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RPEP-13932 · 2025

Does Mixing Collagen With Coffee Reduce Its Absorption? A Clinical Trial Has Answers

Dissolving collagen hydrolysate in coffee altered the absorption of individual amino acids (hydroxyproline and proline showed significant variations) compared to dissolving it in water. However, the bioactive peptides themselves (Pro-Hyp, Hyp-Gly, Gly-Pro-Hyp) were absorbed similarly regardless of whether the collagen was mixed with water or coffee — the key pharmacokinetic measures (iAUC, peak concentration, time to peak) were equivalent. Peak concentrations of signature amino acids occurred between 60 and 120 minutes after intake. The polyphenols in coffee appear to affect free amino acid absorption but not the intact bioactive peptide fragments.

Virgilio, N; Schoen, C; van der Steen, B; Kleinnijenhuis, A J; van Holthoon, F L; Vleminckx, S; Silva, C I F; Prawitt, J · Rct

RPEP-13937 · 2025

GLP-1 Agonist Weight Loss Drugs May Cause Female Anorgasmia Through Reduced Blood Flow and Brain Signaling Changes

A female patient developed anorgasmia following initiation of a GLP-1 receptor agonist. The authors propose several mechanisms: the most likely being GLP-1 agonist-induced vasoconstriction of smooth muscle, which reduces oxygen delivery and blood flow to the genitals, hindering genital engorgement, arousal, and the smooth muscle contractions essential for orgasm. Additional proposed mechanisms involve GLP-1 receptor modulation in the hypothalamus, which may decrease dopamine and norepinephrine signaling — neurotransmitters crucial for motivation, pleasure, and orgasm — and disrupt pathways involved in sexual desire and arousal.

Visvabharathy, Vidya; MacPhedran, Sally; Shupp, Katie; King, Benjamin ·

RPEP-13958 · 2025

GLP-1 Drug Dulaglutide Protects Against Parkinson's-Like Brain Damage Caused by High Fructose in Rats

Rats fed 10% fructose for 24 weeks developed Parkinsonian features: cognitive and motor deficits, loss of substantia nigra neurons, dopamine deficiency, and altered expression of α-synuclein, LRRK2, and parkin. These changes were accompanied by insulin resistance, dyslipidemia, neuroinflammation, and apoptosis. All three treatments (dulaglutide 0.2 mg/kg/week SC, empagliflozin 30 mg/kg/day oral, pirfenidone 100 mg/kg/day oral) ameliorated these perturbations when given during the last 4 weeks of the fructose feeding period. Combination therapy (pirfenidone + dulaglutide or pirfenidone + empagliflozin) showed more pronounced effects than individual treatments, demonstrating additive neuroprotection.

Wahba, Alaa S; Mohamad, Hoda E; Abo-Elmatty, Dina M; Mesbah, Noha M; Wahba, Nehal S; El Azzazy, Ahmed S; Sakr, Amr T ·

RPEP-13961 · 2025

Redesigned Cell-Penetrating Peptide Uses a Smart Cleavable Link to Deliver Gene-Silencing RNA into Cancer Cells

The researchers developed PI-linker-cRGD, a prodrug-type bifunctional cell-penetrating peptide with a sterically refined redox-cleavable disulfide linker connecting the membrane-penetrating PI peptide to the cancer-targeting cRGD ligand. The previous version (PI-cRGD) achieved cellular uptake via endocytosis but failed to deliver siRNA to the cytosol because steric hindrance prevented disulfide bond cleavage inside cells. The redesigned linker solved this problem: it allowed thiol-disulfide exchange at the cell surface, activating the CPP to promote membrane translocation and achieving efficient cytosolic siRNA delivery while maintaining low cytotoxicity and cancer-targeting ability.

Wakamori, Keita; Hashikawa, Yuzuki; Urata, Hidehito; Wada, Shun-Ichi ·

RPEP-13962 · 2025

First Evidence That Neuropeptide Y Blood Vessel Constriction Is Overridden by Exercise in Humans

In 12 healthy adults during forearm handgrip exercise (15% maximum): • Phenylephrine (α1-adrenergic) vasoconstriction was attenuated during exercise vs control: ΔFVC -17±9% vs -44±25% (P=0.002), representing 68±18% sympatholysis • NPY (Y1 receptor) vasoconstriction was similarly attenuated: ΔFVC -11±7% vs -32±22% (P=0.029), representing 52±34% sympatholysis • No significant difference in sympatholysis magnitude between PE and NPY (68% vs 52%, P=0.28) This is the first demonstration that NPY-mediated vasoconstriction is sensitive to metabolic inhibition during exercise in humans, confirming that functional sympatholysis extends beyond the classical adrenergic pathway to include the neuropeptide Y system.

Wakeham, Denis J; Hissen, Sarah L; MacNamara, James P; Davis, Scott L; Fadel, Paul J; Levine, Benjamin D; Hearon, Christopher M ·

RPEP-13982 · 2025

Marine Peptide Hydrogel Fights Infection and Speeds Wound Healing in Animal Study

The PTDP hydrogel demonstrated multiple therapeutic properties in a single material. In vitro, it showed potent antioxidant activity, efficiently inhibited both Staphylococcus aureus and Escherichia coli growth, and was compatible with endothelial cells — even promoting their migration and proliferation. In murine full-thickness infected wound models, the hydrogel significantly accelerated wound closure, enhanced neovascularization (new blood vessel formation), and improved collagen deposition. The material's physicochemical properties were also notable: tunable plasticity, high swelling ratios for absorbing wound exudate, sustained hydration retention, and strong substrate adhesion — all important qualities for a practical wound dressing.

Wang, Chuhan; Yu, Dingyi; Liu, Wen; Zhu, Xiang; Zhang, Hanzhe; Zheng, Shuang; Chen, Jingdi ·

RPEP-13983 · 2025

Peptide-Drug Conjugates: The Next Evolution Beyond Antibody-Drug Conjugates for Cancer Treatment

PDCs offer several advantages over ADCs: more accessible industrial synthesis, versatile functionalization, high tissue penetration, rapid clearance, and low immunotoxicity. Three peptide categories serve different delivery functions — tumor-targeting peptides for specificity, cell-penetrating peptides for intracellular delivery, and self-assembling peptides for controlled release and nanostructure formation. PDCs can overcome drug resistance, control drug release, and improve efficacy while reducing off-target toxicity. However, poor pharmacokinetic properties and low bioactivity remain the primary clinical development challenges.

Wang, Dongyuan; Yin, Feng; Li, Zigang; Zhang, Yu; Shi, Chen ·

RPEP-13986 · 2025

Meta-Analysis Confirms Liraglutide Reduces Kidney Damage Marker in Type 2 Diabetes

Across seven RCTs involving 473 participants, liraglutide significantly reduced the albumin-to-creatinine ratio compared to controls (weighted mean difference: -11.76 mg/g, 95% CI -21.71 to -1.81, P = 0.02). Heterogeneity was substantial (I² = 75%). Subgroup analyses identified populations with the greatest benefit: patients with HbA1c > 8.0%, treatment duration > 12 weeks, and age < 60 years all showed significant ACR reductions. Meta-regression found that no single variable (sample size, HbA1c, baseline ACR, duration, or dose) explained the heterogeneity. Sensitivity analysis confirmed stable results, and no publication bias was detected (Begg's P = 0.46, Egger's P = 0.57).

Wang, Feng; Xu, Guangzhong; Feng, Wei; Qu, Gengbao; Li, Pengyu; Li, Kai ·

RPEP-13989 · 2025

Toad-Derived Antimicrobial Peptide in Hydrogel Wound Dressings Accelerated Healing in Infected and Clean Wounds

Researchers developed two hydrogel formulations (carbomer-based and temperature-sensitive chitosan-based) loaded with the antimicrobial peptide cathelicidin-DM, originally isolated from a toad species. Both hydrogels significantly accelerated healing of full-thickness skin wounds in mice — in both infected (S. aureus) and non-infected wounds. The peptide interacted with both hydrogel materials at the molecular level, forming 3D network structures with favorable properties. The hydrogels also demonstrated hemostatic (bleeding-stopping) capabilities.

Wang, Guixi; Huang, Yafei; Shi, Yaoqiang; Han, Qinqin; Zhang, Jinyang; Song, Yuzhu; Li, Chao ·

RPEP-13995 · 2025

Multi-Omics Study Maps How GLP-1, GIP, Insulin, and Glucagon Respond Differently to Various Foods

The study revealed several important findings about peptide hormone dynamics: - GLP-1 and GIP secretion patterns are exclusively explained by postprandial (after-eating) data — fasting measurements miss them entirely - Postprandial multi-omics data significantly improved the ability to explain insulin and glucagon secretion patterns compared to fasting data alone - Hormone secretion and molecular responses showed substantial heterogeneity among macronutrient types (mixed meals vs. four distinct macronutrient loads) - Protein load showed the strongest association with both hepatic (liver) and muscular insulin resistance - Butter load connected most strongly with systemic insulin resistance - Postprandial multi-omics better predicted insulin resistance than fasting data, with hepatic enrichment - Several molecules were identified that mediate interactions between insulin resistance and islet α-cell (glucagon) and β-cell (insulin) function

Wang, Jiachen; Liu, Ling; Liu, Hechun; Qian, Yu; Zhang, Sijie; Zheng, Shuai; Jiang, Hemin; Zhou, Yue; Cheng, Xiaoliang; Fu, Qi; Dai, Hao; Yang, Tao ·

RPEP-13996 · 2025

Meta-Analysis of 10 Trials: Tirzepatide Produces 11.6 kg Average Weight Loss and Improves Heart Health Markers

Across 10 RCTs with 6,257 participants, tirzepatide produced a pooled mean weight reduction of -11.62 kg compared to placebo (95% CI: -14.24 to -9.01, p < 0.001). At the highest dose of 15 mg, weight loss milestones were impressive: 88.1% achieved >5% weight loss, 63.3% achieved >10%, and 51.8% achieved >15%. Significant improvements were observed across cardiometabolic markers including HbA1c, waist circumference, BMI, and lipid profiles. The safety profile was favorable with no increase in serious adverse events or mortality.

Wang, Jian-Ying; Kang, Jyun-Wei; Peng, Tzu-Rong; Chen, Hsin-Yen; Chen, Shih-Ming; Lee, Ming-Chia ·

RPEP-14000 · 2025

Immune-Evading Peptide-Coated Nanoparticles Deliver Anti-Inflammatory Drug to Epileptic Brain Regions

Researchers designed a dual-function nanoliposome system for epilepsy treatment that uses a CD47 mimicry peptide to evade immune clearance and pH sensitivity to target epileptic brain regions. The CD47 peptide coating signals macrophages with a 'don't eat me' message, preventing immune cells from destroying the nanoparticles and enabling prolonged circulation. Because epileptic foci have an acidic microenvironment, the pH-sensitive liposomes preferentially release their drug cargo at the disease site. The system successfully delivered icariin (a plant-derived anti-inflammatory compound) to epileptic brain tissue in mice, significantly alleviating neuronal damage, reducing neuroinflammation and oxidative stress, and improving cognitive dysfunction. Network pharmacology and transcriptomics confirmed the therapeutic mechanism.

Wang, Jing; Du, Yangsa; Su, Guoting; Tang, Weiting; Long, Xiaoyan; He, Yongju; Feng, Li · Animal And Cell

RPEP-14002 · 2025

Giant Salamander Skin Contains Bioactive Peptides with Antimicrobial, Anticancer, and Antidiabetic Properties

Giant salamander skin and secretions contain multiple families of bioactive peptides including brevinins, bombesins, dermaseptins, esculentins, magainins, temporins, tigerinins, and salamandrins. These peptides collectively demonstrate antioxidant, antimicrobial, anticancer, and antidiabetic biological activities. The review identifies potential applications across two industries: food (as multifunctional additives and dietary supplements) and biomedicine (as antimicrobial agents, anticancer leads, and drug delivery vehicles). The nutritional composition of giant salamanders and the production status of cultured specimens are also examined as context for sustainable sourcing.

Wang, Jinghua; Liu, Yuchen; Guo, Hongfei; Chen, Dejing; Abdu, Hassan Idris; Yang, Meng; Pei, Jinjin; El-Aty, A M Abd ·

RPEP-14005 · 2025

How the Peptide LL37 Drives Skin Pigment Loss in Vitiligo

The antimicrobial peptide LL37 was found at elevated levels in vitiligo patients' blood and skin lesions. When keratinocytes (skin cells) were exposed to oxidative stress (H2O2), they released LL37, which then bound to DNA forming LL37-DNA complexes. These complexes activated the TLR9-MyD88 signaling pathway in keratinocytes, increasing secretion of chemokines CXCL9, CXCL10, and CXCL16, which in turn attracted CD8+ T cells — the immune cells that destroy melanocytes in vitiligo. This establishes a mechanistic pathway: oxidative stress → LL37 release → DNA binding → TLR9 signaling → immune cell recruitment → melanocyte destruction.

Wang, Jingying; Mao, Hanxiao; Liu, Rulan; Zeng, Ziyuan; Xie, Lvsha; Yang, Yan; He, Yuanmin ·

RPEP-14012 · 2025

Berberine Disrupts Skeletal Muscle Formation in Lab Tests While Semaglutide Shows No Muscle Effects

Berberine inhibited myofibril assembly at the nascent myofibril stage in embryonic skeletal muscle cells, preventing the normal progression to mature muscle fibers. RT-PCR experiments showed that berberine specifically inhibited mRNA for muscle myosin II heavy chains (a key structural protein) while not affecting muscle actin mRNA in skeletal muscle cells. Importantly, berberine had no effect on myofibril assembly in embryonic heart cells, which may explain clinical reports of berberine being safe for the heart even in cancer patients. In contrast, semaglutide showed no effects on myofibril assembly in either cardiac or skeletal muscle cell cultures, suggesting a cleaner muscle safety profile.

Wang, Jushuo; Fan, Yingli; Dube, Syamalima; Benz, Patricia; Dube, Dipak; Sanger, Jean M; Sanger, Joseph W ·

RPEP-14014 · 2025

Peptides in Skincare: What They Are, How They Work, and Which Ones Actually Have Evidence

Peptides have become major ingredients in the cosmetic and skincare industry due to their potential to boost skin health. This comprehensive review covers peptides from four angles: their sources (natural and synthetic), their biological functions, their specific applications in cosmetics and skincare, and the delivery technologies needed to get them into the skin effectively. The review contextualizes cosmetic peptides within the broader peptide landscape, noting that over 80 peptide-based drugs have reached the market for conditions ranging from diabetes to cardiovascular disease. Peptides in skincare work through multiple mechanisms including signaling collagen production, inhibiting neurotransmitter release (Botox-like effects), carrying metals like copper to skin cells, and inhibiting enzymes that break down collagen and elastin.

Wang, Leyang; Wu, Zhijing; Wang, Xinyu; Wang, Xiaoli; Mao, Jingzhuo; Yan, Yan; Zhang, Lu; Zhang, Zhuzhen · Review

RPEP-14018 · 2025

How Probiotic Bacteria and Their Antimicrobial Peptides Keep Food Fresh Naturally

Probiotics produce antimicrobial peptides (AMPs) — including bacteriocins, enzymes, and peptide-based inhibitors — that kill foodborne pathogens and spoilage organisms. When probiotics and their AMPs are used together, they create a synergistic effect: the probiotics colonize food and form protective biofilms while simultaneously producing AMPs that disrupt bacterial membranes, inhibit cell wall synthesis, and suppress virulence genes. This combination approach extends the shelf life of dairy, meat, and vegetable products by controlling microbial contamination. Many probiotic-derived AMPs are stable at high temperatures and varying pH levels, making them practical for food processing. The review positions probiotic-AMP combinations as natural, label-friendly alternatives to chemical food preservatives.

Wang, Lingling; Ren, Shuanshan; Behan, Atique Ahmed; Arain, Muhammad Asif; Ujjan, Nissar Ahmed; Zeng, Dequan; Li, Yufeng; Ma, Xingming · Review

RPEP-14029 · 2025

Simply Mixing a Cell-Penetrating Peptide with Gene Therapy Viruses Boosts Their Delivery Into Hard-to-Reach Cells

Co-administration of Transportan (TP) with GFP-expressing AAVs and lentivirus enhanced transfection efficiency across multiple cell types with limited cytotoxicity. The approach worked in standard cell lines and, importantly, in difficult-to-transfect cells: the RAW264.7 macrophage cell line, bone marrow-derived macrophages (BMDMs), and retinal pigment epithelium (RPE) cells. The method requires only simple mixing — no specialized equipment, chemical modifications, or complex protocols.

Wang, Nianwu; Hu, Xiangxiang; Pang, Hong-Bo ·

RPEP-14033 · 2025

Novel Dual GLP-1 Fusion Peptide Efsubaglutide Alfa Shows Strong Dose-Response for Blood Sugar and Weight Loss in Diabetes Trial

In 465 drug-naïve T2DM patients (median age 51, mean baseline HbA1c 8.71%) receiving efsubaglutide alfa 1, 2, or 3 mg weekly: - Clear positive exposure-response relationship for all efficacy endpoints at weeks 24 and 52: HbA1c, fasting plasma glucose, meal tolerance glucose AUC, body weight, waist circumference, and BMI - A 10-fold increase in Cmin,ss corresponded to a 1.150% decrease in HbA1c at week 24 - Baseline HbA1c, age, and neutralizing anti-drug antibodies influenced the exposure-response relationship - Treatment-related adverse events (nausea, diarrhea) correlated positively with drug exposure but showed tolerance development over time - The extended half-life from the Fc fusion design supports once-weekly or potentially biweekly dosing

Wang, Qinghua; Jiang, Fan; Xu, Yulong; Lei, Yuyang; Zhang, Li; Sun, Xiaodong ·

RPEP-14034 · 2025

New Long-Acting GLP-1 Drug Efsubaglutide Alfa Shows Clear Dose-Response for Blood Sugar and Weight in Type 2 Diabetes

In 406 patients with type 2 diabetes on stable metformin, efsubaglutide alfa showed a robust inverse correlation between drug exposure and HbA1c, fasting plasma glucose, body weight, and BMI. Doubling steady-state trough concentrations reduced HbA1c by 0.211%, and every 100 ng/mL increase in average steady-state concentration led to a 0.5 kg reduction in body weight at week 24. The drug also positively correlated with C-peptide levels during a meal tolerance test, indicating improved pancreatic beta-cell function. Gastrointestinal adverse events increased with higher exposure but decreased over time, suggesting tolerance development. Baseline HbA1c was identified as a predictor of treatment response.

Wang, Qinghua; Jiang, Fan; Xu, Yulong; Lei, Yuyang; Zhang, Li; Sun, Xiaodong ·

RPEP-14043 · 2025

Designing Triple-Receptor Agonist Peptides That Match Top Obesity Drugs Without Maxing Out Every Receptor

Researchers designed a novel triple-receptor agonist peptide (xGLP/GCG/GIP-32) that activates GLP-1R and GCGR potently but GIPR only weakly. Despite this intentionally unbalanced activation profile, the compound achieved weight loss effects superior to tirzepatide (a dual GLP-1R/GIPR agonist) and metabolic efficacy comparable to retatrutide (a triple agonist), both of which are leading obesity/diabetes drugs. The study revealed that xGLP/GCG/GIP-32 exhibits biased agonism toward GIPR and GCGR, suggesting that maximal potency at all three receptors may not be necessary — and that strategically tuning the ratio of receptor activation could be a more effective design approach for next-generation metabolic peptide drugs.

Wang, Shuang; Liu, Yun; Yan, Zhiming; Huang, Xianxian; Liao, Yonghe; Tang, Chunli; Jing, Lin; Zhou, Zhongbo; Han, Jing; Tang, Weizhong; Jiang, Neng · Preclinical

RPEP-14045 · 2025

Semaglutide Protects Kidneys From Obesity-Related Damage in Mice Through Anti-Inflammatory Pathway

In 48 mice divided into four groups (normal diet, high-fat diet, HFD + semaglutide, HFD + adenosine): - Semaglutide reduced weight in obese mice - Improved glucose and lipid metabolism markers - Reduced inflammation and oxidative stress - Improved glomerular and tubular kidney lesions (confirmed by light and electron microscopy) - Proteomics (LC-MS/MS) identified the Txnip/NLRP3 signaling pathway as involved in obesity-related kidney damage - Western blot confirmed that Txn, Txnip, and NLRP3 protein expression was elevated in obese mice and significantly reduced by semaglutide treatment - Adenosine showed similar protective effects

Wang, Shuqi; Pan, Xiaoyu; Liang, Ruiqing; Chen, Shuchun ·

RPEP-14046 · 2025

Tirzepatide vs. Semaglutide for Type 2 Diabetes in China: Better Health Outcomes but Not Cost-Effective

Tirzepatide 5 mg and 10 mg produced incremental QALYs of 0.05 and 0.09 compared to semaglutide 1 mg. However, the incremental cost-utility ratios were $445,125/QALY and $543,829/QALY respectively — both far exceeding China's willingness-to-pay threshold of $29,600/QALY. Adding tirzepatide to the national health insurance would cost an additional $80-490 million over 5 years, but overall healthcare expenditures could decrease due to reduced out-of-pocket costs for patients.

Wang, Sihua; Fan, Duncong; Yao, Qinhong; Sun, Xiaojie ·

RPEP-14048 · 2025

Nanoparticle Formulation Solves Stability and Delivery Problems for Anticancer Peptide PEN-FFW

Researchers developed a stable nanoformulation for the anticancer peptide PEN-FFW by encapsulating it in carboxymethyl cellulose-PLGA nanoparticles stabilized with polysorbate 80. Optimization using a Box-Behnken design achieved a 50% increase in encapsulation efficiency and enhanced storage stability. The formulation showed superior cellular uptake and cytotoxicity in liver cancer cells in vitro, and significantly greater hepatic retention compared to free peptide in mice.

Wang, Tianqi; Lazareva, Polina A; Malinovskaya, Julia; Panczyk, Tomasz; Wen Hui, Joyce Ang; Dhakal, Namrata; Liu, Beijia; Qin, Qiuhua; Kovshova, Tatyana; Sur, Somok; Vadekhina, Veronika; Ivanova, Anna V; Valikhov, Marat; Reich, Gabriele; Chen, Wenqian; Gelperina, Svetlana; Abakumov, Maxim A; Wacker, Matthias G ·

RPEP-14052 · 2025

How Semaglutide May Protect the Brain After Stroke by Preventing a Type of Cell Death Called Ferroptosis

Using a rat model of ischemic stroke (middle cerebral artery occlusion/reperfusion), semaglutide reduced brain tissue damage and neuronal death. At the molecular level, semaglutide activated GLP-1 receptors to modulate two key pathways: 1. **FoXO1/GPX4 pathway**: Semaglutide regulated the FoXO1 transcription factor and increased GPX4 (a key anti-ferroptosis enzyme), inhibiting autophagy (via reduced Beclin1) and preventing ferroptotic cell death. 2. **DRP1/ACSL4 pathway**: Semaglutide suppressed DRP1-mediated mitochondrial fission (fragmentation), promoted Mfn2-mediated mitochondrial fusion, increased ATP production, and reduced reactive oxygen species (ROS). This improved mitochondrial health and reduced ACSL4-dependent ferroptosis. Bioinformatics analysis predicted these mechanisms, which were then validated through Western blotting, RT-PCR, immunofluorescence, and ELISA experiments.

Wang, Weihua; Pang, Meng; Zhang, Yifeng; Hou, Shuai; Xia, Yulei; Shi, Youkui; Zhang, Xiaojun; Wang, Yanqiang ·

RPEP-14056 · 2025

Semaglutide Achieves 90% Weight Loss Success Rate in Hypothalamic Obesity After Brain Tumor Surgery

In the semaglutide group (n=14), weight decreased significantly from 108.9 ± 20.9 kg to 100.8 ± 20.2 kg at 3 months (p < 0.001) and to 96.1 ± 23.1 kg at 6 months (p < 0.001) — a total loss of ~12.8 kg. At 3 months, 64.3% achieved >5% weight loss; at 6 months, this rose to 90%. The control group (n=9) on lifestyle intervention alone experienced weight gain over the same period. This is particularly notable because hypothalamic obesity is driven by brain damage rather than behavioral factors, and most weight loss interventions are ineffective in this population.

Wang, Xi; Ma, Hailu; Wang, Fang; Long, Hongmei; Li, Chenyang; Nie, Min; Han, Qin; Mao, Jiangfeng; Wu, Xueyan ·

RPEP-14057 · 2025

Defense Peptide Nanoparticles Deliver Gene-Silencing Therapy and Boost Immune Response Against Breast Cancer

The engineered HH2-siEMP2 nanoparticles achieved effective EMP2 gene silencing in breast cancer cells, leading to significant suppression of tumor migration and invasion both in vitro and in vivo. Beyond direct anti-tumor effects, the HH2-cholesterol conjugate demonstrated immunomodulatory properties: promoting Th1 cell expansion (pro-inflammatory, anti-tumor), reducing Th2 cells (which can promote tumor tolerance), decreasing immunosuppressive regulatory T cells (Tregs), and restoring the Th17/Treg balance. The nanoparticles showed optimal size, positive surface charge, excellent serum stability, and enhanced cellular uptake.

Wang, Xiaoyun; Chen, Siliang; He, Gu; Zhu, Yanghui; Zhang, Nan; Gong, Changyang; Li, Xiang; Chen, Yujuan ·

RPEP-14062 · 2025

LL-37 Antimicrobial Peptide Blocks Alzheimer's-Linked Protein Clumping in Lab Studies

LL-37 and three of its truncated fragments all formed hetero-oligomers and nanoclusters with amyloid-beta 40 (Aβ40), inhibiting the formation of amyloid fibrils — the toxic protein clumps associated with Alzheimer's disease. However, the full-length LL-37 and one specific fragment (LL-37₁₉₋₂₈) were the most potent inhibitors. These two peptides formed more hetero-oligomers and smaller nanoclusters with Aβ40, which appear to represent an 'off-pathway' dead end that prevents productive aggregation. At the microscale, they also rapidly formed larger clusters with Aβ, and uniquely affected the elongation phase of fibril growth — a step the other fragments could not influence.

Wang, Xue; Österlund, Nicklas; Pereira Curia, Guadalupe; Mörman, Cecilia; Sternke-Hoffmann, Rebecca; L Ilag, Leopold; Gräslund, Astrid; Wang, Guangshun; Luo, Jinghui · In Vitro

RPEP-14063 · 2025

Protein Znhit1 Reduces Migraine Pain by Suppressing CGRP and NLRP3 Inflammasome Activation

In a nitroglycerin-induced migraine mouse model: - Znhit1 expression was reduced in the trigeminal nucleus caudalis (TNC) — the brain's migraine pain center - Overexpression of Znhit1 produced multiple beneficial effects: - Alleviated thermal and mechanical hyperalgesia (pain hypersensitivity) - Upregulated 5-HT (serotonin) levels - Inhibited c-Fos expression (a marker of neuronal activation) - Reduced CGRP expression (the key migraine neuropeptide) - Downregulated inflammatory markers: IL-6, IL-1β, TNF-α, COX-2, iNOS - Inhibited NLRP3 inflammasome activation In vitro: Znhit1 silencing in microglia enhanced inflammation and apoptosis via NLRP3 activation, which was reversed by the specific NLRP3 inhibitor MCC950 — confirming NLRP3 as the key downstream target.

Wang, Xue; Tang, Jianhua; Hou, Yiwei; Sui, Changbai ·

RPEP-14068 · 2025

GLP-1 Drugs Reduce Fat but Don't Cause Muscle Loss in Diabetic Patients with Sarcopenia

Across 9 randomized controlled trials with 1,089 participants, GLP-1 receptor agonists produced significant reductions in fat-related measures: body fat ratio decreased (MD = -2.76, p < 0.01), fat mass decreased (MD = -8.00, p < 0.01), and BMI decreased (MD = -1.83, p < 0.01). Critically, muscle-related measures were not significantly affected: lean body mass showed a non-significant increase (MD = +4.61, p = 0.31) and skeletal muscle index was also unchanged (MD = +0.59, p = 0.19). Body weight change overall was not statistically significant (MD = -2.25, p = 0.20), suggesting the weight composition shifted favorably from fat to a relatively preserved lean mass.

Wang, Yanying; Lan, Boya; Zhang, Shuo; Mu, Yue; Mi, Jia; Yu, Jing; Zhan, Qun; Luo, Baoling; Lin, Fuyang; Teng, Jia; Wang, Xiuge; Yan, Guanchi ·

RPEP-14081 · 2025

A Gecko-Derived Peptide Gel That Protects Skin from UV-Induced Aging in Mice

A modified cathelicidin peptide derived from geckos — called G3CY-10 — delivered through a microemulsion gel system protected mouse skin against UV-induced photoaging. The gel formulation (lecithin-ethanol-butyl acetate, km = 1:1) showed notable stability and significantly enhanced transdermal delivery of the peptide. In UV-exposed mice, the G3CY-10 gel reduced epidermal thickening, suppressed sebaceous gland overgrowth, and restored collagen fiber density. The peptide worked primarily by blocking UV-induced collagen breakdown and restoring levels of superoxide dismutase (SOD), a key antioxidant enzyme depleted by UV exposure.

Wang, Yunjiao; Ma, Zicheng; Li, Fengshuo; Li, Xuanzeng; Gao, Ningyang; Wang, Junhan; Cai, Shasha · Preclinical

RPEP-14086 · 2025

Genetic Variants Including the Cathelicidin Peptide Gene May Determine Who Gets Rosacea

The review identifies several key genes with polymorphisms associated with rosacea: - CAMP (cathelicidin antimicrobial peptide): Encodes the precursor of LL-37, an antimicrobial peptide whose overexpression drives rosacea-specific inflammation - TLR2 (Toll-like receptor 2): Part of innate immune recognition; variants may alter the skin's inflammatory response to microbes - IL-17: A pro-inflammatory cytokine gene associated with chronic inflammatory skin conditions - HLA (human leukocyte antigen): Immune system genes that determine susceptibility to various inflammatory conditions The disease is characterized as polygenic with environmental modifiers, involving both innate immunity and neurovascular regulation abnormalities.

Wang, Zhuangyi; Zhang, Zhengzhong ·

RPEP-14092 · 2025

What Doctors Need to Know When Performing Procedures on Patients Taking Ozempic and Other GLP-1 Drugs

The review identifies two primary peri-procedural concerns for patients taking GLP-1 receptor agonists: 1. Delayed gastric emptying — GLP-1 agonists slow the rate at which the stomach empties, meaning standard fasting protocols may not adequately ensure an empty stomach before conscious sedation, increasing the risk of aspiration (inhaling stomach contents into the lungs) 2. Blood sugar effects — These drugs lower fasting glucose levels, which has implications for blood sugar management during and after procedures, particularly in diabetic patients who may also be on insulin or other hypoglycemic agents The review emphasizes that current interventional radiology guidelines do not adequately address these GLP-1-specific risks and calls for IR-specific guidance to be developed.

Wani, Suhail; Findakly, Salam; Phan, Tuan; Lukies, Matthew W; Goh, Gerard S; Venn, Georgina; Joseph, Tim; Koukounaras, Jim; Clements, Warren ·

RPEP-14094 · 2025

Meta-Analysis Confirms GLP-1 Drugs Reduce Heart and Kidney Events in Older Adults

Among 44,013 older adults (≥65 years) across 11 randomized controlled trials, GLP-1 receptor agonists significantly reduced: - Composite kidney outcome by 22% (HR: 0.78; 95% CI: 0.70-0.87; P < 0.001) - 3-point major adverse cardiovascular events (MACE) by 14% (HR: 0.86; approximate from context) - Cardiovascular death by 13% Benefits on stroke, myocardial infarction, and heart failure hospitalization showed favorable trends but did not reach statistical significance individually. Importantly, the efficacy in older adults was comparable to younger adults, with no significant interaction between age groups (P > 0.2 for all endpoints).

Waqas, Saad Ahmed; Ali, Dua; Afridi, Muhammad Khalid; Siddiqui, Hasan Fareed; Nazir, Arif; Greene, Stephen J; Khan, Muhammad Shahzeb ·

RPEP-14097 · 2025

A Computer-Aided Recipe for Designing Cyclic Peptide Drugs That Actually Work

Researchers developed a reproducible computational workflow for designing cyclic peptide drugs that combines Rosetta protein modeling, molecular dynamics simulations, chemical synthesis, and X-ray crystallography validation. Using the 'anchor extension' method — starting from an unnatural amino acid known to bind the target and computationally extending the cyclic peptide scaffold — they found high-affinity, selective inhibitors by testing fewer than 50 designed peptides. The method uses a chemical space of all canonical amino acids, their mirror-image variants, and 20 non-canonical amino acids. Originally developed for histone deacetylase (HDAC) inhibitors, the approach has been successfully extended to other targets including kappa-opioid receptors.

Watson, Paris R; Pardo-Avila, Fátima; Hosseinzade, Parisa · Methods

RPEP-14099 · 2025

Anti-CGRP Antibody Reduces Post-Concussion Headache Sensitivity in Mice — But Timing Matters

An anti-CGRP monoclonal antibody partially reduced persistent headache-like sensitivity following mild traumatic brain injury (concussion) in mice. When given before or immediately after repeated head impacts, the antibody partially reduced ongoing tactile hypersensitivity but did not fully prevent it. However, when administered before exposure to headache triggers (CGRP itself or nitric oxide) during the persistent sensitization phase, the antibody fully prevented hypersensitivity. This suggests anti-CGRP therapy may be most effective at blocking the triggers that maintain post-traumatic headache rather than preventing the initial injury response.

Wattiez, Anne-Sophie; Kuburas, Adisa; Castonguay, William C; Fejgin, Kim; Klewe, Ib V; Russo, Andrew F · Animal Study

RPEP-14103 · 2025

New Cell-Penetrating Peptide Designed to Selectively Enter Brain Cells Through Alpha-7 Nicotinic Receptors

The researchers designed chimeric peptides combining regions of rabies virus glycoprotein (RVG) and alpha-bungarotoxin, then screened them for receptor selectivity. They identified a peptide with improved selectivity and apparent potency for the alpha-7 nicotinic acetylcholine receptor (nAChR) subtype compared to the control RVG peptide. In Neuro-2a cells, the peptide's internalization depended on alpha-7 nAChR expression on the cell surface, and it successfully carried small-molecule payloads into neuronal-like cells without significant cytotoxic effects.

Weber, Lahra; O'Brien, Brittany C V; Weltzin, Maegan M ·

RPEP-14106 · 2025

Fermented Soybean Peptides That Taste Savory Also Lower Blood Pressure by Inhibiting ACE

From fermented soybean curds, 11 candidate peptides with potential dual umami and ACE inhibitory activities were identified via nano-HPLC-MS/MS and database screening. Pharmacophore modeling confirmed high ACE inhibition probability (fit values >2) with binding through hydrogen bonds, electrostatic, and hydrophobic interactions. Three synthesized peptides showed the following ACE inhibitory IC50 values: WEEF (85 ± 2 μM), FEF (170 ± 10 μM), and VE (205 ± 5 μM). Umami thresholds were WEEF (0.32 mM) < FEF (0.53 mM) < VE (4.8 mM). WEEF exhibited the best overall dual activity. Nitric oxide (NO) and endothelin-1 (ET-1) production were dose-dependent, further supporting vascular activity.

Wei, Guanmian; Zhao, Feiran; Zhang, Ziyi; Regenstein, Joe M; Sang, Yaxin; Zhou, Peng ·

RPEP-14107 · 2025

Natriuretic Peptide Receptor Deficiency Plus High Salt Diet Triggers Deadly Aortic Tears in Mice

NPR-C was downregulated in aortas of acute thoracic aortic dissection (TAD) patients and in mouse models. Smooth muscle cell-specific NPR-C knockout mice developed TAD when treated with angiotensin II plus high salt diet, but not angiotensin II alone — revealing high salt as a critical trigger. Mechanistically, NPR-C loss activated the ERK1/2 pathway, which decreased PPARγ activity and suppressed HADHB expression, impairing mitochondrial fatty acid oxidation. The NPR-C agonist peptide C-ANP4-23 mitigated TAD progression in disease model mice, and spermidine (which activates the mitochondrial trifunctional protein) also effectively prevented TAD formation.

Wei, Jin-Qiu; Yang, Yi; Zhai, Wen-Hui; Zhao, Jia-Jia; Yang, Yi-Hang; Kang, Yuan-Yuan; Huang, Qi-Fang; Zhang, Wei; Rong, Wu-Wei; Deng, Qian-Wan; Chen, Jing; Ye, Xiao-Fei; Gao, Ping-Jin; Wang, Zhe; Li, Xiao-Dong; Wang, Ji-Guang ·

RPEP-14108 · 2025

Microfluidic Technology Creates Uniform Microspheres for Month-Long Leuprolide Release

Using a glass capillary microfluidic device, researchers produced monodisperse PLGA microspheres with a uniform particle size of 80 μm and a distinct core-shell structure for leuprolide acetate delivery. At an optimal gelatin concentration of 7.5 mg/mL in the inner aqueous phase, microspheres achieved maximum encapsulation efficiency of 80.28% and drug loading of 4.24%. The microspheres sustained leuprolide release for approximately 28 days in vitro. Drug loading increased proportionally with leuprolide concentration in the inner phase. Gelatin incorporation and collecting solution pH were identified as the critical factors controlling encapsulation efficiency.

Wei, Ruoxin; Dou, Jiaze; Wu, Yihui; Li, Jinjin; Cen, Lian; Xi, Zhenhao ·

RPEP-14113 · 2025

Anchoring Honeybee Antimicrobial Peptide to Cell Membranes Boosts Potency 100-Fold but Comes With a Cost

Tethering honeybee defensin-1 (Def1) to cell membranes via a GPI anchor in Drosophila flies boosted antimicrobial potency by approximately 100-fold compared to secreted or untethered forms. Flies with membrane-tethered Def1 showed superior clearance of Pseudomonas aeruginosa and improved survival after infection, with no adverse effects on movement, mating behavior, or sleep under normal conditions. However, under stress conditions — sleep deprivation and chemically induced gut injury — the tethered peptide worsened intestinal barrier damage. This reveals a fundamental trade-off: anchoring antimicrobial peptides to membranes dramatically increases their killing power but can make the host's gut lining more vulnerable during stress.

Wei, Yanan; Sun, Yanying; Zhou, Xinyue; Kim, Doyoun; Lee, Jihyeon; Bang, Jeong Kyu; Kim, Woo Jae ·

RPEP-14116 · 2025

How Semaglutide Was Engineered From a Lab Concept Into a Transformative Drug for Diabetes and Obesity

Semaglutide's development from concept to blockbuster therapy was driven by strategic molecular engineering — amino acid substitutions and a C18 fatty-diacid side chain that extended the peptide's half-life to approximately 160 hours, enabling once-weekly dosing. The SUSTAIN clinical program demonstrated significant HbA1c reductions and weight loss compared to other treatments, plus a 26% decrease in the relative risk of major adverse cardiovascular events (SUSTAIN-6). The STEP trials expanded semaglutide's use to chronic weight management, showing nearly two-thirds of patients achieved at least 15% body weight reduction. Optimal weekly doses were established at 0.5 mg and 1.0 mg in phase II trials. Regulatory approvals from the FDA, EMA, and other agencies were obtained between 2017 and 2021.

Weiskirchen, Ralf; Lonardo, Amedeo · Review

RPEP-14117 · 2025

FDA Database Reveals Unexpected Side Effects of CGRP-Blocking Migraine Drug Atogepant

From 3,552,072 total FAERS reports, 2,876 specifically named atogepant. Women constituted the majority of reporters, concentrated in the 45–65 age group. The top adverse events by significant signal detection included expected effects: migraine (paradoxical worsening), constipation, nausea, vertigo, somnolence, decreased appetite, dizziness, and fatigue. Notably, unexpected adverse event signals were detected for: abnormal dreams, self-injurious ideation, brain fog, tension headache, nightmares, brain neoplasm (likely coincidental), feeling abnormal, euphoric mood, hyperacusis (heightened sound sensitivity), and post-concussion syndrome. All signals were confirmed across four independent detection algorithms (ROR, PRR, BCPNN, EBGM).

Wen, Heli; Ding, Yitian; Chen, Feichi ·

RPEP-14120 · 2025

GLP-1 Drug Biosimilars Could Make Weight Loss and Diabetes Medications Affordable

The review found that liraglutide and semaglutide are the primary GLP-1 receptor agonists being targeted for biosimilar development. Preliminary clinical comparisons of liraglutide biosimilars to the reference product (Victoza/Saxenda) have demonstrated similar clinical efficacy and safety profiles, which is encouraging for regulatory approval. Semaglutide biosimilars and beinaglutide biosimilars are currently under active clinical investigation by pharmaceutical companies worldwide. The authors emphasize that without insurance, the monthly costs of these drugs — $1,418 for liraglutide, $892 for semaglutide, and $974 for tirzepatide — create a significant access barrier not only for diabetes and obesity patients but also for off-label uses like sleep apnea and fatty liver disease that benefit from weight loss.

Wen, Jimmy; Razick, Adam; How-Volkman, Christiane; Bernstein, Ethan; Nadora, Denise; Truong, Alina; Razick, Daniel; Akhtar, Muzammil; Karabala, Muhammad; Frezza, Eldo · Review

RPEP-14122 · 2025

Meta-Analysis of 66,000 Patients Finds Small Pancreatitis Risk With GLP-1 Drugs, No Clear Pancreatic Cancer Link

This meta-analysis of 62 RCTs involving 66,232 patients found a statistically significant but small increased risk of pancreatitis with GLP-1 receptor agonists overall (RR: 1.44, 95% CI 1.09-1.89, p=0.009). However, this significance disappeared when stratified by background medication use — neither the with-background-medication group (RR: 1.28) nor the without-background-medication group (RR: 1.37) reached significance alone. For pancreatic cancer, no overall significant association was found (RR: 1.30, 95% CI 0.86-1.97). A significant association appeared only in the subgroup taking background medications (RR: 1.85, p=0.03), but not without them. The authors note this difference is likely minimal given that many excluded studies had zero events in both arms.

Wen, Jimmy; Nadora, Denise; Bernstein, Ethan; How-Volkman, Christiane; Truong, Alina; Joy, Bethany; Kou, Megan; Muttalib, Zohaer; Alam, Arsh; Frezza, Eldo · Meta Analysis

RPEP-14128 · 2025

Peptide-Mimicking Antibiotic Hybrid Defeats Drug-Resistant MRSA With 99.99% Bacterial Kill in Single Dose

IPMCL-28b, a chimeric ciprofloxacin derivative incorporating three cationic amino acids and a lipophilic n-decanoyl tail connected by a rigid linker, showed potent activity against multiple multidrug-resistant bacterial strains. It achieved a 99.99% (4.4 log) reduction in MRSA skin bacterial load after a single dose in mice. The compound demonstrated high selectivity with low hemolysis (minimal red blood cell damage), significantly reduced likelihood of resistance development compared to ciprofloxacin, and dual mechanism of action — retaining ciprofloxacin's DNA gyrase inhibition while gaining membrane-disrupting capability. Molecular dynamics simulations confirmed stronger membrane interactions than ciprofloxacin alone.

Wen, Qi; He, Yuhang; Chi, Jiaying; Wang, Luyao; Ren, Yixuan; Niu, Xiaoke; Yang, Yanqing; Chen, Kang; Zhu, Qi; Lin, Juncheng; Xiang, Yanghui; Xie, Junqiu; Chen, Wenteng; Yu, Yongping; Wang, Baohong; Wang, Bo; Zhang, Ying; Lu, Chao; Wang, Kairong; Teng, Peng; Zhou, Ruhong ·

RPEP-14130 · 2025

Can GLP-1 Drugs and Other New Diabetes Medications Prevent Diabetic Eye Disease?

Novel antidiabetic medications including GLP-1 receptor agonists, SGLT-2 inhibitors, and dual GIP/GLP-1 agonists target the key molecular pathways underlying early diabetic retinopathy: microvascular damage, inflammation, oxidative stress, and advanced glycation end products. These drugs may have the potential to reduce progression of non-proliferative diabetic retinopathy (NPDR), though clinical trial confirmation is expected. The review also highlights that advanced diagnostic technologies — ultra-widefield fundus photography, OCT, OCTA, and AI-based algorithms — achieve over 95% accuracy in detecting NPDR and can predict systemic cardiovascular risk from retinal imaging.

Wen, Song; Xu, Chenglin; Yuan, Yue; Chen, Lijiao; Ren, Yishu; Xu, Zhimin; Jin, Jianlan; Li, Jiyu; Zhou, Ligang ·

RPEP-14133 · 2025

3D-Bioprinted Collagen Peptide Scaffolds Guide Stem Cells to Grow Ligament-Like Tissue

Researchers developed a 3D-bioprinted hydrogel scaffold using methacrylated collagen peptide combined with xanthan gum (COPMA-XG) that overcomes the traditional limitations of collagen peptides in tissue engineering — namely low viscosity and poor printability. The resulting bioinks showed self-healing properties, rapid UV-curing, tunable mechanical strength, and stable structure in culture medium. When loaded with human bone marrow stem cells (hMSCs) and cultured for 28 days, the bioprinted constructs were biocompatible and promoted stem cell proliferation and differentiation into ligament-like tissue, with increased production of extracellular matrix, collagen type I, and scleraxis (a ligament-specific marker).

Weng, Hongjuan; Decarli, Monize Caiado; He, Lei; Chen, Wen; van Rijt, Sabine; Bernaerts, Katrien V; Moroni, Lorenzo · In Vitro

RPEP-14139 · 2025

The GRADE Trial: Liraglutide Led Weight Loss While Weight Gain on Other Diabetes Drugs Worsened Heart and Kidney Outcomes

In 4,980 participants followed for 5 years (mean age 57, BMI 34.3, HbA1c 7.5%): First-year weight changes: • Liraglutide: -3.5 kg (95% CI: -3.8 to -3.2) • Sitagliptin: -1.07 kg (-1.4 to -0.78) • Insulin glargine: +0.45 kg (+0.16 to +0.74) • Glimepiride: +0.89 kg (+0.60 to +1.2) • All groups P significant for differences Weight gain consequences (per kg, independent of drug): • HbA1c >7.5%: HR 1.05 (95% CI: 1.04-1.07) • Cardiovascular disease: HR 1.03 (1.005-1.06) • Kidney disease: HR 1.03 (1.01-1.06) • Lower diabetes treatment satisfaction • Baseline weight (not weight gain) predicted new-onset neuropathy

Wexler, Deborah J; Garvey, W Timothy; Ghosh, Alokananda; Kazemi, Erin J; Krause-Steinrauf, Heidi; Ahmann, Andrew J; Brown-Friday, Janet; Casula, Sabina; Cherrington, Andrea L; Elasy, Tom A; Fortmann, Stephen P; Krakoff, Jonathan A; Mudaliar, Sunder; Tiktin, Margaret; Younes, Naji ·

RPEP-14141 · 2025

Oral Semaglutide 25 mg Produces 13.6% Weight Loss in People with Obesity (OASIS 4 Trial)

At 64 weeks, oral semaglutide 25 mg produced a mean body weight reduction of 13.6% versus 2.2% for placebo (estimated difference: -11.4 percentage points; 95% CI: -13.9 to -9.0; P < 0.001). Participants on semaglutide were significantly more likely to achieve weight loss thresholds of 5%, 10%, 15%, and 20% or more (P < 0.001 for all comparisons). Physical function quality of life (IWQOL-Lite-CT score) also improved significantly with oral semaglutide versus placebo (P < 0.001). Gastrointestinal adverse events were the most common side effects, occurring in 74.0% of semaglutide patients versus 42.2% of placebo patients.

Wharton, Sean; Lingvay, Ildiko; Bogdanski, Pawel; Duque do Vale, Ruben; Jacob, Stephan; Karlsson, Tobias; Shaji, Chaithra; Rubino, Domenica; Garvey, W Timothy ·