Mapping alternative splicing events in colorectal cancer.

Although aberrant splicing events of genes are closely related to the development and progression of colorectal cancer (CRC), the mapping of abnormal splicing events, especially alternative splicing (AS) event types and the underlying effects, remain investigational. In the present study, we analyzed a public RNA-seq database (GSE138202) and identified 14,314 significant AS events in CRC patients compared to healthy individuals. Most of the key genes such as oncogenes involved in the development of CRC have different AS event types.

Inhibition of ACOX1 enhances the therapeutic efficacy of obeticholic acid in treating non-alcoholic fatty liver disease and mitigates its lipotoxicity.

Background And Aims: High-dose Obeticholic acid exhibits promise for non-alcoholic fatty liver disease (NAFLD) treatment but can induce lipotoxicity. Our study sought to understand this mechanism and propose a solution.

Approach And Results: In a non-alcoholic fatty liver disease (NAFLD) model induced by a high-fat diet in FXR mice, we pinpointed that FXR regulated the expression of ACOX1 through RNA-Seq analysis.

Research progress on the mechanism of cholesterol-25-hydroxylase in intestinal immunity.

Inflammatory bowel disease (IBD), a general term encompassing Crohn's disease (CD) and ulcerative colitis (UC), and other conditions, is a chronic and relapsing autoimmune disease that can occur in any part of the digestive tract. While the cause of IBD remains unclear, it is acknowledged that the disease has much to do with the dysregulation of intestinal immunity. In the intestinal immune regulatory system, Cholesterol-25-hydroxylase (CH25H) plays an important role in regulating the function of immune cells and lipid metabolism through catalyzing the oxidation of cholesterol into 25-hydroxycholesterol (25-HC).

Obeticholic Acid Induces Hepatoxicity Via FXR in the NAFLD Mice.

Obeticholic acid (OCA), a potent farnesoid X receptor (FXR) agonist, is a promising drug for nonalcoholic fatty liver disease (NAFLD); however, it can cause liver injury, especially at high doses. Here, we investigated the role of FXR in the high-dose OCA-induced hepatoxicity in the condition of the NAFLD mouse model. Wild-type (WT) mice and FXR mice were administered with over-dose OCA (0.

Obeticholic acid inhibits hepatic fatty acid uptake independent of FXR in mouse.

Objective: Obeticholic acid (OCA), a farnesoid X receptor (FXR) agonist, is believed to alleviate nonalcoholic fatty liver disease (NAFLD) by decreasing hepatic lipogenesis in an FXR-dependent manner. Here, we revealed a novel mechanism by which OCA improves NAFLD by affecting hepatic long-chain fatty acids (LCFAs) uptake.

Methods: Stably transfected HEK-293 cells expressing fatty acid transport protein 5 (FATP5) were established to examine fatty acid uptake; FXR, human (h) FATP5, and FXR/hFATP5 mouse models were incorporated to explore the effects of OCA on FATP5 ex vivo and in vivo.