Nucleotide-binding domain, leucine-rich repeat, and pyrin domain-containing protein 3 inflammasome: From action mechanism to therapeutic target in clinical trials

World Journal of Gastrointestinal Oncology, Journal Year: 2025, Volume and Issue: 17(2)

Published: Jan. 18, 2025

The nucleotide-binding domain, leucine-rich repeat, and pyrin domain-containing protein 3 (NLRP3) inflammasome is a critical modulator in inflammatory disease. Activation mutation of NLRP3 can cause severe inflammation diseases such as chronic infantile neurologic cutaneous articular syndrome, Muckle-Wells familial cold autoinflammatory syndrome 1. To date, great effort has been made to decode the underlying mechanisms activation. priming activation drive maturation release active interleukin (IL)-18 IL-1β pyroptosis, which significantly trigger many including diseases, immune disorders, metabolic neurodegenerative diseases. investigation therapeutic target for disease treatment hot topic both preclinical studies clinical trials. Developing potent inhibitors downstream IL-1 attracts wide-spectrum attention research pharmaceutical fields. In this minireview, we first updated molecular involved associated signaling pathways. We then reviewed cellular pathways obesity, diabetes, other addition, briefly roles cancer growth relative checkpoint therapy. Finally, trials with treatments targeting its were summarized.

Language: Английский

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Lycopene mitigates paclitaxel-induced cognitive impairment in mice; Insights into Nrf2/HO-1, NF-κB/NLRP3, and GRP-78/ATF-6 axes

Progress in Neuro-Psychopharmacology and Biological Psychiatry, Journal Year: 2025, Volume and Issue: unknown, P. 111262 - 111262

Published: Jan. 1, 2025

Language: Английский

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Carotenoids Improve Obesity and Fatty Liver Disease via Gut Microbiota: A Narrative Review

Food Science & Nutrition, Journal Year: 2025, Volume and Issue: 13(3)

Published: March 1, 2025

ABSTRACT Carotenoids are natural micronutrients found in plants and microorganisms, but not synthesized by animals. show various biological activities, including antioxidant properties, regulation of cell growth, modulation gene expression immune responses. The rising global incidence fatty liver disease (FLD) obesity highlights the importance carotenoids chronic progressive conditions. Gut microbiota (GM) dysbiosis is associated with development progression FLD due to effects metabolites such as lipopolysaccharide (LPS), bile acids (BAs), short‐chain (SCFAs). Furthermore, GM may affect intestinal barrier integrity. This review evaluates potential impact on function, their subsequent FLD. We searched through a wide range databases, Web Science, Scopus, EMBASE, PubMed, collect data for our non‐systematic English literature. lycopene, zeaxanthin, fucoxanthin, capsanthin, astaxanthin, lutein can regulate composition improve affecting energy expenditure, food intake, lipid profile, fat deposition, enzymes, inflammatory markers, glucose homeostasis, acids. These SCFAs LPS. Our findings that dietary supplementation positively regulating

Language: Английский

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Dual roles of the TLR2/TLR4/NLRP3-H-PGDS-PGD2 axis in regulating the inflammatory response in Escherichia coli-infected bovine bone marrow-derived macrophages and endometrial tissue

Theriogenology, Journal Year: 2025, Volume and Issue: unknown, P. 117374 - 117374

Published: March 1, 2025

Language: Английский

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Therapeutic role of Prunella vulgaris L. polysaccharides in non-alcoholic steatohepatitis and gut dysbiosis

Journal of Integrative Medicine, Journal Year: 2025, Volume and Issue: unknown

Published: March 1, 2025

Language: Английский

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The role and mechanism of pyroptosis and potential therapeutic targets in non-alcoholic fatty liver disease (NAFLD)

Frontiers in Cell and Developmental Biology, Journal Year: 2024, Volume and Issue: 12

Published: July 3, 2024

Non-alcoholic fatty liver disease (NAFLD) is a clinical pathological syndrome characterized by the excessive accumulation of fat within cells, which can progress to end-stage in severe cases, posing threat life. Pyroptosis distinct, pro-inflammatory form cell death, differing from traditional apoptosis. In recent years, there has been growing research interest association between pyroptosis and NAFLD, encompassing mechanisms functions progression as well potential therapeutic targets. Controlled activate immune eliciting host responses shield body harm. However, undue activation may worsen inflammatory responses, induce cellular or tissue damage, disrupt potentially impact function. This review elucidates involvement key molecular players, including NOD-like receptor thermal protein domain associated 3(NLRP3) inflammasome, gasdermin D (GSDMD), caspase family, pathogenesis NAFLD. It emphasizes promising prospects targeting approach for NAFLD offers valuable insights into future directions field treatment.

Language: Английский

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The Role of Antioxidants in the Treatment of Metabolic Dysfunction-Associated Fatty Liver Disease: A Systematic Review

Antioxidants, Journal Year: 2024, Volume and Issue: 13(7), P. 797 - 797

Published: June 29, 2024

Non-alcoholic fatty liver disease (NAFLD) is a global public health problem that causes liver-related morbidity and mortality. It also an independent risk factor for non-communicable diseases. In 2020, proposal was made to refer it as "metabolic dysfunction-associated (MAFLD)", with concise diagnostic criteria. Given its widespread occurrence, treatment crucial. Increased levels of oxidative stress cause this disease. This review aims evaluate various studies on antioxidant therapies patients MAFLD. A comprehensive search relevant research conducted the PubMed, SCOPUS, ScienceDirect databases, resulting in identification 87 met inclusion total, 31.1% human used natural antioxidants, 53.3% synthetic 15.5% both antioxidants. human-based studies, antioxidants showed 100% efficacy MAFLD, while effective results only 91% investigations. animal-based research, were fully demonstrated effectiveness 87.8% evaluations. conclusion, their form are more helpful preserving correct balance pro-oxidants useful way monitor treatment.

Language: Английский

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Ginsenoside Rg2 Attenuates Aging-Induced Liver Injury via Inhibiting Caspase 8-Mediated Pyroptosis, Apoptosis and Modulating Gut Microbiota

The American Journal of Chinese Medicine, Journal Year: 2024, Volume and Issue: 52(05), P. 1427 - 1449

Published: Jan. 1, 2024

Aging is an irresistible natural law of the progressive decline body molecules, organs, and overall function with passage time, resulting in eventual death. World Health Organization data show that aging correlated a wide range common chronic diseases elderly, essential driver many diseases.

Language: Английский

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Gut microbiota–NLRP3 inflammasome crosstalk in metabolic dysfunction-associated steatotic liver disease

Clinics and Research in Hepatology and Gastroenterology, Journal Year: 2024, Volume and Issue: 48(8), P. 102458 - 102458

Published: Sept. 2, 2024

Nonalcoholic fatty liver disease (NAFLD) is a chronic associated with metabolic dysfunction, ranging from hepatic steatosis or without mild inflammation to nonalcoholic steatohepatitis, which can rapidly progress fibrosis and even cancer. In 2023, after several rounds of Delphi surveys, new consensus recommended renaming NAFLD as dysfunction-associated steatotic (MASLD). Ninety-nine percent patients meet the MASLD criteria related cardiovascular risk factors under "multiple parallel hits" lipotoxicity, insulin resistance (IR), proinflammatory diet, an intestinal microbiota disorder, previous research on remains valid. The NLRP3 inflammasome, well-known member pattern recognition receptor (PRR) family, be activated by danger signals transmitted pathogen-associated molecular patterns (PAMPs) damage-associated (DAMPs), well cytokines involved in immune inflammatory responses. activation inflammasome pathway triggers production IL-1β IL-18. MASLD, while changes composition metabolites occur, disrupted also generate IL-18 damaging barrier, negatively regulating gut–liver axis, further aggravating MASLD. Therefore, modulating gut–microbiota–liver axis through may emerge novel therapeutic approach for patients. this article, we review evidence regarding functions their interactions disease.

Language: Английский

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Nicotinamide Riboside Ameliorates Fructose-Induced Lipid Metabolism Disorders in Mice by Activating Browning of WAT, and May Be Also Related to the Regulation of Gut Microbiota

Nutrients, Journal Year: 2024, Volume and Issue: 16(22), P. 3920 - 3920

Published: Nov. 17, 2024

This study aims to observe the preventive effect of nicotinamide riboside (NR) on fructose-induced lipid metabolism disorders and explore its mechanism.

Language: Английский

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