Inhibitors of the NLRP3 inflammasome pathway as promising therapeutic candidates for inflammatory diseases (Review)

International Journal of Molecular Medicine, Journal Year: 2023, Volume and Issue: 51(4)

Published: March 21, 2023

The inflammasome regulates innate immunity by serving as a signaling platform. Nod‑like receptor protein 3 (NLRP3) inflammasome, equipped with NLRP3, the adaptor apoptosis‑associated speck‑like (ASC) and pro‑caspase‑1, is far most extensively studied well‑characterized inflammasome. A variety of stimuli can activate NLRP3 When activated, recruits ASC activates resulting in inflammatory cytokine maturation secretion, which associated inflammation pyroptosis. However, aberrant activation has been linked to various diseases, including atherosclerosis, ischemic stroke, Alzheimer's disease, diabetes mellitus bowel disease. Therefore, emerged promising therapeutic target for diseases. In present review, systematic searches were performed using 'NLRP3 inhibitor(s)' 'inflammatory disease(s)' key words. By browsing literature from 2012 2022, 100 articles retrieved, 35 excluded they reviews, editorials, retracted or unavailable online, 65 included. According retrieved literature, current understanding pathway diseases was summarize, inhibitors targeting other components products highlighted. Additionally, review briefly discusses novel efforts clinical research.

Language: Английский

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Efferocytosis in atherosclerosis

Nature Reviews Cardiology, Journal Year: 2024, Volume and Issue: 21(11), P. 762 - 779

Published: May 15, 2024

Language: Английский

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Modulation of M1 and M2 macrophage polarization by metformin: Implications for inflammatory diseases and malignant tumors

International Immunopharmacology, Journal Year: 2025, Volume and Issue: 151, P. 114345 - 114345

Published: March 1, 2025

Language: Английский

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Progress in the treatment of diabetic cardiomyopathy, a systematic review

Pharmacology Research & Perspectives, Journal Year: 2024, Volume and Issue: 12(2)

Published: Feb. 26, 2024

Diabetic cardiomyopathy (DCM) is a condition characterized by myocardial dysfunction that occurs in individuals with diabetes, the absence of coronary artery disease, valve and other conventional cardiovascular risk factors such as hypertension dyslipidemia. It considered significant consequential complication diabetes field medicine. The primary pathological manifestations include hypertrophy, fibrosis, impaired ventricular function, which can lead to widespread necrosis. Ultimately, this progress development heart failure, arrhythmias, cardiogenic shock, severe cases even resulting sudden cardiac death. Despite several decades both fundamental clinical research conducted globally, there are currently no specific targeted therapies available for DCM practice, incidence mortality rates failure remain persistently high. Thus, article provides an overview current treatment modalities novel techniques pertaining DCM, aiming offer valuable insights support researchers dedicated investigating complex condition.

Language: Английский

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Exosomal NEDD4L derived from HG+oxLDL-induced vascular endothelial cells accelerates macrophage M1 polarization and oxLDL uptake by ubiquitinating IκBα and PPARγ

Cell Biology and Toxicology, Journal Year: 2025, Volume and Issue: 41(1)

Published: Jan. 7, 2025

Vascular endothelial cell-derived exosomes are thought to mediate disease progression by regulating macrophage polarization. However, its mechanism in diabetes mellitus (DM)-related atherosclerosis (AS) progress is unclear. High-glucose (HG) and oxLDL were used induce human cardiac microvascular cells (HCMECs) mimic DM-related AS model. The conditioned medium (CM) from HG+oxLDL-induced HCMECs was incubated with THP1-M0 monocytes treated LPS or oxLDL. mRNA levels of M1/M2 polarization markers, NEDD4L, IκBα PPARγ determined qRT-PCR. Flow cytometry analyze marker. Dil-labeled oil red O staining performed assess uptake cells. inflammatory factors examined using ELISA. Transmission electron microscope for observing foam cell formation exosome morphology. protein p-Smad1/Smad1, p-Smad2/Smad2, p-IκBα/IκBα, p-P65/P65, anti-lipid metabolism-related NEDD4L tested western blot. interaction between assessed Co-IP assay. CM could promote M1 polarization, formation, inhibiter GW4869 eliminated these effects. overexpressed HCMECs, which be taken up Exosomal knockdown inhibited reducing the p-IκBα/IκBα p-P65/P65. reduce expression through ubiquitination. HCMECs-derived exosomal enhance ubiquitination facilitate uptake, thus accelerating AS.

Language: Английский

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Post-traumatic stress disorder, diabetes mellitus, and alpha-lipoic acid

INTERNATIONAL JOURNAL OF ENDOCRINOLOGY (Ukraine), Journal Year: 2025, Volume and Issue: 21(1), P. 82 - 94

Published: Feb. 23, 2025

Post-traumatic stress disorder (PTSD) is a prognostic factor for the development of metabolic syndrome (MetS), type 2 diabetes mellitus (T2DM), increases risk cardiometabolic pathologies and neurodegenerative diseases. At same time, T2DM MetS can also cause major neurosis-like psychiatric symptoms characteristic PTSD. Their influence manifested through negative effects on central nervous system, in particular Oxidative chronic low-grade inflammation play an important role pathophysiology PTSD, MetS, T2DM, making them main therapeutic targets. Targeted oxidative stress, mitochondrial metabolism disorders, use antioxidants, α-lipoic acid (ALA), positively affect not only course comorbidities but manifestations In vitro vivo studies have demonstrated that ALA modulates number pathways associated with stress. addition, results clinical trials confirm antioxidant mechanism action patients obesity, 1 2. The neuroprotective activity being actively studied proving promising as approach treatment PTSD Despite significant potential ALA, its application limited by several barriers. particular, lack standardized protocols, well detailed assessment effectiveness alone. pharmacokinetic profile remains limited, which one factors hinder use. this context, there are certain prospects transportation systems based nanoparticles, potentially solve these problems. technologies so­lid lipid nanoparticles such niosomes, liposomes, nanostructured carriers micelles provide possibility local or systemic ALA. However, further preclinical needed to definitively determine feasibility search was conducted Scopus, Science Direct (from Elsevier) PubMed, including MEDLINE databases. keywords used were “α-lipoic acid”, “post-traumatic disorder”, “diabetes mellitus”, “metabolic syndrome”. A manual bibliography publications identify study could be found during online search.

Language: Английский

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Role of Peripheral NLRP3 Inflammasome in Cognitive Impairments: Insights of Non-central Factors

Molecular Neurobiology, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 25, 2025

Language: Английский

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Oral Hygiene and Cardiovascular Health

Hygiene, Journal Year: 2025, Volume and Issue: 5(2), P. 14 - 14

Published: April 3, 2025

The human oral microbiome plays a vital role in maintaining and systemic health. This diverse microbial community includes over 700 bacterial species, some of which are implicated developing diseases, particularly cardiovascular diseases (CVDs). Research highlights strong association between periodontal disease increased risk, suggesting that good hygiene practices may reduce the incidence CVDs. Porphyromonas gingivalis Fusobacterium nucleatum drive chronic inflammation disease; these bacteria can extend beyond mouth contribute to inflammatory responses. factors, including C-reactive protein (CRP), interleukins (IL-1, IL-6), tumor necrosis factor-alpha (TNF-α), damage blood vessels, impair endothelial functions, promote atherosclerosis, all key events CVD progression. Additionally, pathogens accelerate plaque formation arteries, increasing risk ischemic heart brain diseases. Studies show 28% individuals with disease. Treating improve function markers, emphasizing health management as potential preventive strategy for CVD. Public initiatives emphasize early treatment crucial broader care.

Language: Английский

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The Alterations and Roles of Glycosaminoglycans in Human Diseases

Polymers, Journal Year: 2022, Volume and Issue: 14(22), P. 5014 - 5014

Published: Nov. 18, 2022

Glycosaminoglycans (GAGs) are a heterogeneous family of linear polysaccharides which composed repeating disaccharide unit. They also linked to core proteins form proteoglycans (PGs). GAGs/PGs major components the cell surface and extracellular matrix (ECM), they display critical roles in development, normal function, damage response body. Some properties (such as expression quantity, molecular weight, sulfation pattern) GAGs may be altered under pathological conditions. Due close connection between these function GAGs/PGs, alterations often associated with enormous changes physiological/pathological status cells organs. Therefore, serve marker molecules disease. This review aimed investigate structural range diseases, such atherosclerosis, cancer, diabetes, neurodegenerative disease, virus infection. It is hoped provide reference for disease diagnosis, monitoring, prognosis, drug development.

Language: Английский

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Association of triglyceride-glucose index with the risk of incident aortic dissection and aneurysm: a large-scale prospective cohort study in UK Biobank

Cardiovascular Diabetology, Journal Year: 2024, Volume and Issue: 23(1)

Published: Aug. 2, 2024

Triglyceride-glucose (TyG) index is an emerging surrogate indicator of insulin resistance, which has been demonstrated as a risk factor for various cardiovascular diseases including coronary syndrome, in-stent restenosis, and heart failure. However, association TyG with incident aortic dissection (AD) aneurysm (AA) remains to be investigated.

Language: Английский

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