Crosstalk between Oxidative Stress and Inflammatory Liver Injury in the Pathogenesis of Alcoholic Liver Disease

International Journal of Molecular Sciences, Год журнала: 2022, Номер 23(2), С. 774 - 774

Опубликована: Янв. 11, 2022

Alcoholic liver disease (ALD) is characterized by the injury, inflammation, and scarring in owing to excessive alcohol consumption. Currently, ALD a leading cause for transplantation. Therefore, extensive studies (in vitro, experimental models humans) are needed elucidate pathological features pathogenic mechanisms underlying ALD. Notably, oxidative changes have been recognized as signature trait of Progression linked generation highly reactive free radicals reactions involving ethanol its metabolites. Furthermore, hepatic stress promotes tissue injury and, turn, stimulates inflammatory responses liver, forming loop that progression Accordingly, accumulating further knowledge on relationship between inflammation may help establish viable therapeutic approach treating

Язык: Английский

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Pathogenesis of Alcohol-Associated Liver Disease

Journal of Clinical and Experimental Hepatology, Год журнала: 2022, Номер 12(6), С. 1492 - 1513

Опубликована: Май 31, 2022

Excessive alcohol consumption is a global healthcare problem with enormous social, economic, and clinical consequences. While chronic, heavy causes structural damage and/or disrupts normal organ function in virtually every tissue of the body, liver sustains greatest damage. This primarily because first to see absorbed from gastrointestinal tract via portal circulation second, principal site ethanol metabolism. Alcohol-induced remains one most prevalent disorders leading cause death or transplantation disease. Despite extensive research on pathophysiology this disease, there are still no targeted therapies available. Given multifactorial mechanisms for alcohol-associated disease pathogenesis, it conceivable that multitherapeutic regimen needed treat different stages spectrum

Язык: Английский

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Ethanol and its Nonoxidative Metabolites Promote Acute Liver Injury by Inducing ER Stress, Adipocyte Death, and Lipolysis

Cellular and Molecular Gastroenterology and Hepatology, Год журнала: 2022, Номер 15(2), С. 281 - 306

Опубликована: Окт. 13, 2022

Язык: Английский

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The role of neutrophils in alcohol-related hepatitis

Journal of Hepatology, Год журнала: 2023, Номер 79(4), С. 1037 - 1048

Опубликована: Июнь 6, 2023

Alcohol-related liver disease is a major cause of disease-associated mortality, with inpatient care being contributor to its clinical and economic burden. hepatitis (AH) an acute inflammatory form alcohol-related disease. Severe AH associated high short-term infection common death. The presence increased numbers circulating hepatic neutrophils. We review the literature on role neutrophils in AH. In particular, we explain how are recruited inflamed their antimicrobial functions (chemotaxis, phagocytosis, oxidative burst, NETosis) may be altered highlight evidence for existence 'high-density' 'low-density' neutrophil subsets. also describe potentially beneficial roles resolution injury through effects macrophage polarisation regeneration. Finally, discuss manipulation recruitment/function used as therapeutic strategy For example, correction gut dysbiosis could help prevent excess activation, or treatments aim enhance miR-223 function development markers that can reliably distinguish subsets animal models accurately reproduce human will crucial facilitating translational research this important field.

Язык: Английский

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Age‐dependent loss of hepatic SIRT1 enhances NLRP3 inflammasome signaling and impairs capacity for liver fibrosis resolution

Aging Cell, Год журнала: 2023, Номер 22(5)

Опубликована: Март 31, 2023

Abstract Our studies indicate that the longevity factor SIRT1 is implicated in metabolic disease; however, whether and how hepatocyte‐specific signaling involved liver fibrosis remains undefined. We characterized a functional link of age‐mediated defects to NLRP3 inflammasome during age‐related fibrosis. In multiple experimental murine models fibrosis, we compared development young old mice, as well liver‐specific knockout (SIRT1 LKO) mice wild‐type (WT) mice. Liver injury, inflammation were assessed histologically quantified by real‐time PCR analysis. model hepatotoxin‐induced displayed more severe persistent than injury after cessation, inhibition SIRT1, induction NLRP3, infiltration macrophages neutrophils, activation hepatic stellate cells (HSCs), excessive deposition remodeling extracellular matrix. Mechanistically, deletion hepatocytes resulted IL‐1β induction, pro‐inflammatory response, mimicking ability aging impair resolution established an mouse model, chronic‐plus‐binge alcohol feeding‐induced was attenuated treatment with MCC950, selective inhibitor. ameliorated alcoholic repressing reducing hepatocyte‐derived danger signaling—ASK1 HMGB1. conclusion, age‐dependent lead inflammation, which turn impairs capacity resolve aging.

Язык: Английский

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Involvement of SIRT1-mediated aging in liver diseases

Frontiers in Cell and Developmental Biology, Год журнала: 2025, Номер 13

Опубликована: Фев. 20, 2025

Liver disease is a significant global health issue, responsible for millions of deaths annually. Aging, characterized by the gradual decline in cellular and physiological functions, impairs tissue regeneration, increases susceptibility to liver diseases, leads health. Silent information regulator 1 (SIRT1), NAD⁺-dependent deacetylase, has emerged as pivotal factor modulating age-related changes liver. SIRT1 preserves function regulating essential aging-related pathways, including telomere maintenance, epigenetic modifications, senescence, intercellular communication, inflammation, mitochondrial function. Notably, levels naturally with age, contributing progression increased vulnerability injury. This review summarizes regulatory role aging its impact on diseases such fibrosis, alcoholic associated (ALD), metabolic dysfunction-associated steatotic (MASLD), steatohepatitis (MASH), hepatocellular carcinoma (HCC). We also discuss emerging therapeutic approaches, activators, gene therapy, nutritional interventions, which are evaluated their potential restore mitigate progression. Finally, we highlight future research directions optimize SIRT1-targeted therapies clinical applications conditions.

Язык: Английский

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MiR-223 as a Regulator and Therapeutic Target in Liver Diseases

Frontiers in Immunology, Год журнала: 2022, Номер 13

Опубликована: Март 16, 2022

MicroRNAs (miRNAs) are endogenous non-coding single-stranded small molecule RNAs consisting of 20-24 nucleotides that highly conserved in species evolution. Expression miRNAs is strictly tissue-specific, and it chronological fungi plants, as well animals. MiR-223 has been shown to play a key role innate immunity, dysregulation its expression contributes the pathogenesis multiple inflammatory diseases, cancers. In this article biosynthesis functions miR-223 immunity reviewed, liver physiopathology therapeutic prospects highlighted.

Язык: Английский

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Mesenchymal stromal/stem cells and their extracellular vesicles in liver diseases: insights on their immunomodulatory roles and clinical applications

Cell & Bioscience, Год журнала: 2023, Номер 13(1)

Опубликована: Сен. 5, 2023

Abstract Liver disease is a leading cause of mortality and morbidity that rising globally. dysfunctions are classified into acute chronic diseases. Various insults, including viral infections, alcohol or drug abuse, metabolic overload, may inflammation fibrosis, to irreversible liver dysfunction. Up now, transplantation could be the last resort for patients with end-stage disease. However, still faces unavoidable difficulties. Mesenchymal stromal/stem cells (MSCs) their broad ranging anti-inflammatory immunomodulatory properties can effectively used treating diseases but without limitation associated transplantation. In this review, we summarize discuss recent advances in characteristics MSCs potential action mechanisms MSCs-based cell therapies We also draw attention strategies potentiate therapeutic through pre-treatments gene modifications. Finally, progress toward clinical application extracellular vesicles

Язык: Английский

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SQSTM1/p62 and Hepatic Mallory-Denk Body Formation in Alcohol-Associated Liver Disease

American Journal Of Pathology, Год журнала: 2023, Номер 193(10), С. 1415 - 1426

Опубликована: Март 9, 2023

Sequestosome 1 (SQSTM1/p62; hereafter p62) is an autophagy receptor protein for selective primarily due to its direct interaction with the microtubule light chain 3 that specifically localizes on autophagosome membranes. As a result, impaired leads accumulation of p62. p62 also common component many human liver disease-related cellular inclusion bodies, such as Mallory-Denk intracytoplasmic hyaline α1-antitrypsin aggregates, well bodies and condensates. acts intracellular signaling hub, it involves multiple pathways, including nuclear factor erythroid 2-related 2, NF-κB, mechanistic target rapamycin, which are critical oxidative stress, inflammation, cell survival, metabolism, tumorigenesis. This review discusses recent insights in quality control, role formation degradation stress granules aggregates regulation pathways pathogenesis alcohol-associated disease.

Язык: Английский

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The double‐edged role of neutrophil heterogeneity in inflammatory diseases and cancers

MedComm, Год журнала: 2023, Номер 4(4)

Опубликована: Июль 23, 2023

Neutrophils are important immune cells act as the body's first line of defense against infection and respond to diverse inflammatory cues. Many studies have demonstrated that neutrophils display plasticity in diseases cancers. Clarifying role neutrophil heterogeneity cancers will contribute development novel treatment strategies. In this review, we presented a review on understanding from traditional perspective high-resolution viewpoint. A growing body evidence has confirmed double-edged tumors. This may be due lack precise specific subsets disease. Thus, elucidating involved would benefit precision medicine. Thusly, summarized relevance actions comprehensively. Meanwhile, also discussed potential intervention strategy for neutrophils. is intended deepen our cancers, while hold promise neutrophil-related diseases.

Язык: Английский

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