RPEP-15680 · 2026Obese (HFD) female mice showed insulin resistance, elevated NF-κB-associated pro-inflammatory cytokines (IL-1β, IL-6, TNF-α), oxidative stress, reduced SIRT1/SIRT6/FOXO3a/NRF1/eNOS, elevated FOXO1/iNOS, decreased progesterone and estradiol, elevated FSH and LH, disrupted ovarian morphology, oocyte lipid accumulation and DNA damage, and reduced fertility.
Semaglutide treatment alleviated all of these dysfunctions: restoring SIRT1 and SIRT6 levels, reducing inflammation and oxidative stress, improving hormone balance, correcting ovarian structure, reducing oocyte damage, and improving fertility outcomes via modulation of the SIRT-associated pathway.
Matiki, Tashinga Walter; Ul Haq Shah, Mohd Zahoor; Yin, Lin; Liu, Rui; Zhu, Kejing; Lin, Zhongliang; Sheng, Jianzhong; Hefeng, Huang ·
RPEP-15682 · 2026Among 65 patients, 31% had impaired coronary flow reserve (CFR). BNP showed diagnostic accuracy for impaired CFR with AUC=0.74 (95% CI 0.60-0.88), while casual blood glucose had AUC=0.64 (95% CI 0.49-0.80). Combining both markers improved discrimination (p=0.03).
For structural CMD (CFR<2.0 and IMR≥25), elevated BNP (AUC=0.77, 95% CI 0.59-0.95) and higher urine albumin-to-creatinine ratio (AUC=0.71, 95% CI 0.52-0.90) were significantly associated, but casual blood glucose was not. BNP emerged as the most consistent biomarker across both functional and structural CMD definitions.
Matsumoto, Kotaro; Otsuka, Kenichiro; Kagawa, Shunsuke; Yamaura, Hiroki; Miura, Tsubasa; Sugioka, Kazuya; Saitoh, Wataru; Okamoto, Akihiro; Kajio, Go; Fujisawa, Naoki; Yamaguchi, Tomohiro; Shimada, Takenobu; Hayashi, Yusuke; Shibata, Atsushi; Ito, Asahiro; Yamazaki, Takanori; Fukuda, Daiju ·
RPEP-15686 · 2026Among 112,532 FDA adverse event reports analyzed from 2015-2024, GLP-1 receptor agonists were associated with a much higher share of administration-related reactions (63%) compared to injectable insulin (39%). Reports of dosing issues and administration errors for GLP-1s increased starting in Q4 2022 and continued rising through 2023 and 2024 — a pattern not seen for insulin. This increase coincided temporally with national GLP-1 drug shortages that began in March 2022.
Mattingly, T Joseph; Duru, Emeka Elvis; Conti, Rena M ·
RPEP-15689 · 2026Compounded GLP-1 receptor agonists were associated with significantly higher rates of adverse events compared to FDA-approved versions across the board. Key findings from 81,078 FAERS reports (707 compounded):
- Suicidality: 6.34× higher odds with compounded products
- Cholecystitis (gallbladder inflammation): 3.39× higher odds
- Abdominal pain: 2.84× higher odds
- Hospitalization: 2.35× higher odds
- Preparation errors: 48.92× higher odds
- Contamination: 19× higher odds
- Compounding/manufacturing issues: 8.51× higher odds
Compounded products did show lower odds of dosing errors (0.24×) and administration errors (0.29×).
McCall, Kenneth L; Mastro Dwyer, Keri A; Casey, Ryan T; Samana, Tasnia N; Sulicz, Ewa K; Tso, Susannah Y; Yalanzhi, Emma R; Piper, Brian J · Observational
RPEP-15692 · 2026In patients with type 2 diabetes and moderate-to-severe chronic kidney disease (CKD), 6 months of dulaglutide treatment significantly lowered plasma levels of 14 out of 21 proteins previously linked to progression to end-stage kidney disease. The most dramatically affected were 8 TNF receptor family proteins (TNF-R1, -R2, -R3, -R4, -R6B, -R7, -R19L, -R27) — key drivers of inflammation and cell death pathways.
In contrast, these same proteins increased in patients on insulin glargine. The differences were most pronounced in patients with worse baseline kidney function, higher albumin leakage, higher HbA1c, or higher BMI — suggesting dulaglutide's kidney-protective effects may be strongest in the sickest patients. Kidney injury molecule 1 (KIM1), a marker of tubular damage, declined in both groups equally.
McFarlin, Brandon E; Tye, Sok Cin; Satake, Eiichiro; Md Dom, Zaipul I; Kechter, Afton; Wilson, Jonathan M; Krolewski, Andrzej S; Duffin, Kevin L · Post Hoc Analysis Of RCT
RPEP-15695 · 2026Compared to baseline standard-of-care treatment, both drug classes improved outcomes:
- **SGLT2 inhibitors**: +0.24 QALYs, +$5,000 lifetime cost → $21,400 per QALY gained
- **GLP-1 receptor agonists**: +0.23 QALYs, +$27,000 lifetime cost → much higher cost per QALY
Both reduced lifetime rates of cardiovascular and renal events. However, SGLT2 inhibitors were consistently cost-effective in sensitivity analyses. In 62% of probabilistic sensitivity analysis iterations, GLP-1 RA were dominated — meaning they produced fewer QALYs at a higher cost than SGLT2 inhibitors. The authors noted GLP-1 RA cost-effectiveness could improve if benefits beyond typical diabetes complications (e.g., weight loss, dementia prevention) are considered and if generic formulations become available.
McNally, Ethan S; Marques, Pedro; Possik, Elite; Pandya, Ankur; Tsoukas, Michael A; Mavrakanas, Thomas A; Dasgupta, Kaberi; Gupta, Nisha; Sharma, Abhinav; Russell, W Alton ·
RPEP-15697 · 2026GLP-1 receptors in vascular smooth muscle cells (VSMCs) are essential for semaglutide to lower blood pressure in mice. When VSMC GLP-1R expression was eliminated, semaglutide could no longer reduce blood pressure, despite continuing to reduce food intake, body weight, and blood glucose normally.
In contrast, GLP-1 receptors on Tie2+ endothelial cells and immune cells were dispensable — mice lacking GLP-1R in these cell types still showed normal blood pressure reduction with semaglutide. The VSMC GLP-1R was also required for semaglutide's effects on increasing glomerular filtration rate and promoting natriuresis (sodium excretion).
Proteomic analysis revealed that semaglutide treatment changed protein expression in the renal artery and kidney related to platelet aggregation, fibrin clot formation, lipid metabolism, and pro-apoptotic signaling — all abolished in mice lacking VSMC GLP-1R. Additionally, semaglutide directly relaxed pre-constricted blood vessels in an ex vivo artery preparation.
Medak, Kyle D; Koehler, Jacqueline A; Baggio, Laurie L; Gonzalez-Rellan, Maria J; Wong, Chi Kin; Cao, Xiemin; Rao, Vivikta; Kao, Sean; Cui, Yu; Fu, Jiayi; Liaw, Easton; Kabir, M Golam; Zhang, Jie; Wei, Jin; Drucker, Daniel J ·
RPEP-15700 · 2026The study identified 17 shared genes between GLP-1 protein targets (from UniProt) and diabetic nephropathy-associated genes (from GeneCards), including STAT3, EP300, MAPK1, and INSR (insulin receptor). These formed a densely connected network cluster enriched in:
- Insulin response pathways
- Hypoxia adaptation
- Apoptosis regulation
- Glucose metabolism
Molecular docking with HADDOCK demonstrated direct and favorable binding of GLP-1 to STAT3, PIK3R1, and EP300 — suggesting noncanonical mechanisms involving transcriptional regulation and epigenetic modulation that go beyond the classical GLP-1 receptor signaling pathway.
Melo, Wanderson Gabriel Gomes de; Dos Santos Silva, Regina Lúcia; Santos Soares, Ianahanna Duarte; de Sousa Barbosa, Bruno; Cardoso de Brito, Felipe; Argôlo Neto, Napoleão Martins; Bezerra, Dayseanny de Oliveira ·
RPEP-15702 · 2026Among eight linear arginine-rich peptides tested, R4F4 showed the strongest antibacterial activity, but its effectiveness was significantly reduced in the presence of human serum and trypsin (a digestive enzyme). The D-amino acid version (D-R4F4) and cyclic version of R4F4 maintained their antimicrobial activity even in the presence of proteases.
The modified peptides worked through multiple mechanisms simultaneously: altering bacterial membrane permeability, modulating intracellular reactive oxygen species levels, and changing gene expression profiles related to metabolic pathways. They also showed substantial antibiofilm activity — both preventing biofilm formation and disrupting mature biofilms — with good cytocompatibility (safety for human cells).
Mendes, Bruno; Castelletto, Valeria; Hamley, Ian W; Barrett, Glyn ·
RPEP-15715 · 2026Adding semaglutide to canagliflozin produced superior outcomes compared to canagliflozin alone in 211 patients with diabetic nephropathy over 6 months. The combination therapy showed significantly better results across multiple measures: albumin-to-creatinine ratio (145.87 vs 158.11 mg/g, p=0.002), HbA1c (7.08% vs 7.42%, p=0.005), LDL cholesterol (86.74 vs 94.86 mg/dL, p=0.032), free fatty acids (0.46 vs 0.52 mmol/L, p=0.002), and insulin resistance index (3.94 vs 4.08, p=0.011).
Pancreatic β-cell function also improved with combination therapy (51.22 vs 49.36, p=0.022), and adverse event rates were comparable between groups with no increase in gastrointestinal side effects.
Miao, Yan; He, Pan; Wang, Dan-Yu; Yan, Lei; Cao, Hui-Xia; Shao, Feng-Min ·
RPEP-15717 · 2026LEAP2 demonstrated dose-dependent effects across different experimental models:
• In human and mouse hepatocyte cultures: LEAP2 inhibited lipid accumulation, confirming a direct effect on liver cell fat metabolism.
• In mice on standard diet: Central (brain) administration of LEAP2 reduced hepatic lipid deposition.
• In young mice on high-fat diet: LEAP2 did not prevent diet-induced steatosis but did attenuate hepatic inflammation.
• In aged mice: LEAP2 failed to suppress both age-associated inflammation and steatosis.
The progressive loss of LEAP2 effectiveness from normal conditions to high-fat diet to aging suggests a resistance phenomenon, similar to insulin or leptin resistance seen in obesity and metabolic syndrome.
Miguéns, Marta V; Quintela-Vilariño, Carmen; Casado, Sabela; de Oliveira-Diz, Tadeu; Müller, Timo D; Nogueiras, Rubén; Diéguez, Carlos; Tovar, Sulay ·
RPEP-15719 · 2026Over 10,033 GLP-1 receptor agonist exposures were reported to U.S. poison centers from 2012 to 2023. After semaglutide's weight loss approval in July 2021, case volumes more than doubled (3,113 pre-approval vs. 6,920 post-approval). Semaglutide became the dominant agent, accounting for 64.2% of post-approval reports.
The exposed population shifted younger and more female, consistent with the drug's new weight loss demographic. Most cases involved unintentional therapeutic errors with mild gastrointestinal symptoms. However, the proportion of cases requiring healthcare facility involvement increased significantly from 23.0% to 33.5% (RR = 1.46, p < 0.001). Segmented Poisson regression showed semaglutide exposures increased an additional 9.9% per quarter after approval.
Miller, Jordan; Miller, Robert; Varney, Shawn M; Han, David ·
RPEP-15722 · 2026At a concentration of 1 μM, topiramate strongly inhibited the electrical activity of orexigenic NPY/AgRP neurons in the arcuate nucleus of the hypothalamus. This is the first study to demonstrate this effect.
The mechanism was unexpected: despite topiramate's well-established actions at GABAA receptors, the inhibition of NPY/AgRP neurons did not involve GABAA receptors. Instead, the effect required synaptic transmission and was blocked by GABAB receptor antagonists and potassium channel blockers, suggesting topiramate enhances GABAergic inhibitory tone through a GABAB-mediated pathway. Notably, topiramate had negligible effects on anorexigenic POMC neurons, demonstrating selectivity for the hunger-promoting neural population.
Minbashi Moeini, Moein; Lavoie, Olivier; Caron, Alexandre; Williams, Kevin W; Michael, Natalie J ·
RPEP-15724 · 2026Tα1 significantly enhanced CD8+ T cell-mediated apoptosis of MDA-MB-231 breast cancer cells and CD44+ cancer stem-like cells, suppressed tumor cell proliferation, and increased granzyme B secretion beyond what standard CD3/CD28 stimulation alone achieved.
In exhausted T cells, Tα1 partially restored effector function and reduced expression of three key immune checkpoint receptors: PD-1, TIM-3, and LAG-3. A complementary transcriptomic analysis using a four-gene Tα1 Response Index (TLR9, TLR2, IRF1, NLRC5) applied to 1,112 breast cancer patients from TCGA confirmed positive correlations with antigen presentation and cytotoxic programs, with enrichment in CD8-like T cells in single-cell datasets.
Mishra, Smriti; Telang, Gaurang; Sureshbabu, Anurag; Kulkarni, Samruddhi; Thayagrajan, Senthil; Kumar, A W Santhosh; Singh, Rajshri ·
RPEP-15726 · 2026For total shoulder arthroplasty (TSA), the pooled 90-day complication rate was 18.1% for GLP-1 users versus 15.9% for non-users, with no statistically significant difference (OR = 0.86, 95% CI: 0.36–2.07, P = 0.74). At 2 years, rates were nearly identical: 3.8% vs 3.7% (OR = 1.24, 95% CI: 0.73–2.00, P = 0.42).
For arthroscopic procedures, GLP-1 users showed notably lower 90-day complication rates. After rotator cuff repair, complications were 11.0% vs 27.4% in non-users. After capsular release for adhesive capsulitis, rates were 2.5% vs 4.8%. Re-tear rates after rotator cuff repair were also lower in GLP-1 users at 2 years (12.5% vs 18.3%), though these arthroscopic findings were from limited studies described narratively rather than pooled.
Moews, Logan D; Kunze, Kyle N; Thamrongskulsiri, Napatpong; Vega, Tomas F; Morgan, Jacob T; Nishioka, Tanner; Chahla, Jorge; Verma, Nikhil N ·
RPEP-15727 · 2026In a propensity-score-matched study of 86,083 pairs of diabetes patients, GLP-1 receptor agonist users had no increased or decreased risk of colorectal cancer compared to DPP-4 inhibitor users (OR=0.99, 95% CI: 0.84–1.17). However, GLP-1RA users had a modestly higher incidence of colonic polyps (5.9% vs. 5.3%; OR=1.12, 95% CI: 1.08–1.17).
The polyp finding persisted even when patients with pre-existing polyps were excluded from the analysis, strengthening the signal. However, the absolute difference was small (0.6 percentage points), and colonic polyps are very common and usually benign.
Moh'd Mari, Anwar Alshaakh; Alamin, Faris; Le, Minh Anh; Rizvi, Ali; Mansi, Ishak A · Cohort
RPEP-15730 · 2026Across 15 studies published between 2020 and 2024, fish-derived antimicrobial peptides (AMPs) demonstrated broad-spectrum anticancer activity against diverse cancer cell lines. The primary killing mechanisms were apoptosis and necrosis triggered through reactive oxygen species (ROS) generation, mitochondrial dysfunction, and DNA damage. Notably, these peptides showed selective cytotoxicity — preferentially killing cancer cells while being less toxic to normal cells. Some also exhibited antiangiogenic properties (blocking tumor blood vessel formation).
Mohd Noordin, Muhammad Akram; Najm, Ahmed Abdulkareem; Dyari, Herryawan Ryadi Eziwar; Law, Douglas; Fazry, Shazrul ·
RPEP-15731 · 2026This review provides a comprehensive guide to managing the toxicities of peptide receptor radionuclide therapy (PRRT) with lutetium-177 DOTATATE in neuroendocrine tumor patients. Toxicities can be acute, subacute, or long-term, affecting multiple organ systems. Key management topics include screening for clonal hematopoiesis before treatment (a risk factor for blood cancers), steroid prophylaxis to prevent carcinoid crisis and bowel obstruction, and evidence-based monitoring strategies for kidney and bone marrow toxicity.
Mohindroo, Chirayu; Ramirez, Robert A · Review
RPEP-15733 · 2026Enzymatic hydrolysis of wine lees proteins with alcalase, flavourzyme, and protease produced peptides with both ACE inhibitory and antimicrobial activities. Protease hydrolysate showed the highest antimicrobial activity against E. coli, associated with a high proportion of positively charged peptides.
In silico gastrointestinal digestion simulation identified 34 ACE-inhibitory peptide sequences from the hydrolysates. Of these, 8 di-/tripeptides (AF, AW, GF, GL, GW, PL, PM, VW) were predicted to have positive human intestinal absorption. VW and AW showed the strongest ACE binding energies (lower than -8.0 kcal/mol) in molecular docking. All predicted peptides were non-toxic with desirable drug-like properties per Lipinski's rule-of-five.
Monasterio, Romina; Iram, Daraksha; Knuf, Franziska; Caspers-Weiffenbach, Rita; Fontana, Ariel ·
RPEP-15735 · 2026After propensity score matching in 2,516 patients (1,258 per group), semaglutide and tirzepatide showed no significant difference in the composite of all-cause mortality and heart failure hospitalization over a median 24-week follow-up (HR 1.14, 95% CI 0.89–1.46, p=0.286). Individual components were also similar: all-cause death HR 1.24 (p=0.531) and HF hospitalization HR 1.10 (p=0.471). Results were consistent regardless of diabetes status.
Monzo, Luca; Savarese, Gianluigi; Duarte, Kevin; Baudry, Guillaume; Petrie, Mark C; Girerd, Nicolas ·
RPEP-15737 · 2026Weekly low-dose liraglutide (1.2 mg/week) reduced interdialytic weight gain from 5.72% to 2.72% and decreased thirst from 10/10 to 3/10 on an analog scale in a non-diabetic hemodialysis patient with refractory polydipsia. The treatment stabilized blood pressure and improved dialysis tolerance in a patient whose management was severely limited by baseline hypotension and hemodynamic instability. The mechanism is proposed to be GLP-1 receptor-mediated modulation of neural circuits controlling thirst, independent of glycemic effects.
Mora-Bravo, Franklin; Morales, Pamela T; Pincay, Gabriela; Pineda, Samantha; Morales, Brayan ·
RPEP-15741 · 2026The DNA prime-peptide boost immunization strategy elicited the strongest CD8+ T-cell responses compared to homologous DNA-only or peptide-only approaches. These T cells showed both effector and memory precursor phenotypes and formed circulating and skin-resident memory T cells.
In prophylactic settings, this regimen delayed B16F10 melanoma growth and rejected EL4 lymphoma cells expressing a self-antigen. Therapeutically, the DNA prime-peptide boost eliminated EL4 tumors expressing the neo-epitope model in most mice. When targeting two bona fide neoepitopes of the MC38 tumor model, the strategy elicited neoepitope-specific CD8+ T-cell responses and a marked therapeutic effect that could be enhanced by combining with anti-PD-1 antibody.
Morgado-Cáceres, Pablo; Hofmann-Vega, Francisca; Figueroa, Diego; Saavedra-Almarza, Juan; Gálvez-Cancino, Felipe; Díaz, Ximena; Menares, Evelyn; Roa, Eduardo; Hidalgo, Sofia; Varas-Godoy, Manuel; Borgna, Vincenzo; Lladser, Alvaro ·
RPEP-15744 · 2026The review highlights α-conotoxins RgIA4 and GeXIVA[1,2] as lead candidates for CIPN treatment. These peptides specifically target α9-containing nicotinic acetylcholine receptors (nAChRs), which play critical roles in both neuronal excitability and inflammatory responses in peripheral and central sensory pathways.
These conopeptides demonstrate dual therapeutic mechanisms: direct blockade of pain signaling through ion channel modulation, and reduction of neuroinflammation through neuroimmune pathway modulation. In animal models of CIPN, these peptides have shown disease-modifying potential rather than just symptom relief. Recent peptide engineering advances have improved their cross-species compatibility, receptor selectivity, and serum stability for potential clinical development.
Mosayyebi, Bashir; Faradonbeh, Davood Rabiei; Hosseindoost, Saereh; Arsanjani, Amirhossein Akbarpour; Negahdari, Babak; Majedi, Hossein; Malekshahi, Ziba Veisi ·
RPEP-15749 · 2026The incretin effect — where gut hormones boost insulin secretion after eating — is fully functional in developing 2-week-old rat pups, with an incretin effect of 63% (meaning 63% of the insulin response to oral glucose came from gut-stimulated incretin hormones rather than glucose alone).
Critically, when the researchers gave standard therapeutic doses of a DPP-4 inhibitor (linagliptin) or a GLP-1 receptor agonist (liraglutide) to the pups, neither drug caused dangerous drops in blood sugar. This is significant because hypoglycemia is the major concern when treating high blood sugar in preterm infants.
The findings suggest that incretin-based therapies could be a safer approach to treating hyperglycemia in extremely premature babies compared to insulin, which carries substantial hypoglycemia risk.
Motokura, Kouji; Tomotaki, Seiichi; Tomobe, Yutaro; Takita, Junko; Kawai, Masahiko · Animal Study
RPEP-15752 · 2026Glucocorticoid receptors (GR) are abundantly expressed in human dorsal root ganglion (DRG) sensory neurons — the same neurons that produce CGRP, the key pain-signaling neuropeptide. Specifically, GR was found to co-localize extensively with CGRP in pain-sensing C-fibers and Aδ-fibers, and was concentrated in medium-diameter neurons (40-65 μm). In animal models, GR activation reduced inflammatory pain through rapid non-genomic mechanisms, while mineralocorticoid receptors (MR) had the opposite effect — promoting pain. Clinically, epidural steroid injections provided at least 3 months of pain relief in patients with chronic radicular pain. Together, the findings suggest that steroids relieve pain partly by acting on GR in CGRP-producing pain neurons, and that MR blockade could enhance this effect.
Mousa, Shaaban A; Metwally, Elsayed Y; Li, Xiongjuan; Tafelski, Sascha; Retana Romero, Oscar Andrés; Piontek, Jörg; Treskatsch, Sascha; Schäfer, Michael; Shaqura, Mohammed · Translational (Human Tissue + Animal + Clinical)
RPEP-15753 · 2026Researchers discovered that the rabies virus phosphoprotein (RABV-P) has previously unknown RNA-unwinding activities — both helicase-like (energy-dependent) and chaperone-like (energy-independent). This is the first such activity identified in any rhabdovirus.
Critically, two designed peptides (P90 and P110) targeting the protein's oligomerization domain effectively inhibited rabies virus replication in cells, demonstrating a new therapeutic strategy against this nearly 100% fatal disease.
Mu, Jingfang; Wang, Caiqian; Shu, Ting; Xiong, Xiaobei; Ren, Yujie; Gong, Rui; Zhao, Ling; Zhou, Xi · Laboratory
RPEP-15756 · 2026Sixteen Yorkshire swine with diet-induced metabolic syndrome and surgically induced coronary artery disease were randomized to semaglutide (n=8) or control (n=8) for 5 weeks. Semaglutide-treated animals showed significantly improved left ventricular filling, end diastolic volume, stroke volume, and cardiac index (all p<0.05).
The mechanism was identified as enhanced vascular proliferation in the peri-ischemic myocardium — semaglutide stimulated growth of collateral blood vessels around the blocked coronary artery. Coronary arteriole vasoactivity was also improved, with enhanced vessel relaxation. Molecular analysis revealed pro-angiogenic pathway activation in the ischemic territory, including changes in proteins involved in blood vessel formation. The study provides the first mechanistic evidence that GLP-1 receptor agonism directly improves coronary collateralization in the setting of chronic ischemic cardiomyopathy.
Muir, Kelsey C; Stone, Christopher; Harris, Dwight D; Kanuparthy, Meghamsh; Broadwin, Mark; Hamze, Jad; Feng, Jun; Sellke, Frank W ·
RPEP-15760 · 2026A Streptomyces pratensis strain (S26-11) isolated from Himalayan soil in Kargil, Ladakh was identified as a new production source for echinomycin. This is the first report of S. pratensis producing echinomycin.
The study provided the first demonstration of echinomycin-mediated modulation of key genes associated with Staphylococcus aureus biofilm formation and pathogenicity. When piperine was used as an adjuvant, it lowered echinomycin's minimum inhibitory concentration (MIC) and potentially limited the emergence of resistant MRSA mutants, suggesting reduced risk of antimicrobial resistance development.
Murtaza, Mohd; Bhasin, Nitika; Kumari, Priya; Kour, Avleen; Choudhary, Poonam; Kushwaha, Manoj; Sharma, Sandeep; Jaglan, Sundeep ·
RPEP-15767 · 2026Cecropin A (an insect-derived antimicrobial peptide) showed immunomodulatory effects in chicken ileal explant cultures without cytotoxicity. At the higher dose (6.25 µg/mL), it increased IL-2 production (an immune activation signal) and elevated claudin-3 expression (a tight junction protein that strengthens the gut barrier). Under inflammatory conditions (Poly I:C challenge), the lower dose of cecropin A (3.125 µg/mL) reduced IL-6 (an inflammatory cytokine). Cell viability remained unaffected at both doses.
Márton, Rege Anna; Varga, Olivér; Vincent, Naveen Joseph; Tráj, Patrik; Sebők, Csilla; Kemény, Ágnes; Mackei, Máté; Neogrády, Zsuzsanna; Molnár-Nagy, Viviána; Mátis, Gábor ·
RPEP-15770 · 2026Coarse-grained molecular dynamics simulations of GLP-1R in four conformational states revealed that cholesterol hotspots vary between receptor states, with increased cholesterol enrichment around the receptor in active conformational states. Active states showed more favorable cholesterol interaction energetics and increased residence times compared to inactive and partially active states.
Subtle differences were observed between GLP-1-bound and exenatide-bound receptor states, highlighting ligand-specific effects on cholesterol interactions. The findings demonstrate that cholesterol selectively associates with the active state of GLP-1R, suggesting that membrane cholesterol content could modulate receptor signaling.
Naglekar, Amit; Chattopadhyay, Amitabha; Sengupta, Durba ·
RPEP-15772 · 2026Ultrasmall (~3 nm) oligopeptide-stabilized gold nanoclusters functionalized with survivin-targeting siRNA and Her2 antibodies outperformed the commercial transfection agent Lipofectamine2000 in delivering gene-silencing therapy to breast cancer cells. The system achieved potent survivin knockdown, significant reduction in cell proliferation, and served as a fluorescent imaging agent for real-time tracking — all without triggering cytotoxicity.
Nair, Resmi V; Santhakumar, Hema; Govindachar, Divya Maldepalli; Modi, Jitendra; Subramani, Sivaselvam; Periyasamy, Ganga; Ueda, Motoki; Ito, Yoshihiro; Jayasree, Ramapurath S ·
RPEP-15774 · 2026Two amaranth-derived peptides, SFNLPILR and FNLPILR, demonstrated potent ACE inhibition with IC₅₀ values of 0.075 mM and 0.055 mM, respectively. Both peptides showed selective or minimal modulation of ACE2 enzymatic activity, suggesting they can suppress the harmful arm of the renin-angiotensin system while preserving the protective arm.
Molecular docking revealed that both peptides interact with ACE's catalytic residues through their shared LR motif. Transepithelial transport studies using Caco-2 cell monolayers confirmed that peptide fragments can cross the intestinal barrier, supporting potential oral bioavailability.
Nardo, Agustina E; Suárez, Santiago E; García Fillería, Susan F; Añón, M Cristina; Quiroga, Alejandra V ·
RPEP-15775 · 2026This CME review outlines several key points about GLP-1-based therapies and skin health:
- GLP-1 receptors have broad cellular distribution, including in tissues relevant to skin biology
- GLP-1 receptor agonists attenuate pro-inflammatory cytokine signaling while promoting anti-inflammatory pathways
- Emerging evidence supports relevance in dermatology for:
- Improvement in psoriasis
- Improvement in hidradenitis suppurativa (HS)
- Enhanced wound healing
- Modulation of nociceptive (pain) signaling
- Dual GLP-1/GIP receptor agonists (like tirzepatide) may have additional mechanisms beyond single GLP-1 agonists
- The immunomodulatory effects are mechanistically distinct from the metabolic effects
Narla, Shanthi; Narla, Radhika R; Corbett, John A ·
RPEP-15776 · 2026Early clinical evidence from case reports, small cohorts, and short-duration trials suggests GLP-1 RAs may benefit several dermatologic conditions:
- Psoriasis: reductions in Psoriasis Area and Severity Index (PASI) scores
- Hidradenitis suppurativa (HS): improved disease activity and patient-reported symptoms
- Wound healing: fewer wound complications in retrospective datasets
These effects likely reflect both direct immunomodulation and indirect metabolic benefits (weight loss and reduced systemic inflammation). However, GLP-1 RAs can also cause dermatologic adverse events including pruritus (itching), drug eruptions, alopecia (hair loss), and acne, in addition to systemic side effects like gastrointestinal intolerance and biliary disease.
Narla, Shanthi; Narla, Radhika R ·
RPEP-15778 · 2026Mitochondrial transcription factors (Tfam, Tfb1m, Tfb2m) were significantly reduced in the left ventricle of spontaneously hypertensive rats (SHR) compared to normotensive controls (WKY). TNF-α treatment of H9c2 cardiomyoblasts similarly suppressed these mitochondrial transcription factors.
Angiotensin-(1-7) reversed the TNF-α-mediated repression of all three mitochondrial transcription factors in vitro. The mechanism involved the PGC-1α-YY1 transcriptional complex: TNF-α prevented formation of this complex, allowing YY1 alone to repress mitochondrial transcription factor genes. Ang-(1-7) restored PGC-1α-YY1 complex formation, reactivating transcription. This establishes the PGC-1α-YY1 complex as a molecular switch and Ang-(1-7) as a regulator of cardiac mitochondrial biogenesis under inflammatory conditions.
Natarajan, Bhargavi; Vijayakumar, Anupama; Iyer, Dhanya R; Venkatraman, Janani; Arige, Vikas; Khan, Abrar A; Barthwal, Manoj K; Kontos, Christopher; Mahapatra, Nitish R ·
RPEP-15781 · 2026For semaglutide (both subcutaneous and oral) and tirzepatide, the ED50 ratio (Phase 3 vs Phase 1) for nausea and vomiting was significantly greater than 1, confirming that dose escalation builds genuine physiological tolerance to gastrointestinal side effects.
Across all approved incretin-based medications, a higher ED50 ratio — indicating more tolerance development — was associated with longer drug escalation periods and a greater number of dose-escalation steps. Critically, this tolerance ratio was also significantly associated with larger reductions in HbA1c and body weight, demonstrating that tolerance enables higher therapeutic doses and better clinical outcomes.
Nauck, Michael A; Punov, Viktoria; Kang, Yu Mi; Lim, Soo ·
RPEP-15782 · 2026GLP-1 receptor agonists provide: highly effective glycemic control with low hypoglycemia risk; significant weight loss; reduced major adverse cardiovascular events (heart attack, stroke, cardiovascular death); reduced heart failure hospitalizations; reduced albuminuria and slowed eGFR decline (kidney protection); prevention of type 2 diabetes in obesity; regression of liver steatosis and prevention of fibrosis; and symptomatic improvement in obstructive sleep apnea and knee osteoarthritis.
Next-generation developments include: dual GLP-1-glucagon and GLP-1-amylin agonists; triple GIP-GLP-1-glucagon agonists with greater weight loss potential; small-molecule oral GLP-1 agonists; and exploration of neurodegenerative disease and substance use disorder indications.
Nauck, Michael A; Tuttle, Katherine R; Tschöp, Matthias H; Blüher, Matthias ·
RPEP-15789 · 2026A 13-atom butylaminoalkenyl tether with SS configuration was identified as the most effective i,i+7 ACH staple. Orientation reversal substantially enhanced helicity and this effect transferred across helical registers. The optimized staple conferred significant proteolytic resistance, linking structural preorganization to biochemical resilience.
Nguyen, Ha T N; Lee, Su-Yeon; Tran, Duc V H; Kim, Young-Woo ·
RPEP-15792 · 2026In 10 poisoned patients treated with high-dose insulin, the median elimination half-life of insulin after discontinuation was 1.8 hours (IQR 1.4–4.0 h; range 1.23–9.8 h) — substantially shorter than previously reported values of up to 18.8 hours. The half-life was not significantly affected by insulin dosage, treatment duration, or kidney disease.
C-peptide (a marker of the body's own insulin production) tracked with blood glucose levels despite the high external insulin, and concentrations remained mostly within normal reference ranges, suggesting that glucose supplementation during treatment was not excessive. Hyperinsulinemia typically resolved within 24 hours of stopping high-dose insulin.
Nic Ionmhain, Úna; Coulson, Lori; Roberts, Darren M ·
RPEP-15799 · 2026Among 740,370 type 2 diabetes patients (20,459 matched pairs), GLP-1 receptor agonist users showed no increased risk of developing acute pancreatitis. When pancreatitis did occur, GLP-1 RA users had dramatically better outcomes:
- Complicated pancreatitis: 68% lower risk (HR 0.32, 95% CI 0.14-0.74)
- Parenteral nutrition needs: 72% lower (HR 0.28, 95% CI 0.09-0.83)
- Sepsis: 29% lower (HR 0.71, 95% CI 0.59-0.84)
- Acute kidney injury: 46% lower (HR 0.54, 95% CI 0.49-0.60)
- Shock: 48% lower (HR 0.52, 95% CI 0.36-0.75)
- Mechanical ventilation: 77% lower (HR 0.23, 95% CI 0.16-0.33)
- All-cause mortality: 55% lower (HR 0.45, 95% CI 0.41-0.49)
The trend toward lower uncomplicated pancreatitis risk (HR 0.71) did not reach statistical significance (95% CI 0.49-1.01).
Nieto, Luis M; Martinez, John; Narvaez, Sharon I; Ko, Donghyun; Kim, Do Han; Vega, Kenneth J; Chawla, Saurabh ·
RPEP-15800 · 2026The Charge-Alternating Spherical MLP (CAS-MLP) platform uses a two-layer protection strategy. Structurally, membrane-lytic peptides are grafted onto a poly(disulfide) backbone in a bottlebrush architecture, which protects them from enzymatic breakdown and extends their time in circulation. Chemically, detachable charge-alternating reagents neutralize the peptides' lytic activity during transit, preventing hemolysis and off-target damage.
Activation is sequential: after cancer-targeting ligands guide the nanoparticle into tumor cells, the acidic endosomal environment triggers removal of the charge-alternating shield. Then the reductive cytosol degrades the disulfide backbone, releasing individual active peptides. In vivo testing demonstrated potent tumor growth suppression with negligible side effects, solving the safety problem that has blocked membrane-lytic peptides from clinical use.
Ning, Lubin; Xu, Rui; Qin, Chaoke; Sun, Lei; Shao, Liming; Zhang, Hongrui; Yan, Li; Ren, Gengzhi; Sun, Xiuying; Chang, Hao; Cheng, Xiangdong; Jia, Fie · Animal Study
RPEP-15804 · 2026GLP-1 analogs have demonstrated the ability to reduce substance use in preclinical studies, decreasing alcohol and nicotine consumption in rodents and non-human primates by modifying neurotransmitter activity in brain reward pathways. These medications also showed neuroprotective effects, reducing the oxidative stress and neuroinflammation caused by chronic substance use.
Early clinical trials are beginning to show promise for translating these preclinical findings to humans, though evidence remains preliminary. The review highlights that GLP-1 analogs could address a major unmet need, given the limited success of existing pharmacotherapies for alcohol use disorder and the overall lack of effective treatments for substance use disorders.
Noemi Torres, Isabel; Barroso Alverde, Maria Jimena · Review
RPEP-15806 · 2026At 1 year, GLP-1 RA initiators had 18.5 NAION events per 100,000 people compared to 7.2 per 100,000 among DPP-4 inhibitor initiators. The adjusted risk ratio was 2.56 (95% CI: 1.44-4.86), with an absolute risk difference of 11.3 per 100,000.
The risk was highest during the first 6 months of use and diminished with longer treatment duration. Subgroup analyses showed higher risk in patients under 50 years old, men, ever-smokers, and those with a hemoglobin A1c reduction of 1% or more — suggesting that rapid blood sugar lowering may be a contributing factor.
Noh, Yunha; Yin, Hui; Ben Ghezala, Inès; Yu, Oriana H Y; Suissa, Samy; Azoulay, Laurent ·
RPEP-15809 · 2026The review synthesizes evidence that cathelicidin peptides serve multiple roles in gut-brain communication. In the gut, cathelicidin maintains intestinal barrier integrity, shapes microbiota composition, and regulates innate immune signaling. Gut-derived metabolites including short-chain fatty acids and vitamin D influence cathelicidin expression, creating feedback loops between diet, microbiome, and mucosal defense.
In the CNS, cathelicidin shows a striking functional dichotomy: when produced by neurons, it acts as a neuroprotective modulator, but when delivered by peripheral immune cells infiltrating the brain, it exacerbates glial-mediated inflammation. This context-dependent behavior — where the same peptide can protect or harm depending on its source and local environment — is a key insight for understanding neuroinflammatory disease mechanisms.
Nourizadeh, Mehrdad; Ghahari, Amir Arsalan; Zandi, Ehsan; Rasouli, Seyedeh Zeynab; Davari, Shaghayegh; Hoseinzadeh, Mobina; Nourazar, Mir Alireza ·
RPEP-15819 · 2026Two metabolically stable peptides targeting the gastrin-releasing peptide receptor (GRPR) — [68Ga]Ga-PKB2 and [68Ga]Ga-PKB3 — were successfully labeled with gallium-68 for PET imaging. Both showed high tumor uptake in prostate cancer xenografts (16 ± 3%IA/g and 17 ± 2%IA/g, respectively), fast blood clearance below 0.5%IA/g at 2 hours, and low nanomolar receptor affinity.
[68Ga]Ga-PKB3 showed significantly higher uptake in GRPR-expressing pancreas tissue and lower kidney uptake than PKB2, suggesting a potentially better safety profile. PET/CT images clearly delineated tumors, and both tracers are proposed as diagnostic counterparts to their lutetium-177-labeled therapy versions, forming a theranostic pair.
Obeid, Karim; Bezverkhniaia, Ekaterina; Tolmachev, Vladimir; Orlova, Anna; Kanellopoulos, Panagiotis · Animal
RPEP-15821 · 2026In db/db diabetic mice treated with liraglutide (300 μg/kg/day IP for 2 weeks):
- **Vascular function**: Endothelium-dependent relaxation was significantly improved in mesenteric resistance arteries.
- **Endothelial signaling**: In high-glucose-treated HUVECs, liraglutide restored eNOS phosphorylation (at Ser1177) and nitric oxide production.
- **Gut microbiome**: Diabetes caused marked dysbiosis with reduced alpha diversity and depletion of short-chain fatty acid (SCFA)-producing taxa. Liraglutide substantially restored microbial diversity and enriched beneficial genera including Lachnospiraceae and Lactobacillus.
- **Butyrate connection**: Low-dose butyrate independently enhanced nitric oxide production in endothelial cells, supporting a causal link between microbiome changes and vascular improvement.
Oh, Eun Yi; Suh, Soo Hwan; Byeon, Seonhee; Lee, Jooyong; Lee, Young-Ho; Choi, Soo-Kyoung ·
RPEP-15825 · 2026A patient with slowly progressive type 1 diabetes mellitus (SPIDDM) developed bilateral lower-leg edema and approximately 7 kg of weight gain shortly after starting basal-bolus insulin therapy with insulin aspart and insulin degludec. Cardiac function was normal on echocardiography and B-type natriuretic peptide levels were within the reference range, ruling out heart failure.
The edema resolved rapidly within nine days following modification of the insulin regimen and dietary sodium restriction to 8 g/day of salt, without requiring diuretics. The improvement likely reflected the combined effects of glycemic stabilization, fluid-electrolyte balance, and possible formulation-related factors rather than a direct difference between insulin types.
Okamura, Emi; Harada, Norio; Okuno, Kana; Yamamoto, Kana; Murakami, Takaaki; Ueda, Yohei; Yabe, Daisuke ·
RPEP-15833 · 2026GLP-1 receptor agonists (semaglutide, liraglutide, tirzepatide) showed improvement in patient-reported mental wellbeing across several clinical trials. Initial pharmacovigilance data raised concern about a possible association with suicidality, but subsequent robust cohort studies and meta-analyses have refuted this association.
Compared to other obesity interventions: behavioral interventions showed no harm and modest mental health benefits; bariatric surgery improved depression and anxiety short-to-medium-term but some studies reported increased suicidality after 5 years; other pharmacotherapies (orlistat, bupropion/naltrexone, phentermine/topiramate) showed mixed psychiatric impacts. Overall, most weight loss interventions appear psychologically safe or beneficial.
Osborne, Darin; Abdelgadir, Elamin ·
RPEP-15834 · 2026Researchers successfully grew miniature intestine models (enteroids) from jejunum tissue taken during gastric bypass surgery in people with severe obesity. These enteroids contained functional GLP-1-producing cells and secreted active GLP-1 in response to glucose.
Critically, enteroids from patients with both obesity and type 2 diabetes had a reduced ability to release GLP-1 when exposed to high glucose, compared to enteroids from obese patients without diabetes or with prediabetes. This confirms that the impaired GLP-1 response seen in T2D is an intrinsic defect in the gut's hormone-producing cells, not just a secondary effect of the disease.
Osinski, Céline; Martinez-Oca, Paula; Moret, Dounia; Genser, Laurent; Poitou, Christine; Soula, Hédi Antoine; Clément, Karine; Serradas, Patricia; Ribeiro, Agnès · Human Cells
RPEP-15836 · 2026After propensity score matching: Tirzepatide vs. dulaglutide (9,233 pairs) — tirzepatide had lower modified MACE (IR 31.3 vs 39.4 per 1,000 person-years; HR 0.80, 95% CI 0.65-0.99), driven by 40% lower all-cause mortality (HR 0.60, 95% CI 0.43-0.83). Post hoc analysis showed lower pneumonia hospitalization with tirzepatide vs dulaglutide. Tirzepatide vs. semaglutide (25,266 pairs) — modified MACE rates were similar (IR 23.7 vs 23.2; HR 1.03, 95% CI 0.90-1.17).
Ostrominski, John W; Ortega-Montiel, Janinne; Wexler, Deborah J; Everett, Brendan M; Cromer, Sara J; Byrne, Caroline F; Glynn, Robert J; Paik, Julie M; Patorno, Elisabetta ·