Identification of Novel Therapeutic Targets for MAFLD Based on Bioinformatics Analysis Combined with Mendelian Randomization DOI Open Access

Jia-Lin Ren,

Min Wu

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(7), С. 3166 - 3166

Опубликована: Март 29, 2025

Metabolic-associated fatty liver disease (MAFLD) is a chronic condition with limited therapeutic options. To identify novel drug targets, we integrated bioinformatics, Mendelian randomization (MR), and colocalization analyses. Using the Gene Expression Omnibus (GEO) database, identified differentially expressed genes constructed protein–protein interaction (PPI) networks, pinpointing 10 hub genes. MR analyses revealed that Ubiquitin-like PHD ring finger domains 1 (UHRF1) causally associated MAFLD driven by same causal variant locus, suggesting its potential as target. Molecular docking disogenin candidate small-molecule targeting UHRF1. Drug affinity responsive target stability (DARTS) assays confirmed direct binding between UHRF1 disogenin. In vitro, significantly reduced mRNA protein levels induced free acids (FFA) in AML12 HepG2 cells, accompanied decreased cellular total cholesterol (TC) triglyceride (TG) levels. vivo, administration alleviated hepatic lipid accumulation, inflammation, fibrosis methionine/choline-deficient (MCD)-diet-fed mice. This study identifies promising for validates agent, providing foundation further investigation.

Язык: Английский

Dual Modulator of FXR and HSD17B13: Revitalizing FXR Therapies in MASH DOI
Changhong Wei,

Yun Liu,

Zhiming Yan

и другие.

Journal of Medicinal Chemistry, Год журнала: 2025, Номер unknown

Опубликована: Март 5, 2025

Dual modulation of FXR and HSD17B13 presents a promising strategy for treating metabolic dysfunction-associated fatty liver disease (MAFLD) steatohepatitis (MASH). Compound 6, groundbreaking dual modulator HSD17B13, validates the concept significantly enhancing function, reducing inflammation fibrosis across various MAFLD models.

Язык: Английский

Процитировано

0
Identification of Novel Therapeutic Targets for MAFLD Based on Bioinformatics Analysis Combined with Mendelian Randomization DOI Open Access

Jia-Lin Ren,

Min Wu

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(7), С. 3166 - 3166

Опубликована: Март 29, 2025

Metabolic-associated fatty liver disease (MAFLD) is a chronic condition with limited therapeutic options. To identify novel drug targets, we integrated bioinformatics, Mendelian randomization (MR), and colocalization analyses. Using the Gene Expression Omnibus (GEO) database, identified differentially expressed genes constructed protein–protein interaction (PPI) networks, pinpointing 10 hub genes. MR analyses revealed that Ubiquitin-like PHD ring finger domains 1 (UHRF1) causally associated MAFLD driven by same causal variant locus, suggesting its potential as target. Molecular docking disogenin candidate small-molecule targeting UHRF1. Drug affinity responsive target stability (DARTS) assays confirmed direct binding between UHRF1 disogenin. In vitro, significantly reduced mRNA protein levels induced free acids (FFA) in AML12 HepG2 cells, accompanied decreased cellular total cholesterol (TC) triglyceride (TG) levels. vivo, administration alleviated hepatic lipid accumulation, inflammation, fibrosis methionine/choline-deficient (MCD)-diet-fed mice. This study identifies promising for validates agent, providing foundation further investigation.

Язык: Английский

Процитировано

0