RPEP-11816 · 2025The htsFLT01/MiRGD nanocomplex, delivered at an optimal nitrogen-to-phosphorus (N/P) ratio of 14, successfully transfected MCF7 breast cancer cells and produced dual anti-cancer effects:
1. Anti-angiogenic activity: The htsFLT01 gene encodes sFLT01 protein, which acts as a VEGF decoy receptor to block pathological blood vessel formation that tumors depend on for growth.
2. Pro-apoptotic activity: Expression analysis revealed increased levels of FADD (Fas-Associated Death Domain Protein), CASP8 (Caspase-8), and TP53 (p53) — key genes in the extrinsic apoptotic pathway that triggers programmed cell death.
This dual mechanism suggests a synergistic relationship between blocking tumor blood supply and directly inducing cancer cell death.
Khoshandam, Mohadeseh; Soheili, Zahra-Soheila; Hosseinkhani, Saman; Samiee, Shahram; Latifi-Navid, Hamid; Kalhor, Naser; Soltaninejad, Hossein ·
RPEP-11818 · 2025GLP-1 or GLP-1/GIP agonists significantly improved both KCCQ quality of life scores and 6-minute walking distance compared to placebo in heart failure patients. IV iron was the only other therapy to achieve improvements on both outcomes.
SGLT2 inhibitors improved KCCQ scores but not 6-minute walking distance. MRA, ARNI, vericiguat, and ivabradine showed no significant differences in KCCQ scores versus placebo/control. Beta-blockers, ARNI, MRA, SGLT2 inhibitors, and ivabradine showed no significant improvement in 6-minute walking distance.
Kido, Kazuhiko; Hashiguchi, Masayuki; Guglin, Maya ·
RPEP-11825 · 2025SeqDA-HLA achieved an AUC of up to 0.9856 and accuracy as high as 94.08% on benchmark datasets, outperforming 14 state-of-the-art methods for peptide-HLA class I binding prediction. The model maintained strong performance across peptide lengths ranging from 8 to 14 amino acids and across diverse HLA alleles.
Beyond prediction accuracy, the model provides interpretable results by highlighting anchor residues and binding motifs that align with experimentally validated biological findings. When fine-tuned on an Influenza virus dataset, it successfully predicted how single amino acid mutations affect binding.
Kim, Gihyeon; Jo, Geonhui; Kim, Minjeong; Cho, Soo Young; Choi, Jang-Hwan ·
RPEP-11826 · 2025Over 12 months of follow-up using propensity score-matched cohorts, galcanezumab users had significantly lower cost increases than rimegepant users: 21% lower increase in all-cause total medical and pharmacy costs, and 76% lower increase in migraine-related total costs.
Treatment persistence was also notably better with galcanezumab. The median time to discontinuation (using a >60-day gap definition) was 244.6 days for galcanezumab versus 178.1 days for rimegepant. Galcanezumab users were 1.8 times less likely to discontinue treatment (HR = 1.81, 95% CI: 1.56–2.10, p < 0.0001).
Kim, Gilwan; Hoyt, Margaret; Zakharyan, Armen; Durica, Jennifer; Wallem, Alexandra; Viktrup, Lars ·
RPEP-11833 · 2025The review identifies a nuanced psychiatric profile for GLP-1 receptor agonists:
**Positive evidence:**
- Substance use disorders: consistent evidence for therapeutic benefit, particularly for alcohol use disorders
- Dementia: several cohort studies indicate reduced risk, suggesting neuroprotective effects
**Mixed evidence:**
- Depression and anxiety: conflicting results from large observational studies, largely due to confounding by indication and methodological differences
**Safety concerns addressed:**
- Suicidality: initial reports raised alarm, but well-controlled active-comparator studies found no increased risk. Initial findings were likely driven by methodological limitations
- Safety in high-risk psychiatric populations: not yet established
The overall profile suggests therapeutic potential but calls for caution in psychiatrically vulnerable patients.
Kim, JinWoo ·
RPEP-11845 · 2025The review synthesizes evidence showing that metabolic syndrome features (hyperglycemia, insulin resistance, oxidative stress, altered adipokines) promote brain tumor growth, proliferation, and treatment resistance. GLP-1 receptor agonists and DPP-4 inhibitors target both metabolic and inflammatory aspects of brain tumors. Metformin activates AMPK and inhibits mTOR to impair tumor proliferation. Thiazolidinediones can induce tumor cell apoptosis and synergize with other therapies. All these approaches represent potential drug repurposing strategies.
Kim, Young-Kook; Song, Juhyun ·
RPEP-11851 · 2025Fourteen patients with overweight/obesity and hazardous drinking (AUDIT score ≥8) were prescribed GLP-1 RAs (semaglutide n=8, tirzepatide n=5, liraglutide n=1) alongside standard dietary and exercise counseling. After a mean of 9.6 months of treatment, both BMI and AUDIT scores decreased significantly.
Patients in the 'very high' AUDIT group (score ≥15) showed more pronounced reductions in drinking scores compared to those in the 'high' group (score 8-14). Effect sizes were large, indicating a substantial magnitude of the GLP-1 RA effect on hazardous drinking behavior.
King, Andrea C; Wellendorf, Claire; Atkinson, Emily A; de Carvalho, Maria Eduarda Amaral; Fridberg, Daniel J; Pannain, Silvana ·
RPEP-11859 · 2025After propensity score matching (23,240 patients per group), combining SGLT2 inhibitors with GLP-1 receptor agonists versus SGLT2 inhibitor monotherapy produced:
- All-cause death: 2.8% vs 6.3% (HR 0.43, 95% CI 0.39-0.48, p<0.001) — a 57% relative risk reduction
- Hospitalization: 32.9% vs 36.4% (HR 0.87, 95% CI 0.84-0.90, p<0.001) — a 13% relative risk reduction
These results were observed over a 1-year follow-up period in patients with both heart failure and type 2 diabetes.
Kishimori, Takefumi; Kato, Takao; Wada, Atsuyuki; Tani, Akira; Yamaji, Ryosuke; Koike, Jumpei; Iwasaki, Yoshihiro; Matsumoto, Takahiro; Yagi, Takafumi; Okada, Masaharu ·
RPEP-11865 · 2025In this randomized, double-blind clinical trial of 1,389 predominantly low-risk patients undergoing elective coronary artery bypass grafting or aortic valve replacement:
- 170 patients (24%) in the exenatide group and 165 patients (24%) in the placebo group experienced the primary composite endpoint (death, stroke, renal failure requiring dialysis, or new/worsening heart failure)
- No significant difference in time to first event between groups
- No significant difference in rates of adverse events
- Median follow-up was 5.9 years (range 2.5–8.3 years)
- The study also tested liberal vs. restrictive oxygenation during bypass in a 2×2 factorial design, finding no difference there either (HR 1.0; 95% CI 0.83–1.3; p = 0.80)
Exenatide was administered as a 17.4 µg infusion during cardiopulmonary bypass and for the first hour after weaning from bypass.
Kjaergaard, Jesper; Møller, Christian Holdflod; Wiberg, Sebastian; Mikkelsen, Astrid Duus; Møller-Sørensen, Hasse; Ravn, Hanne Berg; Ravn, Jesper; Olsen, Peter Skov; Høfsten, Dan E; Boesgaard, Søren; Køber, Lars; Nilsson, Jens Christian; Hassager, Christian ·
RPEP-11870 · 2025ANP and BNP significantly reduced alveolar fluid clearance (AFC) in isolated rat lungs. The AFC rate dropped from 0.49 ± 0.02 mL/h in control rats to 0.26 ± 0.013 mL/h with ANP treatment and 0.19 ± 0.005 mL/h with BNP treatment.
The mechanism involved downregulation of active sodium transport components in alveolar epithelial cells, including Na+,K+-ATPase and epithelial sodium channels (ENaC). The peptides enhanced ubiquitination and degradation of αENaC through increased levels of Nedd4-2. In compensated congestive heart failure (CHF), ANP further reduced AFC, but in decompensated CHF, ANP partially restored AFC, revealing a stage-dependent role for natriuretic peptides in lung fluid regulation.
Knany, Yara; Kinaneh, Safa; Khoury, Emad E; Zohar, Yaniv; Abassi, Zaid; Azzam, Zaher S ·
RPEP-11871 · 2025In rats with STZ-induced brain insulin resistance (a model of sporadic Alzheimer's):
• STZ-icv rats showed impaired spatial learning (Morris water maze), fear-motivated memory deficits (passive avoidance), reduced hippocampal neurogenesis, and downregulated insulin/glucose metabolism genes
• 4 weeks of liraglutide (0.3 mg/kg subcutaneous) did NOT reverse spatial learning deficits in the Morris water maze
• Liraglutide WORSENED passive avoidance performance (fear-motivated memory)
• Liraglutide partially restored dysregulated gene expression in hippocampus and prefrontal cortex related to insulin signaling and glucose metabolism
• However, liraglutide additionally stimulated neuroinflammation — potentially counteracting its beneficial gene expression effects
Knezovic, Ana; Hosch, Michael; Hamann, Catharina Sophia; Popp, Sandy; Ortega, Gabriela; Osmanovic-Barilar, Jelena; Grünblatt, Edna; Monoranu, Camelia; Riederer, Peter; Salkovic-Petrisic, Melita; Schmitt-Böhrer, Angelika ·
RPEP-11880 · 2025Doppelgänger peptides — molecular mimics of endogenous hormones or neuropeptides — have been discovered in many venomous organisms, poisonous species, parasites, and pathogens. While traditionally discovered anecdotally, the explosion of genomic sequence data combined with computational screening tools reveals they are far more prevalent than previously recognized.
These peptides evolved to manipulate the signaling systems of other organisms, making them inherently bioactive at relevant receptors. This positions them as candidates for translational applications in peptide-based therapeutics, building on the precedent set by venom-derived drugs like exenatide (from Gila monster) and ziconotide (from cone snails).
Koch, Thomas L; Robinson, Samuel D; Safavi-Hemami, Helena ·
RPEP-11889 · 2025The review identified 53 phase 2/3 trials covering 36 emerging antiobesity drugs or combinations. Key findings:
- Almost half of drugs in phase 2 trials are incretin analogs
- Completed phase 2 incretin-based therapies achieved 7.4-24.2% mean weight loss
- Oral semaglutide 50mg is the only drug to have completed a phase 3 trial
- 14 ongoing phase 3 trials include: GLP-1 RAs (ecnoglutide, orforglipron, TG103), GLP-1/amylin (CagriSema), GLP-1/glucagon dual agonists (mazdutide, survodutide), GLP-1/GIP/glucagon triple agonist (retatrutide)
- 4 trials were withdrawn or terminated
The review highlights that data on mortality, cardiovascular outcomes, long-term safety, cost-effectiveness, and underrepresented populations remain critical gaps.
Kokkorakis, Michail; Chakhtoura, Marlene; Rhayem, Caline; Al Rifai, Jana; Ghezzawi, Malak; Valenzuela-Vallejo, Laura; Mantzoros, Christos S ·
RPEP-11896 · 2025The Ex-D3 variant (Glu3Asp substitution of exendin-4) showed several advantages over standard exendin-4 as a GLP-1R imaging probe:
- C-terminal modification for iodine-125 labeling did not significantly alter GLP-1R binding affinity (confirmed by surface plasmon resonance)
- Ex-D3-C40 induced weaker hypoglycemic effects than Ex-4-C40 in mice, reducing the safety risk
- Iodine-125 labeled Ex-D3 achieved significantly higher pancreatic accumulation than labeled Ex-4
- Higher pancreas-to-blood and pancreas-to-muscle ratios, indicating better imaging contrast
- Ex vivo autoradiography confirmed specific binding to GLP-1R-expressing pancreatic β-cells
- The higher internalization rate of Ex-D3 likely contributes to improved tissue accumulation
Kondo, Naoya; Yonezawa, Maiko; Hirano, Fuko; Temma, Takashi ·
RPEP-11906 · 2025Across 18 RCTs (1,402 participants; mean age 13.7 years; 59.3% female; median treatment 0.51 years), GLP-1 RAs vs. placebo showed:
- HbA1c: -0.44% (95% CI: -0.68% to -0.21%)
- Fasting glucose: -9.92 mg/dL (95% CI: -16.20 to -3.64)
- Body weight: -3.02 kg (95% CI: -4.98 to -1.06)
- BMI: -1.45 (95% CI: -2.40 to -0.49)
- BMI SDS: -0.20 (95% CI: -0.36 to -0.05)
- BMI percentile: -7.24% (95% CI: -12.97% to -1.51%)
- Systolic blood pressure: -2.73 mmHg (95% CI: -4.04 to -1.43)
- GI adverse events: increased (log RR 0.75)
- Suicidal ideation/behaviors: no significant difference vs. placebo
All efficacy outcomes reached statistical significance, supporting GLP-1 RAs for pediatric use.
Kotecha, Pareeta; Huang, Wenxi; Yeh, Ya-Yun; Narvaez, Valerie Martino; Adirika, Darlene; Tang, Huilin; Bernier, Angelina V; Westen, Sarah C; Smith, Steven M; Bian, Jiang; Guo, Jingchuan ·
RPEP-11907 · 2025Among approximately 2,000 children and adolescents (mean age ~14.2 years, ~61% female) with up to 4 years of follow-up:
- Suicidal ideation/behaviors: GLP-1 RA users had significantly lower risk (HR 0.11, 95% CI 0.02-0.86; risk difference -10.45 per 1,000 person-years)
- Depression: GLP-1 RA users had significantly lower risk (HR 0.37, 95% CI 0.17-0.78; risk difference -25.64 per 1,000 person-years)
- Anxiety: No significant difference (HR 1.13, 95% CI 0.69-1.84; risk difference 5.95 per 1,000 person-years)
All comparisons were against prevalent metformin users.
Kotecha, Pareeta; Lee, Yao An; Bernier, Angelina V; Westen, Sarah C; Smith, Steven M; Zhang, Pengyue; Hannon, Tamara S; Bian, Jiang; Guo, Jingchuan ·
RPEP-11908 · 2025GLP-1 receptor agonists and dual incretin agonists (like tirzepatide) are increasingly prioritized over basal insulin for type 2 diabetes due to superior efficacy, cardiovascular benefits, weight loss, and safety. However, basal insulin remains indispensable for patients with advanced beta-cell failure, severe hyperglycemia, or contraindications to newer agents. The review advocates personalized, pathophysiology-driven therapy selection including integration of new once-weekly insulin formulations.
Koufakis, Theocharis; Patoulias, Dimitrios; Popovic, Djordje S; Tsimihodimos, Vasileios ·
RPEP-11914 · 2025Mitotic cancer cells redistribute their ribosomes toward the 5' untranslated region and the beginning of the coding sequence, leading to enhanced translation of thousands of upstream open reading frames (uORFs) and upstream overlapping open reading frames (uoORFs). These non-canonical translation products are presented on the cancer cell surface via HLA molecules after treatment with mitotic inhibitors.
Functional assays confirmed that these newly presented peptide epitopes provoke T cell-mediated killing of cancer cells, demonstrating that mitotic arrest creates a window of immune vulnerability for tumors.
Kowar, Alexander; Becker, Jonas P; Del Pizzo, Rossella; Tang, Zhiwei; Champagne, Julien; Wellach, Kathrin; Samimi, Kiana; Galindo-Albarrán, Ariel; Körner, Pierre-René; Montenegro Navarro, Jasmine; Elía, Andrés; Tilghman, Fiona Megan; Sakeer, Hanan; Mendoza-Parra, Marco Antonio; Riemer, Angelika B; Agami, Reuven; Loayza-Puch, Fabricio ·
RPEP-11915 · 2025A validated UPLC-Q-ToF/MS method was developed with an LLOQ of 34.6 ng/mL and linearity from 35–10,000 ng/mL. Accuracy ranged from 86.7% to 88.9% recovery, with intraday precision <2.65% RSD and interday precision <6.22% RSD. The method was successfully applied to a pharmacokinetic study in rabbits given oral lunasin-rich processed soybeans at two doses (6.56 and 19.1 g/kg), confirming oral bioavailability of lunasin.
Kowmudi, Gullapalli; Anoop, Karthika; Varshini, Magham Sai; Nagappan, Krishnaveni; Konanki, Sreenath; Praveen, Thaggikuppe Krishnamurthy ·
RPEP-11920 · 2025In 106 patients with obesity-related heart failure with preserved ejection fraction (HFpEF), tirzepatide reduced left ventricular (LV) mass by 11 g (95% CI: -19 to -4 g, P = 0.004) and paracardiac adipose tissue by 45 mL (95% CI: -69 to -22 mL, P < 0.001) compared to placebo over 52 weeks.
The reduction in LV mass correlated with weight loss (P < 0.02) and tended to correlate with waist circumference and blood pressure changes (P = 0.06 for both). LV mass changes also correlated with reductions in LV end-diastolic volume and left atrial volumes (P < 0.03 for all), indicating broader cardiac remodeling benefits.
Kramer, Christopher M; Borlaug, Barry A; Zile, Michael R; Ruff, Dustin; DiMaria, Joseph M; Menon, Venu; Ou, Yang; Zarante, Angela M; Hurt, Karla C; Murakami, Masahiro; Packer, Milton ·
RPEP-11921 · 2025Semaglutide demonstrated direct cardioprotective effects on isolated human cardiomyocytes from three groups: non-failing hearts, aortic stenosis with HFpEF-like phenotype, and end-stage HFrEF.
Key findings included: reduction of late sodium current (INa) in diseased cardiomyocytes to levels comparable with non-failing hearts; decreased diastolic sarcoplasmic reticulum (SR) calcium leak; improved systolic calcium transients and contractility in both AS and HFrEF tissue; and dose-dependent improvement of myocardial contractility in multicellular preparations. These effects were mediated through GLP-1 receptor agonism (blocked by exendin 9-39) and were comparable to CaMKII inhibition.
Krammer, Thomas; Baier, Maria J; Hegner, Philipp; Zschiedrich, Tilman; Lukas, David; Wolf, Matthias; Le Phu, Christian; Lutz, Vanessa; Evert, Katja; Kozakov, Kostiantyn; Li, Jing; Holzamer, Andreas; Maier, Lars S; Provaznik, Zdenek; Bers, Donald M; Wagner, Stefan; Mustroph, Julian ·
RPEP-11928 · 2025All five included studies showed consistent systolic blood pressure reductions with oral semaglutide, ranging from -2.60 to -12.74 mmHg. Diastolic blood pressure effects were less consistent. Total cholesterol was reduced across all studies (-8.80 to -22.19 mg/dL). Four of five studies reported favorable LDL cholesterol reductions (-7.6 to -18.0 mg/dL) and triglyceride reductions (-11.00 to -40.13 mg/dL).
HDL cholesterol showed the least consistent pattern: three studies found a non-significant increasing trend, while one reported a mild increase. The authors concluded that oral semaglutide may offer cardiovascular benefits comparable to subcutaneous semaglutide, with the advantage of improved patient adherence.
Krishnanda, Stanislaus Ivanovich; Christabelle, Marie; Yausep, Oliver Emmanuel; Sugiharto, Caroline; Vincent, Leroy David; Agarwal, Raksheeth; Damara, Ivan; Harbuwono, Dante Saksono ·
RPEP-11936 · 2025In expanded eligibility cohorts reflecting real clinical practice:
- Semaglutide vs sitagliptin (n=58,333): HR 0.58 (95% CI 0.51-0.65) — 42% risk reduction for heart failure hospitalization or all-cause mortality
- Tirzepatide vs sitagliptin (n=11,257): HR 0.42 (95% CI 0.31-0.57) — 58% risk reduction
- Tirzepatide vs semaglutide head-to-head (n=28,100): HR 0.86 (95% CI 0.70-1.06) — no statistically meaningful difference
Benchmarking analyses emulating the STEP-HFpEF DM and SUMMIT trials showed high agreement, validating the real-world study design. No substantially increased safety risks were identified.
Krüger, Nils; Schneeweiss, Sebastian; Fuse, Kenshiro; Matseyko, Sofiya; Sreedhara, Sushama Kattinakere; Hahn, Georg; Schunkert, Heribert; Wang, Shirley V ·
RPEP-11943 · 2025The review identifies several pharmacological agents showing encouraging clinical trial results for MASLD treatment: resmetirom (a thyroid hormone receptor-β agonist), GLP-1 receptor agonists like semaglutide, PPAR agonists (pioglitazone, saroglitazar), SGLT2 inhibitors, and vitamin E. Emerging therapies including tirzepatide (dual incretin agonist) and FGF analogs are highlighted as potentially transformative.
A structured treatment algorithm for non-cirrhotic MASLD (F0-F3 fibrosis) is presented, incorporating only drugs available in India and stratified by diabetes status and fibrosis severity.
Kumar, Ashish ·
RPEP-11944 · 2025The review identifies several categories of diabetes vaccine candidates currently under investigation:
1. IA-2 peptide vaccines — targeting the autoimmune destruction of beta cells in Type 1 diabetes by inducing immune tolerance to islet autoantigens.
2. Incretin-based vaccines — designed to enhance the body's GLP-1 signaling for long-lasting glucose regulation in Type 2 diabetes.
3. Glucose-regulating vaccines — targeting inflammatory and insulin resistance pathways.
4. Protein-based vaccines — using various protein antigens to modulate immune responses relevant to diabetes.
These approaches target different disease mechanisms including autoimmunity, inflammation, and insulin resistance across both Type 1 and Type 2 diabetes.
Kumar, Mithilesh; Wasnik, Apoorva; Sagar, Vidya; Priya, Neha; Kujur, Anit; Kumar, Dewesh ·
RPEP-11945 · 2025pLM4CPPs outperformed existing state-of-the-art CPP prediction models with improvements of 4.9-5.5% in accuracy, 9.3-10.2% in Matthews correlation coefficient, and 14.1-19.6% in sensitivity.
Among the protein language models tested, ESM-1280 achieved 89.6% accuracy with 97.8% specificity, while ProtT5-XL BFD showed the best overall performance with 90.1% accuracy, 80.2% MCC, 88.5% sensitivity, and 91.7% specificity. The consensus approach combining multiple models further enhanced prediction reliability. The tool is freely available as a web server and open-source code on GitHub.
Kumar, Nandan; Du, Zhenjiao; Li, Yonghui ·
RPEP-11949 · 2025Self-assembled peptide nanostructures represent a versatile platform for cancer drug delivery with several key advantages: they can encapsulate both hydrophobic and hydrophilic drugs, they can be engineered with stimuli-responsive elements for site-specific drug release, and they offer improved selectivity for tumor tissue over healthy tissue.
Metal-coordinated peptide assemblies add further capabilities by enhancing structural stability, enabling triggered release of anticancer therapeutics, and addressing limitations of conventional peptide self-assembly. Both linear and cyclic peptide architectures are being explored for these applications.
Kumar, Vijay Bhooshan ·
RPEP-11952 · 2025A middle-aged male with well-controlled type 2 diabetes and social alcohol use developed asymptomatic elevations in ALT and AST while taking semaglutide. A comprehensive workup — including undetectable blood ethanol, normal viral hepatitis panel, and unremarkable liver ultrasound — found no alternative cause.
After semaglutide was discontinued, transaminase levels declined rapidly, supporting a diagnosis of drug-induced liver injury (DILI). The mechanism remains unclear but may involve idiosyncratic metabolic stress, weight loss effects, or biliary dysfunction.
Kundu, Rupayan; Shtoff, Lyudmila ·
RPEP-11953 · 2025Lu-177-DOTATATE peptide receptor radionuclide therapy (PRRT) — normally used for neuroendocrine tumors — showed promising results in 7 patients with advanced thyroid cancer that no longer responded to radioiodine. SSTR PET scans confirmed high somatostatin receptor uptake in metastases (SUVmax 10.4 ± 8.6), particularly in bone.
Among 5 patients receiving continuous PRRT, 60% achieved tumor control by volume and RECIST criteria. The 2 patients who had treatment breaks still showed stable disease at follow-up, and when PRRT was restarted, their tumors responded again — suggesting the treatment remains effective even after interruption. No severe adverse events (Grade 3-5) occurred in either group.
Kunte, Sophie Carina; Wenter, Vera U; Holzgreve, Adrien; Sheikh, Gabriel T; Widjaja, Liam; Gildehaus, Franz Josef; Lindner, Simon; Schirrmacher, Ralf; Spitzweg, Christine; Auernhammer, Christoph J; Werner, Rudolf A; Zacherl, Mathias J · Observational Study
RPEP-11958 · 2025Liraglutide significantly reduced lipid droplet accumulation and myocardial fibrosis in both cell and mouse models of diabetic cardiomyopathy. The drug decreased expression of fibrosis markers TGF-β1, collagen I, and collagen III. It achieved these protective effects by activating AMPK, which improved mitochondrial function, boosted antioxidant gene expression, enhanced insulin signaling, and reduced oxidative stress in heart cells.
Kuo, Chien-Yin; Tsou, Sing-Hua; Kornelius, Edy; Chan, Kuei-Chuan; Chang, Kai-Wei; Li, Jung-Chi; Huang, Chien-Ning; Lin, Chih-Li · Animal And Cell
RPEP-11961 · 2025In 197 patients without heart failure or diabetes followed for a median of 10.6 years, NT-proBNP >125 pg/mL was associated with a 2.54-fold increased risk (HR 2.54, 95% CI 1.34-4.82, p=0.004) of developing chronic kidney disease (eGFR <60 mL/min/1.73 m²) or dying from any cause. After multivariate adjustment, the association remained significant (adjusted HR 2.23, 95% CI 1.10-4.52, p=0.026), confirming NT-proBNP as an independent predictor of renal and mortality outcomes.
Kuo, Y N; Lin, C H; Wang, J S ·
RPEP-11963 · 2025Three isolates each of MRSA and nontypeable Haemophilus influenzae (NTHI), when released from biofilms using an anti-DNABII monoclonal antibody, became significantly more sensitive to killing by three respiratory antimicrobial peptides: human β-defensin 1 (hBD-1), human β-defensin 3 (hBD-3), and the cathelicidin LL-37.
This vulnerability is a transient phenotype linked to increased membrane permeability in newly released bacteria. In three animal models of biofilm infections, the DNABII-directed monoclonal antibody alone (without co-delivered antibiotics) induced biofilm disruption with rapid bacterial clearance and disease resolution, suggesting that innate immune effectors including antimicrobial peptides drive the clearance.
Kurbatfinski, Nikola; Jurscisek, Joseph A; Wilbanks, Kathryn Q; Goodman, Steven D; Bakaletz, Lauren O ·
RPEP-11973 · 2025In the massive SELECT cardiovascular outcomes trial, semaglutide 2.4 mg weekly was actually safer overall than placebo for serious adverse events: 33.4% of semaglutide patients had SAEs versus 36.4% on placebo (p<0.001), driven largely by fewer cardiac events (11.5% vs 13.5%).
However, more patients stopped semaglutide due to side effects (16.6% vs 8.2%), with gastrointestinal problems being the main reason (10.0% vs 2.0%). Gallbladder disorders were slightly more common with semaglutide (2.8% vs 2.3%, p=0.04), mainly gallstones rather than inflammation. Crucially, suicide and self-injury rates were identical and very low in both groups (0.11%). No new safety concerns were identified.
Kushner, Robert F; Ryan, Donna H; Deanfield, John; Kokkinos, Alexander; Cercato, Cintia; Wilding, John; Burguera, Bartolome; Wu, Chau-Chung; Craciun, Anca-Elena; Pall, Denes; Hramiak, Irene; Hjelmesæth, Jøran; Harder-Lauridsen, Nina M; Weimers, Petra; Jeppesen, Ole Kleist; Kallenbach, Klaus; Lincoff, A Michael; Lingvay, Ildiko · Randomized Controlled Trial (Safety Analysis)
RPEP-11975 · 2025Across 10 studies, the meta-analysis found:
- Patients who developed heart failure post-ACS had significantly higher baseline BNP levels (standardized mean difference: 0.95, 95% CI: 0.54–1.37, p<0.001)
- However, the odds ratio for HF occurrence based on baseline BNP was not significant (OR: 1.83, 95% CI: 0.11–29.07, p=0.67)
- 8 of 10 individual studies showed a positive association between baseline BNP and post-ACS heart failure
This discrepancy suggests that while BNP is elevated in those who develop HF, the variation between studies is too large for a single cutoff to be clinically useful.
Kusumowardani, Alivia Retra; Yudhisthira, Narendra Lintang ·
RPEP-11976 · 2025Over two years, subcutaneous semaglutide users (n=310) lost a mean 7.5% body weight (16.7 pounds), while oral semaglutide users (n=57) lost 4.4% (8.7 pounds) — a statistically significant difference (p<0.01). For the clinically meaningful threshold of ≥10% weight loss, 32.9% of injection users achieved it versus 17.5% of pill users (p=0.03).
The proportion achieving ≥5% weight loss was not significantly different between formulations (58.7% vs 50.9%, p=0.34). An unexpected finding was an age effect within oral semaglutide users: older patients achieved better weight loss than younger ones (p=0.02), a pattern not seen in the subcutaneous group. Regression analyses adjusting for confounders confirmed these findings.
Kwon, Jimmy; Thiara, Diana; Watanabe, Jonathan H ·
RPEP-11977 · 2025Both pre-conjugation and post-conjugation of LinTT1 (AKRGARSTA) to PCL-PEG nanoparticles enabled binding to the target protein p32 in cell-free assays, but only when methyl-terminated PCL-PEG was used as diluent — acid-terminated polymer abolished target binding. Peptide conjugation via maleimide-thiol chemistry was confirmed by GPC and fluorescence. An unexpected morphological transformation from spheres to vesicles occurred upon peptide conjugation regardless of method. The pre-conjugation approach yielded smaller, more homogeneous nanoparticles.
Känkänen, Voitto; Hirvonen, Sami-Pekka; Teesalu, Tambet; Hirvonen, Jouni; Balasubramanian, Vimalkumar; Santos, Hélder A ·
RPEP-11979 · 2025Encapsulating LL-37 (the only human cathelicidin antimicrobial peptide) in hyaluronic acid-based nanogels increased its retention in the lungs by 36% compared to unformulated LL-37 after intratracheal administration. Without nanogel protection, approximately 85% of LL-37 was cleared from the lungs within 48 hours. The nanogel formulation also reduced the amount of peptide reaching the liver and kidneys, potentially decreasing the toxicity risks associated with high-dose antimicrobial peptide therapy.
The researchers used radiolabeled tracking (67-gallium for LL-37, 111-indium for the nanogel polymer) with SPECT/CT imaging to non-invasively monitor both the peptide and its carrier in real time in mice.
Kłodzińska, Sylvia N; Esposito, Tullio V F; Agnoletti, Monica; Rodríguez-Rodríguez, Cristina; Blackadar, Colin; Wu, Lan; Thakur, Aneesh; Nahrstedt, Jessica; Rades, Thomas; Saatchi, Katayoun; Häfeli, Urs O; Mørck Nielsen, Hanne · Animal
RPEP-11989 · 2025Among 2,216 patients with type 2 diabetes and chronic kidney disease discharged from an Australian hospital (2020–2024), only 21.3% were prescribed an SGLT2 inhibitor and 7.4% a GLP-1 agonist — despite strong evidence these drugs improve renal and cardiovascular outcomes. Only 3.6% received semaglutide specifically, and a mere 0.1% received finerenone. One-third (33.2%) of patients were discharged on none of the four recommended protective drug classes. Encouragingly, prescribing trends improved over the study period: SGLT2 inhibitor prescriptions rose from 7.9% to 38.7% (P<0.001) and GLP-1 agonist prescriptions from 6.3% to 11.7% (P=0.007).
Lan, Nick S R; McFadden, Ben; Johnson, Andrew; Shedden, Phillip; Fegan, P Gerry; Puttagunta, Harish; Ho, Sharon; Gillett, Richard; Swaminathan, Ramyasuda; Dwivedi, Girish ·
RPEP-11990 · 2025Metabolic variability signatures — natural fluctuations in heart rate, blood pressure, lipid levels, glucose, and body weight — can predict treatment responses and health outcomes. Increased variability in most metabolic parameters predicts worse outcomes. The Constrained Disorder Principle (CDP) describes how biological systems function within optimal variability ranges. AI platforms based on CDP can leverage rather than suppress this variability to enhance therapeutic outcomes, and this approach could be applied to personalize GLP-1 receptor agonist therapy for metabolic disorders.
Landau, Jakob; Tiram, Yariv; Ilan, Yaron ·
RPEP-11994 · 2025Using RNAscope combined with immunohistochemistry, the researchers found that most GLP-1 receptor (GLP1R), cholecystokinin A receptor (CCKAR), and neuropeptide Y2 receptor (NPY2R) neurons in the nodose ganglia co-expressed all three receptors. These triple-positive neurons were preferentially located in the right nodose ganglion.
Dual retrograde labeling with distinct tracers confirmed that neurons co-expressing GLP1R, CCKAR, and NPY2R innervated both the stomach and the distal colon — meaning individual nerve cells sample chemical signals from the entire gastrointestinal tract. Additional receptor subtypes (NTSR1, GPR65, 5-HT3A) showed different distribution patterns, with NTSR1 and GPR65 neurons nearly always co-expressing both receptors.
Lansbury, Elizabeth Laura; Vana, Vasiliki; Lund, Mari Lilith; Ludwig, Mette Q; Mamedova, Esmira; Gautron, Laurent; Arnold, Myrtha; Egerod, Kristoffer Lihme; Kuhre, Rune Ehrenreich; Holst, Jens Juul; Rekling, Jens; Schwartz, Thue W; Pankratova, Stanislava; Dmytriyeva, Oksana ·
RPEP-11997 · 2025In 935 CKD patients with validated kidney event outcomes:
- CKD273 peptide classifier confirmed as predictor of major adverse kidney events (≥40% eGFR decline or kidney failure)
- In silico simulation of 6 interventions: mineralocorticoid receptor antagonist, SGLT2 inhibitor, GLP-1 receptor agonist, ARB, olive oil diet, and exercise
- Simulated optimal interventions reduced median CKD273 from 0.57 to 0.039 (P < 0.0001)
- The combination of all available treatments was NOT the most frequently predicted optimal intervention — personalization mattered
- Patients with higher baseline scores required more complex combinations
- Approach uses individual urinary peptide profiles + known treatment effects on peptide abundance
Latosinska, Agnieszka; Mina, Ioanna K; Nguyen, Thi Minh Nghia; Golovko, Igor; Keller, Felix; Mayer, Gert; Rossing, Peter; Staessen, Jan A; Delles, Christian; Beige, Joachim; Glorieux, Griet; Clark, Andrew L; Schanstra, Joost P; Vlahou, Antonia; Peter, Karlheinz; Rychlík, Ivan; Ortiz, Alberto; Campbell, Archie; Rupprecht, Harald; Persson, Frederik; Mischak, Harald; Siwy, Justyna ·
RPEP-12000 · 2025The patient successfully completed 4 cycles of PRRT with 177Lu-DOTATATE despite having sickle cell anemia, a condition that could potentially complicate this type of therapy. Renal, hematologic, and liver lab values remained stable throughout treatment. Post-treatment, the disease remained stable for up to 13 months, and serum chromogranin A levels — a key tumor marker for neuroendocrine tumors — declined by 45%.
This is the first reported case demonstrating that PRRT can be safely administered to patients with sickle cell anemia, a population typically excluded from clinical trials due to concerns about hematologic complications.
Lawal, Ismaheel O; Gbolahan, Olumide B; Marcus, Charles; Jones, Aaron T; Shaib, Walid L; Muzahir, Saima ·
RPEP-12003 · 2025Using two-photon calcium imaging in awake adult mice, researchers found that monocular deprivation produced comparable ocular dominance shifts regardless of whether VIP peptide or GABA signaling was disrupted. However, disrupting GABA signaling from VIP interneurons specifically impaired the recovery of binocular responses after the deprived eye was reopened. Running enhanced contralateral eye responses in visual cortex, but this eye-specific modulation was altered during recovery and depended on VIP signaling pathways.
Lebedeva, Anna; Kling, Friedrich; Rakela, Benjamin; Stryker, Michael P; Sun, Jennifer Y ·
RPEP-12009 · 2025The CHA-DEX-MEPI hydrogel demonstrated sustained release of both dexamethasone and mepivacaine for more than 72 hours, compared to rapid clearance with standard solution injections.
In activated macrophages, the hydrogel prolonged reduction of inflammatory cytokine gene expression for three days compared to a simple drug solution.
In rats with chronic constriction nerve injury, the hydrogel significantly reduced both cold and mechanical allodynia (pain from normally non-painful stimuli) beginning seven days post-injury. At 14 days post-injury, the hydrogel produced sustained reductions in key nociceptive markers including TRPV1, TRPA1, and importantly CGRP — a neuropeptide directly involved in pain transmission and neurogenic inflammation.
Lee, Daye; Han, Gong Ho; Kim, Seong Jun; Ko, Wan-Kyu; Kim, Min Je; Ju, Gi-Beom; Sheen, Seung Hun; Hong, Je Beom; Cho, Min Jai; Sohn, Seil ·
RPEP-12011 · 2025Intravenous BPC-157 at doses of 10 mg and 20 mg was well-tolerated in two healthy adults with no adverse effects. Blood work monitoring showed no measurable effects on heart, liver, kidney, thyroid, or blood glucose biomarkers across the three-day study period.
This is the first published study examining intravenous BPC-157 administration in humans. Both participants had previously received IV BPC-157, and the IRB-approved protocol used escalating doses over two consecutive days.
Lee, Edwin; Burgess, Kailynd · Pilot Study
RPEP-12013 · 2025D-allulose, a rare low-calorie sugar, reduced obesity in mice fed a high-fat diet by stabilizing the GLP-1 receptor through a specific molecular mechanism. The sugar works by inhibiting a stress-response pathway (the IRE1α-RIDD axis) in cells that would otherwise degrade the GLP-1 receptor. Crucially, the anti-obesity effects disappeared completely in mice genetically lacking the GLP-1 receptor, proving that D-allulose's weight-regulating benefits depend entirely on a functioning GLP-1 receptor. The study also identified the GLP-1 receptor as a previously unknown target of the RIDD decay pathway.
Lee, Geum-Hwa; Lee, Hwa-Young; Lim, Young Jae; Kim, Ji-Hyun; Rah, So-Young; Chung, Myung Ja; Park, Se Young; Sa, Soonok; Lee, Hyewon; Soh, Yunjo; Kim, Junghyun; Chae, Han-Jung · Animal Study
RPEP-12017 · 2025Two peptides (SpA h1 and SpA h2) were designed based on the Fc-binding helices of the Z34C domain from Protein A. Lactam stapling — introducing a chemical bridge between lysine and glutamic acid residues at positions i and i+4 — significantly increased their alpha-helical content as measured by circular dichroism spectroscopy.
The stapled peptides showed markedly improved IgG-binding performance in fluorescence-based capture assays. Surface plasmon resonance confirmed specific, concentration-dependent Fc binding. Critically, (s)SpA h1 demonstrated enhanced resistance to α-chymotrypsin digestion compared to its linear counterpart and showed strong Fc selectivity with minimal Fab binding — properties essential for practical antibody purification and bioconjugation applications.
Lee, Jung Gu; Lee, Inseo; Kim, Joo-Young; Kim, Suin; Jeong, Woo-Jin; Kim, Ji-Eun ·
RPEP-12020 · 2025Two engineered variants of the AtMP2 peptide (AtMP2-1 and AtMP2-2), generated through systematic directed evolution, demonstrated higher antimicrobial activity against Gram-positive bacteria than the parent AtMP2 peptide, as measured by Minimum Inhibitory Concentration (MIC) and Kirby-Bauer disk diffusion assays. Activity against Gram-negative bacteria was comparatively lower.
Cytotoxicity testing using SRB assays on HS-27 (human fibroblast) and Vero cell lines showed both variants were safe at 20 µg/mL. Molecular docking analysis revealed strong binding interactions with bacterial proteins involved in cell death pathways, including SecA, RpoB, GyrA, ClpP, and MetG, with more negative scores indicating stronger binding.
Lee, Li Ting; Ang, Arnold; Najm, Ahmed; Adnan, Adura Mohd; Nordin, Akram Mohd; Mahmood, Ibrahim; Dunkhorol, Sarantuya; Fazry, Shazrul; Law, Douglas ·
RPEP-12021 · 2025Long-acting GLP-1 receptor agonists — both injectable and oral forms — significantly reduced cardiovascular events, heart failure hospitalizations, kidney complications, and death in people with type 2 diabetes. Across 10 randomized trials with over 71,000 participants, GLP-1 RAs reduced major adverse cardiovascular events by 14% (HR 0.86), heart failure hospitalization by 14%, composite kidney outcomes by 17%, and all-cause mortality by 12%.
Critically, there was no significant difference in benefits between subcutaneous (injectable) and oral formulations, and no increased risks of severe hypoglycemia, retinopathy, or pancreatic events were found.
Lee, Matthew M Y; Sattar, Naveed; Pop-Busui, Rodica; Deanfield, John; Emerson, Scott S; Inzucchi, Silvio E; Mann, Johannes F E; Marx, Nikolaus; Mulvagh, Sharon L; Poulter, Neil R; Badve, Sunil V; Pratley, Richard E; Perkovic, Vlado; Buse, John B; McGuire, Darren K · Meta Analysis
RPEP-12024 · 2025The review identifies several key developments in amylin receptor agonist research:
• Amylin receptors are heterodimers of the calcitonin receptor and receptor activity-modifying proteins (RAMPs) — a unique and druggable receptor architecture
• Multiple amylin analogs are in preclinical and clinical development for obesity
• Combination therapy (amylin analog + other anti-obesity peptide drugs) has demonstrated higher clinical efficacy in reducing body weight than monotherapy
• Combination therapy is likely to be the first clinical application where an amylin analog is used for obesity
• Amylin receptor activators may have a more favorable adverse effect profile than GLP-1 receptor agonists
• Key engineering advances: mutations enhancing receptor affinity/potency, lipidation for long-acting properties, and methods for measuring selective amylin receptor activation
Lee, Sangmin ·