Metformin Inhibits the NLRP3 Inflammasome via AMPK/mTOR-dependent Effects in Diabetic Cardiomyopathy

International Journal of Biological Sciences, Journal Year: 2019, Volume and Issue: 15(5), P. 1010 - 1019

Published: Jan. 1, 2019

Metformin is a widely used antidiabetic drug for type 2 diabetes that can play cardioprotective role through multiple pathways.It recognized agonist of AMP-activated protein kinase (AMPK) blocks mitochondrial complex I.The NLRP3 inflammasome has been demonstrated to be activated in diabetic cardiomyopathy (DCM).However, the metformin regulating signaling pathway DCM remains unclear.It reported AMPK inhibit by activating autophagy.The aim this study was investigate whether AMPK/mTOR DCM.In study, streptozotocin-induced C57BL/6 mice and high glucose-treated primary cardiomyocytes from neonatal were treated with or an inhibitor compound C. Echocardiography, hematoxylin-eosin Masson staining showed function morphology hearts improved after treatment, whereas these parameters deteriorated intervention inhibitor.Immunohistochemical staining, immunofluorescence western blot assays indicated expression levels mTOR, NLRP3, caspase-1, IL-1β GSDMD-N decreased model reversed administration vivo vitro.Mechanistically, our results activate AMPK, thus improving autophagy via inhibiting mTOR alleviating pyroptosis DCM.Thus, we provide novel information treatment DCM.

Language: Английский

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A Bibliometric Analysis of Pyroptosis From 2001 to 2021

Frontiers in Immunology, Journal Year: 2021, Volume and Issue: 12

Published: Aug. 18, 2021

Pyroptosis is a new programmed cell death discovered in recent years. plays an important role various diseases. Nevertheless, there are few bibliometric analysis systematically studies this field. We aimed to visualize the research hotspots and trends of pyroptosis using help understand future development basic clinical research.The articles reviews regarding were culled from Web Science Core Collection. Countries, institutions, authors, references keywords field visually analyzed by CtieSpace VOSviewer software.A total 2845 included. The number significantly increased yearly. These publications mainly come 70 countries led China USA 418 institutions. identified 605 among which Thirumaladevi Kanneganti had most significant articles, Shi JJ was co-cited often. Frontiers immunology journal with studies, Nature commonly cited journal. After analysis, common nod like receptor family pyrin domain containing 3 inflammasome, apoptosis, death, gasdermin D, mechanism, caspase-1, others current developing areas study.Research on flourishing. Cooperation exchanges between institutions must be strengthened future. related pathway mechanism pyroptosis, relationship other types deaths as well diseases have been focus developmental research.

Language: Английский

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NLRP3 inflammasome, an immune‐inflammatory target in pathogenesis and treatment of cardiovascular diseases

Clinical and Translational Medicine, Journal Year: 2020, Volume and Issue: 10(1), P. 91 - 106

Published: March 1, 2020

Abstract Inflammation is an important process involved in several cardiovascular diseases (CVDs), and nod‐like receptor family pyrin domain containing 3 (NLRP3) inflammasome a vital player innate immunity inflammation. In this review, we aim to provide comprehensive summary of the current knowledge on role involvement NLRP3 pathogenesis treatment CVDs. functions as molecular platform, triggers activation caspase‐1 cleavage pro‐IL‐1β, pro‐IL‐18, gasdermin D (GSDMD). Cleaved NT‐GSDMD forms pores cell membrane initiates pyroptosis, inducing death release many intracellular pro‐inflammatory molecules. triggered via inter‐related pathways downstream K + efflux, lysosomal disruption, mitochondrial dysfunction. addition, Golgi apparatus noncoding RNAs are gradually being recognized play roles activation. Many investigations have revealed association between CVDs, including atherosclerosis, ischemia/reperfusion (I/R) injury heart failure induced by pressure overload or cardiomyopathy. Some existing medications, orthodox natural medicines, used for CVD been newly discovered act inflammasome. pathway components such NLRP3, caspase‐1, IL‐1β may be considered novel therapeutic targets Thus, key molecule further research focused development inflammasome‐based targeted therapies CVDs clinical evaluation these essential.

Language: Английский

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Inflammatory signalling in atrial cardiomyocytes: a novel unifying principle in atrial fibrillation pathophysiology

Nature Reviews Cardiology, Journal Year: 2022, Volume and Issue: 20(3), P. 145 - 167

Published: Sept. 15, 2022

Language: Английский

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GSDME-mediated pyroptosis promotes the progression and associated inflammation of atherosclerosis

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: Feb. 18, 2023

Abstract Pyroptosis, a type of Gasdermin-mediated cell death, contributes to an exacerbation inflammation. To test the hypothesis that GSDME-mediated pyroptosis aggravates progression atherosclerosis, we generate ApoE and GSDME dual deficiency mice. As compared with control mice, −/− /ApoE mice show reduction atherosclerotic lesion area inflammatory response when induced high-fat diet. Human atherosclerosis single-cell transcriptome analysis demonstrates is mainly expressed in macrophages. In vitro, oxidized low-density lipoprotein (ox-LDL) induces expression Mechanistically, ablation macrophages represses ox-LDL-induced inflammation macrophage pyroptosis. Moreover, signal transducer activator transcription 3 (STAT3) directly correlates positively regulates expression. This study explores transcriptional mechanisms during development indicates could be potential therapeutic approach for atherosclerosis.

Language: Английский

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Activating cGAS–STING axis contributes to neuroinflammation in CVST mouse model and induces inflammasome activation and microglia pyroptosis

Journal of Neuroinflammation, Journal Year: 2022, Volume and Issue: 19(1)

Published: June 10, 2022

Neuroinflammation-induced injury is intimately associated with poor prognosis in patients cerebral venous sinus thrombosis (CVST). The cyclic GMP-AMP synthase-stimulator of interferon gene (cGAS-STING) axis a cytoplasmic double-stranded DNA (dsDNA) sensing pathway has recently emerged as crucial mediator neuroinflammation ischemic stroke. However, the role cGAS-STING modulating post-CVST inflammation and underlying mechanisms involved remain unclear.A CVST model was induced by ferric chloride male C57BL/6J mice. selective cGAS inhibitor RU.521, STING agonist 2'3'-cGAMP, siRNA were delivered intranasal administration or intraventricular injection. Post-CVST assessments included rotarod test, TUNEL staining, Fluoro-Jade C dihydroethidium western blotting, qPCR, immunofluorescence, immunohistochemistry, ELISA flow cytometry.cGAS, STING, NLRP3 GSDMD significantly upregulated after mostly microglia mouse brain. triggered release dsDNA into cytoplasm elicited an inflammatory response via activating axis. RU.521 decreased levels downstream cytokines, suppressed expressions inflammasome pyroptosis-pertinent components containing cleaved caspase-1, GSDMD, GSDMD-C, pro- IL-1β, IL-1β/pro-IL-1β. Besides, treatment also reduced oxidative stress, lessened numbers neutrophils, ameliorated neuronal apoptosis, degeneration along neurological deficits post-CVST. 2'3'-cGAMP delivery enhanced related mediators, pyroptosis-relevant proteins, whereas these alterations abrogated silencing siRNA.Our data demonstrate that repression diminishes neuroinflammatory burden highlight this approach potential therapeutic tactic CVST-mediated pathologies.

Language: Английский

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Pyroptosis is a critical immune-inflammatory response involved in atherosclerosis

Pharmacological Research, Journal Year: 2021, Volume and Issue: 165, P. 105447 - 105447

Published: Jan. 29, 2021

Language: Английский

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Role of Reactive Oxygen Species in Aging and Age-Related Diseases: A Review

ACS Applied Bio Materials, Journal Year: 2022, Volume and Issue: 5(9), P. 4028 - 4054

Published: Aug. 31, 2022

Research on the role of reactive oxygen species (ROS) in aging process has advanced significantly over last two decades. In light recent findings, ROS takes part cells along with contributing to various physiological signaling pathways. Antioxidants being cells' natural defense mechanism against ROS-mediated alteration, play an imperative maintain intracellular homeostasis. Although complete understanding regulated is yet be fully comprehended, current insights into sources cellular and their correlation age-related diseases are portrayed this review. addition, results effect antioxidants homeostasis as well advances clinical trials also discussed detail. The future perspective ROS-antioxidant dynamics antiaging research marshaled provide directions for fields.

Language: Английский

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Current understanding of plant-derived exosome-like nanoparticles in regulating the inflammatory response and immune system microenvironment

Pharmacological Research, Journal Year: 2023, Volume and Issue: 190, P. 106733 - 106733

Published: March 15, 2023

Natural compounds are widely used to prevent and treat various diseases due their antioxidant anti-inflammatory effects. As a kind of promising natural compound, plant-derived exosome-like nanoparticles (PELNs) extracted from multivesicular bodies edible plants, including vegetables, foods, fruits, mainly regulate the cellular immune response pathogen attacks. Moreover, PELNs could remarkably interfere with dynamic imbalance between pro-inflammatory effects, facilitating maintain homeostasis microenvironment. may serve as better alternative animal-derived exosomes (ADEs) owing widespread sources, cost-effectiveness, easy accessibility. can mediate interspecies communication by transferring cargoes such proteins, lipids, nucleic acids plant cells mammalian cells. This review summarizes biogenesis, composition, classification exosomes; common separation, purification, characterization methods PELNs, potential advantages over ADEs; immunomodulatory functions in colitis, cancer, inflammation-associated metabolic diseases. Additionally, future perspectives challenges associated clinical application discussed.

Language: Английский

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Silica nanoparticles induce pyroptosis and cardiac hypertrophy via ROS/NLRP3/Caspase-1 pathway

Free Radical Biology and Medicine, Journal Year: 2022, Volume and Issue: 182, P. 171 - 181

Published: Feb. 24, 2022

Language: Английский

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