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BPC-157 as an Investigational Peptide Therapeutic: Biopharmaceutical Challenges, Formulation Strategies, and Translational Development Barriers.
Pharmaceutics
Diana-Maria Mateescu, Dragos-Mihai Gavrilescu, Florin Eugen Constantinescu +7 more
Background/Objectives: BPC-157 (body protection compound 157) is a synthetic pentadecapeptide derived from a gastric protein fragment with reported cytoprotective and regenerative properties across multiple organ systems. Despite over three decades of preclinical research demonstrating consistent biological activity, its pharmaceutical development remains rudimentary, with no approved formulation, no validated dosing regimen, and no completed Phase II clinical trial. This review critically evaluates BPC-157 from a biopharmaceutical and drug development perspective, examining its physicochemical and pharmacokinetic properties, formulation challenges across routes of administration, the pharmacokinetic-pharmacodynamic disconnect that characterizes its preclinical profile, and the regulatory and translational barriers that currently preclude clinical advancement. Methods: A narrative review of the literature was conducted using PubMed/MEDLINE, Embase, and Cochrane Library from database inception to April 2026. Search terms included "BPC-157", "BPC157", "body protection compound 157", "pentadecapeptide", and "GEPPPGKPADDAGLV", each combined with "pharmacokinetics", "formulation", "biopharmaceutics", "drug delivery", "clinical trial", "toxicology", and "regulatory". Patent databases (Espacenet, Google Patents) and regulatory agency websites (FDA, EMA, WADA) were searched independently. Searches were supplemented by forward and backward citation tracking of key references. Articles were selected based on relevance to biopharmaceutical characterization, pharmacokinetics, formulation science, clinical evidence, and regulatory status; pharmacodynamic studies were included insofar as they inform translational development. Evidence was synthesized with emphasis on pharmaceutical characterization, formulation science, and translational feasibility; no formal quality assessment instrument was applied, consistent with the narrative review design. Results: BPC-157 exhibits unusual stability in gastric juice and demonstrates activity via oral, parenteral, and topical routes, yet its human pharmacokinetic profile remains critically undercharacterized despite a recently published formal preclinical ADME study in two species confirming a sub-30-min plasma half-life, linear dose-proportional kinetics, and intramuscular bioavailability of 14-51% depending on species. A plasma half-life of under 30 min-confirmed preclinically and in a preliminary two-subject human pilot-contrasts with prolonged biological effects lasting hours to days-a disconnect with significant implications for dosing strategy and formulation design. No pharmaceutical-grade formulation has been developed or validated. The peptide lacks bcs classification data, permeability characterization, and formal excipient compatibility studies. Available clinical data derive from fewer than 30 subjects across three uncontrolled pilot studies, none of which employed standardized pharmaceutical preparations. Conclusions: BPC-157 presents a compelling but pharmaceutically underdeveloped profile. The primary barrier to clinical translation is not the absence of biological activity, but the absence of fundamental pharmaceutical science: characterized formulations, validated pharmacokinetics, and a coherent drug development strategy. Addressing these biopharmaceutical gaps is a prerequisite for any meaningful clinical program.
A novel quinazolinone insulin receptor inhibitor and its synergy with an EGFR inhibitor in glucose-driven glioblastoma.
Mol Oncol
Patryk Rurka, Wioleta Cieślik, Wojciech Płaziński +7 more
Aberrant signaling through insulin-like growth factor 1 receptor (IGF1R) and epidermal growth factor receptor (EGFR) drives glioblastoma (GBM) progression and therapy resistance. Herein, we describe the synthesis and biological evaluation of W1B, a novel styrylquinazolinone-based small-molecule inhibitor. In antiproliferative assays, W1B exhibited potent submicromolar activity against a panel of GBM cell lines. Kinase assays and binding studies confirmed strong inhibition and high binding affinity toward IGF1R. Molecular docking suggested possible interactions with both IGF1R and EGFR, with W1B adopting distinct binding poses in each kinase domain. In cellular studies, W1B reduced IGF1R and EGFR protein levels in LN229 cells and suppressed Akt phosphorylation. Under high-glucose conditions, however, W1B only retained inhibitory activity toward IGF1R, resulting in attenuated effects on the Akt/mTOR axis and underscoring the influence of glucose-dependent signaling rewiring on drug efficacy. Combination studies revealed that W1B acts synergistically with the EGFR inhibitor dacomitinib, effectively overcoming compensatory activation of parallel pathways. Biomimetic lipophilicity and in silico pharmacokinetic analyses indicated that styrylquinazolinone has the potential to cross the blood-brain barrier (BBB). The in vivo studies on Danio rerio have shown a good safety profile, as well as strong antitumor potential of the tested compound. Therefore, these findings establish W1B as a promising derivative for the development of next-generation dual IGF1R/EGFR inhibitors in GBM.
TEAD4 Promotes Myogenic Differentiation of Porcine Skeletal Muscle Satellite Cells.
Animals (Basel)
Huanhuan Zhou, Jiayi Zeng, Xiaoyu Zhang +3 more
Skeletal muscle satellite cells are indispensable for muscle growth and regeneration, and their myogenic differentiation is precisely controlled by transcription factors. As a core member of the TEAD family, TEAD4 participates in various biological processes, yet its function and regulatory mechanism in porcine skeletal muscle satellite cells (PSCs) remain largely unknown. High-purity PSCs were isolated and identified from 7-day-old Large White piglets. Combined approaches of siRNA-mediated TEAD4 knockdown, RT-qPCR, Western blotting, immunofluorescence, EdU assays, and transcriptome sequencing were applied to explore the role of TEAD4 during myogenic differentiation. TEAD4 expression was gradually upregulated during PSC differentiation and positively correlated with myogenic marker genes. Knockdown of TEAD4 did not affect PSC proliferation but significantly suppressed myogenic differentiation, as indicated by reduced expression of myogenic genes and blocked myotube formation. Transcriptomic analysis demonstrated that DEGs were highly enriched in metabolic pathways, particularly the AMPK signaling pathway. TEAD4 knockdown led to excessive upregulation of PRKAG3 and prominent induction of SLC2A4. Collectively, these results indicate that TEAD4 promotes myogenic differentiation in PSCs, likely by maintaining metabolic homeostasis. This study provides the first characterization of TEAD4 in porcine skeletal muscle satellite cells and demonstrates that it promotes myogenic differentiation.
Transcriptomic and Proteomic Analysis of the Skeletal Muscle Revealed the Effects and Mechanism of Mulberry Leaf Flavonoids on Alleviating Exercise-Induced Muscle Damage in Mongolian Horses.
Animals (Basel)
Aopan Geng, Xuejiao Wang, Lianhao Li +4 more
The scientific evidence regarding the use of plant-derived extracts to alleviate exercise-induced muscle damage in horses remains limited. Mulberry leaf flavonoids (MLFs) are the primary bioactive constituents of a traditional medicinal plant and are potent antioxidants. The aim of this study was to investigate the protective effects of MLFs against exercise-induced muscle damage. In this study, twelve Mongolian horses were used in a 3 × 3 Latin square design to investigate the protective effects of MLFs. Our results showed that high-intensity exercise negatively impacted the immune status, metabolic state, myofibrillar structure, and antioxidant capacity of the horses. Conversely, MLFs significantly reduced blood levels of white blood cells (WBC), monocytes (MON), aspartate aminotransferase (AST), creatine kinase (CK), and malondialdehyde (MDA) across various exercise distances and during recovery. Simultaneously, MLFs increased serum glutathione peroxidase (GPx), superoxide dismutase (SOD), and total antioxidant capacity (T-AOC). Mechanistically, transcriptomic analysis revealed that dietary MLFs upregulated genes associated with myofibrillar structural proteins (MYOZ2, MYOM3), the antioxidant defense system (GPX3, SOD3), and skeletal muscle satellite cell proliferation and differentiation (MYOD1, MRF6). Furthermore, quantitative proteomics indicated the enrichment of the PI3K-Akt and TGF-β signaling pathways, as well as ECM-receptor interactions, suggesting their potential involvement in regulating protein metabolism and facilitating myofibrillar restoration. Overall, MLFs effectively alleviated inflammation, metabolic disorder, and exercise-induced muscle damage. Under the tested conditions, a daily dosage of 10 g MLFs provided superior protective effects.
mRNA splicing in turkey muscle satellite cells is dynamically altered upon thermal challenge.
PLoS One
Ashley A Powell, Gale M Strasburg, Sandra G Velleman +1 more
Regulation of gene expression at the transcriptional and post-transcriptional levels is essential for proper development and growth, with tightly coordinated cellular processes supporting key biological functions. While transcription determines the available mRNA pool, post-transcriptional modifications such as alternative splicing (AS) increase transcriptome complexity and enable the production of diverse protein isoforms. In muscle, AS is critical in generating muscle-specific proteins required for normal development and function and may be particularly susceptible to disruption by thermal stress. This study examines how thermal challenges-both cold and heat-affect muscle biology by analyzing AS events during the proliferation and differentiation of skeletal muscle satellite cells (SCs). Isoform identification and AS analyses were performed on RNA-seq data from a prior study of skeletal muscle SCs derived from commercial turkeys and exposed to three temperature conditions (33°C, 38°C, or 43°C) during proliferation or differentiation. Analyses revealed 61,266 predicted splicing events across 5,202 annotated genes. Significant differential splicing was observed in all temperature comparisons, and between proliferating and differentiating cells at each temperature. Additionally, there was a strong association between differentially spliced genes (DASs) and differentially expressed genes (DEGs). This study provides a comprehensive catalog of splice isoforms for future functional analyses, many of which are likely to result in protein variants that influence SC proliferation, differentiation, and ultimately, muscle development and performance.
Three-dimensional culture enhances the antimicrobial activity of mesenchymal stem cells against Shiga toxin-producing Escherichia coli O157:H7 in vitro.
J Appl Microbiol
Mesude Bicer, Esengül Öztürk, Fatma Sener +2 more
This study examines the in vitro antibacterial activity of palatal adipose tissue-derived mesenchymal stem cells (PAT-MSCs) and the expression of antimicrobial peptide LL-37, with a particular focus on the effect of three-dimensional (3D) nanofibrillar cellulose-based hydrogel against Shiga toxin-producing Escherichia coli (STEC) harboring stx1 and/or stx2 genes isolated from mastitis milk in Turkey.
Optimized LL-37-Derived Peptides Exhibit Antitubercular Activity, Induce Membrane Disruption, and P-Type ATPase Transcriptional Responses in Mycobacterium tuberculosis.
Biomolecules
Paola A Santos, Milena Maya-Hoyos, Luz Mary Salazar +6 more
Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), remains a major cause of morbidity and mortality worldwide, particularly due to the emergence of drug-resistant strains. Membrane-active antimicrobial peptides (AMPs) represent attractive therapeutic candidates because they target bacterial envelope integrity and disrupt essential cellular processes. We evaluated two rationally designed LL-37-derived peptides: a truncated C-terminally amidated analog (LL37-1) and a modified variant incorporating N-terminal acetylation and a single D-amino acid substitution (D-LL37). Dose-response analysis demonstrated that D-LL37 exhibited greater antimycobacterial potency, with lower inhibitory concentrations of 90% (IC90) and 50% (IC50) values (18.40 ± 0.39 μM and 10.11 ± 0.60 μM, respectively) compared with LL37-1 (25.44 ± 0.36 μM and 15.45 ± 1.40 μM). Fluorescence-based permeability assays revealed partial membrane disruption (36% and 44% at IC90 for LL37-1 and D-LL37, respectively), which was supported by ultrastructural alterations observed by scanning electron microscopy, including bacillary shortening, rough surface formation, cell clusters, and the presence of cellular debris, all of which are consistent with membrane damage. RT-qPCR analysis demonstrated significant upregulation of the P-type ATPase genes ctpF, ctpA, and ctpH following D-LL37 exposure. Collectively, these findings indicate that optimized LL-37-derived peptides exert antitubercular activity associated with envelope perturbation and coordinated activation of ion transport-related stress responses.
The Effects of GLP-1 Receptor Agonists on Retinal Microvascular Alterations.
Biomedicines
Stamatios Lampsas, Gerasimia-Marina Chardalia, Chrysa Agapitou +6 more
Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have revolutionized the management of type 2 diabetes mellitus (T2DM) by providing robust glycemic control alongside significant cardioprotective and renoprotective benefits. This review synthesizes current mechanistic, preclinical, and clinical evidence regarding the impact of GLP-1RAs on retinal microvasculature and summarizes the current clinical evidence of GLP-1RA-induced retinal complications. GLP-1RAs exert pleiotropic effects on the retinal microvasculature, offering protection by amelioration of endothelial function, reduction in oxidative stress, inflammation, microvascular remodeling, and preservation of the blood-retinal barrier (BRB). Despite these mechanistic advantages, emerging clinical data have raised concerns regarding potential retinal adverse events associated with GLP-1RA therapy. Observational studies and pharmacovigilance analyses have suggested possible associations with non-arteritic anterior ischemic optic neuropathy (NAION), diabetic macular edema (DME), vitreous hemorrhage, retinal detachment, macular hole formation, and progression of diabetic retinopathy (DR), particularly in the context of semaglutide use. Most evidence comes from retrospective studies or secondary endpoints, limiting causal inference. Retinal complications associated with GLP-1RAs remain heterogeneous and inconclusive, requiring careful evaluation of potential risks across diverse patient populations. Future research should conduct large, randomized trials with standardized ocular endpoints, detailed imaging, and stratified analyses to clarify GLP-1RA retinal safety.
Angioedema After Accidental Semaglutide Dosing Error: A Case Report.
J Clin Med
Bryan D Kraft, Sarah Matuszak
Background: Glucagon-like peptide-1 receptor agonist (GLP-1 RA) use has increased exponentially as studies show significant benefits in cardiovascular and renal diseases and obesity. Accessibility to the public also increased after compounding pharmacies began direct-to-consumer distribution. Gastrointestinal side effects are common; however, hypersensitivity reactions are rare. Case Presentation: A 50-year-old female with a history of obesity, hypertension, and lisinopril-induced angioedema presented to the Emergency Department with swelling of the lips, tongue, and throat developing four hours after her first injection of compounded semaglutide for weight loss. She was treated with epinephrine, corticosteroids, and antihistamines, but due to progressive airway edema, she required intubation and mechanical ventilation for four days. After extubation, she reported accidentally injecting a ten-fold higher dose (2 mg) of semaglutide than was appropriate for the first dose. The hospitalization was complicated by hypoglycemia requiring dextrose infusion, but was otherwise unremarkable, and she was discharged home on day 7. Based on the temporal onset after semaglutide injection, this presentation was most consistent with GLP-1 RA-induced angioedema. While she also had a history of lisinopril-induced angioedema five years earlier, and had been taking valsartan for hypertension, the remoteness of the lisinopril exposure made this less likely. Conclusions: Semaglutide use may be associated with severe angioedema within hours of administration. Given the overlapping indications and patient populations, angioedema appearing in patients taking both GLP-1 RAs and ACE inhibitors may become increasingly common and present a diagnostic dilemma. Diagnosis of hypersensitivity to GLP-1 RAs can be supported with history and positive skin testing. Clinicians should be aware that inexperienced patients are at the highest risk of dosing errors.
Glucagon-like Peptide-1 Therapy in Obesity-Related Heart Failure with Preserved Ejection Fraction: Mechanisms, Clinical Evidence, and Implications.
J Clin Med
Malak Moones Abedi, Ibrahim Alabid, Wasim I I Alghoul +7 more
Background: Glucagon-like peptide-1 (GLP-1)-based therapies offer significant cardiometabolic benefits. Obesity-related heart failure with preserved ejection fraction (HFpEF) arises from a complex interplay of increased lipids, chronic inflammation, and metabolic disturbances. These factors not only exacerbate the disease but also affect GLP-1 pathways, supporting the potential role of GLP-1-based therapies in targeting this condition. Objective: This review aimed to synthesize the current evidence on GLP-1-based therapy in HFpEF, focusing on mechanisms of action, clinical outcomes, and practical significance. Methodology: A narrative review using PubMed and Scopus was conducted, including studies published between January 2020 and March 2026. Evidence from randomized trials, pooled analyses, mechanistic studies, and observational data was incorporated. Results: GLP-1-based therapies, including semaglutide and tirzepatide, demonstrated significant improvements in symptoms, exercise capacity, and quality of life. These benefits are closely linked to weight loss, reduced inflammation, and improved congestion indices. Tirzepatide use has also been associated with a reduction in heart failure-related complications. The underlying mechanisms likely involve coordinated effects on metabolism, inflammation, hemodynamics, and cardiac remodeling. Current evidence suggests that its efficacy in improving morbidity rates is stronger than its efficacy in reducing mortality rates. Conclusions: GLP-1-based therapies offer a promising, phenotypically targeted approach to managing obesity-associated HFpEF. However, their long-term effects on mortality remain unclear, highlighting the need for further research. Further studies should refine patient selection and define optimal clinical integration.
Semaglutide and risk of Non-Arteritic Anterior Ischemic Optic Neuropathy (NAION) in type 2 diabetes mellitus: A systematic review and meta-analysis.
Graefes Arch Clin Exp Ophthalmol
Stamatios Lampsas, Chrysa Agapitou, Evangelos Oikonomou +5 more
The use of Glucagon-like peptide-1 receptor agonists (GLP-1RAs) has expanded dramatically worldwide, with semaglutide being one of the most widely utilized agents. Nonarteritic anterior ischemic optic neuropathy (NAION) has been associated with GLP-1RAs use from emerging pharmacovigilance data. This systematic review and meta-analysis sought to evaluate the risk of NAION in patients with type 2 diabetes mellitus (T2DM).
The Obesity-OSA-Arrhythmia Axis: Pathophysiological Mechanisms and Translational Therapeutic Targets.
Life (Basel)
Fulvio Cacciapuoti, Ilaria Caso, Antonietta Buonomo +5 more
Obesity and obstructive sleep apnea (OSA) frequently coexist and synergistically contribute to cardiovascular disease through interconnected mechanical, metabolic, and autonomic mechanisms. This interplay promotes myocardial electrical instability and structural remodeling, favoring the development and persistence of cardiac arrhythmias, particularly atrial fibrillation. Among the key mediators linking obesity to arrhythmogenesis, epicardial adipose tissue has emerged as a relevant factor that may contribute to local pro-inflammatory, pro-fibrotic, and autonomic effects on the myocardium. In parallel, OSA-related intermittent hypoxia and intrathoracic pressure swings further amplify electrical instability and autonomic imbalance, reinforcing a self-sustaining arrhythmogenic substrate. Therapeutic strategies are increasingly shifting toward upstream interventions targeting these underlying mechanisms. Metabolic therapies, including the dual GIP/GLP-1 receptor agonist tirzepatide, have demonstrated substantial weight reduction and improvement in OSA severity, with potential indirect benefits on arrhythmic risk through modulation of visceral adiposity, inflammation, and metabolic dysfunction. On the electrophysiological side, cardioneuroablation has emerged as a potentially investigational option in selected patients with vagally mediated bradyarrhythmias, although its role remains to be fully defined. Overall, these observations support an integrated, phenotype-driven approach combining respiratory therapy, metabolic modulation, and targeted electrophysiological interventions. This framework may help redefine therapeutic priorities, shifting from symptom control toward modification of the underlying arrhythmogenic substrate and improvement of long-term cardiovascular outcomes.
Tirzepatide data: safety always comes first!
Expert Opin Drug Saf
Miodrag Janić, Syed Arman Rabbani, Mohamed El-Tanani +4 more
Tirzepatide, a dual GIP and GLP-1 receptor agonist, offers unprecedented efficacy for type 2 diabetes and obesity. Due to its rapid global adoption, understanding its complete safety spectrum is urgently needed to guide responsible prescribing and mitigate public health risks.
Liraglutide Modifies Gut Microbiota Without Modulating Doxorubicin-Induced Toxicity in Rats.
Antioxidants (Basel)
Carolina R Tonon, Marina G Monte, Paola S Ballin +15 more
Doxorubicin is an effective chemotherapeutic agent, but it causes gastrointestinal toxicity that impairs treatment efficacy and quality of life. This study investigated the effects of liraglutide, a GLP-1 analog, on acute doxorubicin-induced gut toxicity in rats. Sixty male Wistar rats were assigned to four groups: Control (C), Doxorubicin (D), Liraglutide (L), and Doxorubicin + Liraglutide (DL). Groups L and DL received liraglutide (0.6 mg/kg, s.c.) for two weeks. D and DL were given a single dose of doxorubicin (20 mg/kg, i.p). After 48 h, the distal colon, feces, and blood were collected. Results: Doxorubicin caused crypt disruption, goblet cell loss, apoptosis, and reduced fecal short-chain fatty acids. Levels of TNF-α, NF-κB, Bcl-2, TLR4, and antioxidant enzymes were unchanged among groups. Microbiota analysis showed similar α-diversity but altered β-diversity. Doxorubicin reduced Bacteroidetes and increased Proteobacteria, with higher Arcanobacterium and Clavibacter genera abundance. Liraglutide alone decreased Bacteroidetes and increased Corynebacterium and Actinobaculum genera. Combined treatment showed no significant effects. We conclude that acute doxorubicin administration induces intestinal structural damage, reduces short-chain fatty acids, and changes microbiota composition. Although liraglutide alters microbial profiles, it does not attenuate doxorubicin-induced gut toxicity.
Diabetes Mellitus and Stroke: Pathophysiological Connections and Therapeutic Potential of GLP-1 and GLP-1/GIP Receptor Agonists.
Pharmaceutics
Maria-Alexandra Paceana, Liliana Mititelu Tartau, Ianis Kevyn Stefan Boboc +5 more
Both diabetes mellitus (DM) and stroke are major global health challenges with high morbidity and mortality. DM is a major risk factor for stroke, contributing to both increased incidence and worse clinical outcomes. Incretin-based therapies, including glucagon-like peptide-1 receptor agonists (GLP-1 RAs), as well as dual agonists like tirzepatide, have demonstrated significant cardiovascular benefits, raising interest in their potential cerebrovascular effects. This narrative review examines the pathophysiological links between DM and stroke and summarizes recent clinical evidence on the efficacy of GLP-1 RAs and dual GLP-1/GIP receptor agonists (GLP-1/GIP RAs) in stroke prevention and management. Current evidence from large cardiovascular outcome trials supports the role of GLP-1 RAs in reducing major adverse cardiovascular events, including stroke, primarily in the context of primary and secondary prevention. Findings suggest that semaglutide and liraglutide may reduce non-fatal stroke incidence, decrease hospitalizations, and improve neurological outcomes in patients with prior stroke. Comparative analyses of major trials suggest that, although stroke reduction may be a class effect of GLP-1 RAs, meaningful differences exist between individual agents, likely due to variations in pharmacokinetics, receptor affinity, and study populations. Additionally, much of the evidence in acute stroke derives from early-phase or ongoing trials, warranting cautious interpretation. Novel therapies, including orforglipron and retatrutide, as well as combinations like Maridebart cafraglutide and CagriSema, may expand future therapeutic options for individuals at high cerebrovascular risk. GLP-1-based therapies show promising neurovascular effects, but large-scale, long-term studies are needed to define their role in post-stroke management and cerebrovascular risk reduction. Overall, GLP-1 RAs should currently be regarded primarily as agents for long-term vascular risk reduction rather than established therapies for acute stroke. While potential neuroprotective effects are emerging, these require confirmation in adequately powered randomized trials. Future studies should aim to identify the patient subgroups most likely to benefit and to determine whether specific agents confer advantages in acute cerebrovascular contexts. A better understanding of the mechanisms underlying potential neuroprotection will be essential to determine whether these therapies can be effectively integrated into stroke management strategies.
[Liraglutide improves cardiac structure and function in mice with advanced diabetic nephropathy and massive proteinuria].
Nan Fang Yi Ke Da Xue Xue Bao
Yanzhen Yan, Wen Yang, Wangwang Li +3 more
To investigate the effects of liraglutide on cardiac structure and function in a mouse model of diabetic nephropathy at the massive proteinuria stage.
The Emerging Role of Glucagon-like Peptide 1 (GLP-1)-Based Medications in the Treatment of Heart Failure, with a Focus on Heart Failure with Preserved or Mildly Reduced Ejection Fraction.
Medicina (Kaunas)
Rachel Su Min Lee, Jas-Mine Seah, Sara Baqar +6 more
Glucagon-like Peptide 1 (GLP-1)-based medications have been extensively studied for the management of type 2 diabetes, obesity, chronic kidney disease, and atherosclerotic cardiovascular disease. More recently, their potential role in preventing and treating heart failure has gained increasing attention. Given the strong pathophysiological links among diabetes, obesity, and heart failure, GLP-1-based medications represent a promising therapeutic option to improve morbidity and mortality across these interconnected conditions. In this review, we summarise and discuss recent studies involving GLP-1-based medications that have reported on HF-related outcomes. There is increasing evidence that these medications have beneficial effects on HF outcomes in patients with heart failure with preserved ejection fraction and possibly in those with mildly reduced ejection fraction. The usefulness of GLP-1-based medications in reduced ejection fraction HF remains to be defined.
Searching for New Pharmacological Treatments of Alcohol Use Disorder (AUD): Focus on GLP-1 Receptor Agonists.
Int J Mol Sci
Jolanta B Zawilska, Ewa Zwierzyńska, Jakub Wojcieszak
Alcohol use disorder (AUD) remains a crucial public health challenge worldwide. The currently available medications for AUD remain limited in the number and efficacy, meaning that the development of new treatments is of critical importance. Agonists of glucagon-like peptide-1 receptor (GLP-1RAs) have recently received attention as a potential anti-addiction treatment, particularly in AUD. This review presents data from preclinical studies in rodents and non-human primates, registered clinical trials, observational studies, and social media posts, investigating the effects of GLP-1RAs on alcohol-related behaviors and consumption. Several GLP1-RAs and tirzepatide (a dual agonist of GLP-1R and glucose-dependent insulinotropic polypeptide receptor; GIP-R) reduced alcohol consumption and alcohol-seeking behaviors, alcohol-induced locomotor stimulation and memory of alcohol reward, and suppressed relapse drinking in rodents. In addition, they prevent acute alcohol from activating the mesolimbic dopamine system. There are limited human data on the role of the GLP-1 system in AUD. In registered clinical trials, exenatide, semaglutide, and dulaglutide reduced alcohol consumption. Pharmacoepidemiologic studies documented a decreased risk of alcohol-related events in AUD patients using various GLP-1RAs and tirzepatide. Together, existing preclinical and clinical data suggest that GLP-1 is involved in the AUD process and imply the role of GLP1-RAs as a tentative treatment for AUD.
Clonal Hematopoiesis of Indeterminate Potential as an Emerging Interdisciplinary Risk Factor in Alzheimer's Disease: Current Evidence and Future Directions.
Biomedicines
Klara Kopp, Patricia Silva, Frederik Damm +1 more
Clonal hematopoiesis of indeterminate potential (CHIP) is an age-related condition affecting over 10-20% of individuals older than 70 years, characterized by the expansion of hematopoietic stem cell clones carrying somatic mutations in leukemia-associated driver genes in the absence of overt hematologic disease. Initially recognized as a precursor to hematologic malignancies, CHIP has since been implicated in diverse non-malignant disorders, notably increasing the risk of cardiovascular events by 40%. Recent epidemiological and experimental evidence suggests a potential disease-modifying influence of CHIP in neurodegenerative diseases, particularly Alzheimer's disease (AD), although findings remain heterogeneous and sometimes contradictory. This review synthesizes recent evidence linking CHIP to AD risk, neuropathology, and disease progression. In this study, we summarize population-based cohort studies reporting a 36 to 54% reduction in the odds of clinical AD among CHIP carriers, alongside emerging data indicating that DNMT3A and TET2 mutations may exert divergent effects on neurodegeneration. Mechanistic insights from experimental models are examined, highlighting the ability of mutated myeloid cells to infiltrate the central nervous system and modulate neuroinflammation and amyloid clearance. We discuss conflicting findings and analyze how CHIP-driven vascular disease and stroke confound neuroprotective signals. We propose that CHIP may differentially influence AD and vascular contributions to cognitive impairment and dementia, shaping mixed dementia phenotypes. Methodological challenges, including survivor bias, competing risks, variable mutation detection thresholds, and incomplete Apolipoprotein E stratification, are discussed. Ultimately, our review clarifies that CHIP is not a simple protective factor, but a complex systemic modulator that reshapes the neurodegenerative and vascular drivers of cognitive decline, necessitating cross-disciplinary neuro-hematology collaboration to establish its role as a novel risk stratificator for improving diagnostic precision and personalizing clinical outcomes in Alzheimer's disease.
Ceramic-Integrated Eddy Current Sensor for Blade Tip Clearance Measurement: Design and Performance Evaluation.
Sensors (Basel)
Qiang Miao, Zhichun Liu, Qijian Liu
Blade tip clearance (BTC) is a critical parameter for the thrust, fuel consumption, and operational safety of aero-engines, and its accurate monitorinfg is of significant engineering importance. Traditional eddy current sensors (ECS) in BTC measurement often employ wound coil structures, which suffer from issues such as poor consistency and limited geometric shapes, restricting further optimization of electromagnetic performance. This paper proposes a novel ECS based on ceramic-integrated printed coils. The ECS uses screen printing technology to directly print metal coils onto ceramic substrates and integrate them into a single unit, allowing the coils to be designed with high precision into any topology structure, with high consistency, structural stability, and high temperature tolerance. Performance studies indicate that the sensor can be manufactured with an accuracy of 0.2 mm or better, and the sensor with a line width and spacing of 0.2 mm performed the best in the test. Not only does it exhibit the best electromagnetic performance at room temperature, but it also shows an electromagnetic performance variation of less than 1% after a 24 h aging test at 800 °C. Additionally, it provides stable peak-to-peak and periodic responses to changes in BTC within the range of 0 to 600 rpm for the fan motor. This study provides a promising method for accurate and stable BTC measurement at high temperatures.