Metabolic syndrome and cardiovascular diseases: Going beyond traditional risk factors

Diabetes/Metabolism Research and Reviews, Journal Year: 2021, Volume and Issue: 38(3)

Published: Oct. 8, 2021

Metabolic syndrome (MS) is a chronic non-infective characterised clinically by set of vascular risk factors that include insulin resistance, hypertension, abdominal obesity, impaired glucose metabolism, and dyslipidaemia. These are due to pro-inflammatory state, oxidative stress, haemodynamic dysfunction, ischaemia, which overlap in 'dysmetabolic' patients. This review aimed evaluate the relationship between traditional components MS with cardiovascular disease (CVD), inflammation, stress. MEDLINE-PubMed, EMBASE, Cochrane databases were searched. Chronic low-grade inflammatory states metaflammation often accompanied metabolic changes directly related CVD incidence, such as diabetes mellitus, obesity. Moreover, an increase serum concentration cytokines, mainly interleukin-1 β (IL-1β), IL-6, tumour necrosis factor-α (TNF-α), originating from chronically inflamed adipose tissue associated The reactive oxygen species overloads antioxidant systems causing post-translational alterations proteins, lipids, DNA leading Hyperglycaemia contributes stress production advanced glycosylation end products (AGEs) cellular molecular dysfunction. Oxidative inflammation senescence CVD. should not be seen only being triggered classical factors. Atherosclerosis multifactorial pathological process several triggering aetiopathogenic mechanisms. Its medium long-term repercussions, however, invariably constitute significant cause morbidity mortality. Implementing preventive therapeutic measures against oxy-reductive imbalances has unquestionable potential for favourable clinical outcomes medicine.

Language: Английский

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Non-Alcoholic Fatty Liver Disease: Metabolic, Genetic, Epigenetic and Environmental Risk Factors

International Journal of Environmental Research and Public Health, Journal Year: 2021, Volume and Issue: 18(10), P. 5227 - 5227

Published: May 14, 2021

Non-alcoholic fatty liver disease (NAFLD) is one of the most frequent causes chronic in Western world, probably due to growing prevalence obesity, metabolic diseases, and exposure some environmental agents. In certain patients, simple hepatic steatosis can progress non-alcoholic steatohepatitis (NASH), which sometimes lead cirrhosis its complications including hepatocellular carcinoma. Understanding mechanisms that cause progression NAFLD NASH crucial be able control advancement disease. The main hypothesis considers it multiple factors act together on genetically predisposed subjects suffer from insulin resistance, nutritional factors, gut microbiota, genetic epigenetic factors. this article, we will discuss epidemiology NAFLD, overview several topics influence development possible complications.

Language: Английский

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SGLT-2 Inhibitors in NAFLD: Expanding Their Role beyond Diabetes and Cardioprotection

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(6), P. 3107 - 3107

Published: March 13, 2022

Non-alcoholic fatty liver disease (NAFLD) is an 'umbrella' term, comprising a spectrum ranging from benign, steatosis to non-alcoholic steatohepatitis, fibrosis and eventually cirrhosis hepatocellular carcinoma. NAFLD has evolved as major health problem in recent years. Discovering ways prevent or delay the progression of become global focus. Lifestyle modifications remain cornerstone treatment, even though various pharmaceutical interventions are currently under clinical trial. Among them, sodium-glucose co-transporter type-2 inhibitors (SGLT-2i) emerging promising agents. Processes regulated by SGLT-2i, such endoplasmic reticulum (ER) oxidative stress, low-grade inflammation, autophagy apoptosis all implicated pathogenesis. In this review, we summarize current understanding pathophysiology, specifically focus on potential impact SGLT-2i development progression, providing evidence vitro, animal human studies. Given evidence, further mechanistic studies would advance our exact mechanisms underlying pathogenesis beneficial actions context treatment.

Language: Английский

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Computational modeling of imines based anti-oxidant and anti-esterases compounds: Synthesis, single crystal and In-vitro assessment

Computational Biology and Chemistry, Journal Year: 2023, Volume and Issue: 104, P. 107880 - 107880

Published: May 8, 2023

Language: Английский

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Contributing roles of mitochondrial dysfunction and hepatocyte apoptosis in liver diseases through oxidative stress, post-translational modifications, inflammation, and intestinal barrier dysfunction

Cellular and Molecular Life Sciences, Journal Year: 2024, Volume and Issue: 81(1)

Published: Jan. 12, 2024

Abstract This review provides an update on recent findings from basic, translational, and clinical studies the molecular mechanisms of mitochondrial dysfunction apoptosis hepatocytes in multiple liver diseases, including but not limited to alcohol-associated disease (ALD), metabolic dysfunction-associated steatotic (MASLD), drug-induced injury (DILI). While ethanol-inducible cytochrome P450-2E1 (CYP2E1) is mainly responsible for oxidizing binge alcohol via microsomal ethanol system, it also metabolizing many xenobiotics, pollutants, chemicals, drugs, specific diets abundant n-6 fatty acids, into toxic metabolites organs, liver, causing pathological insults through organelles such as mitochondria endoplasmic reticula. Oxidative imbalances (oxidative stress) promote covalent modifications lipids, proteins, nucleic acids enzymatic non-enzymatic mechanisms. Excessive changes stimulate various post-translational (PTMs) transcription factors, histones. Increased PTMs proteins inactivate enzymes involved reduction oxidative species, acid metabolism, mitophagy pathways, leading dysfunction, energy depletion, apoptosis. Unique other organelles, control signaling cascades bioenergetics (fat metabolism), inflammation, apoptosis/necrosis hepatocytes. When homeostasis shifted, these pathways become altered or shut down, likely contributing death with activation inflammation hepatic stellate cells, fibrosis cirrhosis. will encapsulate how contributes hepatocyte several types diseases order provide recommendations targeted therapeutics.

Language: Английский

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Steatotic Liver Disease: Pathophysiology and Emerging Pharmacotherapies

Pharmacological Reviews, Journal Year: 2024, Volume and Issue: 76(3), P. 454 - 499

Published: Jan. 30, 2024

Steatotic liver disease (SLD) displays a dynamic and complex phenotype. Consequently, the metabolic dysfunction-associated steatotic (MASLD)/metabolic steatohepatitis (MASH) therapeutic pipeline is expanding rapidly in multiple directions. In parallel, non-invasive tools for diagnosing monitoring responses to interventions are being studied, clinically feasible findings explored as primary outcomes interventional trials. The realization that distinct subgroups exist under umbrella of SLD should guide more precise personalized treatment recommendations facilitate advancements pharmacotherapeutics. This review summarizes recent updates pathophysiology-based nomenclature outlines both effective pharmacotherapeutics those MASLD/MASH, detailing their mode action current status phase 2 3 clinical Of extensive arsenal MASLD/MASH pipeline, several have been rejected, whereas other, mainly monotherapy options, shown only marginal benefits now tested part combination therapies, yet others still development monotherapies. Although successful drug candidate (or combinations) remains elusive, such approaches will ideally target MASH fibrosis while improving cardiometabolic risk factors. Due urgent need novel strategies potential availability safety tolerability data, repurposing existing approved drugs an appealing option. Finally, it essential highlight and, by extension, MASLD be recognized approached systemic affecting organs, with vigorous implementation interdisciplinary coordinated plans. Significance Statement SLD, including, among others, MASH, considered most prevalent chronic condition than one-fourth global population. aims provide information regarding pathophysiology, diagnosis, management line guidelines Collectively, hoped provided furthers understanding state direct implications stimulates additional research initiatives.

Language: Английский

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Exploring the Multifaceted Landscape of MASLD: A Comprehensive Synthesis of Recent Studies, from Pathophysiology to Organoids and Beyond

Biomedicines, Journal Year: 2024, Volume and Issue: 12(2), P. 397 - 397

Published: Feb. 8, 2024

Non-alcoholic fatty liver disease (NAFLD) is a widespread contributor to chronic globally. A recent consensus on renaming was established, and metabolic dysfunction-associated steatotic disease, MASLD, chosen as the replacement for NAFLD. The disease’s range extends from less severe previously known non-alcoholic (NAFL), more intense steatohepatitis (MASH), (NASH), characterized by inflammation apoptosis. This research project endeavors comprehensively synthesize most studies encompassing wide spectrum of topics such pathophysiology, risk factors, dietary influences, lifestyle management, genetics, epigenetics, therapeutic approaches, prospective trajectory particularly exploring its connection with organoids.

Language: Английский

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Activation of SIRT1 by SRT1720 Alleviates Dyslipidemia, Improves Insulin Sensitivity and Exhibits Liver-Protective Effects in Diabetic Rats on a High-Fat Diet: New Insights into the SIRT1/Nrf2/NFκB Signaling Pathway

European Journal of Pharmaceutical Sciences, Journal Year: 2025, Volume and Issue: 206, P. 107002 - 107002

Published: Jan. 6, 2025

Insulin resistance and diabetes are associated with non-alcoholic fatty liver disease (NAFLD) steatohepatitis (NASH) conditions, which distinguished by metabolic dysfunction, oxidative stress inflammation. Sirtuin 1 (SIRT1), a NAD

Language: Английский

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Overexpression of NAG-1/GDF15 prevents hepatic steatosis through inhibiting oxidative stress-mediated dsDNA release and AIM2 inflammasome activation

Redox Biology, Journal Year: 2022, Volume and Issue: 52, P. 102322 - 102322

Published: April 27, 2022

Language: Английский

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Dual-Channel Fluorescent Probe for Detecting Viscosity and ONOO^– without Signal Crosstalk in Nonalcoholic Fatty Liver

Analytical Chemistry, Journal Year: 2022, Volume and Issue: 94(50), P. 17439 - 17447

Published: Dec. 7, 2022

Nonalcoholic fatty liver disease (NAFLD) is a global health issue. Peroxynitrite and viscosity have recently been found to be potential biomarkers of NAFLD. Therefore, it great significance develop dual-response fluorescent probes for simultaneous detecting peroxynitrite viscosity. We report herein new probe (CQ) that can simultaneously detect at two independent channels without signal crosstalk. CQ shows high selectivity, rapid response, good water solubility, low cytotoxicity, mitochondrial localization properties. In particular, responds sensitively with off-on fluorescence changes 710 505 nm, respectively. The wavelength gap between these more than 200 ensuring there no crosstalk during detection. With this property, the was applied image concentration pathogenesis All results show powerful tool detection provides diagnostic method

Language: Английский

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