RPEP-12025 · 2025The review reveals that N-glycosylation enhances pharmacodynamic properties of class B1 GPCRs including receptor-ligand binding and activation potency. Key findings by receptor type:
- Calcitonin and amylin receptors: N-glycosylation apparently enhanced binding affinity of peptide ligands, with specific critical N-glycosylation sites identified
- GIP and secretin receptors: Also have critical individual N-glycosylation sites that drive the whole glycosylation effect
- GLP-1 and CRF1 receptors: Each glycosylation site collectively contributes to the overall effect, rather than one site being dominant
- Calcitonin gene-related peptide receptor: Has identified critical N-glycosylation sites
The review also addresses potential mechanisms by which sugar modifications enhance peptide ligand binding affinity at the molecular level.
Lee, Sangmin; Jin, Jeongwoo; Song, Hyeseon; Jang, Jaehyeok ·
RPEP-12030 · 2025At 52 weeks, sacubitril/valsartan produced a significantly greater absolute reduction in interstitial volume (a measure of cardiac fibrosis) compared to valsartan alone (-5.2 ± 5.4 vs. -2.5 ± 3.1 mL; P = 0.006), despite equivalent 24-hour systolic blood pressure (125 ± 11 vs. 126 ± 11 mmHg; P = 0.762). Secondary endpoints favoring sacubitril/valsartan included reductions in LV mass, left atrial volume, estimated LV filling pressure, NT-proBNP, and high-sensitivity troponin T.
Lee, Vivian; Dalakoti, Mayank; Zheng, Qishi; Toh, Desiree-Faye; Boubertakh, Redha; Bryant, Jennifer A; Aw, Tar-Choon; Lee, Chi-Hang; Richards, A Mark; Butler, Javed; Díez, Javier; Foo, Roger; Cook, Stuart A; Lam, Carolyn Sp; Le, Thu-Thao; Chin, Calvin Wl ·
RPEP-12034 · 2025Maternal behavior is orchestrated by a network of neuropeptides — primarily oxytocin, prolactin, and placental lactogens — that physically reshape the mother's brain during pregnancy and the postpartum period. These peptides rewire neural circuits connecting the hypothalamus to reward centers (nucleus accumbens, ventral tegmental area), making infant cues intrinsically motivating and rewarding.
Prolactin's role extends far beyond milk production: it drives adult neurogenesis, neuroprotection, and neuroplasticity in the maternal brain. Other peptides including galanin, spexin, PACAP, CRH, and TIP-39 also contribute. Dysregulation of these neuropeptide systems is linked to postpartum psychiatric disorders.
Leff-Gelman, Philippe; Pellón-Díaz, Gabriela; Camacho-Arroyo, Ignacio; Palomera-Garfias, Nadia; Flores-Ramos, Mónica · Review
RPEP-12035 · 2025The SOUL trial demonstrated that oral semaglutide (14 mg daily) significantly reduced the risk of major adverse cardiovascular events (MACE) by 14% compared to placebo in 9,650 high-risk adults with type 2 diabetes (HR 0.86, 95% CI 0.77-0.96, p=0.006). The primary composite outcome included cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke. The benefit was consistent across subgroups, including those already taking SGLT2 inhibitors. This was the first trial to establish cardiovascular benefit for an oral GLP-1 receptor agonist.
Lehenbauer, Katy S; Nelson, Adam J; Nodari, Savina; Sverdlov, Aaron L; Harrington, Josephine ·
RPEP-12041 · 2025The review identifies several key aspects of marine animal defensins:
• Marine defensins exhibit activity against bacteria, viruses, and fungi through multiple mechanisms — membrane binding, channel formation, and lipid II interaction
• The ocean's unique ecological environment has produced defensins with rich biodiversity and special molecular features compared to terrestrial defensins
• Beyond antimicrobial activity, marine defensins also have immune-regulatory and reproductive functions
• Nanotechnology approaches — including antimicrobial peptide-antibiotic conjugates, nanonets, and nanoparticle-based delivery systems — can enhance their antibacterial potency and broaden their spectrum of activity
• Marine defensins are classified primarily from fish and shellfish sources, with distinct structural characteristics and evolutionary trajectories
Lei, Yining; He, Dangui; Zhao, Xiao; Miao, Lixia; Cao, Zhijian ·
RPEP-12044 · 2025FDG PET/CT imaging revealed diffuse increased radiotracer uptake throughout the pancreas in a clinically asymptomatic 83-year-old man. Standard CT showed no structural abnormality, but subsequent lipase testing confirmed subclinical pancreatitis. The patient was taking tirzepatide (a dual GIP/GLP-1 receptor agonist), and after excluding other potential causes, the pancreatitis was attributed to this medication.
This case demonstrates that GLP-1 receptor agonist-associated pancreatitis can be entirely subclinical — detectable only through metabolic imaging or laboratory testing, not symptoms.
Lenkov, Robert; Berman, Tyler; Mehmi, Inderjit; Mehta, Pareen ·
RPEP-12049 · 2025Semaglutide use was associated with a 67% reduction in IBD-related surgery risk (HR 0.33, 95% CI 0.13-0.83). Among 89 tirzepatide users, none required IBD-related surgery (versus 2 matched controls), though the sample size was too small for statistical significance. GLP-1 use significantly reduced serum C-reactive protein (CRP), suggesting anti-inflammatory effects. No differences were found in all-cause hospitalization, IBD-hospitalization, or pancreatitis rates between GLP-1 users and non-users overall.
Notably, Black GLP-1 users had increased all-cause hospitalization risk (HR 1.59, CI 1.11-2.29) but not IBD-specific hospitalization or surgery, suggesting factors beyond IBD may be driving this disparity.
Levine, Jake; Lee, Yao An; Pham, Angela; Guo, Jingchuan; Dai, Hao; Radwan, Rotana M; Bian, Jiang; Novikov, Aleksey; Sheer, Amy ·
RPEP-12071 · 2025ProteaC-digested collagen hydrolysate showed the highest DPP-IV inhibitory activity with an IC50 of 0.58 ± 0.02 mg/mL. The enzyme preferentially cleaved at glycine and hydrophobic amino acid residues at the P1' position and showed strong preference for hydroxyproline at the P1 position. Large amounts of Gly-Pro-type peptides consisting of 4, 6, and 9 amino acids were released. The dynamic release followed a clear pattern: precursor peptides → target active peptides → shorter peptides.
Li, Jiaxin; Yang, Danyin; Xu, Qiongyao; Huang, Mingtao; Zheng, Lin; Zhao, Mouming ·
RPEP-12074 · 2025Liraglutide (1 mg/kg/day) improved insulin resistance and reduced body weight and fat mass in high-fat diet-induced obese mice. At the cellular level, liraglutide suppressed adipocyte hypertrophy (fat cell enlargement) and upregulated browning markers PGC1α, UCP1, and ATGL in both obese adipose tissues and cultured 3T3-L1 adipocytes.
Metabolomics analysis revealed that liraglutide elevated COX-2 signaling and prostaglandin levels in subcutaneous fat. Critically, COX-2 inhibition completely abolished liraglutide's effects on adipogenesis and lipolysis, and impaired adaptive thermogenesis during cold exposure. This demonstrates that COX-2 activation is required for liraglutide's fat-burning effects.
Li, Jingyi; Wu, Hailian; Ma, Wenhui; Yuan, Tao; Chen, Xiaopan; Pan, Yong ·
RPEP-12078 · 2025In 8,922 propensity-matched patients (4,461 per group), GLP-1 receptor agonists showed comparable risks versus pioglitazone for major adverse liver outcomes (HR 0.94, 95% CI 0.66–1.34) and MACE (HR 0.99, 95% CI 0.80–1.22). However, GLP-1 receptor agonists significantly reduced heart failure risk (HR 0.65, 95% CI 0.51–0.83) — a 35% reduction. Results were consistent across intention-to-treat and per-protocol analyses and robust across subgroup analyses.
Li, Lanlan; Lui, David Tak-Wai; Fong, Carol Ho-Yi; Chow, Wing-Sun; Au, Ivan Chi-Ho; Xiong, Xi; Lang, Brian Hung-Hin; Wong, Carlos King-Ho; Lee, Chi-Ho ·
RPEP-12079 · 2025Hydrocarbon stapling — using a chemical 'staple' to lock peptides into their spiral (alpha-helical) shape — has become the most widely adopted peptide stabilization strategy. The technique uses ruthenium-catalyzed ring-closing metathesis, a chemical reaction that forms a hydrocarbon bridge across one face of the peptide helix.
Recent advances include multiple-stapling (more than one staple per peptide), stitched peptides, aza-stapled peptides, and the integration of rigid anchoring amino acids that expand structural diversity. New modifications also enable imaging capabilities, such as Raman-active diyne bridges for diagnostic applications.
Li, Linji; Li, Rong; Jiang, Yanan; Chao, Jingru; Chen, Si; Liao, Hongli; Li, Xiang · Review
RPEP-12082 · 2025Cec4 demonstrated comprehensive activity against carbapenem-resistant Klebsiella pneumoniae through multiple mechanisms:
- Rapid antibacterial killing at low concentrations
- Biofilm inhibition and eradication at just 8 µg/mL
- Synergistic enhancement of traditional antibiotics when used in combination
- Dual mechanism: destruction of bacterial cell membrane integrity (confirmed by TEM, SEM, confocal microscopy, and flow cytometry) plus binding to bacterial DNA and RNA
- In vivo efficacy confirmed in a mouse skin wound infection model
- Transcriptomic analysis revealed the molecular pathways underlying its antibacterial activity
Li, Lu; Zeng, Yang; Tian, Minfang; Cao, Huijun; Qiu, Zhilang; Guo, Guo; Shen, Feng; Wang, Yuping; Peng, Jian ·
RPEP-12090 · 2025Researchers screened enzymatic hydrolysates from squid (Todarodes pacificus) skin for peptides that inhibit angiotensin-converting enzyme (ACE), a key enzyme in blood pressure regulation. Using mass spectrometry (Nano LC-MS/MS) and computational analysis, they identified candidate peptides with ACE-inhibitory activity. Molecular docking studies confirmed favorable binding interactions between the identified peptides and ACE's active site. The findings establish squid skin as a viable marine source for producing blood pressure-lowering bioactive peptides.
Li, Mingyuan; Liang, Qianqian; Zhang, Yurui; Jiang, Xin; Gu, Yuan; Song, Xin; Wang, Xichang; Shi, Wenzheng · In Vitro + In Silico
RPEP-12091 · 2025The review of clinical evidence for sacubitril/valsartan in ESRD patients with heart failure found:
Benefits (particularly in patients with reduced ejection fraction):
- Improved ventricular remodeling (reversed harmful heart enlargement)
- Enhanced left ventricular ejection fraction (better heart pumping)
- Reduced mortality rates
- Reduced heart failure rehospitalization rates
Safety:
- No significant increased risk of hyperkalemia (high potassium — a major concern in dialysis patients)
- No significant increased risk of hypotension
- Favorable overall safety profile
Mechanism: Sacubitril/valsartan simultaneously regulates the RAAS (renin-angiotensin-aldosterone system) and enhances natriuretic peptide signaling, providing dual cardiovascular protection.
Li, Peiyun; Li, Yupei; Zhang, Ling ·
RPEP-12100 · 2025Across 26 included studies:
- Preclinical: 15 of 18 studies (83%) showed significant antidepressant-like effects. The mechanisms involved enhanced neuroplasticity, reduced neuroinflammation, and neurotransmitter alterations.
- Observational: 4 of 5 studies reported reductions in depressive symptoms in human patients.
- Clinical trials: Only 1 of 3 showed statistically significant antidepressant effects.
The disconnect between strong preclinical evidence and weak clinical trial results highlights the typical challenge of translating animal findings to human therapeutics, and suggests that more and larger clinical trials are needed before conclusions can be drawn.
Li, Sophie; Sabbah, Sami George; Kwan, Angela T H; McIntyre, Roger S ·
RPEP-12102 · 2025Food-derived ACE-inhibitory peptides — obtained through natural extraction, enzymatic hydrolysis, or fermentation of foods — can block the angiotensin-converting enzyme (ACE), a key driver of high blood pressure. This review maps the landscape of these peptides: their food sources, how they're produced, their structural characteristics, and their antihypertensive activity in both lab and animal studies.
The production method significantly shapes which peptides are generated and how well they work — peptide chain length, amino acid composition, and sequence all determine ACE-inhibitory potency. Bioavailability remains a key challenge, as peptides must survive digestion to reach the bloodstream.
Li, Ting; Du, Wanjia; Huang, Huiyan; Wan, Luzhang; Shang, Chenglong; Mao, Xue; Kong, Xianghui · Review
RPEP-12108 · 2025Salivary nitrate acts as a neuromodulatory signal that coordinates oral mucosal regeneration through sensory neuron activation. When nitrate was depleted (via salivary duct ligation or dietary restriction), wound healing was impaired with reduced epithelial proliferation, abnormal collagen organization, and suppressed VEGF and TGF-β expression. These deficits were rescued by nitrate supplementation.
The mechanism depends on the nitrate transporter sialin (Slc17a5): nitrate uptake through sialin promotes reinnervation of myelinated sensory nerve fibers and stimulates release of regenerative neuropeptides — calcitonin gene-related peptide (CGRP), vasoactive intestinal peptide (VIP), and neuropeptide Y. Sensory neuron-specific sialin knockout mice failed to respond to nitrate therapy, confirming sialin's essential role.
Li, X; Cao, Z; Chen, X; Xu, Y; Liu, H; Wang, X; Wang, J; Hu, L; Wang, S ·
RPEP-12111 · 2025Semaglutide (score: 77.8) and dulaglutide (76.3) ranked highest among four once-weekly GLP-1 RAs, driven by superior HbA1c reduction and proven cardiovascular benefit. Both received "strongly recommended" classification. Exenatide microspheres (70.2) was also strongly recommended, primarily due to favorable cost. PEG loxenatide (62.9) received a weak recommendation due to narrower reimbursement and lower international adoption. Safety profiles were comparable across all four agents.
Li, Xiao; Qiu, Zhihong; Xue, Chaojun; Ren, Xiaokai; Dong, Zhanjun ·
RPEP-12112 · 2025The review establishes that GLP-1 receptor agonists delay gastric emptying as a key mechanism of action, which means patients may have retained gastric contents even after standard fasting periods before surgery. This creates a risk of pulmonary aspiration during anesthesia induction.
Recommendations include: careful preoperative assessment of GLP-1 RA medication details (drug type, dose, timing of last dose), pre-anesthesia gastric ultrasound to assess stomach contents, rapid sequence induction if gastric content retention is suspected, and additional monitoring during the perioperative period. The review emphasizes the need for thorough documentation of any GLP-1-related adverse events during anesthesia to build the evidence base for future guidelines.
Li, Xiao-Yu; Jin, Yun; Feng, Xiu-Ye; Wang, Rui-Chun; Chen, Jun-Ping; Lu, Bo ·
RPEP-12121 · 2025COVID-19 patients with coexisting coronary artery disease had significantly higher levels of sST2, myeloperoxidase, ALT, AST, BNP, and hs-cTnI, along with longer hospitalizations, more ICU admissions, and higher rates of heart failure and acute coronary syndrome compared to COVID-19 patients without CAD.
Multivariate analysis identified sST2 as an independent risk factor for COVID-19 patients with CAD (odds ratio 1.122). sST2 correlated positively with coronary angiography Gensini score (r=0.474, p<0.001) and was significantly elevated in patients with severe coronary disease (Gensini score ≥32). ROC analysis showed sST2 predicted ICU admission, hospital stay duration, and heart failure/ACS morbidity comparably to the invasive Gensini score.
Li, Xueqin; Tian, Yaxin; Cao, Hongyan; Cheng, Jinfang ·
RPEP-12123 · 2025Single-cell RNA sequencing in a perioperative ischemic stroke (PIS) mouse model identified a novel Spp1+ macrophage/microglia subgroup with enriched anti-inflammatory pathways and distinct lipid metabolic reprogramming. These cells express GLP-1 receptors, confirmed by immunofluorescence.
Semaglutide treatment resulted in:
- Significant reduction in cerebral infarct volume in PIS mice compared to ischemic stroke alone
- Increased proportion of Spp1+Edu+Iba-1+ cells (proliferating protective microglia) at 3 days post-PIS
- Significant attenuation of neuroinflammatory markers
- Significant improvement in sensorimotor function within 3 days
These findings reveal a novel protective immune cell subset and demonstrate it can be therapeutically expanded by semaglutide.
Li, Yan; Fan, Qiuyue; Pang, Rui; Cai, Ling; Qi, Jie; Chen, Weijie; Zhang, Yueman; Chen, Chen; Yu, Weifeng; Li, Peiying ·
RPEP-12126 · 2025Across 22 RCTs (15,347 participants), semaglutide significantly reduced systolic blood pressure (MD -2.90 mmHg, 95% CI -3.70 to -2.11, P<0.01) and diastolic blood pressure (MD -0.86 mmHg, 95% CI -1.34 to -0.38, P<0.01). Subgroup analysis: non-diabetic populations showed greater reductions (SBP -5.02 mmHg, DBP -1.96 mmHg) versus diabetic populations (SBP -1.87 mmHg, DBP -0.43 mmHg). Higher dose (2.4 mg) significantly lowered SBP by 4.31 mmHg and DBP by 1.84 mmHg. Sensitivity analysis confirmed robust results.
Li, Yihan; Xue, Kefan; Hu, Rui; Hu, Xiao; Guo, Ran; Guo, Hongxia; Li, Gang ·
RPEP-12128 · 2025The review systematically catalogs how three major neuropeptides influence colorectal cancer immunity:
1. **Substance P** — modulates immune cell recruitment and inflammatory responses in the tumor microenvironment
2. **Calcitonin gene-related peptide (CGRP)** — influences immune cell function and may affect how the tumor evades immune surveillance
3. **Vasoactive intestinal peptide (VIP)** — has immunomodulatory effects that can reshape the tumor's immune landscape
These neuropeptides, along with neurotransmitters and neurotrophic factors, form a complex neuroimmune axis that significantly impacts colorectal cancer progression and the tumor's ability to escape immune destruction.
Li, Ying; Yang, Sheng-Ya; Zhang, Ying-Ru; Wang, Yan ·
RPEP-12130 · 2025Chitosan-coated EDB nanoparticles (CS-EDB NPs) achieved 83.5% exenatide encapsulation efficiency, ~277 nm particle size, and -16.2 mV zeta potential. Compared to uncoated NPs, the chitosan coating reduced mucus penetration by 1.1-fold but increased cellular uptake by 2.15-fold and transepithelial transport by 1.77-fold. Uptake was primarily energy-dependent endocytosis with partial macropinocytosis. The NPs achieved 13.29% pharmacological bioavailability and effectively regulated blood glucose, serum lipids, and improved islet function with long-term oral administration.
Li, Yiyao; Tian, Huixian; Zeng, Han; Zhang, Yu; Yin, Tian; He, Haibing; Gou, Jingxin; Tang, Xing ·
RPEP-12132 · 2025Liraglutide regulates lipid metabolism through a newly identified ZBTB20-LPL pathway:
**In vitro (3T3-L1 adipocytes):**
- Reduced lipid droplets and triglyceride (TG) levels
- Altered expression of genes involved in fatty acid metabolism, lipogenesis, fatty acid oxidation, and adipocyte browning
- Downregulated ZBTB20, a transcriptional suppressor
- ZBTB20 overexpression confirmed it inhibits LPL (lipoprotein lipase) expression
**In vivo (ob/ob obese mice, 4 weeks):**
- Improved blood lipid levels
- Reduced adipose tissue volume and adipocyte size
- Confirmed ZBTB20-LPL pathway regulation in adipose tissue
This establishes a molecular mechanism: liraglutide → reduced ZBTB20 → increased LPL → enhanced lipid breakdown.
Li, Yue; Gao, Rui; Yang, Zhiyan; Zong, Huiying; Li, Yan ·
RPEP-12135 · 2025GLP-1 receptor agonists (semaglutide, liraglutide), metformin, SGLT-2 inhibitors (dapagliflozin), and berberine all interact with gut microbiota to exert therapeutic effects in type 2 diabetes. Each drug modulates metabolic homeostasis, immune response, and gut barrier function through microbiome changes. Notably, each drug can have conflicting effects on gut flora depending on timing and mode of administration. The gut microbiota may also impact drug safety profiles, suggesting bidirectional drug-microbiome interactions.
Li, Yushan; He, Ziling; Li, Chunyan; Huang, Jing; Yu, Zheng ·
RPEP-12141 · 2025Researchers engineered a probiotic bacterium (Lactococcus lactis) to produce lactoferrin antimicrobial peptides (lactoferricin and lactoferrampin) and fed it to chickens. The engineered probiotic inhibited pathogenic E. coli (APEC-O78) and Staphylococcus aureus in vitro, and when added to chicken feed it improved growth performance, boosted immune markers (serum IgG, intestinal SIgA), suppressed pro-inflammatory cytokines (IL-1β, IL-12, IFN-γ, TNF-α), and restored gut microbiome balance disrupted by infection.
The construct was designed without antibiotic resistance genes and included a fluorescent marker for tracking — addressing safety concerns about engineered probiotics entering the food chain.
Li, Zhuoran; Wang, Xueying; Zheng, Dianzhong; Han, Fuzhen; Li, Yue; Zhou, Han; Li, Jiaxuan; Cui, Wen; Jiang, Yanping; Wang, Xiaona; Xie, Weichun; Tang, Lijie · Animal
RPEP-12144 · 2025Bitter taste receptors (TAS2Rs) in the intestines do far more than detect bitter flavors — they regulate the release of gut hormones like GLP-1, control gastric emptying, and influence appetite, satiety, and energy balance. This review reveals that TAS2Rs interact with other taste receptors in the gut through shared signaling pathways, creating a complex network that affects metabolic health and disease progression.
TAS2R expression is influenced by genetics, gut microbiome composition, age, and sex. Environmental chemicals can also alter TAS2R expression, potentially contributing to metabolic disorders. The review positions TAS2Rs as promising therapeutic targets but warns that any intervention must account for the intricate crosstalk between different taste receptor systems in the gut.
Liang, Jiafan; Chen, Jiahui; Zhao, Guoping; Wang, Yanbo · Review
RPEP-12151 · 2025The human antimicrobial peptide HNP1 (human neutrophil α-defensin 1) — normally part of the body's immune defense — paradoxically promotes biofilm formation by the dangerous hospital-acquired pathogen Acinetobacter baumannii. HNP1 was found in the lung fluid of infected patients and interacts with the bacterial outer membrane protein OmpA to enhance biofilm production.
As a result of this HNP1-enhanced biofilm, A. baumannii becomes more tolerant to antibiotics and more effectively colonizes host cells and tissues. This represents a striking example of a pathogen co-opting a host defense peptide for its own benefit.
Liao, Chongbing; Liu, Qihui; Luo, Gan; Luo, Yinyue; Yao, Dan; Wang, Qingxia; Zhang, Jue; Wu, Yang; Jin, Jialin; Xu, Dan; Lu, Wuyuan · In Vitro
RPEP-12153 · 2025The MSI-1 antimicrobial peptide was covalently attached to a chitosan/polyvinyl alcohol hydrogel containing Prussian blue nanoparticles (PBNPs). The dual-mode system demonstrated:
- Sustained bactericidal activity against S. aureus and E. coli for 24 hours through the antimicrobial peptide surface
- Photothermal heating to 48.3°C within 10 minutes under 808 nm near-infrared light, sufficient to disrupt bacterial biofilms
- Over 90% cell survival in co-culture for 3 days, indicating biocompatibility
- No damage to major organs in animal experiments
The mild photothermal temperature avoids thermal damage to healthy tissue while still being effective against biofilms.
Liao, Zhiyi; Li, Jiayi; Ni, Wenqiang; Zhan, Rixing; Xu, Xisheng ·
RPEP-12156 · 2025Extracellular vesicles from stem cells engineered with the CGRP antagonist peptide CGRP8-37 showed multimodal therapeutic effects in osteoarthritis. In vitro, the EVs downregulated inflammatory markers (TNF, TLR4, MAPK8) in nerve cells and promoted cartilage-building gene expression. In vivo (mouse model), intra-articular injection reduced pain behaviors, preserved cartilage structure, restored stem/progenitor cell localization, and trended toward reducing Substance P levels. The EVs carried anti-inflammatory miRNAs, proteins including neprilysin (which degrades the pain peptide Substance P), and 11 long non-coding RNAs linked to joint homeostasis.
Liebmann, Kevin; Castillo, Mario; Jergova, Stanislava; Rahimi, Behnaz; Kaplan, Lee D; Best, Thomas M; Sagen, Jacqueline; Kouroupis, Dimitrios ·
RPEP-12163 · 2025Among 1,976 propensity-matched T2DM patients (988 GLP-1RA users, 988 non-users) without baseline KOA, GLP-1RA treatment was associated with significantly lower KOA risk: 4.66% vs 8.81% developed KOA (adjusted HR = 0.852, 95% CI 0.784-0.930, P < 0.001).
Among 744 propensity-matched T2DM patients with existing KOA (372 GLP-1RA users, 372 non-users), GLP-1RA treatment was associated with lower total knee replacement rates: 10.48% vs 18.82% underwent TKR (adjusted HR = 0.913, 95% CI 0.885-0.977, P = 0.015). Kaplan-Meier survival analysis confirmed significantly different cumulative risk curves for both outcomes (log-rank P < 0.001 for both).
Lin, Chih-Ping; Chung, Chi-Hsiang; Lu, Chieh-Hua; Su, Sheng-Chiang; Kuo, Feng-Chih; Liu, Jhih-Syuan; Li, Peng-Fei; Huang, Chia-Luen; Ho, Li-Ju; Chen, Kuan-Chan; Chang, Chun-Yung; Lin, Ming-Shiun; Liu, Yi-Chen; Cheng, An-Che; Lin, Hong-Han; Kuo, Shi-Wen; Lee, Chien-Hsing; Hsieh, Chang-Hsun; Hung, Yi-Jen; Liu, Hsin-Ya; Guo, Lan-Yuen; Chien, Wu-Chien ·
RPEP-12165 · 2025The microneedle patch loaded up to 2.21 mg of liraglutide in just 0.9 cm² — nearly two orders of magnitude more drug than conventional dissolving microneedle patches of the same size. Each application delivered up to 0.93 mg into skin with less than 6.8% dosing variability.
Compared to subcutaneous injection, the microneedle patch achieved relative bioavailability of 69.8% in rats and 46.3% in minipigs, with faster initial absorption. In diabetic rats, the patch produced similar blood sugar-lowering effects to injection. After 7 days of daily application to the same site on minipigs, only mild erythema (redness) was observed within the first 4 hours, with no lasting skin irritation.
Lin, Hongbing; Liu, Jinbin; Hou, Yulin; Yu, Zhiyan; Hong, Juan; Yu, Jianghong; Chen, Yu; Hu, Jingwen; Xia, Dengning ·
RPEP-12168 · 2025Semaglutide protected diabetic mouse hearts from inflammation-driven damage through a specific molecular pathway: Sirt3 → RKIP → TBK1-NF-κB. In diabetic mice, semaglutide reduced cardiac fibrosis, improved heart function, decreased oxidative stress, and suppressed cardiomyocyte death. The anti-inflammatory effect worked through cAMP/PKA signaling rather than blood sugar reduction — meaning the heart benefits were independent of glucose control.
Critically, when RKIP (Raf kinase inhibitor protein) was knocked out, semaglutide lost its cardioprotective effects, confirming this pathway is essential. The same decrease in RKIP expression and activation of inflammatory signaling was found in human diabetic heart tissue, suggesting this mechanism is clinically relevant.
Lin, Kaibin; Wang, Ai; Zhai, Changlin; Zhao, Yun; Hu, Huilin; Huang, Dong; Zhai, Qiwei; Yan, Yan; Ge, Junbo · Animal
RPEP-12174 · 2025Multi-omic analysis of 24 GBM patients identified an average of 148 mutated genes and 200 mutation sites per patient, with no dominant shared mutations across the cohort. An average of 107 neoantigen candidates were predicted per patient. Very few neoantigens were shared by more than two patients, and no dominant shared neoantigen could be identified.
A minimum of 11 peptides was required to create a bulk vaccine covering all 24 patients, ensuring each patient had at least one targetable neoantigen. The tumor immune microenvironment was dominated by NK cells and Th1 cells. TCR/BCR repertoires showed clustered CDR3 sequences in tumors with reduced diversity compared to peripheral blood, suggesting tumor-specific immune responses were already present but limited.
Lin, Qingtang; Wei, Yukui; Xu, Geng; Wang, Leiming; Ling, Feng; Chen, Xiaojie; Cheng, Ye; Zhou, Yiming ·
RPEP-12176 · 2025GLP-1RAs significantly reduced BMI, body weight, waist circumference, waist-to-hip ratio, and abdominal girth (all P < 0.0001). For glucose homeostasis, they significantly reduced fasting insulin, 2-hour OGTT glucose, and HOMA-IR. HDL was slightly reduced. Hormone levels (DHEAS, SHBG, total/free testosterone, FAI) were unchanged. Safety: increased nausea (P = 0.02), vomiting (P = 0.04), and dizziness (P = 0.03).
Lin, Shike; Deng, Yan; Huang, Jing; Li, Meiyan; Sooranna, Suren Rao; Qin, Minzhen; Tan, Bing ·
RPEP-12178 · 2025This review found that C-peptide — a byproduct released when the pancreas makes insulin — is underused in managing type 2 diabetes. While it's well established as a diagnostic tool for type 1 diabetes, the evidence suggests C-peptide levels can also predict how well patients respond to different diabetes medications and help forecast disease progression in type 2 diabetes. The review highlights a gap between C-peptide's potential clinical value in T2D and how little it's actually used in practice.
Lin, YeunYi; McCrimmon, Rory J; Pearson, Ewan R ·
RPEP-12184 · 2025CGRP expression was significantly reduced in both the cornea and trigeminal ganglion of mice with experimentally induced dry eye disease, establishing a biological rationale for replacement therapy.
In cultured human corneal epithelial cells under stress conditions, CGRP promoted cell proliferation, reduced programmed cell death, and lowered expression of inflammatory cytokines TNF-α, IL-1β, and IL-6.
In live mice with dry eye, topical CGRP applied three times daily for two weeks significantly decreased corneal fluorescein staining scores (a measure of surface damage), increased tear break-up time, and preserved the corneal epithelium. CGRP also reduced infiltrating CD45+ immune cells and inflammatory cytokine expression in the cornea, though it did not significantly affect immune cells in the conjunctiva.
Lin, Zhirong; Verma, Bhupender; Zhu, Shuyan; Zidan, Asmaa A; Najafi, Sheyda; Naderi, Amirreza; Elbasiony, Elsayed; Yin, Jia ·
RPEP-12190 · 2025Serum levels of hBD-2 and S100A8/A9 were significantly elevated immediately after the race in both marathon and half-marathon runners compared to baseline and sedentary controls, then returned to baseline by seven days postrace.
In runners who developed exercise-induced bronchoconstriction (EIB), S100A8 levels remained slightly elevated during recovery, and hBD-2 was modestly increased. Critically, S100A8 levels showed a negative correlation with lung function parameters including forced expiratory volume and mid-expiratory flows — meaning higher peptide levels were associated with worse airway function. Angiogenin and major basic protein (MBP) did not show the same pattern.
Lingitz, Marie-Therese; Kühtreiber, Hannes; Auer, Lisa; Mildner, Michael; Krenn, Claus G; Aigner, Clemens; Moser, Bernhard; Bekos, Christine; Ankersmit, Hendrik Jan ·
RPEP-12191 · 2025Once-weekly IcoSema (combining insulin icodec and semaglutide in a single injection) demonstrated superior HbA1c reduction compared to semaglutide alone over 52 weeks: -1.35% vs -0.90% (treatment difference -0.44%, p<0.0001). IcoSema also produced significantly greater fasting glucose reduction (-2.48 vs -1.43 mmol/L). However, semaglutide alone was significantly better for weight: -3.70 kg vs +0.84 kg with IcoSema. Rates of clinically significant hypoglycemia and gastrointestinal side effects were similar between groups.
Lingvay, Ildiko; Benamar, Malik; Chen, Liming; Fu, Ariel; Jódar, Esteban; Nishida, Tomoyuki; Riveline, Jean-Pierre; Yabe, Daisuke; Zueger, Thomas; Réa, Rosângela ·
RPEP-12193 · 2025In a discrete-choice experiment, 70-85% of episodic migraine patients preferred an oral daily pill profile (like the CGRP receptor antagonist atogepant) over injectable CGRP monoclonal antibody profiles, even when efficacy was similar. The two most important treatment attributes were: (1) absence of nausea and (2) oral pill administration rather than injection or infusion. Patients valued oral delivery approximately 2.5 times more than avoiding mild nausea.
Lipton, Richard B; Gandhi, Pranav; Myers, Kelley; Bussberg, Cooper; Stokes, Jonathan; Nahas, Stephanie J ·
RPEP-12199 · 2025Among 265 endocrinology medical staff surveyed, the average knowledge score was 11.77 out of 16 (73.6%), the attitude score was 39.30 out of 50 (78.6%), and the practice score was 27.70 out of 35 (79.1%). While these scores are above midpoint, they indicate meaningful gaps in professional proficiency with these commonly prescribed medications.
Structural equation modeling revealed strong causal pathways: knowledge significantly influenced both attitude (β = 0.976, P < 0.001) and practice (β = 1.289, P < 0.001), while attitude also significantly affected practice (β = 0.627, P < 0.001). This confirms that improving knowledge is the most effective lever for improving prescribing behavior.
Liu, Bingling; Wu, Xueyi; Zou, Xiao; Sheng, Jianjian; Yu, Jie ·
RPEP-12200 · 2025Analysis of 48,214 FAERS reports (57.5% female) found that GLP-1 receptor agonist plus metformin combination therapy had lower adverse event rates than either drug alone (monotherapy). Common AEs were nausea and weight loss. Unexpected safety signals included kidney injury and pancreatic cancer. Gender-specific patterns emerged: males reported more renal calculi and early-onset AEs (within 30 days), while females experienced more delayed AEs (beyond 360 days). Weight loss was consistent across all demographic groups.
Liu, Boyi; Huang, Ruizhe; Zhang, Wenchao; Tian, Jie; Yao, Xian; Chen, Danna ·
RPEP-12207 · 2025The review identifies several key concerns with compounded semaglutide:
1. Quality control gaps: Compounded semaglutide products currently available may lack the rigorous quality controls historically associated with compounded medications, leading to risks of dosing errors and adverse outcomes.
2. Fraudulent products: The global compounded semaglutide market has seen batches of counterfeit products, adding a layer of safety risk beyond quality variation.
3. Regulatory complexity: While compounding is legal when following federal and state regulations, the line between lawful and unlawful compounding has become blurred in the semaglutide market.
4. Provider opportunity: Pharmacists and healthcare providers are uniquely positioned to direct patients to legitimate compounded sources, counsel on proper dosage and administration, and minimize safety risks.
Liu, Grace; Jarema, Marissa; Mo, Millie; Stievater, Trish ·
RPEP-12212 · 2025Semaglutide significantly ameliorated osteoporosis in rats when combined with jaw bone marrow mesenchymal stem cell (JBMMSC) intervention. The drug markedly increased calcified nodule formation and alkaline phosphatase (ALP) activity, demonstrating enhanced osteogenic potential.
Mechanistically, semaglutide operates through dual pathways: (1) promoting osteogenic and adipogenic differentiation via the BMP2/STAT3/TET3/SHP2 signaling axis, and (2) preserving stem cell stemness and proliferation via the CREB/YAP/BRD4 axis. Western blot analysis confirmed significant upregulation of p-CREB, OCT4, BMP2, and RUNX2 proteins in semaglutide-treated JBMMSCs. These mechanisms were validated by rescue experiments, confirming the dual pathway model.
Liu, Huiming; Tian, Yawei; Bao, Xiaoxue; Li, Yukun ·
RPEP-12216 · 2025Exendin-4 inhibited the progression of diabetic retinopathy in both a high-glucose-induced human retinal endothelial cell (HREC) model and a streptozotocin (STZ)-induced rat model of diabetic retinopathy.
The peptide's protective effects included reduced cell death, inhibited abnormal blood vessel tube formation, and suppressed inflammatory markers. Mechanistically, Exendin-4 downregulated TGFB2 (transforming growth factor beta-2) expression. When TGFB2 was overexpressed in cells, Exendin-4's protective effects were reversed, establishing TGFB2 as the mediating pathway.
Liu, Jufen; Wang, Huijing; Huang, Cuiting ·
RPEP-12224 · 2025Across 32 randomized controlled trials with 2,783 participants, GLP-1 receptor agonists were associated with resolution of metabolic dysfunction-associated steatohepatitis (MASH) without worsening fibrosis at a relative risk of 3.33 (95% CI 2.38–4.66, I²=12.9%), demonstrating remarkable consistency across studies.
GLP-1 RAs reduced liver fat content by a weighted mean difference of -4.34% (95% CI -5.88 to -2.81), though with high heterogeneity (I²=95.3%). They also significantly improved liver function tests, serum triglycerides, body weight, BMI, waist circumference, and HbA1c. Gastrointestinal side effects were increased.
DPP-4 inhibitors showed no significant effects on any liver or metabolic parameter except HbA1c (WMD -0.62%, 95% CI -0.91 to -0.33), establishing a clear distinction between the two incretin-based drug classes for liver disease.
Liu, Lili; Xia, Ying; Wang, Bian; Zhang, Yiyu ·
RPEP-12228 · 2025Two egg white-derived ACE-inhibitory peptides (RADHPFL and YAEERYPIL) were encapsulated into liposomes using a controlled microfluidic self-assembly process. β-Glucan was grafted onto the liposomal surface to target intestinal M cells via the Dectin-1 receptor.
Encapsulation significantly improved gastrointestinal stability of the peptides and preserved their ACE inhibitory activity compared to free peptides.
In spontaneously hypertensive rats (SHR), both single-dose and continuous administration of the β-glucan-functionalized liposomes produced superior antihypertensive effects compared to both free peptides and unmodified liposomes. The blood pressure reduction was mediated through modulation of the renin-angiotensin system, improved renal and cardiac function, and amelioration of endothelial dysfunction.
Liu, Meijun; Qiao, Fengzhi; Wang, Shaolei; Ding, Wenhao; Xuan, Shichao; De Souza, Cristabelle; Asif Javaid, Muhammad; Zhang, Zhe; Yi, Huaxi; Zhang, Lanwei; Lin, Kai ·
RPEP-12235 · 2025Semax improved functional recovery in a mouse spinal cord injury model, as measured by footprint analysis, Basso locomotor scores, and inclined plane tests. The mechanism was traced through a novel pathway:
1. Semax targets the μ-opioid receptor (Oprm1)
2. This regulates the ubiquitin-specific protease USP18
3. USP18 controls deubiquitination of the FTO protein (fat mass and obesity-associated protein)
4. This stabilizes lysosomal membranes, reducing lysosomal membrane permeabilization (LMP)
5. Reduced LMP prevents pyroptosis (inflammatory cell death)
RNA sequencing, network pharmacology, and molecular docking confirmed the μ-opioid receptor as Semax's molecular target. USP18 knockdown experiments validated its role in the pathway.
Liu, Rongjie; Chen, Yituo; Huang, Haosheng; Li, Xiang; Lv, Junlei; Jiang, Liting; Jiang, Hongyi; Wu, Chenyu; Chen, Weikai; Xu, Hongwei; Zhu, Zhefan; Cai, Haoxu; Xiao, Jian; Yin, Lihui; Ni, Wenfei ·
RPEP-12243 · 2025Preclinical studies demonstrate that semaglutide significantly reduces alcohol consumption and relapse of alcohol addiction in rats. The GLP-1 system, described as a gut-brain peptide pathway, is implicated in the neurobiology of addictive behaviors, making the GLP-1 receptor a promising therapeutic target for alcohol use disorder.
The review notes that semaglutide may be particularly effective for overweight patients with AUD, given its dual effects on metabolism and brain reward pathways. However, safety concerns include gallbladder disease and complications from delayed gastric emptying, necessitating careful evaluation before broader clinical use.
Liu, Tingting; Shi, Fuqiang; Guo, Zhihua; Li, Hongwu; Qin, Di ·