NLRP3 inflammasome in hepatic diseases: A pharmacological target

Biochemical Pharmacology, Journal Year: 2023, Volume and Issue: 217, P. 115861 - 115861

Published: Oct. 18, 2023

Language: Английский

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Exploring the role of genetic variations in NAFLD: implications for disease pathogenesis and precision medicine approaches

European journal of medical research, Journal Year: 2024, Volume and Issue: 29(1)

Published: March 20, 2024

Abstract Non-alcoholic fatty liver disease (NAFLD) is one of the leading causes chronic diseases, affecting more than one-quarter people worldwide. Hepatic steatosis can progress to severe forms NAFLD, including NASH and cirrhosis. It also may develop secondary diseases such as diabetes cardiovascular disease. Genetic environmental factors regulate NAFLD incidence progression, making it a complex The contribution various risk factors, type 2 diabetes, obesity, hyperlipidemia, diet, sedentary lifestyle, exacerbation injury highly understood. Nevertheless, underlying mechanisms genetic variations in occurrence or its deterioration still need be clarified. Hence, understanding susceptibility essential for controlling course current review discusses genetics’ role pathological pathways lipid glucose metabolism, insulin resistance, cellular stresses, immune responses. Additionally, explains components induction progression lean individuals. Finally, highlights utility knowledge precision medicine early diagnosis treatment patients.

Language: Английский

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Targeting cell death in NAFLD: mechanisms and targeted therapies

Cell Death Discovery, Journal Year: 2024, Volume and Issue: 10(1)

Published: Sept. 7, 2024

Language: Английский

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Autoimmune hepatitis: Current and future therapies

Hepatology Communications, Journal Year: 2024, Volume and Issue: 8(6)

Published: June 1, 2024

Autoimmune hepatitis (AIH) is a chronic inflammatory liver disease that can lead to cirrhosis and failure. AIH present in all ages, races, ethnicities, but it predominantly affects women. As heterogeneous disease, presents variably different patients, making diagnosis treatment challenge. Currently, the standard for comprises immunosuppressants; however, their long-term use associated with adverse effects. The pathogenesis of complex, involving T cells, macrophages, plasma cells invade periportal parenchyma an cascade result damage. Due complexity pathogenesis, targets several pathways. However, unlike other autoimmune diseases which targeted treatments have been approved, there has little progress made advancing paradigm AIH. Major obstacles include challenges conducting clinical trials, particularly patient recruitment ensuring diverse range backgrounds; poorly defined outcomes assess response improved quality life; lack study designs account stage variations treatment. A focus on individualized steroid-free approaches needed improve prognosis minimize steroid-associated

Language: Английский

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Exploring the health benefits of food bioactive compounds from a perspective of NLRP3 inflammasome activation: an insight review

Critical Reviews in Food Science and Nutrition, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 26

Published: Jan. 6, 2025

The food industry has been focusing on bioactive compounds with multiple physiological and immunological properties that benefit human health. These compounds, including polyphenols, flavonoids, terpenoids, have great potential to limit inflammatory responses especially NLRP3 inflammasome activation, which is a key innate immune platform for inflammation. Current studies revealed numerous promising activities unraveling metabolic disorders excessive by directly indirectly regulating the activation. This review explores hazards, microbial abiotic factors, may trigger NLRP3-mediated illnesses It also highlights in can suppress activation through various mechanisms, linking its inhibition different pathways. Especially, this provided further insight into NLRP3-related targets where interact block process, as well mechanisms how these facilitate inactivation processes.

Language: Английский

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Nuclear factor erythroid 2‐related factor 2 ameliorates disordered glucose and lipid metabolism in liver: Involvement of gasdermin D in regulating pyroptosis

Clinical and Translational Medicine, Journal Year: 2025, Volume and Issue: 15(3)

Published: Feb. 24, 2025

Abstract Background The epidemic of metabolic dysfunction‐associated fatty liver disease linked to excessive high‐fat diet (HFD) consumption has sparked widespread public concern. Nuclear factor erythroid 2‐related 2 (NRF2) been reported improve glucose/lipid metabolism, lipid degeneration and alleviate HFD‐induced inflammation. However, its pathways mechanisms action are not fully understood. Methods To confirm the effect NRF2 on metabolism in liver, Nrf2‐/‐ mice as well liver‐specific Nrf2 knockout mice, AAV‐TBG‐Nrf2 were employed. hyperinsulinemic‐euglycemic clamp was utilized determine glucose metabolism. elucidate pyroptosis, we performed western blots, immunofluorescence, quantitative real‐time PCR, Flow cytometry experiments. Finally, chromatin immunoprecipitation‐seq dual‐luciferase reporter assay used underscore transcriptional regulatory Gsdmd. Results We found that overexpression inhibited expression inflammatory cytokines pyroptosis markers, including cle‐Caspase1, NLRP3 N‐terminus gasdermin D (N‐GSDMD) both vivo vitro, while deficiency opposite. Specifically, with up‐regulated, GSDMD decreased Gsdmd partially reversed pro‐inflammatory phenotype. Mechanistically, demonstrate binds promoter at −2110 ‐ 1130 bp site, inhibiting thereby improving steatosis. Conclusion Our data indicate is an effective inhibitor a multi‐target treatment obesity‐related diseases. Key points MAFLD associated increased hepatocytes expression. alleviates by suppressing pyroptosis. directly inhibits regulate Targeting NRF2–pyroptosis (GSDMD) axis offers potential therapeutic strategy for MAFLD.

Language: Английский

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Sodium Alginate Prevents Non-Alcoholic Fatty Liver Disease by Modulating the Gut–Liver Axis in High-Fat Diet-Fed Rats

Nutrients, Journal Year: 2022, Volume and Issue: 14(22), P. 4846 - 4846

Published: Nov. 16, 2022

Previous studies have suggested that the sodium alginate (SA) is beneficial for treatment of non-alcoholic fatty liver disease (NAFLD), while potential mechanisms are largely unknown. The present study aimed to clarify effects and SA in preventing NAFLD via gut−liver axis. Thirty-two male Sprague−Dawley rats were randomly divided into four groups: normal control group (NC); high-fat diet (HFD); HFD with 50 mg/kg/d (LSA); 150 (HSA). After 16 weeks, scarified collect blood tissues. results indicated significantly reduced their body weight, hepatic steatosis, serum triglyceride (TG), alanine transaminase (ALT) tumor necrosis factor α (TNF-α) levels increased high-density lipoprotein-cholesterol (HDL-C) comparison (p < 0.05). elevated mRNA protein expression genes related toll-like receptor 4 (TLR-4)/nuclear factor-kappa B (NF-κB)/nod-like 3 (NLRP3) inflammatory signaling pathway HFD-fed was notably suppressed by SA. In terms gut microbiota, LSA showed a higher fecal abundance Oscillospiraceae_UCG_005, Butyricicoccaceae_UCG_009 Colidextribacter compared HSA had unclassified_Lachnospiraceae, Oscillibacter HFD-associated community addition, treated significant increase short chain acids (SCFAs) decline lipopolysaccharide (LPS) Moreover, modulated bacteria microbial metabolites correlated amelioration NAFLD-related indices activation TLR4/NF-κB/NLRP3 pathway. conclusion, prevented mechanism modulation

Language: Английский

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Gut–Liver Axis and Non-Alcoholic Fatty Liver Disease: A Vicious Circle of Dysfunctions Orchestrated by the Gut Microbiome

Biology, Journal Year: 2022, Volume and Issue: 11(11), P. 1622 - 1622

Published: Nov. 6, 2022

Non-alcoholic fatty liver disease (NAFLD) is a prevalent, multifactorial, and poorly understood with an increasing incidence worldwide. NAFLD typically asymptomatic coupled other symptoms of metabolic syndrome. The prevalence rising in tandem the obesity. In Western hemisphere, one most prevalent causes transplantation. Recent research suggests that gut microbiome dysbiosis may play significant role pathogenesis by dysregulating gut–liver axis. so-called “gut–liver axis” refers to communication feedback loop between digestive system liver. Several pathological mechanisms characterized alteration axis, such as impairment barrier increase intestinal permeability which result endotoxemia inflammation, changes bile acid profiles metabolite levels produced microbiome. This review will explore axis disruption, mediated dysbiosis, on development.

Language: Английский

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Resveratrol improves emamectin benzoate-induced pyroptosis and inflammation of Ctenopharyngodon idellus hepatic cells by alleviating oxidative stress/endoplasmic reticulum stress

Fish & Shellfish Immunology, Journal Year: 2023, Volume and Issue: 142, P. 109148 - 109148

Published: Oct. 6, 2023

Language: Английский

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Mitochondrial Dysfunction in Metabolic Dysfunction Fatty Liver Disease (MAFLD)

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(24), P. 17514 - 17514

Published: Dec. 15, 2023

Nonalcoholic fatty liver disease (NAFLD) has become an increasingly common in Western countries and the major cause of cirrhosis or hepatocellular carcinoma (HCC) addition to viral hepatitis recent decades. Furthermore, studies have shown that NAFLD is inextricably linked development extrahepatic diseases. However, there currently no effective treatment cure NAFLD. In addition, 2020, was renamed metabolic dysfunction (MAFLD) show its pathogenesis closely related disorders. Recent reported MAFLD associated with mitochondrial hepatocytes hepatic stellate cells (HSCs). Simultaneously, stress caused by structural functional disorders stimulates occurrence accumulation fat lipo-toxicity HSCs. interaction between liver-gut axis also a new point during MAFLD. this review, we summarize effects several potential strategies for MAFLD, including antioxidants, reagents, intestinal microorganisms metabolites.

Language: Английский

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