Xenobiotica 45 (10), 921929
TPS is a secretion pathway that appears to play diverse roles in several Gram-negative bacteria and includes a large secreted protein (generally referred to as TpsA) and a channel-forming barrel outer membrane activator/transport protein (TpsB) (Henderson et al., 2004
Introduction Alcohol-associated liver disease (ALD) presents a significant global public health challenge due to its strong link to excessive alcohol consumption.1 2 ALD is the leading cause of liver-related mortality, encompassing a wide range of liver disorders, from simple hepatic steatosis to more severe conditions like alcohol-associated hepatitis (AH), cirrhosis, and eventually hepatocellular carcinoma (HCC).2 3 The progression of ALD is influenced by a complex interplay of genetic, environmental and metabolic factors, highlighting the urgent need to deepen our understanding of its pathogenesis to develop effective prevention and treatment strategies.4 5 The pathophysiology of ALD is multifaceted, involving numerous interconnected mechanisms triggered by alcohol metabolism.6 On ingestion, alcohol is primarily metabolised in hepatocytes by enzymes such as alcohol dehydrogenase (ADH) and cytochrome P450 2E1 (CYP2E1), producing acetaldehyde and reactive oxygen species (ROS).6 These byproducts induce oxidative stress, lipid peroxidation and the formation of DNA and protein adducts, causing direct hepatocellular damage and impaired cellular functions.6 7 Chronic alcohol consumption also disrupts the gut epithelial barrier, increasing intestinal permeability and allowing bacterial products like lipopolysaccharides (LPS) to enter the portal circulation.8 This translocation exacerbates liver injury by activating macrophages and recruiting neutrophils, which release pro-inflammatory cytokines and chemokines that amplify the local inflammatory response.7 Alcohol-induced protein adducts can also trigger an adaptive immune response by activating T cells, while chronic alcohol use impairs CD4 + T cell immunometabolism, promoting their differentiation into a pro-inflammatory phenotype.9 Hepatic stellate cells (HSCs) play a pivotal role in the progression of ALD
Before you start taking any over-the-counter (OTC) vitamins or supplements, Dr
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