RPEP-16205 · 2026Across 84 lesions in 21 pigs, PuraStat-treated wounds showed significantly greater re-epithelialization-to-defect ratios versus controls (p = 0.03), particularly after EMR. Endoscopic measurements showed 33% mean wound size reduction in the PuraStat group (p = 0.001). Histopathological analysis of defect area reduction approached but did not reach significance (p = 0.055). No adverse events were observed. The effect was more pronounced in EMR-induced lesions than ESD-induced lesions.
Tachecí, Ilja; Šembera, Štěpán; Zimandlová, Dana; Morávková, Paula; Vejvalková, Kateřina Geisler; Radochová, Věra; Ryška, Aleš; Cyrany, Jiří ·
RPEP-16211 · 2026At 6 months, 31.7% of the 4,309 enrollees met adherence criteria, with mean weight loss of 16.9% (±8.6; 98.0% achieved ≥5% reduction). At 12 months, 16.1% were adherent with mean weight loss of 22.7% (±7.2; 100% achieved ≥5% reduction). First-month weight loss was the strongest predictor of 6- and 12-month outcomes. Sustained weekly weight tracking and health coach messaging were strongly associated with retention and greater weight loss. Paradoxically, very frequent weight tracking in month one correlated with poorer outcomes. Side effects were common but mostly mild/moderate and did not predict dropout.
Talay, Louis; Hom, Jason; Scott, Tamara; Ahuja, Neera ·
RPEP-16212 · 2026Combining antimicrobial peptides (AMPs) with conventional antibiotics produces synergistic antibacterial effects against multidrug-resistant (MDR) bacteria. The synergy works because AMPs disrupt bacterial membranes, which allows antibiotics to penetrate more effectively — essentially punching holes that let the drugs in. This combination approach can restore susceptibility to antibiotics that bacteria had become resistant to.
The review identifies key mechanisms driving this synergy: increased membrane permeability, enhanced porin-dependent antibiotic uptake, and immunomodulatory effects that boost the host's own defenses. However, significant translational barriers remain, including peptide instability, pharmacokinetic mismatches between AMPs and antibiotics, potential toxicity, and strain-dependent variability in whether synergy actually occurs.
Talha, Muhammad; Roque-Borda, Cesar Augusto · Review
RPEP-16217 · 2026Tirzepatide dramatically reduced the formation of thoracic aortic aneurysm and dissection (TAAD) in mice — from 88.9% to 50.0% — and cut related deaths from 83.3% to 38.9%. The drug prevented pathological widening of the aorta in all three segments (ascending, arch, and descending) and preserved elastic fiber integrity.
The mechanism involved two key pathways: tirzepatide suppressed the NLRP3 inflammasome (reducing IL-1β, IL-6, and MCP-1 inflammation), and it prevented vascular smooth muscle cells from losing their contractile phenotype — a critical event in aneurysm development. In vitro experiments on human aortic smooth muscle cells confirmed that tirzepatide directly reversed the cellular changes that lead to weakened blood vessel walls.
Tan, Liao; Liu, Jie; Shi, Ruizheng; Liu, Yubo · Animal
RPEP-16219 · 2026Among 75,243 U.S. adults with type 2 diabetes and established atherosclerotic cardiovascular disease, semaglutide users had a 22% lower risk of major adverse cardiovascular events (MACE) compared to dulaglutide users (HR 0.78, 95% CI 0.70–0.87, p<0.001).
MACE incidence rates were 25.7 per 1,000 person-years for semaglutide versus 33.0 for dulaglutide. After entropy balancing to account for baseline differences, all standardized mean differences were below 0.1, indicating well-matched cohorts.
Tan, Xi; Liang, Yuanjie; Xie, Lin; Harton, Joanna; Gutierrez, Cynthia; Muhammad, Chalak; Swift, Caroline; de Havenon, Adam · Retrospective Cohort
RPEP-16221 · 2026GLP-1 receptor agonists were not associated with increased risk of most psychiatric disorders compared to SGLT2 inhibitors or DPP-4 inhibitors in adults with type 2 diabetes. However, a modest association with anxiety disorder was observed. The study used target trial emulation — a rigorous real-world evidence method that mimics the design of a randomized clinical trial using observational data — to compare psychiatric outcomes across these three diabetes drug classes.
Tang, Huilin; Lu, Yiwen; Zhang, Bingyu; Zhang, Dazheng; Zhou, Ting; Chen, Jiajie; Lu, Ying; Lyu, Tianchu; Zheng, Kai; Chen, Yong · Observational
RPEP-16225 · 2026The study established NPY5R as a therapeutic target in lung adenocarcinoma through multiple lines of evidence:
- High NPY5R expression in lung tumors correlated with poor patient prognosis
- NPY5R expression was associated with immune cell infiltration in tumors
- Euphorbia Factor L2 (EFL2) targeted NPY5R and inhibited A549 lung cancer cell proliferation and migration while inducing cell death (apoptosis)
- Genetic knockdown of NPY5R further enhanced anti-tumor effects
- Combining NPY5R knockdown with EFL2 treatment synergistically activated ECM, PI3K-Akt, and MAPK pathways
- Four potential molecular targets downstream of NPY5R were identified via RNA sequencing
Tao, Pengzhuo; Liu, Wei; Wang, Yongfu; Xue, Yajing; Liu, Changmin; Yuan, Yizhen; Leu, Kim Fey; Chen, Shilin; Song, Chi ·
RPEP-16226 · 2026Teduglutide therapy in a patient with short bowel syndrome requiring home parenteral nutrition led to significant clinical and nutritional improvement: 70% reduction in parenteral nutrition requirements, spontaneous closure of enterocutaneous fistulas, and sufficient intestinal adaptation to enable surgical bowel reconstruction.
Following surgery, the patient achieved full enteral autonomy — completely independent of intravenous nutrition. She later developed grade 1 obesity, highlighting the completeness of the nutritional recovery. The case demonstrates teduglutide's potential as a bridging therapy that can create conditions for surgical intervention and ultimate intestinal independence.
Tapia-Sanchiz, María Sara; Sampedro-Núñez, Miguel Antonio; Jiménez-Blanco, Sara; Molina-Baena, Begoña ·
RPEP-16231 · 2026A 35-year-old man with class II obesity (BMI 37.8) and severe lumbar spinal epidural lipomatosis (SEL) causing progressive neurogenic claudication was treated with tirzepatide instead of surgery. After one year of treatment, he lost approximately 60 pounds, experienced marked symptom resolution, and repeat MRI showed near-complete regression of the epidural fat deposits that had been compressing his spine.
This is the first reported case of pharmacological weight loss reversing SEL, eliminating the need for surgical decompression.
Tazhibi, Masih; Liu, David D; Chalif, Joshua I; Ali, Rohaid; Chi, John H ·
RPEP-16233 · 2026The review covers 16 drugs that entered Parkinson's clinical trials after preclinical evaluation, across four categories: L-DOPA-induced dyskinesia treatment (buspirone, JM-010, befiradol, mesdopetam, foliglurax, dipraglurant), parkinsonism treatment (tavapadon), disease modification (prasinezumab, cinpanemab, nilotinib, minzasolmin, exenatide, NLY01, liraglutide, lixisenatide, semaglutide). For each drug, the review examines whether preclinical efficacy translated to clinical outcomes and identifies factors that influenced translational success or failure.
Teil, Margaux; Huot, Philippe ·
RPEP-16244 · 2026Over two years, insured patients who had Roux-en-Y gastric bypass (RYGB) surgery paid $704 less in out-of-pocket healthcare costs than matched patients treated with GLP-1 receptor agonists (semaglutide or tirzepatide) for type 2 diabetes and obesity.
In the first year, costs were similar between groups ($2,301 for RYGB vs. $2,179 for GLP-1 RAs, p=0.15). But in the second year, RYGB costs dropped significantly to $1,277 while GLP-1 RA costs remained at $2,104 (p<0.01), driven by the ongoing prescription costs of the medications.
Thiyagarajan, Sibi; Wall-Wieler, Elizabeth; Liu, Yuki; Zheng, Feibi; Edwards, Michael · Observational
RPEP-16248 · 2026The review identifies three key mitochondria-derived peptide (MDP) families and their roles in liver health:
- Humanin: The first discovered MDP; protects hepatocytes from stress-induced cell death (apoptosis) and modulates lipid metabolism, exerting hepatoprotective effects in fatty liver disease
- MOTS-c: Activates AMPK (a master metabolic regulator), regulates nuclear gene expression, suppresses fibrotic and inflammatory signaling, and restores mitochondrial function in MASLD and fibrosis models
- SHLPs (1-6): Particularly SHLP2, which enhances mitochondrial function, improves insulin sensitivity, supports glucose homeostasis, and mitigates oxidative stress
MDPs work both inside cells (modulating mitochondrial activity, oxidative stress, apoptosis) and outside cells (autocrine, paracrine, endocrine signaling), establishing a novel paradigm where mitochondrial DNA function extends well beyond energy production.
Thoudam, Themis; Zeng, Ge; Gao, Hui; Jiang, Yanchao; Huda, Nazmul; Yang, Zhihong; Ma, Jing; Liangpunsakul, Suthat ·
RPEP-16250 · 2026The review provides a comprehensive overview of LAB-derived bacteriocins:
- Classification updated into Classes I-III based on structure and genetics
- Biosynthesis regulated by quorum sensing (bacterial communication) and two-component signaling systems
- Health benefits extend beyond antimicrobial activity to include anti-cancer effects, achieved primarily through membrane disruption mechanisms
- Production can be enhanced through metabolic engineering, synthetic biology, combination therapies, and novel purification methods
- Key challenge: scaling production while maintaining efficacy and overcoming barriers to clinical translation
Tian, Shuhua; Ma, Shaotong; Xia, Yujie; Huang, Ke ·
RPEP-16255 · 2026At equivalent weight loss (~15% total weight loss):
- Surgery: significant increases in postprandial fullness and decreases in hunger and prospective eating; diet: no significant changes
- Food cravings decreased in both groups initially, but only surgery maintained reduced cravings at one year
- Postprandial GLP-1 nearly doubled after surgery (p<0.0001) but did not change with LCD (p=0.34)
- GLP-1 increase correlated with increased fullness after surgery (r=0.69, p=0.038)
At one year, surgery produced 30.2% total weight loss vs 14.6% for LCD (p<0.0001), consistent with the hormonal and appetite advantages documented at the equivalent weight loss timepoint.
Tolbert, Lelia; Borden, Sarah; Leskowitz, Jamie; Ramakrishnan, Rajasekhar; Reid, Tirissa; Krikhely, Abraham; Bessler, Marc; Korner, Judith ·
RPEP-16256 · 2026Meta-analyses showed distinct benefits for each treatment modality. Mindfulness-based CBT significantly improved total Female Sexual Function Index (FSFI) scores and subscales for desire, arousal, and orgasm. Flibanserin improved total FSFI and the desire subscale. Bremelanotide improved total FSFI along with desire and arousal subscales.
All three treatments reduced distress as measured by the Female Sexual Distress Scale. No head-to-head studies comparing CBT to pharmacotherapy were identified. Of 36 included studies, 26 were randomized controlled trials and 10 were single-arm trials.
Toledo, Rafaela Germano; Winkelman, William D; Reyes-Gonzalez, Daniela; Bergeron, Sophie; Fladger, Anne; Hacker, Michele R; Anand, Mallika ·
RPEP-16264 · 2026Higher GLP-1 receptor expression (genetically proxying GLP-1RA use) was causally associated with lower risk of type 2 diabetes (OR 0.94, 95% CI 0.92–0.97) and myocardial infarction (OR 0.97, 95% CI 0.95–1.00).
Metabolic improvements mediated the MI protection:
- HbA1c: 36.67% of the effect (95% CI 3.89–69.44%)
- BMI: 28.86% (95% CI 2.62–55.10%)
- Triglycerides: 18.52% (95% CI 1.47–35.57%)
- HDL-cholesterol: 18.28% (95% CI 1.45–35.12%)
- Systolic blood pressure: 11.55% (95% CI 0.33–22.76%)
Critically, multivariate MR adjusting for all metabolic traits showed no direct effect of GLP-1R expression on MI (β = -0.003, P = 0.12), meaning the cardiovascular benefit is fully mediated through metabolic improvements.
Tong, Jingkai; Li, Nana; Hu, Fang; Yue, Yingying ·
RPEP-16267 · 2026GLP-1 agonists were associated with a statistically significant 3-fold increase in resolution of MASH without worsening fibrosis (RR 3.03, p<0.05) compared to controls. They also significantly improved liver fibrosis, weight loss, HbA1c, and alanine aminotransferase levels (SMD -0.54, p=0.008).
Importantly, in patients without type 2 diabetes, GLP-1 agonists showed no significant effect on weight loss (SMD -0.97, p=0.12) or fibrosis improvement (RR 1.54, p=0.24). Overall adverse events were slightly higher with GLP-1 agonists (RR 1.10, p<0.05), but serious adverse events were comparable between groups.
Tornea, Denisia Adelina; Goldis, Christian; Isaic, Alexandru; Motofelea, Alexandru Catalin; Sima, Alexandra Christa; Ciocarlie, Tudor; Crintea, Andreea; Diaconescu, Razvan Gheorghe; Motofelea, Nadica; Goldis, Adrian ·
RPEP-16269 · 2026Over three months, oral semaglutide 14 mg (n=10) significantly outperformed metformin XR 2000 mg (n=17) for weight loss: -6.5 ± 3.6 kg vs. -1.6 ± 2.5 kg (95% CI: -7.6 to -2.2; P=0.001). BMI reduction was also superior: -2.0 ± 1.2 vs. -0.3 ± 0.9 kg/m² (P=0.001).
Genetic findings (exploratory):
- OCT1 rs34130495 was associated with HDL cholesterol change in metformin-treated participants (β=+0.340 mmol/L per minor allele; P=0.0026; q=0.063 at 10% FDR)
- GLP1R rs6923761 showed nominal trends for weight and BMI change in semaglutide users (P≈0.06-0.07) but did not survive FDR correction
The authors describe these as hypothesis-generating data supporting the feasibility of genotype-guided diabetes treatment studies.
Tourtourikov, Ivan; Kalinkova, Maria; Ivanov, Peter; Mileva-Popova, Rene; Tafradjiiska-Hadjiolova, Radka; Handjieva-Darlenska, Teodora; Kadiyska, Tanya ·
RPEP-16272 · 2026CGRP in the amygdala — a brain region critical for pain processing — selectively modulated cold sensitivity but not mechanical sensitivity in two mouse models of neuropathic pain. Infusing CGRP into the amygdala reduced cold sensitivity in nerve injury (SNI) and chemotherapy-induced (paclitaxel) neuropathy models, while blocking CGRP with the antagonist CGRP 8-37 increased cold sensitivity. Notably, the effects were complex: they depended on which side of the brain was injected, which paw was tested, and whether the neuropathy was caused by nerve injury or chemotherapy. CGRP had no effect on mechanical pain sensitivity in either model.
Trail, Alexis D; Allen, Heather N; Paul, Blesson; Nelson, Tyler S; Widner, James A; Lewter, Lakeisha; Tack, See H; Neilan, Rachael Miller; Kolber, Benedict J · Animal Study
RPEP-16285 · 2026In this subgroup analysis of the landmark FLOW trial (3,533 participants, median 3.4-year follow-up), once-weekly semaglutide 1 mg reduced the primary composite kidney outcome by 24% (HR 0.76, 95% CI 0.66-0.88) and all-cause death by 20% (HR 0.80, 95% CI 0.67-0.95) compared to placebo in people with type 2 diabetes and chronic kidney disease.
Critically, these benefits were consistent across the full spectrum of CKD severity — from milder to advanced kidney disease. Whether patients had eGFR above 60 or below 30, semaglutide provided similar protection. One standout finding: patients with the most severe kidney damage (UACR ≥2000 mg/g) had the largest mortality reduction — 53% lower death risk (HR 0.47). The primary outcome included kidney failure (≥50% eGFR decline, eGFR <15, dialysis, transplant) and death from kidney or cardiovascular causes.
Tuttle, Katherine R; Mann, Johannes F E; Mayrdorfer, Manuel M; Rayner, Brian; Pugliese, Giuseppe; Pratley, Richard E; Perkovic, Vlado; Mahaffey, Kenneth W; Kashihara, Naoki; Jeppesen, Ole K; Gumprecht, Janusz; Correa-Rotter, Ricardo; Cherney, David Z I; Bosch-Traberg, Heidrun; Arici, Mustafa; Rossing, Peter · Randomized Controlled Trial
RPEP-16290 · 2026Semaglutide improved Physical Component Summary (PCS) scores at both weeks 15 and 30, with effect sizes exceeding the minimally important difference. Causal mediation analysis estimated that approximately half of the total PCS improvement at week 30 was mediated through weight change, though indirect effects did not reach statistical significance individually.
No significant effects were found for Mental Component Summary (MCS) scores or PANSS-6 psychiatric symptom scores. This suggests semaglutide's benefits in schizophrenia are primarily physical rather than psychological, at least over 30 weeks.
Uhrenholt, N; Ganeshalingam, A; Arnfred, S; Gæde, P; Pedersen, A K; Larsen, P V; Frystyk, J; Bilenberg, N ·
RPEP-16291 · 2026Among 8,200 UK patients starting GLP-1 receptor agonists for type 2 diabetes, 41.1% discontinued within one year. Discontinuation was highest with oral semaglutide (55.8%), followed by subcutaneous semaglutide (46.4%), and lowest with dulaglutide (36.9%). Dose titration was frequently delayed — only 58% of semaglutide users reached recommended maintenance doses after 4 weeks, while 21% remained on starting doses.
Patients without obesity were more likely to discontinue (49.2%) than those with BMI ≥30 (37–40%). By the 10th prescription, nearly half of subcutaneous semaglutide users were still on 0.5 mg rather than the 1 mg maintenance dose. Cardiovascular disease status did not significantly affect persistence patterns.
Ulrich, Franziska S; Napoli, Nicola; Nielsen, Morten Frost; Burden, Andrea M · Observational
RPEP-16293 · 2026Using AI-driven proteomics and RNA sequence integration, the researchers mapped disrupted gene circuits following TBI and identified specific therapeutic targets including redox-sensitive mitochondrial regulators and neuroimmune interface genes. They then designed peptide-nanoparticle formulations in silico that incorporate targeting ligands for disrupted circuits and redox-sensitive release mechanisms. The platform demonstrates a closed-loop, data-guided strategy integrating AI-based gene network profiling with rational nanocarrier design, validated computationally through coarse-grained molecular simulations.
Uner, Burcu Yesildag; Demir, Alper; Zhou, Pingkun; Taskiran, Ekim Z; Wassenaar, Tsjerk ·
RPEP-16299 · 2026GLP-1 receptor agonists slow gastric emptying as part of their mechanism of action, which creates a new challenge for anesthesiologists: patients on these drugs may have food or liquid remaining in their stomachs even after standard fasting periods before surgery. This residual gastric content increases the risk of regurgitation and pulmonary aspiration during anesthesia — a potentially life-threatening complication.
The risk is particularly elevated for patients who already have gastroparesis (delayed stomach emptying) or who are undergoing procedures without a protected airway (such as sedation without intubation). The article reviews international consensus guidelines and provides structured recommendations for perioperative risk stratification and management of patients on GLP-1 drugs.
Valkeniers, Karolien; Wallyn, An; Van de Putte, Peter; Hogg, Rosemary M G · Review
RPEP-16308 · 2026Among 6,700 propensity-matched obese patients (matched on 82 variables), GLP-1RA users had significantly lower AF recurrence after ablation: 6.66% vs. 7.72% (HR 0.82, 95% CI 0.76–0.88, p=0.01). All-cause mortality was 27% lower (HR 0.73, 95% CI 0.59–0.91, p=0.01). Heart failure hospitalization was 20% lower (HR 0.80, 95% CI 0.71–0.90, p=0.001). There was no significant difference in need for repeat ablation procedures. These benefits were observed over a median 2-year follow-up (IQR 0.8–3.2 years).
Venier, Sandrine; Defaye, Pascal; Lochon, Lisa; Benali, Rémi; Bisson, Arnaud; Carabelli, Adrien; Diouf, Youssou; Jacon, Peggy; Fauchier, Laurent ·
RPEP-16309 · 2026Pre-stroke weight loss achieved through GLP-1R activation with semaglutide, and more potently through dual co-activation of GLP-1 and NPY2 receptors, improved post-stroke functional recovery in diabetic mice. This recovery effect was independent of glycemic regulation — it occurred upstream of blood sugar control, driven by weight loss itself.
Post-stroke recovery in type 2 diabetic mice was inversely associated with peripheral IGF-1 levels. Additionally, when semaglutide and/or BI8271 were administered acutely (1 and 24 hours after reperfusion), they provided direct neuroprotection — improving grip strength, reducing stroke volume, and increasing surviving neuron counts — independently of their metabolic effects.
A diet-switching control group that achieved the same weight loss range confirmed that pharmacological weight loss provided benefits beyond what simple caloric restriction offered.
Vercalsteren, Ellen; Karampatsi, Dimitra; Neicu, Maria; Romanitan, Mihaela Oana; Haebel, Peter; Bleymehl, Katherin; Nyström, Thomas; Klein, Thomas; Darsalia, Vladimer; Patrone, Cesare ·
RPEP-16312 · 2026In the phase 3a REDEFINE 1 trial (n=3,417; 68 weeks), CagriSema 2.4 mg/2.4 mg vs. placebo showed:
- Systolic BP change: -10.9 vs. -2.8 mmHg
- Diastolic BP change: -5.4 vs. -1.7 mmHg
- BP target achievement at week 68: 63.0% vs. 32.0%
- Among resistant hypertension patients (n=167): 42.0% vs. 29.3% reached BP targets (OR 1.7; 95% CI 0.7-4.4)
- 39.6% of CagriSema patients on antihypertensive medications decreased or stopped treatment vs. 18.8% with placebo
The blood pressure reductions were clinically relevant across a wide range of subgroups including those stratified by baseline BMI, hypertension status, and resistant hypertension.
Verma, Subodh; Böttcher, Morten; Brown, Paul; Dicker, Dror; Rubino, Domenica; Sbraccia, Paolo; Sharma, Arya M; Smedegaard, Lærke; Sørrig, Rasmus; Garvey, W Timothy ·
RPEP-16325 · 2026This review argues that GLP-1 receptor agonists should be understood as integrative regulators of pancreatic beta-cell function, not just appetite suppressors. The authors detail how GLP-1 modulates multiple intracellular mediators — calcium, glutamate, GABA, serotonin, and urocortin-3 — each with complex and sometimes contradictory roles in triggering insulin release.
The review highlights emerging evidence that GLP-1 analogs also affect mitochondrial shape and the cell's oxidative balance. Because beta-cells have relatively low levels of antioxidant enzymes and depend heavily on both glycolytic and mitochondrial metabolism to produce insulin, GLP-1's influence on mitochondrial dynamics and reactive oxygen species may be central to keeping these cells functional and alive.
The authors identify three mechanistic dimensions — intracellular neurotransmitters, mitochondrial remodeling, and redox control — as the most promising areas for advancing understanding of how GLP-1 works at the cellular level.
Vogt, Éverton L; Kowaltowski, Alicia J · Review
RPEP-16328 · 2026GLP-1 receptor agonists directly affect ovarian biology — not just through weight loss, but by acting on ovarian cells themselves. In women with PCOS, these drugs improved menstrual regularity, reduced free testosterone, and increased sex hormone-binding globulin. Liraglutide combined with metformin significantly improved IVF pregnancy rates, while exenatide increased natural conception rates. At the molecular level, GLP-1 receptor activation promotes granulosa cell growth through FOXO1 signaling and modifies steroid hormone production by suppressing key steroidogenic enzymes. However, animal studies raised concerns about potential ovarian and uterine damage at certain doses, including oxidative stress, granulosa cell death, and uterine inflammation.
Voros, Charalampos; Chatzinikolaou, Fotios; Papapanagiotou, Ioannis; Polykalas, Spyridon; Mavrogianni, Despoina; Koulakmanidis, Aristotelis-Marios; Athanasiou, Diamantis; Kanaka, Vasiliki; Bananis, Kyriakos; Athanasiou, Antonia; Athanasiou, Aikaterini; Papadimas, Georgios; Tsimpoukelis, Charalampos; Vaitsis, Dimitrios; Karpouzos, Athanasios; Daskalaki, Maria Anastasia; Kanakas, Nikolaos; Theodora, Marianna; Thomakos, Nikolaos; Antsaklis, Panagiotis; Loutradis, Dimitrios; Daskalakis, Georgios · Systematic Review
RPEP-16332 · 2026In 4,056 adults with obesity and no known major psychopathology from the SURMOUNT trials, tirzepatide was not associated with increased depression risk compared to placebo. At week 72, tirzepatide-treated participants had significantly lower PHQ-9 depression scores (1.9 vs. 2.4; treatment difference -0.6; p < 0.001) and were less likely to shift to a more severe depression category (18.2% vs. 24.3%; p < 0.001). Suicidal ideation was reported by 0.6% in both groups, and suicidal behavior (nonfatal) occurred in 0.1% on tirzepatide vs. 0% on placebo. Psychiatric adverse events were similar between groups.
Wadden, Thomas A; Oquendo, Maria A; Kushner, Robert F; Cao, Dachuang; Karanikas, Chrisanthi A; Kechter, Afton; Murphy, Madhumita A ·
RPEP-16342 · 2026The APD6 platform now houses 5,188 peptide records, broken down into 3,306 natural, 1,380 synthetic, and 239 predicted antimicrobial peptides. The database introduces the most comprehensive antimicrobial peptide information pipeline (AMPIP) to date, covering the full research lifecycle from discovery through clinical trials. New positive and negative datasets for factors like pH stability, salt tolerance, serum effects, and resistance potential have been added to support more advanced AI prediction models beyond the current focus on activity and hemolysis alone.
Wang, Guangshun; Schmidt, Cindy; Li, Xia; Wang, Zhe ·
RPEP-16344 · 2026The combination of aztreonam, colistin (polymyxin), and tigecycline successfully controlled a carbapenem-resistant Enterobacteriaceae (CRE) infection complicated by pneumonia and renal impairment in a neonate. The infant required invasive mechanical ventilation initially but showed improved respiratory function, managed spontaneous breathing, and was eventually discharged without significant adverse events.
The authors emphasize that combining peptide antibiotics (polymyxins) with other drug classes effective against resistant gram-negative bacteria can lower mortality in neonatal CRE pneumonia.
Wang, Han; Tan, Yangyang ·
RPEP-16350 · 2026Researchers discovered that electrical stimulation activates a signaling pathway (YAP1/pSTAT3/NRP1) in sensory neurons that promotes the growth of CGRP-positive nerve fibers into healing tendons. Building on this finding, they engineered a bifunctional piezoelectric patch made from P(VDF-TrFE) and regenerated silk fibroin composites that, when activated by ultrasound, generates localized electrical signals to drive sensory nerve and blood vessel growth while simultaneously reducing tissue adhesion.
In both rat and Bama minipig models of tendon injury, the patch markedly enhanced tendon regeneration and reduced adhesion scores by approximately 50% compared to controls.
Wang, Jiayi; Wang, Fan; Liu, Jingwen; Xiao, Yao; Li, Zhaoyang; Liu, Xiaonan; Zhang, Peilin; Wang, Fei; Cui, Wenguo; Liu, Shen · Animal
RPEP-16352 · 2026Using GFP genetic labeling and microscopic imaging, approximately 50 NPF-expressing neurons were identified in the adult Drosophila brain, organized into five major anatomical clusters with distinct projection patterns targeting different brain regions.
Beyond previously known P1, P2, and L1 neurons, the study identified two ventrolateral NPF-expressing neurons per hemisphere. These neurons have cell bodies in the protocerebrum but project centrifugally to the optic lobes (visual processing centers), positioning them as a potential neural link between the NPF neuromodulatory system and changes in visual attention — a connection not previously described.
Wang, Jing; Lehmann, Fritz-Olaf ·
RPEP-16355 · 2026Encapsulating bovine lactoferricin (BLfcin) — an antimicrobial peptide from milk — in chitosan nanoparticles significantly enhanced its antibacterial activity against S. aureus and E. coli compared to the free peptide. The nanoparticles were 101–136 nm in size with 72% encapsulation efficiency.
In a mouse model of mastitis (breast infection), the BLfcin nanoparticles reduced bacterial load, decreased mammary inflammation, and boosted antioxidant enzyme levels without causing toxicity. Transcriptomic analysis revealed that the nanoparticle formulation suppressed bacterial genes related to ribosomes, ABC transporters, and two-component signaling systems — explaining the enhanced killing.
Wang, Kaiming; Gao, Yumeng; Jiang, Zhenlin; Tong, Jinjin; Zhang, Hua · Preclinical (In Vitro + Animal)
RPEP-16358 · 2026This review catalogs six primary mechanisms by which self-assembling peptide (SAP) nanomedicines cross cell membranes to deliver cancer drugs: (1) classical endocytosis, (2) fluoride-modified transmembrane transport, (3) macropinocytosis-mediated transport, (4) flexible cyclic peptide-mediated transport, (5) receptor-mediated transport, and (6) cell-penetrating peptide-mediated endocytosis.
For tumor-specific targeting, SAP nanomedicines incorporate three categories of targeting peptides: those that home to tumor cells directly, those that target tumor blood vessel endothelial cells, and those that target the tumor microenvironment. The review emphasizes that combining self-assembly properties with specific targeting peptides enables precise drug delivery to tumors while minimizing damage to healthy tissue.
Wang, Luxi; Tang, Ying; Mao, Yifei; Chen, Rui; Luo, Xin; Xu, Junrong; Li, Chunlai; Xie, Beibei; Li, Peng · Review
RPEP-16359 · 2026The PCN-CuS-JQ/RGD nanoplatform executes a multi-step delivery cascade: RGD peptide targets integrin-overexpressing tumor cells → the MOF carrier decomposes intracellularly, releasing CuS-JQ/RGD units → these enter the nucleus and bind BRD4 → NIR-II laser irradiation triggers photothermal BRD4 degradation. This process simultaneously induces immunogenic cell death (ICD) and downregulates PD-L1, creating synergy with anti-PD-L1 checkpoint blockade therapy. In bilateral tumor mouse models, the combination significantly enhanced immunotherapy efficacy beyond either approach alone.
Wang, Luyi; Wu, Jiasha; Ji, Rui; Qiang, Sufeng; Shen, Yulin; Zuo, Yan; Jian, Shiqin; Liu, Siyao; Xu, Fusheng; Hu, Honggang; Hu, Xiaochun ·
RPEP-16360 · 2026Across 25 randomized controlled trials (n=2,481), GLP-1 receptor agonists significantly increased the resolution of MASH without fibrosis worsening, with an odds ratio of 4.04 (95% CI: 2.69–6.05). However, fibrosis improvement without steatohepatitis worsening did not reach statistical significance.
Subgroup analysis of semaglutide trials showed improved NASH Activity Score (NAS ≥2-point decrease) and steatosis grade but no significant changes in weight, waist circumference, liver enzymes, or lipid levels. Trial sequential analysis confirmed the evidence was sufficient for MASH resolution (required information size = 197 patients reached) but insufficient for fibrosis improvement (required 1,693 patients, not yet reached). GRADE assessment rated the evidence as high certainty for both primary outcomes.
Wang, Mei-Jun; Jiang, Yu-Nuo; Li, Pei-Pei; Wu, Yuan-Jie ·
RPEP-16364 · 2026After 36 weeks of semaglutide treatment, 28 women with obesity lost an average of 16.9 kg. But within 12 weeks of stopping the drug, 71.4% regained weight (averaging +5.1 kg) and 78.5% experienced appetite rebound (≥30% increase in hunger scores plus ≥300 kcal/day increase in intake).
The mechanistic investigation — using both human data and parallel rat studies — found that weight regain was accompanied by gut microbiota dysbiosis (increased Firmicutes/Bacteroidota ratio), decreased ursodeoxycholic acid levels, reduced hypothalamic TGR5 expression, and reactivation of hunger-promoting brain signals (AgRP/NPY) while satiety signals (POMC/MC4R) weakened. However, some improvements in liver and fat tissue metabolism partially persisted through maintained AMPK/SIRT1 activation.
Wang, Ning; Guo, Haonan; Song, Lin; Wang, Jingyue; Hu, Shuyuan; Wang, Mingxi; Zhang, Duowen; Jing, Yingyu; Zhang, Yifan; Wang, Mengjun; Wang, Ting; Sun, Bo · Clinical Trial
RPEP-16373 · 2026By combining cyclization (closing the peptide into a ring) and D-amino acid substitution (using mirror-image amino acids), researchers transformed a linear antimicrobial peptide called P-07 into PT-17 — a dramatically more stable version that resists enzymatic breakdown. PT-17 retained broad-spectrum killing activity against multidrug-resistant (MDR) bacteria, showed a high therapeutic index (meaning it kills bacteria at much lower concentrations than those toxic to human cells), disrupted bacterial membranes rapidly, showed low potential to trigger resistance, and worked synergistically with conventional antibiotics. In mice infected with MDR E. coli, PT-17 significantly reduced bacterial loads in major organs with no detectable toxicity.
Wang, Taoran; Tian, Long; Zeng, Jiangmin; Ning, Ziyao; Zhang, Li; Zhao, Chunhui; Jiang, Shuyuan; Zeng, Chunlan; Han, Jiaqi; Luan, Liang; Ye, Weifeng; Meng, Qingbin · Animal
RPEP-16375 · 2026The review identifies four main gastrointestinal barriers to oral peptide delivery: harsh pH environment, enzymatic degradation, the mucus layer, and the intestinal epithelial barrier. Current strategies to overcome these include chemical modifications (like PEGylation and cyclization), permeation enhancers that temporarily open tight junctions, encapsulation techniques (enteric coatings, hydrogels), and novel delivery systems including ingestible microneedle devices and nanoparticle-based carriers.
The authors conclude that no single strategy adequately overcomes all four barriers, and that synergistic integration of multiple approaches — combining protection, permeation enhancement, and targeted delivery — is the most promising path toward effective oral peptide therapeutics.
Wang, Xiaofan; Wang, Keke; Fang, Yitan; Zhang, Youxi; Yi, Lixin; Li, Xiaohong; Zhao, Qinfu; Zhu, Xu; Cai, Shuang; Wan, Long ·
RPEP-16376 · 2026Ajapocin showed potent activity against V. parahaemolyticus and V. vulnificus with MICs of 6-12 μM — comparable to Polymyxin B. In vivo efficacy was demonstrated in both zebrafish (single dose, 1 mg/mL) and mouse models (multiple doses reduced bacterial burden and accelerated wound healing). No cytotoxicity was observed in ZF4 or HaCaT cells up to 32 μM. One week of daily intraperitoneal injection caused no hepatic or renal toxicity confirmed by histopathology and blood chemistry.
The mechanism involves targeting negatively charged bacterial membrane components, enhancing membrane permeation, inducing depolarization, and causing membrane destruction — a membranolytic pattern that is difficult for bacteria to develop resistance against.
Wang, Xiaofei; Hong, Xiao; Liu, Wanting; Xu, Yujun; Chen, Roushi; Chen, Fangyi; Wang, Ke-Jian; Wang, Luxi ·
RPEP-16379 · 2026Eight weeks of semaglutide treatment in diabetic ApoE-/- mice reversed cardiac microvascular damage caused by high-fat diet and streptozotocin-induced diabetes. Semaglutide preserved microvascular structure and density, reduced perivascular fibrosis, and protected through multiple molecular mechanisms: reducing advanced glycation end products (AGEs) and their receptors, activating the Nrf2/HO-1/NQO1 antioxidant pathway, inhibiting the MCP-1/CCR2a/NF-κB inflammatory pathway, lowering inflammatory cytokines, and reducing cell death (apoptosis).
Diabetic mice showed disrupted cardiac microvascular architecture and reduced vessel density, both of which semaglutide attenuated or reversed.
Wang, Xinye; Wang, Xiaoting; Zhuang, Hong; Lu, Guangzhen; Zhao, Gang · Animal
RPEP-16382 · 2026Researchers used computational modeling to design cell-penetrating peptides (CPPs) optimized for transdermal delivery, then loaded them with siRNA targeting ADAM17 — a protein that drives TNF-α-mediated inflammation in psoriasis. The peptide carriers successfully penetrated the skin's stratum corneum, were taken up by immune cells in the dermis, and suppressed ADAM17 expression and TNF-α inflammatory responses.
A skin-adhesive spray formulation containing the peptide-siRNA complexes ameliorated psoriatic pathology in both human 3D skin models and a mouse psoriasis model. Multiplex imaging revealed the peptide carriers reprogrammed immune-epithelial cell cross-talk in the tissue microenvironment.
Wang, Yefeng; Wu, Siwen; He, Yilin; Zhang, Jiani; Chen, Yujiao; Zhou, Lei; Li, Xiaopeng; Yang, Li · Preclinical
RPEP-16385 · 2026Among 388,359 Medicare beneficiaries newly diagnosed with T2DM (9,584 with Alzheimer's), overall treatment initiation within one year was lower for individuals with AD. Those with AD who did start treatment were more likely to receive insulin and less likely to receive metformin, SGLT2 inhibitors, or GLP-1 receptor agonists.
In adjusted models, Alzheimer's disease was associated with lower odds of any antidiabetic treatment initiation and, among those who started treatment, lower odds of initiating newer agents like GLP-1 RAs and SGLT2 inhibitors. The findings reveal a treatment disparity that may have clinical consequences given emerging evidence of cardiovascular and neuroprotective benefits of these newer drug classes.
Wang, Yingqi; Alexander, G Caleb; Mehta, Hemalkumar B ·
RPEP-16387 · 2026AH-12, engineered from the minimal inhibitory fragment of salivary Histatin 5 through N-terminal modification, amidation, and acetylation, demonstrated dual therapeutic activity:
**Antibacterial effects:**
- Killed Fusobacterium nucleatum, Porphyromonas gingivalis, and Streptococcus gordonii (key periodontal pathogens)
- Worked via bacterial membrane lysis
- Suppressed FadA adhesin secretion in F. nucleatum (reducing bacterial attachment)
**Anti-inflammatory effects:**
- Stabilized mitochondrial calcium (Ca²⁺) levels
- Reduced mitochondrial reactive oxygen species (mtROS) overproduction
- Prevented mitochondrial DNA (mtDNA) release
- Attenuated inflammatory cascades driven by mitochondrial dysfunction
**Delivery innovation:**
- GelMA hydrogel (GelMA@AH-12) enabled controlled release in periodontal pockets
- In vivo studies validated efficacy in animal periodontitis models
Wang, Yuanchen; Zhang, Shuting; Sun, Jinrong; Zhang, Qian; Zhang, Xi ·
RPEP-16392 · 2026Eucommia bark extract (EBE) dramatically attenuated high-fat-diet-induced weight gain, oxidative stress, inflammation, lipid accumulation, and liver fibrosis in MASLD mice. The complete mechanistic chain was mapped:
1. EBE selectively expanded Faecalibacterium prausnitzii (a major butyrate-producing bacterium) in the gut
2. This increased colonic butyric acid levels
3. Butyrate activated GPR43 receptors on enteroendocrine cells (confirmed by GPR43 knockdown abolishing the response)
4. GPR43 activation drove GLP-1 synthesis, raising circulating GLP-1 levels
5. GLP-1 enhanced AMPK phosphorylation in the liver via GLP-1 receptor signaling
6. Activated AMPK suppressed lipogenesis (fat creation) and promoted lipophagy (fat breakdown)
Critically, EBE did not directly trigger GLP-1 release in STC-1 cells in vitro — the effect was entirely microbiome-mediated. Fecal microbiota transplantation from EBE-treated donors recapitulated all metabolic improvements in recipient mice.
Wang, Zhineng; Zhu, Ying; Wang, Guohua; Sun, Mayu; Yao, Wenbo; Ba, Qian ·
RPEP-16393 · 2026Over 24 months, both bariatric surgery and GLP-1 drugs (semaglutide/tirzepatide) produced substantial fat loss and moderate lean mass loss, but surgery was dramatically more effective. Surgery patients lost 49.7% of their fat mass versus 18.0% for GLP-1RA patients at 24 months. Lean mass loss was 11.7% with surgery versus 3.3% with GLP-1 drugs. Crucially, both groups improved their lean-to-fat ratio — meaning the weight lost was predominantly fat, not muscle. The lean-to-fat ratio improved to 2.0 with surgery and 1.5 with GLP-1 drugs at 24 months. Men preserved lean mass better than women, especially on GLP-1 drugs.
Wang, Zicheng; Wang, Lei; Zhang, Xinmeng; Lowery, Brandon D; Shaffer, Lauren Lee; Chen, You; Wells, Quinn S; Flynn, Charles R; Williams, Brandon; Spann, Matthew; Srivastava, Gitanjali; Samuels, Jason M; Yu, Danxia · Observational
RPEP-16396 · 2026The review reveals that estrogen has a close transcriptional relationship with calcitonin gene-related peptide (CGRP) and its receptor component RAMP1, both central targets of current migraine therapies. Falling plasma levels of estrogen, progesterone, and hypothalamic oxytocin may trigger migraine attacks, while higher levels appear protective.
Oxytocin receptors have recently been found to be expressed in the trigeminovascular system (TGVS), the key neural pathway in migraine. Estrogen, acting through multiple receptor subtypes, influences expression levels of both oxytocin and its receptor, creating a hormonal-peptide axis that may explain the three-fold higher migraine prevalence in women.
Warfvinge, Karin; Edvinsson, Jacob C A; Maddahi, Aida; Edvinsson, Lars ·
RPEP-16398 · 2026Vitamin C conjugation serves as a versatile 'Trojan horse' platform for drug delivery. When drugs like diclofenac, aspirin, and naproxen are linked to vitamin C, they gain improved transport across the blood-brain barrier via SVCT-mediated uptake, opening potential treatments for neurodegenerative disorders. Antiviral conjugates such as saquinavir-vitamin C show enhanced oral absorption by bypassing efflux mechanisms.
Peptide-vitamin C conjugates leverage the antioxidant properties of vitamin C alongside peptide-based cellular targeting, providing synergistic benefits particularly in cosmetics and dermatology. Protein conjugates using carriers like human serum albumin (HSA) and bovine serum albumin (BSA) facilitate improved systemic transport, while nanostructure incorporation enhances oxidative stability and intracellular delivery through endocytosis.
Wavhale, Sarika R; Shaikh, Anwar R ·