Gut-liver axis: Recent concepts in pathophysiology in alcohol-associated liver disease

Hepatology, Год журнала: 2024, Номер 80(6), С. 1342 - 1371

Опубликована: Май 1, 2024

The growing recognition of the role gut microbiome’s impact on alcohol-associated diseases, especially in liver disease, emphasizes need to understand molecular mechanisms involved governing organ-organ communication identify novel avenues combat diseases. gut-liver axis refers bidirectional and interaction between liver. Intestinal microbiota plays a pivotal maintaining homeostasis within axis, this significant disease. intricate intestine involves multiple cellular components each organ that enable them carry out their physiological functions. In review, we focus approaches understanding how chronic alcohol exposure impacts microbiome individual cells intestine, as well ethanol machinery required for intraorgan interorgan communication.

Язык: Английский

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NLRP3 Inflammasome in Acute and Chronic Liver Diseases

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(8), С. 4537 - 4537

Опубликована: Апрель 20, 2024

NLRP3 (NOD-, LRR-, and pyrin domain-containing protein 3) is an intracellular complex that upon external stimuli or contact with specific ligands, recruits other components, forming the inflammasome. The inflammasome mainly mediates pyroptosis, a highly inflammatory mode of regulated cell death, as well IL-18 IL-1β production. Acute chronic liver diseases are characterized by massive influx pro-inflammatory enriched in reactive oxygen species (ROS) damage-associated molecular patterns (DAMPs) promote assemblage activation As major cause cytokine storm, exacerbates diseases, even though it might exert protective effects regards to hepatitis C B virus infection (HCV HBV). Here, we summarize current knowledge concerning function both acute disease post transplant setting, focusing on mechanisms involved activity.

Язык: Английский

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Oxidative stress in alcoholic liver disease, focusing on proteins, nucleic acids, and lipids: A review

International Journal of Biological Macromolecules, Год журнала: 2024, Номер 278, С. 134809 - 134809

Опубликована: Авг. 16, 2024

Язык: Английский

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Efferocytosis in liver disease

JHEP Reports, Год журнала: 2023, Номер 6(1), С. 100960 - 100960

Опубликована: Ноя. 16, 2023

The process of dead cell clearance by phagocytic cells, called efferocytosis, prevents inflammatory necrosis and promotes resolution repair. Defective efferocytosis contributes to the progression numerous diseases in which death prominent, including liver disease. Many gaps remain our understanding how macrophages carry out this goes awry various types diseases. Studies thus far have suggested that, upon injury, resident Kupffer cells (KCs) infiltrating monocyte-derived (MoMϕs) clear limit inflammation, and, through macrophage reprogramming, repair damage. However, unusual settings, can promote In review, we will focus on acute chronic diseases, metabolic dysfunction-associated steatohepatitis. Understanding mechanisms consequences has potential shed new light disease pathophysiology suggest treatment strategies prevent progression.

Язык: Английский

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Major generation route of cytotoxic protein adducts derived from acetaldehyde, a metabolite of alcohol

Medical Hypotheses, Год журнала: 2024, Номер 189, С. 111385 - 111385

Опубликована: Май 31, 2024

The habitual excessive consumption of alcohol has been implicated in the onset and/or progression alcoholic-associated liver/brain diseases (ALD/ABD), lung disease, rheumatoid arthritis, and cardiac tissue injury. Alcohol (ethanol) is metabolized to acetaldehyde (AA), a two-carbon carbonyl compound that reacts with proteins form covalent AA-protein adducts (AAPAs). We herein propose AA liver brain generate AAPAs, which contribute alcohol-induced injury neurotoxicity vivo, respectively. viability hepatocytes was significantly lower culture treated AAPAs than Nε-(ethyl)lysine (NEL), reduced Schiff bases, or control culture. Furthermore, correlation observed between staining for AAPA 4-hydroxy-2-nonenal severity ALD both rats humans. chronic produces reactive oxygen species, have pathogenesis ALD. Moreover, dose-dependent increase neuronal cell death noted cortical neurons incubated completely suppressed by an anti-AAPA antibody, but not anti-NEL antibody. epitopes detected brains individuals alcohol-related damage. also shown ABD. hypothesis proposed strongly cytotoxic are iminobutane structures, differ from known structures NEL. suggest importance structural epitope as toxic moieties cells alcoholism.

Язык: Английский

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Ginsenoside Rg1: A bioactive therapeutic agent for diverse liver diseases

Pharmacological Research, Год журнала: 2025, Номер unknown, С. 107571 - 107571

Опубликована: Янв. 1, 2025

Diverse liver diseases are characterised by late diagnosis and rapid progression have become one of the major threats to human health. To delay transition from benign tissue lesions a substantial organ injury, scientists gradually applied natural compounds derived plants as complementary therapy in field hepatology. Ginseng (Panax ginseng C. A. Meyer) is tonic traditional Chinese herbal medicine, products, including ginsenoside Rg1 (G-Rg1), which kind 20(S)-protopanaxatriol saponin with relatively high biological activity, can be isolated roots or stems ginseng. Given these information, this review aimed summarise discuss metabolic mechanisms G-Rg1 regulation diverse measures improve its bioavailability. As monomer medicine multitarget pharmacological effects, provide significant therapeutic benefits alleviation alcoholic disease, nonalcoholic fatty fibrosis, viral hepatitis, etc., mainly rely on inhibition apoptosis, strengthening endogenous anti-inflammatory antioxidant mechanisms, activation immune responses efflux transport signals, pathological changes caused lipid deposition, inflammation, oxidative stress, accumulation hepatotoxic product, etc. However, poor bioavailability must overcome clinical application value. In summary, focusing hepatoprotective will new insights into development resources their pharmaceutical products target treatment diseases.

Язык: Английский

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Phenotypic Characteristics of Peripheral Blood Lymphocytes in Patients with Alcohol Dependence in the Dynamics of the Post-Abstinence State

Psikhiatriya, Год журнала: 2025, Номер 22(5), С. 49 - 58

Опубликована: Янв. 8, 2025

Background: the damaging effect of ethanol on cells, systems and organs determines relevance studying role immune system in pathogenesis alcohol dependence (alcoholism). The literature reported contradictory data effects cellular immunity that is conditioned by various research techniques, approaches to formation groups, disease stages. Objective: determine phenotypes lymphocytes peripheral blood from patients with time course post withdrawal state. Patients: 52 male aged 30–60 years were examinedwho diagnosed according ICD-10 Mental Behavioral Disorders due Use Alcohol (dependence syndrome — F10.21 F10.30), their duration was 15.0 ± 9.5 years, including 12 alcoholic liver (ALD). investigations conducted post-withdrawal state: after detoxification (1 point) days 14–17 treatment (2 point). 25 conditionally healthy men served as controls, comparison group included 20 neurotic disorders. Methods: populations/subpopulations determined cytometer BD FACS Calibur (Becton Dickinson, USA); reagent kits same firm used. T-lymphocytes (CD3+ ), B-lymphocytes (CD19+ T-helpers/Т-inducers CD4+ cytotoxic Т-lymphocytes CD8+ NK cells (CD3–CD16+ CD56+ ) revealed percent population absolute values. Results: point 1 study, patients, relation controls group, had an elevated Т-helpers-inducers, a reduced number cells. After therapy, CD3+ remain elevated, decrease; (ALD) reduced. Conclusion: phenotype alcohol-dependent at early stage postwithdrawal state characterized elevation , reduction During some populations are normalized, except for T-lymphocytes, well ALD. Immune imbalance indicates instability need additional treatment.

Язык: Английский

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Transitioning from NAFLD to MAFLD and MASLD: the toxic relationship with alcohol consumption

Exploration of Medicine, Год журнала: 2025, Номер unknown

Опубликована: Янв. 13, 2025

Alcohol is a well-known toxic etiologic factor for liver injury. Metabolic substrates of alcohol (especially acetaldehyde) have major responsibility and genetic susceptibility, alterations in microbiota immune system are important co-factors this Major injury hepatocellular lipid accumulation. Therefore the relationship between non-alcoholic alcoholic fatty diseases should been defined clearly. Recently two committees adopted new terminologies such as metabolic-associated disease (MAFLD), metabolic dysfunction-associated steatotic (MASLD), dysfunction alcohol-related (MetALD), (ALD) instead (NAFLD). These were based on effects syndrome liver. consumption was differently according to these nomenclatures. MAFLD intake (regardless amount) “dual etiology disease” Delphi consensus MASLD, MetALD, or ALD daily amount.

Язык: Английский

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Genetic associations between orexin genes and phenotypes related to behavioral regulation in humans, including substance use

Molecular Psychiatry, Год журнала: 2025, Номер unknown

Опубликована: Янв. 29, 2025

Язык: Английский

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Amelioration of Alcoholic Hepatic Steatosis in a Rat Model via Consumption of Poly-γ-Glutamic Acid-Enriched Fermented Protaetia brevitarsis Larvae Using Bacillus subtilis

Foods, Год журнала: 2025, Номер 14(5), С. 861 - 861

Опубликована: Март 3, 2025

Alcoholic hepatic steatosis (AHS) is a common early-stage symptom of liver disease caused by alcohol consumption. Accordingly, several aspects AHS have been studied as potential preventive and therapeutic targets. In this study, novel strategy was employed to inhibit fatty accumulation counteract through the consumption microorganism-fermented Protaetia brevitarsis larvae (FPBs). By using an rat model, we assessed efficacy FPB examining lipid profile liver/serum function tests evaluate metabolism modulation. After administration, profile-including high-density lipoprotein, total cholesterol, triglycerides-and histopathological characteristics exhibited improvement in animal model. Interestingly, amelioration via FPBs administration potentially associated with poly-γ-glutamic acid (PγG), which produced Bacillus species during fermentation. These findings support formulation natural remedies for non-clinical studies, suggesting that PγG-enriched are valuable ingredient functional foods, providing ameliorative effect on AHS.

Язык: Английский

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