RPEP-11223 · 2025Fermenting wheat with the yeast Candida phyllophila J14-4 increased angiotensin-converting enzyme (ACE) inhibition activity by 46.05%. Peptide components under 3 kDa in the fermented wheat showed strong ACE-inhibitory activity, with the most potent peptide reaching 93.23% inhibition. In spontaneously hypertensive rats, the antihypertensive effect of the fermented wheat was comparable to captopril, a standard prescription ACE inhibitor drug.
Guo, Xing; Wang, Maomao; Cheng, Yifan; Hu, Zeyu; Yuan, Yahong; Yue, Tianli · Animal
RPEP-11224 · 2025After three months of sacubitril/valsartan treatment, median pulmonary artery pressure in peritoneal dialysis patients dropped from 48.00 mmHg to 33.00 mmHg (P<0.001).
The percentage reduction in pulmonary artery pressure was -30.0% with sacubitril/valsartan versus -8.6% with ARB alone (P<0.001) — more than three times greater.
Heart failure biomarkers NT-proBNP (N-terminal B-type natriuretic peptide precursor) and cardiac troponin I were both significantly reduced after sacubitril/valsartan treatment. Left ventricular remodeling was also attenuated. Standard ARB therapy did not show significant advantages compared to sacubitril/valsartan on any of these measures.
Guo, Yanhong; Zhao, Silu; Zhang, Xuewen; Gou, Rong; Wang, Liuwei; Wang, Yulin; Zhai, Zihan; Yu, Lu; Tang, Lin ·
RPEP-11226 · 2025NT-proBNP is a widely used biomarker for heart failure, but its diagnostic accuracy in HFpEF (heart failure with preserved ejection fraction) is compromised by age, obesity, atrial fibrillation, and kidney dysfunction. This review proposes a structured clinical pathway that combines adjusted NT-proBNP thresholds, clinical scoring systems like the H2FPEF and HFA-PEFF scores, and multimodal imaging to improve diagnosis of this commonly missed condition.
HFpEF accounts for approximately 50% of all heart failure cases globally but remains one of the most underdiagnosed cardiovascular conditions because its symptoms mimic those of other age-related conditions.
Gupta, Mukulesh; Kumar, Dinesh; Gupta, Tuhina · Review
RPEP-11229 · 2025This perspective proposes combining continuous glucose monitoring (CGM) with GLP-1 receptor agonists like semaglutide for personalized obesity management, even in people without diabetes. CGM provides real-time metabolic feedback that could help optimize GLP-1 therapy by tracking glucose variability and behavioral patterns, while GLP-1 drugs address appetite dysregulation and hyperinsulinemia. However, the authors acknowledge a critical evidence gap: no randomized controlled trials have assessed this combination specifically for obesity in non-diabetic populations. They also note that CGM-derived metrics remain unstandardized in this context and suggest that AI-driven CGM analysis could predict individual responsiveness to GLP-1 therapy.
Gupta, Pragati; Pozzilli, Paolo · Perspective
RPEP-11231 · 2025A 42-year-old woman with recurrent hypertriglyceridemia-induced acute pancreatitis was started on a GLP-1 receptor agonist despite the conventional concern about pancreatitis risk with this drug class. The outcomes were markedly positive:
- 15% body weight loss achieved
- Sustained triglyceride reduction maintained
- No recurrence of acute pancreatitis while on GLP-1RA therapy
This challenges the blanket avoidance of GLP-1RAs in patients with pancreatitis history and suggests that when severe hypertriglyceridemia is the root cause, the triglyceride-lowering benefit may outweigh the theoretical pancreatitis risk.
Guralwar, Chinmay; Mitsuhashi, Shuji; Ashkar, Motaz; Chedid, Victor G ·
RPEP-11236 · 2025Vasoactive intestinal peptide (VIP) reduced SARS-CoV-2 infection of epithelial cells through a dual mechanism. First, VIP downregulated both ACE2 and TMPRSS2 — the two proteins the virus uses to enter cells — at both the mRNA and surface protein levels. Second, VIP upregulated a protease called ADAM10, which physically strips ACE2 and TMPRSS2 from the cell surface (a process called shedding).
The combined effect of these two mechanisms — reduced production plus active removal — resulted in fewer viral entry points on cell surfaces and a measurably reduced infection rate when cells were challenged with a SARS-CoV-2 pseudovirus. The researchers suggest the ADAM10 connection may have implications beyond COVID-19.
Gutzler, Charlotte; Höhne, Kerstin; Bani, Daniele; Kayser, Gian; Fähndrich, Sebastian; Ambros, Michael; Hug, Martin J; Rieg, Siegbert; Falcone, Valeria; Müller-Quernheim, Joachim; Zissel, Gernot; Frye, Björn C · In Vitro
RPEP-11237 · 2025In rats subjected to cerebral ischemia-reperfusion injury, Cortexin treatment significantly reduced total oxidant status (TOS) and increased total antioxidant status (TAS) compared to untreated injury groups. The ischemia and I/R groups showed significantly elevated TOS (p = 0.012 and p = 0.005) and decreased TAS (p = 0.000) versus controls.
Cortexin also modulated the expression of key biomarkers in brain tissue: OPG (a protective factor against cell death), RANK/RANKL (inflammatory signaling), and TRPC1 (calcium channel involved in neuronal function). The effects were observed at both 1 mg/kg and 2 mg/kg doses. However, some inflammatory markers remained elevated despite treatment, suggesting Cortexin partially but not completely reversed the inflammatory response.
Guven, Cengiz; Türk, Ahmet; Koçak, Seda; Zencirci, Busra; Yalcin, Alper; Aydın, Hasan; Doğukan, Mevlut · Animal Study
RPEP-11244 · 2025In the PCOS rat model, hypothalamic expression of both Kiss1 (kisspeptin) and Cgrp (calcitonin gene-related peptide) genes was significantly elevated compared to healthy controls (p≤0.05). Treatment with naringenin at both dose levels (20 mg/kg and 50 mg/kg) significantly reduced Kiss1 and Cgrp gene expression compared to the untreated PCOS group (p≤0.05).
This represents a novel mechanistic finding — while naringenin's effects on PCOS have been previously reported, this is the first demonstration that its benefits may involve modulation of hypothalamic kisspeptin and CGRP signaling pathways.
Habibi, Manizheh; Mahmoudi, Fariba; Haghighat, Khadijeh; Khazali, Homayoun ·
RPEP-11247 · 2025Key findings from cell line and patient-derived organoid (PDO) experiments:
1. Endometrial cancer cell lines (Hec50, KLE, Ishikawa) all express GLP-1 receptors (confirmed by qPCR and Western blot)
2. GLP-1R agonist treatment induces its own receptor expression through positive feedback
3. Patient-derived organoids from 6 individuals with grade 1 endometrial carcinomas showed significant viability reduction with levonorgestrel + semaglutide combination — in both progesterone receptor-high AND progesterone receptor-low tumors
4. Most striking: semaglutide upregulated not only membrane GLP-1R but also nuclear progesterone receptors (PR) and membrane progesterone receptors (PGRMC1/2)
5. This creates a synergistic feedback loop: semaglutide makes tumors more responsive to levonorgestrel, while levonorgestrel makes them more responsive to semaglutide
Hagemann, Andrea R; Hagemann, Ian S; Mutch, David G; Devor, Eric J; Malmrose, Paige K; Zhang, Yuping; Morrison, Abigail M; Thiel, Kristina W; Leslie, Kimberly K ·
RPEP-11249 · 2025Fremanezumab, an anti-CGRP monoclonal antibody, effectively reduced migraine frequency, acute medication use, and headache-related disability in adults with migraine complicated by medication overuse. Clinical trial post hoc analyses showed significant reductions in monthly migraine days, acute headache medication use days, and HIT-6 disability scores compared to placebo over 12 weeks. Real-world studies demonstrated sustained reductions in monthly headache days at 6 months and a high reversion rate from medication overuse headache after one year of treatment.
Hajjaj, Ibrahim; Baraldi, Carlo; Pellesi, Lanfranco ·
RPEP-11260 · 2025GLP-1 receptors are widely distributed across multiple organ systems — brain, lungs, pancreas, stomach, heart, and endometrium — which explains the broad therapeutic potential of GLP-1 receptor agonists beyond their original diabetes indication.
Recent studies demonstrate physiological effects across these organ systems: blood glucose regulation and pancreatic beta-cell function, weight management through appetite suppression and metabolic effects, cardiovascular protection including reduced major adverse cardiovascular events, potential neuroprotective effects relevant to neurodegenerative diseases, and positive influences on musculoskeletal health. While clinical efficacy for diabetes and obesity is well established, many of these expanded indications are still being investigated.
Hammad, Bisma Fatima; Zafar, Nimrah; Ullah, Muneeb; Faisal, Syeda Jazilah; Iftikhar, Fizzah; Waheed, Haadia; Muzaffar, Muhammad Waleed; Ahmed, Khadija; Ashraf, Faz; Zahid, Komal; Akhtar, Maimoona; Mahmmoud Fadelallah Eljack, Mohammed ·
RPEP-11265 · 2025The peptide-drug conjugate MEL-dKLA — combining melittin (which selectively binds M2-like macrophages) with the pro-apoptotic peptide dKLA — preferentially bound to and killed tumor-associated macrophages (TAMs) that promote cancer growth. In cell culture, treating M2 macrophages with MEL-dKLA reduced their ability to stimulate prostate cancer cell proliferation, migration, and invasion.
In a mouse prostate cancer model, MEL-dKLA treatment significantly reduced tumor growth, decreased CD163+ M2 macrophages in tumors, and increased CD8+ killer T cell infiltration — effectively reprogramming the tumor microenvironment from immunosuppressive to immune-active.
Han, Ik-Hwan; Choi, Ilseob; Kim, Soyoung; Kwon, Minjin; Choi, Hyojung; Bae, Hyunsu ·
RPEP-11266 · 2025Researchers developed new chemical building blocks (cyclic dipeptide-derived hydroxylamines) that enable peptide ligation at fully native sites — meaning no unnatural amino acids are left behind at the joining point. They demonstrated the method by synthesizing two challenging targets: ubiquitin (for protein research) and tirzepatide (the GLP-1/GIP dual agonist drug).
The tirzepatide synthesis was particularly notable because the drug contains non-standard features — amino-isobutyric acid (Aib) residues and a fatty acid side chain — that make it extremely difficult to produce by traditional methods. The new approach successfully joined unprotected peptide segments at 'nonobvious' junctions like Leu-Ile and Lys-Ile.
Han, Jiling; Hirao, Kohtaro; Mikami, Toshiki; Nötel, Nicolas Y; Seidl, Leonardo L; Bode, Jeffrey W · Methodology
RPEP-11268 · 2025The cell-penetrating peptide penetratin (PEN) exhibits a nonmonotonic concentration threshold effect when interacting with sphingomyelin membranes. At optimal concentrations, PEN promotes structural ordering that facilitates membrane crossing, but beyond this threshold, it causes excessive disruption that reduces efficiency.
The study revealed asymmetric chain reorganization in lipid molecules, with sphingosine terminal methyl orientation shifting from 32° to 55° depending on conditions, while N-alkyl chain angles remained stable (32°–38°). At high lipid packing density (30 mN/m), elevated hydrogen-bond networks correlate with non-bonded peptide carbonyl states, while low density (10 mN/m) promotes hydrogen-bonded peptide adsorption to the membrane surface.
Han, Linyu; Liu, Caihe; Zhang, Yuening; Qin, Xujin; Guo, Yuan; Liu, Minghua; Zhang, Zhen ·
RPEP-11269 · 2025The review integrates foundational and recent research to describe four hierarchical levels of neural control over colorectal motility and defecation:
1. Cortical and hypothalamic centers in the brain
2. Pontomedullary cell groups in the brainstem
3. Lumbosacral defecation centers in the spinal cord
4. The enteric nervous system (ENS) within the gut wall
The critical link between the central nervous system (CNS) and ENS is provided by parasympathetic preganglionic (PPG) neurons, which express a wide range of amine and peptide receptors. These receptors — including those for ghrelin, dopamine, and serotonin — are identified as potential therapeutic targets for constipation. The importance of CNS-ENS coordination is demonstrated by the severe constipation that follows spinal cord injury or occurs in Parkinson's disease, and by the failed defecation seen in Hirschsprung and Chagas diseases when the ENS is absent.
Han, Myat Noe; Furness, John B; Ringuet, Mitchell T; Montenegro, Ella; Wu, Hongkang; Hossain, Mohammed Akhter; Diwakarla, Shanti; Dehkhoda, Farhad; Furness, Sebastian G B ·
RPEP-11277 · 2025Using brain slices from mutant mice with functional inactivation of either ACE catalytic domain, researchers demonstrated that only N-terminal domain inactivation reduced the degradation of Met-enkephalin-Arg-Phe (MERF) to Met-enkephalin. C-terminal domain inactivation had no effect. A selective N-terminal domain inhibitor (RXP 407) reduced degradation of both exogenously applied and endogenously released MERF, while leaving degradation of Met-enkephalin and Leu-enkephalin unaffected.
Hanak, Filip; Swanson, Jessica L; Felczak, Krzysztof; Bernstein, Kenneth E; More, Swati S; Rothwell, Patrick E · Preclinical Mechanistic
RPEP-11278 · 2025After propensity score matching of 3,652 first-trimester pregnant women with T2D (average age 36.2 years in the GLP-1RA group), maternal all-cause mortality was comparable between GLP-1RA-exposed and control cohorts at 42 weeks. Secondary maternal outcomes — gestational hypertension, preeclampsia, and eclampsia — were also comparable. Fetal cardiac and kidney anomaly risks were not increased in the GLP-1RA-exposed group. The analysis used a global EHR database of over 140 million patients.
Hanif, Muhammad; Hays, Allison G; Nagarajan, Jai S; Sah, Shiva P; Weinstock, Ruth S; Taub, Cynthia C ·
RPEP-11285 · 2025Across 601 trials (309,503 participants for HbA1c; 168,489 for MACE), GLP-1 receptor agonists showed greater cardiovascular risk reduction in younger vs. older people (HR 1.47 per 30-year age increment, 95% CrI 1.07-2.02 — meaning less benefit with age). Conversely, SGLT2 inhibitors showed greater cardiovascular protection in older vs. younger people (HR 0.76 per 30-year increment, 95% CrI 0.62-0.93). For HbA1c, GLP-1 drugs lowered it more in older patients for mono/dual therapy, while SGLT2 inhibitors lowered it less with increasing age. No consistent sex × treatment interactions were found for either drug class.
Hanlon, Peter; Butterly, Elaine; Wei, Lili; Wightman, Heather; Almazam, Saleh Ali M; Alsallumi, Khalid; Crowther, Jamie; McChrystal, Ryan; Rennison, Heidi; Hughes, Katherine; Lewsey, Jim; Lindsay, Robert; McGurnaghan, Stuart; Petrie, John; Tomlinson, Laurie A; Wild, Sarah; Adler, Amanda; Sattar, Naveed; Phillippo, David M; Dias, Sofia; Welton, Nicky J; McAllister, David A ·
RPEP-11289 · 2025CGRP levels in both plasma and cerebrospinal fluid were not elevated in patients with idiopathic intracranial hypertension (IIH) compared to headache controls or healthy controls. No differences were found after adjusting for BMI, age, and smoking. CGRP levels were not associated with having migraine-like headache, chronic headache, or any headache versus no headache in IIH patients. However, plasma CGRP correlated significantly with CSF CGRP levels (p<0.0001). The results suggest basal CGRP levels do not differ in IIH, though the role of CGRP in IIH headache remains unclear.
Hansen, Nadja Skadkær; Korsbaek, Johanne Juhl; Bak, Lasse Kristoffer; Jørgensen, Niklas Rye; Beier, Dagmar; Jensen, Rigmor Højland ·
RPEP-11303 · 2025In a 25-year Markov model of 13,650 Aboriginal and Torres Strait Islander Australians with cardiovascular disease and obesity (without type 2 diabetes), semaglutide was projected to prevent 929 additional fatal CVD events and 13,480 non-fatal CVD events compared to standard care. The program would save 8,628 disability-adjusted life years at an additional cost of approximately $26 million per year to the Australian government — less than 0.2% of annual CVD expenditure. The incremental cost-effectiveness ratio was $75,206/DALY.
Hargovan, Satyen; Hunt, Nadine; Kostakis, Hara; Chow, Clara K ·
RPEP-11306 · 2025In a 61-year-old female with Class III obesity who had lost significant weight on semaglutide, PET/CT imaging showed FDG uptake in a right level II lymph node consistent with her known neck mass. However, the scan also revealed extensive brown adipose tissue (BAT) activation throughout the cervical and supraclavicular regions and mediastinum, which mimicked diffuse regional metastasis.
Careful fusion of anatomical CT data with functional PET data was required to distinguish metabolically active brown fat from malignant disease. Without this careful interpretation, the brown fat activation could have led to misdiagnosis of widespread cancer and unnecessary aggressive treatment.
Harrison, Daron B; Phillips, Alisa L; Tansey, James B; Clarke, Travis J; Wood, C B; Nedzi, Lucien; Schwartz, David L; Makowski, Liza; Hayes, D N; Newman, Grace; Gleysteen, John P ·
RPEP-11308 · 2025Adding efruxifermin (an FGF21 analog) to GLP-1 receptor agonist therapy in patients with MASH, liver fibrosis, and type 2 diabetes produced dramatic liver fat reduction: 65% decrease in hepatic fat fraction compared to just 10% with GLP-1 RA alone over 12 weeks (P < .0001). The combination also improved markers of liver injury, fibrosis, glucose metabolism, and lipid levels while maintaining the weight loss benefits of the GLP-1 RA.
Safety was a key focus: the combination appeared well-tolerated with a safety profile comparable to either drug alone. The most common side effects were mild-to-moderate GI events. Only one patient discontinued due to nausea, and there were no treatment-related serious adverse events. Nearly half the patients were on semaglutide, with the remainder on dulaglutide or liraglutide.
Harrison, Stephen A; Frias, Juan P; Lucas, K Jean; Reiss, Gary; Neff, Guy; Bollepalli, Sureka; Su, Yan; Chan, Doreen; Tillman, Erik J; Moulton, Ali; de Temple, Brittany; Zari, Arian; Shringarpure, Reshma; Rolph, Timothy; Cheng, Andrew; Yale, Kitty · Randomized Controlled Trial (Phase 2b)
RPEP-11312 · 2025At three months, erenumab produced statistically significant improvements across all outcomes: monthly migraine days reduced by 1.78 (95% CI: -2.37 to -1.20, P < 0.00001), monthly medication days reduced by 1.36 (95% CI: -1.92 to -0.81, P < 0.00001), HIT-6 headache impact score improved by 2.83 points (95% CI: -3.83 to -1.82, P < 0.00001), and 52% more patients achieved ≥50% reduction in migraine days (RR: 1.52, 95% CI: 1.31 to 1.76, P < 0.00001). Subgroup analysis showed greater efficacy in patients with prior treatment failures. No significant difference between 70 mg and 140 mg doses except for medication day reduction.
Haseeb, Mohamed E; Mohammed, Hazem E; Yaser, Hatem; Hanen, George; Nasser, Mohamed; Yaser, Shehab; Bady, Zeyad ·
RPEP-11314 · 2025Across 3 RCTs with 922 patients, once-weekly semaglutide versus once-daily liraglutide produced: significantly greater weight loss (WMD -4.55 kg, 95% CI -6.43 to -2.67, p<0.01), greater HbA1c reduction (WMD -0.46%, 95% CI -0.84 to -0.08, p=0.02), and greater fasting plasma glucose reduction (WMD -1.23 mmol/L, 95% CI -1.51 to -0.95, p<0.01). Safety was comparable: severe adverse events (OR 1.66, p=0.38) and GI adverse events (OR 1.84, p=0.14) did not significantly differ between groups.
Hashmi, Tallal Mushtaq; Ahmed, Mushood; Haider, Ali; Naseem, Salman; Jafar, Uzair; Hussain, Munir; Iqbal, Javed; Ali, Waqar; Ahmed, Raheel ·
RPEP-11317 · 2025Tirzepatide received FDA approval in 2024 for managing obesity in adults with obstructive sleep apnea. The dual GIP/GLP-1 receptor agonist works by promoting weight loss, which reduces the breathing interruptions characteristic of OSA and enhances sleep quality.
The review highlights that tirzepatide has potential implications for oral health, including the management of periodontal disease, dental implant procedures, and orthodontic interventions. Dental care providers should understand these connections as part of multidisciplinary OSA management that combines lifestyle modifications, pharmaceutical interventions, oral appliance therapy, and surgical options.
Hassan, Mohamed G; Hassan, Dina G; Hassan, Gamaleldin A ·
RPEP-11322 · 2025A small peptide (JAL-TA9) that can break down amyloid-beta — the toxic protein in Alzheimer's disease — successfully reaches the brain when delivered through the nose, but not when injected into the bloodstream. After nasal administration in rats, the peptide was detectable in cerebrospinal fluid at 0.115 μg/mL within 10 minutes, while IV injection produced undetectable brain levels.
The peptide has an extraordinarily short blood half-life (<1 minute), making IV delivery useless. But it's far more stable in cerebrospinal fluid than in blood, making the nose-to-brain route ideal. Brain distribution data showed the peptide first reaches the olfactory bulb (peak at 5 min), then moves sequentially to frontal brain (30 min) and occipital brain (60 min), confirming direct nose-to-brain transport.
Hatakawa, Yusuke; Tanaka, Akiko; Furubayashi, Tomoyuki; Katsumi, Hidemasa; Nakamura, Rina; Konishi, Motomi; Akizawa, Toshifumi; Sakane, Toshiyasu · Preclinical Pharmacokinetics Study (Rat/Mouse)
RPEP-11329 · 2025Recombinant human collagen III (rhCol III) peptides significantly upregulated matrix remodeling genes in human fibroblasts, including Collagen types I and III, Elastin, Fibrillin 1, and Hyaluronic acid synthases 1, 2, and 3. In a novel 3D filler biomimetic skin model, the peptides directly bound to the dermal scaffold and demonstrated beneficial effects on both skin layers: improved epidermal regeneration (shown by Ki67 and COL17A1 markers) and enhanced dermal remodeling (FBN1 and glycosaminoglycans).
Transcriptomic analysis revealed the peptides downregulated inflammation, senescence, and apoptosis pathways while upregulating integrin binding and extracellular matrix formation — suggesting mechanisms for skin rejuvenation beyond simple volume filling.
He, Chunyan; Wang, Ranran; Zhang, Qiao; Wang, Yehong; Huang, Nan ·
RPEP-11331 · 2025Two patients developed symptomatic ketotic hypoglycemia after sleeve gastrectomy, characterized by low insulin, low C-peptide, and elevated beta-hydroxybutyrate levels during fasting (at 40 and 65 hours respectively). Morning cortisol and IGF-1 were normal, ruling out adrenal or growth hormone deficiency.
Dietary management was inadequate. Treatment with semaglutide resulted in complete resolution of hypoglycemic episodes in one patient and significant reduction in the other. The mechanism likely involves reduced hepatic, renal, or intestinal gluconeogenesis after bariatric surgery, or a possible unmasked inborn error of metabolism.
He, Jinwen; Phillips, Liza; Nisbet, Janelle; Morton, Adam ·
RPEP-11333 · 2025Among 2,215 biliary adverse event reports, 1,709 involved GLP-1 RAs and 506 involved DPP-4 inhibitors. Key reporting odds ratios:
- Semaglutide: ROR 4.06 (95% CI 3.76–4.39) for biliary disorders
- Liraglutide: ROR 3.88 (95% CI 3.50–4.29)
- DPP-4 inhibitors overall: ROR 3.09 (95% CI 2.83–3.37)
- Sitagliptin specifically: ROR 3.46 (95% CI 3.13–3.83)
Both semaglutide and liraglutide showed significant associations with gallbladder disorders, gallstone disorders, and infectious biliary disorders. Liraglutide, alogliptin, sitagliptin, and linagliptin were also linked to biliary malignant tumors. DPP-4 inhibitors had a higher proportion of serious outcomes (76.88%) compared to GLP-1 RAs (51.55%).
He, Long; Li, Jinwei; Cheng, Xiong; Luo, Li; Huang, Yilan ·
RPEP-11335 · 2025The lead azapeptide analogue, AzaA8/R34-GLP-1 (AzaA8), demonstrated resistance to dipeptidyl peptidase-4 (DPP-4) degradation for over 24 hours — a dramatic improvement over native GLP-1 which is degraded within minutes. Despite the backbone modification, AzaA8 maintained picomolar potency at the GLP-1 receptor.
In lean mice, AzaA8 improved oral glucose tolerance. In high-fat diet-induced obese mice, chronic administration reduced body weight, decreased both leptin and insulin levels, and enhanced glucose handling. No detectable inflammatory adverse effects were observed, supporting the safety profile of this azapeptide approach.
He, Mingzhu; Cheng, Kai Fan; VanPatten, Sonya; Torres, Marcelo D T; Jabari, Bayan Al; Mughrabi, Ibrahim T; Ballarín-González, Borja; Son, Myoungsun; de la Fuente-Nunez, Cesar; Al-Abed, Yousef ·
RPEP-11336 · 2025IGF1 regulates the expression of multiple appetite-controlling neuropeptides in hypothalamic neurons. In both mouse and human models, IGF1 modulated expression of AgRP, NPY, POMC, CART, spexin, galanin, and FAM237B, producing an overall appetite-suppressing (anorexigenic) profile. IGF1 receptors were found in both NPY/AgRP and POMC neurons, with higher expression in POMC neurons.
Critically, the study discovered that hyperinsulinemia (chronically high insulin levels) induces IGF1 resistance in hypothalamic neurons by reducing IGF1R protein and mRNA through over-activation of PI3K-FOXO1 signaling. This provides a novel mechanism linking metabolic disease to disrupted neuropeptide signaling in the brain.
He, Wenyuan; Loganathan, Neruja; Belsham, Denise D · In Vitro
RPEP-11339 · 2025The Pre-GRU deep learning model combined with molecular docking successfully identified ACE-inhibitory peptides from quinoa:
- Model accuracy: R²train = 0.86-0.88, R²test = 0.53-0.55
- 4 out of 7 synthesized candidate peptides showed ACE inhibition activity (57% hit rate)
- NLFRP was the most potent: IC50 = 3.33 ± 0.19 μM
- Molecular docking revealed NLFRP forms tetrahedral coordination with ACE's zinc-binding HEXXH motif, explaining its strong binding
- Transfer learning from adjacent peptide lengths addressed the common problem of limited training data
- Balanced MSE loss function improved prediction accuracy despite imbalanced datasets
He, Yanan; Deng, Zhiyang; Lyu, Yujiao; Yan, Yan; Liu, Jun; Liu, Haijie ·
RPEP-11346 · 2025A 28-year-old woman with obesity and POTS (postural orthostatic tachycardia syndrome) experienced significant worsening of her condition while using tirzepatide for weight loss. Despite having successfully controlled her POTS through exercise training (reducing heart rates to normal values), tirzepatide caused a 20-30 beats/min increase in both supine and standing heart rates — far exceeding the typical ~3 bpm increase seen with GLP-1 drugs. She also experienced recurrence of orthostatic intolerance symptoms.
This magnitude of heart rate increase with tirzepatide in a POTS patient has not been previously reported.
Hedge, Eric T; Grappe, Shannon R; Vernino, Steven; Almandoz, Jaime P; Levine, Benjamin D ·
RPEP-11348 · 2025Retatrutide, the triple-receptor agonist (GIP/GLP-1/glucagon), showed kidney-protective effects in two phase 2 trials. In people with type 2 diabetes, retatrutide 12 mg reduced urine albumin-to-creatinine ratio (UACR) by 37% versus placebo at 36 weeks, though kidney filtration rate (eGFR) was unchanged. In people with obesity but no diabetes, retatrutide 12 mg reduced UACR by 31.5% and increased eGFR by 8.5 ml/min/1.73m² at 48 weeks.
The eGFR improvement in the obesity group was confirmed using three different measurement methods (creatinine-based, cystatin C-based, and combined), strengthening confidence in the finding. However, since most participants had normal baseline albuminuria, the absolute reductions were modest.
Heerspink, Hiddo J L; Lu, Zeqing; Du, Yu; Duffin, Kevin L; Coskun, Tamer; Haupt, Axel; Hartman, Mark L · Rct Post Hoc
RPEP-11351 · 2025Meta-analysis of clinical studies demonstrated that GLP-1 receptor agonists significantly improved motor function in Parkinson's disease:
- MDS-UPDRS Part III (motor examination) in ON state: mean difference = -2.88 points (p=0.01, I²=30%)
- The low heterogeneity (I²=30%) indicates consistent effects across studies
- However, GLP-1 RA treatment was associated with higher incidence of adverse events across all safety outcomes
The review also examined motor complications (Part IV) and motor experiences of daily living (Part II), as well as gastrointestinal and systemic side effects.
Helal, Mohamed Mohsen; AbouShawareb, Hala; Abbas, Omarfayez Hussein; Haddad, Roaa; Zain, Youmna; Osman, Ahmed S A; Hassan, Amr K ·
RPEP-11354 · 2025Among 153,044 patients with documented semaglutide and/or tirzepatide use in the American Family Cohort (a nationwide US primary care EHR database spanning 2021-2024), 8.2% had documented use of compounded formulations. This proportion increased over time as drug shortages drove more patients to compounding pharmacies.
Users of compounded formulations had notably different demographics: they were more likely to be female, non-Hispanic White, non-diabetic, and living in areas of lower socioeconomic deprivation. They also had longer mean therapy durations (10.0 months for compounded-only users vs. 7.8 months for brand-name-only users). The documented rate of 8.2% was substantially lower than the ~23% estimated by surveys, suggesting significant undocumented use outside coordinated primary care.
Hendrix, Nathaniel; Velásquez, Esther E; Pham, Harry; Bazemore, Andrew ·
RPEP-11357 · 2025The review identifies several key findings regarding obesity pharmacotherapy in adults over 60:
• Nine anti-obesity medications are currently approved, but clinical trial evidence in older adults is predominantly limited to incretin-based therapies: liraglutide, semaglutide, and tirzepatide
• GLP-1 receptor agonists enhance weight loss and reduce cardiometabolic events in older populations
• Critically, these drugs help maintain muscle mass during weight loss — addressing the primary safety concern in elderly obesity treatment
• Recent evidence supports that intentional weight loss in older adults with overweight/obesity is effective and safe, reducing the historical reluctance to prescribe anti-obesity medications
• Lifestyle interventions with emphasis on resistance training remain the foundation, with pharmacotherapy as an adjunct for refractory cases
Henney, Alex E; Wilding, John P H; Alam, Uazman; Cuthbertson, Daniel J ·
RPEP-11359 · 2025Long-term (6-day) exposure of human islet microtissues to proinflammatory cytokines (IL-1β, IFN-γ, TNF-α) created a type 1 diabetes-like phenotype with dose-dependent suppression of glucagon secretion at low glucose (2.8 mmol/L), reduced insulin and somatostatin secretion, decreased ATP content, increased cell death, and diminished key transcription factors (ARX, NKX6.1).
Critically, while incretin treatment during cytokine exposure did not prevent damage, acute treatment with [D-Ala2]-GIP (with or without liraglutide) or tirzepatide after cytokine exposure partially restored low-glucose glucagon secretion. Alpha cells also retained partial responsiveness to L-arginine stimulation despite cytokine damage.
Henriksen, Kristine; Rufer, Chantal; Title, Alexandra C; Jawurek, Sayro; Hartmann, Bolette; Holst, Jens J; Knop, Filip K; Yesildag, Burcak; Størling, Joachim ·
RPEP-11360 · 2025Machine learning tools screened two peptide libraries (8,192 and 512 sequences) rich in tryptophan and arginine residues. The top 220 peptides were synthesized and tested against MRSA (S. aureus USA 300).
Six lead AMPs showed low IC₅₀ values against MRSA and were further characterized for: MICs against MRSA, E. faecalis, K. pneumoniae, E. coli, and P. aeruginosa; low red blood cell lysis (non-hemolytic); structural behavior in model membranes; and activity against cancer cell lines (HepG2, CHO, PC-3). The approach produced a large family of active, soluble, non-toxic antimicrobial peptides.
Henson, Bridget A B; Li, Fucong; Álvarez-Huerta, José Ausencio; Wedamulla, Poornima G; Palacios, Arianna Valdes; Scott, Max R M; Lim, David Thiam En; Scott, W M Hayden; Villanueva, Monica T L; Ye, Emily; Straus, Suzana K ·
RPEP-11361 · 2025Across 8 studies including 112 patients with primary and secondary brain tumors, RGD peptide PET tracers targeting αvβ3 integrin demonstrated several advantages:
- Superior tumor-to-background ratios compared to standard [¹⁸F]FDG PET, enabling better detection of brain tumors against the naturally high glucose metabolism of brain tissue
- Strong correlation between integrin expression on tumors and tracer uptake in studies with histopathological validation
- Ability to predict treatment response: significant reductions in SUVmax (maximum standardized uptake value) after chemoradiotherapy and bevacizumab were linked to better patient prognosis
- Zero adverse events related to the radiotracers across all studies
Henssen, Dylan; Herings, Siem; Sabri, Osama; Hesse, Swen; van der Kolk, Anja; Arens, Anne; Gotthardt, Martin ·
RPEP-11363 · 2025Among 1,598 propensity-matched pairs (3,196 total patients), GLP-1 agonist users showed:
No increased aspiration risk: 0.81% vs 1.25% (P=0.39, not significant).
Reduced 90-day complications: DVT/PE 0.44% vs 0.94% (P=0.04); acute kidney injury 0.94% vs 1.69% (P=0.04); extended hospital stays (≥3 days) 15.96% vs 18.65% (P=0.04).
No differences at 1 year: DVT/PE 1.56% vs 2.00% (P=0.36); pseudoarthrosis/nonunion 2.82% vs 3.25% (P=0.50).
Importantly, GLP-1 drugs did not impair bone fusion (pseudoarthrosis rates were equivalent), addressing another theoretical concern about these medications in spine surgery.
Heo, Kevin Y; Barchick, Stephen R; Sowa, Aubrie M; Chao, Myra; Rajan, Prashant V; Goh, Brian C; Yoon, Sangwook T ·
RPEP-11368 · 2025Using a newly developed computational platform called AMPcombi, combined with metagenomics, structural modeling, and experimental validation, the researchers identified actifensins — a novel family of Actinomyces-derived defensin-like antimicrobial peptides — in dental biofilms spanning 100,000 years.
Actifensins were found across all time periods and in samples from humans, Neanderthals, and nonhuman primates, indicating remarkable evolutionary conservation. Phylogenetic and structural analyses revealed shared ancestry between ancient (paleo-) and modern actifensins, with evidence of positive selection driving adaptive diversification.
Critically, experimental validation confirmed that both ancient and modern actifensins maintained antimicrobial activity, demonstrating that these peptides have been functional weapons in microbial competition for at least 100,000 years.
Herbst, Rosa; Ibrahim, Anan; Hübner, Alexander; Knüpfer, Uwe; Regestein, Lars; Wiedemann, Christoph; Hellmich, Ute A; Warinner, Christina; Stallforth, Pierre ·
RPEP-11369 · 2025Peptide-based hydrogels offer several advantages as controlled drug delivery systems: they self-assemble from simple peptide building blocks, are biocompatible, closely mimic the body's extracellular matrix, and can be fine-tuned in their physical properties.
Beta-sheet forming peptide sequences are highlighted as particularly versatile building blocks for hydrogel formation. The review identifies an emerging trend toward affinity-based drug release systems, which use molecular recognition rather than simple diffusion to control when and how much drug is released — offering more precise therapeutic dosing compared to conventional hydrogel approaches.
Heremans, Julie; Ballet, Steven; Martin, Charlotte ·
RPEP-11371 · 2025Pulsed electric field (PEF) treatment at 15 and 20 kV/cm significantly improved enzymatic hydrolysis of salmon by-product proteins. When both the enzyme (flavourzyme) and the salmon protein were treated with PEF, the degree of hydrolysis increased from 9.6% to 16.6% and peptide yield increased from 10.6% to 18.7% — nearly doubling output.
PEF treatment modified the protein's tertiary structure by decreasing surface hydrophobicity and intrinsic fluorescence, making the protein more accessible to enzymatic cleavage. The treatment also shifted the molecular weight distribution of the resulting peptides, increasing the proportion of smaller peptides (3 and 5 kDa). Optimal antioxidant and anti-ACE activities were achieved at 50 Hz and 15 kV/cm.
Herrera-Lavados, Carolina; Tabilo-Munizaga, Gipsy; Carvajal-Mena, Nailín; Jara-Quijada, Erick; Martínez-Oyanedel, José; Pérez-Won, Mario ·
RPEP-11376 · 2025All six MODY patients (5 with HNF1A variants, 1 with PAX4/PDX1 variants) showed improvement on incretin-based therapy:
- HbA1c reductions: 1.0-4.1 percentage points (from baseline range 7.3-10.6%)
- Weight loss: 2.6-29 kg (from baseline BMI range 25.1-36.7 kg/m²)
- Three of four insulin-treated patients discontinued insulin entirely
- Two insulin-naïve patients maintained good glycemic control without needing insulin
This is notable because HNF1A-MODY patients are known to have enhanced sensitivity to incretins due to their genetic variant's effect on beta cell function.
Hilal, Abdalla; Afandi, Bachar; Almazrouei, Raya ·
RPEP-11379 · 2025The BASIC index formula — BNP × age² / (sodium × hemoglobin × eGFR) — was evaluated in 1,065 chronic heart failure outpatients with systolic dysfunction followed for a median of 47 months.
Key results:
- AUC: 0.73 (0.70-0.76) vs. 0.69 (0.66-0.72) for BNP alone (p < 0.001)
- Optimal cut-off: 9.3 (sensitivity 71.4%, specificity 62.3%, PPV 66.5%, NPV 67.5%)
- Patients with BASIC index > 9.3: adjusted hazard ratio for all-cause mortality = 2.70 (95% CI: 2.20-3.22)
- During follow-up, 545 of 1,065 patients (51.2%) died
- Median BASIC index: 11.7 (IQR: 3.5-33.7)
Hipólito-Reis, Helena; Guimarães, Carolina; Elias, Catarina; Gouveia, Rita; Madureira, Sérgio; Reis, Catarina; Fonseca, Ana Margarida; Grijó, Carlos; Neves, Ana; Matos, Mariana; Rocha, Helena; Almeida, Jorge; Lourenço, Patrícia ·
RPEP-11380 · 2025A 23-year-old woman with slowly progressive type 1 diabetes (SPIDDM) who had poor blood sugar and weight control on insulin, dapagliflozin, and metformin achieved significant improvements after adding oral semaglutide. Her glycemic control improved enough to discontinue insulin entirely, she lost weight, and her eating behaviors improved. This case suggests GLP-1 RAs could be a valuable therapeutic option for SPIDDM — a form of autoimmune diabetes where some insulin production remains.
Hirai, Taro; Kitada, Munehiro; Endo, Keita; Hayashi, Koichi; Suzuki, Toshihiko ·
RPEP-11381 · 2025Among 219 Japanese diabetes patients treated with tirzepatide in real-world clinical practice, the discontinuation rate due to gastrointestinal adverse events was approximately 1.3% — dramatically lower than the 6-10% rates reported in Western clinical trials.
Dietary questionnaire data revealed a key behavioral pattern: patients reported reduced appetite specifically for high-fat and high-calorie foods, while maintaining their consumption of traditional Japanese low-carbohydrate foods such as fish and lean meat. This selective dietary shift toward the lower-fat traditional Japanese diet may have reduced the gastrointestinal burden that causes many Western patients to discontinue treatment.
Hiraide, Takahiro; Suzuki, Yoshihiko; Yamamoto, Satoko; Yagihashi, Soroku; Sano, Motoaki ·
RPEP-11392 · 2025The multi-society expert panel recommends:
1. All patients should be asked about GLP-1RA and GLP-1/GIPRA use before any procedure requiring sedation or anesthesia
2. These medications should be continued in the peri-procedural period (not stopped)
3. A 24-hour clear fluid diet followed by standard 6-hour fasting is recommended for all patients on these drugs
4. If the liquid diet was not completed, gastric ultrasound or minimally sedated gastroscopy should assess stomach contents, and intravenous erythromycin may be used
5. The absence of gastrointestinal symptoms cannot be relied upon for risk assessment
6. No adequate cessation period can currently be recommended to ensure gastric emptying returns to baseline
Hocking, Samantha L; Scott, David A; Remedios, Matthew L; Horowitz, Michael; Story, David A; Greenfield, Jerry R; Boussioutas, Alex; Devereaux, Benedict; Andrikopoulos, Sofianos; Shaw, Jonathan E; Olesnicky, Benjamin L ·
RPEP-11404 · 2025GLP-1 receptor agonists reduce cardiovascular risk primarily through anti-atherosclerotic effects: they improve endothelial function, reduce inflammation, prevent blood clot formation, and stabilize arterial plaques. SGLT2 inhibitors achieve cardiovascular protection through different mechanisms: increasing sodium excretion, reducing plasma volume, promoting ketone body utilization in heart and kidney tissue, and lowering oxidative stress and uric acid levels.
The review concludes that these complementary mechanisms make the two drug classes suitable for different patient profiles, and their combination may offer additive cardiovascular benefits.
Homoródi, Nóra; Varga, Éva; Szabó, Zoltán; Sztanek, Ferenc; Harangi, Mariann ·