[Research progress of the regulation of orphan nuclear receptors on chronic liver diseases].

The development of chronic liver disease can be promoted by excessive fat accumulation, dysbiosis, viral infections and persistent inflammatory responses, which can lead to liver inflammation, fibrosis and carcinogenesis. An in-depth understanding of the etiology leading to chronic liver disease and the underlying mechanisms influencing its development can help identify potential therapeutic targets for targeted treatment. Orphan nuclear receptors (ONRs) are receptors that have no corresponding endogenous ligands to bind to them. The study of these ONRs and their biological properties has facilitated the development of synthetic ligands, which are important for investigating the effective targets for the treatment of a wide range of diseases. In recent years, it has been found that ONRs are essential for maintaining normal liver function and their dysfunction can affect a variety of liver diseases. ONRs can influence pathophysiological activities such as liver lipid metabolism, inflammatory response and cancer cell proliferation by regulating hormones/transcription factors and affecting the biological clock, oxidative stress, etc. This review focuses on the regulation of ONRs, mainly including retinoid related orphan nuclear receptors (RORs), pregnane X receptor (PXR), leukocyte cell derived chemotaxin 2 (LECT2), Nur77, and hepatocyte nuclear factor 4α (HNF4α), on the development of different types of chronic liver diseases in different ways, in order to provide useful references for the therapeutic strategies of chronic liver diseases based on the regulation of ONRs.

[Effects of plumbagin on expression of TNF-alpha and PDGF-BB in human hepatic stellate cells activated by leptin].

OBJECTIVE: To investigate the effect of plumbagin on the expression of TNF-alpha and PDGF-BB in human hepatic stellate cells (HSC-LX2) activated by Leptin. METHODS: HSC-LX2 were cultured in vitro and stimulated by Leptin for 24 hours then treated with different concentrations of plumbagin for 24 hours, the expressions of TNF-alpha mRNA and PDGF-BB mRNA were determined by Realtime quantitative PCR, the protein expressions of TNF-alpha and PDGF-BB were determined-by Western blotting. RESULTS: The expressions of TNF-alpha mRNA and PDGF-BB mRNA of treatment groups were significantly reduced, especially in high dose group (P < 0.01), and Western blotting analyses revealed similar trends in protein expression. CONCLUSION: Plumbagin may prevent the formation of hepatic fibrosis and its mechanism may be related to decreasing the level of mRNA of TNF-alpha and PDGF-BB and the protein of PDGF-BB.