RPEP-16405 · 2026WALVAP demonstrated 6.25-fold higher DPP-IV inhibitory activity than the parent peptide KALVAP (IC₅₀: 360.39 vs 1,372.57 μmol/L in Caco-2 cells), while WPLVAP showed 3.52-fold improvement. Both peptides retained the ACE-inhibitory (blood pressure-lowering) activity of the original KALVAP.
In oral glucose tolerance tests in C57BL/6 mice, both WALVAP and WPLVAP significantly improved glucose metabolism by promoting secretion of insulin (11.13% and 11.61% increase), GLP-1 (11.12% and 11.61% increase), and GIP (7.58% and 7.66% increase). Molecular dynamics simulations revealed that both peptides inhibit DPP-IV primarily through interactions with key binding site residues Glu205, Trp629, Glu206, Arg125, and Arg429.
Wen, Huan; Lan, Jing; Dang, Kuo; Wang, Yanli; Pan, Daodong; Gao, Xinchang; Dang, Yali ·
RPEP-16408 · 2026Robust clinical trial data now supports GLP-1 RA efficacy across multiple conditions beyond diabetes: significant weight loss in obesity, improved cardiovascular outcomes, preserved renal function in chronic kidney disease, and benefits in metabolic dysfunction-associated steatotic liver disease (MASLD, formerly NAFLD). Heart failure with preserved ejection fraction (HFpEF) has emerged as a particularly promising indication.
Additional trials are underway to strengthen the evidence base for these newer indications. The review also notes that innovations including oral GLP-1 formulations and combination therapies (such as dual GLP-1/GIP agonists) may expand access and improve treatment adherence.
West, Lucianne; Patolia, Harsh; Chapman, Brittany; Laffin, Luke; Vest, Amanda R; Sauer, Andrew J; Martyn, Trejeeve ·
RPEP-16418 · 2026Across 31 preclinical and pharmacologic studies, GLP-1 receptor agonists were consistently associated with increased glutamate release, activation of NMDA and AMPA receptors, and enhanced release of neurotrophic factors linked to neurogenesis, neurodifferentiation, and synaptic plasticity. Crucially, the food intake suppression caused by GLP-1 RAs was found to be dependent on AMPA receptor signaling but not NMDA receptor signaling, suggesting a specific mechanistic pathway for the anti-obesity effects of these drugs.
Wong, Sabrina; Le, Gia Han; Teopiz, Kayla; McIntyre, Roger S ·
RPEP-16420 · 2026The review finds that AMP-based surface coatings for medical devices have progressed from simple surface immobilization techniques to sophisticated matrix-based systems that offer improved stability, biocompatibility, and controlled release of antimicrobial activity. AMPs are particularly suited for this application due to their broad-spectrum antimicrobial activity and structural versatility.
However, despite extensive in vitro and small-scale in vivo studies demonstrating efficacy against biofilm formation on devices like endotracheal tubes, catheters, and implants, clinical translation remains very limited. Key barriers include regulatory ambiguity around peptide-coated devices and high production costs.
Wouters, Milan; Van Moll, Laurence; Derin, Emine; Van Looy, Sara; De Vooght, Linda; Delputte, Peter; Cos, Paul ·
RPEP-16424 · 2026After 1:1 propensity score matching of 23,106 patients per group from the TriNetX global network:
Tirzepatide vs SGLT2 inhibitors in MASLD:
- Primary composite (mortality + MACE + MALO): HR 0.72 (95% CI: 0.63-0.83) — 28% reduction
- All-cause mortality: HR 0.55 (95% CI: 0.43-0.71) — 45% reduction
- Major adverse cardiovascular events: HR 0.68 (95% CI: 0.58-0.80) — 32% reduction
- Major adverse liver outcomes: HR 0.66 (95% CI: 0.54-0.80) — 34% reduction
All associations were consistent across subgroups stratified by age, sex, BMI, and comorbidities, demonstrating robust benefit.
Wu, Jheng-Yan; Lin, Yu-Min; Hsu, Wan-Hsuan; Liu, Ting-Hui; Tsai, Ya-Wen; Huang, Po-Yu; Chuang, Min-Hsiang; Yu, Tsung; Lai, Chih-Cheng ·
RPEP-16436 · 2026The review identifies several key roles for neprilysin in musculoskeletal health. NEP degrades pro-inflammatory neuropeptides like substance P, reducing local inflammation in joints and muscles. It also breaks down endogenous opioids, playing a role in pain regulation.
In stem cell research, NEP promotes osteogenic (bone), chondrogenic (cartilage), and myogenic (muscle) differentiation of mesenchymal stem cells. The NEP inhibitor sacubitril promotes cartilage growth plate thickening and bone growth in animal models of chondrodysplasia, while NEP activators — rather than inhibitors — promote muscle growth in castrated rats. This tissue-specific directional difference is an important finding.
Wu, Zuping; Wang, Ying; Wu, Na; Lu, Mingcheng; Shi, Jiejun ·
RPEP-16437 · 2026A 48-year-old man with morbid obesity (153 kg), extensive spinal epidural lipomatosis, and critical lumbar stenosis underwent a non-surgical treatment strategy:
- Semaglutide initiated for GLP-1-mediated weight loss
- Medical cannabis for non-opioid pain control
- Over 1 year follow-up: weight decreased from 153 kg to 93.8 kg (59.2 kg loss)
- MRI demonstrated near-complete regression of epidural fat
- Resolution of spinal stenosis
- Major improvement in pain and mobility
- Patient remained neurologically intact
- Surgery was successfully avoided
- Reported as the first documented case of SEL reversal through medical weight loss alone
Wurm, Lennard M; Koch, Peter; Ertel, Wolfgang; Laue, Dominik ·
RPEP-16443 · 2026Vildagliptin (a DPP-4 inhibitor that preserves endogenous GLP-1) selectively reduced two triglyceride species — TG(54:4) and TG(54:5) — during intraduodenal fat infusion (each P < 0.01), without significantly affecting total triglycerides.
Critically, when endogenous GLP-1 signaling was blocked with exendin(9-39) during vildagliptin treatment, plasma total triglycerides increased significantly (P < 0.001), along with elevations in 10 individual triglyceride species (P < 0.05 each). This reversal upon GLP-1 blockade provides direct evidence that endogenous GLP-1 contributes to physiological regulation of postprandial triglyceride appearance in type 2 diabetes.
Xie, Cong; White, Jake B; Huang, Weikun; Horowitz, Michael; Rayner, Christopher K; Verjans, Johan W; Snel, Marten F; Psaltis, Peter J; Wu, Tongzhi ·
RPEP-16447 · 2026A cumulative liraglutide dose of 18 mg over 3 days (10x the recommended maximum of 1.8 mg/day) induced severe DKA with pH 6.9, markedly elevated β-hydroxybutyrate, and hyperkalemia. Conventional DKA management (IV fluids, insulin, electrolyte correction) failed to correct the profound acidosis. Salvage hemodialysis was required and rapidly stabilized metabolic parameters. This represents one of the most severe documented cases of GLP-1 receptor agonist overdose-induced DKA.
Xu, Hekai; Zhang, Yuqin ·
RPEP-16456 · 2026The researchers successfully combined E. coli surface display with co-culture techniques to produce intracellularly modified RiPPs (ribosomally synthesized and post-translationally modified peptides) extracellularly. A brevicidine-mimicking mutant peptide was modified intracellularly by two enzymes — OspR (introducing ornithine residues) and SyncM (introducing a methyllanthionine ring) — then displayed on the E. coli surface using Lpp-OmpA and Omp1 proteins.
In a co-culture with separate E. coli cells displaying the leader peptidase LahT150 (via the ice nucleating protein InaK), the modified peptide was successfully cleaved and detected in the culture supernatant, where its antimicrobial activity was confirmed. Surface display efficiency exceeded 90% using the Lpp-OmpA and Omp1 systems.
Xu, Yanli; Kuipers, Oscar P ·
RPEP-16457 · 2026The review identifies several technology platforms poised to reshape GLP-1-based therapy delivery:
1. **Oral small-molecule agonists** — non-peptide compounds that activate GLP-1 receptors and can be taken as pills, avoiding injections entirely
2. **Ultralong-acting injectable technologies** — formulations designed to extend dosing intervals far beyond the current once-weekly standard
3. **Continuous-acting implantable pumps** — devices that deliver GLP-1 drugs steadily without patient intervention
4. **Smart-acting electronic devices** — technology-enabled delivery systems that can adjust dosing
5. **Nutrient-induced cell therapies** — engineered cells that produce GLP-1 in response to food intake, mimicking natural physiology
6. **Noninvasive delivery systems** — alternative routes that bypass needles entirely
Each approach addresses different patient needs and clinical challenges, from needle phobia to treatment adherence.
Xu, Yining; Drucker, Daniel J; Traverso, Giovanni; Beloqui, Ana ·
RPEP-16463 · 2026Among 139,173 diabetic patients with chronic limb-threatening ischemia (CLTI), GLP-1 receptor agonist users had significantly lower 5-year rates of major amputation (HR 0.745, 95% CI 0.679–0.816), all-cause mortality, and myocardial infarction compared to non-users after propensity score matching (15,743 patients per group). The reduction in ischemic stroke did not reach statistical significance (p=0.353). These benefits persisted after adjusting for demographics, comorbidities, concurrent medications, and laboratory values.
Yahyavi, Ashkan; Zokaei Nikoo, Maedeh; Hussein, Leen; Katara, Aarti; Perez, Jaime A; Shishehbor, Mehdi H ·
RPEP-16465 · 2026In isolated female rat trigeminal ganglion Ah-type neurons:
- VIP (100 nM) significantly increased firing frequency of repetitive discharge
- VIP narrowed action potentials and increased down-stroke velocity
- VIP deepened after-hyperpolarization (AHP)
- AP and repolarization changes were reversed by Iberiotoxin (BK channel blocker), except AHP which was abolished by Apamin (SK channel blocker)
- All VIP-mediated increases in firing frequency and repolarization changes were completely blocked by PG97-269 (VPAC1 antagonist)
- PG-99-465 (VPAC2 antagonist) had no effect
- PG97-269 alone slightly but significantly reduced baseline firing
- Conclusion: VIP excites female-specific Ah-type neurons via VPAC1, which also plays a minor role in basal neuroexcitation
Yan, Feng; Zhong-Xuan, Pan; Li-Li, Tan; Luo, Fang; Hai-Ying, Ding ·
RPEP-16472 · 2026GLP-1 receptor agonists were associated with a 23% reduction in hepatocellular carcinoma (HCC) risk (HR 0.77, 95% CI 0.66–0.90) and a 21% reduction in non-HCC liver-related events (HR 0.79, 95% CI 0.65–0.95) compared to other glucose-lowering therapies.
SGLT-2 inhibitors showed similar liver protection: 24% reduction in HCC (HR 0.76, 95% CI 0.67–0.86) and 18% reduction in liver-related events (HR 0.82, 95% CI 0.73–0.92).
DPP-4 inhibitors showed no protection against HCC (HR 1.12, 95% CI 0.91–1.39) and were associated with a 24% increased risk of liver-related events (HR 1.24, 95% CI 1.15–1.34).
In patients with chronic liver disease specifically, GLP-1 receptor agonists were uniquely associated with reduced hepatic decompensation (HR 0.79, 95% CI 0.71–0.88).
Yang, Jiwon; Hwang, Yeongseok; Ju, Jin-Sung; Han, Seungbong; An, Jihyun; Shim, Ju Hyun ·
RPEP-16480 · 2026FK2, a 9-amino-acid peptide derived from the silk of corn (Zea mays L.), was shown to inhibit renal fibrosis both in living mice and in cell cultures. The researchers identified IKKβ as the direct molecular target of FK2. By binding to IKKβ, FK2 simultaneously blocks two major signaling pathways — IKKβ/NF-κB (which drives inflammation) and TGF-β1/Smad2/3 (which drives tissue scarring).
This dual suppression reduced the inflammatory response and inhibited two key processes that contribute to kidney scarring: macrophage-to-myofibroblast transition (MMT), where immune cells transform into scar-producing cells, and epithelial-mesenchymal transition (EMT), where kidney lining cells lose their normal identity and become fibrotic.
Yang, Runling; Feng, Xiaocui; Zhang, Jianfeng; Chen, Tianyi; Wang, Wenqian; Liu, Yangrui; Chen, Wanru; Bai, Jingya; Zhang, Bangzhi · Animal And Cell
RPEP-16482 · 2026The VapBC5 crystal structure was solved at 2.24 Å resolution, revealing a heterotetrameric 2:2 assembly. The antitoxin VapB5 suppresses the toxin VapC5 through an extensive network of hydrogen bonds and salt bridges.
Functional studies showed VapC5 promotes antibiotic-tolerant survival under fluoroquinolone stress (persister cell formation), while VapB5 counteracts this phenotype. Antitoxin-derived peptides were designed, screened in E. coli, and a selected peptide was validated in M. abscessus where it attenuated VapC5-associated persistence-related phenotypes. Structure-guided mutagenesis confirmed that multiple antitoxin-toxin contacts must be disrupted to unmask VapC5 activity.
Yang, Sheng; Zheng, Shuping; Feng, Zhihua; Lin, Miaofang; Liu, Min; Chiang, Zu-Chian; Chen, Qi ·
RPEP-16483 · 2026From 1,983 peptides identified in the gastrointestinal digest of royal jelly proteins, 237 had high predicted bioactivity scores (≥0.8). After further screening, 49 soluble candidates were selected, and ACE inhibition was the most commonly predicted function.
Molecular docking showed all 49 peptides bound ACE more strongly (-6.9 to -10.9 kcal/mol) than the positive control captopril (-5.6 kcal/mol). In vitro testing confirmed two top performers: FRYR (IC50 = 608 μmol/L, mixed-type inhibitor) and FFRNR (IC50 = 684 μmol/L, competitive inhibitor). FRYR's superior potency was explained by its unique ability to coordinate with the zinc catalytic center of ACE — the same site that pharmaceutical ACE inhibitors target.
Yang, Wanyu; Hu, Xiaodi; Zhang, Tianrong; Zhao, Ming; Li, Qiongmin; Sang, Mengnan; Fan, Jinling; Zhao, Yuan; Zhang, Bin ·
RPEP-16490 · 2026GLP-1 receptor agonist users had a significantly lower rate of major adverse cardiovascular events (MACE) compared to DPP-4 inhibitor users: 31.6 vs. 36.5 per 1,000 person-years (SHR 0.88, 95% CI 0.80–0.97). The cardiovascular death reduction was particularly striking: SHR 0.72 (95% CI 0.62–0.85), representing a 28% lower rate. There was no effect modification by CKD stage, albuminuria level, or concurrent SGLT2 inhibitor use — meaning the cardiovascular benefit was consistent regardless of kidney disease severity or other cardioprotective medications.
Yau, Kevin; Ray, Joel G; Jeyakumar, Nivethika; Luo, Bin; Abdullah, Sheikh; Dixon, Stephanie N; Wing, Sara; Clemens, Kristin K; Castrillon-Ramirez, Fabio; Udell, Jacob A; Meraz-Munoz, Alejandro; Young, Ann; Harel, Ziv; Perl, Jeffrey; Leiter, Lawrence A; Garg, Amit X; Cherney, David Z I; Wald, Ron ·
RPEP-16503 · 2026Liraglutide produced striking improvements across all measured outcomes in the chronic rotator cuff tear model:
- **Fatty infiltration**: 1.11 ± 0.75% vs 11.82 ± 3.89% (P<0.001) — a roughly 90% reduction
- **Internal rotation**: 79 ± 38° vs 70 ± 2° (P<0.001)
- **External rotation**: 55 ± 2° vs 48 ± 3° (P<0.001)
- **Nerve-muscle signal strength**: 19.43 ± 8.77 mV vs 7.61 ± 3.15 mV (P=0.028) — more than doubled
Histological analysis confirmed markedly decreased adipocyte deposition and preserved muscle fiber morphology in the liraglutide group. These results suggest GLP-1 receptor agonists can attenuate the otherwise irreversible muscle degeneration following rotator cuff tears.
Yoon, Jong Pil; Park, Sung-Jin; Kim, Dong-Hyun; Lee, Hyun Joo; Kim, Jun-Young; Pham, Dinh The; Cho, Chul-Hyun; Chung, Seok Won ·
RPEP-16506 · 2026Three target trial emulations using propensity score-matched real-world data compared dementia outcomes across diabetes medications over two years:
- Tirzepatide vs. SGLT2 inhibitors (n=14,462): HR 0.66 (95% CI 0.47–0.93, p=0.02) for dementia
- Semaglutide vs. SGLT2 inhibitors (n=57,959): results not specified for dementia HR
- Tirzepatide vs. semaglutide (n=12,246): HR 0.69 (95% CI 0.48–0.99, p=0.04) for dementia
Tirzepatide also showed lower all-cause mortality vs. both semaglutide (HR 0.72, 95% CI 0.58–0.90) and SGLT2 inhibitors (HR 0.29, 95% CI 0.23–0.37). Both tirzepatide and semaglutide reduced major adverse cardiovascular events (MACE) compared to SGLT2 inhibitors.
Younis, Alhena; Henney, Alex E; Riley, David R; Anson, Matthew; Zhao, Sizheng S; Ibarburu, Gema H; Malik, Rayaz A; Su, Li; Lip, Gregory Y H; Cuthbertson, Daniel J; Alam, Uazman ·
RPEP-16507 · 2026Six Dap/Dab-modified analogues of the arginine-rich peptide W3R6 were synthesized and tested:
• Lead compound W3R6-A1: MIC against MRSA improved from 6.25 μM to 0.78 μM (8-fold enhancement)
• All analogues showed reduced cytotoxicity: >80% mammalian cell viability at 100 μM
• W3R6-A2 and -A3 showed improved serum stability (higher residual amounts after 3 hours)
• Dap-modified analogues disrupted bacterial cell membranes and biofilms
• Lower tendency to induce drug resistance compared to conventional antibiotics
• In vivo efficacy in two mouse infection models:
- Burn infection: reduced bacterial load and tissue damage
- Peritonitis-sepsis: decreased bacterial burden and pro-inflammatory cytokines (TNF-α, IL-6, IL-1β)
• No in vivo toxicity observed
Yu, Chunlin; Guo, Feilu; Nie, Xin; Shang, Dejing; Dong, Weibing ·
RPEP-16508 · 2026The review organizes peptide-based biomaterials into three major functional categories:
1. **Peptide excipients**: Cell-penetrating peptides (CPPs) enable intracellular delivery via direct membrane penetration or endocytosis; tight junction modulating peptides open passages between cells; peptide surfactants and stabilizers protect drug formulations.
2. **Self-assembling peptides**: These spontaneously form nanospheres, cyclic nanotubes, nanovesicles, micelles, hydrogels, and depot systems for controlled and sustained drug release.
3. **Peptide linkers**: Used in antibody-drug conjugates (ADCs), peptide-drug conjugates (PDCs), and prodrugs to achieve site-specific drug release triggered by tumor-associated enzymes or pH changes.
Optimization strategies include cyclization, stapling, D-amino acid incorporation, functional motif integration, and AI-assisted combinatorial discovery.
Yu, Dedong; Han, Nari; Son, Hyejeong; Kim, Sun Jo; Kweon, Seho · Review
RPEP-16513 · 2026Self-decreasing pH hydrolysis produced soybean peptides with the most potent hepatoprotective activity among three hydrolysis strategies tested. After simulated digestion and absorption through a Caco-2/HepG2 co-culture model, these peptides significantly reduced liver damage markers — AST levels dropped to 5.01 U/L and ALT to 0.91 U/L in ethanol-injured liver cells.
Two key peptides were identified: PFPRPQP, which activates the Nrf2 antioxidant pathway by binding to Keap1, and PIPFPR, which targets CYP2E1 (the enzyme that generates toxic acetaldehyde during alcohol metabolism) for potential enzyme inhibition. Both peptides contain an aromatic-Pro-Arg/Lys (Φ-P-R/K) core motif that molecular docking and amino acid substitution experiments showed is essential for their hepatoprotective activity. The sequential hydrolysis group had the highest apparent permeability coefficient (44.47 × 10⁻⁷ cm/s) but not the strongest protective effect, demonstrating that absorption efficiency alone doesn't determine efficacy.
Yu, Shengjuan; Zhang, Qiaoli; Liu, Wanlu; Han, Yu; Jenis, Janar; Liu, Xinqi; Li, He ·
RPEP-16517 · 2026Among 210 MDD patients divided into three groups:
- Premenopausal women (n=80): NPY = 280.80 ± 35.50 pg/mL (highest)
- Men (n=65): NPY = 250.50 pg/mL (estimated from differences)
- Postmenopausal women (n=65): NPY = 252.10 pg/mL (estimated from differences)
Key findings:
- Premenopausal women's NPY was significantly higher than men (Δ=30.30, p=0.007) and postmenopausal women (Δ=28.70, p=0.009)
- No difference between postmenopausal women and men (Δ=1.60, p=0.989)
- Similar group patterns were seen for appetite (VAS scores)
- NPY positively correlated with appetite (r=0.422-0.437)
- The NPY-appetite correlation was strongest in premenopausal women and weakest in postmenopausal women (β=0.007, p=0.021)
- Correlation held after controlling for depression severity
Yuan, Qianfa; Wang, Li; Zhuang, Yuan; Lin, Duoduo; Xu, Zhizhong; Wen, Chunyan; Su, Weichao; Huang, Zhiyuan; Qiu, Yan ·
RPEP-16525 · 2026PeptideNet achieved strong predictive accuracy on independent test datasets across five bioactive peptide categories:
• Antiviral peptides: 93% accuracy
• Antimicrobial peptides: 94% accuracy
• Antioxidative peptides: 84% accuracy
• Anti-cell-penetrating peptides: 89% accuracy
• Antihemolytic peptides: 87% accuracy
ESM-2 protein language model embeddings consistently outperformed other feature representations (ESM-1, ProtBert, physicochemical descriptors) across all peptide types. The hybrid CNN-BiGRU architecture captured both local sequence motifs and long-range dependencies in peptide sequences. Visualization analysis confirmed the model learned meaningful representations and identified conserved amino acid patterns linked to bioactivity.
Zahid, Hamza; Maryam; To Chong, Kil; Tayara, Hilal ·
RPEP-16527 · 2026Across 7 studies totaling 317 patients with grade 3 (G3) gastro-entero-pancreatic neuroendocrine neoplasms:
- Objective response rate (ORR): 34% (95% CI: 22–46%) — meaning about one-third of patients had measurable tumor shrinkage
- Disease control rate (DCR): 64% (95% CI: 52–76%) — meaning nearly two-thirds had their disease stabilize or shrink
- Median progression-free survival: 13.88 months (95% CI: 10.33–18.64)
- Median overall survival: 29.95 months (95% CI: 19.80–45.30)
The treatments used were [¹⁷⁷Lu]Lu-DOTA-TATE and/or [⁹⁰Y]Y-SSA, which are radioactive versions of somatostatin analog peptides that target receptors on tumor cells.
Zampella, Emilia; Piscopo, Leandra; Green, Roberta; Cantoni, Valeria; Nappi, Carmela; Gaudieri, Valeria; Caiazzo, Elisa; Scaglione, Mariano; Cuocolo, Alberto; Klain, Michele ·
RPEP-16537 · 2026Nanoplastic exposure (20 nm polystyrene particles) worsened asthma in mice through a multi-step mechanism: the particles activated PLA2 in lung tissue, producing inflammatory metabolites that upregulated TRPV1 channels. This triggered release of neuropeptides substance P and calcitonin gene-related peptide (CGRP), which activated NF-κB signaling and amplified Th2 inflammation (elevated IL-4, IL-5, IL-13). Simultaneously, nanoplastics disrupted gut microbiota, increasing gram-negative bacteria that released LPS, activating the intestinal TLR4/NF-κB pathway and fueling lung inflammation through the gut-lung axis. Reduced short-chain fatty acid production from dysbiosis further enhanced lung PLA2 activity, creating a self-reinforcing PLA2-TRPV1-neuropeptide feedback loop.
Zeng, Xin; He, Chuhao; Li, Jitong; Feng, Qing; Lu, Zhenjie; Li, Long; Qiao, Yongkang; Han, Wei; Wang, Faming; Chen, Mingqing; Lu, Chan; She, Rong; Wu, Yang; Sun, Yanling; Yang, Xu; Ma, Ping; Lu, Surui ·
RPEP-16542 · 2026Researchers created an oral delivery system for melittin — a bee venom peptide with anti-arthritic properties — by encapsulating it in a multi-layered micro-nano system. Sialic acid-decorated melittin nanoparticles were embedded in calcium alginate microgels, then coated with probiotic biofilms. This probiotic coating protected melittin from stomach acid destruction and helped it adhere to the intestinal wall.
The system accumulated in mesenteric lymph nodes (gut immune centers) and modulated key immune cell ratios — Th1/Th2 and Th17/Treg — in both lymph nodes and spleen tissue. This rebalancing of the immune system successfully alleviated arthritis progression in the animal model while reducing the off-target adverse effects that normally limit melittin's clinical use.
Zhang, Fangke; Ding, Tao; Zheng, Jiancheng; Li, Nan; Li, Zechuan; Wang, Xuefei; Du, Yawei; Hu, Weiguo; Cui, Wenguo; Guo, Weisheng · Animal And Cell
RPEP-16543 · 2026The CKAAKN peptide-conjugated nanoliposome (ORI@CPD-Lipo) demonstrated:
- Average particle size of ~100 nm with good stability and biosafety
- Selective internalization into BxPC-3 pancreatic cancer cells within 1–4 hours in vitro, compared to minimal uptake in normal HPDE6-C7 cells
- Significantly higher tumor uptake in vivo over 1–48 hours compared to normal pancreatic tissue, with increasing ratios over time
- Enhanced antitumor effect compared to free oridonin, non-targeting liposomes, and CKAAKN-blocked controls
- The enhanced activity was attributed to peptide-mediated cellular uptake and sustained drug release from nanoparticles
Zhang, Fangxia; Luo, Kunshun; Xuan, Shaoyan; Chen, Teng; Chen, Zhiyong; Yang, Jing; Zhou, Ying; Feng, Tingting; Zhu, Yue; Wang, Zuhua ·
RPEP-16547 · 2026The protein VGLL4 is essential for Paneth cell function and antimicrobial peptide production in the gut. When VGLL4 was deleted from intestinal epithelium, mice had fewer Paneth cells, produced less antimicrobial peptides (including defensins), developed gut microbiome imbalances (dysbiosis), and had impaired intestinal regeneration capacity.
The study identified two distinct mechanisms: VGLL4 teams up with TEAD4 and ATOH1 to drive Paneth cell differentiation via GFI1, and separately forms a complex with TEAD4 and TCF4 to directly induce defensin expression. Notably, VGLL4 expression drops during irradiation injury and DSS-induced colitis, and human colitis datasets also show reduced VGLL4 — suggesting this pathway may be compromised in inflammatory bowel disease.
Zhang, Haoen; Wang, Zuoyun; Wang, Xiaodong; Yu, Wentao; Zhang, Guoying; Zhang, Haijiao; Lu, Yi; Sun, Yang; Lu, Tiantian; Li, Xiaoyu; Yang, Ruizeng; Sun, Jiaqi; Xu, Jinjin; Huang, Shuo; Ma, Xueyan; Ren, Jiale; Tang, Nan; Cheng, Zhonghua; Yu, Jing; Wei, Fang; Zhou, Hu; Li, Jinsong; Qin, Jun; Jin, Yunyun; Zhang, Lei · Animal Study
RPEP-16554 · 2026Researchers developed a new lateral flow test that detects brain natriuretic peptide (BNP) at clinically relevant levels (100 pg/mL threshold) in just 30 minutes at room temperature without requiring enzymes, cold storage, or laboratory equipment. The system uses two aptamers that simultaneously bind BNP, triggering an enzyme-free DNA amplification cascade that produces a visual result on a simple test strip.
Zhang, Menghan; Xu, Tao; Jajesniak, Pawel; Core, Giulia; Zeng, Zhuoer; Shalaby, Maha Mansour Mohamed; Reboud, Julien; Cooper, Jonathan M · Methods Development
RPEP-16560 · 2026Researchers discovered KH-1, the first peptide inhibitor that simultaneously targets two critical cancer-driving proteins: KRAS G12D (the most common mutation in pancreatic cancer) and HDAC (histone deacetylase, a downstream effector). KH-1 bound both targets with nanomolar affinity — Kd of 11.63 nM for KRAS G12D and 20.17 nM for HDAC2.
In lab tests, KH-1 inhibited pancreatic cancer cell growth, invasion, and migration, induced cell death (apoptosis), and arrested cells in the G0/G1 phase. In a mouse xenograft model, KH-1 significantly suppressed tumor growth without causing obvious organ toxicity.
Zhang, Qiaoxuan; Geng, Yifei; Chen, Haitao; Ni, Jiaping; Guan, Lixia; Zhai, Dong Qing; Wang, Yuting; Xu, Shengtao; Niu, Miao-Miao; Zheng, Lufeng; Hu, Weiwei · Preclinical
RPEP-16564 · 2026Researchers designed a new class of antimicrobial peptides inspired by gemini surfactants — twin-headed soap-like molecules. The lead peptide IPr self-assembles into nanoribbon networks through non-covalent forces, which dramatically improves its resistance to enzyme degradation. IPr killed all 10 tested bacterial strains (both Gram-negative and Gram-positive), resisted protease breakdown, and tolerated physiological salt concentrations. It works by disrupting bacterial membranes, triggering a cascade of reactive oxygen species accumulation and ATP leakage. In a mouse peritonitis model, IPr showed excellent biocompatibility and significantly reduced systemic bacterial infection severity.
Zhang, Ruoshi; Sun, Jing; Fu, Chendi; Yu, Hao; Wang, Shenao; Jiao, Yihan; Zhang, Licong; Feng, Xingjun · Animal
RPEP-16575 · 2026Liraglutide significantly inhibited IL-1β-induced inflammation in tendon cells in vitro, enhanced tendon cell anabolism (tissue building), and upregulated the AMPK/SIRT1 pathway. Mechanistically, the GLP-1 receptor was found to interact with SIRT1 to prevent tendon cell apoptosis (programmed cell death) and endoplasmic reticulum stress.
In the in vivo rat rotator cuff injury model, liraglutide effectively promoted tissue regeneration and restored biomechanical strength of the repaired tendon, demonstrating both molecular and functional therapeutic effects.
Zhang, Xiong; Chi, Ruimin; Xu, Jingting; Meng, Chen; Wang, Zhenggang; Ruo, Wanjun; Xin, Fei; Xu, Tao; Guo, Fengjing; Wang, Genchun; Ye, Yaping ·
RPEP-16583 · 2026The CRPPNs (CBD3A6K-RhB-loaded PEG-PLGA nanoparticles) showed uniform morphology, high encapsulation efficiency, and sustained peptide release in vitro. When internalized by dorsal root ganglion (DRG) neurons, they significantly inhibited calcium influx and CGRP release — two key drivers of neuropathic pain signaling.
In a rat chronic constriction injury (CCI) model of the sciatic nerve, a single intraneural injection of CRPPNs produced potent and long-lasting anti-allodynic (reduced sensitivity to touch) and anti-hyperalgesic (reduced pain response) effects that were superior to the free peptide. The mechanism involved downregulation of CaV2.2 expression in both the dorsal root ganglion and spinal cord. Comprehensive biosafety evaluation confirmed excellent biocompatibility.
Zhang, Zhihao; Li, Hao; Liu, Jiarui; Shen, Nana; Zhu, Zhongze; Qi, Xiaoying; Meng, Ming; Wang, Weijiang; Wu, Futong; Qi, Yunkun; Cao, Yong; Ma, Qingming; Xiang, Hongfei ·
RPEP-16591 · 2026Researchers developed ADAPT, an AI-based tool that predicts the functional impact of D-amino acid substitutions in antimicrobial peptides. When integrated into a high-throughput screening pipeline, 80% of the generated peptide variants showed enhanced antibacterial activity. The lead peptide dR2-1 demonstrated exceptional broad-spectrum antimicrobial activity, reduced toxicity, and substantially improved stability compared to the parent peptide. Delivered via an engineered hydrogel, dR2-1 effectively treated skin infections in mice through a membrane-targeting mechanism.
Zhao, Yinuo; Kong, Qingzhou; Gong, Haifan; Li, Lixiang; Fu, Jialu; Wan, Boyao; Wang, Peizhu; Li, Xiaojuan; Wang, Yue; Zhang, Jinghui; Yu, Yanbo; Yang, Xiaoyun; Zuo, Xiuli; Wang, Haina; Li, Yanqing ·
RPEP-16592 · 2026Starting from scorpion toxin BmKTX as a template, the researchers engineered ADIP-6 (BmKTX-K6D/D19K/D33K) through strategic acidic residue redistribution:
- Selectivity: IC50 of 0.8 ± 0.1 nM against hKv1.3; minimal inhibition of other potassium channels even at 1 μM (>1,000-fold selectivity)
- Cellular: Significantly suppressed IL-2 production in Jurkat T cells (confirming functional immunosuppression)
- In vivo: Reduced delayed-type hypersensitivity responses and alleviated disease severity in a rat model of experimental autoimmune encephalomyelitis (EAE), a model for multiple sclerosis
The design strategy — negatively charged residue scanning based on peptide-potassium channel interaction principles — provides a general framework for creating selective channel blockers.
Zhao, Yonghui; Zuo, Zheng; Qin, Chenhu; Chen, Zongyun; Cao, Zhijian; Wu, Yingliang ·
RPEP-16597 · 2026Animal skin collagen contains a unique Gly-Pro-Y sequence structure that is key to producing highly active blood sugar-lowering peptides. These peptides (ASHP) work through competitive inhibition of α-glucosidase (blocking sugar absorption) and DPP-IV (extending the action of natural incretin hormones like GLP-1). Multi-level blood glucose regulation includes improving insulin resistance as a key mechanism.
AI prediction combined with peptide sequence structural analysis has emerged as a crucial strategy for screening the most active peptides from animal skin hydrolysates. Preparation optimization involves high-temperature collagen extraction followed by physical pretreatment and enzyme-specific hydrolysis.
Zheng, Xiaoshan; Guo, Yongxiang; Sun, Dingyan; Shi, Wenzheng; Lu, Ying ·
RPEP-16605 · 2026Two frog-derived antimicrobial peptides (Temporin-GHaR and Temporin-GHaK) showed synergistic antibacterial activity when combined with the antibiotic polymyxin B against both Pseudomonas aeruginosa and E. coli, achieving a fractional inhibitory concentration index (FICI) below 0.5 — the threshold for true synergy.
The combination worked by synergistically disrupting both outer and inner bacterial membranes, inhibited biofilm formation at lower concentrations than either agent alone, and enhanced destruction of mature E. coli biofilms. Critically, the combination did not increase hemolytic toxicity to mouse red blood cells, suggesting a favorable safety profile.
Zhou, Jinqi; Wang, Yuhuan; Xue, Zhiju; Hu, Fang; Deng, Wenhuan; Tang, Jingxuan; Chen, Yuran; Wang, Rong; Zhang, Yingxia · Laboratory
RPEP-16609 · 2026Combination therapies targeting multiple MASH pathways — including GLP-1RAs with FGF-21 analogues or THR-β agonists, and GLP-1/glucagon dual agonists — show promise for improving both liver pathology and systemic metabolic outcomes beyond what single agents can achieve.
Zhou, Xiao-Dong; Fan, Qiong-Yue; Byrne, Christopher D; Targher, Giovanni; Muthiah, Mark D; Huang, Daniel Q; Chen, Qin-Fen; Noureddin, Mazen; Li, Wenhao; Ratziu, Vlad; Loomba, Rohit; Francque, Sven M; Sanyal, Arun J; Zheng, Ming-Hua ·
RPEP-16610 · 2026Incorporating non-natural amino acids into antimicrobial peptides (AMPs) addresses key limitations that have hindered their clinical development: protease degradation, production challenges, safety concerns, and activity retention. Non-natural amino acids with unique structures and properties can optimize AMP-target interactions, expand functional capabilities, and improve stability against enzymatic breakdown. The review covers how these modifications can enhance antibacterial, antiviral, and anticancer properties of AMPs while overcoming the barriers to large-scale application.
Zhou, Yan; Li, Xinghao; Yang, Ke; Zhu, Yin; Ma, Yunqi ·
RPEP-16611 · 2026Researchers designed UDA-6, a long-acting stapled peptide that potently activates both amylin (AMY3R) and calcitonin (CTR) receptors, using a novel on-resin Ugi macrocyclization chemistry based on salmon calcitonin. The stapled design enhanced helical stability and extended the half-life to support once-weekly dosing. In diet-induced obese rats, UDA-6 alone produced substantial weight loss and improved metabolic and liver parameters.
When combined with semaglutide or tirzepatide, UDA-6 achieved synergistic effects — up to 41% vehicle-adjusted body weight reduction and near-normalized liver fat profiles. This combination performance significantly exceeded what either drug class achieved alone.
Zhou, Yaqi; Xu, Pu; Lu, Jiang; Xu, Shujing; Qiu, Wenting; Ning, Xiao; Xu, Jiean; Zheng, Nan ·
RPEP-16626 · 2026The two cases showed strikingly different outcomes despite similar tumor grades (WHO grade 2; Ki-67: 7% and 8%). Patient 1 (age 55) achieved eight years of stable disease with multimodal therapy including somatostatin analogues, PRRT, and chemotherapy, though she developed bilateral hip osteoarthrosis from prolonged high calcium. Patient 2 (age 34) had refractory hypercalcemia that responded only partially to zoledronate, high-dose denosumab, and maximal somatostatin therapy, and she succumbed to progressive disease. Calcium levels tracked reliably with disease activity in both cases.
Zueva, Alexandra; Loh, Ee Wen; Masuka, Shamiso; Wadsley, Jonathan; Newell-Price, John; Munir, Alia ·
RPEP-16627 · 2026Across 12 studies, tirzepatide produced significantly greater weight loss than semaglutide. Tirzepatide users lost an additional 4.61% body weight (95% CI: -6.03 to -3.20, p<0.00001) and 4.76 kg more (95% CI: -6.09 to -3.42, p<0.00001) than semaglutide users.
Tirzepatide users were also significantly more likely to reach key weight loss milestones: 1.52× more likely to lose ≥5%, 2.33× more likely to lose ≥10%, 2.82× more likely to lose ≥15%, and 2.28× more likely to lose ≥20% of body weight. All comparisons were statistically significant.
Zufry, Hendra; Hariyanto, Timotius Ivan · Meta Analysis
RPEP-16628 · 2026The cinnamoyl-coumarin-RGD peptide conjugate (PS-GG(KG)₃G-RGD) formed a stable 1:1 inclusion complex with cucurbit[8]uril (CB[8]) with a high binding constant of (5.0 ± 0.2) × 10⁶ M⁻¹, remaining stable under acidic conditions relevant to tumor microenvironments. Circular dichroism confirmed a stable beta-sheet conformation with high temperature stability.
Critically, the CB[8] complexation modulated the fluorescence lifetime without significantly altering singlet oxygen generation — meaning the therapeutic light-activated mechanism was preserved. In MCF-7 breast cancer cells, the supramolecular assembly significantly enhanced phototoxicity compared to the conjugate alone, demonstrating that the molecular container approach synergizes with peptide-targeted photosensitizer delivery.
Zúñiga, Benjamín; Rivero-Jerez, Paula S; Pino, Sofia Pérez-Del; Bravo-Cabezas, Francisco; Mura, Francisco; Barrias, Pablo; Acuña-Castillo, Claudio; Faúndez, Mario A; Aspeé, Alexis; Zúñiga-Núñez, Daniel; Fuentealba, Denis ·
RPEP-16629 · 2026Semaglutide does far more to fat tissue than simply shrinking it. This review synthesizes evidence showing the drug fundamentally remodels adipose tissue at the molecular level — shifting it from a pro-inflammatory, lipid-storing state toward one that's more oxidative, insulin-sensitive, and metabolically flexible.
Key effects include: enhanced mitochondrial biogenesis and energy-burning capacity, activation of beige fat programming (converting white fat cells toward brown-fat-like energy expenditure), reduced fat tissue inflammation and immune cell infiltration, improved adipokine signaling, reduced fibrosis and tissue stiffness, and depot-specific effects on visceral versus subcutaneous fat. These changes collectively improve insulin sensitivity and reduce ectopic fat deposition in organs like the liver.
Ábel, Tatjana; Csobod Csajbókné, Éva · Narrative Review
RPEP-16630 · 2026sST2 and galectin-3 levels showed differences across heart failure subtypes classified by ejection fraction, suggesting potential utility as diagnostic biomarkers for heart failure classification.
Çetin, Mustafa; Tanrıverdi, Zulkif; Demirbağ, Recep; Altıparmak, İbrahim Halil; Biçer Yeşilay, Asuman; Tascanov, Mustafa Begenc; Fedai, Halil; Toprak, Kenan; Koyuncu, İsmail ·
RPEP-16631 · 2026Plasma CA125 correlated significantly with hs-cTn (r=0.315) and proBNP (r=0.423) and weakly inversely with LVEF (r=−0.186) in ACS patients.
Çolak, Nazlı Dilek; Karabağ, Turgut; Çalışkan, Onuralp; Tezcan, Songül ·
RPEP-16633 · 2026GLP-1-based peptide therapeutics have achieved 15-25% weight loss in obesity treatment, a level previously thought achievable only through bariatric surgery. This breakthrough was driven by two key innovations: fatty acid conjugation technology combined with peptide backbone engineering to enable once-weekly dosing, and the development of unimolecular dual and poly-agonists that activate multiple hormone receptor pathways beyond GLP-1 alone.
The review highlights that while these second-generation therapies offer excellent efficacy and safety, significant barriers remain in scaling up manufacturing infrastructure to meet global demand for hundreds of millions of potential patients.
Østergaard, Søren ·
RPEP-16635 · 2026The review establishes that LL-37 and ceragenins contribute to wound healing through multiple complementary mechanisms: strong broad-spectrum antimicrobial activity that prevents wound infection; anti-biofilm properties that address one of the main causes of chronic wound persistence; promotion of cell migration and proliferation essential for tissue closure; and modulation of inflammatory responses to reduce excessive scarring and healing complications.
Ceragenins offer specific advantages over the natural LL-37 peptide: they are non-peptide mimics resistant to proteolysis (enzymatic degradation), maintain activity in varying environmental conditions (pH, salt concentration), and retain anti-biofilm activity. Their stability in the protease-rich wound environment — where natural peptides are rapidly degraded — is a critical practical advantage.
Łuckiewicz, Milena; Wnorowska, Urszula; Zakrzewska, Magdalena; Błażejczyk, Idalia; Daniluk, Tamara; Kondziołka, Wioleta; Savage, Paul B; Bucki, Robert; Piktel, Ewelina ·