NLRP3 blockade by MCC950 suppressed osteoclastogenesis via NF-κB/c-FOS/NFATc1 signal pathway and alleviated bone loss in diabetes mellitus

Molecular and Cellular Endocrinology, Journal Year: 2024, Volume and Issue: 594, P. 112382 - 112382

Published: Sept. 28, 2024

Language: Английский

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Dapansutrile Regulates Mitochondrial Oxidative Stress and Reduces Hepatic Lipid Accumulation in Diabetic Mice

Current Issues in Molecular Biology, Journal Year: 2025, Volume and Issue: 47(3), P. 148 - 148

Published: Feb. 25, 2025

(1) Background: Hepatic lipid accumulation is the initial factor in metabolic-associated fatty liver disease (MAFLD) type 2 diabetics, leading to accelerated damage. The NOD-like receptor protein 3 (NLRP3) inflammasome plays a critical role this process. Dapansutrile (DAPA) novel NLRP3 inhibitor; however, its effect on ectopic remains unclear. This study aimed investigate therapeutic of DAPA hepatic diabetic mouse model and potential mechanisms. (2) Methods: effects deposition function under metabolic stress were evaluated vivo using db/db high-fat diet (HFD) + streptozotocin (STZ) models. Additionally, mechanism cellular deposition, mitochondrial oxidative stress, inflammation assessed HepG2 cells treated with free acids (FFA) DAPA. (3) Results: Our findings indicated that treatment improved glucose metabolism mice, particularly addressing heterotopic insulin resistance. also ameliorated mitochondrial-related functions through NLRP3-Caspase-1 signaling axis. (4) Conclusions: Targeting may represent approach for diabetes-related diseases.

Language: Английский

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Berberine Suppresses Influenza A Virus-Triggered Pyroptosis in Macrophages via Intervening in the mtROS-MAVS-NLRP3 Inflammasome Pathway

Viruses, Journal Year: 2025, Volume and Issue: 17(4), P. 539 - 539

Published: April 7, 2025

Infection with influenza A virus (IAV) may trigger excessive inflammatory responses, leading to severe viral pneumonia and accelerating disease progression. Therefore, controlling these responses is crucial for the prevention treatment of caused by IAV. Berberine (BBR), an isoquinoline alkaloid extracted from traditional Chinese medicine, possesses extensive pharmacological activities. However, its immunoregulatory effects molecular mechanisms in context IAV infection require further investigation. This study explored impact BBR on macrophage pyroptosis induced infection. Our findings revealed that effectively inhibits release IL-1β TNF-α suppresses gasdermin D (GSDMD)-mediated a dose-dependent manner. Further research indicates alleviates IAV-infected cells reducing mitochondrial reactive oxygen species (mtROS), inhibiting antiviral signaling protein (MAVS) expression blocking activation NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome. Experiments using siRNA knockdown MAVS confirmed pivotal role BBR’s inhibition IAV-induced pyroptosis. provides scientific basis application as anti-inflammatory drug diseases directs future endeavors.

Language: Английский

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NLRP3 inflammasome: structure, mechanism, drug-induced organ toxicity, therapeutic strategies, and future perspectives

RSC Medicinal Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

This review aims to shed light on how drugs cause toxicity and summarizes developing therapies prospective therapeutic approaches that will target the NLRP3 inflammasome unit.

Language: Английский

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Nod-like receptor protein 3 inflammasome-mediated pyroptosis contributes to chronic NaAsO2 exposure-induced fibrotic changes and dysfunction in the liver of SD rats

Ecotoxicology and Environmental Safety, Journal Year: 2024, Volume and Issue: 275, P. 116282 - 116282

Published: April 1, 2024

The metalloid arsenic, known for its toxic properties, is widespread presence in the environment. Our previous research has confirmed that prolonged exposure to arsenic can lead liver fibrosis injury rats, while precise pathogenic mechanism still requires further investigation. In past few years, Nod-like receptor protein 3 (NLRP3) inflammasome been found play a pivotal role occurrence and development of injury. this study, we administered varying doses sodium arsenite (NaAsO

Language: Английский

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Pathological mechanisms and crosstalk among various cell death pathways in cardiac involvement of systemic lupus erythematosus

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: Sept. 5, 2024

Systemic lupus erythematosus (SLE) is a prevalent autoimmune disease primarily characterized by the involvement of multiple systems and organs. Cardiovascular primary cause mortality in patients with SLE, though mechanisms underlying increased cardiovascular risk SLE remain unclear. Recent studies indicate that abnormal activation programmed cell death (PCD) signaling crosstalk among various forms are critical immunopathogenesis SLE. Furthermore, apoptosis, necroptosis, pyroptosis, NETosis, ferroptosis recognized as key cellular processes pathogenesis closely linked to cardiac involvement. This review uniquely explores intricate between other pathways, discussing their roles interactions Investigating interplay PCD understanding disease's offers opportunities for new therapeutic interventions. The integration precision medicine innovative strategies targeting these complex pathways holds promise enhancing treatment prospects

Language: Английский

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Transcriptomic and Immunopathological Profiles of Inflammasomes in Different Clinical Forms of American Cutaneous Leishmaniasis

Microorganisms, Journal Year: 2025, Volume and Issue: 13(5), P. 980 - 980

Published: April 24, 2025

American cutaneous leishmaniasis (ACL), caused by Leishmania (Leishmania) amazonensis and L. (Viannia) braziliensis, presents a wide spectrum of clinical immunopathological manifestations, ranging from localized (LCL) to severe forms like anergic diffuse (ADCL) mucocutaneous (MCL). Despite evidence the immune response’s complexity, role inflammasomes in disease severity parasite persistence remains unclear. We investigated transcriptomic profiles inflammasome components patient lesions across spectrum. Genes such as NLRP3, AIM2, NLRP12, NLRC4, CASP1, CASP5, GSDMD, IL1B all evaluated proteins, showed higher expression ACL compared healthy controls. Distinct activation patterns were observed: MCL, hyperreactive form, elevated IL-1β, indicating an intensified inflammatory environment. ADCL, hyporeactive displayed increased NLRP12 NLRC4 with reduced GSDMD. Localized transitional profiles, highlighting ACL’s multifactorial pathogenesis. These findings advance our understanding mechanisms ACL, identifying potential therapeutic targets modulate inflammation improve management.

Language: Английский

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Renoprotective effect of rosmarinic acid by inhibition of indoxyl sulfate-induced renal interstitial fibrosis via the NLRP3 inflammasome signaling

International Immunopharmacology, Journal Year: 2024, Volume and Issue: 135, P. 112314 - 112314

Published: May 23, 2024

Language: Английский

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Mechanism of Vaginal Epithelial Cell Pyroptosis Induced by the NLRP3 Inflammasome in Vulvovaginal Candidiasis

American Journal of Reproductive Immunology, Journal Year: 2024, Volume and Issue: 92(1)

Published: July 1, 2024

ABSTRACT Problem Vulvovaginal candidiasis (VVC) is a common mucosal fungal infection, and Candida albicans the main causative agent. The NLRP3 inflammasome plays an important role in VVC, but underlying mechanism unknown. Method of Study Vaginal epithelial cells were divided into three groups: control, C. strain SC5314 (wild‐type, WT), WT+ Matt Cooper Compound 950 (MCC950, specific inhibitor). After human vaginal pretreated with 1 µmol/L MCC950 for 2 h, (MOI = 1) was cocultured 12 h. cell supernatants collected, LDH detected, IL‐1β IL‐18 levels determined by ELISA. expression pyroptosis‐related proteins NLRP3, Caspase‐1 p20 GSDMD measured Western blotting analysis. protein N‐terminus (GSDMD‐N) detected immunofluorescence. Results In this study, we showed that WT induced pyroptosis cells, as indicated proinflammatory cytokine upregulated p20, GSDMD‐N. reversed changes these cytokines cells. Conclusion activated to induce pyroptosis. inhibited inflammasome, reduced pyroptosis, decreased release inflammatory cytokines.

Language: Английский

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Therapeutic Potential of MCC950 in Restoring Autophagy and Cognitive Function in STZ-Induced Rat Model of Alzheimer's Disease

Molecular Neurobiology, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 20, 2024

Language: Английский

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