LIX1L aggravates MASH-HCC progression by reprogramming of hepatic metabolism and microenvironment via CD36.

Limb expression 1-like protein (LIX1L) is an essential player in liver disorders, but its function in metabolic dysfunction-associated steatohepatitis (MASH) and associated hepatocellular carcinoma (HCC) progression remains obscure. Here, we identify LIX1L as a key integrative regulator linking lipid metabolism and inflammation, adipose tissue and hepatic microenvironment, which promotes MASH progression. LIX1L significantly upregulates in MASH patients, mouse models, and palmitic acid-stimulated hepatocytes.

Lefamulin Overcomes Acquired Drug Resistance via Regulating Mitochondrial Homeostasis by Targeting ILF3 in Hepatocellular Carcinoma.

Acquired resistance represents a critical clinical challenge to molecular targeted therapies such as tyrosine kinase inhibitors (TKIs) treatment in hepatocellular carcinoma (HCC). Therefore, it is urgent to explore new mechanisms and therapeutics that can overcome or delay resistance. Here, a US Food and Drug Administration (FDA)-approved pleuromutilin antibiotic is identified that overcomes sorafenib resistance in HCC cell lines, cell line-derived xenograft (CDX) and hydrodynamic injection mouse models.

TKF, a mexicanolide-type limonoid derivative, suppressed hepatic stellate cells activation and liver fibrosis through inhibition of the YAP/Notch3 pathway.

Background: Liver fibrosis is a common scarring response and may ultimately lead to liver cancer, unfortunately, there is currently no effective antifibrotic drug approved for human use. Limonoids exhibit a broad spectrum of biological activities; however, the potential role of limonoids against fibrosis is largely unknown.

Purpose: This study investigates the antifibrotic activities and potential mechanisms of TKF (3-tigloyl-khasenegasin F), a natural mexicanolide-type limonoid derivative.