Publications by authors named "Jeeval Mehta"
Article Synopsis
- Severe alcohol-associated hepatitis (AH) is a serious liver disease characterized by increased neutrophil infiltration, but the impact of alcohol on neutrophil function is still not fully understood.
- Researchers discovered that Bruton's tyrosine kinase (BTK) is elevated in neutrophils of AH patients and is activated by alcohol through TLR4 signaling, linked to liver damage.
- In mouse models, inhibiting BTK or knocking it out in specific immune cells reduced neutrophil activity and damage to the liver, suggesting that targeting BTK and its interaction with CD84 might offer new treatments for AH.
Binge drinking in obese patients positively correlates with accelerated liver damage and liver-related death. However, the underlying mechanism and the effect of alcohol use on the progression of metabolic-dysfunction-associated steatotic liver disease (MASLD) remain unexplored. Here, we show that short-term feeding of a metabolic-dysfunction-associated steatohepatitis (MASH) diet plus daily acute alcohol binges for three days induce liver injury and activation of the NLRP3 inflammasome.
View Article and Find Full Text PDFObjective: Alcohol use in metabolic dysfunction-associated steatohepatitis (MASH) is associated with an increased risk of fibrosis and liver-related death. Here, we aimed to identify a mechanism through which repeated alcohol binges exacerbate liver injury in a high fat-cholesterol-sugar diet (MASH diet)-induced model of MASH.
Design: C57BL/6 mice received either chow or the MASH diet for 3 months with or without weekly alcohol binges.
Article Synopsis
- Chronic liver injury from cholestasis leads to significant tissue damage, fibrosis, and kidney complications; IRF3 plays a key role in regulating inflammation and cell death in this process.
- In studies with patients and mice models of cholestasis, increased phosphorylation of IRF3 was linked to higher tissue damage in the liver and kidneys, while IRF3 knockout mice showed reduced damage and inflammation.
- The study highlights a potential mechanism where bile acids activate IRF3, which then upregulates ZBP1, suggesting that the IRF3-ZBP1 pathway could be crucial in understanding and addressing cholestatic liver and kidney injuries.
Background & Aims: Various intracellular pathways regulate inflammation in NASH. Cyclic GMP-AMP synthase (cGAS) is a DNA sensor that activates STING and plays a role in inflammatory diseases. Here, we explored the role of cGAS in hepatic damage, steatosis, inflammation, and liver fibrosis in mouse models of NASH.
View Article and Find Full Text PDFArticle Synopsis
- Kupffer cells and macrophage activation contribute to liver issues in alcoholic liver disease (ALD), leading to fat buildup, inflammation, and fibrosis, with increased MØ and T cells observed in patients.* -
- The study tested the dual CCR2/5 inhibitor, cenicriviroc (CVC), in a mouse model and found it effectively reduced liver injury and fat buildup related to alcohol consumption, whether given preventively or as treatment.* -
- CVC also normalized markers of liver fibrosis and inflammation, increased T-cell numbers, and prevented harmful effects on liver cells, suggesting it may be a potential treatment for ALD.*