Реферат
Hepatotoxicity induced by bioactive constituents in traditional Chinese medicines or herbs,such as bavachin(BV)in Fructus Psoraleae,has a prolonged latency to overt drug-induced liver injury in the clinic.Several studies have described BV-induced liver damage and underlying toxicity mechanisms,but little attention has been paid to the deciphering of organisms or cellular responses to BV at no-observed-adverse-effect level,and the underlying molecular mechanisms and specific indicators are also lacking during the asymptomatic phase,making it much harder for early recognition of hepatotoxicity.Here,we treated mice with BV for 7 days and did not detect any abnormalities in biochemical tests,but found subtle steatosis in BV-treated hepatocytes.We then profiled the gene expression of hepatocytes and non-parenchymal cells at single-cell resolution and discovered three types of hepatocyte subsets in the BV-treated liver.Among these,the hepa3 subtype suffered from a vast alteration in lipid metabolism,which was characterized by enhanced expression of apolipoproteins,carboxylesterases,and stearoyl-CoA desaturase 1(Scd1).In particular,increased Scd1 promoted monounsaturated fatty acids(MUFAs)syn-thesis and was considered to be related to BV-induced steatosis and polyunsaturated fatty acids(PUFAs)generation,which participates in the initiation of ferroptosis.Additionally,we demonstrated that mul-tiple intrinsic transcription factors,including Srebf1 and Hnf4a,and extrinsic signals from niche cells may regulate the above-mentioned molecular events in BV-treated hepatocytes.Collectively,our study deciphered the features of hepatocytes in response to BV insult,decoded the underlying molecular mechanisms,and suggested that Scd1 could be a hub molecule for the prediction of hepatotoxicity at an early stage.
Реферат
Objective:To investigate the effect of Huayu Jiedu prescription （HYJDP） on gut microbiota and fecal metabolites in mice with endometriosis. Method:Normal female C57BL/6J mice were divided into normal control group （CO）， endometriosis group （EM） and Chinese medicine Huayu Jiedu decocotion group （CM）. CO and EM groups received normal saline and CM group received HYJDP by intragastric administration. Untargeted metabolomics method was used to detect metabolites in fecal supernatant of mice， and receiver operating characteristic （ROC） analysis was used to screen the differential metabolites， 16S rRNA high-throughput sequencing was used to detect the gut microbiota， and Spearman correlation coefficient was used to represent the degree of correlation between differential metabolites and intestinal flora. Lipopolysaccharides （LPSs） in intestinal wall tissue， serum and peritoneal lavage fluid were detected by enzyme-linked immunosorbent assay （ELISA）. The expression of Vimentin and E-cadherin in ectopic lesions was detected by immunohistochemistry. Result:HYJDP alleviated the disorders of fecal metabolites and gut microbiota in EMS mice， especially with the recovered levels of homoveratric acid， melilotoside C and physapubescin in fecal supernatant. In the comparison of these three factors between EM group and CO group as well as between EM group and CM group， the variable important in projection （VIP） value was both above 2， and AUC in ROC analysis was both >0.9. As compared with EM group， HYJDP restored the abundance of species such as <italic>Lachnospiraceae_NK4A136_group</italic>， <italic>Lactobacillus</italic> and <italic>Blautia </italic>（<italic>P</italic><0.05）. In addition， the level of LPS in peritoneal fluid supernatant of EM group was significantly higher than that of CO group （<italic>P</italic><0.05） and CM group （<italic>P</italic><0.05）. The protein expression of vimentin and E-cadherin in endometriosis decreased significantly （<italic>P</italic><0.05）. Conclusion:HYJDP which can improve the intestinal environment and reduce the level of LPS in mice with endometriosis， is an effective drug for the treatment of endometriosis.