Mechanistic study of Hederagenin against liver injury by inhibiting AIM2-mediated PANoptosis via the JAK2/STAT3 signaling pathway.

Myricetin alleviates hepatic ischemia-reperfusion injury in mice by inhibiting the inflammatory response and ferroptosis through farnesoid X receptor (FXR).

USP15 regulates TRIM21/GSDMD pathway to affect lipopolysaccharide-induced acute liver injury.

Metformin is associated with the suppression of the TNF-α/iNOS/TIMP-1 axis-mediated liver injury and fibrosis secondary to diabetes.

Pasteurella multocida causes liver pyroptosis in broilers through the MAPK-NLRP3-GSDMD signaling pathway.

Intestinal epithelial peroxisome proliferator-activated receptor γ deficiency exacerbates insulin resistance in mice with metabolic dysfunction-associated steatohepatitis.

Heat stroke causes life-threatening liver injury, but its molecular basis remains poorly understood. We investigated whether ALKBH5-mediated N6-methyladenosine (m6A) demethylation stabilizes Hmgb1 transcripts and promotes hepatocyte pyroptosis through the NLRP3 inflammasome. We also developed mesenchymal stem cell membrane-coated glycyrrhizic acid liposomes (MMGLs) as a targeted therapeutic strategy. RNA-seq of HS rat livers revealed significant enrichment of pyroptosis pathways, with ALKBH5 identified as a hub gene. Mechanistically, heat stress upregulated ALKBH5, which demethylated HMGB1 mRNA, preventing its degradation and enhancing transcript stability. This stabilization led to increased intracellular High-mobility group box 1 (HMGB1) abundance, nucleocytoplasmic translocation, and extracellular release, subsequently activating the NLRP3-Caspase-1-GSDMD axis. Alkbh5 knockdown shortened Hmgb1 half-life and attenuated pyroptosis, whereas HMGB1 supplementation restored it. To target this axis, we engineered MMGLs (encapsulation efficiency: 81.7%), which exhibited superior inflammatory homing compared to unmodified liposomes. In HS rats, MMGLs achieved rapid hepatic accumulation, significantly reduced serum alanine aminotransferase/aspartate aminotransferase, and suppressed Interleukin-1 beta (IL-1β)/IL-18. MMGLs restored redox homeostasis by decreasing reactive oxygen species/malondialdehyde and boosting reduced glutathione/superoxide dismutase, thereby preserving hepatocyte architecture and inhibiting pyroptosis. This study identifies an epitranscriptomic mechanism in HS-induced liver injury, in which ALKBH5-dependent stabilization of Hmgb1 mRNA amplifies pyroptotic signaling. MMGLs provide a biomimetic nanotherapeutic strategy to interrupt this inflammatory cascade. ALKBH5-mediated m6A demethylation stabilizes HMGB1 to drive hepatocyte pyroptosis during HS. MMGLs effectively target this axis, offering a promising therapeutic approach for acute liver damage. Antioxid. Redox Signal. 45, 173-197.

CRISPR screen identifies MAP2K3 as a key target for oleuropein to alleviate deoxynivalenol-induced hepatic injury.

Yakuchinone A alleviates hepatic ischemia-reperfusion injury in aging livers via the SESN2/AKT1/NRF2 pathway.

Ergothioneine alleviates hepatic steatosis by modulating PCYT2 to restore the phosphatidylethanolamine-ACOT8 homeostasis.

Optimizing clofibrate with eugenol contributes a novel hypolipidemic agent with minimal liver injury.

Resveratrol and tomato pectin synergistically ameliorated metabolic disorder in high-fat-diet mice through the microbiota-gut-liver axis.

Magnesium isoglycyrrhizinate ameliorates ceritinib-induced hepatotoxicity by restoring mitochondrial homeostasis.

Genistein combined with aerobic exercise protects against alcoholic liver injury through PI3K/AKT/GSK3β signaling.

Fisetin promotes liver regeneration by inducing β-catenin-mediated inhibition of p53 and suppression of TGF-β.

Syringaldehyde attenuates deltamethrin-induced hepatic tissue injury by modulating oxidative stress, inflammation, and apoptosis via the Nrf2/HO-1 pathway.

Application of HepaRG mono- and HepaRG:THP-1 cocultures as immune responsive hepatotoxicity models.

Coassembling a fluorescent probe with liver-targeted lipid nanoparticles for precise diagnosis of drug-induced liver injury

Rougan Granules ameliorates liver fibrosis through autophagy regulation: Insights from HPLC-Q-TOF-MS/MS, network pharmacology, and experimental validation.

Development of an analytical method for simultaneous determination of 38 bile acids and its application in studying the mechanism of WuZhi Pian against rifampicin-induced liver injury