Alcohol-Associated Liver Disease Outcomes: Critical Mechanisms of Liver Injury Progression.

Alcohol-associated liver disease (ALD) is a substantial cause of morbidity and mortality worldwide and represents a spectrum of liver injury beginning with hepatic steatosis (fatty liver) progressing to inflammation and culminating in cirrhosis. Multiple factors contribute to ALD progression and disease severity. Here, we overview several crucial mechanisms related to ALD end-stage outcome development, such as epigenetic changes, cell death, hemolysis, hepatic stellate cells activation, and hepatic fatty acid binding protein 4.

Role of AMPK-SREBP Signaling in Regulating Fatty Acid Binding-4 (FABP4) Expression following Ethanol Metabolism.

Fatty acid binding protein-4 () is not normally expressed in the liver but is induced in alcohol-dependent liver disease (ALD)). This study sought to identify mechanisms whereby ethanol (EtOH) metabolism alters triglyceride accumulation and production. Human hepatoma cells which were stably transfected to express alcohol dehydrogenase (ADH) or cytochrome P4502E1 (CYP2E1) were exposed to EtOH in the absence/presence of inhibitors of ADH (4-methylpyrazole) or CYP2E1 (chlormethiazole).

Ectodysplasin-A mRNA in exosomes released from activated hepatic stellate cells stimulates macrophage response.

Introduction: The interaction between activated hepatic stellate cells (aHSCs) and macrophages is central to liver fibrosis development. The cargo contained within aHSC exosomes (aHSC-EXOs) and how aHSC-EXOs affect macrophage function is poorly understood.

Methods: RNA from aHSC-EXOs was separated into small (<200-basepairs) and large (≥200-basepairs) RNA species, transfected into macrophages, and macrophage IL-6 and TNFα mRNA expression and protein secretion measured.

Cytochrome P450 2E1-dependent hepatic ethanol metabolism induces fatty acid-binding protein 4 and steatosis.

Background: Hepatic steatosis is an early pathology of alcohol-associated liver disease (ALD). Fatty acid-binding protein-4 (FABP4, a FABP not normally produced in the liver) is secreted by hepatocytes in ALD and stimulates hepatoma proliferation and migration. This study sought to investigate the mechanism[s] by which hepatic ethanol metabolism regulates FABP4 and steatosis.

Hepatic stellate cell-derived exosomes modulate macrophage inflammatory response.

Background: Hepatic stellate cell (HSC) differentiation/activation is central to liver fibrosis and is innately linked to the immune response to liver injury. Exosomes (EXOs) are important means of communication between cell populations. This study sought to characterize EXO release from HSCs and the effect of HSC-EXOs on macrophage cytokine release/function.

Fatty acid binding protein-4 promotes alcohol-dependent hepatosteatosis and hepatocellular carcinoma progression.

Fatty liver disease (hepatosteatosis) is a common early pathology in alcohol-dependent and obese patients. Fatty acid binding protein-4 (FABP4) is normally expressed in adipocytes and macrophages and functions as a regulator of intracellular lipid movement/storage. This study sought to investigate hepatic FABP4 expression and function in alcoholic liver disease (ALD) and hepatocellular carcinoma (HCC).

Drought stress responses in crops.

Among the effects of impending climate change, drought will have a profound impact on crop productivity in the future. Response to drought stress has been studied widely, and the model plant Arabidopsis has guided the studies on crop plants with genome sequence information viz., rice, wheat, maize and sorghum.