RPEP-11421 · 2025Current evidence shows that switching from complex insulin regimens to once-daily fixed-ratio combinations (FRCs) of basal insulin + GLP-1 RA provides equivalent glycemic control with additional benefits: reduced body weight, lower total daily insulin dose, fewer daily injections, and no increase (or a reduction) in hypoglycemia.
Two FRC products are currently available: iGlarLixi (insulin glargine + lixisenatide) and IDegLira (insulin degludec + liraglutide). The review provides a practice-oriented clinical algorithm for simplifying complex insulin regimens using these combinations.
Horváth, Luděk; Novodvorský, Peter; Haluzík, Martin ·
RPEP-11423 · 2025A bioinformatically designed 20-amino acid antimicrobial peptide demonstrated potent activity against Acinetobacter baumannii with an MIC of 64 µg/mL. The peptide reduced persister cell populations by 75% within 24 hours — a critical finding since persister cells are responsible for chronic and recurring infections. It also inhibited biofilm formation and altered expression of the pmrB and lasI genes involved in antibiotic resistance and quorum sensing. Cytotoxicity to mammalian cells was moderate (8–17% reduction in cell viability).
Hosseini, Mandana; Hosseini, Farzaneh; Amirmozafari, Nour; Sepahy, Abbas Akhavan ·
RPEP-11428 · 2025Analysis of 1,412 verified lanthipeptide biosynthetic gene clusters revealed a statistically significant co-localization with phage defense systems (including restriction-modification systems and CRISPR components) and bacterial competence genes within a 40 kb span. This pattern was observed across diverse species including Paenibacillus larvae, Corynebacterium matruchotii, Bacillus, Enterococcus, and Streptococcus.
Anti-phage defense proteins were found near 1.2% of sampled regions, including the anti-restriction protein ArdA. The findings suggest an evolutionary model where antimicrobial peptide production, DNA defense, and horizontal gene transfer form an integrated system — bacteria kill competitors, absorb their DNA, and protect the newly acquired genetic material.
Hourigan, David; Hill, Colin; Ross, R Paul ·
RPEP-11434 · 2025In a large real-world study of nearly 460,000 patients, tirzepatide was associated with a 44% higher risk of osteoporosis or fragility fractures compared to other GLP-1 receptor agonists (HR 1.44, 95% CI 1.22–1.69). Tirzepatide users were also 61% more likely to start osteoporosis therapy (HR 1.61, 95% CI 1.22–2.12).
Compared to non-users, tirzepatide showed a 48% higher risk of osteoporosis/fracture (HR 1.48, 95% CI 1.26–1.75), while other GLP-1 agonists showed no significant increase (HR 1.07, 95% CI 1.00–1.15).
This suggests the bone risk may be specific to tirzepatide — possibly related to its dual GLP-1/GIP mechanism or the more rapid and greater weight loss it produces — rather than a class effect shared by all GLP-1 drugs.
Hsu, Yung-Han; Liang, Yu-Cheng; Chan, Ka-Chon; Chou, Yu-Hsuan; Wu, Hung-Tsung; Ou, Horng-Yih · Retrospective Cohort
RPEP-11436 · 2025An RNA-sequencing-only computational pipeline successfully identified neoantigens in mouse breast cancer (4T1), lung cancer (LLC), and one human breast cancer patient. In vitro, these neoantigen peptides triggered specific T-cell responses in BALB/c mice and the human patient. The neoantigen peptide group showed increased CD3+/CD137+ T cells (activated, tumor-specific T cells), with significant infiltration into tumor tissues. In vivo therapeutic evaluation demonstrated significant antitumor efficacy in mouse models.
Hu, Hongye; Xiong, Yicheng; Lu, Danhong; Sun, Weihong; Su, Xiaoping; Mo, Danni; Chen, Lu; Wang, Guan; Wang, Jiayan; Zhang, Xiaohua; Lu, Mingdong; Huang, Guanli ·
RPEP-11440 · 2025Semaglutide reduced fat accumulation in liver cells by acting on nearby immune cells (macrophages) rather than directly on the liver cells themselves. In a co-culture system, semaglutide downregulated the IRE1α-XBP1-C/EBPα signaling pathway in macrophages, which reduced inflammation and indirectly improved hepatocyte health — reducing fat buildup, improving autophagy (cellular cleanup), and decreasing cell death. This suggests semaglutide's liver benefits may work partly through immune modulation rather than direct effects on liver cells.
Hu, Qin; Zhang, Li; Tao, YiTing; Xie, ShuangLin; Wang, AiYun; Luo, Caiying; Yang, RenHua; Shen, Zhiqiang; He, Bo; Fang, Yu; Chen, Peng · In Vitro
RPEP-11444 · 2025Mudskipper β-def2 (muβ-def2, 43 amino acids, +4.5 net charge) demonstrated broad-spectrum bactericidal activity with MBCs ranging from <1 μM for S. aureus to 32 μM for L. monocytogenes. Rapid killing kinetics were observed (A. veronii eradication within 160 minutes). Activity persisted across 28°C-100°C and pH 5.5-9.0. The mechanism involves selective targeting of prokaryotic membrane phospholipids followed by downstream DNA interactions after membrane permeabilization. Pathogen-associated molecular patterns (PAMPs) competitively inhibited peptide activity.
Hu, Ya-Zhen; Tan, Ning-Xi; Cao, Jia-Feng; Chen, Jiong ·
RPEP-11449 · 2025KF6 peptide administered at 10 mg/kg for 5 weeks to spontaneously hypertensive rats (SHRs) effectively lowered both diastolic blood pressure (DBP) and systolic blood pressure (SBP). The peptide decreased serum levels of ACE, angiotensinogen (AGT), aldosterone (ALD), and angiotensin II (ANG II).
Beyond blood pressure reduction, KF6 ameliorated cardiac and renal injury by inhibiting fibrosis, inflammation, and oxidative stress. Mechanistically, it inhibited the ACE-ANG II-AT1 axis while activating the protective ACE2-Ang(1-7)-MAS1L pathway in both the kidney and heart. The peptide also improved intestinal microbiota composition, increasing beneficial Prevotella and Phascolarctobacterium while decreasing potentially harmful Alistipes, Clostridium_IV, Nosocomiicoccus, and Allobaculum.
Huan, Pengtao; Sun, Liping; Chen, Shupeng; Zhong, Yujie; Zhuang, Yongliang ·
RPEP-11451 · 2025Liraglutide significantly reduced levels of pro-inflammatory cytokines IL-1β, TNF-α, and IL-6 in bronchoalveolar lavage fluid and improved alveolar architecture in hyperoxia-exposed neonatal rats.
At the molecular level, liraglutide decreased mRNA and protein expression of ACE, AngII, and AT1R (P < 0.05) while increasing ACE-2 and Ang(1-7) expression (P < 0.05) at postnatal days 3, 7, and 14. When A779, a Mas receptor antagonist, was co-administered, liraglutide's protective effects were abolished, confirming the ACE-2/Ang(1-7)/Mas axis as the critical mechanism.
Huang, Binglong; Luo, Han; Chen, Rou Yi; Li, Yeshan; Xiang, Min; Ao, Dang; Lin, Shaozhu; Liu, Ling ·
RPEP-11454 · 2025Four novel cathelicidin genes (cathelicidin-1 through cathelicidin-4) were cloned from tiger frog H. rugulosus, encoding peptides of 153, 188, 132, and 160 amino acids respectively. Sequence comparison revealed highly diverse structures among the four cathelicidins. Each showed distinct tissue-specific expression patterns in healthy frogs, with expression levels changing in tissue- and time-dependent manner when frogs were challenged with A. hydrophila bacteria over 72 hours.
Synthetic cathelicidin-1 and cathelicidin-2 exhibited broad-spectrum in vitro antimicrobial activity through two mechanisms: excessive induction of reactive oxygen species (ROS) and direct disruption of microbial membrane structure. In vivo, intraperitoneal injection of cathelicidin proteins significantly increased marine medaka fish resistance to bacterial challenges, demonstrating cross-species antimicrobial protection.
Huang, Danni; Gao, Fulong; Huang, Yixin; Zheng, Ronghui; Fang, Chao; Huang, Wenshu; Wang, Kejian; Bo, Jun ·
RPEP-11460 · 2025Using house musk shrews (Suncus murinus) — one of the few small mammals that produce motilin — researchers demonstrated for the first time that the peptide hormone motilin directly stimulates food intake linked to gastric motility. Plasma motilin levels were elevated during phase III contractions of the migrating motor complex, and food intake was higher during these contractions. Intravenous motilin administration increased feeding during phase I (though less potently than ghrelin).
Critically, motilin's feeding effect was completely abolished by vagotomy, proving the signal travels through the vagus nerve. Motilin also activated appetite-regulating neurons in the brainstem and hypothalamus, including neuropeptide Y neurons in the arcuate nucleus.
Huang, Jin; Watanabe, Ayumi; Kanaya, Moeko; Gomi, Ayano; Yokoyama, Haruka; Ishii, Hikari; Nakamura, Yusuke; Azuma, Morio; Konno, Norifumi; Kaiya, Hiroyuki; Sakai, Takafumi; Sakata, Ichiro ·
RPEP-11466 · 2025D-type peptide dendrimers demonstrated superior autophagy-inducing potential compared to both L-type dendrimers and free chemotherapeutics, as confirmed by TEM and Western blot. The histidine-modified dendrimer terminals enabled efficient lysosomal escape after cell internalization, leading to rapid drug release. The dendrimers synergized with encapsulated chemotherapeutic agents to enhance autophagy-mediated cancer cell death, serving both as carriers and active therapeutic components.
Huang, Shaoteng; Cai, Xiaofeng; Zhang, Mingbo; Yao, Wenjie; Fang, Quanhui; Dong, Yiwen; Zhang, Yong; Chen, Yang; Zhuang, Junyang; Li, Ning ·
RPEP-11472 · 2025Researchers built a programmable nanovaccine platform using peptide nucleic acid (PNA) scaffolds that can be loaded in a single step with three components: a cancer-targeting peptide antigen (SIINFEKL from ovalbumin), an immune-boosting adjuvant (CpG), and a dual-targeting ligand (LLP2A) that homes to both immune cells and melanoma cells via α4β1 integrin.
In mice with melanoma, this nanovaccine activated dendritic cells for antigen presentation, triggered strong CD8+ T cell and natural killer cell responses, caused significant tumor regression, and prolonged survival. The modular design allows swapping in different antigens and targeting ligands for personalized cancer vaccines.
Huang, Yanyu; Huang, Cuiqing; Pandita, Sakshi; Ieong, Chon Man; Wang, Yongheng; Wang, David; Chen, Jifeng; Jauregui-Matos, Victorio; Beelen, Alessandra Maria Arabelle; Shiau, Ya-Ping; Tang, Shiqi; Zhao, Junwei; Zong, Qiufang; Tang, Menghuan; Cong, Zhaoqing; Li, Yuanpei; Beal, Peter A; David, Sheila S; Wang, Aijun; Wang, Duo; Xiao, Zeyu; Lam, Kit S · Animal
RPEP-11476 · 2025The review's comparative findings across obesity treatment modalities:
- **GLP-1 receptor agonists**: ~15-20% weight reduction, but high ongoing costs place ICERs above conventional willingness-to-pay benchmarks, meaning they rarely meet standard cost-effectiveness thresholds at current pricing.
- **Endoscopic sleeve gastroplasty (ESG)**: ~15% weight loss with favorable cost-effectiveness, particularly in class I obesity (BMI 30-35).
- **Metabolic/bariatric surgery (MBS)**: 25-30% weight loss with improvements in survival and quality of life. Consistently rated highly cost-effective and sometimes cost-saving, especially for class II (BMI 35-40) and class III (BMI 40+) obesity.
ESG is generally more economically favorable than GLP-1 RAs in class I obesity, while MBS dominates for more severe obesity. Head-to-head ESG vs. MBS comparisons remain limited.
Huh, Yeon-Ju ·
RPEP-11489 · 2025The novel cathelicidin peptide HcCATH-KL30 (CATH) showed potent antifungal activity against free-floating C. albicans but was ineffective against biofilm-embedded fungi. To overcome this limitation:
- CATH was loaded into bilayer dissolving microneedles (DMNs) with indocyanine green (ICG) for photodynamic therapy
- Near-infrared irradiation generated reactive oxygen species that disrupted the biofilm matrix
- With the biofilm broken, CATH penetrated to kill the fungal cells
- In vitro, ex vivo, and in vivo results showed ~94% reduction in fungal burden
- Mechanism confirmed by qRT-PCR and propidium iodide staining
This is the first time this antimicrobial peptide has been explored through a drug delivery platform.
Hussain, Yaseen; Dormocara, Amos; Li, Huifang; Li, Chengguo; Khan, Muhammad Kamran; Ma, Yonghao; Leng, Gang; Wang, Yipeng; You, Ben-Gang; Cui, Jing-Hao ·
RPEP-11491 · 2025The review identifies three key hypothalamic nuclei — the arcuate nucleus, paraventricular hypothalamic area, and dorsomedial hypothalamus — as primary targets where GLP-1 signals are integrated to regulate feeding, body weight, and blood sugar. Natural GLP-1, produced by specific neurons in the brainstem (nucleus tractus solitarius), and pharmaceutical GLP-1 receptor agonists engage these circuits through both shared and distinct pathways. The authors highlight that circuit redundancy and context-dependent signaling help explain why GLP-1 drugs produce robust weight loss effects.
Hwang, Eunsang; Portillo, Bryan; Williams, Kevin W ·
RPEP-11497 · 2025This review proposes a paradigm shift in understanding epicardial adipose tissue (EAT) inflammation: rather than being purely harmful, EAT inflammation may be a necessary process for fat tissue remodeling and an adaptive response to GLP-1 and GIP peptide drug treatment. Epicardial fat expresses both GLP-1 and GIP receptors, suggesting these peptide drugs interact directly with this cardiac fat depot.
Activation of EAT GLP-1R and GIP-R may induce a beneficial balance — increasing healthy fat cell formation (adipogenesis) while reducing dangerous ectopic fat accumulation around the heart. This reframing suggests the cardiovascular benefits of liraglutide, semaglutide, and tirzepatide may be partly mediated through beneficial EAT inflammation and remodeling.
Iacobellis, Gianluca ·
RPEP-11498 · 2025In all patients, miR16, miR155, and miR181a were significantly higher in coronary epicardial fat (CORO-EAT) and left atrial epicardial fat (LA-EAT) compared to subcutaneous fat (SAT). In the liraglutide group specifically, miR16 and miR181a were significantly higher in CORO-EAT vs. SAT, and miR155 and miR181a were higher in LA-EAT vs. SAT. Liraglutide-treated patients had significantly better intra-operative glucose control (146 ± 21 vs 160 ± 21 mg/dL, p<0.01) independent of weight loss.
Iacobellis, Gianluca; Goldberger, Jeffrey J; Lamelas, Joseph; Martinez, Claudia A; Sterling, Carlos Munoz; Bodenstab, Monica; Frasca, Daniela ·
RPEP-11504 · 2025Among 2,747 propensity-matched patients per group (mean age 68), GLP-1 RA therapy showed significant advantages over bariatric surgery:
- Acute heart failure events: 38.9% vs 44.6% (HR 0.78, 95% CI 0.72-0.85) — 22% lower
- All-cause death: 11.1% vs 14.8% (HR 0.71, 95% CI 0.61-0.82) — 29% lower
- All-cause hospitalizations: 66.4% vs 77.3% (HR 0.62, 95% CI 0.58-0.66) — 38% lower
- Myocardial infarction: similar between groups (HR 0.99)
- Stroke: similar between groups (HR 0.87, not significant)
Weight loss was comparable: mean BMI at follow-up was 38.0 (GLP-1 RA) vs 37.7 (surgery), with no significant difference. However, blood sugar control was better after surgery (HbA1c 6.8 vs 7.4, P<0.001).
Ibrahim, Ramzi; Han, William; Wang, Winston; Kau, Ethan; Said, Nada; Forst, Beani; Pham, Hoang N; Abdelnabi, Mahmoud; Salih, Mohammed; Ali, Nima B; Farina, Juan; Lester, Steven J; Lee, Kwan; Ayoub, Chadi; Arsanjani, Reza ·
RPEP-11520 · 2025Semaglutide and tirzepatide — originally developed for type 2 diabetes and obesity — show promise as add-on treatments to insulin in type 1 diabetes (T1D), double diabetes, and latent autoimmune diabetes in adults (LADA). Evidence from mostly real-world studies suggests these GLP-1-based drugs improve glucose control, promote weight loss, may preserve remaining beta-cell function, and provide additional metabolic benefits in T1D patients.
The concept of 'double diabetes' — T1D patients who also develop insulin resistance, obesity, or metabolic syndrome — is emerging as a significant clinical challenge. Neither semaglutide nor tirzepatide is currently approved for T1D, but off-label use is growing as overweight and obesity increasingly affect T1D populations.
Infante, Marco; Silvestri, Francesca; Padilla, Nathalia; Pacifici, Francesca; Pastore, Donatella; Pinheiro, Marcelo Maia; Caprio, Massimiliano; Tesauro, Manfredi; Fabbri, Andrea; Novelli, Giuseppe; Alejandro, Rodolfo; De Lorenzo, Antonino; Ricordi, Camillo; Della-Morte, David · Review
RPEP-11521 · 2025The review identifies obstructive sleep apnea (OSA) and obesity hypoventilation syndrome (OHS) as serious sleep-related comorbidities in obese children, often coexisting with insulin resistance, type 2 diabetes, hypertension, and non-alcoholic fatty liver disease.
GLP-1 receptor agonists are highlighted as a promising pharmacologic intervention for pediatric obesity, but the review concludes that their use in children remains constrained by limited data — particularly regarding their impact on sleep disorders. The authors emphasize that it is currently unclear whether GLP-1 agonist-induced weight loss translates into improvements in OSA, OHS, or related outcomes like cognitive function and psychosocial wellbeing in pediatric populations.
Inja, Ravali; Cielo, Christopher ·
RPEP-11522 · 2025A patient with mild binge eating disorder, type 2 diabetes, and obesity was treated with dulaglutide 0.75 mg weekly. At 6-week follow-up, improvements were observed in the Binge Eating Scale (BES) score, BMI, body weight, and BED symptoms. Dulaglutide was well tolerated with no reported adverse drug events.
While dulaglutide was initiated for diabetes management, the concurrent improvement in binge eating behaviors suggests GLP-1 receptor agonists may have dual benefits in patients with comorbid BED and metabolic conditions. The case adds to an emerging evidence base for GLP-1 drugs in eating disorders, though the mechanism — whether through appetite suppression, reward pathway modulation, or both — requires further investigation.
Innocent, Britnee; Elmaoued, Amre A; Cowart, Kevin; White, Raechel T ·
RPEP-11528 · 2025TRAPseq profiling revealed that NPY neurons in the central amygdala co-express orexigenic (appetite-stimulating) gene markers while showing minimal overlap with anorexigenic markers, confirming their role as hunger-promoting cells. Under combined high-fat diet and stress (HFDS), distinct gene clusters activated involving fatty acid metabolism, stress response pathways, and feeding-related neuropeptide production.
Immunohistochemistry revealed long-range projections from CeA NPY neurons to the lateral habenula, periaqueductal gray, and parvicellular reticular formation — brain regions involved in reward, pain, and motor responses. Lipid-sensing mechanisms and synaptic modulating pathways were identified as principal stress targets within the CeA-NPY circuit.
Ip, Chi Kin; Zhang, Lei; Tasan, Ramon; Herzog, Herbert ·
RPEP-11529 · 2025In 17 ankle joints from OA patients, CGRP and substance P expression were significantly upregulated in sclerotic subchondral bone. Both neuropeptides showed strong positive correlations with:
- Hounsfield unit (HU) values (bone density on CT)
- Subchondral bone plate thickness
- Modified Mankin scores (cartilage degeneration severity)
CGRP expression appeared earlier than substance P, detectable at moderate degeneration stages. TRAP-positive osteoclast numbers also increased with disease progression and followed a distribution pattern matching CGRP and SP expression, suggesting a functional relationship between neuropeptide signaling and bone remodeling.
Ishibashi, Saori; Nakasa, Tomoyuki; Ikuta, Yasunari; Sakurai, Satoru; Moriwaki, Dan; Chujo, Taro; Adachi, Nobuo ·
RPEP-11538 · 2025The CH401 antigenic peptide was conjugated with the adjuvant Pam3CSK4 and formulated into cationic lipid nanoparticles (LNPs) smaller than 100 nm using a precision microflow device (iLiNP). This system enabled size-controlled formulation and systematic optimization of the vaccine platform.
The self-adjuvanting peptide-LNP vaccines demonstrated enhanced immunogenicity with precise modulation of antigen-specific immune responses. Supplemental adjuvants could be incorporated to further fine-tune immune activation. The vaccines elicited potent immune responses in humanized mouse models, supporting translational potential for human application.
Ito, Keita; Manabe, Yoshiyuki; Ohshima, Shino; Maeki, Masatoshi; Tokeshi, Manabu; Inaba, Hiroshi; Matsuura, Kazunori; Kabayama, Kazuya; Kametani, Yoshie; Fukase, Koichi ·
RPEP-11539 · 2025A 63-year-old woman with stage 3b diabetic kidney disease was prescribed dulaglutide 0.75 mg/week due to persistent albuminuria despite maximum tolerated dose of azilsartan. At 2-month follow-up, serum creatinine increased and subsequently doubled. No other causes of kidney injury (including volume depletion) were identified.
Kidney biopsy revealed active mononuclear cell-predominated interstitial nephritis alongside diabetic nephropathy, without immune complex accumulation. After discontinuing dulaglutide, kidney function achieved almost complete recovery without steroid therapy. The patient was successfully rechallenged with azilsartan and chlorthalidone, confirming dulaglutide as the causative agent.
Itsathitpaisarn, Raweekarn; Suksawad, Nattavong; Wongwikrom, Watsapol; Surintrspanont, Jerasit; Thongsricome, Thana ·
RPEP-11543 · 2025Using adeno-associated virus vectors to deliver PYY and exendin-4 encoding genes to the salivary glands of wild-type male mice, researchers found that oral presence of these satiety peptides significantly altered taste-related behavioral responsiveness across multiple taste qualities. In vitro experiments on isolated taste bud cells confirmed that PYY and exendin-4 directly influence the responsiveness of these primary sensory cells.
This builds on previous work showing that PYY knockout mice had altered taste responsiveness and that restoring PYY expression in salivary glands rescued normal taste behavior. The current study extends these findings to normal mice with intact peptide signaling, demonstrating that exogenous peptide application can modulate taste even when the endogenous system is already functional.
Iyer, Satya; Montmayeur, Jean-Pierre; Zolotukhin, Sergei; Dotson, Cedrick D · Animal Study
RPEP-11547 · 2025In telemetry-implanted Göttingen minipigs (n=6-8 per study):
- Liraglutide (3 nmol/kg, Day 7): significant HR increase (P<0.01), no BP changes — matching human clinical observations
- MC4 receptor agonist LY2112688 (0.1-0.15 mg/kg, Day 4): significant increases in HR (P<0.05), MAP (P<0.01), SBP (P<0.01), and DBP (P<0.05) — matching the hypertensive effect that halted MC4RA clinical development
- Urocortin-2 infusion: significant HR increase (P<0.05) and SBP decrease (P<0.05) — matching known vasodilatory effects in humans
All three peptides qualitatively reproduced their known human cardiovascular profiles, though absolute magnitudes may differ between species.
Jacobsen, Julie; Christoffersen, Berit Ø ·
RPEP-11553 · 2025In Wolfram syndrome rats, GABA monotherapy had no significant effect on diabetes, while liraglutide monotherapy (0.4 mg/kg/day) effectively delayed progression. However, the GABA (1 g/kg/day) plus liraglutide combination reversed the diabetic phenotype entirely: glucose homeostasis was significantly enhanced, insulin and C-peptide secretion improved, and beta-cell mass increased.
Remarkably, the combination therapy fully restored Langerhans islet architecture, correcting the intra-islet ratio of alpha, beta, and delta cells to normal proportions. Both liraglutide alone and combination therapy increased GAD65/67-positive beta cells, indicating improved beta-cell health, but only the combination achieved complete phenotype reversal.
Jagomäe, Toomas; Velling, Sandra; Tikva, Tessa Britt; Maksimtšuk, Varvara; Gaur, Nayana; Reimets, Riin; Kaasik, Allen; Vasar, Eero; Plaas, Mario ·
RPEP-11558 · 2025Of 44 participants who had failed anti-CGRP monoclonal antibodies (88.6% chronic migraine), atogepant at 3 months produced:
- 18.2% achieved ≥50% reduction in monthly headache days (MHDs)
- 25.0% achieved ≥30% reduction in MHDs
- 33.3% achieved ≥50% reduction in moderate-to-severe headache days (MSHDs)
- Median MHDs decreased from 24.5 to 21.5 (p=0.011)
- Median MSHDs decreased from 15.0 to 12.0 (p=0.001)
- 59.1% reported some degree of improvement on Patient Global Impression scale
- Acute medication days and HIT-6 disability scores also significantly decreased
- Constipation occurred in 31.8%; 11.4% discontinued due to side effects
Jaimes, Alex; Rodríguez-Vico, Jaime; Pajares, Olga; Eguilior Caffarena, Ignacio; Nystrom Hernández, Anna Lena; Gómez, Andrea; Porta-Etessam, Jesús ·
RPEP-11562 · 2025The review identifies shared inflammatory cascades between obesity and osteoarthritis, suggesting these are not merely co-occurring conditions but mechanistically linked through common inflammatory pathways. GLP-1 receptor agonists, which are peptide-based therapeutics, demonstrate anti-inflammatory properties beyond their metabolic effects, making them potential candidates for simultaneously addressing both obesity and osteoarthritis-related inflammation.
Jamal, Naadir; Hollabaugh, William; Scott, Leon; Takkouche, Sahar ·
RPEP-11565 · 2025The evidence on semaglutide's impact on lean mass (muscle) is contradictory. Some studies show that while semaglutide causes decreases in both lean mass and fat mass, the ratio of lean mass to total body mass actually improves — meaning fat is lost proportionally faster than muscle. However, larger clinical trials have found significant reductions in lean mass, raising concerns about muscle loss.
This contradiction makes the real-world impact unclear: semaglutide users are definitely losing some muscle along with fat, but whether this represents a clinically meaningful problem — or simply the normal lean mass loss that accompanies any significant weight reduction — remains debated.
Jamialahmadi, Tannaz; Eid, Ali H; Gadde, Kishore M; Almahmeed, Wael; Kroh, Matthew; Al Zein, Mohammad; Sahebkar, Amirhossein · Opinion Review
RPEP-11567 · 2025Deleting Tcf4 in mouse intestinal cells produced several major findings:
1. Paneth cells — the main producers of α-defensin antimicrobial peptides in the small intestine — were completely lost, and antimicrobial peptide expression was abolished.
2. Loss of Tcf4 shifted secretory progenitor differentiation from Paneth cells toward goblet cells, revealing Tcf4 as the binary switch between these two cell fates.
3. The gut microbiota was disrupted when Paneth cells and their defensins disappeared, demonstrating the critical role of these peptides in maintaining microbial balance.
4. Alternative secretory progenitors compensated by producing Wnt ligands to maintain stem cell function and epithelial renewal even without Paneth cells.
5. In colon adenomas, Paneth-like tumor cells that express defensins and Wnt3 ligands also require Tcf4 for their identity. Losing Tcf4 converts them to goblet cells, potentially disrupting tumor self-renewal.
Janeckova, Lucie; Stastna, Monika; Hrckulak, Dusan; Berkova, Linda; Kubovciak, Jan; Onhajzer, Jakub; Kriz, Vitezslav; Dostalikova, Stela; Mullerova, Tereza; Vecerkova, Katerina; Tenglerova, Marketa; Coufal, Stepan; Kostovcikova, Klara; Blumberg, Richard S; Filipp, Dominik; Basler, Konrad; Valenta, Tomas; Kolar, Michal; Korinek, Vladimir ·
RPEP-11569 · 2025CPPpred-En achieved state-of-the-art performance on two benchmark datasets:
- CPP924 dataset: 97.27% accuracy, MCC = 0.964
- MLCPP 2.0 dataset: 96.10% accuracy, MCC = 0.707
- Outperformed all existing prediction tools on both datasets
The key innovation was combining:
- Multiple protein language model (PLM) features (learned representations from large protein databases)
- Conventional peptide features (physicochemical properties, amino acid composition)
- Ensemble learning across multiple machine learning classifiers
- High-performing feature-classifier combinations selected and integrated
The model showed strong generalization across different datasets, demonstrating robustness.
Jang, Yong Eun; Kwon, Minjun; Kim, Seok Gi; George, Nimisha Pradeep; Hwang, Ji Su; Basith, Shaherin; Lee, Gwang ·
RPEP-11573 · 2025Mango leaf extract (MLE) stimulated GLP-1 secretion from intestinal L-cells through two signaling pathways (MAPK and Wnt), and when given to diabetic rats at 40 mg/kg, it significantly reduced fasting blood glucose, body weight, cholesterol, triglycerides, and HbA1c. MLE also lowered DPP-IV levels (the enzyme that breaks down GLP-1), resulting in increased circulating GLP-1 comparable to the diabetes drug sitagliptin.
The active compound mangiferin was identified at 165.67 μg/g in the crude extract, and molecular docking confirmed its interaction with the relevant signaling proteins.
Jariyapongskul, Amporn; Boonsri, Pornthip; Sungwienwong, Itthipol; Dolsophon, Kulvadee; Apiratikul, Nuttapon; Jittangprasert, Piyada; Sitthisuk, Pornnapa; Rungsiwiwut, Ruttachuk; Samosorn, Siritron; Suksamrarn, Sunit; Watanapokasin, Ramida · Animal And Cell
RPEP-11576 · 2025Three years of once-weekly tirzepatide in people with obesity and prediabetes produced sustained weight loss of 12-20% (dose-dependent) versus 1.3% with placebo. Most remarkably, tirzepatide reduced progression to type 2 diabetes by 93% (1.3% vs 13.3%, HR 0.07, p<0.001). Even after 17 weeks off treatment, diabetes protection persisted (2.4% vs 13.7%, HR 0.12). The most common side effects were GI symptoms, mostly mild-moderate during dose escalation, with no new safety signals over 3 years.
Jastreboff, Ania M; le Roux, Carel W; Stefanski, Adam; Aronne, Louis J; Halpern, Bruno; Wharton, Sean; Wilding, John P H; Perreault, Leigh; Zhang, Shuyu; Battula, Ramakrishna; Bunck, Mathijs C; Ahmad, Nadia N; Jouravskaya, Irina ·
RPEP-11586 · 2025GLP-1 receptors on the choroid plexus (the brain structure that produces cerebrospinal fluid) directly modulate CSF production and intracranial pressure in rats. When researchers activated GLP-1 receptors centrally (directly in the brain), CSF secretion increased and intracranial pressure rose. When they blocked GLP-1 receptors, CSF secretion decreased. Crucially, these effects only occurred with central (brain) administration — not peripheral (body) injection — indicating the relevant receptors are on the CSF-facing side of the choroid plexus.
GLP-1R expression was confirmed in the choroid plexus at both mRNA and protein levels, and the receptor modulated transporter activity in the choroid plexus tissue.
Jensen, Mette N; Israelsen, Ida M E; Wardman, Jonathan H; Jensen, Dennis B; Andersen, Daniel B; Toft-Bertelsen, Trine L; Rath, Martin F; Holst, Jens Juul; Rosenkilde, Mette M; MacAulay, Nanna · Animal
RPEP-11592 · 2025Across 52 studies (1990–2025), the review identified several key findings: (1) Periodontitis may impair GLP-1 signaling and worsen glucotoxicity and lipotoxicity in diabetes/obesity. (2) Periodontopathic bacteria, notably P. gingivalis, produce DPP-4-like enzymes that degrade GLP-1 and potentially disrupt glucose regulation. (3) GLP-1 RAs (liraglutide, exendin-4) demonstrated anti-inflammatory, osteoprotective, and regenerative effects in preclinical periodontal models. (4) Host and microbial DPP-4 activity serves as a key mechanistic link between periodontal inflammation and systemic insulin resistance.
Jeong, Natalie; Chuang, Lin-Hsin; Ho, Yolanda ·
RPEP-11595 · 2025Semaglutide produced greater total weight loss than caloric restriction alone, even when calorie intake was matched between groups. Both treatments reduced muscle mass and strength to a similar extent, indicating that semaglutide's effect on muscle is primarily driven by reduced energy intake rather than a direct drug effect on muscle tissue.
Importantly, transcriptomic analyses of skeletal muscle revealed distinct molecular responses between semaglutide-treated and calorie-restricted mice, suggesting the drug does have unique effects at the gene expression level despite similar functional outcomes.
After discontinuation, both lean mass and fat mass rebounded to baseline levels within six weeks, and muscle size and strength were comparable across all groups at the end of the withdrawal period.
Jeromson, S; Baranowski, B; Akcan, M; Waters, B D; Eisner, K; Bellucci, A; Trang, S; Abolhassani, A; Tello-Palencia, M A; Schweitzer, A; Stefanska, B; Mitchell, C J; Wright, David C ·
RPEP-11596 · 2025Fish scales and bones contain 30-40% organic collagen matrix and 60-70% hydroxyapatite. Modern extraction methods achieve collagen yields of 25-35%, with ultrasound and microwave-assisted techniques reducing processing from days to minutes while preserving bioactivity.
Key health findings include: antioxidant capacities comparable to or exceeding vitamins C and E; ACE-inhibitory peptides lowering blood pressure in preclinical models; and clinical trial evidence that 10 g daily fish collagen peptide supplementation for 8-12 weeks improves skin hydration, elasticity, wrinkle reduction, and reduces osteoarthritis-related joint pain. Nanocarrier delivery systems (nanoliposomes, nanoemulsions) enhance bioavailability and stability.
Jeyachandran, Sivakamavalli; Aman, Mohammed ·
RPEP-11599 · 2025In this phase 3 NEJM-published trial (GLORY-1), mazdutide — a GLP-1/glucagon dual agonist — produced significant weight loss in 610 Chinese adults with obesity or overweight over 48 weeks. The 6 mg dose achieved 14.01% body weight reduction at week 48 (vs. 0.30% for placebo), and the 4 mg dose achieved 11.00%. At week 48, 49.5% of participants on the 6 mg dose lost ≥15% of their body weight. Both doses improved all prespecified cardiometabolic measures. Discontinuation rates due to adverse events were remarkably low (0.5-1.5%), with GI side effects being mostly mild to moderate.
Ji, Linong; Jiang, Hongwei; Bi, Yan; Li, Hua; Tian, Junhang; Liu, Dexue; Zhao, Yuzhu; Qiu, Wei; Huang, Chongbing; Chen, Lei; Zhong, Shao; Han, Jie; Zhang, Yawei; Lian, Qiufang; Yang, Ping; Lv, Lingchun; Gu, Jieyu; Liu, Zihan; Deng, Huan; Wang, Yanqi; Li, Li; Pei, Lijuan; Qian, Lei · Rct
RPEP-11610 · 2025In nine heart failure patients with CardioMEMS implants treated with GLP-1 receptor agonists for 6 months, body weight decreased from 123.6 to 117.2 kg (p=0.047). Systolic pulmonary artery pressure fell from 38.9 to 34.0 mmHg (p=0.045), diastolic from 20.0 to 17.8 mmHg (p=0.019), and mean from 27.3 to 24.3 mmHg (p=0.018).
Weight loss correlated significantly with reductions in systolic PAP (r=0.69, p=0.04) and mean PAP (r=0.72, p=0.029). Importantly, guideline-directed medical therapy and loop diuretic doses remained unchanged throughout, suggesting the hemodynamic improvements were attributable to GLP-1 RA treatment rather than changes in background therapy.
Jiang, Haoran; Wattanachayakul, Phuuwadith; Kittipibul, Veraprapas; Nicolsen, Erika; McVeigh, Todd; Kamneva, Oksana; Fudim, Marat ·
RPEP-11614 · 2025Aged obese UM-HET3 mice subjected to three cycles of liraglutide treatment followed by withdrawal (ON/OFF group) developed hyperleptinemia and visceral fat expansion, resulting in impaired metabolic health compared to both untreated controls and continuously treated mice.
Importantly, while the ON/OFF mice regained fat mass after each treatment cycle, they consistently failed to restore lean mass. This unfavorable shift in body composition — losing muscle but regaining fat — suggests that intermittent GLP-1 therapy may increase vulnerability to sarcopenia, the age-related loss of muscle mass and function.
Jiang, Nisi; Yin, Jiyuan; Lawrence, Noah; Meng, Jieyi; Maeyens, Laurence T; Xu, Ziying; Li, Xin; Ekane, Mbolle; Chaudhary, Ariana; Cao, Pengju; Li, Guannan; Solis-Herrera, Carolina; Zhu, Yi; Zhao, Shangang ·
RPEP-11618 · 2025Liraglutide treatment reduced blast-induced permanent hearing loss and facilitated hearing restoration as measured by auditory brainstem response (ABR). The effects varied by condition: in earplug-protected ears, pre-blast liraglutide reduced acute damage severity; in open ears, liraglutide facilitated post-injury hearing restoration.
Wave I suprathreshold amplitude analysis showed pre-injury treatment mitigated blast-induced temporary damage to the peripheral auditory system. Histopathological examination confirmed that liraglutide protected cochlear hair cells against blast injury. Higher-intensity blasts (15-25 psi) caused more severe and permanent damage than lower-intensity blasts (3-5 psi). Optimal protective effects were achieved when liraglutide was administered before injury.
Jiang, Shangyuan; Cai, Qunfeng; Bien, Alexander G; Gan, Rong Z; Jiang, Yijie ·
RPEP-11620 · 2025The stearyl-modified cell-penetrating peptide S-Cr9T formed stable complexes with plasmid DNA and significantly enhanced both cellular uptake and transfection efficiency in vitro. Optimal performance was achieved at a nitrogen-to-phosphate (N/P) ratio of 0.25.
High-content imaging showed that S-Cr9T-plasmid complexes stably adhered to cell membranes, promoting efficient intracellular delivery. In vivo, S-Cr9T significantly increased antigen expression and triggered robust immune responses: a threefold increase in IFN-γ secretion (a key marker of cellular immunity) and several hundred-fold increases in antibody levels compared to controls.
These results demonstrate that lipid modification of cell-penetrating peptides can overcome the major delivery barrier limiting DNA vaccine efficacy.
Jiang, Sheng; Zu, Cheng; Wang, Bin; Zhong, Yiwei ·
RPEP-11621 · 2025The AI-optimized multienzyme combination MC5 achieved 89.08% ACE inhibition at 1 mg/mL, significantly outperforming single-enzyme hydrolysis. After simulated digestion, ACE inhibition decreased by only 6.87%. In hypertensive rats, MC5 reduced systolic blood pressure to 125 mmHg and diastolic to 89 mmHg. The treatment significantly lowered TNF-α and IL-6, increased SOD, GSH-Px, GR, and CAT activity, reduced serum renin (1.25-fold) and ET-1 (1.04-fold), and increased NO content 3.15-fold. Four potent peptides were identified: LPEW, LKPTPEGDL, LNYW, and LLL.
Jiang, Shuai; Mo, Fan; Li, Wenhan; Yang, Sirui; Li, Chunbao; Jiang, Ling ·
RPEP-11622 · 2025Researchers discovered a self-reinforcing feedback loop — CREB→KIF1A→CGRP→CREB — that drives chronic migraine. CREB directly activates transcription of KIF1A (a motor protein), which physically associates with CGRP and promotes its transport and expression. CGRP signaling then feeds back to reactivate CREB, creating a positive loop. Disrupting any component of this axis — inhibiting CREB, knocking down KIF1A, or blocking the CGRP receptor — effectively reduced migraine-like pain behaviors and molecular markers of central sensitization in mice.
Jiang, Wei; Yu, Peng; Shi, Yan-Min; Zhang, Li-Xi; Cai, Meng-Tan; Yang, Yu; Dong, Ming ·
RPEP-11625 · 2025From 28 engineered dodecapeptides (12 amino acids) based on the antibacterial core of human cathelicidin, two leads emerged: d12 (linear) and d24 (hydrocarbon-stapled). Both killed carbapenem-resistant A. baumannii clinical isolates with MICs of 2.5–20 µg/mL by binding and penetrating bacterial membranes in a lipid A-dependent manner. In two mouse infection models — irradiation-assisted pulmonary infection and intra-abdominal sepsis — both peptides significantly reduced bacterial load and improved survival. The stapled d24 outperformed d12 in the sepsis model due to improved resistance to enzymatic degradation.
Jiang, Yiyi; Zhao, Gaomei; Gong, Yali; Chen, Yin; Li, Chenwenya; Han, Songling; Deng, Youcai; Zhao, Jinghong; Wang, Junping; Wang, Cheng ·
RPEP-11626 · 2025This review explains the mechanisms behind why multi-receptor agonists produce greater weight loss than single GLP-1 agonists alone in non-diabetic obese adults. The dual GIP/GLP-1 agonist tirzepatide activates both receptors, enhancing appetite suppression and metabolic effects beyond what GLP-1 alone achieves. GLP-1/glucagon dual agonists add glucagon's ability to increase energy expenditure and fat burning. Triple GLP-1/GIP/glucagon agonists combine all three mechanisms — appetite reduction, enhanced metabolic rate, and improved fat utilization — potentially offering the greatest weight loss of all. Each additional receptor target adds complementary mechanisms that address different aspects of energy balance.
Jiang, Yuchen; Zhu, Huijuan; Gong, Fengying · Review
RPEP-11629 · 2025Using 3D-QSAR (quantitative structure-activity relationship) modeling with both CoMFA and CoMSIA methods, the researchers developed reliable predictive models for ACE inhibitory peptide activity. The CoMFA model achieved cross-validated R² of 0.660 and predictive R² of 0.667, while CoMSIA achieved 0.646 and 0.645 respectively.
Molecular docking revealed how these peptides bind at the ACE active site, with binding characteristics consistent with the 3D-QSAR contour maps. Based on these computational insights, three novel tripeptides were designed as prospective ACE inhibitors. All three showed effective ACE inhibition when tested experimentally using the DOJINDO ACE Kit-WST reagent, validating the computational design approach.
Jiao, Fenglin; Yang, Jinlin; Wang, Fangfang; Peng, Shanli; Zhou, Bo ·