RPEP-14143 · 2025Orforglipron produced significant placebo-adjusted decreases in blood pressure, LDL cholesterol, triglycerides, ApoB, ApoC3, and hsCRP in both the T2D study (N=361, 26 weeks) and the obesity study (N=234, 36 weeks). Improvements in CV risk markers at 12 mg were of similar magnitude to those seen at 24, 36, and 45 mg doses, suggesting a plateau effect for cardiovascular benefits. The improvements were consistent across both populations — people with type 2 diabetes and people with obesity alone — indicating the cardiovascular benefits are not limited to diabetic patients.
Wharton, Sean; Rosenstock, Julio; Konige, Manige; Lin, Yanzhu; Duffin, Kevin; Wilson, Jonathan; Banerjee, Hiya; Pirro, Valentina; Kazda, Christof; Mather, Kieren ·
RPEP-14149 · 2025Using an endothelial cell-specific senescent mouse model, researchers identified a novel neuroimmune pathway driving intrinsic skin aging. Senescent endothelial cells secrete pro-inflammatory SASP factors that activate dermal neurons to produce calcitonin gene-related peptide (CGRP). This CGRP triggers mast cell degranulation through a non-IgE-mediated pathway, leading to dermal thinning, collagen degradation, and delayed wound healing. Pharmacological stabilization of mast cells or inhibition of the EC-SASP-CGRP pathway significantly attenuated all three hallmarks of intrinsic skin aging.
Wicaksono, Satrio Adi; Ryanto, Gusty Rizky Teguh; Suzuki, Yoko; Hara, Tetsuya; Ikeda, Koji; Fukumoto, Takeshi; Hirata, Ken-Ichi; Otake, Hiromasa; Emoto, Noriaki ·
RPEP-14153 · 2025Both Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) produced significant weight loss and dramatically increased postprandial secretion of the distal gut peptides GLP-1 and PYY — hormones involved in satiety and blood sugar regulation. Gastric emptying was significantly accelerated after both procedures.
A notable difference emerged: oro-cecal transit time (how fast food travels from mouth to large intestine) was significantly accelerated after SG but not after RYGB. Despite the parallel increases in peptide release and faster motility, no significant correlations were found between changes in gut peptide levels, changes in GI motility, and clinical outcomes like weight loss.
Wilbrink, Jennifer A; van Avesaat, Mark; Nienhuijs, Simon W; Stronkhorst, Arnold; Masclee, Ad A M ·
RPEP-14156 · 2025A new data-independent acquisition (DIA) mass spectrometry approach dramatically improved the detection of rare bacterial peptides displayed on immune cells. Using Listeria monocytogenes as a model pathogen, researchers showed that DIA workflows found additional human and bacterial immunopeptides missed by the standard data-dependent (DDA) method. Their most powerful approach used DIA-NN software to generate and search predicted peptide libraries covering approximately 150 million immunopeptide precursors, outperforming all other methods at identifying MHC class I peptides — the molecular targets that guide vaccine and immunotherapy design.
Willems, Patrick; Staes, An; Miret-Casals, Laia; Demichev, Vadim; Devos, Simon; Impens, Francis · Methods
RPEP-14160 · 2025In six healthy volunteers who received intranasal [13N]oxytocin, PET/MRI scans showed high tracer uptake in the nasal cavity within the first 5 minutes, followed by decline and systemic absorption. Tracer was detectable in brain regions between 25-45 minutes post-administration, but uptake was low and variable between individuals.
Tracer uptake in the trigeminal ganglia and brain showed no clear dose-dependency. One participant with rhinitis showed altered uptake and clearance patterns, suggesting nasal health affects delivery. The nasal cavity was identified as the dose-limiting organ for radiation safety. The researchers concluded that [13N]oxytocin via intranasal administration is not well suited for central nervous system receptor imaging at this stage.
Winterdahl, Michael; Nielsen, Erik Nguyen; Hansen, Søren B; Dias, André Henrique; Vendelbo, Mikkel Holm; Jakobsen, Steen; Yeomans, David ·
RPEP-14162 · 2025Gastrointestinal adverse effects occur in 65–84% of patients treated with incretin-based anti-obesity medications (liraglutide, semaglutide, tirzepatide), with nausea and diarrhea being the most common. These symptoms are primarily caused by altered gastric motility and hormone-mediated changes in appetite signaling. Preventive strategies including slow dose titration, dietary counseling, and supportive medications can improve tolerability and treatment continuation.
Witaszek, Tomasz; Biesiada, Aleksander; Iskra-Trifunović, Joanna; Babicki, Mateusz; Mastalerz-Migas, Agnieszka; Kłoda, Karolina ·
RPEP-14165 · 2025Bariatric surgery consistently reduces MMP-9 levels and normalizes MMP-2 activity in obese patients, contributing to improved extracellular matrix integrity, reduced inflammation, and enhanced insulin sensitivity. These changes reflect a correction of the tissue-remodeling dysfunction characteristic of obesity.
GLP-1 receptor agonists and dual GLP-1/GIP agonists achieve substantial weight loss and glycemic control, but current evidence regarding their direct effects on MMP activity remains limited. This gap suggests that the tissue-level effects of pharmacotherapy may not fully replicate those of surgery, despite comparable weight loss outcomes.
Wiśniewski, Konrad; Choromańska, Barbara; Maciejczyk, Mateusz; Dadan, Jacek; Myśliwiec, Piotr ·
RPEP-14167 · 2025A 55-year-old male with an ACTH-secreting pituitary neuroendocrine tumor (PitNET) underwent over a decade of treatments:
- Recurrent transsphenoidal resections (multiple surgeries)
- Gamma knife irradiation
- Somatostatin analog therapy
- Steroidogenesis inhibitors
None achieved lasting control. Metastatic bone deposits were eventually discovered. Only after initiating 177Lu-DOTATATE PRRT did the patient achieve sustained clinical improvement (symptoms), biochemical improvement (hormone levels), and structural improvement (tumor shrinkage).
The authors note that the limited published cases of PRRT in metastatic PitNET show mostly favorable outcomes: tumor stability and/or shrinkage with limited adverse events (primarily mild blood count reductions).
Wolf, Katherine I; Lu, Zhonglin; Hesseltine, Elizabeth A; Wong, Ka-Kit; Worden, Francis P; Else, Tobias ·
RPEP-14170 · 2025The clinical development of oral semaglutide progressed through key phases:
- Phase 1: Demonstrated dose-dependent HbA1c and body weight reductions; characterized pharmacokinetics and drug interactions with food, disease states, and concomitant medications; established optimal dosing conditions (fasting, minimal water, 30-minute wait before eating)
- Phase 2: Confirmed significant HbA1c and weight reductions comparable to subcutaneous semaglutide, guiding dose selection (3 mg, 7 mg, 14 mg)
- Phase 3 (PIONEER program): Demonstrated significant HbA1c reduction, weight loss, and cardiovascular safety
- The absorption enhancer SNAC (sodium N-[8-(2-hydroxybenzoyl)amino]caprylate) was key to enabling gastric absorption and peptide stability
- Oral semaglutide (Rybelsus) became the first approved oral GLP-1 RA for T2DM
Won, Heejae; Cho, Joo-Youn; Lee, SeungHwan ·
RPEP-14176 · 2025Across 30 randomized controlled trials involving 37,072 patients, GLP-1 receptor agonists reduced systolic blood pressure by an average of 3.37 mmHg (95% CI -3.95 to -2.80) and diastolic blood pressure by 1.05 mmHg (95% CI -1.46 to -0.65) compared to placebo in overweight or obese patients.
The blood pressure lowering effect was consistent regardless of whether patients had diabetes, which GLP-1 drug formulation was used, how long treatment lasted, or whether the drug was injected or taken orally — with the exception of exenatide. Meta-regression found no significant correlation between blood pressure reduction and baseline age, sex, HbA1c, weight, BMI, or existing hypertension status.
Wong, Hon Jen; Toh, Keith Zhi Xian; Teo, Yao Hao; Teo, Yao Neng; Chan, Mark Y; Yeo, Leonard L L; Eng, Pei Chia; Tan, Benjamin Y Q; Zhou, Xin; Yang, Qing; Dalakoti, Mayank; Sia, Ching-Hui · Meta Analysis
RPEP-14178 · 2025Based on NHANES 2015-2018 data, approximately 93.4 million US adults (38% of the adult population) would meet SURMOUNT-1 trial eligibility criteria for tirzepatide treatment.
Applying the weight loss effects observed with tirzepatide 15 mg in SURMOUNT-1: 70.6% (65.9 million people) would achieve at least 15% weight reduction, and 56.7% (53.0 million) would achieve at least 20% weight reduction. This would translate to 58.8% fewer people with obesity — a reduction of 55.0 million individuals.
For cardiovascular impact, estimated 10-year CVD risk dropped from 10.1% to 7.7% after modeling tirzepatide treatment effects — a 2.4% absolute risk reduction (23.6% relative). This translates to approximately 2.0 million preventable cardiovascular disease events over 10 years among the eligible population without existing CVD.
Wong, Nathan D; Karthikeyan, Hridhay; Fan, Wenjun ·
RPEP-14184 · 2025Two novel chimeric peptides (EM-1-DLS and EM-2-DLS) combining opioid endomorphin sequences with a ghrelin receptor antagonist fragment produced potent pain relief in mice with significantly reduced tolerance development. EM-1-DLS was approximately 8 times more potent than endomorphin-1 alone and acted through κ-opioid, μ-opioid, and ghrelin (GHS-R1α) receptors simultaneously.
Critically, EM-1-DLS induced an acute tolerance ratio of only 2.33-fold, compared to 5.19-fold for endomorphin-1 alone — a roughly 55% reduction in tolerance development. Cross-tolerance ratios between the chimeric peptides and endomorphins ranged from 0.92 to 1.76, confirming reduced tolerance.
Wu, Bing; Cheng, Songxia; Liu, Fuyan; Wei, Jia; Liu, Yongling; Qian, Teng; Ding, Jiali; Xu, Biao; Wei, Jie · Animal
RPEP-14187 · 2025In this large UK cohort of adults aged 60+ with type 2 diabetes, SGLT2 inhibitors were associated with a 14% lower dementia risk compared to DPP4 inhibitors in the intention-to-treat analysis (HR 0.86, 95% CI 0.79–0.94), increasing to a 30% reduction with continuous use (HR 0.70, 95% CI 0.60–0.82). GLP-1 receptor agonists showed no significant difference from DPP4 inhibitors in the intention-to-treat analysis (HR 0.95, 95% CI 0.87–1.04), but continuous GLP-1RA use was associated with a 21% lower risk (HR 0.79, 95% CI 0.64–0.97).
GLP-1RAs and SGLT2 inhibitors showed comparable dementia risk in head-to-head comparison (HR 0.98, 95% CI 0.87–1.11).
Wu, Che-Yuan; Alkabbani, Wajd; Shah, Baiju R; Kapral, Moira K; Edwards, Jodi D; Maxwell, Colleen J; Swardfager, Walter · Cohort
RPEP-14191 · 2025The researchers designed H3B10-22R-(13/17αF), a 14-residue single-chain stapled peptide that acts as a potent and selective RXFP3 antagonist. Compared to the previous best RXFP3 antagonist (H3B1-22R):
- 12-fold improved serum stability
- Enhanced helical structure and antagonist potency
- High RXFP3 selectivity and binding affinity
- Significantly inhibited RXFP3 agonist-induced food intake in rats in vivo
This represents a major simplification from the native relaxin-3 molecule (two chains, three disulfide bonds) to a drug-like single-chain peptide.
Wu, Hongkang; Praveen, Praveen; Riches, Isabelle; Suresh, Devika P; Gil-Miravet, Isis; Navarro-Sánchez, Mónica; Olucha-Bordonau, Francisco E; Rosengren, K Johan; Bathgate, Ross A D; Hossain, Mohammed Akhter ·
RPEP-14194 · 2025After propensity score matching of 42,300 patients (21,150 per group), tirzepatide was associated with significantly reduced risks of: all-cause mortality (HR 0.443, 95% CI: 0.336-0.583, representing a 56% risk reduction), major adverse cardiovascular events (HR 0.731, 95% CI: 0.622-0.859, a 27% risk reduction), and major adverse kidney events (HR 0.427, 95% CI: 0.343-0.530, a 57% risk reduction). These associations were consistent across subgroups stratified by age (except 18-39 years), sex, BMI, and CPAP use. Sensitivity analyses confirmed robustness.
Wu, Jheng-Yan; Chen, Chia-Chen; Ling Tu, Wan; Hsu, Wan-Hsuan; Liu, Ting-Hui; Tsai, Ya-Wen; Huang, Po-Yu; Chuang, Min-Hsiang; Hung, Kuo-Chuan; Yu, Tsung; Lai, Chih-Cheng ·
RPEP-14195 · 2025After propensity score matching, 10,269 patients in each group were compared:
- Primary composite outcome (mortality + MACE + MAKE): No significant difference (HR 0.87, 95% CI 0.66-1.15, p = 0.335)
- All-cause mortality: No significant difference (HR 0.90, 95% CI 0.56-1.46, p = 0.672)
- MACE: No significant difference (HR 1.16, 95% CI 0.85-1.56, p = 0.344)
- MAKE (kidney events): Tirzepatide significantly lower (HR 0.60, 95% CI 0.42-0.87, p = 0.006) — a 40% reduction in kidney complications
Wu, Jheng-Yan; Lin, Yu-Min; Hsu, Wan-Hsuan; Liu, Ting-Hui; Tsai, Ya-Wen; Huang, Po-Yu; Chuang, Min-Hsiang; Yu, Tsung; Lai, Chih-Cheng ·
RPEP-14198 · 2025GLP-1RA use was associated with a 42% lower risk of dementia compared to DPP-4 inhibitors (HR 0.58, 95% CI 0.55–0.61, P < .0001). The drugs were also linked to a 38% lower risk of Alzheimer's disease (HR 0.62) and a 38% lower risk of vascular dementia (HR 0.62). Patients on GLP-1RAs were 24% less likely to be prescribed dementia-related medications (HR 0.76). These risk reductions were consistent across subgroups stratified by age, sex, and specific GLP-1RA type.
Wu, Jheng-Yan; Lin, Yu-Min; Hsu, Wan-Hsuan; Liu, Ting-Hui; Tsai, Ya-Wen; Huang, Po-Yu; Chuang, Min-Hsiang; Yu, Tsung; Lai, Chih-Cheng ·
RPEP-14201 · 2025The CatBoost machine learning model achieved the highest AUC of 0.809 for predicting three-year all-cause mortality in HF-AF patients, outperforming five other ML approaches. Of 558 patients, 215 (38.5%) reached the primary endpoint of death during median follow-up of 1,185 days.
SHAP analysis identified the top five predictive features: NYHA heart failure classification, absolute lymphocyte count (ALC), high-sensitivity C-reactive protein (hs-CRP), B-type natriuretic peptide (BNP), and age. Notable feature interactions were found between lymphocyte count and NYHA class, and between lymphocyte count and BNP, suggesting these biomarkers provide complementary prognostic information.
Wu, Jiacan; Tao, Guanghong; Xie, Siyuan; Yang, Han; Qi, Fenglin; Bao, Naiyue; Li, Zhuo; Chang, Guanglei; Xiao, Hua ·
RPEP-14208 · 2025The pooled relative risk of esophageal cancer in patients using GLP-1 receptor agonists compared to control agents was 0.46 (95% CI 0.13-1.59; p=0.725; I²=0%), indicating no increased risk and a non-significant trend toward reduced risk. There was no heterogeneity between studies (I²=0%).
Subgroup analyses stratified by age, intervention duration, BMI category, and indication (T2DM vs. obesity) consistently showed no association between GLP-1 RA use and increased esophageal cancer risk. No significant within-class differences were found among different GLP-1 receptor agonists.
Wu, Qi; Zeng, Yan; Liu, Yong; Teng, Fangyuan; Zhou, Tiejun; Guo, Man; Jiang, Zongzhe; Xu, Yong ·
RPEP-14210 · 2025MALDI-TOF mass spectrometry combined with PLS-DA statistical analysis could rapidly distinguish spontaneous bacterial peritonitis (SBP) from noninfected ascites by analyzing protein and lipid fingerprints directly from ascitic fluid — without the need for bacterial culture. Alpha-defensins, particularly human neutrophil peptides HNP-1 and HNP-2, emerged as promising SBP biomarkers. A novel fibrinogen fragment peptide (SSSYSKQFTSSTSYNRGDSTFES) was associated with non-infected ascites. Combining HNP-2 with this fibrinogen peptide achieved an AUC of 0.956 for SBP diagnosis — far superior to current clinical indicators.
Wu, Qiong; Wei, Bo; Zhang, Han; Shen, Jiayi; Yang, Xinyan; Qiu, Chengtong; Tao, Jian; Wang, Shijie; Wang, Junxue; Xie, Ying; Du, Yiping; Wu, Ting ·
RPEP-14211 · 2025PPI45 and PPI47 achieved high production yields (1.82 and 2.13 g/L, respectively — 2.19x and 2.60x higher than parent peptide PPI42). Both formed self-assembled hydrogels with distinct viscosities and showed pearl necklace-like protofibril structures on TEM. They demonstrated potent anti-MRSA activity (MIC 4-16 µg/mL) with sustained bactericidal effect after drug clearance. The mechanism involved 20-38% membrane disruption at 2x MIC within 2 hours, confirmed by SEM showing membrane damage and bacterial collapse. Safety testing showed minimal hemolysis on murine red blood cells and low cytotoxicity on human HaCaT epidermal cells.
Wu, Quanlong; Deng, Mengyin; Mao, Ruoyu; Yang, Na; Hao, Ya; Cao, Manli; Teng, Da; Wang, Jianhua ·
RPEP-14217 · 2025The GLP-1-Fc mRNA successfully encoded and produced GLP-1-Fc protein both in cell culture (HEK293T cells) and in living mice. In db/db diabetic mice, the mRNA treatment produced significantly higher GLP-1-Fc protein levels than controls, effectively reduced blood glucose after single and repeated administrations, and increased GLP-1 receptor expression. The glucose-lowering efficacy was comparable to dulaglutide (the existing GLP-1 protein drug). Intraperitoneal delivery did not cause tissue damage.
Wu, Xiaoying; Qiao, Jingtao; Xiao, Fei; Guo, Lixin ·
RPEP-14218 · 2025This review maps five distinct mechanisms by which antimicrobial peptides (AMPs) promote skin wound healing beyond just killing bacteria: (1) stimulating keratinocyte migration and proliferation to close wounds, (2) promoting collagen synthesis and tissue remodeling, (3) driving angiogenesis (new blood vessel formation), (4) modulating the immune response to reduce excessive inflammation, and (5) providing broad-spectrum antimicrobial activity against bacteria, fungi, and viruses.
The review also covers structural modifications (like cyclization and amino acid substitutions) and delivery systems (hydrogels, nanoparticles) that improve AMP stability and efficacy in wound settings. Several AMPs are now in clinical trials for wound healing applications.
Wu, Yifan; Liu, Tingting; Jin, Lili; Wang, Chuyuan; Zhang, Dianbao · Review
RPEP-14219 · 2025The STEP-HFpEF, STEP-HFpEF DM, and SUMMIT trials demonstrated that incretin-based therapies — both GLP-1 receptor agonists and dual GIP/GLP-1 receptor agonists — significantly improved heart failure symptoms, reduced heart failure worsening events, and induced weight loss in obese HFpEF patients, regardless of whether they also had diabetes.
The review also notes that SGLT2 inhibitors and non-steroidal MRAs show prognostic benefits in HFpEF with post hoc analyses suggesting enhanced efficacy in higher-BMI subgroups. The authors propose that combining incretin-based therapies with SGLT2 inhibitors and non-steroidal MRAs may be the optimal evidence-based strategy for this patient population.
Wu, Ying; Song, Meiyan; Chen, Xiaomin; Chen, Wen; Wu, Meifang; Lin, Liming ·
RPEP-14222 · 2025GLP-1 receptor agonists significantly delay gastric emptying, which raises the risk of retained gastric contents in patients presenting for endoscopic procedures. This is a key safety concern because residual food in the stomach during sedation increases aspiration risk. The review highlights that healthcare practitioners need evidence-based protocols for managing GLP-1 users before, during, and after gastrointestinal procedures, including considerations about medication timing and fasting instructions.
Wunder, Linda; Lee, Rebecca; Dalpé Welliver, Dawn ·
RPEP-14226 · 2025This review of 66 studies found consistent evidence that oral hydrolyzed collagen peptide supplementation improves skin elasticity, hydration, and wrinkle reduction. Effective doses ranged from 1 to 10 g daily, with benefits appearing after 4 to 8 weeks, and a dose as low as 2.5 g/day showed measurable skin improvements. Combining collagen peptides with vitamins, minerals, and antioxidants provided additional benefits including improved skin radiance and reduced pore size.
The review also identified that poor sleep impairs skin hydration, increases transepidermal water loss, and reduces elasticity — suggesting that sleep quality may significantly modulate the effectiveness of collagen peptide supplementation.
Xerfan, Ellen M S; Souza, Maingredy Rodrigues; Facina, Anamaria S; Tufik, Sergio; Andersen, Monica L · Review
RPEP-14227 · 2025In db/db diabetic mice with full-thickness wounds, dulaglutide delivered via subcutaneous injection around the wound:
- Increased VEGF expression and Ki67 proliferation marker, accelerating wound closure
- In vitro, promoted keratinocyte (HaCaT cell) proliferation and migration under high glucose conditions
- High glucose induced ferroptosis markers: increased Fe²⁺, ROS, and MDA; decreased GSH and SOD
- Dulaglutide reversed all ferroptosis markers
- Mechanism: dulaglutide activated Nrf2 signaling, increasing Gpx4 and Slc7a11 expression to inhibit ferroptosis
- Results consistent in both in vivo (mouse wounds) and in vitro (cell culture) models
Xi, Liuqing; Du, Juan; Lu, Yan; Xue, Wen; Xia, Yuxuan; Chen, Tingxu; Xiao, Yang; Xu, Nuo; Wang, Yansheng; Gao, Jianfang; Li, Wenyi; Huang, Shan ·
RPEP-14234 · 2025HEC88473, a GLP-1/FGF21 dual agonist given as weekly subcutaneous injections for 5 weeks, produced dose-proportional reductions in liver fat measured by MRI-PDFF. The best-performing dose (30.6 mg) achieved a 47.21% relative reduction in liver fat (p = 0.0143) versus 15.05% with placebo. Patients with higher baseline fat (PDFF >8%) were more likely to achieve >30% relative reductions.
Blood sugar control also improved significantly: HbA1c dropped by up to 1.10% in the 68.0 mg group versus 0.31% with placebo, along with reductions in fasting and post-meal glucose levels. Lipid profiles improved across dose groups. The drug was generally well tolerated, with GI disorders being the most common adverse event (48.3%), mostly mild to moderate.
Xiang, Lin; Wang, Guixia; Zhuang, Yulei; Luo, Lin; Yan, Jiangyu; Zhang, Hong; Li, Xiaojiao; Xie, Can; He, Qingwei; Peng, Yuyu; Chen, Hong; Li, Qianqian; Li, Xiaoping; Guo, Linfeng; Lv, Guoyue; Ding, Yanhua · Rct
RPEP-14242 · 2025Recombinant myticofensin-B1 (65 amino acids, 6 conserved cysteine residues forming 3 disulfide bonds) was successfully expressed in Pichia pastoris with a confirmed molecular weight of 8,849.9 Da matching the theoretical prediction. LC-MS/MS confirmed structural fidelity.
The recombinant peptide demonstrated broad-spectrum antimicrobial activity with stronger inhibition against Gram-negative bacteria. Scanning electron microscopy revealed the peptide affected different bacterial species through different physical mechanisms. Importantly, it showed very low hemolytic activity against sheep red blood cells (indicating safety for blood cells) and weak cytotoxicity against human A549 lung cancer cells.
Xiao, Wenhui; Song, Fang; Chen, Chuanyue; Huang, Fangfang; Yang, Qiaomei; Zhang, Xiaolin; Liao, Zhi ·
RPEP-14245 · 2025Direct injection of exendin-4 (25 ng) into the dorsolateral septum (dLS) significantly reduced ethanol operant self-administration in male high-responder rats but had no effect in male low responders or females. In relapse tests, intra-dLS exendin-4 reduced reacquisition of ethanol self-administration — a model of relapse to drinking after abstinence — but did not affect prime + context-induced reinstatement of ethanol seeking, a model of cue/context-triggered relapse.
Importantly, the alcohol reduction occurred without sustained changes in 24-hour food intake or body weight, indicating the effect was specific to reward processing rather than general appetite suppression. Retrograde tracing confirmed that the dLS receives direct input from GLP-1-producing neurons in the nucleus tractus solitarius (NTS), establishing an anatomical basis for this signaling pathway.
Xiao, Yuqing; Yap, Jo Ann; Ong, Zhi Yi ·
RPEP-14250 · 2025Key safety comparisons from the network meta-analysis:
- Liraglutide 3.0mg had significantly higher overall adverse events (OR 1.53-2.00) versus both semaglutide and tirzepatide
- Tirzepatide showed higher severe hypoglycemia risk (<54 mg/dL) and more injection-site reactions
- Tirzepatide demonstrated superior safety for neoplasms vs liraglutide (OR 5.15, 95% CI 1.28-20.74) and vs semaglutide (OR 3.55, 95% CI 1.10-11.54)
- Tirzepatide also showed fewer respiratory infections/nasopharyngitis
- GLP-1 monoagonists had fewer diarrhea events but more abdominal pain/dyspepsia
- Non-T2DM patients had significantly more adverse events than T2DM patients (P<0.05)
- No significant differences by race, BMI, or treatment duration
Xie, Zeyu; Liang, Zhuoru; Xie, Yilin; Zheng, Guimei; Cao, Weiling ·
RPEP-14251 · 2025The review identifies multiple mechanisms by which GLP-1 receptor agonists benefit the eye:
- Retinal ganglion cell (RGC) rescue via calcium channel and GABAergic modulation — protecting the nerve cells critical for vision
- Mitochondrial protection through PINK1/Parkin-mediated mitophagy and ERK1/2-HDAC6 signaling — clearing damaged mitochondria to prevent cell death
- Anti-inflammatory effects via cytokine reduction and immune cell recruitment inhibition
- Retinal vascular stabilization and extracellular matrix homeostasis
- Anti-angiogenic properties that inhibit pathological new blood vessel growth
Clinical evidence shows reduced glaucoma incidence and potential diabetic retinopathy benefits. However, conflicting evidence highlights context-dependent risks, including early DR worsening when glycemic control improves rapidly in poorly controlled diabetic patients.
Xie, Zhixuan; Yang, Zuyi; Tian, Dianzhe; Chen, Youxin ·
RPEP-14254 · 2025The review synthesizes three key lines of evidence linking oxytocin to autism: (1) reduced oxytocin levels and mutations in the oxytocin system have been documented in autism patients; (2) in animal models with oxytocin system deficits, social behavior problems mirror aspects of autism and can be rescued by administering oxytocin; and (3) clinical trials using intranasal oxytocin have shown some ability to alleviate social interaction deficits in autistic individuals.
However, clinical outcomes have been inconsistent, suggesting that multiple factors influence treatment response. The neuropeptide's established roles — increasing attention to social cues, elevating salience of socially relevant stimuli, and enhancing social learning and reward — provide the mechanistic basis for its therapeutic potential in autism.
Xing, Chuan; Yu, Xiang ·
RPEP-14261 · 2025PanPep's reported performance was successfully reproduced on original datasets. On a newly curated independent dataset, PanPep showed superior generalization to unseen antigens with few or no known TCR binders compared to control tools.
The framework was successfully extended to peptide-TCRα and peptide-TCRαβ binding prediction, demonstrating applicability in more biologically relevant contexts. However, PanPep showed limitations in early binder enrichment (identifying the top binders from large pools) and reduced robustness to novel TCRs not seen during training, indicating sensitivity to training data composition and negative sampling strategies.
Xu, Dong; He, Fei; Wang, Xianyu ·
RPEP-14263 · 2025Starting from capromorelin, researchers designed compound 4b, a novel oral ghrelin receptor (GHSR-1a) agonist with an EC50 of 0.49 nM — making it 100-fold more potent than ibutamoren (MK-677) at stimulating endogenous growth hormone release in rats. At oral doses as low as 0.1 mg/kg, compound 4b effectively triggered GH secretion. In young rats, 10 days of oral treatment increased both body weight and body length. In dogs, the compound showed 43.6% oral bioavailability with a 1.2-hour half-life.
Xu, Hang; Liu, Meng; Jia, Xiangyu; Zhao, Sheng; Xia, Yuanfeng; Lu, Biao; Yang, Fanglong; Wang, Siqin; Jin, Lei ·
RPEP-14265 · 2025Inflammatory stress activated the enzyme nSMase2 in insulin-producing beta cells, generating ceramide-enriched extracellular vesicles (EVs) that carried distinct miRNA cargo linked to beta-cell function. These ceramide-loaded EVs impaired glucose-stimulated insulin secretion in neighboring healthy beta cells — an effect that was blocked when nSMase2 was knocked down in the parent cells. A GLP-1 receptor agonist was also able to modulate beta-cell EV ceramide content. Plasma EVs from children with recent-onset type 1 diabetes showed elevated ceramide species, confirming clinical relevance.
Xu, Jerry; Amalaraj, Irene; De Oliveira, Andre; Harris-Kawano, Arianna; Enriquez, Jacob R; Mirmira, Raghavendra G; Eder, Josie G; Burnet, Meagan C; Díaz Ludovico, Ivo; Flores, Javier E; Nakayasu, Ernesto S; Sims, Emily K ·
RPEP-14266 · 2025Researchers identified the first buccalin receptor in the sea slug Aplysia californica, designated apBuc/AstA-R. All 19 mature buccalin peptides activated this G protein-coupled receptor in a dose-dependent manner, with EC50 values ranging from 23 to 320 nM.
Critically, the study found cross-activity: fruit fly allatostatin A peptides and human kisspeptin could also activate this Aplysia receptor, while human galanin could not. This supports the hypothesis that the mollusk buccalin/allatostatin A signaling system is evolutionarily related to the mammalian galanin and kisspeptin systems — peptide families important in reproduction, metabolism, and appetite.
Xu, Ju-Ping; Ding, Xue-Ying; Jin, Qing-Chun; Zhang, Yi-Long; Chang, Jian-Hui; Jiang, Hui-Min; Li, Ya-Dong; Fu, Ping; Zhang, Yan-Chu-Fei; Liu, Cui-Ping; Mao, Rui-Ting; Liu, Cheng-Yi; Li, Fan; Wu, Shao-Qian; Cropper, Elizabeth C; Zhang, Guo; Jing, Jian · Basic Research
RPEP-14269 · 2025Using molecular dynamics simulations, researchers revealed how three different types of GLP-1 receptor agonists — a biased small molecule (CHU-128), a balanced small molecule (danuglipron), and a balanced peptide (Peptide 19) — each produce distinct structural changes in the receptor. Each ligand induced unique helix packing arrangements and conformational dynamics, explaining at the atomic level why different drugs activate different downstream signaling pathways from the same receptor.
The simulations showed that biased versus balanced agonists produce fundamentally different receptor shapes, which determines whether the receptor preferentially signals through G-proteins, β-arrestin, or both.
Xu, Marc; Vogel, Horst; Yuan, Shuguang · Computational
RPEP-14270 · 2025CGRP (calcitonin gene-related peptide) is emerging as a key mediator of tumor-nerve crosstalk that drives cancer growth, suppresses anti-tumor immunity, and contributes to cancer-associated symptoms. The concept of 'CGRP-mediated neural addiction' describes how tumors hijack neural signaling through CGRP to remodel their microenvironment and sustain growth, positioning CGRP as a promising therapeutic target for disrupting tumor-nerve interactions.
Xu, Miaochun; Yu, Yang; Cao, Canhui ·
RPEP-14271 · 2025The review identifies multiple neuroimmune mechanisms in the tumor microenvironment: norepinephrine and cortisol modulate dendritic cell priming, NK cell cytotoxicity, CD8+ T-cell function, and myeloid polarization to create immunosuppression. Neuropeptides including CGRP contribute to immune evasion. Tumors drive their own neural innervation (tumor-associated neurogenesis), creating positive feedback loops. Therapeutic strategies discussed include β-adrenergic blockade, CGRP receptor antagonism, and inhibition of neurotrophic factors (NGF, BDNF). Combining immune checkpoint inhibitors with neuromodulation is proposed to overcome drug resistance.
Xu, Nuo; Bian, Saiyan; Lyu, Pin; He, Xuyang; Zheng, Wenjie ·
RPEP-14280 · 2025Oral administration of Val-Trp (VW) at 40 mg/kg effectively reduced both systolic and diastolic blood pressure in spontaneously hypertensive rats (SHRs). The peptide works through a dual mechanism: it directly inhibits ACE by binding to the enzyme's active pocket, and it activates the eNOS/NO/cGMP signaling pathway, which promotes nitric oxide production, increases cGMP, decreases intracellular calcium, and ultimately relaxes blood vessels.
Molecular studies revealed that VW binds to ACE through a spontaneous exothermic process involving hydrogen bonding and hydrophobic interactions, causing structural changes in the enzyme that prevent its normal substrate from binding.
Xu, Yang; Dou, Zishan; Liu, Jingli; Yahia, Zineb Ould; Chen, Wei ·
RPEP-14283 · 2025Glutamatergic neurons derived from migraine patient iPSCs showed functional abnormalities compared to healthy controls. Ion channel dysfunction was observed in sodium and potassium channel function via patch-clamp recordings. Expression of migraine-associated molecules was altered, including CGRP (calcitonin gene-related peptide), P2RX3 (a pain receptor), and c-Fos (a marker of neuronal activation).
These findings collectively suggest that intrinsic neuronal dysfunction — present even in lab-grown cells outside the body — may contribute to migraine pathology. The study establishes the feasibility of using iPSC-derived neurons as a human-specific migraine research model.
Xu, Yueyue; Yao, Yitian; Sun, Li; Chen, Li; Li, Chenyang; Wang, Wenyuan; Yang, Jiajun ·
RPEP-14284 · 2025Among 15,811 commercially insured adults who started semaglutide for weight management, 46% discontinued within the first 5 months. Discontinuation was strongly linked to out-of-pocket costs: rates ranged from 41% in the lowest copayment quintile ($1-$54/month) to 51% in the highest quintile ($161-$1,460/month). Most users deviated from the recommended monthly dose-escalation schedule. Similar discontinuation rates (48%) were observed in patients starting after supply shortages resolved (post-October 2023), indicating the problem is not supply-driven.
Xu, Yunwen; Carrero, Juan J; Chang, Alexander R; Inker, Lesley A; Zhang, Donglan; Mukhopadhyay, Amrita; Blecker, Saul B; Horwitz, Leora I; Grams, Morgan E; Shin, Jung-Im ·
RPEP-14285 · 2025The fish phosvitin-derived antimicrobial peptide Pt5-1c enhanced angiogenesis (new blood vessel formation) in both murine full-thickness wound models and zebrafish vascular defect models. In vitro, Pt5-1c promoted endothelial cell motility, adhesion, survival, filopodia protrusion, and tube formation. It upregulated proangiogenic growth factors VEGF, PDGF, FGF, and EGF. The signaling pathways involved were PI3K/AKT/mTOR, p38 MAPK, and HIF-1-VEGF axis.
Xuan, Cuiling; Li, Mei; Zhang, Peng; Wang, Yunchao; Li, Hongyan; Gao, Zhiqin; Zhang, Shicui; Wu, Fei ·
RPEP-14292 · 2025GLP-1 and ghrelin act as opposing regulators of the insulin system at three key levels: pancreatic beta cells (GLP-1 stimulates insulin release, ghrelin suppresses it), vagal afferent neurons, and hypothalamic arcuate nucleus neurons. Critically, their timing is complementary — ghrelin rises and acts before meals while GLP-1 rises and acts after meals. This preprandial/postprandial interplay with insulin creates an integrated circadian control system for appetite, blood sugar, and metabolism.
Yada, Toshihiko; Dezaki, Katsuya; Iwasaki, Yusaku · Review
RPEP-14300 · 2025In 16 participants who completed the 12-week study, the glucose infusion rate (GIR, the gold standard measure of insulin sensitivity) increased from 3.21 to 5.16 mg/min/kg — a 61% improvement (p significant). HbA1c decreased from 63.4 to 43.6 mmol/mol (7.95% to 6.14%, p < 0.001). Body weight decreased by 4.9 kg (5.0%, p < 0.001). Fat mass decreased by 9.1%, muscle mass by 1.8%, and fat percentage by 4.5%. Glucagon decreased from 28.8 to 20.8 pg/ml.
Critically, simple linear regression showed no significant relationship between changes in GIR and changes in any other clinical variable, indicating that the insulin sensitivity improvement was not explained by weight loss, fat reduction, or other measurable metabolic changes alone.
Yamaguchi, Yuko; Kuwata, Hitoshi; Imura, Masahiro; Moyama, Shota; Usui, Ryota; Matsushiro, Mari; Hamamoto, Yoshiyuki; Yamada, Yuichiro; Seino, Yutaka; Yamazaki, Yuji ·
RPEP-14304 · 2025Dual GIP/GLP-1 receptor agonists, led by tirzepatide, provide superior glycemic control and weight loss compared to selective GLP-1 receptor agonists alone, demonstrating synergistic effects between the two incretin pathways. GIP, historically overlooked due to reduced beta-cell responsiveness in type 2 diabetes, has been rehabilitated as a therapeutic target through dual agonism.
The review identifies multiple cardiovascular protective mechanisms of incretin hormones: improved lipid metabolism, blood pressure reduction, enhanced endothelial nitric oxide activity, suppressed macrophage inflammation, decreased foam-cell formation, and atherosclerotic plaque stabilization. Emerging triple agonists and genotype-guided incretin therapy represent the next frontier.
Yamanouchi, Dai ·
RPEP-14306 · 2025Self-assembling peptide hydrogel (0.8%) produced a bone-volume-to-total-volume (BV/TV) ratio of 0.34 ± 0.09 at 56 weeks, which was not significantly higher than the empty control cage. BMP-2 (50 ng/μL) with bone chips achieved the highest BV/TV ratio of 0.78 ± 0.05, significantly exceeding bone chips alone (p<0.01) and peptide hydrogel with bone chips (p<0.05). The results indicate that peptide hydrogels benefit from combination with osteoinductive factors like BMP-2.
Yamauchi, Ippei; Nakashima, Hiroaki; Ito, Sadayuki; Segi, Naoki; Ouchida, Jun; Morita, Yoshinori; Ode, Yukihito; Nagatani, Yasuhiro; Okada, Yuya; Ando, Kei; Imagama, Shiro ·
RPEP-14308 · 2025In a secondary analysis of a pilot RCT, the GLP-1 agonist exenatide showed stronger smoking cessation benefits in specific patient subgroups. Exenatide (added to nicotine patch) worked better than placebo plus nicotine patch in people who smoked more than 20 cigarettes per day (posterior probability 81.7%), those without obesity (PP = 94.4%), those without prediabetes (PP = 76.0%), and those with no or minimal depression (PP = 91.2%).
A striking genetic finding emerged: exenatide was more effective only in individuals with the CHRNA rs16969968 GG genotype (PP = 88.6%), a nicotine receptor gene variant associated with smoking behavior. This suggests that GLP-1 drugs for smoking cessation may be most effective in a specific subset of smokers — heavy smokers who are not obese, not depressed, and carry a particular genetic profile.
Yammine, Luba; de Dios, Constanza; Suchting, Robert; Green, Charles E; Nielsen, David A; Walss-Bass, Consuelo; Schmitz, Joy M · Secondary Analysis Of Randomized Controlled Trial
RPEP-14310 · 2025In adult congenital heart disease (CHD) patients who underwent coronary artery bypass grafting (CABG), perioperative use of GLP-1 receptor agonists was associated with a 32% reduction in one-year hospital readmission rates (OR = 0.68, p = 0.0118) compared to non-users after propensity score matching.
Importantly, GLP-1 RA use did not increase mortality (OR = 0.747, p = 0.35), nor did it increase rates of any postoperative complications including acute kidney injury, heart attack, stroke, or arrhythmia. Known GLP-1-related side effects like gastroparesis and abnormal weight loss showed no difference between groups. The study suggests GLP-1 agonists are safe to use around heart bypass surgery and may reduce the likelihood of hospital readmission.
Yan, Jason H; McKinnerney, Joey; Al Janabi, Taysir; Chahal, Anwar; Malik, Adnan; Vranian, Michael N; Kashyap, Rahul · Retrospective Cohort Study