Pathogenic mechanisms and regulatory factors involved in alcoholic liver disease

Yan, Chuyun; Hu, Wanting; Tu, Jinqi; Li, Jinyao; Liang, Qionglin; Han, Shuxin

doi:10.1186/s12967-023-04166-8

Cited by 34 publications

(6 citation statements)

References 300 publications

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“…Lipid accumulation induces steatosis in NAFLD, whereas ethanol toxicity causes steatosis in ALD [ 7 , 8 ]. Chronic alcohol exposure stimulates the activation of sterol regulatory element binding protein-1c (SREBP-1c) in ALD, which regulates lipid synthesis [ 9 ]. NAFLD is associated with a similar impairment in lipid metabolism.…”

Section: Introductionmentioning

confidence: 99%

Enzyme-Treated Zizania latifolia Ethanol Extract Improves Liver-Related Outcomes and Fatigability

Ahn,

Kim,

Kim

et al. 2024

Foods

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Long-term hepatic damage is associated with human morbidity and mortality owing to numerous pathogenic factors. A variety of studies have focused on improving liver health using natural products and herbal medicines. We aimed to investigate the effect of enzyme-treated Zizania latifolia ethanol extract (ETZL), which increases the content of tricin via enzymatic hydrolysis, for 8 weeks on liver-related outcomes, lipid metabolism, antioxidant activity, and fatigue compared to a placebo. Healthy Korean adult males aged 19–60 years were randomized into ETZL treatment and placebo groups, and alcohol consumption was 24.96 and 28.64 units/week, respectively. Alanine transaminase, a blood marker associated with liver cell injury, significantly decreased after 8 weeks compared to the baseline in the ETZL treatment group (p = 0.004). After 8 weeks, the treatment group showed significant changes in the levels of high-density lipoprotein and hepatic steatosis index compared to the baseline (p = 0.028 and p = 0.004, respectively). ETZL treatment tended to reduce antioxidant-activity-related factors, total antioxidant status, and malondialdehyde, but there was no significant difference. In the multidimensional fatigue scale, ETZL treatment showed a significant reduction in general fatigue and total-fatigue-related values after 8 weeks compared to the baseline (p = 0.012 and p = 0.032, respectively). Taken together, the 8-week treatment of enzyme-treated Zizania latifolia ethanol extract demonstrated positive effects on liver-related outcomes, lipid metabolism, and mental fatigue without adverse effects on safety-related parameters.

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Section: Introductionmentioning

confidence: 99%

Enzyme-Treated Zizania latifolia Ethanol Extract Improves Liver-Related Outcomes and Fatigability

Ahn,

Kim,

Kim

et al. 2024

Foods

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“…ALD is the primary cause of chronic liver disease, and its end stages are associated with higher complication rates of spontaneous peritonitis and hepatic encephalopathy than other liver diseases ( Bhandari et al, 2020 ). Research indicates that a compromised mucosal barrier and severe dysbiosis of the intestinal microbiota are factors in the immunological imbalance in the gut–liver axis that causes intrahepatic inflammation in ALD ( Yan et al, 2023 ). Similarly, in the present study, we discovered that alcohol exposure severely damaged the intestinal barrier, resulting in the depletion of potential probiotic genera, such as Lactobacillus , Clostridium IV, and Akkermansia , and the enrichment of opportunistic pathogens, such as Oscillibacter , Escherichia / Shigella , and Alistipes , in ALD.…”

Section: Discussionmentioning

confidence: 99%

Symbiotic combination of Akkermansia muciniphila and inosine alleviates alcohol-induced liver injury by modulating gut dysbiosis and immune responses

Wei,

Pan,

Guo

et al. 2024

Front. Microbiol.

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BackgroundAlcoholic liver disease (ALD) is exacerbated by disruptions in intestinal microecology and immune imbalances within the gut–liver axis. The present study assesses the therapeutic potential of combining Akkermansia muciniphila (A. muciniphila) with inosine in alleviating alcohol-induced liver injury.MethodsMale C57BL/6 mice, subjected to a Lieber-DeCarli diet with 5% alcohol for 4 weeks, served as the alcoholic liver injury model. Various analyzes, including quantitative reverse transcription polymerase chain reaction (qRT-PCR), ELISA, immunochemistry, 16S rRNA gene sequencing, and flow cytometry, were employed to evaluate liver injury parameters, intestinal barrier function, microbiota composition, and immune responses.ResultsCompared to the model group, the A. muciniphila and inosine groups exhibited significantly decreased alanine aminotransferase, aspartate aminotransferase, and lipopolysaccharide (LPS) levels, reduced hepatic fat deposition and neutrophil infiltration, alleviated oxidative stress and inflammation, and increased expression of intestinal tight junction proteins (Claudin-1, Occludin, and ZO-1). These effects were further pronounced in the A. muciniphila and inosine combination group compared to individual treatments. While alcohol feeding induced intestinal dysbiosis and gut barrier disruption, the combined treatment reduced the abundance of harmful bacteria (Oscillibacter, Escherichia/Shigella, and Alistipes) induced by alcohol consumption, promoting the growth of butyrate-producing bacteria (Akkermansia, Lactobacillus, and Clostridium IV). Flow cytometry revealed that alcohol consumption reduced T regulatory (Treg) populations while increasing those of T-helper (Th) 1 and Th17, which were restored by A. muciniphila combined with inosine treatment. Moreover, A. muciniphila and inosine combination increased the expression levels of intestinal CD39, CD73, and adenosine A2A receptor (A2AR) along with enhanced proportions of CD4+CD39+Treg and CD4+CD73+Treg cells in the liver and spleen. The A2AR antagonist KW6002, blocked the beneficial effects of the A. muciniphila and inosine combination on liver injury in ALD mice.ConclusionThis study reveals that the combination of A. muciniphila and inosine holds promise for ameliorating ALD by enhancing the gut ecosystem, improving intestinal barrier function, upregulating A2AR, CD73, and CD39 expression, modulating Treg cells functionality, and regulating the imbalance of Treg/Th17/Th1 cells, and these beneficial effects are partly A2AR-dependent.

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“…Liver injury generally refers to damage to the liver due to one or more causes, including rupture of the liver by trauma and various liver diseases such as viral hepatitis, drug-induced hepatitis, alcoholic hepatitis, non-alcoholic fatty liver disease, and autoimmune liver disease [144][145][146][147]. Caffeine has been reported to be associated with acute liver injury.…”

Section: Nedd4/nedd4l and Liver Injurymentioning

confidence: 99%

NEDD4 and NEDD4L: Ubiquitin Ligases Closely Related to Digestive Diseases

Xu,

Jiang,

et al. 2024

Biomolecules

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Protein ubiquitination is an enzymatic cascade reaction and serves as an important protein post-translational modification (PTM) that is involved in the vast majority of cellular life activities. The key enzyme in the ubiquitination process is E3 ubiquitin ligase (E3), which catalyzes the binding of ubiquitin (Ub) to the protein substrate and influences substrate specificity. In recent years, the relationship between the subfamily of neuron-expressed developmental downregulation 4 (NEDD4), which belongs to the E3 ligase system, and digestive diseases has drawn widespread attention. Numerous studies have shown that NEDD4 and NEDD4L of the NEDD4 family can regulate the digestive function, as well as a series of related physiological and pathological processes, by controlling the subsequent degradation of proteins such as PTEN, c-Myc, and P21, along with substrate ubiquitination. In this article, we reviewed the appropriate functions of NEDD4 and NEDD4L in digestive diseases including cell proliferation, invasion, metastasis, chemotherapeutic drug resistance, and multiple signaling pathways, based on the currently available research evidence for the purpose of providing new ideas for the prevention and treatment of digestive diseases.

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Pathogenic mechanisms and regulatory factors involved in alcoholic liver disease

Cited by 34 publications

References 300 publications

Enzyme-Treated Zizania latifolia Ethanol Extract Improves Liver-Related Outcomes and Fatigability

Enzyme-Treated Zizania latifolia Ethanol Extract Improves Liver-Related Outcomes and Fatigability

Symbiotic combination of Akkermansia muciniphila and inosine alleviates alcohol-induced liver injury by modulating gut dysbiosis and immune responses

NEDD4 and NEDD4L: Ubiquitin Ligases Closely Related to Digestive Diseases

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