RPEP-15837 · 2026The WL12 peptide conjugated with the photoabsorber IR700 (WL12-IR700) successfully induced cancer cell death when activated by near-infrared light. Cell killing was both light dose-dependent and drug concentration-dependent, confirming the dual-trigger mechanism. In PD-L1-positive cell cultures, NIR-PIT with WL12-IR700 caused characteristic morphological changes associated with photoimmunotherapy-mediated cell death. In mouse xenograft models, the treatment significantly suppressed tumor growth and extended overall survival compared to controls.
Otani, Takuya; Kondo, Naoya; Kanai, Ayaka; Hanaoka, Hirofumi ·
RPEP-15840 · 2026Using both genetic analysis (Mendelian randomization) and a meta-analysis of clinical studies, researchers found no causal link between GLP-1 receptor activation and seven mental disorders: anxiety, bipolar disorder, chronic depression, depression, eating disorders, suicide, and schizophrenia. All genetic odds ratios were non-significant after correction.
The meta-analysis of real-world clinical data confirmed these findings, showing no significant differences between GLP-1RA users and controls for suicidal ideation/behavior (OR=0.92, p=0.67), anxiety (OR=1.03, p=0.93), or depressive symptoms (SMD=-0.25, p=0.39). However, one notable exception emerged: GLP-1RA users showed significantly reduced eating disorder symptoms (SMD=-0.71, p=0.006).
Ouyang, Chenhao; Zhang, Xiaoyue; Zhang, Minghai; Miao, Yan; Zhu, Zicheng; Zeng, Yunting; Ban, Hong; Wu, Yuting; Peng, Nanqin; Ling, Jitao; Li, Chen; Zhang, Deju; Yu, Peng; Zhang, Jing; Liu, Xiao; Huang, Tongsheng · Meta Analysis
RPEP-15844 · 2026The review identifies peptides' central role in AD at both pathological and therapeutic levels: Pathogenic peptides (Aβ oligomers, hyperphosphorylated tau fragments) drive synaptic failure, mitochondrial dysfunction, and neuroinflammation. Endogenous neuropeptides provide compensatory neuroprotective, trophic, and homeostatic effects. Therapeutic advances include aggregation inhibitors, receptor-selective neuropeptide analogues, cell-penetrating peptide conjugates, and approaches targeting proteostasis, insulin/incretin signaling, neurotrophic support, and microglial activation. Critical barriers include blood-brain barrier penetration, metabolic stability, off-target effects, and need for biomarker-guided patient stratification.
Pahal, Sonu; Gupta, Arushi; Kumar, Vivek; Singh, Prashant; Kaushik, Monu; Pahal, Vishvender; Atluri, Geethika; Chaudhary, Amit ·
RPEP-15845 · 2026In 512 randomized patients (erenumab 140 mg n=254, placebo n=256) over 3 months:
- Primary endpoint: Monthly hours of moderate-severe headache pain reduced by 7.95 hours vs. placebo (95% CI: -11.45 to -4.46, p<0.001)
- Functional impact (MFIQ): All four domains significantly improved vs. placebo (all p<0.001): physical functioning (-7.36), usual activities (-7.10), social functioning (-6.82), emotional functioning (-7.05)
- Breakthrough migraine attacks: Shorter duration at moderate+ pain intensity (-1.07 hours, p=0.013) and lower peak pain intensity (-0.48, p=0.011)
- Safety: Grade 3 adverse events 1.6% vs 1.2% placebo; no grade 4 or fatal events
- Study conducted at 61 sites across North America and Europe (2020-2023)
Paiva da Silva Lima, Gabriel; Rao, Renata; Szabó, Gyöngyi; Szklener, Sebastian; Tassorelli, Cristina; Nastaj, Marcin; Chou, Denise E; Khodavirdi, Ani C; Chehrenama, Mahan; Zhu, Yineng; Bhatia, Ajay K; Dodick, David W ·
RPEP-15848 · 2026The review synthesizes evidence showing NPY's dual role in neurodegeneration:
1. **As a biomarker**: NPY expression is altered in Alzheimer's, Parkinson's, Huntington's, ALS, Machado-Joseph disease, diabetic retinopathy, and glaucoma, potentially serving as a marker for disease progression.
2. **As a neuroprotective agent**: NPY alleviates excitotoxicity, oxidative stress, mitochondrial dysfunction, and neuroinflammation while promoting neurogenesis, synaptic plasticity, and cellular resilience.
3. **Through specific signaling cascades**: NPY acts via PI3K/Akt, MAPK/ERK, and p38K pathways through its receptor subtypes to control cell survival, protein homeostasis (proteostasis), and inflammation.
Palanivel, Viswanthram; Salkar, Akanksha; Shenoy, Avinash; Eva, Taslima Akter; Perera, Rumandee; Chitranshi, Nitin; Gupta, Veer; You, Yuyi; Mirzaei, Mehdi; Graham, Stuart L; Gupta, Vivek; Basavarajappa, Devaraj ·
RPEP-15851 · 2026Oreoch-1, a 23-amino-acid cationic peptide from Nile tilapia, demonstrated anti-virulence activity against enteroinvasive E. coli (EIEC) at concentrations of 6.25-12.5 μM. Rather than killing bacteria directly, the peptide interfered with EIEC's invasion process in colon cells (Caco-2). Oreoch-1 modulated expression of seven key virulence factors (ial, icsA, icsB, ipaB, ipaC, virB, virF) and five inflammatory cytokines (IL-6, IL-8, IL-1β, TNF-α, TGF-β).
This dual action — reducing bacterial virulence while modulating the host inflammatory response — represents a fundamentally different approach from conventional antibiotics that simply try to kill bacteria.
Palma, Francesca; Giugliano, Rosa; Chianese, Annalisa; Della Marca, Roberta; Monti, Alessandra; Doti, Nunzianna; Zannella, Carla; Galdiero, Massimiliano; De Filippis, Anna ·
RPEP-15858 · 2026Using phage display, the team identified a peptide (CRBP3) that specifically binds CCR7 and is internalized by both immature and mature dendritic cells. After footpad injection, CRBP3 accumulated in popliteal lymph nodes.
When conjugated to the OVA257-264 antigen, the CRBP3-OVA257-264 vaccine significantly increased MHC-I/peptide complex formation on dendritic cells and boosted IFN-γ production and proliferation of antigen-specific CD8+ T cells. In tumor models, CRBP3-conjugated vaccines carrying either OVA257-264 or HPV16 E749-57 peptides produced potent antitumor responses. The CRBP3-E749-57 vaccine achieved complete tumor regression in TC-1 tumor-bearing mice — a model resistant to anti-PD-1 checkpoint blockade — and conferred long-lasting protection against tumor rechallenge.
Pang, Liwei; Wang, Mingshuang; Fan, Jiani; Sun, Yingjie; Han, Jingjing; Shen, Wenhui; Yang, Bingqian; Hu, Xiaonan; Sun, Yixuan; Kong, Yanan; Qi, Yuanming; Wu, Yahong; Gao, Yanfeng ·
RPEP-15861 · 2026PDCs are small (~1-3 kDa) targeted therapeutics that use homing peptides to deliver cytotoxic drugs to tumors, offering superior tissue penetration and faster clearance compared to antibody-drug conjugates (ADCs, ~150 kDa). Currently, only one PDC is FDA-approved: lutetium (177Lu)-DOTATATE (Lutathera) for neuroendocrine tumors. Other PDCs in development include paclitaxel-Angiopep-2 (ANG1005) for brain tumors and LyP-1-doxorubicin conjugates for triple-negative breast cancer. Key challenges remain: premature drug release, metabolic clearance, variable receptor expression across tumors, and manufacturing scale-up. Melflufen, another PDC, faced clinical setbacks.
Parang, Keykavous; Do, Thuy; Dinh, Clare; Davani-Davari, Dorna; Foroughi, Max; Khong, Troy; Moazen, Mahsa; Nasrolahi Shirazi, Amir ·
RPEP-15862 · 2026Three eligible studies (one RCT and two cohort studies) provided data on tirzepatide's diabetes prevention effects:
Tirzepatide vs. placebo:
- At 176 weeks (~3.4 years): HR = 0.07 (95% CI: <0.01-0.1; P<0.001) — a 93% risk reduction
- At 193 weeks (~3.7 years): HR = 0.12 (95% CI: 0.1-0.2; P<0.001) — an 88% risk reduction
Tirzepatide vs. semaglutide:
- At 12 months: HR = 0.73 (95% CI: 0.58-0.92; P<0.001) — a 27% risk reduction
All comparisons were statistically significant. The hazard ratios against placebo are particularly dramatic, suggesting tirzepatide nearly eliminates the risk of diabetes progression in the treatment period.
Pardeshi, Geeta; Kumbhar, Uddhav T; Kaviprawin, Mogan; Debnath, Aninda; Dubey, Ashok Kumar; Deshmukh, Kalyani; Goyal, Chanchal; Gandhi, Aravind P ·
RPEP-15864 · 2026Using a 7% random sample of Medicare data comparing new users of four diabetes drug classes, GLP-1RA users showed a significantly lower mean frailty index change of -0.007 (95% CI: -0.011 to -0.004) and SGLT-2i users showed -0.005 (95% CI: -0.008 to -0.002) compared to DPP-4i users over one year. Sulfonylurea users showed no significant difference from DPP-4i users.
Mediation analyses revealed that these associations were minimally mediated by cardiovascular or safety events, suggesting the anti-frailty effects operate through independent mechanisms such as metabolic improvements, inflammation reduction, or body composition changes.
Park, Chan Mi; Thanapluetiwong, Saran; Chen, Xiecheng; Oh, Gahee; Ko, Darae; Kim, Dae Hyun ·
RPEP-15866 · 2026Researchers engineered positively charged bile acid-peptide conjugates (PCBs) that self-assemble with negatively charged semaglutide through electrostatic interactions, forming stable nanoparticles approximately 279 nm in size. The best candidate, PCB4, created 'PBSG nanocomplexes' that significantly enhanced semaglutide's absorption through the intestinal wall via bile acid transporter-driven endocytosis.
In a high-fat diet mouse model, oral PBSG nanocomplexes improved semaglutide's therapeutic efficacy compared to unformulated semaglutide. The nanocomplexes also elevated GLP-1 expression in vivo through a dual mechanism: directly delivering semaglutide and simultaneously modulating bile acid metabolism. This approach hijacks the body's own bile acid transport system to shuttle peptide drugs across the intestinal barrier.
Park, So-Hyeon; Ma, Gaeun; Park, Seong Jin; Yang, Seong-Bin; Seo, Minho; Lee, Jun-Hyuck; Kweon, Seho; Park, Jooho · Animal And Cell
RPEP-15870 · 2026In 26 adults with type 1 diabetes on insulin pump therapy, semaglutide rapidly reduced total and bolus insulin requirements — significantly by day 7 — while basal insulin reductions became significant by day 32. By day 77, carbohydrate ratios increased 4.1%, correction factors increased 11.2%, and basal rates decreased 7.9%. The insulin reductions were primarily driven by reduced food intake (less carbohydrate consumption) rather than improved insulin sensitivity.
Despite these rapid changes, hypoglycemia was rarely above 4% of time during follow-ups, suggesting that CGM and automated insulin delivery technology helped mitigate hypoglycemia risk — though active pump parameter adjustments were still needed.
Pasqua, Melissa-Rosina; Tsoukas, Michael A; Haidar, Ahmad ·
RPEP-15878 · 2026GLP-1 receptor agonists did not accelerate the growth of low-risk papillary thyroid carcinomas. After a median of 25 months on GLP-1RA therapy and 5.5 years of follow-up, 84.2% of tumors in the GLP-1RA group remained stable, compared to 92.1% in the unexposed group — a difference that was not statistically significant (p=0.53).
Among the two tumors in the GLP-1RA group that did grow, the drug did not alter their growth kinetics (they were already growing before GLP-1RA exposure). This provides early reassurance that GLP-1 drugs don't fuel thyroid cancer growth.
Patrizio, Armando; Newman, Samantha K; Tuttle, R Michael; Boucai, Laura · Retrospective Observational Cohort Study
RPEP-15885 · 2026Rimegepant is positioned as a significant addition to migraine prophylaxis, distinguished by its dual use for both acute and preventive treatment — a capability unique among CGRP-targeting therapies. The review integrates evidence through 2025 and identifies several emerging directions:
- Situational prevention (using rimegepant around known migraine triggers)
- Potential combination with traditional preventives or anti-CGRP monoclonal antibodies
- Exploratory use in other CGRP-mediated headache disorders beyond migraine
The drug is described as well-tolerated with a favorable safety profile, though long-term persistence and safety monitoring remain important.
Pellesi, Lanfranco; Scuteri, Damiana; Martelletti, Paolo ·
RPEP-15900 · 2026In 212 type 2 diabetes patients (106 per group) followed for 12 months, subcutaneous semaglutide showed advantages over the oral formulation that differed by sex.
In men, the injectable form produced significantly greater reductions in weight (p=0.010), HbA1c (p=0.037), and LDL cholesterol (p=0.038) compared to oral semaglutide. In women, subcutaneous semaglutide led to significantly lower hepatic steatosis index (p=0.024) and greater reduction in GOT/AST liver enzyme levels (p=0.035) compared to men on the same treatment. Two hundred and eight of 212 patients completed the study (98% retention).
Piccione, Alessandra; Bonsangue, Maria; Barone, Martina; Vigneri, Enrica; Mineo, Mariagrazia Irene; Tomasello, Laura; Maniscalco, Laura; Pantò, Felicia; Arnaldi, Giorgio; Guarnotta, Valentina ·
RPEP-15910 · 2026Tirzepatide use in a 63-year-old non-diabetic woman provoked severe postprandial hypoglycemia that led to the diagnosis of insulinoma. The incretin-based mechanism of tirzepatide (stimulating glucose-dependent insulin secretion via GLP-1 and GIP receptors) exacerbated the already excessive insulin production from the tumor, causing dangerously low blood sugar levels.
This case establishes that tirzepatide can unmask or worsen insulinoma-related hypoglycemia and highlights the need to include insulinoma in the differential diagnosis when patients on incretin-based therapies develop unexpected hypoglycemic episodes.
Polisky, Michael; Kamel, Dina; Ku, Jeong-Hee ·
RPEP-15911 · 2026Patients with a less than 30% reduction in NT-proBNP during hospitalization (ΔNT-proBNP < 30%) were discharged on significantly lower doses of guideline-directed medical therapy (GDMT) medications. This association was significant regardless of clinical characteristics or in-hospital management. The in-hospital NT-proBNP burden and trajectory, as markers of residual congestion, were directly associated with underutilization of recommended heart failure medications at discharge.
Polovina, Marija; Tomić, Milenko; Janković, Milica; Civrić, Danka; Stojićević, Andrea; Stanković, Stefan; Pejović, Teodora; Viduljević, Mihajlo; Krljanac, Gordana; Ašanin, Milika; Stanković, Sanja; Seferović, Petar M ·
RPEP-15913 · 2026The literature review found that most clinical studies support an association between MASLD and PAD, particularly in the context of hepatic steatosis (fat accumulation in the liver). Evidence for associations with more advanced stages (steatohepatitis or fibrosis) is limited due to few biopsy-confirmed MASLD studies.
Management strategies for both conditions overlap significantly, centering on lifestyle modifications (diet, exercise, smoking cessation) and shared comorbidity management. Notably, GLP-1 receptor agonists and emerging dual and triple peptide agonists (investigated for MASLD) may provide cardiovascular benefits relevant to PAD. Established PAD medications like statins and aspirin may also benefit MASLD.
Polyzos, Stergios A; Orfanidou, Myrsini; Kountouras, Jannis; Goulas, Antonis ·
RPEP-15915 · 2026People with coronary artery calcium scores of ≥400 had nearly double the risk of major cardiovascular events compared to those with scores of 0 (HR: 1.97). When modelling 3.3 years of semaglutide therapy, the number needed to treat to prevent one major cardiovascular event dropped from 151 for CAC=0 to just 34 for CAC≥400. The incremental cost-effectiveness ratio also improved dramatically: $625,863/QALY for CAC=0 versus $168,666/QALY for CAC≥400, though neither crossed the traditional willingness-to-pay threshold.
Ponnana, Sai Rahul; Zhang, Tong; Sirasapalli, Santosh Kumar; Chen, Zhuo; Dazard, Jean-Eudes; Surya, Niketh; Elhussain, Shamsa; Sivanantham, Kanimozhi; Okyere, Robert; Neeland, Ian J; Rajagopalan, Sanjay; Deo, Salil V ·
RPEP-15916 · 2026Among 9,650 participants with T2D and atherosclerotic CVD and/or CKD (median follow-up 47.5 months), 2,229 (23.1%) had heart failure at baseline. In participants with HF, oral semaglutide reduced the composite HF outcome (HF hospitalization, urgent HF visit, or CV death) by 22% (HR 0.78; 95% CI: 0.63-0.96). No significant benefit was seen in participants without HF (HR 1.01; 95% CI: 0.84-1.20).
The most striking subgroup result: patients with HF with preserved ejection fraction (HFpEF) showed a 41% reduction (HR 0.59; 95% CI: 0.39-0.86), while those with reduced ejection fraction (HFrEF) showed no significant benefit (HR 0.98; 95% CI: 0.70-1.38). MACE reduction with semaglutide was consistent regardless of HF status (HR 0.83 in HF; HR 0.86 in no HF). Serious adverse events were similar between semaglutide and placebo in the HF population.
Pop-Busui, Rodica; Rasmussen, Søren; Deanfield, John E; Buse, John B; Marx, Nikolaus; Mulvagh, Sharon L; Inzucchi, Silvio E; Mann, Johannes F E; Emerson, Scott S; Poulter, Neil R; Engelmann, Mads D M; Hovingh, G Kees; Bayer Tanggaard, Katrine; Birkenfeld, Andreas L; Connelly, Kim A; Haluzik, Martin; Cavender, Matthew A; Kellerer, Monika; Jhund, Pardeep S; Gregersen, Søren; Nielsen, Olav Wendelboe; Lam, Carolyn S P; McGuire, Darren K ·
RPEP-15921 · 2026Three retrospective studies showed that neoadjuvant GLP-1 receptor agonists in obese patients awaiting abdominal wall hernia repair:
- Achieved significantly greater or equivalent weight loss and BMI reductions compared to conventional lifestyle modifications alone
- Did not match pre-operative bariatric surgery in total weight loss and BMI reduction
- Were associated with earlier surgery dates when weight loss was the barrier to proceeding, outperforming both lifestyle modifications and bariatric surgery timelines
- Were not associated with increased post-operative complications or hernia recurrence rates
The review concludes there may be a promising role for GLP-1 drugs as a neoadjuvant bridge to surgery in obese hernia patients.
Prabhakaran, Swetha; Wells, Oliver; Tsui, Lap Wah; Kong, Joseph Cherng Huei ·
RPEP-15922 · 2026Despite effective antiretroviral therapy (ART) that suppressed HIV to undetectable levels in blood, HIV RNA and HIV-derived peptides (from Env and Pol proteins) were still detectable in the cerebrospinal fluid (CSF) of people with HIV-associated neurocognitive disorders (HAND). This was found even though ART drug concentrations in the CSF exceeded the levels needed to suppress active HIV replication.
Critically, although HIV RNA and peptides were present in the CSF, the virus could not establish productive infection when tested in permissive immune cells — suggesting the brain harbors latently infected cells that express viral proteins without producing infectious virus. This non-replicative viral expression, rather than active infection, may drive the neuroinflammation and cognitive decline seen in HAND patients on ART.
Prates, Gabriela S; Li, Xiaoyi; Folgosi, Victor; Shabangu, Ciniso S; Souza, George G; Apoliano, Carlos; Gascon, Maria R; Monteiro, Mariana A; Gualqui, Carolina; Santos Eichler, Rosangela; Gomes, Helio; Katuwal, Nikesh; Gilbert, Cassandra; Tang, Yuyang; Casseb, Jorge; Jiang, Guochun · Observational
RPEP-15925 · 2026The review identifies a divergence between short-term and long-term findings:
Short-to-mid-term trials (semaglutide, liraglutide in obesity):
- Handgrip strength was statistically preserved despite reductions in lean soft tissue mass
- Tirzepatide combined with resistance and aerobic training did not add strength benefits beyond exercise alone in young men
Longer-term data (older adults with type 2 diabetes):
- Longitudinal and retrospective studies reported reductions in handgrip strength with prolonged semaglutide use
- Accelerated sarcopenia was observed
- Potential detrimental effects on neuromuscular health
Key insight: lean soft tissue loss is NOT a reliable predictor of muscle strength change following GLP-1/GIP agonist use — strength can be preserved despite mass loss (short-term) or decline despite what appears to be proportional mass loss (long-term).
Prokopidis, Konstantinos ·
RPEP-15930 · 2026At 6 months post-sleeve gastrectomy, mean total weight loss was 26.5 ± 6% across both groups. Both high-IR and low-IR patients showed enhanced GLP-1 and GLP-2 secretion in response to meal tolerance testing after surgery.
At baseline, the high-IR group had higher relative abundance of Prevotella species (associated with adverse metabolic and inflammatory profiles). After surgery, the high-IR group experienced more pronounced microbiome changes: increases in Akkermansia and Veillonella species and decreases in Prevotella. Enhanced GLP-1 and GLP-2 responses correlated with weight loss and metabolic improvement, with this correlation being particularly strong in the low-IR group. These findings suggest insulin resistance status at baseline shapes both the microbiome remodeling and incretin peptide responses to surgery.
Puig, Rocío; Rodríguez-Peña, M-Mar; Hernández-Montoliu, Laura; Astiarraga, Brenno; Martínez, Eva; Balibrea, Jose M; Llauradó, Gemma; Tarascó, Jordi; Caballero, Albert; Joaquín, Clara; Puig-Domingo, Manel; Vilarrasa, Nuria; Fernández-Veledo, Sonia; Vendrell, Joan; Pellitero, Silvia ·
RPEP-15931 · 2026KR-12-functionalized PLGA nanofiber scaffolds demonstrated dual functionality. For bone regeneration, human bone marrow mesenchymal stem cells on these scaffolds showed enhanced alkaline phosphatase (ALP) activity, increased calcium and collagen deposition, and upregulated expression of key bone markers: collagen type I (COL1), osteopontin (OPN), and osteocalcin (OCN), confirmed by immunofluorescence staining.
For infection prevention, the scaffolds potently inhibited biofilm formation by both multidrug-resistant (MRSA, P. aeruginosa) and non-MDR (E. coli, S. aureus) bacteria. The peptide was covalently conjugated to the nanofibers via cold atmospheric plasma (CAP) treatment — a novel approach for KR-12/PLGA combination not previously reported.
Pulat, Günnur; Bilgiç, Eda; Sezer, Buse ·
RPEP-15932 · 2026Glucose and fructose elicited significant cephalic phase insulin and C-peptide release at 2 minutes. Sucralose did not produce a significant group-level response at 2 minutes but did elicit peak responses comparable to glucose and fructose. Individual variability in both timing and magnitude was substantial across all three stimuli.
Pullicin, Alexa J; Lim, Juyun ·
RPEP-15936 · 2026Four cell-penetrating peptides (R10, 10R-RGD, cRGD-10R, and iRGD-10R) were tested for delivering siRNA to silence LDHC in triple-negative breast cancer cells. Key results:
- All CPP:siRNA complexes formed uniform nanocomplexes of 129-168 nm with low polydispersity
- CPP-mediated siRNA delivery successfully silenced LDHC expression in TNBC cells
- LDHC silencing inhibited tumor growth in zebrafish xenograft models
- The approach showed a favorable safety profile with no significant toxicity
- LDHC silencing also enhanced sensitivity to olaparib, a DNA damage response drug, in clonogenic assays
This represents the first proof-of-concept for CPP-mediated LDHC targeting as a cancer therapy strategy.
Qasem, Hanan; Naik, Adviti; Gomez, Tricia; Ponraj, Janarthanan; Jafar, Umar; Sikhondze, Martin; Thomas, Remy; Mahmoud, Khaled A; Decock, Julie ·
RPEP-15941 · 2026Ferritin nanocages remained largely intact after 30 minutes of simulated gastric digestion and were highly resistant to intestinal proteolysis. In vivo, orally administered ferritin reached the intestinal tract without significant degradation. The GLP-1-ferritin fusion (HLG) was absorbed via TfR1-mediated endocytosis in Caco-2 monolayers. Oral HLG significantly reduced blood glucose levels and food intake in type 2 diabetic mice, while oral exenatide alone showed no such effects.
Qian, Yiran; Chang, Xiaoxi; Sun, Mingyang; Chen, Yunqi; Zang, Jiachen; Lv, Chenyan; Zhao, Guanghua; Zhang, Tuo ·
RPEP-15945 · 2026Synthetic long peptide (SLP) and mRNA vaccine platforms have demonstrated the ability to induce robust antigen-specific T-cell responses and modulate the tumor microenvironment in melanoma. Advances in next-generation sequencing and computational neoantigen prediction have enabled personalized vaccine design targeting patient-specific tumor mutations. These vaccines mechanistically synergize with immune checkpoint inhibitors, enhancing efficacy without adding systemic toxicity. The neoadjuvant (pre-surgical) setting is highlighted as particularly promising due to intact tumor antigens and draining lymphatic architecture for optimal immune priming.
Qin, Jiaxing Jason; Wang, Yang; Sandhu, Shahneen ·
RPEP-15948 · 2026In a propensity-matched cohort of 3,825 GLP-1RA users and 14,920 controls undergoing gastrointestinal endoscopy (63% colonoscopy, 25% EGD, 12% bidirectional):
- Postprocedure pneumonia: 0.13% vs 0.25% (OR 0.56, 95% CI: 0.22-1.45) — no significant difference
- 30-day postprocedural hospitalization: 1.9% vs 2.6% (OR 0.76, 95% CI: 0.59-0.98) — GLP-1 users actually had lower rates
- No significant association with urgent care visits, emergency department visits, or 7- or 30-day mortality
Results were adjusted for sedation type (conscious sedation vs. monitored anesthesia care) and study year. The findings held across procedure types.
Qiu, Chunyuan; Chen, Qiaoling; Tovar, Stephanie; Kwok, Karl; Hernandez Conte, Antonio T; Ferrara, Jammie T; Desai, Vimal; Shi, Jiaxiao M; Giap, Andrew Q; Wu, Bechien U ·
RPEP-15949 · 2026In ApoE-/- mice on a high-fat diet, atherosclerotic symptoms (inflammation, aortic plaques, elevated blood lipids) appeared at 6-10 weeks, while diabetes symptoms (elevated fasting blood glucose, pancreatic damage, insulin imbalance) emerged at 14 weeks — establishing that prolonged atherosclerosis precedes diabetes in this model. Chensinin-1b treatment alleviated progression of both atherosclerosis and type 2 diabetes, with the greatest benefit observed when treatment was initiated in the early stage of disease.
Qiu, Zhongpeng; Fan, Fan; Li, Zhenjia; Sun, Yue; Shang, Dejing ·
RPEP-15950 · 2026Three anti-inflammatory peptides (PHP1, GPA1, GPD1) were identified from rice protein using receptor-based screening. The lead peptide PHP1 was successfully produced via recombinant expression in E. coli at 28.5 ± 3 mg/L using a fusion tag system. PHP1 significantly reduced pro-inflammatory cytokines (TNF-α, IL-1β, IL-6) and nitric oxide in LPS-stimulated macrophages.
Mechanistically, PHP1 directly bound to NF-κB1 with a binding affinity of KD = 7.631 μmol/L and suppressed NF-κB1 phosphorylation — a key step in the inflammatory signaling cascade. The anti-inflammatory effect was validated in a mouse model of systemic inflammation.
Qu, Tingmin; Huang, Ruibo; Wu, Ying; Wu, Hao; Mu, Daichen; Duan, Yanting; Tan, Wenzhi; Huang, Qingming; Hu, Jian; Wen, Li ·
RPEP-15955 · 2026Neuropeptide Y (NPY), a 36-amino-acid peptide, plays a dual destructive role in cardiovascular and blood diseases when dysregulated. In the cardiovascular system, excessive NPY signaling through Y1 receptors promotes vasoconstriction, inflammation, atherosclerosis, heart failure, and hypertension. In blood disorders, NPY influences blood cell production (hematopoiesis), immune cell activity, and blood vessel formation, contributing to thrombosis and leukemia.
The review identifies multiple therapeutic strategies targeting NPY: receptor-specific agonists and antagonists (e.g., [Leu31,Pro34]NPY, BAY 53-6206), enzyme inhibitors (DPP4 and NEP inhibitors that affect NPY breakdown), and natural substances (flavonoids, polyphenols, saponins) that modulate NPY activity.
Rahangdale, Nikita D; Thombre, Kalyani R; Gupta, Krishna R; Umekar, Milind J · Review
RPEP-15966 · 2026In diet-induced obese mice under identical conditions:
- Acute effects: D-allulose rapidly reduced feeding; oral semaglutide reduced it more slowly
- Days 0-3: both profoundly reduced food intake and body weight equally
- Days 4-10: weight loss diminished with oral semaglutide but was maintained with D-allulose
- After treatment cessation: weight rebounded with semaglutide but was maintained with D-allulose
- Both increased muscle grip strength equally
- Mechanism: both activated anorexigenic (appetite-suppressing) leptin-responsive neurons in the hypothalamus, but only D-allulose significantly inhibited orexigenic (appetite-stimulating) ghrelin-responsive neurons
- D-allulose works via both vagal afferent and central nervous routes; semaglutide mainly via central route
Rakhat, Yermek; Banno, Seiya; Zhantleu, Dauren; Tsunekawa, Shin; Yabe, Daisuke; Seino, Yutaka; Iwasaki, Yusaku; Yada, Toshihiko ·
RPEP-15973 · 2026A 30-year-old man with no known diabetes developed euglycemic diabetic ketoacidosis (EDKA) — a dangerous acid buildup in the blood without the expected high blood sugar — while taking tirzepatide for weight loss combined with intermittent fasting and a low-carbohydrate diet. The combination of a GLP-1/GIP receptor agonist with ketosis-inducing dietary restrictions created a perfect storm for this rare but serious complication.
Raptis, Dimitrios; Theodoropoulos, Panagiotis; Shah, Mandar Kalpesh; Bloomgarden, Noah; Kishore, Preeti · Case Report
RPEP-15974 · 2026Among 106,088 patients (53,924 GLP-1RA, remainder insulin), 1,594 (1.9%) developed cancer. GLP-1RA use was associated with significantly lower risk of liver cancer (HR: 0.47, 95% CI: 0.27-0.82) and pancreatic cancer (HR: 0.23, 95% CI: 0.11-0.51) compared to insulin. Risk of all 14 other cancer types was comparable between groups (all p>0.05), including thyroid cancer — a historical concern with GLP-1 drugs.
Rashid, Zayed; Woldesenbet, Selamawit; Khalil, Mujtaba; Altaf, Abdullah; Zindani, Shahzaib; Mevawalla, Areesh; Sarfraz, Azza; Mumtaz, Khalid; Pawlik, Timothy M ·
RPEP-15979 · 2026TRPM3 activation with the agonist CIM0216 (100 μM) triggered CGRP release from trigeminal ganglia, with indications of enhanced release in female tissues. Immunohistochemistry confirmed that TRPM3 and CGRP colocalize in trigeminal ganglion neurons, and TRPM3 was also detected in cerebral and meningeal arterial structures.
CIM0216 application increased cytosolic calcium in CGRP-expressing trigeminal neurons in transgenic mice. However, subcutaneous CIM0216 did not induce allodynia-like symptoms in rats, suggesting TRPM3 activation alone may be insufficient to produce migraine-like pain behavior in vivo despite triggering CGRP release ex vivo.
Reducha, Philip V; Nielsen, Lukas K S; Jensen, Mette N; Edvinsson, Jacob C A; Kazantzi, Spyridoula; Wæver, Sofia L; Lylloff, Tanja; Westgate, Connar S J; Edvinsson, Lars; Haanes, Kristian A ·
RPEP-15980 · 2026Intranasal administration of nanoparticle-encapsulated NPY (NP-NPY) provided robust protection against 6 Hz-, pentylenetetrazole-, and hyperthermia-induced seizures in two mouse models of SCN1A-derived epilepsy. In Scn1a+/- mutant mice (a Dravet syndrome model), NP-NPY treatment reduced spontaneous seizure frequency.
The nanoparticle formulation overcomes a critical barrier in neuropeptide therapeutics: delivering a 36-amino-acid peptide to the brain through a non-invasive intranasal route, bypassing the blood-brain barrier without requiring surgery or gene therapy.
Reed, Samantha L; Aiani, Lauren M; Faiz, Eesha; Adediran, Emmanuel; Benveniste, Morris; Murnane, Kevin S; D'Souza, Martin; Escayg, Andrew; Wong, Jennifer C ·
RPEP-15987 · 2026The norepinephrine-loaded mineralized electrocompacted collagen scaffold (NE-MEC) promoted osteogenic differentiation of rat bone marrow mesenchymal stem cells while simultaneously upregulating nerve growth factor expression in early stages. This nerve growth factor activity supported peripheral nerve repair and induced production of calcitonin gene-related peptide (CGRP), which then enhanced both osteogenic differentiation and neovascularization.
Additionally, NE-MEC stimulated vascular endothelial growth factor A (VEGFA) expression in regenerating bone tissue and shifted macrophage polarization toward a pro-healing phenotype. Together, these effects created a regenerative feedback circuit coordinating bone, nerve, blood vessel, and immune repair in critical-sized bone defects.
Ren, Zhengyun; Wu, Zhaojun; Wu, Anhang; Zhang, Hui; Lu, Jiachen; Zhang, Jiahao; Weng, Jie; Zhang, Jinhua; Chen, Song; Tan, Huan; Guo, Tailin ·
RPEP-15989 · 2026A meta-analysis of 21 randomized trials with 145,322 participants found that GLP-1 receptor agonists reduced major adverse cardiovascular events (MACE) by 14% (HR=0.86, 95% CI: 0.81–0.91). Both blood pressure reduction and weight loss independently contributed to this cardiovascular benefit.
The key insight: when blood pressure was measured using ambulatory monitoring (a 24-hour wearable device) rather than single office readings, the association between BP reduction and cardiovascular benefit was much stronger. This suggests that GLP-1 drugs' blood pressure effects may be underestimated by standard office BP measurements, and that BP lowering is a more important driver of their cardiovascular protection than previously appreciated.
Renna, Nicolás F; Ramirez, Eliel Ivan; Arrupe, Matias Fernando; Ramirez, Jesica Magalí · Meta Analysis
RPEP-15990 · 2026Genome mining with BAGEL4 and antiSMASH tools identified three new bacteriocin-coding genes in S. dentisani 7746, bringing its total to 14 — the largest bacteriocin repertoire known in any bacterial isolate. All 14 bacteriocins were confirmed to be transcriptionally expressed by RT-PCR.
The bacteriocins are regulated by complete sets of Com (competence) and Blp-like (bacteriocin-like peptide) quorum sensing systems. Eight previously unnamed bacteriocins were designated Denticins A through H. Analysis suggests that part of the Blp-like genomic region was acquired by horizontal gene transfer from pneumococci, explaining the unusually large repertoire.
Revilla-Guarinos, Ainhoa; Camelo Castillo, Anny; Cebrián, Rubén; Ferrer, María D; López-López, Arantxa; Adrados-Planell, Ana; Lahoz Oliva, Sandra; Ledesma, Laura; Hols, Pascal; Mira, Álex ·
RPEP-15992 · 2026This comparative review found that single GLP-1 receptor agonists produce meaningful weight loss in patients who regain weight after bariatric surgery, while dual agonists targeting both GLP-1 and GIP receptors show even greater weight reduction in early studies.
However, the review emphasizes that post-surgical patients face unique challenges — including higher risk of micronutrient deficiencies, gastrointestinal intolerance, and maladaptive eating patterns — that require pharmacotherapy to be integrated with nutritional counseling, psychological support, and long-term multidisciplinary care.
Reytor-González, Claudia; Campuzano-Donoso, Martín; Sarno, Gerardo; Montalvan, Martha; Horowitz, Raquel; Rossetti, Gianluca; Pilone, Vincenzo; Barrea, Luigi; Muscogiuri, Giovanna; Schiavo, Luigi; Simancas-Racines, Daniel · Review
RPEP-15997 · 2026Obesity increases the risk of developing asthma by 30-50% and is one of the most common comorbidities in people with established asthma, with up to 70% of adult asthma patients being overweight or obese. The review challenges the simplistic view that obesity-related asthma is only a "Type-2-low" phenotype, showing instead that excess fat affects asthma across the entire inflammatory spectrum through multiple mechanisms including dysregulated adipokine signaling, systemic inflammation, metabolic dysfunction, and mechanical compression of the lungs.
Critically for the peptide field, the authors call for randomized, placebo-controlled trials of GLP-1 and dual GLP-1/GIP agonist therapies specifically in asthma patients with obesity. Weight reduction — whether through lifestyle changes, drugs, or bariatric surgery — improves asthma symptoms, lung function, and exacerbation risk regardless of the inflammatory subtype. Patients with obesity respond similarly to anti-T2 biologics for reducing exacerbations as lean patients, though symptom and lung function improvements are more variable.
Riemann, Sebastian; Matthys, Imke; Maes, Tania; Lapauw, Bruno; Brusselle, Guy · Review
RPEP-16001 · 2026This review examines whether GLP-1 receptor agonists could help women with obesity improve their fertility by enabling rapid preconception weight loss. Women with elevated BMI take longer to conceive and have poorer outcomes from fertility treatments, and many clinics require a BMI under 30 before starting IVF. GLP-1 drugs offer faster weight loss than diet and exercise alone, and may also reverse some of the metabolic dysfunction associated with obesity and polycystic ovarian syndrome (PCOS) — both of which impair fertility.
The review finds this is an emerging but promising area: GLP-1 agonists could help women reach treatment-eligible weight faster, which matters because reproductive potential declines with age. However, the authors note significant gaps in safety data regarding preconception use and highlight ethical considerations around prescribing these drugs specifically for fertility access.
Roberts, Rachel; Markande, Anurag; Kasaven, Lorraine; Williams, Sarah Chieveley; Faris, Raef; Bracewell-Milnes, Timothy; Thum, Yau; Nicopoullos, James; Jones, Benjamin P · Review
RPEP-16004 · 2026Two methods of conjugating hemagglutinin (HA) to Q11 peptide nanofibers were demonstrated:
1. β-tail co-assembly: Produced increased antibody responses; with KEYA adjuvant, achieved modest increases in antibody breadth and survival against flu challenge
2. SortaseA (SrtA)-mediated ligation: Superior results — augmented antibody responses, significantly increased breadth of antibody binding to HA trimers spanning up to 30 years of antigenic drift from the immunizing antigen, increased hemagglutination inhibition to both homologous and heterologous viruses, and protected against lethal influenza challenge
The KEYA peptide adjuvant (random combinations of lysine, glutamic acid, tyrosine, and alanine) provided non-reactogenic immune enhancement without disrupting HA antigenicity at low concentrations.
Roe, Emily F; Votaw, Nicole L; Lazar, Kat M; Burke, Kaitlyn N; Miranda, Hector A; Fries, Chelsea N; Rock, Michelle L; Macintyre, Andrew N; Stover, Erica L; Huskey, Jessica B; Harris, Summer J; Landon, Chelsea D; Mansouri, Katayoun; Edwards, Robert J; Heaton, Nicholas S; Collier, Joel H ·
RPEP-16007 · 2026After 36 days of efavirenz (10 mg/kg oral) in CD1 mice:
- **Appetite signaling increased**: Serum ghrelin rose, and hypothalamic expression of GHS-R1a (ghrelin receptor) and NPYR1 (neuropeptide Y receptor 1) were upregulated.
- **Eating behavior changed**: Food intake increased and sucrose preference was elevated, consistent with enhanced reward-driven eating.
- **Paradoxical weight loss**: Despite eating more, mice in the efavirenz group lost weight.
- **Metabolic disruption**: Triglycerides and cholesterol increased.
- **Leptin findings**: Serum leptin, soluble leptin receptor (sOB-R), and free leptin index showed that the increased hunger was not caused by reduced satiety signaling — rather, hunger was independently stimulated through the ghrelin/NPY axis.
Rojas-Osornio, Sandra Angélica; Manuel-Apolinar, Leticia; Crespo-Ramírez, Minerva; Paredes-Cervantes, Vladimir; Mata-Marín, Antonio; Molina-López, José; Pérez de la Mora, Miguel; Borroto-Escuela, Dasiel; Martínez-Lara, Ricardo; Tesoro-Cruz, Emiliano ·
RPEP-16009 · 2026The review establishes that AMPs exploit a fundamental difference between bacterial and human cells: bacterial membranes carry a negative charge, while eukaryotic (human) membranes are largely neutral. The positively charged, amphipathic structure of AMPs drives their selective binding to bacteria.
Multiple biophysical techniques can measure distinct aspects of this interaction. Differential scanning calorimetry reveals how peptides alter membrane stability and phase behavior. X-ray diffraction shows structural changes in lipid packing. NMR provides atomic-level detail of peptide orientation within membranes. Fluorescence spectroscopy can track pore formation, permeability changes, and binding affinities in real time. Together, these methods allow researchers to rationally design new AMPs with improved selectivity and potency.
Roldán, A; Fernández-García, P; Lladó, V; Torres, M; Escribá, P V; Salvador-Castell, M ·
RPEP-16010 · 2026In a pooled analysis of 13 hemiplegic migraine patients treated with anti-CGRP monoclonal antibodies, median monthly aura days dropped from 3 to 0.6 (p=0.018) and MIDAS disability scores fell from 88 to 28 (p=0.018) at three months.
Monthly headache days decreased numerically from 18 to 9, though this did not reach statistical significance (p=0.077). Notably, 83% of patients achieved greater than 50% reduction in both headache days and aura frequency, and 75% saw more than 50% improvement in disability scores. No adverse events were reported across the entire cohort.
Romozzi, Marina; Palermo, Matteo; Danno, Daisuke; Katsuki, Masahito; Tosto, Federico; Signorelli, Francesco; Vollono, Catello; Matsumori, Yasuhiko; Calabresi, Paolo; Ornello, Raffaele; Iannone, Luigi Francesco ·
RPEP-16015 · 2026In a 52-week phase 3 trial of 1,698 adults with type 2 diabetes, oral orforglipron was not only non-inferior but statistically superior to oral semaglutide at lowering blood sugar. Orforglipron 36 mg reduced HbA1c by 1.91% from baseline vs. 1.47% for semaglutide 14 mg (treatment difference -0.44%, p<0.0001). Even the lower 12 mg orforglipron dose beat the higher semaglutide 14 mg dose (-0.24% difference, p=0.005).
However, orforglipron came with trade-offs: higher rates of gastrointestinal side effects (58-59% vs. 37-45%), more treatment discontinuations due to adverse events (9-10% vs. 4-5%), and a greater increase in pulse rate (3.7-4.7 bpm vs. 1.0-1.5 bpm).
Rosenstock, Julio; Yabe, Daisuke; Cox, David; Li, Jianghao; Denning, Max; Wu, Wen-Shuo; Liu, Rong; Zhao, Youna · Rct
RPEP-16016 · 2026GIP's effects on inflammation are context-dependent and influenced by tissue-specific receptor expression and metabolic status. Experimental models show both pro-inflammatory and anti-inflammatory effects depending on the setting. GIP/GLP-1 dual agonists have demonstrated improved glycometabolic and inflammatory outcomes in clinical use, but the individual contributions of each pathway remain unclear.
The GIP receptor (GIPR) is expressed on immune cells and tissues beyond the pancreas, providing a biological basis for immunomodulatory effects. The review highlights GIPR as a promising but understudied target in the emerging field of immunometabolism.
Rossi, Giada; Bucciarelli, Loredana; Cimino, Vincenzo; Fiorina, Paolo ·