Study on the mechanism of cholic acid derivatives in traditional Chinese medicine based on the regulation of gene expression

Objective:To investigate the pharmacological action and mechanism of cholic acid derivatives in traditional Chinese medicine(TCM)based on the regulation of gene expression.Methods:Genome-wide gene expression profiles of Michigan Cancer Foundation-7(MCF-7)cells treated with or without 4 cholic acid derivatives were detected by gene chip technology.Similarities in upregulated and downregulated genes were analyzed using the Connectivity Map(CMap)database.The affinity between cholic acid derivatives and the potential target was confirmed by molecular docking.The cholic acid derivative-regulated pathway enrichment analysis was performed by the STRING database,and the potential pathway was confirmed by in vitro experiments on MD Anderson-Metastatic Breast-231(MDA-MB-231)cells.Results:Compared with the reference genome in the CMap database,the gene expression profiles of cholic acid derivatives were similar to those of antipsychotic,anticancer,anti-inflammatory,and antiinfective drugs.Among them,4 derivatives were associated with antianxiety drugs,and molecular docking results showed that these compounds may act by binding to the ligand-binding site of gammaaminobutyric acid(GABA)receptors.Moreover,the cytoskeletal pathway is one of the pathways enriched in the derivatives.Of them,ursodeoxycholic acid showed significant inhibitory activity on the cytoskeleton formation of MDA-MB-231 cells.Conclusion:The gene expression detection method,combined with CMap and pathway enrichment analysis,could be used to study the mechanism of the active ingredients of TCM.In addition,our research showed that cholic acid derivatives have a potential affinity for membrane receptors,where they can exert anxiolytic activity by modulating opioid receptor,GABA receptor,and dopamine receptor.Moreover,ursodeoxycholic and chenodeoxycholic acid inhibit cytoskeleton formation,probably by acting on membrane proteins to activate the corresponding cytoskeletal pathways.

Cross-sectional Seroprevalence and Genotype of Hepatitis E Virus in Humans and Swine in a High-density Pig-farming Area in Central China

Hepatitis E virus(HEV)infection is a common public health problem in developing countries.However,the current prevalence of HEV and the relationship of HEV genotype between swine and human within high-density pig-farming areas in central China are still inadequately understood.Here,cross-sectional serological and genotypic surveys of HEV among the 1232 general population,273 workers occupationally exposed to swine,and 276 pigs in a high-density pig-breeding area,were undertaken by ELISA and nested RT-PCR methods.Anti-HEV IgG was detected in 26.22%of general population and 48.35%of occupational workers.The prevalence of swine serum HEV-Ag was 6.52%.The prevalence of anti-HEV IgG was significantly higher among the workers occupationally exposed to swine than among the general population.An increased HEV seropositivity risk among the general population was associated with either being a peasant or male and was very strongly associated with the increase of age.Among the occupationally exposed group,the prevalence of anti-HEV IgG antibodies increased with age and working years.Among the 30 HEV-IgM-positive people,the infection rates of clerks in the public,peasants,pork retailers,and pig farmers were higher than those of others.A phylogenetic analysis revealed that all the isolates belonged to subgenotype 4d,and four people and four pigs shared 97.04%-100%sequence homology.This study revealed a high HEV seroprevalence among the general population and workers occupationally exposed to swine in the Anlu City,and supports the notion that swine are a source of human HEV infection.

Discovery of a natural fluorescent probe targeting the Plasmodium falciparum cysteine protease falcipain-2

The Plasmodium falciparum cysteine protease falcipain-2(FP-2) is an attractive antimalarial target. Here, we discovered that the natural compound NP1024 is a nonpeptidic inhibitor of FP-2 with an IC50 value of 0.44 μmol L–1. The most exciting finding is that both in vitro and in vivo, NP1024 directly targets FP-2 in malaria parasite-infected erythrocytes as a natural fluorescent probe, thereby paving the way for an integration of malaria diagnosis and treatment.