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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Nature of the Association between Rheumatoid Arthritis and Cervical Cancer and Its Potential Therapeutic Implications

Nutrients, Journal Year: 2024, Volume and Issue: 16(15), P. 2569 - 2569

Published: Aug. 5, 2024

It is now established that patients with rheumatoid arthritis (RA) have an increased risk of developing cervical cancer (CC) or its precursor, intraepithelial neoplasia (CIN). However, the underlying mechanisms this association not been elucidated. RA characterized by unresolved chronic inflammation. suggested human papillomavirus (HPV) infection in exacerbates inflammation, increasing CC. The tumor microenvironment CC also marked which aggravates manifestations both conditions. Gut and vaginal dysbiosis are considered potential contribute to inflammation aggravation manifestations. Numerous clinical pre-clinical studies demonstrated beneficial effects various nutritional approaches attenuate including polyunsaturated fatty acids their derivatives, specialized pro-resolving mediators (SPMs), probiotics, prebiotics, certain diets. We believe successful resolution correction dysbiosis, combination current anti-RA anti-CC therapies, a promising therapeutic approach for This could reduce development HPV-infected patients.

Language: Английский

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Copper induced cytosolic escape of mitochondrial DNA and activation of cGAS-STING-NLRP3 pathway-dependent pyroptosis in C8-D1A cells

Ecotoxicology and Environmental Safety, Journal Year: 2024, Volume and Issue: 285, P. 117085 - 117085

Published: Sept. 24, 2024

Language: Английский

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A new perspective on targeting pulmonary arterial hypertension: Programmed cell death pathways (Autophagy, Pyroptosis, Ferroptosis)

Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 181, P. 117706 - 117706

Published: Nov. 23, 2024

Language: Английский

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Glibenclamide reverses cardiac damage and NLRP3 inflammasome activation associated with a high refined sugar diet

European Journal of Pharmacology, Journal Year: 2024, Volume and Issue: unknown, P. 177035 - 177035

Published: Oct. 1, 2024

Language: Английский

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Broad-spectrum inflammasome inhibition by thiomuscimol

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

Published: Nov. 16, 2024

Abstract Inflammasome formation, arising from pathogen or internal activating signals, is a key step in canonical pyroptosis, gasdermin-mediated inflammatory cell death. Inhibition of pyroptosis has great clinical relevance due to its involvement many different disease states. Current inhibitors either only inhibit the final lytic step, which still allows signal release, single inflammasome, does not account for inherent redundancy activation other pathways. Here, we show that thiomuscimol, structural analog lysis inhibitor muscimol, exhibits unique inhibitory activity upstream plasma membrane rupture. We find thiomuscimol inhibits inflammasome as well downstream caspase-1 activation, initiated by multiple pyroptotic regardless whether NLR recruitment relies on ASC adapter protein. The ability block inflammasomes opens door development therapeutics with increased applications broadly pathological settings.

Language: Английский

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Copper Induced Astrocyte Cytosolic Escape of Mitochondrial DNA and Activation of Cgas-Sting-Nlrp3 Pathway-Dependent Pyroptosis

Published: Jan. 1, 2024

Language: Английский

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Modulating NLRP3 splicing with antisense oligonucleotides to control pathological inflammation

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 6, 2024

Inflammation has an essential role in healing. However, over-active inflammation disrupts normal cellular functions and can be life-threatening when not resolved. The NLRP3 inflammasome, a component of the innate immune system, is intracellular multiprotein complex that senses stress-associated signals, and, for this reason promising therapeutic target treating unresolved, pathogenic inflammation. Alternative splicing

Language: Английский

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