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These genetic damages compromise stem cell function, promote abnormal mutations, and increase the risk for cancer and blood disorders ( + ratio, reduces ATP production, and disrupts fatty acid oxidation, leading to steatosis and mitochondrial injury ( By weakening the intestinal barrier, alcohol allows bacterial lipopolysaccharide (LPS) to reach the liver and activate TLR4 signaling in Kupffer cells, amplifying hepatic inflammation ( 3.2 Alcohols role in HBV pathogenesis In HBV-infected individuals, alcohol further enhances liver damage by promoting viral replication and impairing immune responses, which contributes to increased hepatitis activity

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doi: 10.1016/S2095-3119(13)60417-7 146 ZhouP.AdeelM.ShakoorN.GuoM.HaoY.AzeemI.et al

however, other forms of ROS also contribute as the nitric oxide (NO) generated by NO synthases, which diffuses into mitochondria and modulates mitochondrial function by competing with O 2 at respiratory complex IV thereby slowing respiration (Collins et al., 2 O 2 in thiol oxidation modulating the function of proteins (Collins et al., 2014)

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Yet, important gaps remain regarding the mechanism by which Mn causes these