RPEP-15489 · 2026In SURMOUNT-5 at 72 weeks, 23.1%-33.9% of tirzepatide-treated participants reached proposed treat-to-target (TtT) thresholds compared to 14.2%-20.7% with semaglutide. Those reaching targets had greater weight reduction than the overall population.
Among participants reaching a waist-to-height ratio (WHtR) <0.53, 77% achieved low disease activity to remission (meeting goals for at least 4 of 5 defined cardiometabolic risk parameters), with an odds ratio of 2.31 (p<0.001) compared to those not reaching this target. The BMI threshold was not statistically associated with quality of life outcomes (SF-36v2 physical component score).
le Roux, Carel W; Busetto, Luca; Aronne, Louis; Horn, Deborah Bade; Dimitriadis, Georgios K; Falcon, Beverly; Garcia-Perez, Luis-Emilio; Valderas, Elisa Gomez; Gibble, Theresa Hunter; Senyucel, Cagri; Dunn, Julia P ·
RPEP-15491 · 2026The SYNCHRONIZE-1 trial baseline characteristics (n=725 from 14 countries):
- Mean age: 47.1 years; 59.4% female
- Mean BMI: 37.9 kg/m²; mean waist circumference: 115.2 cm
- Geographic distribution: 47.3% North America, 21.0% Europe, 20.0% East Asia
- Obesity complications: hypertension (40.0%), dyslipidaemia (33.7%), prediabetes (30.2%)
- Mean HbA1c: 5.5%, eGFR: 93.0 mL/min/1.73 m², SBP/DBP: 127.0/82.7 mmHg
- Mean LDL cholesterol: 116.4 mg/dL; 21.8% on lipid-lowering drugs
Participants were randomized 1:1:1 to survodutide 3.6 mg, 6.0 mg, or placebo for 76 weeks. Primary endpoints are percent body weight change and achievement of ≥5% weight reduction at Week 76.
le Roux, Carel W; Wharton, Sean; Bozkurt, Biykem; Platz, Elke; Bleckert, Gabriele; Ajaz Hussain, Samina; Brueckmann, Martina; Startseva, Elena; Kloer, Isabel M; Kaplan, Lee M ·
RPEP-15492 · 2026The dual-model framework (CAmidPred) successfully addressed the gap in AMP prediction for chemically modified peptides:
- The Explainable Boosting Machine extracted interpretable, actionable sequence-level design rules for C-amidated AMPs — providing researchers with understandable guidelines rather than black-box predictions
- The fine-tuned ESM2 deep learning model provided reliable deployment-grade activity classification
- Design rules were validated against published alanine-scanning experiments, confirming the model's biological relevance
- The framework identified a pardaxin variant with improved activity against E. coli, demonstrating practical utility for targeted AMP design
- C-terminal amidation improves AMP structural stability, membrane interaction, and protease resistance — properties the framework accounts for
Le, Dang-Huy; Zhu, Yujie; Zhang, Tianmeng; Li, Wenyi; Hung, Andrew; Houshyar, Shadi; Le, Tu C ·
RPEP-15495 · 2026Among 218 adults on GLP-1 receptor agonists undergoing upper endoscopy, retained gastric content (RGC) was observed in 20.6% of patients. Nine procedures were terminated prematurely due to retained content. One aspiration event and one intraprocedural intubation occurred. Despite the high prevalence of retained stomach content, the overall incidence of severe complications or adverse outcomes was low.
Le, Kim; Prasad, Sanjay; Shah, Rajesh ·
RPEP-15496 · 2026Out of 241 flavonoid compounds screened computationally, isobavachalcone (IBC) showed the highest binding energy to DPP-4 and the lowest IC50 value, making it the most potent inhibitor identified. In Caco-2 intestinal cells, IBC reduced DPP4 mRNA and protein expression.
In mice on a high-fat diet, IBC reduced hyperglycemia more effectively than sitagliptin by increasing circulating GLP-1 and insulin levels. IBC also decreased DPP-4 activity and expression while increasing GLUT2 expression in the liver and GLUT4 expression in muscles — both critical glucose transporters. Additionally, IBC promoted human skeletal muscle cell proliferation and differentiation, indicating potential benefits for diabetes-related muscle atrophy.
Lee, Eun Ju; Shaikh, Sibhghatulla; Ahmad, Khurshid; Lee, Si Han; Choi, Jae-Moon; Lee, Yong Ho; Choi, Inho ·
RPEP-15498 · 2026Among 90 chronic migraine patients (27 on dual CGRP therapy, 63 on mono therapy):
- Dual therapy reduced headache severity by 20% vs 10% with mono therapy (p = 0.039)
- Dual therapy patients averaged 4 fewer headache days, with some experiencing up to 14 fewer days, though this did not reach statistical significance (p = 0.112)
- No significant differences in other migraine-associated symptoms (nausea, photophobia, etc.)
- Adverse events were mild in both groups with no serious events or discontinuations
- Both treatment approaches used CGRP ligand-targeting antibodies combined with receptor-targeting small molecules for synergistic blockade
Lee, Ho Hyun; Cheung, Anita J; Lee, Anson Y; Jahansooz, Julia R; Weldon, Edward J; Ishikawa, Kyle M; Yoshioka, Reyn; Woo, Man Ian; Liquard, Lana; Kim, Eonjung Angeline; Carrazana, Enrique; Liow, Kore K ·
RPEP-15499 · 2026From 881 screened articles, 13 met inclusion criteria: 10 case reports and 3 cohort studies examining pregnancy outcomes after periconceptional GLP-1 receptor agonist exposure.
Key findings across all included studies:
- No increased risk of major congenital malformations in any study
- No pregnancy losses or elective terminations reported in any study
- Minor complications reported in case reports included: emergency cesarean delivery, preeclampsia, macrosomia (large baby), shoulder dystocia, and transient neonatal hypoglycemia
- These minor complications are common in pregnancies complicated by pre-existing diabetes and obesity
Lee, In Ok; Ghiasi, Maryam; Wong, Karen; Walker, Mark ·
RPEP-15508 · 2026Three weeks of treatment with the GLP-1 receptor agonist dulaglutide significantly suppressed copeptin levels — a stable surrogate marker for vasopressin (the antidiuretic hormone) — by 12% compared to placebo in euvolemic participants.
The median within-subject copeptin difference was -0.7 pmol/L (p=0.047). This suppression was independent of dulaglutide's effects on blood pressure, BMI, or nausea incidence, suggesting a direct effect of GLP-1 signaling on the vasopressin system rather than a secondary consequence of other GLP-1 actions.
This is the first evidence that GLP-1 receptor agonists directly inhibit the vasopressin system, offering a physiological explanation for why GLP-1 drugs reduce fluid intake and urine output.
Leibnitz, Svenja; Winzeler, Bettina; Refardt, Julie; Vogt, Deborah R; Sailer, Clara O; Christ-Crain, Mirjam · Secondary Analysis Rct
RPEP-15510 · 2026Researchers developed peptide-based tracers for the E3 ligase SPSB2, a key component in designing PROTAC degrader drugs. Degron peptide sequences recognized by SPSB2 were conjugated with cell-penetrating peptides (CPPs) to achieve cellular delivery. A high-resolution crystal structure was obtained, and biophysical techniques confirmed binding. Confocal microscopy and BRET-based assays demonstrated successful cellular delivery and potent target engagement. This provides a blueprint for developing peptide-based tools to evaluate new E3 ligase targets for PROTAC drug design.
Lenz, Christopher; Elson, Lewis; Dopfer, Johannes; Farges, Frederic; Krämer, Andreas; Löhr, Frank; Müller, Susanne; Guéret, Stéphanie M; Waldmann, Herbert; Dötsch, Volker; Saxena, Krishna; Knapp, Stefan ·
RPEP-15512 · 2026The patient, a 39-year-old man with a prior episode of unilateral brachial neuritis, developed recurrent bilateral upper limb weakness following a 70-pound weight loss over 8 months on semaglutide. Specific deficits included bilateral radial sensory loss, finger extensor paralysis, right triceps weakness, and decreased left grip strength.
Corticosteroids provided pain relief but motor and sensory deficits persisted despite physiotherapy. This represents the first reported case linking semaglutide use with brachial plexus neuritis (Parsonage-Turner syndrome).
Lesinszki, Lukács S; Khalili, Radmanesh; Jiang, Haiyang; Jha, Shivangi; Bernad, Peter G ·
RPEP-15517 · 2026Chronic kidney disease contributes to cognitive impairment through the gut-kidney-brain axis, with uremic toxins (amplified by gut dysbiosis) damaging the blood-brain barrier, reducing neurogenesis, and promoting neuroinflammation. The review proposes an integrated approach combining plant-based diets (Mediterranean, DASH), physical activity, and pharmacological therapies including GLP-1 receptor agonists and SGLT2 inhibitors for synergistic protection of both kidney and brain function.
Levassort, Hélène; Decaix, Théodore; Michon, Pierre-Louis; Pépin, Marion; Lilamand, Matthieu ·
RPEP-15521 · 2026High-dose liraglutide significantly improved functional and tissue outcomes in a mouse spinal cord injury model by suppressing microglial pyroptosis — an inflammatory form of cell death. These benefits were completely abolished in mice lacking the GLP-1 receptor (GLP-1R-/- mice), confirming the effect is GLP-1R-dependent.
The study mapped a novel signaling pathway: GLP-1R → PI3K/Akt → TFEB → FANCC upregulation → p38 suppression → NLRP3 inflammasome inhibition. Critically, when FANCC was knocked down, liraglutide's anti-inflammatory effects were blocked, establishing FANCC as an essential mediator of this neuroprotective cascade.
Li, Guangshen; Luo, Yang; Zhu, Tianyu; Chen, Chunmao; Qian, Zhanyang; Li, Haijun ·
RPEP-15527 · 2026Both low-dose (50% DAG) and high-dose (100% DAG) 1,3-diacylglycerol significantly reduced fasting blood glucose, insulin, and triglycerides in T2DM rats to near-control levels over 8 weeks. 1,3-DAG restored colonic morphology, increased GPR41 receptor expression, and elevated GLP-1 and PYY secretion while reducing serum lipopolysaccharide (a marker of gut barrier leakage).
Gut microbiota analysis showed enrichment of Bacteroidota and depletion of Proteobacteria, with increased short-chain fatty acids (acetate, propionate, valerate). Bacteroidota taxa negatively correlated with blood sugar and lipid markers, while Proteobacteria positively correlated with LDL-C. The benefits appear mediated through a gut microbiota → SCFA → GPR41 → GLP-1 signaling axis.
Li, Jiaomei; Wang, Hao; Yang, Jiekai; Wang, Yicheng; Jia, Guo; Gu, Jiaojiao ·
RPEP-15528 · 2026GYG1 (glycogenin-1) emerged as a dual-function biomarker for GLP-1 receptor agonist therapy: baseline GYG1 levels predicted the trajectory of weight loss (BMI slope), while changes in GYG1 during treatment tracked ongoing treatment response (%BMI change).
The GLP-1RA GZR18 produced dose-dependent BMI reductions, with the 48 mg biweekly dose yielding the steepest declines. Gene set enrichment analysis revealed that starch/sucrose metabolism pathways modulated ongoing drug efficacy through integrated molecular networks.
Li, Lijun; Hou, Mengyu; Gao, Qiannan; Dong, Ruihua ·
RPEP-15529 · 2026LPS preconditioning at 10-500 ng/mL enhanced hADSC proliferation (maximal at 500 ng/mL) without increasing apoptosis. It markedly upregulated antimicrobial peptides LL-37 and HBD-2, improving S. aureus and E. coli inhibition. In vivo, 500 ng/mL LPS-conditioned medium accelerated infected wound healing, increased collagen deposition, and reduced iNOS expression.
Li, Linling; Diao, Jielin; Wang, Feng; Wang, Xia; Liu, Yicai; Fu, Xiaoming ·
RPEP-15532 · 2026The MCF@CA hydrogel system, when activated by ultrasound, delivered CGRP-conjugated nanoparticles that simultaneously modulated the immune microenvironment and scavenged reactive oxygen species. In diabetic wound models, the treatment enhanced collagen deposition, promoted macrophage polarization from the pro-inflammatory M1 state to the anti-inflammatory M2 phenotype, and improved local blood supply — all of which contributed to significantly faster wound closure compared to controls.
Li, Mofan; Wang, Mengxin; Wang, Haonan; Sun, Yang; Zhang, Yongyue; Xu, Shuyu; Zhang, Tianjiao; Shama, Shiti; Liang, Xiaolong; Wang, Shumin ·
RPEP-15534 · 2026From 24,776 T2DM patients with unruptured intracranial aneurysms identified in the TriNetX Research Network, propensity score matching produced 2,651 patients in each group (GLP-1RA users vs. non-users).
GLP-1RA use was associated with significantly reduced risk of nontraumatic subarachnoid hemorrhage (SAH):
- 3-year follow-up: HR 0.62 (95% CI: 0.44–0.88) — 38% risk reduction
- 5-year follow-up: HR 0.65 (95% CI: 0.47–0.92) — 35% risk reduction
Follow-up laboratory values showed no significant differences between groups, suggesting the protective effect is not simply mediated by metabolic improvements.
Li, Sean Y; Sonti, Anisha; Kaelber, David C; Ben-Israel, David; Bowles, Alfred; Reddy, Deven; Kelly, Michael L ·
RPEP-15535 · 2026Parthenolide (PTL), a natural compound found in feverfew, was identified as a high-affinity agonist of the bitter taste receptor TAS2R4 that stimulates GLP-1 secretion from human intestinal cells in a dose-dependent manner. Direct binding to TAS2R4 was confirmed by cellular thermal shift assays, and molecular docking revealed strong interactions including hydrogen bonding with specific receptor residues.
The mechanism involves PTL activating TAS2R4, which upregulates phospholipase C β2 (PLCβ2) to produce IP3, triggering calcium release inside the cell. This calcium increase drives GLP-1 vesicle fusion and secretion. Calcium also activates the TRPM5 channel, further amplifying the signal. This establishes parthenolide as a natural compound that can boost the body's own GLP-1 production through a bitter taste receptor pathway.
Li, Shanshan; Chen, Ye; Song, Zhaosu; Ou, Penghui; Duan, Yujing; Liu, Qinglei; Wang, Wei · In Vitro
RPEP-15538 · 2026At 10 mg/kg, the D-enantiomer peptide DN6NH2 achieved 81.82% survival in tilapia with A. veronii peritoneal infection, compared to 51.52% for the parent peptide N6NH2 and just 30.30% for the conventional antibiotic florfenicol at the same dose.
Histopathology showed DN6NH2-treated fish had significantly reduced inflammation, bleeding, and necrosis in liver, intestine, spleen, and gills. DN6NH2 also alleviated excessive immune responses in the spleen and head kidney and significantly reduced NF-κB p65 levels in the spleen, demonstrating both antimicrobial and immunomodulatory dual-function activity.
Li, Ting; Yang, Na; Teng, Da; Mao, Ruoyu; Hao, Ya; Han, Huihui; Wu, Yankang; Wang, Xiumin; Wang, Jianhua ·
RPEP-15541 · 2026Intracerebroventricular liraglutide administered 1 hour before cecal ligation and puncture (CLP) alleviated neurological impairment scores and reduced glial cell activation, neuronal loss, and neurodegeneration in the hippocampus of septic mice. In vitro, liraglutide suppressed neuron-microglia interaction under LPS stimulation. Liraglutide also inhibited mitochondrial damage and oxidative stress in hippocampal neurons. The mechanism involved restoring diminished p-AKT levels while reversing STAT3 phosphorylation in hippocampal neurons. Neurological severity scores, weight loss, food intake, and survival were monitored for up to 5 days post-CLP.
Li, Xiaoming; Wang, Jun; Zhang, Rongji; He, Haoran; Wang, Linjue; Wang, Yuliang; Yi, Hongyu ·
RPEP-15544 · 2026Exenatide (the first GLP-1 receptor agonist peptide drug) was found to improve hepatic insulin resistance by directly binding to and upregulating PPARδ, which in turn suppresses pyroptosis — an inflammatory form of cell death. Knocking down PPARδ abolished exenatide's protective effects, while activating PPARδ enhanced them, confirming PPARδ as a key mediator.
Clinically, T2DM patients carrying the AA genotype at PPARD rs3777744 and having higher baseline insulin resistance (HOMA-IR) showed a superior response to exenatide, suggesting this genetic variant could serve as a biomarker for personalized GLP-1 therapy.
Li, Xizhi; Zhou, Tingting; Wu, Yixi; Sun, Jiayi; Wang, Ziyu; Huang, Yuhan; Xu, Ke; Ling, Hongwei; Li, Na; Yang, Tingting; Wang, Tao ·
RPEP-15550 · 2026T2DM mice showed decreased blood perfusion, reduced red blood cell tissue fraction, diminished oxygen saturation, and lower hemoglobin concentration in pancreatic microcirculation compared to controls. Liraglutide treatment significantly ameliorated these impairments, partially restoring the balance between blood perfusion and oxygen saturation and normalizing the disrupted coherence between oxygenated hemoglobin and speed-resolved blood perfusion.
The study also validated a new algorithm-based framework for simultaneously monitoring microhemodynamics and oxygen profiles in the pancreas, providing a tool for future research on pancreatic microcirculation.
Li, Yuan; Wang, Yingyu; Wang, Bing; Liu, Weiqi; Xu, Mengting; Zhang, Xiaoyan; Liu, Xueting; Ling, Hao; Zhang, Xu; Liu, Mingming; Xiu, Ruijuan ·
RPEP-15560 · 2026The engineered TCR3-T cells demonstrated significantly enhanced avidity for the KRAS G12V8-16 neopeptide compared to the original TCR0-T cells, translating to effective tumor cell killing both in vitro and in vivo.
Critically, TCR3-T cells overcame multiple tumor immune-evasion mechanisms: they killed tumor cells highly expressing PD-L1, proliferated despite exposure to indoleamine 2,3-dioxygenase (IDO), resisted transforming growth factor β (TGF-β) suppression, and recruited other immune cells to the tumor site via chemokines. TCR3-T cells retained specificity for the KRAS neopeptide with no reactivity against normal cells.
Liang, Zhaoduan; Guan, Fengqiong; Wu, Bingling; Chen, Wenfang; Tian, Ye; Cai, Wenxuan; Li, Yi ·
RPEP-15565 · 2026In cross-sectional analysis of up to 61,830 participants, all three cardiac peptide markers — MR-proADM, MR-proANP, and NT-proBNP — were consistently associated with lower kidney function (eGFR) and higher CKD prevalence. Per 1 standard deviation increase in log-transformed NT-proBNP (corresponding to a 2.71-fold concentration increase), eGFR was 2.35 ml/min/1.73m² lower. Participants in the highest NT-proBNP group had 5.72-fold higher odds of CKD compared to the lowest group.
In longitudinal analysis of 4,205 individuals, higher baseline NT-proBNP predicted faster eGFR decline: -1.37 ml/min/1.73m² per 1 SD increase over 10 years, and higher CKD incidence. Associations were stronger in participants with existing cardiovascular disease and diabetes, suggesting the heart-kidney peptide connection is especially important in these high-risk populations.
Lin, Jie-Sheng; Zeller, Tanja; Koenig, Wolfgang; Jousilahti, Pekka; Kee, Frank; Iacoviello, Licia; Tunstall-Pedoe, Hugh; Söderberg, Stefan; Cesana, Giancarlo; Palmieri, Luigi; Salomaa, Veikko; de Man Lapidoth, Julia; De Ponti, Roberto; Donfrancesco, Chiara; Lorenz, Thiess; Kuulasmaa, Kari; Blankenberg, Stefan; Peters, Annette; Thorand, Barbara ·
RPEP-15570 · 2026LRSG08 (sequence: GITIQCILPGFVVSKLSKLK) demonstrated potent antibacterial activity with MIC values of 2 μg/mL against V. parahaemolyticus and V. alginolyticus, and 125 μg/mL against V. vulnificus. Over 80% bacterial killing was achieved within 2.5 hours.
Mechanism of action studies revealed that LRSG08 selectively accumulates on the V. parahaemolyticus cell surface, disrupts membrane integrity causing nucleic acid leakage, and exhibits concentration-dependent binding to genomic DNA. In vivo, LRSG08 significantly increased zebrafish survival from V. parahaemolyticus infection to 80% at 72 hours. Safety profiling showed the peptide is nonhemolytic and has low cytotoxicity in vitro.
Lin, Rong; Feng, Bo; Wang, Mingyao; Aweya, Jude Juventus; Liang, Duo; Jin, Ritian; Weng, Wuyin; Yang, Shen ·
RPEP-15577 · 2026PYY deficiency is closely linked to insulin resistance development. The two circulating forms have distinct roles: PYY(3-36) acts primarily through Y2 receptors in the hypothalamus (suppressing appetite) and in peripheral tissues (adipose, skeletal muscle, liver) to enhance insulin sensitivity. PYY(1-36) acts through Y1 receptors to protect pancreatic beta cells and fine-tune insulin secretion. PYY(3-36) also promotes weight loss by delaying gastric emptying, indirectly improving insulin resistance through weight reduction. The review identifies PYY as playing an important role in glucose homeostasis.
Liu, Chunyan; Ren, Na; Zhang, Haixin; Ma, Jian ·
RPEP-15581 · 2026A new chemical method for modifying tryptophan residues in peptides at a specific position (C7) was developed using rhodium catalysis. When applied to antimicrobial peptides, this modification dramatically enhanced antifungal activity against Aspergillus fumigatus by up to 49-fold over the unmodified parent peptide.
The modified tryptophan residues also functioned as fluorescent probes with environment-sensitive, turn-on fluorescence, enabling wash-free imaging of bacterial cells. The method showed broad substrate compatibility, excellent selectivity, and high functional group tolerance.
Liu, Lei; Zhao, Yanyang; Su, Yiming; Wang, Boning; Xiong, Yue; Wang, Tianhang; Hua, Xiude; Ye, Yonghao; Shi, Zhuangzhi; Wang, Huan · Laboratory
RPEP-15583 · 2026Using a β-turn engineering strategy, researchers designed a short antimicrobial peptide called W2PG that achieved broad-spectrum antibacterial activity (MIC 4–8 μM) with low hemolysis and cytotoxicity, plus improved protease and serum stability over typical AMPs. The peptide kills bacteria by disrupting their membranes through concentration-dependent permeabilization and depolarization.
In mouse infection models, W2PG performed comparably to polymyxin B — a last-resort antibiotic — without observable organ toxicity, demonstrating real in vivo therapeutic potential.
Liu, Meng; Jiang, Peng; Ruan, Binghui; Cui, Yunfei; Zhang, Junjie; Ye, Yuxiu; Zhangsun, Dongting; Luo, Sulan; Wu, Yong ·
RPEP-15591 · 2026Sema4D was identified as the key regulator of bone fragility in type 2 diabetes through proteomics and deep screening analysis. Exendin-4 (a GLP-1 receptor agonist) improved bone biomechanical properties by decreasing serum Sema4D levels and promoting osteogenesis via CRMP2 activation. Metformin had minimal direct effect on Sema4D but enhanced exendin-4's action through a miR-140-3p-STAT3-miR-3657 signaling cascade that increased GLP-1 receptor expression. Anti-Sema4D treatment alone improved bone strength comparably to the combination of metformin and exendin-4. Blood glucose control was not the primary factor in bone remodeling.
Liu, Xuanchen; Wang, Mo; Xu, Bin; Ma, Xue; Jiang, Yangzi; Huang, Hai; Shi, Zengzeng; Wu, Hao; Wu, Zhigang; Guo, Shuo; Zhao, Jungang; Zhao, Jian; Li, Xiaokang; Liang, Li; Guo, Zheng; Shi, Lei; Sun, Chao; Wang, Ning ·
RPEP-15596 · 2026An untargeted metabolomic analysis of 14 probiotic strains identified 3,333 metabolites in their cell-free supernatants (postbiotics), with 1,262 metabolites shared across all strains. Bifidobacterium postbiotics contained significantly higher amino acid and peptide content (48.44%) compared to Lactobacillus, with glutamic acid peptides being particularly prevalent.
Indole derivatives — compounds important for immune regulation through the aryl hydrocarbon receptor — were found in all strains, but their types differed: 3-indoleacrylic acid was more concentrated in Lactobacillus, while indole-3-lactic acid was more prevalent in Bifidobacterium. These findings suggest different probiotic species produce distinct bioactive peptide and metabolite profiles.
Liu, Yue; Sun, Yuhang; Fang, Bing; Wang, Ran; Lan, Hanglian; Zhao, Wen; Hung, Wei-Lian; Zhao, Liang; Zhang, Ming · Laboratory
RPEP-15602 · 2026Substance P (SP) nerve fibers were found in 90% of aldosterone-producing adenomas (APAs) examined, and the neurokinin 1 receptor (NK1R) was strongly expressed in these tumors. Functional experiments showed that SP stimulated aldosterone secretion in 6 out of 10 APA cultures. The NK1R antagonist aprepitant — an already approved drug — blocked SP-induced aldosterone secretion in 3 of 4 responsive cultures tested.
In perifused tissue explants, SP also influenced aldosterone pulsatility, enhancing overall mineralocorticoid output. These results suggest the SP-NK1R pathway may be a druggable target for treating primary aldosteronism in a subset of patients.
Lopez, Antoine-Guy; Duparc, Céline; Renouf, Sylvie; D'Agostino, Margot; De Sousa, Kelly; Amar, Laurence; Defortescu, Guillaume; Manceau, Gilles; Sabourin, Jean-Christophe; Fernandes-Rosa, Fabio Luiz; Zennaro, Maria-Christina; Meatchi, Tchao; Nicolas, Gaël; Louiset, Estelle; Lefebvre, Hervé · In Vitro
RPEP-15603 · 2026The review identifies several key mechanisms of gut-brain communication:
• A direct enteroendocrine cell-neural circuit that allows gut cells to signal the brain in real time
• Microbiome-mediated pathways that influence brain function and behavior
• Neuroimmune interactions linking gut inflammation to neurological and psychiatric conditions
Critically, the review demonstrates that GLP-1 receptor agonists for obesity and guanylyl cyclase C agonists for irritable bowel syndrome achieve their therapeutic effects by acting on these gut-brain pathways — not just through local gut effects. This reframes how we understand these widely prescribed peptide drugs.
Lorsch, Zachary S; Liddle, Rodger A ·
RPEP-15608 · 2026Researchers identified ACE-inhibitory peptides produced during fermentation of djulis (a Taiwanese grain) with Monascus purpureus (red yeast). The protein hydrolysates from fermented dehulled djulis achieved 40.71% ACE inhibition by day 8 — approaching the 43.33% inhibition achieved by captopril, a widely prescribed blood pressure drug.
Using computational screening and proteomics, they identified a 9-amino-acid peptide called DK9 (DAAGYVADK) as the lead candidate. Molecular docking showed DK9 binds ACE with a binding affinity of -9.174 kcal/mol, stronger than captopril's -5.77 kcal/mol. DK9 works as a competitive inhibitor, and computational safety profiling predicted low toxicity and favorable drug-like properties.
Lu, Jheng-Jhe; Cheng, Kuan-Chen; Khumsupan, Darin; Hsieh, Chen-Che; Hsieh, Chang-Wei; Santoso, Shella Permatasari; Angkawijaya, Artik Elisa; Kuo, Hsing-Chun · In Vitro
RPEP-15612 · 2026In a meta-analysis of 7 RCTs (330 women with PCOS), liraglutide significantly improved both metabolic and reproductive outcomes: it increased menstrual frequency (g=1.76), reduced BMI (g=-0.52), improved insulin resistance (HOMA-IR g=-0.52), lowered luteinizing hormone and free androgen index, and modestly increased sex hormone-binding globulin. Adverse events were mainly mild GI symptoms. Ovulation and pregnancy outcomes could not be pooled due to insufficient data from the included trials.
Lu, Yu-Ting; Chang, Po-Han; Chen, Hsuan-Ju; Hsueh, Ya-Wen; Chang, Chia-Wei; Hsu, Hsi-Chen; Yang, Tung-Chuan; Lin, Wu-Chou; Chang, Hsun-Ming · Meta Analysis
RPEP-15615 · 2026The review categorizes rejection biomarkers by clinical utility:
- Well-validated molecular tools: Donor-derived cell-free DNA (ddcfDNA) and gene expression profiling (GEP) demonstrate strong discriminative capacity for acute rejection and are commercially available
- Emerging biomarkers: MicroRNAs (miRs) and extracellular vesicles (EVs) show considerable potential but require further validation
- Conventional biomarkers with limitations: B-type natriuretic peptide (BNP), cardiac troponins, and creatine kinase-MB (CK-MB) offer limited specificity for rejection — they detect cardiac stress broadly but cannot distinguish rejection from other causes
The review highlights a clear shift from conventional peptide/protein biomarkers toward molecular-based approaches for post-transplant surveillance.
Luo, Yijie; Lai, Junlin; Li, Chenghao; Wang, Guohua ·
RPEP-15627 · 2026The review identifies selenopeptides as a new class of anticancer agents with several key features:
Sources and synthesis: Selenopeptides can be derived from selenium-rich foods through enzymatic hydrolysis, or synthesized via solid-phase and liquid-phase peptide synthesis
Multiple anticancer mechanisms:
- Modulation of the PI3K/Akt signaling pathway (a master regulator of cell growth and survival)
- Activation of immune cells to attack tumors
- Inhibition of angiogenesis (blocking new blood vessel formation that tumors need to grow)
- Induction of cancer cell apoptosis (programmed cell death)
Evidence from in vitro, in vivo, and preliminary clinical studies confirms selenopeptides can inhibit cancer cell proliferation and reduce tumor markers.
Ma, Mingyu; Zhou, Xiaotong; Qiao, Xinyue; Li, Linling; Cheng, Shuiyuan; Lu, Yingtang; Cheng, Hua ·
RPEP-15628 · 2026The researchers identified a novel family of nonribosomal peptides designated paenitracins, representing the first bacitracin-type peptides reported in the Paenibacillus genus. Key features include:
- Three previously unseen amino acid substitutions distinguish paenitracins from canonical bacitracins
- Potent activity against gram-positive pathogens, including vancomycin-resistant Enterococcus faecium E155
- Discovered through a novel MassQL (mass spectrometry query language)-based approach combined with molecular networking
The study also provided a comprehensive genus-wide inventory of nonribosomal peptides produced by 227 taxonomically diverse Paenibacillus strains, establishing a resource for future antibiotic discovery.
Machushynets, Nataliia V; Elsayed, Somayah S; Du, Chao; Lysenko, Vladyslav; de la Cruz, Mercedes; Sanchez, Pilar; Genilloud, Olga; Martin, Nathaniel I; Liles, Mark R; van Wezel, Gilles P ·
RPEP-15631 · 2026The chemoenzymatic conjugation reaction produced trastuzumab-MMAE with a high yield of drug-to-antibody ratio (DAR) 2, meaning exactly two MMAE peptide payloads were attached to each antibody — a critical quality attribute for ADC efficacy and safety.
Microfluidic icIEF-UV/MS analysis separated and identified intact proteoforms of both unconjugated trastuzumab and the ADC, detecting shifts in isoelectric point and mass that confirmed successful conjugation. Trace levels of enzymatic and conjugation intermediates were also detected.
RP-HPLC peptide mapping with EAD fragmentation corroborated these findings at the peptide level, localized post-translational modifications on the antibody structure, and validated that MMAE was site-specifically conjugated to the glycan structure attached at asparagine-300.
Mack, Scott; Liu, Haichuan; Andersson, Erica; Zhang, Yuzhuo ·
RPEP-15632 · 2026A post-Roux-en-Y gastric bypass patient developed profound micronutrient deficiencies and acute liver injury after initiating semaglutide therapy, requiring ICU admission, parenteral (IV) nutrition, and endoscopic bypass reversal. The case illustrates a 'dual-hit' mechanism where GLP-1 receptor agonists compound the nutrient absorption limitations already present after bariatric surgery, creating a potentially life-threatening nutritional crisis.
Madej, Juliana; Gonzaga, Ernesto Robalino; Naveed, Mariam ·
RPEP-15644 · 2026Combining SGLT-2 inhibitors with GLP-1 receptor agonists was associated with a 29% lower risk of death from any cause compared to SGLT-2 inhibitors alone (HR 0.71, 95% CI 0.63–0.80) in over 21,000 matched pairs of type 2 diabetes patients. The combination also showed a 19% reduction in the cardiovascular composite outcome (HR 0.81) and a 22% reduction in heart failure risk (HR 0.78). These benefits were consistent across patient subgroups and multiple sensitivity analyses.
Maier, Gregor A; Hennig, Beata; Rathmann, Wolfgang; Kuss, Oliver · Observational
RPEP-15645 · 2026Intranasal delivery of therapeutic peptides can bypass the blood-brain barrier through nose-to-brain pathways, offering a non-invasive route to deliver Alzheimer's disease treatments directly to the brain. The review identifies key advantages: enhanced stability, rapid absorption, non-invasiveness, and improved patient compliance compared to injection-based delivery. Nanoparticle formulations can further improve the efficacy of intranasally delivered peptides by protecting them from degradation and enhancing their transport through nasal pathways.
Therapeutic peptides targeting critical AD pathological processes — including amyloid aggregation, tau phosphorylation, and neuroinflammation — are promising candidates for this delivery route. However, advancing from encouraging preclinical results to clinical applications remains the central challenge.
Majie, Ankit; Karmakar, Varnita; Ghosh, Arya; Chakraborty, Snigdha; Apurva; Layek, Buddhadev; Gorain, Bapi · Review
RPEP-15648 · 2026Monthly migraine days after discontinuation were still significantly lower than pre-treatment baseline (MD -3.78 days; 95% CI: -4.89 to -2.67), indicating a lasting residual benefit even after stopping therapy.
However, compared to the active treatment period, discontinuation led to a significant worsening: monthly migraine days increased by approximately 2.5 days and acute headache medication use rose by 3.22 days per month. The proportion of patients maintaining ≥50% reduction in migraines dropped substantially after cessation (RR 0.42; 95% CI: 0.33-0.53), meaning most patients who were responding well lost that level of benefit.
Makita, Luana Miyahira; Fagundes, Thales Pardini; Reginato, Pedro Henrique; Carpinelli, Lucca Passow; de Freitas Morais, Giovanna; Montanarin, Renata Trinkel; de Freitas Kleimmann, Rafael; Streit, Rafael Eduardo; Koppanatham, Aishwarya; Rodrigues, Andressa Christine Sales; Piovesan, Elcio Juliato ·
RPEP-15652 · 2026A 41-year-old female with type 1 diabetes developed severe euglycemic diabetic ketoacidosis (euDKA) after initiating tirzepatide for weight loss while already taking empagliflozin and basal-bolus insulin therapy. Key clinical findings:
- Blood pH: 6.96 (critically low; normal is 7.35-7.45)
- Bicarbonate: 1.5 mmol/L (critically low; normal is 22-28 mmol/L)
- Blood glucose: only 190-200 mg/dL (mildly elevated, masking the severity)
- Amylase: 688 U/L (elevated, suggesting possible pancreatic stress from tirzepatide)
- No infection or other precipitating cause was identified
The severity required intubation and intravenous bicarbonate therapy. The patient recovered after intensive insulin and fluid replacement.
Malik, Maliha; Amjad, Hammad; Malik, Khadija; Saleem, Muddassir Syed; Akhtar, Shanzay; Paracha, Muslehuddin; Abid, Mobeen; Shafi, Nabahat; Raza, Ahmed Asad; Samadi, Abedin; Jaffri, Samar Abbas ·
RPEP-15655 · 2026DTNBP1 protein was expressed throughout the SCN, with stronger expression in the dorsal region. Critically, DTNBP1 colocalized with neurons expressing both AVP (arginine vasopressin peptide) and VIP (vasoactive intestinal peptide) — two key neuropeptides that coordinate circadian rhythms across the body. Fluorescent in situ hybridization revealed time-dependent (daily rhythmic) variation of Dtnbp1 transcript expression in these neuropeptide cell bodies.
However, in Sandy (Sdy) mice carrying a loss-of-function Dtnbp1 mutation, there was no significant effect on AVP or VIP expression in the SCN. Transmission electron microscopy showed no effect on synaptic morphology or secretory vesicles. The circadian locomotor activity disruption previously observed in these mice therefore likely involves mechanisms beyond neuropeptide expression changes or gross synaptic architecture alterations.
Maloney, Genavieve Elizabeth; Cloutier, Marie-Ève; Provost, Micah Joseph; Srivastava, Lalit K; Cermakian, Nicolas ·
RPEP-15656 · 2026The electrostatics-stratified framework revealed three distinct antimicrobial peptide classes based on average charge per residue:
1. **Low-charge/length peptides** rely on amphipathic organization through structural compactness — their killing mechanism depends on physical shape and spatial arrangement rather than electrical charge.
2. **Intermediate-charge/length peptides** use a balanced combination of hydrophobicity and electrostatic attraction, employing both mechanisms in concert.
3. **High-charge peptides** couple strong cationic (positive) attraction with lipophilicity and tryptophan residue anchoring to directly disrupt bacterial membranes.
Across all three classes, the hydrophobic moment — a measure of how strongly the peptide's oily and water-loving regions are separated into distinct faces — emerged as a consistently important feature for antimicrobial activity.
Malshikare, Hrushikesh; Priyakumar, U Deva; Chatterjee, Prathit; Sengupta, Durba ·
RPEP-15658 · 2026Across five studies involving 1,128 semaglutide-exposed pregnancies, no clear association with birth defects was identified. One study found a spontaneous abortion rate of 23%, comparable to diabetes and obesity control groups. Another reported an 8.3% prevalence of congenital malformations but no significant risk increase compared to insulin-treated pregnancies. One study linked semaglutide discontinuation to fetal macrosomia and neonatal hypoglycemia. Overall, current evidence does not indicate a consistent increased risk of major congenital malformations from semaglutide exposure.
Mandal, Laura; Andersen, Louise Udby; Luef, Birgitte Møller; Tanvig, Mette Honnens; Vinter, Christina Anne ·
RPEP-15659 · 2026Fermenting milk with a two-strain probiotic consortium (Bacillus spizizenii and Bacillus subtilis) produced bioactive peptides with markedly enhanced multi-functional activity compared to single-strain fermentation. The consortium peptides achieved 90.80% α-amylase inhibition (relevant to diabetes management), 54.17% ABTS radical scavenging (antioxidant activity), and potent antimicrobial activity with MICs of 2.5–5 µg/mL against five bacterial pathogens including Pseudomonas aeruginosa and Staphylococcus aureus.
Maniya, Hina; Singh, Brij Pal; Kumar, Vijay ·
RPEP-15663 · 2026Across 14 studies (13 retrospective cohort) of GLP-1 receptor agonists in adults with IBD:
• 10 of 14 studies reported significant reductions in body weight, BMI, or percent weight loss
• 4 studies demonstrated metabolic improvements: decreased HbA1c and favorable lipid changes
• GLP-1 RA use was NOT associated with increased IBD exacerbations across multiple datasets
• Several large registries reported REDUCED risks among GLP-1 users of: corticosteroid use, hospitalization, and surgery
• Adverse events were primarily gastrointestinal, consistent with non-IBD populations (no excess GI toxicity from underlying IBD)
• The findings suggest potential anti-inflammatory or disease-modifying effects, though this requires prospective confirmation
Maracle, Brooke; Quan, Steven; Hamilton, Patrick; Shaikh, Asma; Hazra, Deepan; Lorenzetti, Diane L; Gold, Stephanie L; Raman, Maitreyi; St-Pierre, Joëlle ·
RPEP-15677 · 2026Emerging evidence suggests that GLP-1 receptor agonists may have anti-inflammatory and immunomodulatory effects relevant to rheumatoid arthritis, beyond their established roles in diabetes and obesity. However, current preclinical and clinical evidence is insufficient to recommend GLP-1 RAs as standard RA therapy. The review identifies mechanistic hypotheses for how these peptide drugs might modulate autoimmune inflammation and calls for well-designed randomized controlled trials.
Massay, Ryan; Malani, Angela; Stubbs, Aaron ·
RPEP-15678 · 2026The review's central finding is a clear distinction between growth factors and BPC 157 in musculoskeletal healing:
**Growth factors** (PDGF, TGF-β1, IGF-1, FGF, VEGF, BMPs): When delivered locally with carriers, they improve tendon, ligament, and muscle healing individually. However, some (PDGF, TGF-β1, IGF-1) fail in muscle lesions specifically, and all show limited or no efficacy in healing the junctions — osteotendinous (tendon-to-bone), myotendinous (muscle-to-tendon), and muscle-to-bone connections.
**BPC 157**: Acts alone without any carrier, combining beneficial effects on tendon, ligament, and muscle injuries simultaneously with junctional healing. In rat studies, it was effective across multiple routes — intraperitoneal injection, oral (intragastric or drinking water), and topical cream application.
Matek, Danijel; Matek, Irena; Japjec, Mladen; Matek, Mirta; Prenc, Jakov; Staresinic, Borna; Staresinic, Eva; Prtoric, Andreja; Sikiric, Suncana; Beketic Oreskovic, Lidija; Oreskovic, Ivana; Strbe, Sanja; Kordic, Mario; Tvrdeic, Ante; Seiwerth, Sven; Sikiric, Predrag; Boban Blagaic, Alenka; Skrtic, Anita; Bojanic, Ivan; Dobric, Ivan; Staresinic, Mario ·