteoarthritis. The evidence, while limited, was consistently positive across both animal and human studies.
Cheng, Jacinta; Solomon, Tia; Estee, Mahnuma; Cicuttini, Flavia M; Lim, Yuan Z · Systematic Review
RPEP-10444 · 2025Over 36 weeks of dose-escalated Mazdutide (2 mg → 4 mg → 6 mg weekly subcutaneous injections) combined with metformin and insulin, this 15-year-old patient achieved: 16.8 kg weight loss (18.89% BMI reduction from 30.64 kg/m²), HbA1c reduction of 21.88% (from 9.60%), uric acid decrease of 37.00% (from 511 μmol/L), triglyceride reduction of 69.02%, total cholesterol decrease of 13.65%, LDL cholesterol decrease of 17.27%, and complete resolution of hepatic steatosis by week 14. No hypoglycemic episodes or adverse events occurred, and benefits were sustained after treatment.
Cheng, Wenfei; Chen, Zilong; Li, Puyu; Zhang, Yingyu; Ma, Yujin; Liu, Peng; Jiang, Hongwei ·
RPEP-10452 · 2025Antimicrobial peptides (AMPs) and peptidomimetics can be combined with conventional antibiotics, quorum sensing inhibitors, metal nanoparticles, and photoresponsive materials to create synergistic therapies that overcome antibiotic resistance. AMPs work primarily by disrupting bacterial cell membranes — a mechanism fundamentally different from conventional antibiotics — which gives them broad-spectrum activity and lower risk of resistance development.
Advanced delivery systems including nanoparticles, hydrogels, microneedle patches, and inhaled formulations can enhance AMP targeting, prolong therapeutic duration, and reduce systemic toxicity. The review argues that combining AMPs with other antimicrobial agents through smart delivery platforms represents the most promising strategy for addressing the global antibiotic resistance crisis.
Chi, Jiaying; Lin, Qiaoni; Jin, Bingrui; Ou, Jiayu; Jiang, Ling; Yang, Xinyu; Guo, Jialiang; Peng, Tingting; Lu, Chao · Review
RPEP-10469 · 2025Among 38,524 patients with type 2 diabetes:
- GLP-1RAs reduced hepatic decompensation risk by 42% vs sulfonylureas (HR 0.58, 95% CI 0.38-0.88)
- SGLT2is reduced risk by 35% vs sulfonylureas (HR 0.65, 95% CI 0.43-0.98)
- GLP-1RAs reduced risk by 41% vs DPP4is (HR 0.59, 95% CI 0.39-0.89)
- Per-protocol analysis showed even stronger GLP-1RA protection (HR 0.43, 95% CI 0.22-0.82, a 57% risk reduction)
- No significant difference between GLP-1RAs and SGLT2is
- 1,743 hepatic decompensation events occurred over median 3.1 years follow-up
Choi, Jonggi; Verma, Ana; Nguyen, Vy H; Przybyszewski, Eric; Song, Jiunn; Carroll, Allison; Michta, Megan; Almazan, Erik; Simon, Tracey G; Chung, Raymond T ·
RPEP-10471 · 2025Semaglutide treatment led to significant reductions in both fat and lean mass in high-fat diet-fed mice. Skeletal muscle OXPHOS efficiency (ATP produced per O2 consumed) increased in permeabilized muscle fibers after semaglutide treatment. Mitochondrial proteomics revealed changes in only two proteins — LYRM7 and TTC19 — both linked to complex III assembly (p<0.05 without multiple testing corrections). No substantial changes in the abundance of OXPHOS subunits were observed, suggesting the efficiency gain comes from assembly optimization rather than increased mitochondrial content.
Choi, Ran Hee; Karasawa, Takuya; Meza, Cesar A; Maschek, J Alan; Manuel, Allison M; Nikolova, Linda S; Fisher-Wellman, Kelsey H; Cox, James E; Chaix, Amandine; Funai, Katsuhiko ·
RPEP-10473 · 2025In a first-in-human investigation, researchers recorded electrical activity directly from the nucleus accumbens — a key brain reward center — of a patient taking tirzepatide (a dual GIP/GLP-1 receptor agonist used for obesity). After starting tirzepatide, the patient experienced increased episodes of severe food preoccupation. These episodes were preceded by a surge in slow-wave (delta-theta, ≤7 Hz) brain activity in the nucleus accumbens, suggesting that the drug modulates reward circuitry in ways that may paradoxically intensify food-related thoughts in some individuals.
Choi, Wonkyung; Nho, Young-Hoon; Qiu, Liming; Chang, Andrew; Campos, Gustavo; Seilheimer, Robert L; Wilent, W Bryan; Bakalov, David; Firdous, Nida; Kerr, Marie; Joshi, Disha; Maze, Gabriella; Topalovic, Uros; Batista, Daniel; Suthana, Nanthia; Amaro, Anastassia; Hayes, Matthew R; Cajigas, Iahn; Cristancho, Mario; Allison, Kelly C; Pesaran, Bijan; Scangos, Katherine W; Gold, Joshua I; Wadden, Thomas A; Halpern, Casey H · Case Study
RPEP-10474 · 2025In the marmoset monkey superior colliculus (a midbrain structure that directs eye and head movements), somatostatin-expressing neurons were found across all cellular layers, accounting for approximately 3–5% of total neurons. These somatostatin-positive neurons were confirmed to be inhibitory (GABAergic), with the highest density (~3,140/mm³) in the top layer (stratum griseum superficiale), decreasing deeper into the structure.
Notably, neither vasoactive intestinal peptide (VIP) nor neuropeptide Y (NPY) were found in any neurons in the superior colliculus, despite being clearly present in neighboring brain structures on the same tissue sections.
Chong, Melissa H Y; Cho, Emmanuel K L; Rosa, Marcello G P; Atapour, Nafiseh · Basic Research
RPEP-10478 · 2025In a propensity-matched cohort of 75,470 patients with type 2 diabetes followed for a median of 5.6 years, SGLT2 inhibitor users had a significantly lower risk of new-onset peripheral artery disease compared to DPP4 inhibitor users (HR 0.79, 95% CI 0.66–0.93). In a three-arm analysis, the risk of PAD was not statistically different between SGLT2 inhibitors and GLP-1 receptor agonists (HR 1.18, 95% CI 0.52–2.68), suggesting both newer drug classes offer similar vascular protection. The findings remained consistent across subgroups regardless of sex, age, or comorbid metabolic diseases.
Chou, Oscar Hou-In; Luo, Zhiyao; Chung, Cheuk To Skylar; Chan, Jeffrey; Li, Huixian; Lakhani, Ishan; Lee, Sharen; Lau, Dawnie Ho Hei; Zhang, Qingpeng; Liu, Tong; Wong, Wing Tak; Cheung, Bernard Man Yung; Lip, Gregory Y H; Leung, Fung Ping; Tse, Gary; Zhou, Jiandong ·
RPEP-10481 · 2025The review identifies three major computational approaches accelerating peptide design: structure-based design (modeling how peptides interact with their targets), molecular dynamics simulations (watching peptide behavior over time), and ligand-based approaches (learning from known active peptides). Machine learning and deep learning methods are increasingly central, with generative AI models now capable of proposing entirely novel peptide sequences. However, key challenges remain: training data is often inconsistent across databases, AI model predictions can be difficult to interpret, and the physics simulations (forcefields) used to model peptide behavior still need improvement.
Choudhury, Priyanka Ray; Mishra, Sai Kumar; Yadav, Siddharth; Singh, Shubhi; Mathur, Puniti ·
RPEP-10483 · 2025Researchers identified novel bioactive peptides from chhurpi — a traditional fermented cheese from the Indian Himalayas — that can inhibit ACE (angiotensin-converting enzyme, a key blood pressure regulator) and reduce oxidative stress markers. Two synthesized peptides stood out: LKPTPEGDL showed the most potent ACE inhibitory activity with an IC50 of 25.82 µmol, while HPHPHLSFM showed superior antioxidant activity by reducing hypochlorous acid (HOCl) with an EC50 of 0.29 mmol.
Both peptides also inhibited myeloperoxidase (MPO), an enzyme linked to inflammation and oxidative damage. The ACE inhibition worked through a non-competitive mixed mechanism, and the peptides retained activity even after simulated gastrointestinal digestion — a critical requirement for any food-derived peptide to be useful.
Chourasia, Rounak; Abedin, Md Minhajul; Phukon, Loreni Chiring; Sarkar, Puja; Sharma, Swati; Sahoo, Dinabandhu; Singh, Sudhir Pratap; Kumar Rai, Amit · In Vitro
RPEP-10484 · 2025A 56-year-old woman on erenumab (a CGRP receptor antagonist monoclonal antibody) for migraine prevention presented with bilateral atypical femur fractures (AFFs) after a mechanical fall. Imaging showed lateral cortical beaking — a hallmark of stress-related atypical fractures typically associated with bisphosphonate use. She required bilateral femoral intramedullary nailing.
The authors note that CGRP has roles in bone biology and that blocking it may affect bone formation, potentially linking CGRP antagonist therapy to atypical fracture risk. This appears to be an early report raising this safety concern.
Choy, Kenneth; McDonald, Jason J; Geiselmann, Matthew; Daubs, Gregory ·
RPEP-10490 · 2025GLP-1-based therapies predominantly reduce adipose tissue, including visceral and ectopic fat depots, but they also produce absolute reductions in lean mass representing 20-30% of total weight loss. This ratio is generally consistent with the lean-to-fat loss ratio seen with other forms of weight loss.
The review highlights sarcopenia (age-related muscle loss) and sarcopenic obesity as conditions of particular concern, given their overlap with the populations being treated with GLP-1 drugs. Data on dual and triple agonists (tirzepatide, retatrutide) are emerging but remain limited. The extent to which lean mass reduction translates into impaired muscle function or increased frailty vulnerability remains unclear.
Chrysavgis, Lampros; Mourelatou, Niki Gerasimoula; Koloutsou, Maria-Evangelia; Rozani, Sophia; Cholongitas, Evangelos ·
RPEP-10497 · 2025Viral insulin/IGF-1-like peptides (VILPs) from grouper iridovirus (GIV) are early viral genes that are secreted during infection. Key findings:
- VILPs activate both insulin receptor (IR) and IGF-1 receptor (IGF1R) phosphorylation and the PI3K pathway
- GIV-VILP selectively interacts with IGF1R in a dose- and time-dependent manner
- Paradoxically: IR inhibition suppresses viral replication, while IGF1R inhibition enhances it, and IGF-1 stimulation reduces replication
- VILPs compete with host IGF-1, attenuating IGF1R signaling and reducing cell proliferation
- This viral mimicry mechanism was confirmed in a zebrafish infection model with transcriptome analysis showing negative regulation of cell cycle pathways
Chuard, Aurelien; Nesarajah, Kalaimagal; Danazumi, Khadija; Reiners, Kaitlin; Zhang, Fa; Levintov, Lev; Lubos, Marta; Žáková, Lenka; Ruggera, Rachel; McMenamin, Sarah; Vashisth, Harish; Jiráček, Jiří; Dimarchi, Richard; Altindis, Emrah ·
RPEP-10499 · 2025After 3 months on compounded semaglutide/cyanocobalamin, 94 participants lost an average of 4.11 kg (4.57% of body weight). Fat mass decreased by 2.67 kg and trunk fat by 1.10 kg. Lean mass decreased by 1.43 kg and skeletal muscle by 0.88 kg in absolute terms, but as a proportion of total body weight, lean and skeletal muscle mass actually increased while fat mass proportion decreased. This demonstrates that body composition improved despite some absolute lean mass loss.
Chun, Elizabeth; Siojo, Alexandra; Rivera, David; Reyna, Kirsten; Legere, Henry; Joseph, Richard; Pojednic, Rachele ·
RPEP-10509 · 2025The meta-analysis found statistically significant reductions across multiple cardiovascular endpoints:
- Hospitalization for heart failure: RR 0.24 (95% CI 0.12–0.57), a 76% reduction
- Cardiovascular death: RR 0.83 (95% CI 0.71–0.98), a 17% reduction
- All-cause death: RR 0.79 (95% CI 0.70–0.89), a 21% reduction
- Non-fatal myocardial infarction: RR 0.76 (95% CI 0.66–0.88), a 24% reduction
- Coronary revascularization: RR 0.76 (95% CI 0.69–0.85), a 24% reduction
- Stroke in diabetic patients: RR 0.65 (95% CI 0.44–0.97), a 35% reduction
Subcutaneous administration showed stronger cardiovascular effects than oral semaglutide (subgroup difference p=0.05). Semaglutide was associated with a higher relative risk of most adverse effects evaluated, though treatment discontinuation rates were only significantly higher for oral semaglutide.
Cleto, André Saad; Schirlo, João Matheus; Beltrame, Mayara; Gomes, Victor Hugo Oliveira; Acras, Isabela Hellmann; Neiverth, Guinter Sponholz; Silva, Breno Bach; Juliatto, Beatriz Moreira Salles; Machozeki, Janete; Martins, Camila Marinelli ·
RPEP-10513 · 2025P. gingivalis maintains an immunoevasive outer membrane containing nonphosphorylated lipid A (NPLA), which evades TLR4 detection, inflammasome activation, and LL-37 antimicrobial peptide killing. Simultaneously, it releases outer membrane vesicles (OMVs) enriched with C4'-monophosphoryl lipid A (C4'-MPLA) — a potent TLR4 agonist.
These OMVs serve as proinflammatory decoys: they engage and redirect TLR4 signaling, inflammasome activation, and LL-37 binding away from the bacterium. Both polymyxin B and the host defense peptide LL-37 blocked OMV-stimulated TLR4 activation in multiple cell types (HEK cells, THP-1 monocytes, endothelial cells). A mutant bacterium lacking the ability to dephosphorylate its membrane lipid A (ΔlpxF) retained C4'-MPLA on its surface and was killed by LL-37, confirming that lipid A modification is the key to immune evasion. Pg 381, which produced more OMVs, showed higher proinflammatory pathogenicity.
Coats, Stephen R; Su, Thet Hnin; Luderman Miller, Zoe; King, Alisa J; Ortiz, Joshua; Reddy, Angel; Alaei, Sarah R; Jain, Sumita ·
RPEP-10514 · 2025The review synthesizes several key findings from recent literature:
1. GLP-1 receptor agonists often surpass lifestyle interventions alone for weight loss and metabolic/cardiovascular improvements
2. Stopping GLP-1 therapy frequently leads to weight regain when lifestyle changes haven't been established
3. Exercise helps preserve muscle mass during GLP-1-mediated weight loss, which is critical because muscle loss reduces metabolic rate and functional capacity
4. Combining GLP-1 agonists with strength training and increased protein intake mitigates the muscle loss problem
5. Long-term weight maintenance is more successful when exercise is part of the treatment plan
6. Future obesity management will likely prioritize integrated pharmacotherapy + lifestyle approaches rather than medication alone
Codella, Roberto; Senesi, Pamela; Luzi, Livio ·
RPEP-10516 · 2025Using a validated diabetes outcomes model and participant-level data from EXSCEL, the researchers simulated how much of exenatide's cardiovascular benefits should result from its improvements in HbA1c, blood pressure, heart rate, LDL cholesterol, triglycerides, and weight.
The model could only explain modest proportions of the observed benefits: 29% for MACE (major adverse cardiovascular events), 15% for all-cause mortality, 18% for cardiovascular death, and 29% for stroke. The model explained more for hospitalization for heart failure (67%) and myocardial infarction (200% — meaning risk factors predicted more benefit than was actually observed for MI). Mediation analysis confirmed that changes in these conventional risk factors up to 12 months did not mediate the reduction in all-cause mortality.
Coleman, Ruth L; Adler, Amanda I; Mentz, Robert J; Fudim, Marat; Sattar, Naveed; Holman, Rury R · Human Rct
RPEP-10520 · 2025Compounding pharmacies and outsourcing facilities face significant legal risks from producing compounded semaglutide and tirzepatide. While drug shortages and lack of insurance coverage for weight-loss use created strong financial incentives, the regulatory framework creates substantial liability.
The review identifies multiple risk areas: FDA enforcement against compounders, patent and trademark infringement claims from brand manufacturers, state-level regulatory actions, and potential liability from adverse patient outcomes. The fact that weight loss prescribing typically falls outside federal healthcare programs reduces some kickback risks but doesn't eliminate the core compounding legality questions.
Combs, Blinn E; Howard, Brad · Review
RPEP-10525 · 2025IbKTP-NH2 was tested against multispecies biofilms containing C. albicans, P. aeruginosa, and S. pneumoniae on polymeric and metallic medical device materials:
- Minimum biofilm inhibitory concentrations (MBIC) ranged from 46.5 to 1 mM for bacterial strains
- SEM analysis showed significant biofilm disruption: reduced extracellular matrix production, decreased cell density, and altered cell morphology
- Effective on both polymeric and metallic surfaces relevant to medical devices
- Demonstrated potential antivirulence properties beyond direct antimicrobial killing
The peptide's dual origin — combining a neuropeptide (kyotorphin) with an anti-inflammatory (ibuprofen) — provides both antimicrobial and potentially anti-inflammatory activity.
Conceição, Katia; de Andrade, Vitor M; de Oliveira, Vitor D M; Ramu, Vasanthakumar G; Heras, Montserrat; Bardaji, Eduard R; Castanho, Miguel A R B; Capella, Aline G ·
RPEP-10528 · 2025The systematic review of 68 peer-reviewed papers established two key findings:
1. Cathelicidin plays a dual role in atopic dermatitis — it contributes to skin barrier function and has direct anti-Staphylococcus aureus activity. Reduced cathelicidin expression in AD patients weakens both defenses.
2. Vitamin D supplementation at 1,000-2,000 IU/day for 1-3 months increases cathelicidin expression and reduces S. aureus abundance and AD severity — but only in individuals with low serum vitamin D (deficiency/insufficiency). There was no evidence supporting supplementation in people with sufficient vitamin D levels.
Connell, Tess; Seidler, Karin; Neil, James ·
RPEP-10531 · 2025NT-proBNP levels were significantly elevated in Parkinson's disease patients with neurogenic orthostatic hypotension (adjusted P = 0.001) and in those with pathologically absent overshoot during the Valsalva Maneuver (adjusted P = 0.001). The peptide marker also correlated significantly with changes in systolic and diastolic blood pressure during the Head-up Tilt Test (P = 0.011 and P = 0.027, respectively) and with the blood pressure response in Valsalva phase III (P = 0.024).
ROC curve analysis revealed that NT-proBNP had high discriminatory power for detecting dysautonomia in Parkinson's patients, achieving an area under the curve of 0.917 (P < 0.0001). NT-proBNP levels also correlated with patients' self-reported cardiovascular symptoms.
Contaldi, Elena; Corradi, Marta; Percetti, Marco; Pilleri, Manuela; Calandrella, Daniela; Isaias, Ioannis U; Pezzoli, Gianni; Del Sorbo, Francesca ·
RPEP-10535 · 2025Nerve injury causes sensory neurons to start producing neuropeptide Y (NPY) — a pain-modulating peptide — for the first time. Researchers genetically deleted NPY specifically from sensory neurons in mice to test whether this newly produced NPY contributes to neuropathic pain. Surprisingly, removing NPY from sensory neurons had no effect on mechanical pain, cold pain, or ongoing pain in two different nerve injury models. The study found that NPY's pain-inhibiting role in the spinal cord is actually mediated by spinal cord interneurons releasing NPY, not by the sensory neurons themselves. This overturns a long-held assumption about the source of pain-modulating NPY after nerve injury.
Cooper, A H; Nie, A; Hedden, N S; Herzog, H; Taylor, B K · Animal Study
RPEP-10537 · 2025VB-87531 is a potent inhibitor of human MOGAT2 (IC50 = 17.4 nM) that, when administered to diet-induced obese mice:
Alone: reduced body weight, food intake, blood cholesterol, and glucose levels with no liver toxicity
Combined with tirzepatide: enhanced weight loss and reduced food intake vs. VB-87531 alone; dose-dependent modulation of both outcomes
Combined with semaglutide: similarly enhanced weight loss and reduced food intake vs. VB-87531 alone
Both combinations significantly lowered insulin and leptin levels while increasing FGF21 (a metabolic hormone linked to fat burning) and PYY (a satiety peptide). The synergistic effects suggest complementary mechanisms: VB-87531 blocks dietary fat absorption while GLP-1/GIP agonists suppress appetite and improve metabolic signaling.
Corbalan, J Jose; Petronella, Brenda A; Huang, Chia-Yu; Beasley, James R; Merritt, James R; Mugrage, Benjamin B; Nickels, Joseph T ·
RPEP-10542 · 2025In a post-hoc analysis of a 32-week, double-blind, placebo-controlled trial (semaglutide n=45, placebo n=39), semaglutide significantly decreased multiple epigenetic aging measures after adjustment for sex, BMI, hsCRP, and sCD163:
- PCGrimAge: -3.1 years (p=0.007)
- GrimAge V1: -1.4 years (p=0.02)
- GrimAge V2: -2.3 years (p=0.009)
- PhenoAge: -4.9 years (p=0.004)
- DunedinPACE: -0.09 units, approximately 9% slower pace of aging (p=0.01)
- OMICmAge: -2.2 years (p=0.009)
- RetroAge: -2.2 years (p=0.030)
Eleven organ-system clocks showed concordant decreases with semaglutide, most prominently in inflammation, brain, and heart clocks. An Intrinsic Capacity epigenetic clock was unchanged.
Corley, Michael J; Dwaraka, Varun; Pang, Alina Ps; Labbato, Danielle; Smith, Ryan; Eckard, Allison Ross; McComsey, Grace A ·
RPEP-10549 · 2025Fat mass reduction from baseline at 36 weeks was dose-dependent: 4.9% with retatrutide 0.5 mg, 15.2% with 4 mg, 26.1% with 8 mg, and 23.2% with 12 mg, compared to 4.5% for placebo and 2.6% for dulaglutide. Versus placebo, the 8 mg dose achieved a 21.6 percentage point greater fat reduction (p<0.0001). The 12 mg dose showed slightly less fat loss than 8 mg, though both were highly significant versus placebo.
Importantly, the proportion of lean mass loss relative to total weight loss was comparable to other obesity treatments, providing reassurance that retatrutide's superior weight loss doesn't come with disproportionate muscle loss. Adverse events were mainly gastrointestinal and similar across groups.
Coskun, Tamer; Wu, Qiwei; Schloot, Nanette C; Haupt, Axel; Milicevic, Zvonko; Khouli, Courtney; Harris, Charles ·
RPEP-10562 · 2025Semaglutide improved symptoms, functional capacity, and weight loss in HFpEF patients but did not reduce HF hospitalizations or mortality. Tirzepatide showed broader benefits, significantly reducing cardiovascular death and worsening HF events in obesity-related HFpEF. For HFrEF, clinical evidence supporting major outcome improvements is lacking, and concerns exist about increased HF hospitalizations, fluid retention, and arrhythmic risk. The review identifies a clear distinction between HFpEF (positive signal) and HFrEF (uncertain/cautious) for GLP-1 RA use.
Crispino, Simone Pasquale; Nusca, Annunziata; Ferro, Aurora; Cricco, Riccardo; Ciancio, Martina; Segreti, Andrea; Cavallari, Ilaria; Sabatino, Mario; Potena, Luciano; Ussia, Gian Paolo; Grigioni, Francesco ·
RPEP-10563 · 2025Co-administration of K-757 (GPR40 agonist) and K-833 (GPR119 agonist) in obese subjects produced dramatic increases in multiple gut peptide hormones: GLP-1 up 3.44x, active GLP-1 up 5.06x, PYY up 8.63x, GIP up 1.65x, CCK up 3.06x, and oxyntomodulin up 5.66x compared to placebo. In the 13-week Phase 2a trial (n=155), the combination produced placebo-adjusted weight loss of -2.78% (p<0.001) and blood pressure reductions of -6.9/-5.4 mmHg.
K-757 alone also elevated gut peptides and produced blood pressure reductions (-5.3/-3.2 mmHg), though weight loss was more modest (-1.42%, p=0.076). GI adverse events were more common with active treatment.
Crutchlow, Michael; Liu, Jiajun; Romero, Christopher; Watkins, Elaine; Zhang, Harry; Arreglado, Anna; Vance, Annemarie; Boisvert, Daniel; Terracina, Giuseppe; Chan, Bryan; Consolati, Matt J; Poterewicz, Gregory; Talaty, Jennifer E; Lauring, Brett ·
RPEP-10570 · 2025This paper describes the design of evoke and evoke+ — two large-scale, randomized, double-blind, placebo-controlled phase 3 trials testing oral semaglutide (14 mg daily) as a disease-modifying treatment for early-stage Alzheimer's disease. Each trial targets 1,840 participants (3,680 total) aged 55-85 with mild cognitive impairment or mild dementia due to Alzheimer's confirmed by amyloid biomarkers. Treatment lasts 156 weeks (104-week main phase + 52-week blinded extension). The primary endpoint is change in Clinical Dementia Rating - Sum of Boxes (CDR-SB) at 104 weeks. The trials also explore effects on AD biomarkers and neuroinflammation through plasma and CSF sub-studies.
Cummings, Jeffrey L; Atri, Alireza; Feldman, Howard H; Hansson, Oskar; Sano, Mary; Knop, Filip K; Johannsen, Peter; León, Teresa; Scheltens, Philip · Clinical Trial Protocol
RPEP-10572 · 2025Using wireless motility capsule testing, researchers measured transit times throughout the entire digestive tract in 10 patients taking GLP-1 receptor agonists. Delayed gastric emptying was observed in 80% of patients (8 out of 10). Delayed whole-gut transit was seen in 44% of patients.
Notably, the 3 patients on semaglutide at 1 mg had the longest gastric emptying times, the most delayed whole-gut transit, and were the only patients who also showed delayed small bowel transit time. This suggests semaglutide may have more pronounced effects on gut motility compared to other GLP-1 drugs in this series.
Cymbal, Michael; Naseem, Zehra; Hoxha, Din; Garg, Samita ·
RPEP-10577 · 2025A single injection of hydrogel-based depot formulations of either semaglutide or tirzepatide maintained therapeutic drug levels for over 6 weeks in a rat diabetes model. These single-dose formulations were equally effective at controlling blood glucose and body weight as daily injections of the same drugs in standard formulations. The hydrogel depot technology is easy to manufacture, injectable, and biocompatible, potentially enabling months-long treatment intervals.
d'Aquino, Andrea I; Dong, Changxin; Nguyen, Leslee T; Yan, Jerry; Jons, Carolyn K; Saouaf, Olivia M; Song, Ye Eun; Eckman, Noah; Kapasi, Sara; Williams, Christian Milton; Doulames, Vanessa Madelyn; Sen, Samya; Manna, Manoj K; Alakesh, Alakesh; Lu, Katie; Hall, Ian; Appel, Eric A ·
RPEP-10581 · 2025The systematic review of 26 articles (2004-2024) identified multiple molecular mechanisms by which glucocorticoids alleviate migraine:
- Reduced calcitonin gene-related peptide (CGRP) levels — CGRP is a neuropeptide central to migraine pathophysiology
- Decreased matrix metalloproteinase-9 (MMP-9) expression — MMP-9 degrades blood-brain barrier integrity
- Inhibited nitric oxide synthesis — nitric oxide drives vasodilation and sensitization
- Modulated transcription factors NF-κB and AP-1 — master regulators of inflammatory gene expression
- Reduced pro-inflammatory cytokines IL-1β and TNF-α
- Limited prostaglandin synthesis via COX-2 inhibition
These pathways collectively suppress both central and peripheral sensitization in the trigeminovascular system.
da Silva Lopes, Luciano; Krymchantowski, Abouch; Jevoux, Carla; Krymchantowski, Ana Gabriela; Maria Coelho de Moura, Camila M; Soares, Adriana A; de Sá, Marco Antônio Pereira; Val, Sabrina Nayara de Araújo; Dos Santos, Renato Mendes; Silva-Néto, Raimundo Pereira ·
RPEP-10584 · 2025GLP-1 receptor agonists, including dual GLP-1/GIP agonists like tirzepatide, demonstrate benefits beyond blood sugar control — including weight loss, improved metabolic health, and potential immune response modulation. Recent studies suggest they may help manage psoriasis and psoriatic arthritis in patients with obesity by reducing inflammation and addressing metabolic abnormalities like insulin resistance and hyperlipidemia. However, the evidence supporting their use specifically for psoriasis and psoriatic arthritis remains limited.
da Silva, Dimitri Luz Felipe; Singla, Shikha; Mease, Philip J ·
RPEP-10585 · 2025Alginate-based hydrogels provided sustained hBD-2 release for over 3 days with stable properties across pH 6-8. In vitro, hBD-2 hydrogels showed excellent biocompatibility and superior cell migration promotion compared to PP4-3.1 hydrogels. In a diabetic mouse wound model, hBD-2 hydrogels significantly: accelerated wound closure, improved re-epithelialization and tissue remodeling, reduced microbial wound load, decreased M1-like macrophages and M1/M2 ratio (shifting toward anti-inflammatory phenotype), reduced CD3+ cells, lowered reactive oxygen species levels, and increased neovascularization and collagen deposition.
Da Silva, Jessica; Leal, Ermelindo C; Gomes, Ana; Gomes, Paula; Calheiros, Daniela; Gonçalves, Teresa; Carvalho, Eugénia; Silva, Eduardo A ·
RPEP-10588 · 2025The probiotic bacterium L. plantarum TCCC11824 produces bioactive peptides that reduce obesity in mice fed a high-fat diet. The crushed bacterial supernatant (LpS) significantly improved blood lipid profiles, reduced liver injury, suppressed inflammation in liver and fat tissue, decreased ectopic fat accumulation, and positively shifted gut microbiota composition.
Researchers identified that the 3-10 kDa fraction of LpS strongly inhibited pancreatic cholesterol esterase and lipase and suppressed HMGCR expression in lipid-disordered cells. Among five predicted candidate peptides (IPR, IEK, PGDR, ETLVK, and QAEQLR), LC-MS/MS confirmed ETLVK as the key peptide responsible for the lipid-lowering effect.
Da, Jia-Yi; Wang, Chang; Feng, Xiaomin; Li, Han-Lu; Zhong, Feiliang; Luo, Xue-Gang ·
RPEP-10593 · 2025In the propensity score-matched cohort of 26,408 adults with obesity and autoimmune disease, GLP-1RA use was associated with significantly lower hazards for multiple outcomes compared to non-use:
- Stroke/TIA: HR 0.87 (95% CI: 0.76-0.99; P = 0.039) — 13% reduction
- Pulmonary embolism: HR 0.69 (95% CI: 0.56-0.86; P = 0.001) — 31% reduction
- Venous thromboembolism: HR 0.83 (95% CI: 0.72-0.95; P = 0.007) — 17% reduction
- ED visits: HR 0.79 (95% CI: 0.75-0.83; P < 0.001) — 21% reduction
- All-cause mortality: HR 0.56 (95% CI: 0.47-0.66; P < 0.001) — 44% reduction
Incidence rates per 1,000 person-years were consistently lower for GLP-1RA users across thromboembolic events.
Dai, Hao; Lee, Yao An; Natalie, Austin; Jackson, Whitney; Pham, Angela; Levine, Jake; Radwan, Rotana; Guo, Jingchuan; Bian, Jiang; Sheer, Amy J ·
RPEP-10595 · 2025In the GLP-1RA vs DPP4i comparison (n=4,920 matched pairs), GLP-1RA users had significantly lower risk of SUD hospitalization (HR 0.76; 95% CI: 0.67-0.86) and OUD hospitalization (HR 0.64; 95% CI: 0.43-0.96). AUD hospitalization showed a non-significant trend (HR 0.76; 95% CI: 0.53-1.08). No significant differences were found between GLP-1RA and SGLT2i users (n=4,620 matched pairs).
Dai, Hao; Radwan, Rotana M; Scheiffele, Grant D; Tang, Huilin; Sheer, Amy; Lin, Hsin-Yueh; Zhang, Pengyue; Adirika, Darlene; Luong, Kate; Bian, Jiang; Guo, Jingchuan ·
RPEP-10598 · 2025Eight weeks of exercise (aerobic, resistance, or combined) in diabetic mice altered gut microbiota composition, increasing Prevotellaceae and Ligilactobacillus. Fecal microbiota transplantation (FMT) from exercised donors to recipient mice:
- Elevated plasma GLP-1 by 0.92 pmol/L (P < 0.001) — surpassing exercise's own modest, non-significant GLP-1 increase
- Enriched Akkermansia in recipient gut
- Enhanced endothelial progenitor cell proliferation (P < 0.007) and migration (P < 0.05)
- Reduced blood glucose by 9.22 mmol/L (P < 0.001)
- Exercise alone reduced body weight by 10.58 g (P < 0.001, aerobic training)
Dai, Xia; Chen, Haiyan; Zhang, Milei; Yang, Qiong; Huang, Zheng; Tang, LiAn ·