RPEP-08639 · 2024Across nine included studies, there was early evidence suggesting GLP-1 receptor agonists may improve obstructive sleep apnea as measured by reductions in the apnoea-hypopnoea index (AHI). However, this finding was not consistent — some studies showed contradictory results.
Of the nine articles, five were randomized clinical trials of variable quality, one was a non-randomized trial, one was a case report, one was a study protocol, and one was an RCT abstract. All studies examined GLP-1RA use in patients with diagnosed OSA or suggestive symptoms. The medications were generally well tolerated, with only minor gastrointestinal side effects reported.
Le, Khang Duy Ricky; Le, Kelvin; Foo, Felicia ·
RPEP-08642 · 2024The modified radiopeptide [203Pb]Pb-PSC-PEG2-TOC showed significantly improved properties versus standard DOTATOC:
- Better receptor binding and tumor accumulation/retention
- Faster renal clearance (reduced kidney toxicity risk)
- [212Pb]Pb-PSC-PEG2-TOC showed dose-dependent therapeutic effect with minimal toxicity
- Fractionated administration (3 doses of 3.7 MBq) achieved:
- 80% overall survival at 120 days
- 70% complete response (tumor disappearance)
- Minimal signs of toxicity
- Structural modifications to chelator (PSC) and linker (PEG2) drove the improvements
Lee, Dongyoul; Li, Mengshi; Liu, Dijie; Baumhover, Nicholas J; Sagastume, Edwin A; Marks, Brenna M; Rastogi, Prerna; Pigge, F Christopher; Menda, Yusuf; Johnson, Frances L; Schultz, Michael K ·
RPEP-08643 · 2024In 12 women with moderate to severe interstitial cystitis who had failed pentosan polysulfate treatment, a single intravesical injection of BPC-157 (10 mg total) around the inflamed bladder area produced complete symptom resolution in 10 of 12 patients (100% success rating). The remaining 2 patients reported 80% improvement. All 12 scored 5/5 on the Global Response Assessment. No adverse events were reported, and no patients dropped out.
Lee, Edwin; Walker, Christopher; Ayadi, Bahram ·
RPEP-08648 · 2024Researchers engineered novel peptide activators of both amylin and calcitonin receptors by systematically mutating rat amylin. By screening the C-terminal fragment of rat amylin for affinity-enhancing mutations, they identified up to twelve mutational combinations that increased binding affinity for both receptor types by over 100-fold.
Three full-length (37 amino acid) rat amylin analogs incorporating these mutations were then tested for receptor activation potency. All three showed 5- to 10-fold greater potency than endogenous rat amylin and outperformed pramlintide, the only clinically approved amylin receptor activator currently used for diabetes management.
Lee, Sangmin · In Vitro
RPEP-08654 · 2024This is a clinical trial protocol (not yet completed). The study will randomize 264 obese women (BMI >30, aged 18-45) with endometrial hyperplasia or early-stage endometrial cancer into three groups:
1. LNG-IUD alone (standard care)
2. LNG-IUD + metformin
3. LNG-IUD + metformin + liraglutide
The hypothesis is that the triple combination will achieve higher complete pathological remission rates than LNG-IUD alone, through both direct metabolic effects and weight loss that reduces estrogen-driven cancer growth. The 12-month trial will also track glucose, insulin levels, weight changes, and histological outcomes.
Leipold, Gergő; Tóth, Richárd; Hársfalvi, Péter; Lőczi, Lotti; Török, Marianna; Keszthelyi, Attila; Ács, Nándor; Lintner, Balázs; Várbíró, Szabolcs; Keszthelyi, Márton ·
RPEP-08656 · 2024Among over 713,000 users of specific diabetes drug classes:
- Higher maximum daily temperatures were linearly associated with increased serious hypoglycemia among users of glimepiride and glyburide (sulfonylureas) but not glipizide (interaction p=0.048)
- An inverse association was found between temperature and DKA among sitagliptin (DPP-4i) users (p=0.016) — less DKA in hotter weather
- Exenatide (GLP-1RA) users showed no significant temperature-DKA association (p=0.080)
- No drug class showed temperature-related changes in sudden cardiac arrest risk
The findings indicate drug-specific and even agent-specific differences in how ambient temperature affects glycemic safety outcomes.
Leonard, Charles E; Bogar, Kacie; Brensinger, Colleen M; Bilker, Warren B; Bell, Michelle L; Flory, James H; Shi, Christopher; Chen, Cheng; Hennessy, Sean ·
RPEP-08657 · 2024The review identifies several key roles of antimicrobial peptides in acne:
- AMPs (human β-defensins, cathelicidin LL-37, dermcidin, RNase-7) are elevated in acne-affected skin
- They function as both antibacterial agents and immune modulators, coordinating host-microbiota interactions
- AMPs improve skin tight junction (TJ) barrier function by activating PI3K, GSK-3, aPKC, and Rac1 proteins
- Elevated AMP expression likely represents a compensatory mechanism to protect skin with impaired permeability
- AMPs link acne immune responses to metabolic signaling (insulin/IGF-1, PI3K/Akt/mTOR/FoxO1, glucotoxicity)
- Acne is associated with decreased diversity of C. acnes phylotypes, with AMPs potentially regulating this dysbiosis
Lesiak, Agata; Paprocka, Paulina; Wnorowska, Urszula; Mańkowska, Angelika; Król, Grzegorz; Głuszek, Katarzyna; Piktel, Ewelina; Spałek, Jakub; Okła, Sławomir; Fiedoruk, Krzysztof; Durnaś, Bonita; Bucki, Robert ·
RPEP-08662 · 2024TC-14, a novel antimicrobial peptide engineered from a Chinese tree shrew cathelicidin (TC-33), exhibited a 432-fold increase in antimicrobial activity compared to the parent peptide. TC-14 adopts an amphipathic α-helical structure and kills bacteria by targeting and rupturing their membranes. Critically, TC-14 showed no cytotoxic or hemolytic activity, high biocompatibility in vivo, and provided significant protection in a mouse skin infection model — demonstrating both potency and safety.
Li, Chenxi; Cai, Ying; Luo, Lin; Tian, Gengzhou; Wang, Xingyu; Yan, An; Wang, Liunan; Wu, Sijing; Wu, Zhongxiang; Zhang, Tianyu; Chen, Wenlin; Zhang, Zhiye ·
RPEP-08669 · 2024From Douchi hydrolysate, five ACE inhibitory peptides were identified: LF, VVF, VGAW, GLFG, and NGK. The tetrapeptide VGAW was the most potent:
- ACE inhibition IC50: 46.6 ± 5.2 µM (competitive inhibitor)
- Excellent thermal and pH stability
- Molecular docking revealed 8 hydrogen bonds between VGAW and ACE
- Lineweaver-Burk plots confirmed competitive inhibition mechanism
- Significantly reduced blood pressure in spontaneously hypertensive rats at 12.5, 25, and 50 mg/kg doses
The optimal enzyme combination for generating these peptides was pepsin-trypsin-chymotrypsin, outperforming 10 single enzymes and 3 other combinations.
Li, Jianfei; Hu, Haohan; Chen, Xiya; Zhu, Haiting; Zhang, Wenhao; Tai, Zhiyuan; Yu, Xiaodong; He, Qiyi ·
RPEP-08681 · 2024Two peptides were identified with ACE inhibitory activity: SNHANQLDFHP (IC₅₀ = 172.07 μM) and PVQVLASAYR (IC₅₀ = 90.69 μM). Molecular docking showed both interact with ACE through hydrogen bonds and hydrophobic interactions.
In endothelial cells (EA.hy926), both peptides decreased endothelin-1 secretion (a vasoconstrictor), increased nitric oxide release (a vasodilator), and upregulated ACE2 activity (the protective arm of the renin-angiotensin system). Both peptides showed good stability against simulated gastrointestinal enzyme digestion, supporting potential oral bioavailability.
Li, Xin; Peng, Chenghai; Xiao, Suyao; Wang, Qun; Zhou, Aimei ·
RPEP-08688 · 2024Two cryo-EM structures were solved: SSTR5-Gi complex with pasireotide at 3.09Å resolution and SSTR5-Gi complex with octreotide at 3.24Å resolution. Structural analysis revealed that pasireotide's preferential binding to SSTR5 is mediated by interactions between its Tyr(Bzl) and DTrp residues and specific SSTR5 binding pocket features.
For octreotide's bias toward SSTR2, key residues were identified: Q2.63, N6.55, F7.35, and extracellular loop 2 (ECL2) of SSTR2 play crucial roles. These findings explain the molecular basis of peptide-receptor selectivity and provide specific structural targets for designing more selective SSTR5-targeted drugs.
Li, Ying-Ge; Meng, Xian-Yu; Yang, Xiru; Ling, Sheng-Long; Shi, Pan; Tian, Chang-Lin; Yang, Fan ·
RPEP-08689 · 2024In a streptozotocin/high-fat diet diabetic rat model, liraglutide treatment produced dose-dependent improvements:
- Significant reductions in blood glucose, serum creatinine, and blood urea nitrogen (P < 0.05)
- Dose-dependent decrease in 24-hour urinary protein excretion and microalbuminuria (P < 0.05)
- Improved glomerular and interstitial damage
- Suppressed expression of endothelial injury markers CD31, CD34, and VE-cadherin (P < 0.05)
- Significantly increased nitric oxide (NO) production (P < 0.05)
- Decreased expression of VEGF, Dll4, and Notch2 protein in the Notch2 signaling pathway (P < 0.05)
- Higher doses showed more pronounced therapeutic effects
Li, Yining; Chen, Yulin; Zhang, Hui; Chen, Weidong; Pan, Yan ·
RPEP-08690 · 2024The RADA16-OPD peptide hydrogel (RADA16 coupled with the osteopontin-derived fragment SVVYGLR) demonstrated superior bone regeneration in a rat skull defect model compared to RADA16 alone or untreated controls. Micro-CT analysis showed higher bone volume/total volume (BV/TV), higher trabecular number (TB.N.), and higher bone mineral density (BMD) at multiple time points.
Histological analysis confirmed more new bone formation and mature collagen production in the RADA16-OPD group. Expression of osteogenic markers alkaline phosphatase (ALP) and osteocalcin (OCN) were elevated. Additionally, immunofluorescence showed significantly higher CD31 (platelet/endothelial cell adhesion molecule) expression, indicating enhanced blood vessel formation. Live/dead staining confirmed the scaffold was non-toxic to rat adipose-derived stem cells (rASCs).
Li, Yong; Tang, Yao; Chen, LiFu; Li, HaiTao; Wang, Hong; Wang, Jian ·
RPEP-08695 · 2024From candidate peptides screened against the METTL3-METTL14 binding interface, RM3 showed the highest anti-cancer potency by both inhibiting METTL3 activity and promoting its proteasomal degradation. The stapled version (RSM3) had enhanced stability and maintained the α-helical structure needed for METTL3 interaction.
In two in vivo tumor models, RSM3 treatment significantly suppressed tumor growth and enhanced apoptosis. Mechanistically, RSM3 increased METTL3 degradation, reduced global RNA m6A methylation levels, upregulated programmed cell death genes, and inhibited cancer-promoting signaling pathways. This dual mechanism — complex disruption plus protein degradation — distinguishes it from competitive small-molecule inhibitors.
Li, Zenghui; Feng, Yuqing; Han, Hong; Jiang, Xingyue; Chen, Weiyu; Ma, Xuezhen; Mei, Yang; Yuan, Dan; Zhang, Dingxiao; Shi, Junfeng ·
RPEP-08699 · 2024Researchers systematically replaced each amino acid in teriparatide (the first FDA-approved bone-building osteoporosis drug) with alanine, one position at a time, to map which residues are essential for its anti-osteoporosis activity. They synthesized and tested 34 teriparatide derivatives.
Five residues proved critical: replacing Gly12, His14, Ser17, Arg20, or Leu24 with alanine dramatically reduced activity — these positions are essential for teriparatide's bone-building function. Conversely, replacing Gly13 or Gln30 with alanine actually increased activity, suggesting these positions are candidates for modification to create more potent next-generation osteoporosis peptides.
Liang, Haiyan; Shen, Huaxing; Zheng, Mengjun; Shi, Yejiao; Li, Xiang · Basic Science (Peptide Chemistry)
RPEP-08701 · 2024After 48 weeks of dulaglutide administration, the composition of intestinal flora changed significantly in newly diagnosed T2DM patients, with a notable reduction in overall bacterial abundance. No significant changes were observed after just 1 week of treatment.
Fasting glucose levels, fasting C-peptide levels, HbA1c levels, and BMI were all found to be closely associated with changes in intestinal flora composition, suggesting that gut microbiome modulation may be one of the mechanisms through which dulaglutide treats type 2 diabetes.
Liang, Lei; Su, XiaoYun; Guan, Yaxin; Wu, Bin; Zhang, Xuxiang; Nian, Xin ·
RPEP-08704 · 2024Among 68,351 incretin therapy case reports in FAERS, 1,327 (1.94%) involved hepatobiliary adverse events, with a pooled reporting odds ratio of 2.85 indicating a positive correlation.
DPP-4 inhibitors showed statistically significant associations with cholelithiasis (gallstones), chronic cholecystitis, and biliary diseases. GLP-1 receptor agonists showed weaker overall associations but were linked to gallbladder/biliary disorders and had higher acute cholecystitis risk. Among specific drugs, liraglutide and semaglutide showed stronger positive correlations among GLP-1 agonists, while sitagliptin, linagliptin, and vildagliptin stood out among DPP-4 inhibitors. The associations may be dose-dependent.
Liang, Yankun; Zhang, Zhenpo; Zheng, Jingping; Wang, Yuting; He, Jiaxin; Zhao, Juanzhi; Su, Ling ·
RPEP-08705 · 2024Linking the antidepressant drug sulpiride to a cell-penetrating peptide (VPALR, derived from the DNA repair protein Ku70) created a conjugate (VPALR-SUL) that crossed the blood-brain barrier more effectively than sulpiride alone. In depressed mice, VPALR-SUL significantly improved two key depression measures — increased struggle time and total distance — compared to sulpiride alone.
Critically, the conjugate also reduced serum prolactin levels — addressing a major side effect of sulpiride. The drug normally can't reach the brain's pituitary gland well enough to suppress prolactin release, causing hyperprolactinemia (elevated prolactin with side effects like sexual dysfunction and breast changes). Pharmacokinetic data showed VPALR-SUL had a longer half-life and better bioavailability than sulpiride alone.
Liang, Yuan; Yang, Yu; Huang, Ruiyan; Ning, Jiangyue; Bao, Xingyan; Yan, Zelong; Chen, Haotian; Ding, Li; Shu, Chang · Animal Study
RPEP-08706 · 2024From 1,444 screened studies, six met inclusion criteria (four RCTs and two protocols). Two RCTs measuring amyloid-beta and tau biomarkers found no difference between GLP-1 RA and placebo groups at end of treatment. Three RCTs with cognitive endpoints also showed no improvement in treated groups. However, GLP-1 drugs provided metabolic benefits including lower BMI and improved glucose tolerance, and may mitigate decline in cerebral glucose metabolism as assessed by 18F-FDG PET imaging, with enhanced blood-brain glucose transport capacity.
Liang, Yulin; Doré, Vincent; Rowe, Christopher C; Krishnadas, Natasha ·
RPEP-08707 · 2024Among 4,109 HF patients (median follow-up 25 months, max 8 years), FFA levels above 0.4-0.42 mmol/L were associated with increased risk of all three outcomes. Patients in the highest FFA tertile had significantly elevated risks versus the lowest tertile:
- CV death & HF hospitalization: HR 1.32 (95% CI: 1.11-1.58)
- CV death alone: HR 1.45 (95% CI: 1.16-1.82)
- All-cause mortality: HR 1.39 (95% CI: 1.15-1.68)
These associations were consistent across HF subtypes (HFpEF and HFmrEF/HFrEF). Combining FFA with the natriuretic peptide biomarker NT-proBNP significantly improved the C-index for predicting outcomes compared to NT-proBNP alone (P < 0.01).
Liao, Guang-Zhi; Liu, Hui-Hui; He, Chun-Hui; Feng, Jia-Yu; Zhuang, Xiao-Feng; Wang, Jing-Xi; Zhou, Ping; Huang, Yan; Zhou, Qiong; Zhai, Mei; Zhang, Yu-Hui; Zhang, Jian ·
RPEP-08716 · 2024The LL37-activated carbon-chitosan (LL37-AC-CS) hydrogel demonstrated effectiveness against three clinically important bacteria: Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus. The hydrogel bound more endotoxin than activated carbon with chitosan hydrogel alone, indicating synergistic toxin-neutralizing capacity. The dressing induced cell migration after 72 hours (promoting wound closure) and showed no cytotoxicity toward normal human dermal fibroblasts (NHDF) after 72 hours of treatment.
The microsphere encapsulation strategy successfully protected LL37 from degradation in wound fluid, maintaining its antimicrobial activity in an environment where the free peptide would normally lose effectiveness.
Lim, Bee-Yee; Azmi, Fazren; Ng, Shiow-Fern ·
RPEP-08718 · 2024VIP-induced glycogen synthesis in astrocytes requires CREB-mediated transcription that is calcium-dependent and requires conventional Protein Kinase C (PKC) but not Protein Kinase A (PKA). VIP also triggers nuclear accumulation of the CREB coactivator CRTC2 in astrocytic nuclei.
Transcriptomic profiling of VIP-stimulated astrocytes identified robust CREB transcription, including genes linked to glucose and glycogen metabolism. VIP-induced and glucose-induced glycogen synthesis share some molecular signatures but also have distinct features, though both require CREB-mediated transcription.
Lim, Wei Lee; Gaunt, Jessica Ruth; Tan, Jia Min; Zainolabidin, Norliyana; Bansal, Vibhavari Aysha; Lye, Yi Ming; Ch'ng, Toh Hean ·
RPEP-08731 · 2024Six drugs targeting CGRP are now approved for preventive treatment of episodic migraine in adults: four monoclonal antibodies (eptinezumab, erenumab, fremanezumab, galcanezumab) and two gepants (rimegepant, atogepant). The monoclonal antibodies and atogepant have demonstrated effectiveness for both episodic and chronic migraine. All CGRP-targeted therapies show favorable safety and tolerability profiles.
These therapies have enabled new paradigms for migraine prevention, moving beyond older drugs that were repurposed from other conditions toward purpose-built treatments designed specifically around the CGRP peptide pathway.
Lipton, Richard B ·
RPEP-08734 · 2024Liraglutide (GLP-1R agonist) attenuated pulmonary inflammation and fibrosis in a silica-induced mouse model. Mechanistically, GLP-1R activation disrupted a newly identified feedback loop between the NLRP3 inflammasome and PFKFB3-driven glycolysis in lung fibroblasts.
Inhibiting either the NLRP3 inflammasome or glycolysis suppressed the other, decreasing lactate production. Excess lactate drives histone lactylation — a chemical modification that turns on pro-fibrotic genes. GLP-1R activation blocked this cascade by: (1) disrupting the NLRP3/glycolysis interaction, (2) preventing lactate-mediated histone lactylation, (3) protecting mitochondria from metabolic stress, and (4) suppressing p300-mediated histone lactylation even when lactate was added directly. GLP-1R activation also blocked macrophage-to-fibroblast activation signaling.
Liu, Chenyang; Zhang, Qun; Zhou, Hong; Jin, Linling; Liu, Chang; Yang, Mingxia; Zhao, Xinyun; Ding, Wenqiu; Xie, Weiping; Kong, Hui ·
RPEP-08735 · 2024In a valproic acid (VPA)-induced female rat model of autism, researchers found that oxytocin and its receptor were overexpressed in the hippocampus and prefrontal cortex — the opposite of what is typically assumed in autism research, where oxytocin deficiency is the prevailing narrative. Administering exogenous oxytocin to healthy female rats actually triggered autism-like behaviors.
Critically, the oxytocin receptor antagonist Atosiban (a peptide drug) significantly improved multiple autism-like deficits in VPA-exposed female rats, including social interaction impairment, anxiety, and repetitive stereotypical behaviors. Atosiban also improved synaptic plasticity that had been impaired by VPA exposure.
Liu, Chunhua; Guo, Zhengyang; Pang, Jiyi; Zhang, Yuying; Yang, Zhuo; Cao, Jianting; Zhang, Tao · Animal
RPEP-08736 · 2024Exendin-4 (GLP-1R agonist) significantly increased the spontaneous firing rate and decreased firing regularity of nigral dopaminergic neurons in normal C57BL/6 mice. Blocking GLP-1 receptors with exendin(9-39) decreased firing rate, confirming that endogenous GLP-1 tonically modulates these neurons.
The excitatory effect involved PKA signaling and TRPC4/5 (transient receptor potential canonical) ion channels. Critically, both exogenous and endogenous GLP-1 maintained their excitatory effects on surviving dopaminergic neurons in a parkinsonian state. Since mild excitatory stimulation promotes neuroprotection and TH expression in dopamine neurons, the GLP-1-mediated excitation may partially contribute to anti-parkinsonian effects.
Liu, Cui; Liu, Wen-Hong; Yang, Wu; Chen, Lei; Xue, Yan; Chen, Xin-Yi ·
RPEP-08738 · 2024UV radiation accelerates skin aging (photoaging) by generating reactive oxygen species that activate matrix metalloproteinases — enzymes that break down collagen. Type I collagen makes up 80–90% of skin collagen, followed by type III (8–12%) and type V (5%). As photoaging progresses, total collagen decreases and the structural matrix of the skin breaks down.
The review finds that supplementing with collagen and collagen-derived peptides can counteract UV-induced skin damage. Both oral collagen peptide supplements and topical collagen-based products are being used increasingly in biomedical and aesthetic applications to restore collagen levels and improve photoaged skin appearance.
Liu, Helei; Dong, Junjuan; Du, Rina; Gao, Yaoxing; Zhao, Pengwei · Review
RPEP-08745 · 2024Type V adenovirus (ADV) was shown to induce tumor-associated macrophage (TAM) polarization to the immunosuppressive M2 phenotype and increase regulatory T cell (Treg) infiltration in the tumor microenvironment — an immunosuppressive feedback loop that counteracts the virus's anti-cancer effects.
Thymosin alpha-1 selectively compensated for these deficiencies by reprogramming M2-like TAMs toward an antitumoral phenotype and reshaping the tumor microenvironment for improved anti-tumor immunity. An engineered adenovirus (ADVTα1) that produces Tα1 directly enhanced anti-tumor efficacy through CD8+ T cell activation, demonstrating that both externally supplied and virus-produced Tα1 effectively orchestrate macrophage reprogramming.
Liu, Kua; Kong, Lingkai; Cui, Huawei; Zhang, Louqian; Xin, Qilei; Zhuang, Yan; Guo, Ciliang; Yao, Yongzhong; Tao, Jinqiu; Gu, Xiaosong; Jiang, Chunping; Wu, Junhua ·
RPEP-08746 · 2024Semaglutide demonstrated greater efficacy in reducing body weight, BMI, and BMI z-score compared to placebo, exenatide, liraglutide, and dulaglutide in children and adolescents. Semaglutide significantly outperformed exenatide in BMI reduction specifically.
Regarding safety, none of the four GLP-1 RAs were associated with higher risks of diarrhea, headache, or abdominal pain versus placebo. Liraglutide was more likely to cause nausea, vomiting, hypoglycemia, and injection-site reactions compared to both placebo and the other GLP-1 RAs. Semaglutide appeared to be the most effective and safest option overall.
Liu, Ligang; Shi, Hekai; Shi, Yufei; Wang, Anlin; Guo, Nuojin; Tao, Heqing; Nahata, Milap C ·
RPEP-08748 · 2024Analysis of the FDA's adverse event database (FAERS) identified 46 tirzepatide-associated adverse drug reactions across 8 organ system classes from over 1.9 million reports between Q2 2022 and Q3 2023.
Many identified adverse events were expected and consistent with drug labeling, including gastroesophageal reflux disease, dyspepsia, and vomiting. However, the analysis also uncovered unexpected signals including incorrect dose administered, injection site hemorrhage, and paradoxically increased appetite. These unexpected signals were associated with injury/procedural complications, general disorders, and metabolic/nutritional disturbances.
Liu, Liyuan · Pharmacovigilance / Database Analysis
RPEP-08752 · 2024This review maps out how the two incretin hormones — GIP and GLP-1 — work across multiple organ systems and why combining their actions in dual agonist drugs produces superior metabolic effects. Key mechanistic differences include: both suppress appetite through brain satiety centers, both stimulate insulin from beta cells, but they diverge on glucagon — GIP promotes glucagon release during low blood sugar (protective against hypoglycemia) while GLP-1 suppresses glucagon during high blood sugar. On fat metabolism, GIP directly promotes fat storage in appropriate tissue while GLP-1 indirectly promotes fat breakdown, and together they maintain healthy fat distribution, reduce ectopic fat, and boost adiponectin secretion.
This complementary biology explains why dual GIP/GLP-1 agonists like tirzepatide can achieve greater weight loss and metabolic improvement than GLP-1-only drugs, while the GIP component provides a safety buffer against hypoglycemia.
Liu, Qiyuan Keith · Review
RPEP-08753 · 2024The ionic liquid-based microemulsion (IL-M) system improved local delivery of GHK-Cu copper peptide through the skin by approximately three-fold compared to conventional delivery while retaining biological function. Mouse experiments confirmed the system's effectiveness for hair growth.
Mechanistically, the IL-M system increased activation of the Wnt/β-catenin signaling pathway — a critical regulator of hair follicle cycling and growth — and upregulated vascular endothelial growth factor (VEGF) expression, which promotes the blood supply to hair follicles. The microemulsion itself was thermodynamically stable, meaning it doesn't separate or degrade over time, which is important for product shelf life.
Liu, Tianqi; Liu, Ying; Zhao, Xiaoyu; Zhang, Liguo; Wang, Wei; Bai, De; Liao, Ya; Wang, Zhenyuan; Wang, Mi; Zhang, Jiaheng ·
RPEP-08757 · 2024Exendin-4 (Ex-4), a GLP-1 receptor agonist, maintained ductus arteriosus (DA) patency in neonatal rats by preventing spontaneous closure that normally occurs within two hours after birth. Ex-4 reduced intimal thickening, attenuated oxygen-induced vasoconstriction in isolated DA rings, and inhibited PDGF-BB-induced proliferation, migration, ROS production, and calcium mobilization in DA smooth muscle cells. All of these effects were blocked by H89, a PKA inhibitor, establishing the GLP-1R/PKA pathway as the mechanism of action.
Liu, Yi-Ching; Tseng, Yu-Hsin; Wu, Yen-Hsien; Tong, Lorraine; Tsai, Siao-Ping; Huang, Shang-En; Wu, Bin-Nan; Lo, Shih-Hsing; Chen, I-Chen; Dai, Zen-Kong; Yeh, Jwu-Lai; Hsu, Jong-Hau ·
RPEP-08762 · 2024Across 15 randomized controlled trials in adults without diabetes, all three incretin analogs produced significant weight loss compared to placebo. Tirzepatide delivered the most weight loss at 15-20.9%, followed by semaglutide at 14.9-17.4%, and liraglutide at 5.7-11.8%. All agents were superior to placebo, with gastrointestinal side effects (nausea, vomiting, diarrhea) being the most common adverse events across all three drugs.
The review establishes a clear hierarchy: tirzepatide (the dual GLP-1/GIP agonist) outperforms semaglutide (a GLP-1 agonist), which in turn substantially outperforms liraglutide (the older GLP-1 agonist). The American Gastroenterological Association already recommends GLP-1 agonists as preferred pharmacotherapy for overweight or obese patients.
Lobkovich, Alison; Kale-Pradhan, Pramodini; Lipari, Melissa · Narrative Review
RPEP-08768 · 2024The review identified multiple beneficial effects of GLP-1 receptor agonists beyond their established roles in diabetes and obesity management. These include reducing ischemia-reperfusion injury (damage caused when blood flow returns after being cut off), improving function across various organs, alleviating substance use disorders, influencing tumor development, regulating bone metabolism, modifying gut microbiota composition, and prolonging the survival of transplanted organs.
These diverse effects point to GLP-1 receptors being present and functionally important in many tissues throughout the body, not just the pancreas and brain regions controlling appetite.
Lu, Chenqi; Xu, Cong; Yang, Jun ·
RPEP-08770 · 2024In a chronic migraine mouse model, repeated nitroglycerin injections progressively decreased AMPK protein expression in the trigeminal nucleus caudalis (TNC), mediated by increased UHRF1 expression. Activating AMPK with AICAR reduced pain hypersensitivity, improved activity, and decreased CGRP and pro-inflammatory cytokines (IL-1β, IL-6, TNF-α) while increasing anti-inflammatory cytokines (IL-4, IL-10). AMPK was located primarily in microglia, and AICAR shifted microglia from the inflammatory M1 phenotype (reduced iNOS) to the anti-inflammatory M2 phenotype (increased Arg1) by inhibiting the NF-κB pathway.
Lu, Guangshuang; Xiao, Shaobo; Meng, Fanchao; Zhang, Leyi; Chang, Yan; Zhao, Jinjing; Gao, Nan; Su, Wenjie; Guo, Xinghao; Liu, Yingyuan; Li, Chenhao; Tang, Wenjing; Zou, Liping; Yu, Shengyuan; Liu, Ruozhuo ·
RPEP-08771 · 2024This review argues that Asian Americans may be unfairly excluded from semaglutide prescriptions for chronic weight management because current eligibility criteria rely on BMI thresholds that don't account for ethnicity-specific differences in body composition. Asians develop metabolic syndrome — including visceral fat accumulation, insulin resistance, and cardiovascular risk — at lower BMI levels than other populations. The review calls for integrating visceral fat measurements and other ethnicity-specific risk predictors into the diagnostic and prescribing framework for metabolic syndrome and semaglutide access.
Lu, Jenny; Williams, Grace; Fanning, Stacey ·
RPEP-08773 · 2024Both ghrelin mimetics — anamorelin and ipamorelin — inhibited cisplatin-induced weight loss by approximately 24% during the delayed phase (48-72 hours) when administered intraperitoneally. Neither reduced emesis via this route. However, anamorelin administered directly into the brain (intracerebroventricularly) reduced acute emesis by 60%, improved food and water consumption by 20-40% during the acute phase, and reduced weight loss by ~23% during the delayed phase. In isolated ileum, anamorelin inhibited contractions by 94.4% (IC50 = 14.0 µM) while ipamorelin achieved 54.4% (IC50 = 11.7 µM). The findings suggest brain penetration is critical for anamorelin's anti-emetic effect.
Lu, Zengbing; Ngan, Man P; Liu, Julia Y H; Yang, Lingqing; Tu, Longlong; Chan, Sze Wa; Giuliano, Claudio; Lovati, Emanuela; Pietra, Claudio; Rudd, John A ·
RPEP-08777 · 2024Researchers engineered a novel antimicrobial peptide called TC-LAR-18 from a tree shrew cathelicidin by increasing its net positive charge from +4 to +8. The modified peptide showed 4- to 128-fold stronger antibacterial activity than the original TC-33, effectively killed both free-floating and biofilm-associated bacteria, and caused no hemolysis or cytotoxicity at concentrations up to 100 μg/mL.
Critically, TC-LAR-18 demonstrated rapid membrane-disrupting action with a low tendency to induce bacterial resistance, and provided significant protection against skin bacterial infections in a mouse model.
Luo, Lin; Cai, Ying; Su, Yunhan; Li, Chenxi; Tian, Gengzhou; Wang, Xingyu; Wu, Zhongxiang; Chen, Wenlin; Zhang, Tianyu; Zhang, Zhiye ·
RPEP-08781 · 2024A topical neuropeptide serum containing 2% acetyl hexapeptide-8, 2% dipeptide diaminobutyroyl, 5% polyhydroxy acids, 5% niacinamide, and 1% laminaria extract appeared to complement botulinum toxin type-A (BTX-A) injections in real-world clinical use. Seven clinicians (5 dermatologists and 2 surgeons) reported that the combination improved skin radiance, reduced fine lines, and reduced wrinkles in diverse patients when the serum was applied twice daily alongside BTX-A injections. The serum reportedly works by stimulating 9 key skin biomarkers.
Lupin, Mark; Bjerring, Peter; Andriessen, Anneke; Chantrey, Jonquille; Fabi, Sabrina Guillen; Liew, Steven; McDonald, Cara; Xiaolei, Qin; White, Stacy ·
RPEP-08785 · 2024Across 13 studies (21,745 patients), the network meta-analysis compared nesiritide, dopamine, tolvaptan, levosimendan, dobutamine, furosemide, spirolactone, and high-dose diuretics (HDD).
Key results:
- HDD had the best efficacy in reducing NT-proBNP levels, with a mean difference of -950.24 (95% CrI: -1,832.21 to -64.12) compared to placebo/conventional treatment.
- Levosimendan significantly improved GFR compared to placebo (MD = 14.46; 95% CrI: 3.88 to 25.97) and tolvaptan (MD = 13.83; 95% CrI: 2.31 to 25.33).
- No significant differences were found in 60-day all-cause mortality or cardiovascular mortality across all drugs.
- Nesiritide did not demonstrate superior efficacy compared to other treatments in this population.
Lv, Qianyu; Wu, Qian; Yang, Yingtian; Li, Lanlan; Ye, Xuejiao; Wang, Shihan; Lv, Yanfei; Wang, Manshi; Li, Yushan ·
RPEP-08792 · 2024The DEPN hydrogel demonstrated a three-stage nitric oxide release strategy: continuous slow release to disperse biofilms, laser-triggered rapid burst release (with photothermal heating) to eliminate pathogens, and sustained slow release to promote tissue remodeling. The hydrogel effectively eliminated a broad spectrum of drug-resistant Gram-positive bacteria, Gram-negative bacteria, and fungal biofilms through synergistic effects of NO, photothermal therapy, and the antimicrobial peptide ε-poly-lysine.
In vitro, the hydrogel promoted proliferation of mouse fibroblasts and migration of endothelial cells. In vivo, it achieved exceptional therapeutic outcomes in mice with MRSA-infected diabetic wounds by eliminating biofilm infection, regulating inflammation, facilitating angiogenesis, and promoting collagen deposition — addressing the multiple barriers that prevent chronic wound healing.
Ma, Huifang; Wang, Tengjiao; Li, Gangfeng; Liang, Jiaheng; Zhang, Jianhong; Liu, Yang; Zhong, Wenbin; Li, Peng ·
RPEP-08796 · 2024Mice genetically lacking both Substance P (Tac1 knockout) and CGRPα (Calca knockout) — two neuropeptides long considered central to pain transmission — displayed largely intact pain responses across every type of pain tested. Mechanical, thermal, chemical, and visceral pain were all preserved. Chronic inflammatory pain and neurogenic inflammation were unaffected. Even neuropathic pain from nerve injury or chemotherapy treatment persisted normally.
Both peptides were confirmed completely absent throughout the nervous system, eliminating the possibility of residual signaling. This definitively shows that even combined loss of these two major pain-associated neuropeptides is not sufficient to block pain transmission.
MacDonald, Donald Iain; Jayabalan, Monessha; Seaman, Jonathan; Balaji, Rakshita; Nickolls, Alec; Chesler, Alexander ·
RPEP-08802 · 2024Pooled analysis of 13 randomized controlled trials demonstrated that tirzepatide significantly improved all measured lipid markers, including cholesterol and triglycerides. Key findings:
- All lipid markers improved with tirzepatide treatment
- A clear dose-response relationship was observed: 5 mg, 10 mg, and 15 mg doses showed progressively greater improvements
- Tirzepatide appeared superior to conventional agents including insulin formulations and traditional GLP-1 agonists for metabolic improvement
- Of 13 included trials, 9 had low risk of bias, 2 moderate, and 2 high risk of bias
Mahar, Muhammad Umar; Mahmud, Omar; Ahmed, Salaar; Qureshi, Saleha Ahmed; Kakar, Wasila Gul; Fatima, Syeda Sadia ·
RPEP-08804 · 2024After a median 2-year follow-up of 181 patients on liraglutide:
• 81.6% of patients (71/87) without retinopathy at baseline remained retinopathy-free
• Among patients with retinopathy at baseline: 25.5% improved, 44.7% showed no change
• Both HbA1c and weight decreased significantly (P<0.001)
• Independent risk factors for retinopathy were: insulin use (OR 2.68), hypertension (OR 2.56), higher HbA1c (OR 1.17 per unit), older age (OR 1.03 per year), and longer diabetes duration (OR 1.04 per year)
• Liraglutide itself was not identified as a retinopathy risk factor
Baseline characteristics: mean age 58.2 years, 72.9% female, median diabetes duration 19 years, median baseline HbA1c 9%, 69.6% on insulin.
Mahzari, Moeber M; Alanazy, Abdulmalik M; Feroz, Zeeshan; Almani, Khalid M; Alghamdi, Meshari A; Almadani, Abdulaziz S; Alzahrani, Majed K; Alibrahim, Ahmed R; Badri, Motasim ·
RPEP-08821 · 2024Of 11 synthesized faba bean-derived peptides:
Antioxidant activity (7 peptides):
- TETWNPNHPEL showed the highest activity: ABTS EC50 = 0.5 ± 0.2 mM; DPPH EC50 = 2.1 ± 0.1 mM
- Other active peptides: NYDEGSEPR, TETWNPNHPE, VIPTEPPH, VIPTEPPHA, VVIPTEPPHA, VVIPTEPPH
ACE inhibitory activity (4 peptides):
- TETWNPNHPEL: IC50 = 43 ± 1 μM (most potent)
- VVIPTEPPHA: IC50 = 50 ± 5 μM
- TETWNPNHPE: IC50 = 90 ± 10 μM
- VIPTEPPHA: IC50 = 123 ± 5 μM
Kinetic studies and molecular docking confirmed all ACE-inhibitory peptides act through a noncompetitive mechanism — they bind to a site other than the enzyme's active site.
Martineau-Côté, Delphine; Achouri, Allaoua; Karboune, Salwa; L'Hocine, Lamia ·
RPEP-08822 · 2024From an initial screen of 1,218 studies, only 5 randomized trials met the inclusion criteria, incorporating 630 total participants treated with exenatide (3 studies) or dulaglutide (2 studies).
Of the five studies assessing therapeutic effects on substance use disorders, three demonstrated a significant decrease in substance use, specifically for alcohol and nicotine. Three studies also reported on metabolic outcomes, showing notable reductions in body weight, BMI, and HbA1c in the GLP-1 receptor agonist-treated groups.
Martinelli, Silvia; Mazzotta, Alessandro; Longaroni, Mattia; Petrucciani, Niccolò ·
RPEP-08827 · 2024Among 57 consecutive adults on GLP-1 RAs (45.6% semaglutide, 22.8% dulaglutide, 19.3% liraglutide, 12.3% tirzepatide) who underwent ESG without drug interruption:
- Zero instances of retained gastric solids
- Zero cases of pulmonary aspiration
- Zero cases of gastroesophageal regurgitation
- Zero episodes of hypoxia during intubation, endoscopy, or recovery
All patients followed a standardized preparation: liquid-only diet for ≥24 hours and nil per os for ≥12 hours before the procedure. The 100% safety record across multiple GLP-1 drugs and across three centers supports the adequacy of this fasting protocol.
Maselli, Daniel B; Lee, Daniel; Bi, Danse; Jirapinyo, Pichamol; Thompson, Christopher C; Donnangelo, Lauren L; McGowan, Christopher E ·
RPEP-08830 · 2024Treatment with liraglutide 3 mg for three months significantly altered the plasma protein profile in patients with obesity. Of 151 dysregulated proteins, 31 were upregulated and 120 downregulated. Proteins involved in inflammation and oxidative stress were decreased, while those involved in glycolytic/lipolytic metabolism and cytoskeletal/endothelial reorganization increased. Top potential biomarkers (AUC 0.999) included upregulated Cystatin-B, major vault protein, and plastin-3, and downregulated multimerin-2, large ribosomal P2, and proline-rich acidic protein 1. Key affected pathways centered around MAPK, AKT, and PKc signaling.
Masood, Afshan; Benabdelkamel, Hicham; Joy, Salini Scaria; Alhossan, Abdulaziz; Alsuwayni, Bashayr; Abdeen, Ghalia; Aldhwayan, Madhawi; Alfadda, Nora A; Miras, Alexander Dimitri; Alfadda, Assim A ·
RPEP-08833 · 2024AJICAP-M is a traceless site-selective conjugation method that uses Fc-affinity peptides to attach drugs to native (unmodified) antibodies at specific lysine residues (Lys248 or Lys288). The technology produces antibody-drug conjugates with:
- Consistent drug-to-antibody ratios
- Enhanced stability compared to traditional ADCs
- Superior in vivo stability demonstrated in comparative animal studies
- Compatibility with continuous-flow manufacturing — a first for site-selective ADC production
The "traceless" aspect means the affinity peptide is removed after conjugation, leaving no foreign material on the final product.
Matsuda, Yutaka; Shikida, Natsuki; Hatada, Noriko; Yamada, Kei; Seki, Takuya; Nakahara, Yuichi; Endo, Yuta; Shimbo, Kazutaka; Takahashi, Kazutoshi; Nakayama, Akira; Mendelsohn, Brian A; Fujii, Tomohiro; Okuzumi, Tatsuya; Hirasawa, Shigeo ·