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Structure-based identification of HNF4α agonists: Rosmarinic acid as a promising candidate for NAFLD treatment.
Comput Struct Biotechnol J
December 2024
National Vaccine Innovation Platform, Scholl of Pharmacy, Nanjing Medical University, Nanjing 211166, China.
Unlabelled: The prevention and treatment of metabolic disorders, such as non-alcoholic fatty liver disease (NAFLD), have emerged as critical global health challenges. Current lipid-lowering pharmacotherapies are associated with side effects, including hepatotoxicity, rhabdomyolysis, and decreased erythrocyte counts, underscoring the urgent need for safer therapeutic alternatives. Hepatocyte nuclear factor 4α (HNF4α) has been identified as a pivotal regulator of lipid metabolism, making it an attractive target for drug development.
View Article and Find Full Text PDFMotif distribution and DNA methylation underlie distinct Cdx2 binding during development and homeostasis.
Nat Commun
January 2025
Department of Stem Cell Biology and Regenerative Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
Transcription factors guide tissue development by binding to developmental stage-specific targets and establishing an appropriate enhancer landscape. In turn, DNA and chromatin modifications direct the genomic binding of transcription factors. However, how transcription factors navigate chromatin features to selectively bind a small subset of all the possible genomic target loci remains poorly understood.
View Article and Find Full Text PDFTherapeutic insight into the role of nuclear protein HNF4α in liver carcinogenesis.
Adv Protein Chem Struct Biol
January 2025
Department of Bio-Medical Sciences, School of Bio Sciences and Technology, Vellore Institute of Technology (VIT), Vellore, Tamil Nadu, India. Electronic address:
Hepatocyte nuclear factor 4-alpha (HNF4α), a well-preserved member of the nuclear receptor superfamily of transcription factors, is found in the liver. It is recognized as a central controller of gene expression specific to the liver and plays a key role in preserving the liver's homeostasis. Irregular expression of HNF4α is increasingly recognized as a crucial factor in the proliferation, cell death, invasiveness, loss of specialized functions, and metastasis of cancer cells.
View Article and Find Full Text PDFElafibranor: A promising therapeutic approach for liver fibrosis and gut barrier dysfunction in alcohol-associated liver disease.
World J Gastroenterol
January 2025
Department of Biochemistry, School of Medicine, College of Medicine, China Medical University, Taichung 404328, Taiwan.
This article discusses the recent study written by Koizumi . Alcohol-associated liver disease (ALD) is a major cause of liver-related morbidity and mortality, which is driven by complex mechanisms, including lipid accumulation, apoptosis, and inflammatory responses exacerbated by gut barrier dysfunction. The study explored the therapeutic potential of elafibranor, a dual peroxisome proliferator-activated receptor alpha/delta agonist.
View Article and Find Full Text PDFDapagliflozin modulates hepatic lipid metabolism through the proprotein convertase subtilisin/kexin type 9/low density lipoprotein receptor pathway.
Diabetes Obes Metab
January 2025
The Second Affiliated Hospital, Zhengzhou University, Zhengzhou, China.
Background: Proprotein convertase subtilisin/kexin type 9 (PCSK9) is mainly secreted by the liver, and plays a crucial role in lipid metabolism disorder. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) can regulate lipid metabolism through various pathways, including reducing visceral fat accumulation, modulating serum lipoprotein levels and alleviating hepatic steatosis. However, the specific regulatory mechanisms remain unclear.
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