The living record of
peptide science.

Activation of PPARγ and CPT1A Mediates the Hepatoprotective Effect of Ginsenoside CK against NAFLD in Rats.

Biol Proced Online

Danfeng Lan, Guishun Sun, Zhiyong Dong +7 more

Nonalcoholic fatty liver disease (NAFLD) is a significant underlying driver of hepatocellular carcinoma; however, current clinical treatment options remain limited. Ginsenoside CK (CK), a natural bioactive compound, has shown promise in modulating lipid metabolism and protecting liver function. Nevertheless, its therapeutic potential against the pathogenesis of NAFLD and the associated molecular pathways is not fully understood. This study employed an integrated strategy that combines transcriptomic analysis with both in vivo and in vitro validation, utilizing a high-fat diet (HFD)-induced rat model to elucidate the efficacy and molecular mechanisms of CK in ameliorating NAFLD.

Shaping the microvascular network: insights into skeletal muscle angiogenesis.

Open Biol

Thomas Gustafsson, Emmanuel Nwadozi, Andrea Tryfonos +1 more

Angiogenesis, the formation of new blood vessels from pre-existing vasculature, is a complex and tightly regulated biological process that plays a fundamental role in both physiological and pathological tissue remodeling by facilitating the delivery of oxygen and nutrients. Over recent decades, extensive research has identified a wide array of factors that regulate the balance between endothelial cell quiescence and activation. This review discusses the cellular events and molecular mechanisms that regulate angiogenesis within skeletal muscle, considering dynamic interactions with the extracellular matrix and highlighting the critical involvement of multiple resident and infiltrating cell types-including myofibres, satellite cells, fibro-adipogenic progenitors, immune cells and pericytes. The current understanding of these regulatory networks is examined in both healthy muscle tissue as part of the phenotype changes that occur during exercise and in pathological conditions that affect skeletal muscle angiogenesis. Particular attention is given to introduce data of emerging high-resolution techniques, especially omics-based approaches such as single-cell RNA sequencing (scRNA-seq) of skeletal muscle tissue. These methodologies hold significant promise for elucidating cell-type-specific roles and intercellular interactions that drive angiogenic processes in both physiological and disease contexts. Despite substantial progress, the precise mechanisms governing angiogenesis in skeletal muscle remain only partially understood.

Human cathelicidin peptide LL-37 compacts nucleic acids and alters neutrophil extracellular trap structure.

Sci Rep

Claudia Zielke, Behzad Rad, Josefine E Nielsen +7 more

The human cathelicidin host defense peptide LL-37 is expressed by many cell types, including neutrophils, macrophages, and epithelial cells, and forms complexes with nucleic acids that can have either beneficial or detrimental health effects. We suggest that these differential impacts are directly connected to the extent of nucleic acid binding by LL-37. Here, we use phage λ DNA and techniques such as high-resolution video microscopy, gel electrophoresis, circular dichroism, and displacement assays to show that LL-37 binds non-specifically to dsDNA, condensing it, followed by formation of progressively larger complexes from smaller domains, until "complete" complexation is attained at a (w/w) ratio of DNA/LL-37 of 1:1.7. The morphology of these complexes is concentration-dependent, with relatively low LL-37 amounts yielding loosely aggregated DNA structures and higher LL-37 concentrations leading to well-defined, disc-like complexes of about 150 nm in diameter. The condensation of nucleic acids, which causes a loss of the characteristic B-DNA features, results from interactions of the phosphodiester backbone with cationic amino acid side chains of the peptide at physiological pH, most likely in A-T rich sequences of the nucleic acid. Our results show that the α-helical structure of the peptide with its amphipathic and hydrophobic surfaces is essential. Finally, we show that LL-37 complexation alters the structure of neutrophil extracellular traps (NETs), causing a significant reduction in projected NET area at high LL-37 concentrations. Our data suggest that LL-37 helps prevent nucleic acid dispersal and condenses dsDNA, which may impact the biophysics of NET clearance.

Cost-effectiveness and budget-impact analysis of tirzepatide in heart failure with preserved ejection fraction and obesity in the German health-care system.

Int J Cardiol

Bent Estler, Hanna Fröhlich, Tobias Täger +3 more

Heart failure with preserved ejection fraction is common, obesity-related, and associated with high symptom burden and healthcare use. Tirzepatide, a dual GIP/GLP-1 receptor agonist, improved symptoms and outcomes in SUMMIT, but its acquisition cost raises concerns about value and affordability.

GLP-1 receptor agonists and surgical care: implications for bariatric Procedures, perioperative Outcomes, and nutritional optimization.

Diabetes Res Clin Pract

Zeyad Elawa, Ahmed Khalil, Ahmed Kardousha +2 more

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are increasingly used for obesity and type 2 diabetes and are now frequently encountered in patients undergoing bariatric and other elective surgeries. Their effects on gastric motility, appetite, and nutrient intake have important implications for perioperative safety, surgical outcomes, and nutritional care.

Ectopic adrenocorticotropic hormone syndrome with Pneumocystis jirovecii pneumonia and pulmonary cryptococcosis: A case report and literature review.

J Int Med Res

Junlan Zhou, Chenyang Liu, Lingling Li +3 more

Ectopic adrenocorticotropic hormone syndrome is a distinct subtype of endogenous Cushing's syndrome characterized by excessive cortisol secretion, which increases susceptibility to opportunistic infections. Herein, we present the case of a male patient in his early 40s who was admitted with fatigue and bilateral lower-extremity edema. Laboratory tests revealed markedly elevated serum adrenocorticotropic hormone and cortisol levels. Ectopic adrenocorticotropic hormone syndrome was confirmed via dexamethasone suppression testing and somatostatin receptor-targeted positron emission tomography-computed tomography, which localized an ectopic adrenocorticotropic hormone-secreting right pulmonary carcinoid tumor (a neuroendocrine tumor). During hospitalization, the patient was diagnosed with concurrent Pneumocystis jirovecii pneumonia and pulmonary cryptococcosis, and he responded favorably to trimethoprim-sulfamethoxazole and fluconazole. This case, supported by a review of the relevant literature, highlights the importance of early infection diagnosis, prompt management, and appropriate prophylaxis in patients with ectopic adrenocorticotropic hormone syndrome to improve prognosis.

Reply to the comment on: Differential effects of human fibromyalgia sera on murine satellite glial cells.

Clin Exp Rheumatol

Francisco Mercado, Angélica Almanza, Laura-Aline Martínez-Martínez +1 more

Changes in Antimicrobial Component Concentrations in Goat Milk Following Intramammary Lipopolysaccharide Administration.

Anim Sci J

Jirapat Jaisue, Moeka Nishimura, Naoki Suzuki +2 more

Mastitis is a major cause of economic losses in dairy production; however, its prevention and treatment remain challenging. Under field conditions, antimicrobial drugs are frequently administered when somatic cell counts (SCCs) are elevated and signs of inflammation are observed, even in the absence of detectable pathogens in milk. As antimicrobial therapy may be unnecessary during the healing phase of inflammation, improved indicators of the mastitis stage are required. Therefore, this study aimed to determine whether changes in milk antimicrobial component (AMC) concentrations could serve as indicators of the inflammatory stage, thereby supporting judicious antimicrobial use. Lactating Tokara goats received an intramammary infusion of lipopolysaccharide (LPS) to induce experimental mastitis, with saline-infused quarters serving as controls. Milk samples were collected for up to 120 h post-infusion to measure SCC and the concentrations of lactoferrin (LF), goat β-defensin 1 (GBD1), cathelicidin-7, S100A8, and milk amyloid A (MAA). SCC peaked at 10 h, whereas GBD1 tended to peak at 4 h, indicating early inflammation. In contrast, LF, S100A8, and MAA, together with the increasing tendency of Cath-7 levels, peaked later (36-84 h) as SCC declined, suggesting an association with the recovery phase. These findings demonstrate that temporal patterns of milk AMCs can be used to stage mastitis progression.

Pharmacovigilance of semaglutide: A descriptive analysis of WHO-VigiAccess reports.

Medicine (Baltimore)

Nasser M Alorfi, Mansour M Alourfi, Ammar Aldabbagh +7 more

Semaglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist, is widely prescribed for type 2 diabetes mellitus and chronic weight management. With its growing global use, continuous pharmacovigilance is essential to detect emerging patterns of adverse drug reactions (ADRs). To describe the global ADRs profile of semaglutide using data from the World Health Organization's (WHO) VigiAccess pharmacovigilance database. A retrospective descriptive analysis was conducted using publicly available ADR data retrieved from the WHO-VigiAccess portal on October 18, 2025. The total number and proportion of ADRs were summarized according to the Medical Dictionary for Regulatory Activities (MedDRA) system organ class (SOC). Demographic information, including age group, sex, geographic region, and reporting year, was reviewed descriptively. A total of 81,770 ADR reports associated with semaglutide were identified. The most frequently reported SOCs were gastrointestinal disorders (28%, n = 42,574), general disorders and administration site conditions (12%, n = 19,200), and injury, poisoning and procedural complications (11%, n = 16,601). Additional categories included nervous system disorders (8%), investigations (7%), and metabolism and nutrition disorders (7%). The majority of ADRs were reported among adults aged 45 to 64 years, with most originating from Europe and the Americas. Annual reporting increased markedly between 2018 and 2025, corresponding with expanded clinical use and obesity-related approvals. Global pharmacovigilance data indicate that semaglutide ADRs are primarily gastrointestinal and systemic in nature, consistent with its known pharmacological effects. Continuous monitoring is warranted to identify emerging safety signals and support optimized patient management as use expands worldwide.

Tirzepatide attenuates neurotoxicity by suppressing inflammation, apoptosis and restoring neurotrophin expression in an Alzheimer's disease-like rat model.

Metab Brain Dis

Mohamed S M Attia, Sheikh F Ahmad, Ahmed Nadeem +7 more

Despite numerous milestones in Alzheimer's disease (AD) research, the disease remains incurable, with a high prevalence and significant financial burdens. As a result, researchers are keen to look for new medications that can help manage or prevent the disease.

The GLP-1 Receptor Agonist Liraglutide Promotes Anticancer Activities in MCF7 Breast and PC-3 Prostate Cancer Cells by Modulating Glycolysis, Oxidative Stress and Adipokines.

J Biochem Mol Toxicol

Bassem Refaat, Mohamed E Elzubier, Akhmed Aslam +2 more

This research explored the anticancer activities of the glucagon-like peptide-1 receptor agonist (GLP1Ra) liraglutide using MCF7 breast and PC-3 prostate cancer cell lines. The study focused on key molecular pathways related to glycolysis and oxidative stress alongside adipokine profiles. The expression of GLP1R and its downstream signalling components (cAMP and PKA) was quantified in untreated and treated cells. Alterations in cell cycle and cell apoptosis were evaluated by a flow cytometer. Expression of oncogenic (CCND1, CCND3, BCL2, survivin) and tumour suppressor (p21, p27, BAX, Caspase-3) proteins, the PI3KAkt/mTOR axis and glycolytic regulators (HIF-α, LDHA, PDHK1, PDH) was examined by Western blot analysis. Adipokine concentrations (adiponectin, leptin, resistin), pro-oxidants (ROS/RNS, MDA, protein carbonyls) and antioxidants (GSH, CAT) were assessed using ELISA. Liraglutide treatment led to pronounced upregulation of GLP1R expression and activation of cAMP/PKA signalling in both cancer cell lines. Antiproliferative effects were evident through induced apoptosis and cell cycle arrest alongside inhibition of CCND1, CCND3, BCL2 and survivin with increased p21, p27, BAX and Caspase-3 expression. The PI3K/Akt/mTOR pathway was suppressed, while its negative regulators, PTEN and AMPKα, were upregulated. Liraglutide also shifted metabolic activity towards oxidative phosphorylation by suppressing HIF-α, LDHA and PDHK1, whereas PDH levels increased. Additionally, liraglutide raised adiponectin levels while reducing leptin and resistin. Oxidative stress markers increased substantially, accompanied by a decrease in antioxidant levels in both cell lines. Liraglutide induced anticancer effects in breast and prostate cancer cells, possibly by promoting oxidative phosphorylation, modulating adipokines and inducing oxidative stress-mediated apoptosis.

Small-Molecule Oral Versus Injectable Glucagon-Like Peptide-1 (GLP-1) Receptor Agonists: Comparative Efficacy, Safety, and Future Clinical Perspectives.

Cureus

Digantkumar Patel

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have transformed the management of type 2 diabetes (T2D), obesity, and cardiometabolic disease by improving glycemic control, promoting clinically meaningful weight loss, and reducing major adverse cardiovascular events (MACE) in selected populations. Historically, GLP-1RA therapy has relied on injectable peptide agonists (e.g., liraglutide, semaglutide, dulaglutide, and exenatide), which mimic native incretin biology but require parenteral administration and cold-chain logistics. In parallel, oral GLP-1RAs have emerged through two distinct strategies: (1) the oral delivery of peptide agonists using absorption enhancers (e.g., oral semaglutide) and (2) true small-molecule, non-peptide GLP-1 receptor agonists (e.g., orforglipron), designed to be orally bioavailable without peptide constraints. This narrative review compares small-molecule oral GLP-1RAs to injectable peptide agonists across efficacy (glycated hemoglobin {HbA1c} lowering, weight reduction, and cardiometabolic outcomes), safety and tolerability (gastrointestinal {GI} adverse events, gallbladder disease, pancreatitis signals, retinopathy considerations, and rare hepatic signals), real-world adherence, and future innovation. Recent phase 3 evidence suggests that oral small-molecule GLP-1RAs can deliver glycemic and weight benefits approaching injectable standards, while high-dose oral peptide formulations may broaden oral options for obesity management. Remaining challenges include long-term outcome data, the optimization of titration to improve tolerability, and equitable access amid rapid market expansion.

In vitro and in vivo activity of colistin-nitroxoline combination against polymyxin heteroresistant carbapenem-resistant Klebsiella pneumoniae.

BMC Microbiol

Xin Chen, Jianping Jiang, Xiaogang Xu +3 more

Carbapenem-resistant Klebsiella pneumoniae (CRKP) has emerged as a critical global health threat, often causing life-threatening infections with limited therapeutic options. Polymyxins are often used as the last-line agent, but its efficacy is limited by heteroresistance-where resistant subpopulations emerge during treatment. To combat this, we evaluated the synergistic activity of colistin combined with nitroxoline against polymyxin heteroresistant (PHR) CRKP subpopulations.

Bridging Trauma and Parkinson's Disease: Mechanisms, Models, and Biomarkers of Post-Traumatic Parkinsonism.

J Neurotrauma

Singh Ankit Satyaprakash, Nitesh Kumar Gupta, Shekhar Singh +2 more

One of the most prevalent neurodegenerative diseases, Parkinson's disease (PD), is generally discussed in terms of aging, genetic predisposition, and environmental exposures. Nonetheless, there is growing evidence that both isolated severe traumatic events and repetitive mild traumatic brain injury may play a significant role in the development of parkinsonian features. This trauma-associated condition, known as Post-Traumatic Parkinsonism Syndrome (PTPS), is becoming more widely acknowledged as a clinically significant but underdiagnosed illness. The differences between PTPS and conditions like chronic traumatic encephalopathy (CTE) are often blurred because, in contrast to idiopathic PD, PTPS typically manifests after a specified latency period following head injury and is often accompanied by overlapping symptoms of cognitive, behavioral, and motor dysfunction. At the pathophysiological level, PTPS is defined by the combination of trauma-induced processes, such as neuroinflammation, axonal injury, and dysregulated acetylation pathways, with mechanisms known to be associated with PD, such as alpha-synuclein aggregation, dopaminergic neuronal loss, and impaired protein clearance. Today, experimental models demonstrate how trauma speeds up or even starts neurodegenerative cascades, providing a unique platform to investigate disease mechanisms outside of the traditional toxin-based paradigms of PD. The current understanding of PD, PTPS, and CTE is summarized in this review, with a focus on risk factors, comparative pathology, and experimental model translational insights. This review emphasizes the significance of acknowledging trauma as more than a trigger but rather as a potential contributor to long-term neurodegeneration and disability by presenting PTPS as a unique but related syndrome within the PD spectrum.

Chronic estrogen supplementation in the aging castrated male rat is not associated with renal injury or activation of the renin angiotensin system.

J Appl Physiol (1985)

Jordan H Mallette, Breland F Crudup, Adrian Oudomrath Speyrer +4 more

The biological effects of chronic estrogen supplementation on renal function and injury with aging in men are unknown. Using an experimental model of feminizing hormone therapy (FHT) induced by 17β-estradiol (E2) (5 mg/kg, s.c.) supplementation plus castration (CTX) in the male Sprague Dawley rat starting at 13-15 months of age, equivalent to a late thirty- to forty-year-old man, we tested the hypothesis that FHT is associated with impaired renal function and renal injury with aging associated with activation of the renin angiotensin system (RAS). However, 24-hour creatinine excretion, plasma creatinine, and creatinine clearance did not differ in E2+CTX compared to Control by 22-24 months of age, or following 9 months of FHT. Lean mass was significantly reduced in E2+CTX versus Control, but creatinine clearance adjusted to lean mass did not differ. Serum cystatin C, a more reliable biomarker for renal function, was unchanged; urinary cystatin C was reduced, suggesting no renal impairment. However, cystatin C clearance was reduced in E2+CTX versus Control, suggesting decreased renal filtration. Proteinuria, urinary KIM-1 (a marker of proximal tubule injury), and glomerular injury score were significantly reduced in E2+CTX versus Control; however, albuminuria did not differ. Renal angiotensinogen mRNA expression was significantly decreased in E2C+TX, whereas urinary angiotensinogen, renal renin, and renal angiotensin type 1 receptor mRNA expression did not differ. Collectively, these results suggest that the biological effects of FHT in the aging male are not associated with increased renal injury or inappropriate activation of the RAS; whether renal function is altered remains unclear.

Assessment of Brain Natriuretic Peptide Levels in Patients Presenting to the Emergency Department With High Blood Pressure.

Cureus

Cihangir Doruk

Hypertension is one of the leading causes of cardiovascular morbidity and mortality worldwide. Although patients presenting to emergency departments (EDs) with high blood pressure (BP) are frequently seen, it is difficult to distinguish patients with true hemodynamic or cardiac stress. Brain natriuretic peptide (BNP), secreted in response to ventricular wall strain, may serve as a useful biomarker. This study was conducted to evaluate BNP levels in patients presenting to the ED with high BP and to examine their relationship with systolic and diastolic pressures according to the antihypertensive treatment status.

[The impact of obesity on natriuretic peptide cut-off values for the diagnosis of heart failure].

Ned Tijdschr Geneeskd

Karim Taha, M Louis Handoko

Measurement of natriuretic peptides (BNP and NT-proBNP) has an important role in diagnosing heart failure. However, in patients with obesity, circulating levels of these peptides are consistently lower, yet current diagnostic cut-off values do not account for this. This article discusses the implications of obesity on natriuretic peptide interpretation, particularly in heart failure with preserved ejection fraction (HFpEF). Recent data show that the conventional rule-out threshold (<125 ng/L) lacks sensitivity in obese patients, potentially missing up to one-third of HFpEF cases. Lowering the cut-off in patients with obesity markedly improves diagnostic accuracy, while adjusted rule-in thresholds enhance specificity. These findings highlight the need for individualized interpretation of natriuretic peptide levels, incorporating body weight to avoid underdiagnosis of HFpEF in patients with obesity.

Maternal obesity and the metabolic syndrome in reproductive health: assessing incretin-based interventions.

Rev Endocr Metab Disord

Luisa Wallentowitz, Mariana G Garcia, Catalina Atorrasagasti +6 more

The global epidemic of overweight and obesity threatens gynecological and reproductive health, necessitating effective therapeutic strategies to improve maternal and fetal long-term health outcomes. This review provides an overview of weight loss interventions and discusses their use in the context of gestation, such as surgical interventions and anti-obesity medications. As the interest in incretin-based therapies has risen substantially, we discuss how incretin-based therapies, including glucagon-like peptide-1 (GLP-1) receptor agonists and GLP-1 receptor agonists and glucose-dependent insulinotropic polypeptide (GIP) dual agonists, might improve reproductive function and could interact with the physiological metabolic changes ensuring a healthy pregnancy. These metabolic adaptations during pregnancy arise from the integration of insulin signaling, lipid metabolism, placental endocrine function, mitochondrial remodeling and inflammatory regulation. Furthermore, we consider not only short-term consequences of maternal overweight and obesity but also focus on fetal long-term health trajectories following pregnancy-related metabolic disorders, as maternal obesity and gestational weight gain are considered risk factors for childhood obesity and overweight.

Converging neurotrophic-immune signaling in autism spectrum disorder: integrative roles of klotho, GDNF/GFRA-1, IGF-1 and GLP-1 pathways.

Metab Brain Dis

Janvi Verma, Rohit Kumar Singh, Supratim Paul +7 more

Autism spectrum disorder (ASD) is a heterogeneous neurodevelopmental condition characterized by deficits in social communication and restricted, repetitive behaviors. Although traditionally linked to synaptic protein dysfunction and neurotransmitter imbalance, growing evidence suggests that broader intracellular signaling networks critically regulate the neurodevelopmental processes disrupted in ASD. This review synthesizes current evidence on four interconnected signaling pathways-Klotho, GDNF/GFRA-1, IGF-1, and GLP-1-and examines their potential roles in ASD pathophysiology within a unified mechanistic framework. These pathways regulate fundamental processes, including neuronal survival, synaptogenesis, dendritic maturation, myelination, modulation of oxidative stress, neuroinflammation, and metabolic homeostasis. Importantly, they converge on shared intracellular cascades such as PI3K/Akt, MAPK/ERK, mTOR, and Wnt/β-catenin, which are increasingly implicated in ASD-related abnormalities in synaptic plasticity and circuit organization. Experimental models demonstrate that dysregulation of these signaling systems can impair hippocampal function, alter excitatory-inhibitory balance, and disrupt structural connectivity. Among them, IGF-1 has shown promising translational potential in clinical trials for syndromic ASD, while GLP-1 receptor agonists and Klotho modulation represent emerging therapeutic avenues. The GDNF/GFRA-1 axis further highlights the importance of trophic support in maintaining synaptic integrity and neuronal resilience. By integrating molecular, preclinical, and clinical findings, this review proposes that convergent dysregulation of trophic and metabolic signaling pathways may contribute to ASD heterogeneity. A systems-level understanding of these interconnected mechanisms may facilitate biomarker development and support the advancement of stratified, pathway-targeted therapeutic strategies.

Glucagon-Like Peptide-1 Receptor Agonists as Adjunctive Therapy for Hidradenitis Suppurativa in Patients With Overweight/Obesity: A Narrative Review of Efficacy, Safety, and Quality-of-Life Outcomes.

Int J Dermatol

Eman Almukhadeb, Khalid Nabil Nagshabandi, Naif Alshehri +3 more

Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease closely associated with obesity and metabolic dysfunction, which contribute to increased disease severity, reduced treatment response, and impaired quality of life. Incretin-based therapies, including glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and dual glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 receptor agonists, are increasingly used for obesity and metabolic disease, prompting interest in their potential adjunctive role in HS management. To synthesize the available human evidence on the use of incretin-based therapies in patients with HS, focusing on clinical outcomes, weight change, and patient-reported measures. A narrative review of the published literature was conducted using major medical databases. Eligible publications included case reports, case series, and observational studies reporting HS outcomes in patients treated with GLP-1 RAs or dual GIP/GLP-1 receptor agonists. Findings were summarized descriptively and interpreted in the context of metabolic modulation. The current evidence base consists predominantly of case-level reports and a limited number of observational cohorts. Across studies, incretin-based therapies were associated with significant weight loss and concurrent improvements in HS disease activity, flare frequency, pain, and quality of life. Improvements in HS outcomes generally paralleled weight reduction, suggesting that metabolic effects play a primary role. Evidence supporting weight-independent anti-inflammatory effects remains limited and inconclusive. Incretin-based therapies appear to offer potential benefit as metabolic adjuncts in HS, particularly for patients with coexisting obesity or metabolic syndrome. However, available data are observational and hypothesis-generating. Prospective controlled studies are required to clarify mechanisms, identify optimal patient populations, and define the role of incretin-based therapies within comprehensive HS management.