Researchers from Medizinische Hochschule Hannover and collaborators thus aimed to elucidate signaling adaptations following MAPK pathway inhibition in BRAFV 600E mutant cholangiocarcinoma (CCA) by generating a BRAF V600E-driven model of CCA.

Liraglutide, a glucagon-like peptide 1 (GLP-1) receptor agonist used in diabetes and obesity, could alleviate depression through a pathway that does not depend on the GLP-1 receptor but instead on the gut microbiota, since the treatment increases the presence of the bacterium Lactobacillus delbrueckii. This symbiotic microorganism produces a lipid that modulates neuronal activity, normalizing the hyperactivation of brain regions in mice involved in emotional processing, which ultimately reduces depressive behaviors.

Researchers from Beijing University of Chinese Medicine described the role of TRIM54 in cirrhosis progression using two independent animal models of chronic liver injury – a DEN-induced rat model and a CCl4-induced mouse model of liver cirrhosis.

Extracellular matrix specialist Engitix Ltd. is teaming up with GSK plc to delve into the mechanisms underlying regression of fibrosis after treatment for chronic liver disease, and identify and validate new drug targets involved in this process.

Researchers from Rectify Pharmaceuticals Inc. presented preclinical efficacy data on RTY-406, a novel dual-acting ABCB4/MDR3 and ABCB11/BSEP modulator, in animal models of primary sclerosing cholangitis.

Genome-wide association studies (GWAS) have identified multiple loci associated with complex diseases, but these are mostly on regulatory genes in the non-coding part of the genome and it has proved difficult to identify the effector genes that they control. Now, researchers in the U.K. have shown how single cell sequencing at scale can be used to precisely link non-coding GWAS loci to specific protein coding genes and cell types.

The microbiome and a frontline innate antimicrobial sensor, Toll-like receptor 5 (TLR5), play an essential role in the development of idiopathic pulmonary fibrosis (IPF). A scientific collaboration led by researchers at the National Institute of Environmental Health Sciences has revealed how TLR5 protects against fibrosis through its ability to modulate the lung microbiome. Their study also shows that activating TLR5 protects against fibrosis and corrects pulmonary dysbiosis.

Transforming growth factor-β-activated kinase 1 (TAK1) is a crucial central signaling molecule of hepatic cell death, inflammation and fibrogenesis through NF-κB and MAPK in metabolic dysfunction-associated steatotic liver disease (MASLD). Its pharmacological inhibition using the TAK1 inhibitor HS-276 was tested in vivo in a murine model of diet-induced MASLD.

There is a growing consensus that alcohol-related liver disease (ALD) should be considered a metabolic disorder under the influence of the gut-liver axis. Metabolome data have highlighted fatty acid-activated G protein-coupled receptors (GPCRs) as the main affected pathways, where the relationship of G-protein-coupled receptor 119 (GPR119) with ALD remains unexplored.

Adipose triglyceride lipase (ATGL), a central mediator of triglyceride hydrolysis and fatty acid mobilization, modulates hepatic lipid homeostasis and metabolic signaling pathways that contribute to the activation of fibrogenic responses.