RPEP-11023 · 2025A peptide-based cancer vaccine overcomes immune evasion in nasopharyngeal carcinoma by restoring the cell's antigen presentation machinery. Peptide-trained T cells upregulated NLRC5 (the most downregulated gene in NPC tumors), restored MHC-I expression, and enhanced tumor cell killing — even in cells where NLRC5 had been experimentally knocked down. The vaccine approach was validated in a mouse tumor model, showing consistent restoration of antigen presentation gene expression in vivo.
Gan, Chai Phei; Kok, Sau Yee; Lee, Bernard Kok Bang; Zulaziz, Natasha; Cheong, Sok Ching; Savelyeva, Natalia; Lim, Kue Peng ·
RPEP-11027 · 2025Preclinical: GLP-1RAs reduce neuroinflammation, improve mitochondrial function, and enhance clearance of toxic proteins in both AD and PD models, leading to improved cognition and dopaminergic neuron survival.
Clinical — Parkinson's: Exenatide and lixisenatide demonstrated motor benefits in trials. However, NLY01 (pegylated exendin) did not meet its primary endpoint, showing not all GLP-1RAs perform equally.
Clinical — Alzheimer's: Mixed cognitive outcomes in early trials, but liraglutide preserved cerebral glucose metabolism on FDG-PET scans — an intriguing biological effect suggesting neuroprotection even without clear cognitive benefit.
The EVOKE and EVOKE+ Phase 3 trials with semaglutide are the definitive tests that could establish GLP-1RAs as neurodegenerative disease treatments.
Gandhi, Ayush; Parhizgar, Alireza ·
RPEP-11028 · 2025In 154 antipsychotic-treated schizophrenia patients with prediabetes and obesity, semaglutide (up to 1.0 mg/week for 30 weeks) versus placebo:
- HbA1c reduced by 0.46% (95% CI -0.56 to -0.36)
- Body weight reduced by 9.21 kg (95% CI -11.68 to -6.75)
- 81% vs 19% achieved HbA1c <5.7% (prediabetes reversal, p<0.001)
- HDL cholesterol improved by 10.81 mg/dL (p=0.007)
- Triglycerides improved by -29.20 mg/dL (p=0.03)
- Physical quality of life improved by 3.75 points on SF-36v2 (p=0.001)
- No significant effect on PANSS-6 schizophrenia symptom score or mental QoL
- 96% completion rate in semaglutide group vs 87% in placebo
- GI symptoms more common with semaglutide; serious adverse events similar between groups
Ganeshalingam, Ashok A; Uhrenholt, Nicolai; Arnfred, Sidse; Gæde, Peter; Düring, Signe; Stenager, Elsebeth N; Bünger, Nick; Pedersen, Andreas K; Bilenberg, Niels; Frystyk, Jan ·
RPEP-11030 · 2025Over 24 months of erenumab treatment in 173 patients (84.9% female, mean age 44.2, 45.7% chronic migraine), significant improvements were observed across all measures (all p < 0.001):
- Monthly migraine days: decreased by 8.8 ± 7.6 (from 16.5 baseline)
- HIT-6 headache impact: decreased by 8.1 ± 8.6 (from 65.9 baseline)
- mMIDAS disability: decreased by 16.6 ± 21.2
- Monthly acute medication days: decreased by 5.2 ± 6.8 (from 11.5 baseline)
- IMPAC family burden: decreased by 6.5 ± 6.6
48.6% had at least one adverse event, 35.3% had drug-related adverse events, but no serious adverse events were attributed to erenumab.
Gantenbein, Andreas R; Kamm, Christian P; Schankin, Christoph J; Zecca, Chiara; Zieglgänsberger, Dominik; Pohl, Heiko; Ryvlin, Philippe; Agosti, Reto; Viceic, Dragana; Parzini, Catherine; Kulartz-Schank, Monika; Arzt, Michael E ·
RPEP-11032 · 2025Heart failure patients with depression (Hamilton Depression Scale score ≥17) showed significantly worse cardiac parameters compared to non-depressed patients:
- Left ventricular ejection fraction: 42.3% ± 6.7% vs 51.6% ± 5.9% (depressed vs non-depressed)
- B-type natriuretic peptide: 1,256 ± 345 pg/mL vs 756 ± 234 pg/mL — a 66% higher level in depressed patients
- Angiotensin II: 86.4 ± 15.7 ng/mL vs 62.5 ± 12.3 ng/mL — a 38% higher level
- TNF-α: 42.5 ± 7.6 pg/mL vs 28.3 ± 5.4 pg/mL
- IL-6 was also significantly elevated in the depressed cohort
These findings suggest depression accelerates cardiac remodeling and left ventricular dysfunction through inflammatory cascades and neuroendocrine overactivation.
Gao, Bo; Gao, Yun-Fan; Chu, Meng-Ting; Yuan, Ke-Fang ·
RPEP-11033 · 2025After 12 weeks, the BBr60 group showed significantly increased fecal butyrate levels (p < 0.001), which correlated with increased GLP-1 and IL-27 levels. Multiple metabolic peptide hormones were significantly elevated in the probiotic group: leptin, adiponectin, C-peptide, pancreatic polypeptide, peptide YY, GIP, and GLP-1 (all p < 0.05). HOMA-IR (insulin resistance) was significantly reduced (p < 0.05).
The anti-inflammatory cytokine IL-27 was upregulated (p < 0.01) while the pro-inflammatory IL-1β was decreased (p < 0.05). In the placebo group, only C-peptide, pancreatic polypeptide, and GIP increased, with no changes in leptin, adiponectin, PYY, GLP-1, or HOMA-IR. Butyrate levels positively correlated with GLP-1 and IL-27, and negatively with IL-1β.
Gao, Dejiao; Dong, Yao; Jia, Zhumin; Bian, Chenying; Zhu, Jianguo; Wu, Ying; Fang, Shuguang; Gu, Shaobin ·
RPEP-11039 · 2025BACE1 was identified as an enzyme that cleaves α-Klotho peptide 951-981 at the F-T residues, confirmed by Coomassie blue staining, western blot, and MALDI-TOF mass spectrometry. When F-T was mutated to K-K, BACE1 could not cleave the peptide, confirming site specificity. Plasma α-Klotho was significantly lower in elderly vs. young participants (p<0.0001). In elderly adults, BACE1 and α-Klotho showed a significant positive correlation (p=0.009, r=0.469) not seen in young adults (p=0.170, r=-0.208), suggesting the BACE1/α-Klotho pathway becomes functionally relevant with aging.
Gao, Xiang; Sun, Zuoli; Hu, Jia; Li, Yuhong; Deng, Qi; Li, Rena ·
RPEP-11043 · 2025Weight loss on semaglutide plateaus at approximately 53 weeks (about 12 months) of treatment, with patients losing an average of 16% body weight. This plateau deviated from the greatest on-treatment weight loss by only 2%, suggesting stable weight is achieved around the 8–12 month mark — the point at which body contouring surgery may be appropriate.
However, the review also found a major concern: after stopping semaglutide, patients regained 62.7% to 74.3% of their greatest on-treatment weight loss. Weight recurrence (defined as regaining ≥25% of lost weight) occurred as early as 12 weeks after discontinuation. This massive weight regain raises serious questions about the durability of surgical outcomes if patients stop the drug after body contouring.
Garbaccio, Noelle C; Smith, Jade E; Posso, Agustin; Schonebaum, Dorien I; Foster, Lacey; Cordero, Justin J; Foppiani, Jose; Alvarez, Angelica Hernandez; Choudry, Umar; Lin, Samuel J · Systematic Review
RPEP-11054 · 2025At 24-month follow-up, GLP-1 receptor agonist users had significantly reduced all-cause mortality compared to SGLT-2 inhibitor users (OR 0.83, 95% CI: 0.80-0.87), representing a 17% relative reduction.
However, GLP-1RA users had higher odds of gastroparesis (aOR 1.24, 95% CI: 1.11-1.38) and gastroesophageal reflux disease (aOR 1.14, 95% CI: 1.11-1.18). Notably, the risk of acute pancreatitis was lower in the GLP-1RA group, alleviating a longstanding safety concern for this drug class.
Garg, Samita; Qapaja, Thabet; Hamid, Osama; Kaya, Gizem; Abdel-Razeq, Rashid; Alayan, Dina; Abu-Rumaileh, Mohammed; Lembo, Anthony; Nissen, Steven ·
RPEP-11056 · 2025Over 21 months, 84 overweight/obese adults with type 1 diabetes using tirzepatide off-label lost an average of 59 pounds (23.4% body weight), while matched controls gained 1.7 pounds. HbA1c dropped 0.50% more in tirzepatide users versus controls. Beyond weight and blood sugar, tirzepatide significantly improved total cholesterol, LDL, triglycerides, systolic blood pressure, and preserved kidney function (eGFR).
Remarkably, the cardiovascular and kidney benefits remained statistically significant even after adjusting for weight loss and HbA1c changes — suggesting tirzepatide has direct protective effects on the heart and kidneys independent of its metabolic benefits. Controls saw significant eGFR decline over the same period.
Garg, Satish K; Kaur, Gurleen; Renner, Drew; Lanning, Monica S; Mason, Emma; Beatson, Christie; Ciesco, Kelly; Snell-Bergeon, Janet · Observational
RPEP-11058 · 2025Estradiol-treated ovariectomized rats showed reduced VPAC2 receptor mRNA in the PVN. VIP-induced appetite suppression was completely blocked by estradiol, while PACAP still reduced food intake in both estrogen-treated and untreated groups. VIP-induced cell activation in the ARC and PVN was blocked by estradiol, but PACAP still activated ARC cells in both groups (PVN activation was blocked only in estrogen-treated rats). VIP increased plasma glucose in both groups; PACAP increased glucose only without estrogen. VIP decreased free fatty acids only with estrogen present.
Garnica-Siqueira, Marcela Cristina; Martins, Andressa Busetti; Monteiro, Érica Cristina Alves Munhoz; Oliveira, Maria Heloisa Bernardes de; Baratto, Carolina Dos Reis; Tsutsui, Fabiano Takeo Komay; Oliveira, Lucas Leonardo França de; Stopa, Larissa Rugila Dos Santos; Souza, Camila Franciele de; Wunderlich, Ana Luiza Machado; Zaia, Dimas Augusto Morozin; Leite, Cristiane Mota; Zaia, Cássia Thaïs Bussamra Vieira; Uchoa, Ernane Torres ·
RPEP-11059 · 2025Sequential hydrolysis with pepsin and trypsin (PTH) produced the most bioactive peptides, showing ABTS radical inhibition above 90% and DPPH radical scavenging of 75–85%. ACE inhibitory activity was exceptional: red worm hydrolysate (RWPH) achieved an IC50 of 0.017 μg/mL — about sixfold more potent than enalapril (IC50 = 0.11 μg/mL). White worm hydrolysate (WWPH) had an IC50 of 0.35 μg/mL.
SDS-PAGE analysis revealed the active peptides were low molecular weight (<10 kDa, primarily 5–9 kDa). Red worm peptides showed low Hill coefficients, indicating gradual and sustained interaction with the ACE enzyme rather than an abrupt on-off binding — a pharmacologically favorable property.
Garrido-Ortiz, Eduardo R; Morales-Camacho, Jocksan I ·
RPEP-11064 · 2025Among 7,881 patients (6,109 on semaglutide, 1,772 on tirzepatide), the mean percentage weight reduction at 1 year was 8.7% overall. Results varied dramatically by discontinuation status:
- Non-discontinuation: 11.9% weight loss (SD 9.2%)
- Late discontinuation (3-12 months): 6.8% weight loss (SD 9.1%)
- Early discontinuation (within 3 months): 3.6% weight loss (SD 8.1%)
All differences were statistically significant (p < 0.001). For patients with prediabetes, glycated hemoglobin (HbA1c) reductions followed the same pattern: 0.4% for continuers, 0.2% for late discontinuers, and 0.1% for early discontinuers. Notably, 80.8% of patients had low maintenance dosages, suggesting most patients were not on the maximum approved doses used in clinical trials.
Gasoyan, Hamlet; Butsch, W Scott; Schulte, Rebecca; Casacchia, Nicholas J; Le, Phuc; Boyer, Christopher B; Griebeler, Marcio L; Burguera, Bartolome; Rothberg, Michael B ·
RPEP-11070 · 2025An Amoc-capped dipeptide co-assembled with β-cyclodextrin under physiological conditions (pH 7.4, 37°C) to form a self-supporting hydrogel with entangled nanofibrillar networks.
The hydrogel demonstrated:
- Inherent antibacterial activity against Gram-positive bacteria Bacillus subtilis and Staphylococcus aureus
- Mechanism of killing: aggregation-induced membrane permeabilization and rupture (confirmed by SEM)
- Shear-thinning behavior enabling easy application
- Biocompatibility with HEK293 and AGS cell lines
- In vivo wound healing confirmed by digital photography and histopathological analysis
- Anti-inflammatory activity via reduction of nitrite levels during healing
Gavel, Pramod K; Rit, Tanmay; Bagde, Pranit Hemant; Parmar, Hamendra S; Jha, Hem Chandra; Das, Apurba K ·
RPEP-11073 · 2025The shortest proteolytic fragment (L3, sequence HPDK) of the MUC7-derived peptide formed the most thermodynamically stable complexes with both Cu(II) and Zn(II) ions and exhibited the strongest antimicrobial activity among all tested sequences. This activity was pH-dependent, consistent with a "nutritional immunity" mechanism where the peptide starves microbes of essential metal ions.
The finding that natural enzymatic cleavage enhances rather than destroys the peptide's function challenges the assumption that proteolysis is purely degradative, suggesting an evolutionary advantage to peptide fragmentation.
Gawłowski, Jakub; Ślusarczyk, Anna; Szarszoń, Klaudia; Zobi, Fabio; Janek, Tomasz; Wątły, Joanna ·
RPEP-11075 · 2025Using 19F-NMR spectroscopy with fluorine probes placed at five positions along Substance P (positions 0, 3, 5, 7, and 8), researchers found that the C-terminal hexapeptide segment is rigidly anchored within NK1R's orthosteric binding pocket, while the N-terminal pentapeptide segment remains flexible and solvent-exposed when bound. Critically, transient interactions between the side chains of Lys3 and Gln5 in Substance P with sites on NK1R significantly impact the peptide's functional potency, as confirmed by cAMP function assays. This reveals that dynamic, short-lived molecular contacts — invisible to static structural methods like cryo-EM — play important roles in peptide-receptor signaling.
Ge, Haoyi; Yang, Lingyun; Chen, Changran; Xu, Yuxin; Liu, Dongsheng; Wüthrich, Kurt ·
RPEP-11076 · 2025GPR40 in hypothalamic AgRP neurons is a novel pathway regulating dietary fat preference. AgRP-specific Gpr40 knockout mice showed reduced fat preference and increased carbohydrate intake. This was not related to behavioral abnormalities. After starvation, knockout mice had diminished metabolic state, increased AgRP neuronal activity, and elevated AgRP and NPY peptide levels, yet reduced fat intake. Inhibiting AgRP neuronal activity in knockout mice rescued fat preference, confirming that GPR40's effects are mediated through neuronal activity modulation. This pathway was specific to AgRP neurons — POMC neurons were not involved.
Ge, Yueping; Zhan, Huidong; Wu, Shanshan; Wang, Jing; Xu, Yang; Liang, Yixiao; Peng, Li; Gao, Ling; Zhao, Jiajun; He, Zhao ·
RPEP-11079 · 2025Researchers engineered the probiotic yeast Saccharomyces boulardii to produce cell-penetrating peptides (CPPs) directly inside the gut, enhancing intestinal absorption of large molecules. Four different CPPs were integrated into the yeast's chromosome: RRL helix, Shuffle, Penetramax, and PN159. In cell culture (Caco-2 model), three of the four CPP-producing strains increased intestinal permeability without causing permanent damage to the gut lining.
In live mice, the PN159-producing yeast strain significantly increased FITC-dextran (a model macromolecule) absorption into the bloodstream over 10 days — without causing gut inflammation. This is the first demonstration that an engineered microorganism can modulate host intestinal permeability to improve macromolecule absorption.
Gelli, Hitesh P; Hedin, Karl Alex; Laursen, Martin F; Uribe, Ruben-Vazquez; Sommer, Morten Otto Alexander · In Vivo
RPEP-11080 · 2025A 13-amino-acid peptide (KD) derived from human semenogelin I self-assembled into a pH-responsive hydrogel whose mechanical properties were tuned by histidine protonation state changes. As pH drifted during assembly, histidine's charge changed, driving the peptide from solution into β-sheet fibrils that formed a hydrogel network.
Cryo-TEM revealed two distinct nanostructures — fibrils and twisted curly nanostructures — that evolved over time. The elastic modulus increased substantially with pH shift, and under buffered conditions the peptide formed hydrogels within the experimental dead time (near-instantaneously). The mechanism centers on charge regulation of a single histidine residue controlling the entire self-assembly process.
Gentile, Luigi; Frohm, Birgitta; Malmendal, Anders; Åkerfeldt, Karin S; Olsson, Ulf; Linse, Sara ·
RPEP-11085 · 2025Tirzepatide's dual GIP/GLP-1 receptor agonism addresses multiple pathophysiological pathways simultaneously: insulin resistance, chronic inflammation, and oxidative stress. Clinical and preclinical data support therapeutic potential across type 2 diabetes, obesity, cardiovascular health, metabolic-associated fatty liver disease (MAFLD), chronic kidney disease (CKD), and neurological disorders including Alzheimer's and Parkinson's diseases.
The review synthesizes evidence showing tirzepatide's efficacy in Asian populations specifically, addressing a gap in the literature since this demographic is frequently underrepresented in global clinical trials despite high rates of metabolic disease.
Ghaleb, Joya; Khouzami, Katy Kaleen; Nassif, Nicolas; Attieh, Philippe; Ajlani, Mohammad Feras Al; Sleiman, Jana Bou; Khalouf, Ali; Harb, Frederic; Azar, Sami; Kannan, Amjad; Ghadieh, Hilda E ·
RPEP-11095 · 2025In 179 Indian patients with type 2 diabetes and obesity (mean BMI ~29.8 kg/m²), biosimilar liraglutide and reference liraglutide both produced significant weight loss over 24 weeks. The biosimilar group lost 5.5 ± 1.2 kg (7.3% body weight) while the reference group lost 7.1 ± 2.6 kg (8.9% body weight). Crucially, the difference between groups was not statistically significant (p = 0.71), confirming non-inferiority.
Glycemic parameters also improved significantly in both arms: HbA1c (p = 0.89 between groups), fasting plasma glucose (p = 0.43), and postprandial glucose (p = 0.17) were all comparable at week 24, with no meaningful advantage for either formulation.
Ghosh, Sujoy; Sethi, Bipin; Kalra, Sanjay; Baruah, Manash P; Mane, Abhishek; Choudhari, Sanjay; Petare, Anup; Jadhav, Mayur; Patil, Saiprasad; Barkate, Hanmant ·
RPEP-11097 · 2025Across two major US claims databases, 22,334 non-diabetic adults initiated tirzepatide between May 2021 and September 2023. Over 70% of users in both databases had at least one obesity-related complication (hypertension, dyslipidemia, or prediabetes). Most started at the 2.5 mg dose, with the most common doses at the sixth fill being 5 mg and 7.5 mg. Six-month persistence ranged from 60.6% to 75.7%, exceeding rates previously reported for GLP-1 receptor agonists. Among those who discontinued, 10-20% restarted during follow-up.
Gibble, Theresa Hunter; Hankosky, Emily R; Meeks, Alexandra; Liao, Birong; Ward, Jennifer; Huang, Ahong; Chinthammit, Chanadda ·
RPEP-11101 · 2025Thirteen women with severe obesity (BMI 47.6 ± 5.6) underwent exercise sessions before and 3 months after Roux-en-Y gastric bypass:
Pre-surgery: No significant GLP-1 or PYY changes with post-meal exercise (all P>0.05)
Post-surgery:
- GLP-1 increased immediately (P=0.0180) and 30 min after exercise (P=0.0380); AUC rose from 2.3 to 14.5 pg/mL×min (P=0.0075) — a 6.3-fold increase
- PYY increased immediately (P=0.0020) and 30 min after exercise (P=0.0360); AUC rose from 9.9 to 224.2 pg/mL×min (P=0.0004) — a 22.6-fold increase
- Insulin AUC decreased (60.7 to 26.3 µU/mL×min; P=0.0457), indicating improved insulin sensitivity
- PP and GIP AUC decreased post-surgery
- Ghrelin levels and inflammatory markers were unchanged
Gil, Saulo; Murai, Igor Hisashi; Dantas, Wagner S; Merege-Filho, Carlos Alberto Abujabra; Leitão, Alice Erwig; Nicoletti, Carolina Ferreira; Lima, Alisson Padilha de; Benatti, Fabiana; Cleva, Roberto de; Santo, Marco Aurélio; Kirwan, John P; Gualano, Bruno; Roschel, Hamilton ·
RPEP-11103 · 2025Aqueous remote loading of leuprolide into PLGA-COOH microspheres achieved ~9.8% drug loading with initial encapsulation efficiency of ~38%. Optimization revealed that high microsphere concentrations (180-240 mg/mL) strongly improved encapsulation efficiency, with quasi-equilibrium reached within 8 hours. Porosity (controlled by inner water phase volume, 0-350 μL) ranged from 38-60%, with minimal initial burst at low porosity. Drug loading and EE were not strongly affected above 50% porosity.
A theoretical framework was derived showing that encapsulation efficiency depends on binding strength/capacity, polymer water content, and initial polymer concentration, while loading additionally depends on peptide/polymer mass ratio.
Giles, Morgan B; Walker, Jennifer; Schwendeman, Steven P ·
RPEP-11105 · 2025Exenatide extended-release did not significantly affect diabetic remission duration compared to placebo (exenatide: 662 days [28-735] vs placebo: 669 days [121-721], p=0.9). Only 3 of 22 cats relapsed during the 2-year study — 1 on placebo (day 212) and 2 on exenatide (days 553 and 558).
However, exenatide did maintain glycemic control: HbA1c remained stable in the exenatide group (-0.05%) but increased significantly in the placebo group (+2.3%, p=0.03). Both groups lost weight during the study. The low relapse rate overall suggests that active management with low-carbohydrate diets and weight control may itself be important for maintaining remission.
Gilor, Chen; Fleeman, Linda M; Hulsebosch, Sean E; Niessen, Stijn J M; Bjørnvad, Charlotte R; Pires, Jully; Hazuchova, Katarina; Mott, Jocelyn; O'Kell, Allison L; Gostelow, Ruth; Rudinsky, Adam J; Cook, Audrey K ·
RPEP-11123 · 2025Systematic mapping of 280 quorum sensing interactions across 21 staphylococcal species revealed substantial differences in inhibitory potencies between human- and animal-associated species. Six new autoinducing peptides (RiPPs) were identified.
S. simulans AIPs showed strong potential as QS inhibitors and were used as a starting point for structure-activity relationship optimization, yielding the most potent inhibitors reported to date for S. epidermidis and S. lugdunensis. An S. simulans AIP showed no evidence of acquired suppression of its inhibitory effect in resistance testing. A peptide inhibitor successfully attenuated MRSA skin infection in a mouse model, demonstrating in vivo anti-virulence activity.
Gless, Bengt H; Sereika-Bejder, Benjamin S; Jensen, Iben; Bojer, Martin S; Tsiko, Katerina; Schmied, Sabrina H; Vitolo, Ludovica; Toledo-Silva, Bruno; De Vliegher, Sarne; Ingmer, Hanne; Olsen, Christian A ·
RPEP-11131 · 2025Across 38 included studies, GLP-1 receptor agonists demonstrated notable impacts on gut microbiota composition, richness, and diversity:
- **Liraglutide**: Promoted growth of beneficial genera with metabolic functions
- **Exenatide/Exendin-4**: Increased metabolism-associated genera in animals, but mixed results in humans with some pro-inflammatory genera also increasing
- **Dulaglutide**: Significantly increased Bacteroides, Akkermansia, and Ruminococcus — genera associated with improved metabolic profiles
- **Semaglutide**: Increased Akkermansia muciniphila (positive metabolic functions) but decreased overall microbial diversity; results varied considerably across studies due to population differences and study duration
Gofron, Krzysztof Ksawery; Wasilewski, Andrzej; Małgorzewicz, Sylwia ·
RPEP-11136 · 2025Preoperative GLP-1 receptor agonist use was associated with a significant reduction in median postoperative length of stay: 3 days vs 4 days (p=0.036). This effect was particularly pronounced among patients undergoing lumbar fusion.
No significant differences were observed between GLP-1RA users and controls in operating room time, 90-day reoperation rates, 90-day readmission rates, or nonroutine discharge rates, suggesting that GLP-1RA use did not negatively impact other surgical outcomes.
Goldman, Samuel N; Mani, Kyle; Scharfenberger, Thomas; Kleinbart, Emily; Hui, Aaron T; De la Garza Ramos, Rafael; Fourman, Mitchell S; Eleswarapu, Ananth S ·
RPEP-11146 · 2025GLP-1 receptor agonists have expanded far beyond their original diabetes/obesity indications. The review identifies four key molecular mechanisms underlying their multi-organ effects: immune/inflammatory pathway modulation, autophagy and pyroptosis regulation, endoplasmic reticulum stress alleviation, and gut microbiome interaction.
Clinical evidence now supports cardiovascular and renal protection (with regulatory approvals). Emerging data suggests potential benefits in liver disease, obstructive sleep apnea, chronic respiratory disorders, neurodegenerative diseases, psychiatric conditions, reproductive dysfunction, obesity-associated cancers, and sepsis — though these applications remain investigational.
Gong, Bing; Li, Couwen; Shi, Zhuang'e; Wang, FuPing; Dai, Ruanxian; Chen, Guobing; Su, Heng ·
RPEP-11150 · 2025Across 6 studies (5 RCTs, 1 cohort; n=4,043), GLP-1RAs reduced the composite of all-cause mortality and HF hospitalization by 27% (HR 0.73; 95% CI: 0.60-0.90; I²=0%). HF hospitalizations alone were reduced by 43% (HR 0.57; 95% CI: 0.32-1.00). All-cause mortality alone was not significantly reduced (HR 0.81; 95% CI: 0.58-1.14). Subgroup analysis showed greater benefits in patients with atrial fibrillation. Five studies evaluated semaglutide and one tirzepatide. RCTs showed low risk of bias.
Gonzales-Uribe, Antony; Ruiz-Cortez, Renato; Collantes-Silva, Nicole; Olivero, Lorenzo; Agarwal, Raksheeth; Arambulo-Castillo, Sebastian; Garcia-Geng, Alonso; Lyu, Xiajie; Mendoza-Quispe, Daniel; Becerra-Gonzales, Victor; Butrous, Hoda ·
RPEP-11152 · 2025Transcriptomic analysis of rapamycin-treated arthritic mice identified neuropeptide Y (NPY) as a differentially expressed gene connecting senescence and inflammation pathways. Rapamycin reduced NPY protein levels along with TNF and the senescence marker β-galactosidase, and also modulated NPY receptor expression (NPY1R, NPY2R) and autophagy genes (Sirt1, Sirt6, Lc3b).
In vitro validation showed that silencing NPY in fibroblast-like synoviocytes (the cells lining arthritic joints) significantly reduced expression of three major inflammatory cytokines — TNF-α, IL-1β, and IL-6 — which are the hallmarks of the senescence-associated secretory phenotype (SASP). NPY silencing also downregulated its own receptors and increased Sirt1 expression, a longevity-associated gene.
González-Chávez, Susana Aideé; Chaparro-Barrera, Eduardo; Loya-Rivera, Mario; Rodríguez-Castillo, Alejandra Jazmín; Prieto-Carrasco, Rodrigo; Aguilera, Renato J; Betancourt, Ana P; Mohl, Jonathon E; Ruizesparza-Hinojos, Daniel Alberto; Ramírez-Pérez, Sergio de Jesús; Bermúdez, Mercedes; Pacheco-Tena, César ·
RPEP-11153 · 2025Adding a histidine tag (His-tag) to pro-apoptotic peptides improved their ability to enter cancer cells in laboratory tests. The KLAK-H peptide showed the strongest anticancer effect against A-549 lung cancer cells, with an IC50 of 33.3 µM, while the EGFR-targeted version NRPD-KLAK-H had an IC50 of 40.9 µM.
Both KLAK-H and NRPD-KLAK-H successfully entered cancer cells (confirmed by immunofluorescence) and induced apoptosis (confirmed by TUNEL assays). However, the CTMP4-based peptides showed poor cellular uptake regardless of targeting modifications.
Interestingly, the EGFR-targeting component (NRPD) did not enhance the anticancer effect as expected — the simpler His-tagged KLAK peptide actually performed slightly better than the targeted version. This suggests that short poly-histidine sequences alone can meaningfully improve cellular uptake of pro-apoptotic peptides.
González-Cruz, Aldo O; Pérez-Trujillo, José Juan; Balderas-Rentería, Isaías; Villa-Cedillo, Sheila Adela; De-León-Covarrubias, Ulises Edgardo; Arredondo-Espinoza, Eder · In Vitro
RPEP-11160 · 2025The near-chromosomal genome assembly of D. vulnerans identified 115 gene loci encoding polypeptide venom toxins, including multigene families and single-copy genes. A gene cluster on chromosome 7 encodes both pain-causing venom peptides and cecropin family antimicrobial peptides.
Key peptide characterization:
- Dv13 (trace component, cecropin-like): potently inhibited Gram-negative bacteria and fungi but only weakly permeabilized mammalian neuronal membranes (EC50 >100 µM)
- Dv11 and Dv12 (abundant in venom, sequence-divergent): potently disrupted mammalian neuronal membranes (EC50 as low as 190 nM — over 500-fold more potent than Dv13) but had reduced antimicrobial activity
Positive selection analysis confirmed strong evolutionary pressure driving the functional transition from immune defense to pain induction.
Goudarzi, Mohaddeseh H; Robinson, Samuel D; Cardoso, Fernanda C; Suryamohan, Kushal; Lawrence, Nicole; Eagles, David A; Hoang, Huy N; Vetter, Irina; Fairlie, David P; Seshagiri, Somasekar; King, Glenn F; Walker, Andrew A ·
RPEP-11161 · 2025Across the SURMOUNT-1, SURMOUNT-3, and SURMOUNT-4 trials (N=3,782), participants with early-onset obesity (diagnosed before age 25) had distinct baseline profiles compared to later-onset obesity: higher BMI (40 vs. 37 kg/m²), larger waist circumference (118 vs. 112 cm), longer obesity duration (20 vs. 11 years), but paradoxically lower HbA1c (5.48% vs. 5.60%), triglycerides (120 vs. 130 mg/dL), and systolic blood pressure (121 vs. 125 mmHg).
Despite these baseline differences, tirzepatide treatment produced remarkably similar outcomes in both groups at 72 weeks: body weight reduction (-23% vs. -22%), waist circumference reduction (-22 vs. -19 cm), HbA1c improvement (-0.51% vs. -0.52%), triglyceride reduction (-32% vs. -31%), and systolic blood pressure reduction (-8 vs. -8 mmHg). These consistent results were replicated across all three SURMOUNT trials.
Gourgari, Evgenia; Srivastava, Gitanjali; Kelly, Aaron S; Mojdami, Donna; Cao, Dachuang; Murphy, Madhumita A; Karanikas, Chrisanthi A; Lee, Clare J ·
RPEP-11166 · 2025OB1111 demonstrated triple-action activity against P. aeruginosa strains PA14 (highly virulent) and PAO1 (moderately virulent):
- Anti-planktonic: Effective inhibitory and bactericidal activity against both strains under standard testing conditions
- Anti-biofilm: Killed bacteria within biofilms; reduced early biofilm attachment at sublethal concentrations
- Anti-virulence: Reduced pyoverdine production (a key virulence factor) under host-mimicking conditions at sublethal doses
- SEM showed membrane deformation and disintegration in both planktonic and biofilm states
- PAO1 biofilms showed somewhat reduced susceptibility compared to PA14 biofilms at sublethal concentrations
- Sublethal doses gradually reduced planktonic growth but showed less efficacy against established biofilms
Grace, Amber; Forte, Othreniel; Sipowe, Aguy; Tadjuidje, Vanella; Sahu, Rajnish; Owen, Donald R; Dennis, Vida A ·
RPEP-11169 · 2025Among 143 GLP-1 RA users in the 319-participant randomized trial:
- HbA1c decreased 0.8% from baseline (8.0 ± 1.2%) with AID, representing a 0.5% improvement vs. CGM group (95% CI: -0.8 to -0.3, p < 0.001)
- Time-in-range (70-180 mg/dL) and hyperglycemia metrics showed statistically significant improvements
- No significant weight difference with AID vs. CGM in GLP-1 users (+0.9 kg, 95% CI: -0.2 to 2.1, p = 0.10)
- In contrast, GLP-1 non-users gained 1.9 kg with AID vs. CGM (95% CI: 0.5 to 3.2, p = 0.007)
- Insulin use was simultaneously reduced alongside glycemic improvements
The combination of improved blood sugar control, reduced insulin requirements, and weight neutrality demonstrates clear additive benefits of combining AID with GLP-1 therapy.
Graham, Timothy E; Raghinaru, Dan; Afreen, Samina; Ahmann, Andrew; Haidar, Ahmad; Raskin, Philip; Tsoukas, Michael A; Lum, John W; Sasson-Katchalski, Ravid; Pinsker, Jordan E; Beck, Roy W ·
RPEP-11170 · 2025In 68 liver transplant recipients with diabetes, GLP-1 receptor agonist therapy added to metformin or insulin significantly reduced fasting glucose, HbA1c, weight, BMI, waist circumference, and total/LDL cholesterol over 18 months. Liver stiffness decreased during the first 6 months. Among 45 patients on insulin at baseline, 33.2% stopped insulin by 6 months and 45.5% by 18 months. Adverse events were low: 26.9% mild nausea, 7.69% discontinued due to GI intolerance. No pancreatitis episodes occurred despite concurrent calcineurin inhibitors, and no immunosuppressant adjustments were needed.
Grancini, Valeria; Cogliati, Irene; Alicandro, Gianfranco; Oliverio, Andreina; Di Benedetto, Clara; Gaglio, Alessia; Lampertico, Pietro; Resi, Veronica; Orsi, Emanuela ·
RPEP-11173 · 2025Among 966 patients prescribed liraglutide via a DTC telemedicine platform:
- 85.6% reported weight loss >2 kg after 50 days, with an average loss of 4.9 kg
- 94.1% adhered to the prescribed regimen
- 39.8% reported adverse events, primarily gastrointestinal
- 86.4% expressed desire to continue treatment despite side effects
- 46.6% had a baseline BMI between 30 and 34.4 kg/m²
- 88.9% were GLP-1 RA-naive (first time using these drugs)
- 70% had long-standing obesity
Gratzke, Monika; von Bueren, Johannes; Garrahy, Edward; Calewaert, Bart; Abeck, Finn; Wuelfing, Christian ·
RPEP-11174 · 2025GLP-1 receptor agonists appear to reduce the intestinal inflammatory burden through two main mechanisms: enhancing intestinal epithelial barrier function (the gut lining's ability to keep harmful substances out) and modulating the gut microbiota composition.
The review also addresses practical considerations including the safety profile of GLP-1 RAs in IBD patients, their impact on bowel preparation for endoscopic procedures (colonoscopies), and their effectiveness for managing the metabolic comorbidities (obesity, diabetes) that commonly accompany IBD. However, the evidence base consists primarily of preclinical studies and early clinical observations rather than definitive trials.
Gravina, Antonietta Gerarda; Pellegrino, Raffaele; Izzo, Michele; De Costanzo, Ilaria; Imperio, Giuseppe; Landa, Fabio; Tambaro, Assunta; Federico, Alessandro ·
RPEP-11178 · 2025Semaglutide significantly improved sperm morphology in obese men with type 2 diabetes and functional hypogonadism, while testosterone replacement therapy (TRT) significantly decreased sperm concentration and total count.
In the semaglutide group, morphologically normal sperm doubled from 2% to 4% (p=0.012). Compared to TRT, the semaglutide group had significantly higher normal sperm count, sperm concentration, and total sperm number after 24 weeks. Both treatments increased total testosterone and improved hypogonadism symptoms, but only TRT improved erectile function scores.
Gregorič, Nadan; Šikonja, Jaka; Janež, Andrej; Jensterle, Mojca · Randomized Open Label Trial
RPEP-11188 · 2025Using yeast surface display and directed evolution, the team identified and optimized peptide mimotopes that bind to FMC63 — the antibody fragment used in clinical CD19 CAR-T products. These peptides were coupled to a lymph node-targeting amphiphilic PEG-lipid carrier (amph-vax) to create a vaccine-like booster.
In both syngeneic and humanized mouse models of B-acute lymphoblastic leukemia/lymphoma, the optimized amph-vax boosters triggered marked expansion and memory development of CD19 CAR-T cells. Mice receiving the peptide vaccine booster showed enhanced control of disease progression compared to those treated with CAR-T cells alone. The approach is designed to be generalizable to any CAR-T cell product.
Grzywa, Tomasz M; Neeser, Alexandra; Ramasubramanian, Ranjani; Romanov, Anna; Tannir, Ryan; Mehta, Naveen K; Cossette, Benjamin; Morgan, Duncan M; Goncalves, Beatriz; Sukaj, Ina; Bergaggio, Elisa; Kadauke, Stephan; Myers, Regina M; Paruzzo, Luca; Ghilardi, Guido; Cozzone, Austin; Schuster, Stephen J; Frey, Noelle; Zhang, Libin; Yousefpour, Parisa; Abraham, Wuhbet; Suh, Heikyung; Ruella, Marco; Grupp, Stephan A; Chiarle, Roberto; Wittrup, K Dane; Ma, Leyuan; Irvine, Darrell J ·
RPEP-11192 · 2025RGD-TAT peptides replaced conventional magnesium ions for DNA nanostructure self-assembly while adding cancer targeting and cell penetration capabilities. The peptide/DNA nanostructures demonstrated high membrane penetration, integrin-mediated cancer cell targeting, and lysosome escape. Using protease-resistant D-type peptides significantly enhanced structural and serum stability.
In a mouse tumor model, the NTD-RGD-TAT-DOX-siKRAS nanotube showed excellent tumor accumulation and anti-cancer effects by simultaneously delivering doxorubicin and suppressing KRAS oncogene expression, combining chemotherapy with gene therapy in a single platform.
Gu, Peng-Cheng; Chen, Chun-Fa; Ma, Lian-Ju; Wang, Lu; Bai, Yan; Yang, Jia-Qi; Zhu, Shu; Li, Quan; Bai, Jia-Hao; Sun, Yang-Yi; Chen, Xin-Hong; Jiang, Xin-Ya; Liu, Qian; Qian, Hang ·
RPEP-11203 · 2025In 10 semaglutide-treated patients, central retinal thickness (CRT) increased approximately 1% (3.76 μm, 95% CI -0.32 to 7.85, P = 0.065) compared to placebo — borderline non-significant. When adjusted for Time in Range (TIR), this effect was further attenuated (P = 0.21), indicating the retinal change was explained by glycemic improvement rather than a direct semaglutide effect.
Across all four treatment groups (semaglutide, empagliflozin, combination, and placebo), increased TIR was independently associated with increased CRT (0.07 μm per unit increase, 95% CI 0.03–0.12, P = 0.002). This confirms that rapid glycemic improvement — by any mechanism — is the driver of early retinal thickness changes.
Gullaksen, Søren; Vernstrøm, Liv; Sørensen, Steffen Skovgaard; Funck, Kristian Løkke; Petersen, Line; Bek, Toke; Poulsen, Per Løgstrup; Laugesen, Esben ·
RPEP-11204 · 2025This meta-analysis of 13 randomized controlled trials (1,552 patients) found that GLP-1 receptor agonists, dual GIP/GLP-1 receptor agonists, and GCGR/GLP-1 receptor agonists all significantly reversed liver fibrosis (OR 3.72, p<0.001) and reduced liver fat content (mean decrease of 18.9%, p<0.001) in people with type 2 diabetes and fatty liver disease. Critically, dual-agonist drugs outperformed single GLP-1 agonists: GIP/GLP-1 agonists (like tirzepatide) showed an OR of 28.90 and GCGR/GLP-1 agonists an OR of 35.31 for liver fat reduction, compared to 8.23 for single GLP-1 agonists alone.
Gunawan, Burhan; Nugroho, Heri; Sibarani, Roy Panusuan · Systematic Review And Meta Analysis
RPEP-11206 · 2025Women with PCOS had significantly lower fasting oxytocin levels (1294 vs 1580 pg/mL, p=0.024) and reduced baseline and postprandial GLP-1 and GIP levels compared to matched controls. Oxytocin and GLP-1 were correlated at all time points, and in healthy controls, early oxytocin changes correlated with hunger and satiety — a relationship absent in women with PCOS. Food cravings were also significantly higher in the PCOS group.
Gunesli, Irmak; Ulug, Elif; Pinar, Aylin Acikgoz; Portakal, Oytun; Yildiz, Bulent O · Cross Sectional
RPEP-11208 · 2025ROR1 was found to be transcriptionally upregulated and overexpressed at the protein level across endometriosis lesions in a dataset of 408 endometriosis samples and 53 controls, validated in 179 tissue microarray samples.
Of three shortlisted compounds (rimegepant, cabergoline, pirenzepine), only rimegepant — a clinically approved CGRP antagonist — significantly reduced viability in 12Z endometriotic cells. In patient-derived organoids from deep infiltrating endometriosis, two of three models showed concentration-dependent antiproliferative and cytotoxic effects with morphological features consistent with cell death, while one model was less responsive.
Gunther, Kate; Liu, Dongli; Stannard, Gill; Holmes, Melissa; Loo, Christine; Guo, Belinda; Bowden, Nikola; Abbott, Jason; Ford, Caroline E ·
RPEP-11212 · 2025Across 55 placebo-controlled trials of 12 GLP-1 receptor agonists in 16,269 participants, maximum weight reduction ranged from 4.25 kg (liraglutide) to 22.6 kg (retatrutide). At 52 weeks, the hierarchy was clear: mono-agonists averaged 7.03 kg, dual-agonists 11.07 kg, and tri-agonists 24.15 kg of weight loss.
Onset times varied considerably: orforglipron showed effects fastest (6.4 weeks) while tirzepatide was slowest to plateau (19.5 weeks). Six drugs showed significant dose-response relationships. Age was negatively correlated with weight loss (younger patients lost more), while baseline weight and BMI had no significant impact on outcomes. GI adverse events (nausea, vomiting, diarrhea, constipation) were significantly more common than placebo, with nausea being the most frequent.
Guo, Haoyang; Yang, Juan; Huang, Jihan; Xu, Ling; Lv, Yinghua; Wang, Yexuan; Ren, Jiyuan; Feng, Yulin; Zheng, Qingshan; Li, Lujin ·
RPEP-11214 · 2025Across 39 RCTs and 99,599 patients, each drug class showed distinct advantages:
**SGLT-2 inhibitors** were superior for HbA1c reduction (MD -0.33), blood pressure lowering (systolic MD -5.52 to -1.50), and weight loss (MD -3.81 to -1.29 kg). Empagliflozin ranked highest for HbA1c and diastolic blood pressure reduction. Canagliflozin ranked best for systolic blood pressure and weight loss.
**GLP-1 receptor agonists**: Liraglutide was the most effective agent for LDL cholesterol reduction (MD -1.58 to -1.41). Semaglutide was the least harmful to estimated GFR, an important consideration in kidney disease patients.
**Finerenone** significantly reduced systolic blood pressure (MD -1.65) and had the lowest urinary tract infection rate.
Safety profiles were generally favorable across all classes, with different drugs showing advantages for specific adverse events.
Guo, Jingyi; Wei, Maoying; Zhang, Wenhua; Jiang, Yijia; Li, Aijing; Wang, Churan; Yin, Dan; Sun, Anning; Gong, Yanbing ·
RPEP-11217 · 2025Tirzepatide added to basal insulin produced significant HbA1c reductions at week 40:
- Tirzepatide 10mg: -2.39% (SE 0.13) vs placebo -0.91% (SE 0.12); difference -1.48% (97.5% CI -1.87 to -1.08; p<0.0001)
- Tirzepatide 15mg: -2.37% (SE 0.13) vs placebo -0.91%; difference -1.45% (97.5% CI -1.85 to -1.06; p<0.0001)
- Tirzepatide 5mg also showed improvements (specific numbers not primary endpoint)
The most common adverse events were gastrointestinal: diarrhea (26-37% vs 8%), decreased appetite (25-32% vs 0%), nausea (5-11% vs 3%), and vomiting (6-9% vs 0%), predominantly mild or moderate.
Guo, Lixin; Dong, Xiaolin; Ma, Jianhua; Liu, Ming; Lu, Yibing; Wang, Hongman; Li, Qingju; Li, Ling; Deng, Yuying; Xu, Jiawei ·
RPEP-11218 · 2025731 participants with T2D were randomized 1:1:1 to 4 mg mazdutide, 6 mg mazdutide, or 1.5 mg dulaglutide for 28 weeks on background oral anti-diabetic drugs. Both mazdutide doses demonstrated non-inferiority AND superiority to dulaglutide for HbA1c change from baseline.
HbA1c treatment differences: 4 mg mazdutide was -0.24% better than dulaglutide (p=0.0032); 6 mg mazdutide was -0.30% better (p=0.0003). Weight loss differences were even more dramatic: 4 mg mazdutide achieved 3.78% more body weight reduction, and 6 mg mazdutide achieved 5.76% more (both p<0.0001). Mazdutide was generally safe but had higher gastrointestinal adverse events than dulaglutide — consistent with its dual-receptor mechanism.
Guo, Lixin; Zhang, Bo; Xue, Xia; Zhang, Xin; Cai, Hanqing; Jiang, Hongwei; Zhang, Lili; Jin, Ping; Wang, Xiaojing; Cheng, Zhifeng; Zhang, Suhe; Geng, Jianlin; Guo, Yushan; Hu, Hanbo; Ma, Qingyang; Li, Li; Du, Haiwei; Han-Zhang, Han; Xue, Fengtai; Deng, Huan; Qian, Lei; Yang, Wenying ·