Immunological mechanisms and emerging therapeutic targets in alcohol-associated liver disease DOI Creative Commons
Haiyuan Shen, Suthat Liangpunsakul, Yasuko Iwakiri

et al.

Cellular and Molecular Immunology, Journal Year: 2025, Volume and Issue: unknown

Published: May 21, 2025

Abstract Alcohol-associated liver disease (ALD) is a major global health challenge, with inflammation playing central role in its progression. As emerges as critical therapeutic target, ongoing research aims to unravel underlying mechanisms. This review explores the immunological pathways of ALD, highlighting roles immune cells and their inflammatory mediators onset We also examine complex interactions between non-parenchymal cells, well crosstalk extra-hepatic organs, including gut, adipose tissue, nervous system. Furthermore, we summarize current clinical on anti-inflammatory therapies discuss promising targets. Given heterogeneity ALD-associated inflammation, emphasize need for precision medicine optimize treatment strategies improve patient outcomes.

Language: Английский

p38γ modulates ferroptosis in brain injury caused by ethanol and cerebral ischemia/reperfusion by regulating the p53/SLC7A11 signaling pathway DOI Creative Commons
Xingyu Zhu, Zhihan Zhao, Yan Zhang

et al.

Cellular Signalling, Journal Year: 2025, Volume and Issue: unknown, P. 111728 - 111728

Published: March 1, 2025

Ischemic stroke, a neurological condition with complicated etiology that is accompanied by severe inflammation and oxidative stress, ethanol (EtOH) may aggravate ischemia/reperfusion (I/R)-induced brain damage. However, the effect of prolonged alcohol intake on acute injury remains ambiguous. As part mitogen-activated protein kinase (MAPK) family, p38γ involved in ferroptosis various diseases. This study explored how effects chronic EtOH consumption caused cerebral I/R. Brain damage was induced mice via administration liquid alcohol-containing diet for 8 weeks, middle artery occlusion reperfusion (MCAO/R), or combination both. We verified significantly exacerbated MCAO/R-induced damage, inflammation. Notably, levels were increased experimental mouse cell models. knockdown markedly attenuated tissue inflammatory infiltration + MCAO/R-treated mice. Mechanistic experiments revealed regulate through p53/SLC7A11 pathway. Overall, our results indicate crucial regulating EtOH- I/R-induced modulating

Language: Английский

Citations

0
Myeloid-derived MANF ameliorates ethanol-induced liver injury by enhancing microRNA-223 expression DOI

Huiyuan Xie,

Ping Zhang,

Shanru Yang

et al.

Journal of Gastroenterology, Journal Year: 2025, Volume and Issue: unknown

Published: March 20, 2025

Language: Английский

Citations

0
Opposite regulation of intestinal and intrahepatic CD8+T cells controls alcohol-associated liver disease progression DOI
Luca Maccioni,

Yukun Guan,

Mariia Kim

et al.

Gut, Journal Year: 2025, Volume and Issue: unknown, P. gutjnl - 334412

Published: April 8, 2025

Background Gut-liver crosstalk plays an important role in alcohol-associated liver disease (ALD) pathogenesis; but underlying mechanisms remain obscure. Objective We examined the regulation of intestinal and intrahepatic CD8 + T lymphocytes their contribution to ALD. Design ALD patients were recruited for evaluation cells. Single-cell RNA sequencing (scRNA seq) was performed analyse peripheral cells Wildtype, CD8-specific Bcl2 transgenic ( Cd8 Bcl-2 ), −/− mice subjected chronic-plus-binge ethanol feeding. Results In patients, duodenal selectively reduced negatively correlated with injury bacterial translocation markers, while markedly increased. ScRNA seq analysis patient livers revealed several populations expressing activation survival genes (eg, ). Transcriptomics functional studies a key prosurvival BCL2 this opposite Mechanistically, feeding specifically duodenum where levels are high. Inducing reversed ethanol-induced loss cells, improved gut barrier function ameliorated ALD, deficiency linked enhanced neutrophil macrophage infiltration liver, exacerbating mice. Conclusions is associated elevation which aggravates ameliorates respectively. Restoration functions may represent novel therapeutic strategy patients.

Language: Английский

Citations

0
Phytochemicals Targeting Inflammatory Pathways in Alcohol-Induced Liver Disease: A Mechanistic Review DOI Creative Commons

Swati Tirunal Achary,

Prerna Gupta,

Ali H. Rajput

et al.

Pharmaceuticals, Journal Year: 2025, Volume and Issue: 18(5), P. 710 - 710

Published: May 11, 2025

Alcoholic beverages play a significant role in social engagement worldwide. Excessive alcohol causes variety of health complications. Alcohol-induced liver disease (ALD) is responsible for the bulk linked fatalities. The activation immune mechanisms has crucial developing ALD. No effective medication promotes function, shields from harm, or aids hepatic cell regeneration. Alcohol withdrawal one most beneficial therapies ALD patients, which improves patient’s chances survival. There demand safe and reasonably priced approaches to treating it. Exploring naturally derived phytochemicals been fascinating path, it drawn attention recent years modulators inflammatory pathways prevention management In this review, we have discussed roles various ALD, highlighting importance intestinal barrier integrity gut microbiota, as well cells inflammation, other pathways, including cGAS-STING, NLRP3, MAPK, JAK-STAT, NF-kB. Further, review also outlines possible targeting these safeguard alcohol-induced injury. We highlighted that immunological using herbal medicine may find place counteract Preclinical vitro vivo investigations shown promising results; nonetheless, more extensive work required properly understand compounds’ action. Clinical are very transferring laboratory knowledge into patient therapy.

Language: Английский

Citations

0
Immunological mechanisms and emerging therapeutic targets in alcohol-associated liver disease DOI Creative Commons
Haiyuan Shen, Suthat Liangpunsakul, Yasuko Iwakiri

et al.

Cellular and Molecular Immunology, Journal Year: 2025, Volume and Issue: unknown

Published: May 21, 2025

Abstract Alcohol-associated liver disease (ALD) is a major global health challenge, with inflammation playing central role in its progression. As emerges as critical therapeutic target, ongoing research aims to unravel underlying mechanisms. This review explores the immunological pathways of ALD, highlighting roles immune cells and their inflammatory mediators onset We also examine complex interactions between non-parenchymal cells, well crosstalk extra-hepatic organs, including gut, adipose tissue, nervous system. Furthermore, we summarize current clinical on anti-inflammatory therapies discuss promising targets. Given heterogeneity ALD-associated inflammation, emphasize need for precision medicine optimize treatment strategies improve patient outcomes.

Language: Английский

Citations

0