Alcohol-associated liver disease

Journal of Clinical Investigation, Год журнала: 2024, Номер 134(3)

Опубликована: Фев. 1, 2024

Alcohol-associated liver disease (ALD) is a major cause of chronic worldwide, and comprises spectrum several different disorders, including simple steatosis, steatohepatitis, cirrhosis, superimposed hepatocellular carcinoma. Although tremendous progress has been made in the field ALD over last 20 years, pathogenesis remains obscure, there are currently no FDA-approved drugs for treatment ALD. In this Review, we discuss new insights into therapeutic targets ALD, utilizing study multiomics other cutting-edge approaches. The potential translation these studies clinical practice therapy deliberated. We also preclinical models interplay metabolic dysfunction, alcohol-associated cancer, heterogeneity some translational research prospects

Язык: Английский

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Alcohol-associated liver cancer

Hepatology, Год журнала: 2024, Номер 80(6), С. 1462 - 1479

Опубликована: Апрель 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.

Язык: Английский

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Inflammation in Alcohol-Associated Hepatitis: Pathogenesis and Therapeutic Targets

Cellular and Molecular Gastroenterology and Hepatology, Год журнала: 2024, Номер 18(3), С. 101352 - 101352

Опубликована: Янв. 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.

Язык: Английский

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Molecular mechanisms in liver repair and regeneration: from physiology to therapeutics

Signal Transduction and Targeted Therapy, Год журнала: 2025, Номер 10(1)

Опубликована: Фев. 8, 2025

Язык: Английский

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The interaction between central and peripheral immune systems in methamphetamine use disorder: current status and future directions

Journal of Neuroinflammation, Год журнала: 2025, Номер 22(1)

Опубликована: Фев. 15, 2025

Methamphetamine (METH) use disorder (MUD) is characterized by compulsive drug-seeking behavior and substantial neurotoxicity, posing a considerable burden on individuals society. Traditionally perceived as localized central nervous system disorder, recent preclinical clinical studies have elucidated that MUD multifaceted influenced various biological systems, particularly the immune system. Emerging evidence suggests both peripheral responses play crucial role in initiation persistence of MUD. Conceptualizing it systemic process prompts significant inquiries regarding mechanisms communication between compartments. Also, whether this intercommunication could serve diagnostic biomarkers or therapeutic targets. This review begins offering an overview mechanistic pertaining to neuroimmune systems. Finally, future directions are suggested through integration innovative technologies multidimensional data promote translation basic research into interventions.

Язык: Английский

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Beyond host defense and tissue injury: the emerging role of neutrophils in tissue repair

AJP Cell Physiology, Год журнала: 2024, Номер 326(3), С. C661 - C683

Опубликована: Янв. 8, 2024

Neutrophils, the most abundant immune cells in human blood, play a fundamental role host defense against invading pathogens and tissue injury. Neutrophils carry potentially lethal weaponry to affected site. Inadvertent perpetual neutrophil activation could lead nonresolving inflammation damage, unifying mechanism of many common diseases. The prevailing view emphasizes dichotomy their function, versus damage. However, injury may also persist during neutropenia, which is associated with disease severity poor outcome. Numerous studies highlight phenotypic heterogeneity functional versatility, indicating that neutrophils more complex roles than previously thought. Emerging evidence indicates actively orchestrate resolution repair facilitate return homeostasis. Thus, mobilize multiple mechanisms limit inflammatory reaction, assure debris removal, matrix remodeling, cytokine scavenging, macrophage reprogramming, angiogenesis. In this review, we will summarize homeostatic tissue-reparative functions across organs. We discuss how healing power might be harnessed develop novel repair-promoting therapies while maintaining functions.

Язык: Английский

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Cell-to-cell and organ-to-organ crosstalk in the pathogenesis of alcohol-associated liver disease

eGastroenterology, Год журнала: 2024, Номер 2(4), С. e100104 - e100104

Опубликована: Дек. 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.

Язык: Английский

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Pathogenesis of Alcohol-Associated Liver Disease

Clinics in Liver Disease, Год журнала: 2024, Номер 28(4), С. 647 - 661

Опубликована: Июль 23, 2024

Язык: Английский

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Targeting the HDAC6/Hint2/MICU1 axis to ameliorate acute liver failure via inhibiting NETosis

Life Sciences, Год журнала: 2025, Номер 366-367, С. 123498 - 123498

Опубликована: Фев. 19, 2025

Язык: Английский

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Therapeutic Effects of DNase I on Peripheral and Local Markers of Liver Injury and Neutrophil Extracellular Traps in a Model of Alcohol-Related Liver Disease

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(5), С. 1893 - 1893

Опубликована: Фев. 22, 2025

Alcohol-related liver disease (ALD) is a leading cause of chronic conditions globally. Chronic alcohol consumption induces damage through various mechanisms, including neutrophil extracellular trap (NET) formation. Extracellular DNA (ecDNA), released from damaged hepatocytes and NETotic neutrophils, has emerged as potential biomarker contributor to pathology. Enzyme DNases could be an effective therapy for the denaturation immunogenic ecDNA. This study investigated circulating ecDNA NET markers in ALD therapeutic effect DNase I murine model ALD. Female C57BL/6J mice were fed control diet (n = 13) or Lieber-DeCarli ethanol 10 days followed by binge dose mimic acute-on-chronic alcoholic injury. From day 5, randomized into group 17) + 5), which received additional treatment every 12 h. Liver analyzed. Circulating NETosis measured fluorometry cytometry, respectively. activity was analyzed with single radial enzyme dispersion assay. The ethanol-fed exhibited increased mortality, infiltration structural liver. Total levels did not differ between groups. higher compared controls daily administration prevented These findings suggest that alcohol-induced injury modestly influences systemic levels. However, can prevent progression enhanced degradation using I.

Язык: Английский

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