Background/aims: Exenatide is a glucagon-like polypeptide-1 analog, whose main clinical use is to treat type 2 diabetes. However, the mechanism of exenatide in mitigating non-alcoholic steatohepatitis (NASH) remains unclear. This study aimed to investigate the and effect of exenatide on NASH.
Methods: Leptin receptor-deficient C57BL/KsJ- db/db male mice were fed with methionine-choline-deficient (MCD) diet for 4 weeks to induce NASH, while oleic acid/LPS-treated HepG2 cells were used as an cell model. Exenatide (20 µg/kg/day, subcutaneous) and specific exenatide inhibitors (20 µg/kg/day, intraperitoneal) were used to determine the effects of exenatide on NASH.
Results: Exenatide treatment inhibited the pyroptosis signaling pathway to attenuate NASH.
Conclusion: To the best of our knowledge, this report provides the first evidence showing that exenatide attenuated NASH by inhibiting the pyroptosis signaling pathway. Exenatide thus has important pathophysiological functions in NASH and may represent a useful new therapeutic target.
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http://dx.doi.org/10.3389/fendo.2021.663039 | DOI Listing |
Immunol Rev
January 2025
Department of Internal Medicine and Paediatrics, Ghent University, Ghent, Belgium.
Inflammasomes are crucial mediators of both antimicrobial host defense and inflammatory pathology, requiring stringent regulation at multiple levels. This review explores the pivotal role of mitogen-activated protein kinase (MAPK) signaling in modulating inflammasome activation through various regulatory mechanisms. We detail recent advances in understanding MAPK-mediated regulation of NLRP3 inflammasome priming, licensing and activation, with emphasis on MAPK-induced activator protein-1 (AP-1) signaling in NLRP3 priming, ERK1 and JNK in NLRP3 licensing, and TAK1 in connecting death receptor signaling to NLRP3 inflammasome activation.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
The Miami Project to Cure Paralysis, Miami, FL, USA.
Background: Stroke and AD patients with gut complications often present worsened neurological outcomes. The goal of this study was to examine the role of extracellular vesicle (EV)-mediated pyroptosis in the bi-directional gut-brain axis after photothrombotic stroke (PTS) in aged 3xTg mice and wildtype (WT) controls.
Method: Twelve-month 3xTg and WT male and female mice underwent PTS using a YAG laser.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi
December 2024
Department of Endocrinology, The Fourth Hospital of Changsha(Changsha Hospital of Hunan Normal University), Changsha 410000, China.
Objective To investigate the role and possible mechanism of glycogen synthase kinase-3 beta (GSK-3β)/cAMP response element binding protein (CREB) signaling pathway in regulating macrophage pyroptosis in the pathogenesis and development of diabetic foot ulcer (DFU). Methods Thirty rats were randomly divided into control group, DFU group and GSK-3β inhibited group, with 10 rats in each group. Fasting blood glucose (FBG) was detected by dynamic blood glucose detector.
View Article and Find Full Text PDFShock
December 2024
Department of Emergency Medicine, Ningbo Medical Center Lihuili Hospital, The Affiliated Lihuili Hospital of Ningbo University, Ningbo, China.
Introduction: Dl-3-n-butylphthalide (NBP), a small molecular compound extracted from celery seeds, has been shown to exhibit diverse pharmacological activities, including anti-inflammatory, antioxidative, and anti-apoptotic effects. Recent studies have highlighted its efficacy in treating various cardiovascular conditions, such as myocardial infarction, hypertrophy, heart failure, and cardiotoxicity. This study aimed to investigate whether NBP could alleviate cardiac dysfunction and injury following hemorrhage-induced cardiac arrest (HCA) in a porcine model and elucidate its potential mechanisms.
View Article and Find Full Text PDFBr J Cancer
January 2025
Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou, China.
Background: Pyroptosis is closely associated with chemotherapeutic drugs and immune response. Here, we investigated whether oxaliplatin, a key drug in FOLFOX-hepatic artery infusion chemotherapy (FOLFOX-HAIC), induces pyroptosis in hepatoma cells and enhances antitumor immunity after tumor cell death.
Methods: Hepatoma cells were treated with oxaliplatin.
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