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Hepatocyte nuclear factor 1alpha (HNF1alpha) is a homeodomain transcription factor that is central to co-ordinated differentiation of a number of cell lineages, including hepatocytes in the liver and islet cells in the pancreas. HNF1alpha interacts directly with other transcription factors and co-factors and is involved in chromatin modification to alter gene expression. To further investigate the pivotal role of HNF1alpha in transcriptional control pathways we utilized RNA interference. An siRNA oligonucleotide specific for HNF1alpha reduced HNF1alpha protein levels by up to 70% in transient transfections of Caco2 cells. The same sequence incorporated into an shRNAi reduced protein levels by up to 90% in stable transfections. Microarray analysis of RNA from cell lines with stable RNAi-mediated down-regulation of HNF1alpha, identified genes known to be regulated by this transcription factor and also novel genes.
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http://dx.doi.org/10.1016/j.bbagrm.2008.03.002 | DOI Listing |
Biochem Pharmacol
September 2025
Pharmacy College of Shihezi University/Key Laboratory of Xinjiang Phytomedicine Resource and Utilization, Ministry of Education/Institute for Safflower Industry Research of Shihezi University, Shihezi University, North 4th Road 221, Shihezi, China. Electronic address:
The etiology of alcoholic fatty liver (AFL) is complex, representing the early reversible stage of alcohol-associated liver disease (ALD). Alleviating oxidative stress, reducing inflammation, and preventing the development of liver fibrosis are considered the most effective strategies for treating AFL. Consequently, we selected isoliquiritigenin (ISL), a flavonoid compound recognized for its anti-inflammatory, antioxidant, and anticancer pharmacological properties.
View Article and Find Full Text PDFPLoS Pathog
September 2025
State Key Laboratory of Breeding Biotechnology and Sustainable Aquaculture, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, China.
Hepatocyte nuclear factor 4 alpha (Hnf4α), a conserved nuclear receptor central to vertebrate liver development and metabolic regulation, emerges here as a pivotal immune regulator in teleosts against complex infectious threats. While its metabolic roles are well-established, Hnf4α's function in bacterial infection, viral infection, and bacterial-viral coinfection-major challenges in global aquaculture-remained uncharacterized. This study reveals that teleost Hnf4α acts as a dual-functional immune checkpoint, essential for combating Aeromonas salmonicida, grass carp reovirus (GCRV), and their coinfection.
View Article and Find Full Text PDFAm J Physiol Cell Physiol
September 2025
Institute of Pharmacology and Toxicology, Goethe University Frankfurt, Frankfurt, Germany.
The A20 binding inhibitor of nuclear factor-kappa B (NF-κB)-1 (ABIN-1) serves as a ubiquitin sensor and autophagy receptor, crucial for modulating inflammation and cell death. Our previous in vitro investigation identified the LC3-interacting region (LIR) motifs 1 and 2 of ABIN-1 as key mitophagy regulators. This study aimed to explore the in vivo biological significance of ABIN1-LIR domains using a novel CRISPR-engineered ABIN1-ΔLIR1/2 mouse model, which lacks both LIR motifs.
View Article and Find Full Text PDFAdv Sci (Weinh)
September 2025
China-New Zealand Joint Laboratory on Biomedicine and Health, State Key Laboratory of Immune Response and Immunotherapy, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, GIBH-HKU Guangdong-Hong Kong Stem Cell and Regenerative Medicine Research Centre, GIBH-CUHK Joint Resea
TP53 mutations are highly associated with hepatocellular carcinoma (HCC), a common and deadly cancer. However, few primary drivers in the progression of HCC with mutant TP53 have been identified. To uncover tumor suppressors in human HCC, a genome-wide CRISPR/Cas9-based screening of primary human hepatocytes with MYC and TP53 overexpression (MT-PHHs) is performed in xenografts.
View Article and Find Full Text PDFDrug Dev Res
September 2025
Department of Pharmaceutics, School of Pharmacy, Center for Nano Drug/Gene Delivery and Tissue Engineering, Jiangsu Provincial Research Center for Medicinal Function Development of New Food Resources, Jiangsu University, Zhenjiang, Jiangsu, China.
Liver cancer is the fourth most deadly cancer worldwide, but existing treatment options are insufficient, thus highlighting the urgent need for new therapeutic agents. Taxanes, known for their anticancer properties, provide a promising avenue for intervention. In this study, a tetracyclic taxane compound with antitumor activity (taxinine) was extracted and isolated from Taxus chinensis (T.
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