Phenotypic Characteristics of Peripheral Blood Lymphocytes in Patients with Alcohol Dependence in the Dynamics of the Post-Abstinence State DOI Creative Commons
Т.П. Ветлугина, E. Epimakhova, V. D. Prokopieva

et al.

Psikhiatriya, Journal Year: 2025, Volume and Issue: 22(5), P. 49 - 58

Published: Jan. 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.

Language: Английский

Dietary fiber alleviates alcoholic liver injury via Bacteroides acidifaciens and subsequent ammonia detoxification DOI
Haiyuan Shen, Liangliang Zhou,

Hao Zhang

et al.

Cell Host & Microbe, Journal Year: 2024, Volume and Issue: 32(8), P. 1331 - 1346.e6

Published: July 2, 2024

Language: Английский

Citations

24
Coordinated action of a gut–liver pathway drives alcohol detoxification and consumption DOI
Yaojie Fu, Bryan Mackowiak, Yuhong Lin

et al.

Nature Metabolism, Journal Year: 2024, Volume and Issue: 6(7), P. 1380 - 1396

Published: June 20, 2024

Language: Английский

Citations

21
Liver diseases: epidemiology, causes, trends and predictions DOI Creative Commons

Can Gan,

Yuan Yuan, Haiyuan Shen

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2025, Volume and Issue: 10(1)

Published: Feb. 4, 2025

Abstract As a highly complex organ with digestive, endocrine, and immune-regulatory functions, the liver is pivotal in maintaining physiological homeostasis through its roles metabolism, detoxification, immune response. Various factors including viruses, alcohol, metabolites, toxins, other pathogenic agents can compromise function, leading to acute or chronic injury that may progress end-stage diseases. While sharing common features, diseases exhibit distinct pathophysiological, clinical, therapeutic profiles. Currently, contribute approximately 2 million deaths globally each year, imposing significant economic social burdens worldwide. However, there no cure for many kinds of diseases, partly due lack thorough understanding development these Therefore, this review provides comprehensive examination epidemiology characteristics covering spectrum from conditions manifestations. We also highlight multifaceted mechanisms underlying initiation progression spanning molecular cellular levels networks. Additionally, offers updates on innovative diagnostic techniques, current treatments, potential targets presently under clinical evaluation. Recent advances pathogenesis hold critical implications translational value novel strategies.

Language: Английский

Citations

6
Timosaponin B II as a novel KEAP1-NRF2 inhibitor to alleviate alcoholic liver disease:Receptor structure-based virtual screening and biological evaluation DOI
Junjie Wang, Baoyi Chen, C. C. Cheng

et al.

Chemico-Biological Interactions, Journal Year: 2025, Volume and Issue: unknown, P. 111390 - 111390

Published: Jan. 1, 2025

Language: Английский

Citations

2
Effects of elafibranor on liver fibrosis and gut barrier function in a mouse model of alcohol-associated liver disease DOI

Aritoshi Koizumi,

Kosuke Kaji, Norihisa Nishimura

et al.

World Journal of Gastroenterology, Journal Year: 2024, Volume and Issue: 30(28), P. 3428 - 3446

Published: July 24, 2024

BACKGROUND Alcohol-associated liver disease (ALD) is a leading cause of liver-related morbidity and mortality, but there are no therapeutic targets modalities to prevent ALD-related fibrosis. Peroxisome proliferator activated receptor (PPAR) α δ play key role in lipid metabolism intestinal barrier homeostasis, which major contributors the pathological progression ALD. Meanwhile, elafibranor (EFN), dual PPARα PPARδ agonist, has reached phase III clinical trial for treatment metabolic dysfunction-associated steatotic primary biliary cholangitis. However, benefits EFN ALD unknown. AIM To evaluate inhibitory effects on fibrosis gut-intestinal dysfunction an mouse model. METHODS was induced female C57BL/6J mice by feeding 2.5% ethanol (EtOH)-containing Lieber-DeCarli liquid diet intraperitoneally injecting carbon tetrachloride thrice weekly (1 mL/kg) 8 weeks. (3 10 mg/kg/day) orally administered during experimental period. Histological molecular analyses were performed assess effect steatohepatitis, fibrosis, integrity. The HepG2 lipotoxicity Caco-2 function evaluated cell-based assays. RESULTS hepatic steatosis, apoptosis, model significantly attenuated treatment. promoted lipolysis β-oxidation enhanced autophagic antioxidant capacities EtOH-stimulated cells, primarily through activation. Moreover, inhibited Kupffer cell-mediated inflammatory response, with blunted exposure lipopolysaccharide (LPS) toll like 4 (TLR4)/nuclear factor kappa B (NF-κB) signaling. improved hyperpermeability restoring tight junction proteins autophagy inhibiting apoptosis proinflammatory responses. protective cells predominantly mediated CONCLUSION reduced accumulation enhancing hepatocyte capacities, suppressing LPS/TLR4/NF-κB-mediated responses function.

Language: Английский

Citations

13
Inflammation in Alcohol-Associated Hepatitis: Pathogenesis and Therapeutic Targets DOI Creative Commons
Dechun Feng, Seonghwan Hwang, Adrien Guillot

et al.

Cellular and Molecular Gastroenterology and Hepatology, Journal Year: 2024, Volume and Issue: 18(3), P. 101352 - 101352

Published: Jan. 1, 2024

Alcohol-associated hepatitis (AH) is an acute-on-chronic liver injury that occurs in patients with chronic alcohol-associated disease (ALD). Patients severe AH have high short-term mortality and lack effective pharmacologic therapies. Inflammation believed to be one of the key factors promoting progression has been actively investigated as therapeutic targets over last several decades, but no inflammatory identified so far. In this review, we discuss how cells mediators produced by these contribute development AH, focus on neutrophils macrophages. The crosstalk between nonparenchymal pathogenesis elaborated. We also deliberate application recent cutting-edge technologies characterizing inflammation AH. Finally, potential for are briefly summarized.

Language: Английский

Citations

12
Oxidative stress in alcoholic liver disease, focusing on proteins, nucleic acids, and lipids: A review DOI

Weiwen Lai,

Jiahua Zhang,

Jiawei Sun

et al.

International Journal of Biological Macromolecules, Journal Year: 2024, Volume and Issue: 278, P. 134809 - 134809

Published: Aug. 16, 2024

Language: Английский

Citations

12
Alcohol-associated liver cancer DOI
Yaojie Fu, Luca Maccioni, Xin Wei Wang

et al.

Hepatology, Journal Year: 2024, Volume and Issue: 80(6), P. 1462 - 1479

Published: April 12, 2024

Heavy alcohol intake induces a wide spectrum of liver diseases ranging from steatosis, steatohepatitis, cirrhosis, and HCC. Although consumption is well-known risk factor for the development, morbidity, mortality HCC globally, alcohol-associated hepatocellular carcinoma (A-HCC) poorly characterized compared to viral hepatitis–associated Most A-HCCs develop after cirrhosis (AC), but direct carcinogenesis ethanol its metabolites A-HCC remains obscure. The differences between HCCs caused by other etiologies have not been well investigated in terms clinical prognosis, genetic or epigenetic landscape, molecular mechanisms, heterogeneity. Moreover, there huge gap basic research practice due lack preclinical models A-HCC. In current review, we discuss pathogenesis, heterogeneity, approaches, epigenetic, profiles A-HCC, insights into prospects future on potential effect cholangiocarcinoma metastasis also discussed.

Language: Английский

Citations

11
Cell-to-cell and organ-to-organ crosstalk in the pathogenesis of alcohol-associated liver disease DOI Creative Commons

Hui Gao,

Yanchao Jiang,

Zeng Ge

et al.

eGastroenterology, Journal Year: 2024, Volume and Issue: 2(4), P. e100104 - e100104

Published: Dec. 1, 2024

Alcohol-associated liver disease (ALD) is a growing global health concern and its prevalence severity are increasing steadily. While bacterial endotoxin translocation into the portal circulation well-established key factor, recent evidence highlights critical role of sterile inflammation, triggered by diverse stimuli, in alcohol-induced injury. This review provides comprehensive analysis complex interactions within hepatic microenvironment ALD. It examines contributions both parenchymal cells, like hepatocytes, non-parenchymal such as stellate Kupffer neutrophils, sinusoidal endothelial driving progression disease. Additionally, we explored involvement mediators, including cytokines, chemokines inflammasomes, which regulate inflammatory responses promote injury fibrosis. A particular focus has been placed on extracellular vesicles (EVs) essential mediators intercellular communication beyond liver. These facilitate transfer signalling molecules, microRNAs proteins, modulate immune responses, fibrogenesis lipid metabolism, thereby influencing progression. Moreover, underscore importance organ-to-organ crosstalk, particularly gut-liver axis, where dysbiosis increased intestinal permeability lead to microbial translocation, exacerbating inflammation. The adipose-liver axis also highlighted, impact adipokines free fatty acids from adipose tissue steatosis inflammation context alcohol consumption.

Language: Английский

Citations

11
Single‐cell landscape of the intrahepatic ecosystem in alcohol‐related liver disease DOI Creative Commons

Xiaofang Zhao,

Senyan Wang,

Qi Liu

et al.

Clinical and Translational Medicine, Journal Year: 2025, Volume and Issue: 15(1)

Published: Jan. 1, 2025

Abstract Alcohol‐related liver disease (ALD) is a common chronic caused by long‐term excessive alcohol consumption and responsible for more than half of all liver‐related deaths worldwide. The molecular mechanisms associated with ALD were not fully understood. In this study, we performed single‐cell RNA sequencing on tissues obtained from patients healthy donors. We identified an ALB + KRT7 epithelial population that expressed both hepatocyte biliary markers significantly expanded in livers. cells demonstrated to have stem cell properties malignant transformation potentials. Moreover, epithelium‐derived organoids promote the tumour growth activating Wnt/β‐catenin signalling cancer cells. Most importantly, blocking Wnt protein secretion or knockdown receptor suppressed promoting effect organoids. Our study provides important insights can be targeted advanced alcohol‐related cirrhosis prevent transformation. addition, our results also uncovered alterations nonparenchymal cells, especially macrophages T/NK populations active inflammation responses hepatitis immunosuppressive microenvironment livers, which likely facilitated progression ALD. Key points This landscape human samples across different stages. epithelium enriched patients, function varied had potential promotion activity. comprehensive changes parenchymal livers lay hidden danger further progression.

Language: Английский

Citations

1