RPEP-16017 · 2026The chitosan-DOTAGA hydrogel formed in situ under physiological conditions via electrostatic and hydrogen bonding interactions, requiring no solvents. Pharmacokinetic comparison in rodents showed dramatic differences:
- IV injection: peptide cleared within 1 hour
- Free subcutaneous NX210c: eliminated within approximately 3 hours
- Hydrogel delivery: peptide levels sustained for 10-15 days with area under the curve (AUC) dozens of times higher than IV
In vivo studies confirmed subcutaneous injectability, gelation ability, biocompatibility, and complete biodegradation within a few weeks.
Rosson, Elise; Thomas, Eloise; Sidi-Boumedine, Jacqueline; Kryza, David; Couderc, Marie; Brichart, Thomas; Geloen, Alain; Montembault, Alexandra; David, Laurent; Lux, François; Godfrin, Yann; Tillement, Olivier ·
RPEP-16030 · 2026This systematic review of GLP-1 receptor agonist psychiatric effects found a mixed but intriguing picture: modest antidepressant effects were observed across studies, and there were signs of potential benefit for eating disorders and substance use disorders — conditions driven by reward system dysregulation. However, the link between GLP-1 drugs and suicidal thoughts remained inconclusive, with studies showing inconsistent results. In people with schizophrenia, GLP-1 drugs improved metabolic health but did not consistently affect psychiatric symptoms.
Sa, Brianna; Maristany, Anthony; Subramaniam, Ashwin; Guillen, Ryan; Buonocore, Brooke; Smith, Audrey; Oldak, Sean E; Padilla, Vanessa ·
RPEP-16046 · 2026GLP-1 receptor agonists have become first-line therapy for multiple clinical settings based on strong scientific evidence for obesity, type 2 diabetes, hypertension, heart failure, and cardiovascular disease. However, concerns about long-term adverse effects lead clinicians to prescribe them for limited periods, often discontinuing once weight reduction is achieved. The review examines evidence comparing the risks of long-term GLP-1RA use (potential adverse effects) against the risks of discontinuation (weight regain, loss of cardiovascular and metabolic benefits).
Salerno, Elia Nunzio Maria; Fumarulo, Isabella; Garramone, Barbara; Vaccarella, Marcello; Ierardi, Carolina; Burzotta, Francesco; Aspromonte, Nadia ·
RPEP-16054 · 2026Out of 3,267 proteins identified in carotid plaque tissue, 15 reached high-confidence significance (q ≤ 0.25) and were all upregulated in vulnerable plaques. These included matrix metalloproteinases (MMP7, MMP9, MMP1), neutrophil-derived proteins (cathelicidin antimicrobial peptide, azurocidin, lactotransferrin, myeloperoxidase), inflammatory regulators (interleukin-1 receptor antagonist, interleukin-4-induced protein), glycolytic enzymes (hexokinase-2 and hexokinase-3), and lipid-handling proteins (lipoprotein-associated phospholipase A2, apolipoprotein B, paraoxonase-1).
An additional 17 exploratory proteins showed nominal significance with at least a 2-fold change, and 366 more proteins reached nominal significance with smaller fold changes.
Sandoval, Camilo Polania; Meschia, James F; Prudencio, Mercedes; Gendron, Tania; Jacobs, Christopher; Beegle, Richard D; Sandhu, Sukhwinder J S; Mangalaparthi, Kiran K; Sung, Jaeyun; Zhao, Xiaowei; Nassar, Aziza; Farres, Houssam; Petrucelli, Leonard; Pandey, Akhilesh; Erben, Young ·
RPEP-16056 · 2026Using AI-guided computational design combined with experimental validation, researchers created a modified antimicrobial peptide called TPF-M1 that effectively kills MRSA (methicillin-resistant Staphylococcus aureus). Starting from a natural peptide called Temporin-PF, they optimized it computationally to achieve an improved anti-MRSA score of 600.0.
TPF-M1 showed enhanced killing activity against 10 different clinical MRSA isolates with good selectivity (meaning it targeted MRSA while showing low toxicity to human cells). At 20 μM, TPF-M1 also effectively reduced MRSA biofilm viability and disrupted biofilm structure — critical because biofilms are a major reason MRSA infections are so difficult to treat.
Santaweesuk, Parweenuch; Khumbungkha, Worada; Ngamsiri, Thararin; Pipattanaboon, Chonlatip; Phanthanawiboon, Supranee; Shoombuatong, Watshara; Kanthawong, Sakawrat · In Vitro
RPEP-16058 · 2026Researchers discovered a previously unknown peptide in the renin-angiotensin system called alamandine-(1-5), or Ala-(1-5). This five-amino-acid peptide is naturally present in the blood of both humans and rodents. It is formed from alamandine by ACE (angiotensin-converting enzyme) activity.
Ala-(1-5) produced a long-lasting blood pressure reduction (approximately 6 hours) in spontaneously hypertensive rats, associated with decreased cardiac output. It also increased baroreflex sensitivity, reduced heart contractility in isolated hearts and cardiomyocytes, and stimulated nitric oxide production through Mas, MrgD, and AT2 receptors. However, its effects on cardiomyocytes and blood vessels specifically required the MrgD receptor, distinguishing it from other renin-angiotensin system peptides.
Santos, Robson A S; Dias, Melissa Tainan Silva; Bessa, Amanda de Sá Martins; Barros, Carolina Fonseca; Itaborahy, Matheus F; da Silva, Filipe Alex; Gonçalves, Sthefanie Chaves de Almeida; Rodrigues-Ribeiro, Lucas; Ferraz, Kamylle Silva; Davel, Ana Paula; Nóbrega, Natália; Silva, Bruno Durante da; Scalzo, Sérgio; Soares, Pedro Alves; Dutra, João Batista Rodrigues; Lula, Ivana; Feng, Isadora Zhong Liang Ferreira; Vieira-Machado, Uri Flegler; de Godoy, Ana Caroline Ventris; Monteiro, Adelson Héric Alves; Eliezeck, Marcos; Sanches, Bruno; Monteiro, André; Magalhães, Gabriela; Soares, Nícia Pedreira; Pereira, Danilo Augusto Alves; Rezende Ribeiro, Júlia; Dias-Pinto, Maria Luiza; de Souza, Leandro Eziquiel; Silva, Amanda de A; Motta-Santos, Daisy; Bader, Michael; Alenina, Natália; Capettini, Luciano Dos Santos Aggum; Peliky Fontes, Marco Antônio; Haibara, Andrea Siqueira; Campos Vilella, Daniel; Verano-Braga, Thiago; Irigoyen, Maria Claudia; Marins, Fernanda Ribeiro; Castro, Carlos Henrique; Simões-E-Silva, Ana Cristina; Guatimosim, Silvia; Leite, M Fatima; Campagnole-Santos, Maria José · Basic Research
RPEP-16059 · 2026Antimicrobial nanocoatings for contact lenses — including antimicrobial peptides like melimine and Mel4, metallic nanoparticles, polymeric layers, and hybrid systems — can achieve greater than 3-log10 (99.9%) bacterial reductions and have reduced corneal infiltrative events in clinical trials. AMPs and peptidomimetics are among the most promising approaches, preventing microbial adhesion and biofilm formation while maintaining lens biocompatibility. The field is moving toward hybrid, stimuli-responsive coatings that activate only under infection-specific conditions.
Sara, Manjulatha; Attard, Samuel; Kumar, Naresh; Willcox, Mark ·
RPEP-16062 · 2026Semaglutide 1 mg weekly for 26 weeks significantly improved HbA1c compared to placebo (mean difference -0.25%, p<0.001) in people with schizophrenia spectrum disorders on clozapine or olanzapine. 43% of semaglutide-treated participants achieved low-risk HbA1c levels (<5.4%) versus only 3% on placebo. Semaglutide also produced significant weight loss (-9.2 kg, p<0.001), waist circumference reduction (-7.0 cm, p<0.001), and fat mass reduction (-6.1 kg, p=0.006). Crucially, psychiatric symptoms did not worsen, and psychiatric adverse events were similar across groups. GI side effects were common but mild and transient.
Sass, Marie R; Klausen, Mette Kruse; Schwarz, Christine R; Rasmussen, Line; Giver, Malte E B; Hviid, Malthe; Schilling, Christoffer; Zamorski, Alexandra; Jensen, Andreas; Gefke, Maria; Storgaard, Heidi; Oturai, Peter S; Kjaer, Andreas; Hartmann, Bolette; Holst, Jens J; Ekstrøm, Claus T; Vinberg, Maj; Correll, Christoph U; Vilsbøll, Tina; Fink-Jensen, Anders ·
RPEP-16065 · 2026Tirzepatide treatment over 72 weeks significantly reduced serum uric acid (SUA) at all three dose levels compared to placebo in the SURMOUNT-1 trial of 2,539 adults with obesity. At week 72, SUA decreased by -0.69 mg/dL (5 mg), -0.92 mg/dL (10 mg), and -0.95 mg/dL (15 mg) versus -0.18 mg/dL with placebo (all p<0.001). Reductions were significant regardless of baseline uric acid level or BMI. Mediation analysis showed that weight reduction explained 72.7% of the SUA decrease, suggesting the effect is primarily driven by weight loss (up to 20.9% body weight reduction).
Sattar, Naveed; Scilletta, Sabrina; Stefanski, Adam; Wang, Hui; Daly, Jack W; Linetzky, Bruno ·
RPEP-16073 · 2026Individual fat body cells expressed antimicrobial peptides at approximately constant rates following infection, but the average rate varied along the anterior-posterior axis — rapid expression in anterior and posterior lobes, slower in the middle. These tissue microenvironments were predefined independently of infection, with the rate-limiting step of AMP induction occurring downstream of peptidoglycan sensing.
The spatial distribution of immune-active microenvironments correlated with heartbeat-dependent fluid flow patterns, paralleling the strategic positioning of immune cells (e.g., Kupffer cells in liver sinusoids) in mammalian organs. Overexpression experiments confirmed that immune signaling capacity varies by position, not just exposure to pathogens.
Schlomann, Brandon H; Pai, Ting-Wei; Sandhu, Jazmin; Ferrer Imbert, Genesis; Graham, Thomas G W; Garcia, Hernan G ·
RPEP-16074 · 2026Liposomes decorated with the iRGD homing peptide (CRGDKGPDC) selectively accumulated in the placentas of pregnant rhesus macaques — without crossing to the fetus. This is a critical proof-of-concept: a peptide-guided nanoparticle can deliver drug payloads specifically to the placenta in a primate model closely resembling human pregnancy.
The iRGD-targeted liposomes were well tolerated with no adverse clinical reactions, no abnormal placental or fetal pathology, and stable maternal blood markers. Importantly, non-targeted (ARA peptide) liposomes showed widespread distribution to both maternal and fetal tissues — demonstrating that the iRGD peptide targeting is what prevents fetal exposure. The approach worked at both early gestation (days 45-64) and mid-gestation (days 84-100).
Schmidt, Jenna K; Mitzey, Ann M; Keding, Logan T; Shaw, Sarah A; Renshall, Lewis; Beards, Frances; Al-Mugotir, Mona H; Simmons, Heather A; Basu, Puja; Schotzko, Michele L; Ren, Emily; Golos, Thaddeus G; Harris, Lynda K · In Vivo
RPEP-16075 · 2026Tirzepatide significantly improved physical function compared to placebo on both primary outcome measures: SF-36 physical function domain (MD 2.26 points; 95% CI 1.76-2.76) and IWQOL-Lite-CT physical function subscale. Both the 10 mg and 15 mg weekly doses showed consistent benefits in subgroup analyses.
However, between-study heterogeneity was extremely high (I² = 99.8%), which limits the interpretability of pooled estimates. The overall certainty of evidence was rated as moderate by GRADE criteria due to risk of bias and inconsistency across studies.
Schmidt, Pedro Henrique Siedschlag; de Souza, Vitor Sodré Nonato; Machado, Luís Guilherme; Rodrigues, João Vitor Ahlf; da Cruz, João Victor Ramos; de Souza, Lis Sodré Nonato; Dos Santos, Bruno Eulálio; Hohl, Alexandre; Ronsoni, Marcelo Fernando; van de Sande-Lee, Simone ·
RPEP-16076 · 2026First-generation obesity medications — phentermine, orlistat, phentermine/topiramate ER, bupropion/naltrexone SR, and liraglutide 3.0 mg — remain effective and clinically relevant despite the arrival of newer incretin-based therapies. While their average weight loss is lower than next-generation drugs, clinical trial data show that a substantial proportion of patients on these agents achieve 10% or more total body weight loss. The review emphasizes these medications as cost-effective, evidence-based tools for managing obesity-related atherosclerosis and other cardiometabolic complications.
Schmitz, Sarah H; Saunders, Katherine H ·
RPEP-16078 · 2026Using mixed lymphocyte-peptide cultures, researchers generated antigen-specific cytotoxic T cells against several tumor-associated antigens, with MAGE, PRAME, and NY-ESO-1 identified as the most potent immunostimulatory peptide targets. When these peptide-specific T cells were co-cultured with head and neck cancer cell lines in the presence of anti-PD-1 antibody, the antigen-specific immune response was significantly increased compared to T cells without checkpoint blockade.
However, combining anti-PD-1 with other checkpoint inhibitors targeting LAG-3 or TIM-3 produced little or no synergistic enhancement, suggesting that PD-1 is the primary checkpoint restraining peptide-specific anti-tumor immunity in this cancer type.
Schuler, Patrick J; Oliveri, Franziska; Puntigam, Lisa; Six, Klara; Kaißer, Carlotta; Maier, Julia; Laban, Simon; von Witzleben, Adrian; Brunner, Cornelia; Messerer, David A C; Schrezenmeier, Hubert; Hoffmann, Thomas K; Goetz, Marlies; Greiner, Jochen ·
RPEP-16082 · 2026Patients with type 2 diabetes taking GLP-1 receptor agonists showed no statistically significant increase in 5-year thyroid cancer risk compared to those taking three other common diabetes drug classes.
GLP-1RA vs SGLT-2 inhibitors (7,736 per group): thyroid cancer rate 0.30% vs 0.48%, RR 0.62 (95% CI 0.37–1.05, P=.07). GLP-1RA vs metformin (5,158 per group): 0.25% vs 0.39%, RR 0.65 (95% CI 0.32–1.31, P=.22). GLP-1RA vs DPP-4 inhibitors (12,570 per group): 0.33% vs 0.37%, RR 0.91 (95% CI 0.60–1.39, P=.67).
In all three comparisons, thyroid cancer rates were numerically lower in the GLP-1RA group, though none reached statistical significance.
Sciscent, Bao Y; Eberly, Hanel W; Lorenz, F Jeffrey; Goldrich, David; Goyal, Neerav; Goldenberg, David ·
RPEP-16083 · 2026Researchers developed oral drugs (K-757 and K-833) that directly target gut enteroendocrine cells via GPR40 and GPR119 receptors to trigger massive release of natural satiety hormones including GLP-1 — essentially mimicking what bariatric surgery does to the gut.
The combination of both receptor agonists produced synergistic hormone secretion in both mouse and human gut tissue (enteroids). In mice, the combination improved glucose tolerance and promoted weight loss. Most remarkably, in phase 1 human trials, the circulating gut hormone levels achieved EXCEEDED those seen after bariatric surgery — suggesting these oral pills could potentially replicate the metabolic benefits of surgery without the knife.
Sebhat, Iyassu K; Murphy, Monika J M; Zheng, Shuqin; Lovelett, Robert J; Engelstoft, Maja; Kosinski, Daniel; Yang, Xiaodong; Dunn, Victoria; Whang, John; Lombardo, Maximilian G; Heilbut, Adrian; Terracina, Giuseppe; Nicholas, Nicole; Leitner, Molly; Consolati, Matthew J; Chan, Bryan; Poterewicz, Gregory; Vance, Annemarie; Liu, Jiajun; Weber, Ann E; Lauring, Brett; Thornberry, Nancy; Pinto, Shirly · Preclinical + Phase 1 Human Trial
RPEP-16088 · 2026Chronic social isolation in male mice reduced oxytocin peptide production and delayed the return of social huddling behavior when the mice were put back together. Exogenous oxytocin treatment prevented both the behavioral and molecular effects of isolation.
The key discovery: astrocytes (brain support cells) in the hypothalamus create a positive feedback loop for oxytocin. When oxytocin stimulates astrocytes, they produce retinoic acid (via the enzyme Aldh1a1), which in turn stimulates more oxytocin production. This means astrocytes act as sensors and amplifiers of neuropeptide levels, directly influencing social behavior.
Selles, Maria Clara; Cooper, Melissa L; Limone, Francesco; Ahmed, Araf; Liddelow, Shane A; Froemke, Robert C; Chao, Moses V · Animal
RPEP-16089 · 2026Marine-derived antimicrobial peptides (AMPs), sourced from invertebrates, extremophiles, and cyanobacteria, exhibit broad-spectrum activity against drug-resistant pathogens through membrane disruption and immunomodulation. These cationic, amphipathic molecules show low resistance propensity and multifunctional bioactivity spanning antimicrobial, antioxidant, and anticancer properties. Advances in machine learning, genomic/metagenomic tools, and synthetic biology are revolutionizing AMP discovery and optimization. Biotechnological innovations in heterologous expression and marine biomass valorization support scalable production aligned with circular economy principles.
Selvaraj, Chandrabose; Desai, Deepali; Santos-Villalobos, Sergio de Los; Jayaprakashvel, Mani; Muthezhilan, Radhakrishnan; Singh, Sanjeev Kumar ·
RPEP-16091 · 2026The review identifies several peptide-based strategies showing preclinical promise against drug-resistant colorectal cancer. Peptide-drug conjugates enhance targeted delivery and antitumor effects. Cell-penetrating peptides improve drug uptake into resistant cells. Pro-apoptotic and oncolytic peptides directly induce tumor cell death through mechanisms that bypass standard resistance pathways.
Peptides can also target multiple resistance mechanisms including DNA repair, cell cycle arrest, apoptosis evasion, gene expression changes, and the tumor microenvironment. The authors introduce a Mechanistic Resistance Profiling (MRP) Framework that classifies peptides by the specific resistance layer they target (efflux, repair, apoptosis, tumor microenvironment, and immune evasion) to guide rational combination therapies.
Sen, Sanjukta; Mitra, Sreemoyee; Karati, Dipanjan ·
RPEP-16098 · 2026GLP-1 receptor agonists are far from experimental novelties — GLP-1 was first discovered in the 1980s, and these drugs have accumulated nearly two decades of clinical experience with millions of patient-years of safety data. Newer agents like semaglutide and tirzepatide use structural modifications that prolong the hormone's action without fundamentally changing its mechanism. Safety data consistently show that side effects are predominantly mild, transient gastrointestinal issues, with no confirmed evidence supporting feared risks such as cancer.
Shah, Priyansh P; Bhattacharya, Romit ·
RPEP-16110 · 2026Fermenting pre-digested soybeans with fructophilic lactic acid bacteria (FLAB) — specifically Apilactobacillus kunkeei and Fructobacillus fructosus — produced elevated levels of bioactive peptides, GABA, and beneficial phenolic compounds. The fermentation boosted low-molecular-weight peptides and generated novel peptide sequences beyond what digestion alone produced. Computer modeling predicted that several of these released peptides and phenolics could cross the blood-brain barrier and target neurotransmitter receptors, suggesting potential psychobiotic (brain-health) applications.
Shazad, Amir; Tlais, Ali Zein Alabiden; Trossolo, Elisabetta; Casagrande Bacchiocchi, Sara; Filannino, Pasquale; Pinto, Daniela; Gobbetti, Marco; Di Cagno, Raffaella · In Vitro
RPEP-16113 · 2026A ~20 nm solid self-emulsifying (SSE) nanovaccine platform that co-delivers peptide antigens with a CpG oligonucleotide adjuvant generated T-cell responses 40-fold higher than conventional emulsified vaccines and achieved complete tumor regression at low doses in mice.
The mechanism is dual: ApoE (apolipoprotein E) adsorbed onto the nanoparticles enhanced lymph node targeting and dendritic cell uptake, while the nanoparticles were also directly internalized by T cells, promoting lipid raft formation that sensitized them to activation. This simultaneous engagement of both dendritic cells and T cells represents a previously unknown dual mechanism for nanovaccine-mediated immune activation.
Shen, Xueying; Fan, Shiqi; He, Jia; Luo, Lanqing; Li, Junyao; Wu, Chengcheng; Yang, Kairu; Xia, Xiaojun; Kuai, Rui · Animal Study
RPEP-16114 · 2026This comprehensive study revealed distinct but complementary roles for GLP-1R and GIPR in periodontal stem cells:
- GIPR agonism promoted PDLSC proliferation via the MAPK/ERK pathway
- GLP-1R agonism enhanced multilineage differentiation capacity
- GLP-1R knockdown upregulated IFIT1/2/3 proteins, which were shown to inhibit translation of differentiation-related mRNAs by interacting with translation initiation factor eIF3C
- In vivo: single and dual receptor agonists improved periodontal regeneration in both wild-type and GLP-1R/GIPR double-knockout periodontitis mice
- Clinical survey: 74 periodontitis patients taking GLP-1R or dual agonists showed significantly better periodontal staging and grading than non-users, with dose-duration relationship
Shen, Yifen; Zhang, Mengjie; Yang, Tao; Wu, Yuxiang; Qiu, Yinfeng; Zhang, Le; Li, Fei; Chen, Minjie; Chen, Qili; Wei, Wenbin; Li, Hua; Shen, Yihang ·
RPEP-16115 · 2026In female rats, the short-acting GLP-1R agonist exendin-4 reduced time spent with males, number of mounts, intromissions, ejaculations, darts, hops, and lordosis intensity. In female mice, the long-acting GLP-1R agonists liraglutide and dulaglutide reduced time spent with male mice and, consequently, lowered mounting and intromission duration.
Neurochemically, the effects in mice potentially involved increased noradrenaline levels in the nucleus tractus solitarii (NTS) and altered glutamate, glutamine, and taurine levels in the lateral septum. Dulaglutide also decreased social novelty-seeking in the three-chamber test, while long-acting agonists increased sociability and novel object exploration time. Effects were both species-dependent and agonist-specific.
Shevchouk, Olesya; Edvardsson, Christian E; Ericson, Mia; Blid Sköldheden, Sebastian; Zhang, Qian; Dreher Nabinger, Debora; Snoeren, Eelke Ms; Westberg, Lars; Jerlhag, Elisabet ·
RPEP-16119 · 2026Among 71 pediatric patients (55 on rimegepant, 26 on atogepant, 10 on both), 58% (32/55) of rimegepant users and 43% (11/26) of atogepant users experienced at least some benefit for headache prevention. This is notable because these were treatment-resistant patients who had already failed a median of 6-7 prior preventive medications.
Side effects were infrequent and mild: only 4 of 55 rimegepant patients and 7 of 26 atogepant patients reported any side effects, with no serious adverse events. An exploratory analysis found that patients with longer headache histories were more likely to benefit (OR 1.41, 95% CI: 1.07-1.85, p=0.014), while those with more severe functional limitations were less likely to respond (OR 0.18, 95% CI: 0.05-0.58, p=0.004).
Shin, Lauren; Mentz, Olivia; Gelfand, Amy A; de Prado, Blanca Marquez; Shapiro, Hannah; Oh, Ann; Onifade, Ogo-Oluwa; Saunders, Jessica; Raj, Nichelle; Szperka, Christina L ·
RPEP-16123 · 2026In class-level analysis across 11 trials, tirzepatide vs. placebo significantly reduced: MACE (HR 0.79, 95% CI 0.69-0.91), cardiovascular mortality (HR 0.77, 95% CI 0.66-0.90), all-cause mortality (HR 0.74, 95% CI 0.65-0.83), non-fatal MI (HR 0.77, 95% CI 0.61-0.97), and non-fatal stroke (HR 0.79, 95% CI 0.64-0.97). In agent-level analysis, tirzepatide reduced MACE vs. placebo (HR 0.81) and vs. lixisenatide (HR 0.79), and showed comparable efficacy to other individual GLP-1RAs. Subgroup and sensitivity analyses were consistent.
Shokravi, Arveen; Seth, Jayant; Mancini, G B John ·
RPEP-16126 · 2026At Week 72, both tirzepatide and semaglutide improved Physical Component Summary scores from baseline. Tirzepatide showed significantly greater improvement in General Health domain scores compared to semaglutide (5.45 vs. 4.20; p = 0.003). All SF-36v2 domain scores improved with both treatments (p ≤ 0.008).
In the subgroup with limited baseline physical function, tirzepatide outperformed semaglutide in Physical Component Summary, Physical Functioning, and General Health scores (p ≤ 0.025). Greater body weight reductions were associated with more improvement in Physical Functioning, Role-Physical, Bodily Pain, General Health, and Vitality scores across both treatments when pooled. Mental Component Summary scores did not differ significantly between treatments.
Shukla, Alpana P; Dunn, Julia P; Gomez Valderas, Elisa; Fraseur Brumm, Julia; Karanikas, Chrisanthi A; Hunter Gibble, Theresa ·
RPEP-16128 · 2026This first-ever systematic review of nonhormonal treatments for adolescent PCOS found that metformin alone modestly reduced BMI (1–2 kg/m²), improved insulin resistance (25% HOMA-IR reduction), and restored menstrual cycles in up to 91% of participants. The SPIOMET combination improved ovulatory function, halved hirsutism scores, reduced visceral and liver fat, and normalized inflammatory markers with benefits lasting up to one year post-treatment. Critically, no clinical trials of GLP-1 receptor agonist monotherapy in adolescents with PCOS were identified, representing a major evidence gap.
Sibal, Rhea; Keogh, Morgan; Latthe, Pallavi; Idkowiak, Jan ·
RPEP-16130 · 2026The expert panel produced 52 consensus statements covering nutritional and lifestyle management for patients on GLP-1-based therapies (GBTs). Key areas addressed include: nutritional factors related to obesity and body composition, physical activity recommendations, and management of common gastrointestinal symptoms (nausea, vomiting, diarrhea, constipation).
The recommendations are organized by treatment phase: before starting a GBT, during active weight loss, during weight maintenance, and upon GBT discontinuation. The panel emphasized that GI side effects, obesity-associated nutritional insufficiencies, and poor long-term adherence may limit the health benefits of these drugs without proper supportive care.
Sievenpiper, J L; Ard, J; Blüher, M; Chen, W; Dixon, J B; Fitch, A; Gigliotti, L; Khunti, K; Lecube, A; Lean, M E J; Mittendorfer, B; Pfeiffer, A F H; Ryan, D H; Vilsbøll, T; Van Gaal, L F ·
RPEP-16132 · 2026Key results from the peptide-PCL conjugate system:
- A 'Fast' peptide sequence was identified via functional mass spectrometry as selectively cleavable by multiple cell types
- Peptide incorporation did not impair cell adhesion (tested with RGDS-PCL)
- Collagenase degradation (21 days): Fast-PCL released 25.77% ± 3.70% Cy3 label vs 11.31% ± 1.01% for scrambled control; mass loss 22.1% vs 18.9%
- hMSC-mediated degradation: Fast-PCL released 26.68% ± 2.17% vs 18.97% ± 1.24% for scrambled control
- Degradation was sequence-dependent (not just bulk hydrolysis), confirming cell-directed proteolytic resorption
- Cy3 real-time labeling enabled quantitative tracking of degradation
Sinad, Korina Vida G; Hunt, Natasha K; Singh, Srujan; Seims, Kelly B; Wu, Yingjie; Pashuck, E Thomas; Grayson, Warren L; Chow, Lesley W ·
RPEP-16138 · 2026In vitro, CB3 pretreatment (50-100 μM) reduced oxidative activity and pro-inflammatory cytokines (IL-6, IL-1β, TNF-α) while increasing anti-inflammatory IL-10 in an epileptiform activity model.
In vivo, early CB3 intervention (20 mg/kg/day, i.p.) after kainic acid-induced status epilepticus significantly delayed seizure onset, reduced seizure frequency and cumulative burden, and preserved hippocampal neuronal integrity. Treated mice showed improved locomotor activity, reduced anxiety, and better spatial working memory. In established chronic epilepsy, CB3 (20 mg/kg/day) produced sustained reduction in recurrent seizure activity and seizure burden with improvements in anxiety, though memory deficits remained unchanged.
Singh, Prince Kumar; Maurya, Shweta; Saadi, Aseel; Sandouka, Sereen; Zhang, Taige; Kadosh, Orya; Sheeni, Yara; Martin, Valeria; Atlas, Daphne; Shekh-Ahmad, Tawfeeq ·
RPEP-16140 · 2026The review identifies several key therapeutic targets and delivery strategies for T2DM:
- GLP-1 receptor agonists: enhance insulin secretion, reduce appetite, and provide cardiovascular benefits
- SGLT2 inhibitors: block renal glucose reabsorption
- AMPK activators: improve cellular energy metabolism
- PPAR-γ modulators: enhance insulin sensitivity
- Glucose absorption inhibitors: reduce dietary glucose uptake
Multi-targeted therapy combining these approaches has demonstrated potential for improved glycemic control, reduced long-term complications, and better safety profiles compared to monotherapy. Precision drug delivery using receptor-targeted carriers can enhance bioavailability and reduce dosing frequency.
Singhal, Priya; Mazumder, Rupa; Rani, Anjna; Debnath, Abhijit ·
RPEP-16142 · 2026Across 14 included studies, GLP-1RAs (liraglutide, semaglutide, exendin-4) consistently modulated autophagy-specific markers in Alzheimer's and Parkinson's disease models: increased beclin-1, LC3-II/LC3-I ratio, ATG7, ATG3, and LAMP1, while normalizing p62 levels. These changes indicate enhanced autophagosome formation and clearance of cellular debris.
In addition to autophagy modulation, GLP-1RAs promoted neurogenesis, enhanced neuroplasticity, and reduced neuroinflammation — suggesting autophagy may be one of several interconnected mechanisms mediating the broad neuroprotective effects of these peptide drugs.
Sioufi, Maria-Christina; Heroiu, Isabela; Wong, Sabrina; Le, Gia Han; Dri, Christine E; Zheng, Yang Jing; Rhee, Taeho Greg; Lo, Heidi Ka Ying; Guillen-Burgos, Hernan F; Teopiz, Kayla M; McIntyre, Roger S ·
RPEP-16143 · 2026At 18 months, GLP-1RA-treated patients were significantly more likely to achieve MASH resolution without worsening fibrosis compared to placebo (OR: 4.16, 95% CI: 2.33-7.42, p<0.001). In a subgroup analysis excluding cirrhotic patients, GLP-1RAs also showed significant fibrosis regression of at least one stage (OR: 2.02, 95% CI: 1.56-2.62, p=0.01).
GLP-1RAs significantly improved all liver histologic features examined: balloon degeneration (a marker of cell injury), lobular inflammation, and steatosis (fat accumulation). The overall nonalcoholic fatty liver disease activity score improved significantly. Serious adverse event rates were comparable between GLP-1RA and placebo groups.
Siranart, Noppachai; Thompson, Christopher C; Jirapinyo, Pichamol ·
RPEP-16144 · 2026Semaglutide and tirzepatide have demonstrated weight loss outcomes that have fundamentally shifted the obesity treatment paradigm. These incretin-based therapies work by modulating GLP-1 (and in tirzepatide's case, also GIP) receptor pathways, leading to decreased caloric intake through appetite suppression.
The review notes that benefits extend beyond weight loss to include metabolic improvements, though challenges remain around long-term efficacy (weight regain after discontinuation), tolerability (gastrointestinal side effects), and accessibility (cost and supply constraints). Future directions include combination therapies and novel molecules with dual or triple receptor activity targeting GLP-1, GIP, and glucagon receptors simultaneously.
Skinner, Karlie; Clements, Jennifer N ·
RPEP-16146 · 2026Using FTIR spectroscopy to analyze rat aortic tissue after unilateral adrenalectomy, researchers found that a single oral dose of BPC 157 (10 ng/kg) produced clear, reproducible molecular changes in the aortic wall at all time points (15 minutes, 5 hours, and 24 hours post-surgery). The spectral changes were concentrated in protein-related bands (amide I and amide II, consistent with collagen/elastin) and lipid C-H stretching bands.
These molecular signatures suggest that BPC 157 promotes rapid extracellular matrix reinforcement and membrane preservation in the vascular wall — providing molecular-level evidence for the peptide's previously observed vascular protective effects.
Smoday, Ivan Maria; Vukovic, Vlasta; Oroz, Katarina; Vranes, Hrvoje; Kalogjera, Luka; Gamulin, Ozren; Vlainic, Josipa; Milavic, Marija; Sikiric, Suncana; Nikolac Gabaj, Nora; Marijancevic, Domagoj; Koprivanac, Antun; Beketic Oreskovic, Lidija; Oreskovic, Ivana; Strbe, Sanja; Barisic, Ivan; Kordic, Mario; Tvrdeic, Ante; Seiwerth, Sven; Sikiric, Predrag; Boban Blagaic, Alenka; Skrtic, Anita · Animal
RPEP-16147 · 2026Over 12 weeks, tirzepatide produced a mean weight loss of 10.3 kg versus 0.7 kg with placebo (treatment difference: -8.7 kg, p<0.0001), representing 8.8% body weight reduction. Every participant (100%) on tirzepatide achieved at least 5% weight loss, and 45% achieved at least 10% loss, compared to 9% and 0% on placebo.
Tirzepatide also improved HbA1c by -0.4% versus placebo (p=0.05) and reduced total daily insulin dose by 24.2 units/day (35.1% reduction vs placebo, p=0.0002). No significant adverse events occurred in either group. Twenty-two of 24 participants completed the study.
Snaith, Jennifer R; Frampton, Ruth; Samocha-Bonet, Dorit; Greenfield, Jerry R ·
RPEP-16149 · 2026LL-37 is expressed by gingival epithelium, salivary glands, and inflammatory cells in the oral cavity. Beyond direct antimicrobial killing, it modulates inflammatory responses, promotes wound healing, and influences cell proliferation and blood vessel formation. Altered LL-37 expression has been associated with periodontitis, dental caries, endodontic infections, and oral squamous cell carcinoma. The review positions LL-37 as both a potential diagnostic biomarker and therapeutic target in oral pathology.
Soman, Drisya; P, Jayanthi; Cm, Mahesh; Radhakrishnan, Rahul ·
RPEP-16150 · 2026A meta-analysis of 7 studies with 11,973 participants found that GLP-1 receptor agonists significantly reduced the incidence of refractory idiopathic intracranial hypertension (IIH), lowered the risk of papilledema by 60% (RR=0.40), and reduced visual disturbances and blindness risk by 49% (RR=0.51). GLP-1RAs also reduced headache incidence (RR=0.74) and monthly headache days (SMD=-0.77).
However, objective visual parameters — visual acuity, visual field measurements, and retinal nerve fiber layer thickness — did not significantly improve. Interestingly, BMI changes were not significant either, suggesting the benefits may come through mechanisms other than weight loss alone.
Song, Jiahao; Fang, Kun; Zhang, Yunzhou; Zhang, Rujiang; Yin, Chengliang; Gao, Daiquan · Meta Analysis
RPEP-16155 · 2026Among 9 RCTs with 3,266 participants, efruxifermin was the only intervention significantly superior to placebo for fibrosis regression (≥1 stage improvement without MASH worsening), ranking highest (SUCRA 77.44), followed by cilofexor + firsocostat (SUCRA 72.38) and aldafermin (SUCRA 71.27).
For MASH resolution, three treatments were significantly superior to placebo: efruxifermin (SUCRA 81.38), semaglutide + cilofexor + firsocostat (SUCRA 74.07), and semaglutide alone (SUCRA 63.88).
Souza, Matheus; Al-Sharif, Lubna; Antunes, Vanio L J; Wong, Shi Yin; Huang, Daniel Q; Loomba, Rohit ·
RPEP-16159 · 2026Standard agonist-based imaging (68Ga-DOTATOC PET/CT) showed insufficient tumor uptake, precluding conventional PRRT. Switching to the antagonist-based tracer (68Ga-NODAGA-LM3 PET/CT) revealed markedly superior and treatment-sufficient uptake in the same patient.
This directly translated to successful therapy: 4 cycles of 177Lu-DOTA-LM3 PRRT produced a positive treatment response. The case demonstrates both diagnostic superiority of antagonist over agonist somatostatin receptor imaging and the feasibility of antagonist-mediated PRRT in patients who fail agonist-based approaches.
Speicher, Tilman; Burgard, Caroline; Rosar, Florian; Bastian, Moritz; Bartholomä, Mark; Maus, Stephan; Ezziddin, Samer ·
RPEP-16162 · 2026NDKD affects one-third to one-half of T2DM patients with kidney disease. IgA nephropathy dominates in Asian populations (25-43%), while membranous nephropathy (20-30%) and FSGS (18-25%) are more common in Western cohorts. Clinical predictors include absence of diabetic retinopathy (OR 0.15 for DKD), diabetes <5 years (OR 5.8 for NDKD), hematuria (OR 7.2), and rapid eGFR decline >5 mL/min/year (OR 4.3). For renoprotection: SGLT2 inhibitors show HR 0.61-0.72, GLP-1 RAs ~0.76, and MRAs ~0.82. AI-assisted histopathology achieves AUC 0.91 for diagnosis.
Sreedharan, Sreenath; M K, Mohandas; K B, Vismaya; Raju, Nikhil ·
RPEP-16163 · 2026Across 10 randomized controlled trials with 665 participants, GLP-1 receptor agonists significantly reduced body weight by 6.17 kg (95% CI: -9.10 to -3.25) and HbA1c by 0.31% (95% CI: -0.40 to -0.22) compared to placebo in individuals with severe mental illness (schizophrenia, schizophrenia-spectrum disorders, bipolar disorder).
Critically, dropout rates were no different between GLP-1 RA and placebo groups — both all-cause (RR 0.98) and adverse-effect dropouts (RR 0.99) — indicating acceptable tolerability in this vulnerable population.
Srisurapanont, Manit; Suttajit, Sirijit; Likhitsathian, Surinporn; Suradom, Chawisa; Maneeton, Benchalak · Meta Analysis
RPEP-16169 · 2026Natural antimicrobial peptides (AMPs) including defensins, cathelicidins, histatins, lactoferricin, protamines, RegIII, and hepcidin demonstrated significant antimicrobial and immunomodulatory effects against major gastrointestinal pathogens including E. coli, Klebsiella pneumoniae, Salmonella, and Shigella. Beyond directly killing bacteria, these peptides modulate host-microbiota interactions, preserve gut barrier integrity, and limit inflammation.
Synthetic peptide analogs such as WR12, D-IK8, MSI-78, and IMX942 showed improved stability, reduced toxicity to human cells, and synergistic effects when combined with conventional antibiotics, suggesting potential use as standalone treatments or combination therapies.
Stepanyan, Lala; Israyelyan, Monika; Gori, Alessandro; Tsaturyan, Avetis; Saribekyan, Zhaklina; Hovsepyan, Kristina; Sargsyan, Tatevik; Pastore, Raffaele; De Luca, Antonio; Roviello, Giovanni N ·
RPEP-16170 · 2026Selective substitution of lysine with serine in the designed AMP G(IIKK)3I-NH2 altered both the charge distribution and amphiphilicity of the peptide, resulting in different structural disruptions to the inner and outer membranes of gram-negative bacteria. Serine-rich AMPs showed improved antimicrobial activity linked to intramembrane aggregation — the peptides clustered within the bacterial membrane, causing more effective disruption. Neutron reflection experiments and molecular dynamics simulations confirmed these distinct mechanistic pathways, demonstrating that rational amino acid substitutions can fine-tune how antimicrobial peptides attack bacterial membranes.
Stephens, Anna; Ge, Tianhao; Ding, Ke; Hollowell, Peter; Clifton, Luke; Hall, Stephen; Li, Peixun; Webster, John R P; Gong, Haoning; Lu, Jian Ren ·
RPEP-16176 · 2026Peptide-linked amikacin conjugates showed powerful synergy with polymyxin B against extensively drug-resistant and pandrug-resistant Klebsiella pneumoniae. Of 31 resistant strains tested, 77% showed synergy when peptide-amikacin conjugates containing tryptophan and cysteine were combined with polymyxin B, including strains carrying multiple resistance enzymes (AMEs and RMTases). The peptide-linked compounds maintained similar mammalian cell toxicity as unmodified amikacin but were dramatically more synergistic with polymyxin B against resistant bacteria.
Story, Sandra; Sharma, Anindra; Maiti, Krishnagopal; Arya, Dev P ·
RPEP-16182 · 2026Researchers engineered a self-contained sensor-effector circuit by bioprinting dorsal root ganglion (DRG) neurons within piezoelectric poly(L-lactide) (PLLA) scaffolds. Upon ultrasound stimulation, the piezoelectric material generated electrical signals that triggered calcium influx in the DRG neurons, enhancing secretion and expression of calcitonin gene-related peptide (CGRP). The released CGRP promoted both osteogenesis and angiogenesis in vitro, and accelerated neuro-vascularized bone regeneration in a rat femoral condyle defect model — demonstrating a bioinspired platform that autonomously links mechanical sensing to peptide-driven bone repair.
Su, Yingze; Wang, Haomin; Liu, Weixi; Chen, Kangming; Min, Yiyang; Zhu, Jinbo; Li, Xueyang; Su, Anning; Yang, Hao; Yang, Lei; Ji, Yun; Zhang, Yuxin; Zheng, Jisi; Yang, Chi; He, Chuanglong; Li, Tao; Chen, Shuo; Wu, Tao; Chen, Xiaodong ·
RPEP-16190 · 2026Tirzepatide significantly reduced body weight and white adipose tissue mass in obese mice, with marked reduction in fat cell size (adipocyte hypertrophy). RNA sequencing revealed coordinated upregulation of thermogenesis and lipid metabolism genes. The drug increased expression of browning markers PGC-1α and UCP1, indicating white fat was converting to a calorie-burning brown-like state.
In cultured 3T3-L1 adipocytes, tirzepatide activated the PGC-1α/UCP1 axis in a cAMP-dependent manner and reduced lipid droplet accumulation. When the adenylyl cyclase inhibitor SQ22536 was added, these browning effects were significantly attenuated, confirming cAMP signaling as the critical mediator.
Sun, Yaqin; Xia, Yin; Ge, Weixing; Li, Qian ·
RPEP-16192 · 2026AI and bioinformatics tools have dramatically accelerated the discovery and design of cell-penetrating peptides (CPPs). This systematic review covers computational tools developed between 2011 and 2025 that predict whether a peptide can cross cell membranes. These tools use various machine learning and AI algorithms to analyze peptide sequences and predict their cell-penetrating potential, replacing slow and expensive trial-and-error laboratory screening.
The review catalogs the landscape of available prediction tools, their underlying algorithms, strengths, and limitations. CPPs can deliver therapeutic cargo including small molecule drugs, proteins, and nucleic acids into cells, making them valuable for drug delivery, gene therapy, and molecular imaging. AI-driven design is enabling researchers to identify novel CPPs faster than ever before.
Sun, Yu; Zhang, Muqing; Liu, Huiting; Wang, Hu · Review
RPEP-16194 · 2026From eight protease hydrolysates of Chlamydomonas reinhardtii, the alkaline protease hydrolysate (CRPA) showed the strongest ACE inhibitory activity. The first ACE-inhibitory peptide identified from this microalga — a five-amino-acid sequence called IDYRY (ID-5) — had an IC50 of 18.54 ± 5.57 μM.
ID-5 was characterized as a noncompetitive ACE inhibitor, meaning it binds to the enzyme at a different site than the substrate. It demonstrated significant antihypertensive activity both in vitro and in spontaneously hypertensive rats (SHRs), with an effective dose corresponding to a human-equivalent dose of approximately 16 mg/kg/day. Molecular dynamics simulations revealed that ID-5 forms unique hydrogen bonds with Asp415 and Arg522 on ACE, a binding mechanism distinct from captopril or lisinopril.
Suo, Qishan; Yue, Yang; Wang, Jing; Wu, Ning; Geng, Lihua; Zhang, Quanbin ·