Abstract:There are no specific ways to prevent and cure human cytomegalovirus (HCMV) infection to date. We investigate the effect and mechanism of baicalein (BAI) and genistein (GEN) used as a drug to inhibit HCMV infection in human astrocyte(AS). RT-qPCR was used to detect the expression changes of viral IE1,IE2 genes. Chromatin immunoprecipitation assay (ChIP) was used to detect the expression change of major immediate early promoter (MIEP). RT-qPCR results showed that compared with HCMV group, 20 μmol/L BAI+HCMV,HCMV+BAI group, and 10 μmol/L GEN+HCMV,HCMV+GEN group can down-regulate the IE1,IE2 genes expressions. ChIP results showed that compared with HCMV group, 20 μmol/L BAI+HCMV,HCMV+BAI group, and 10 μmol/L GEN+HCMV and HCMV+GEN group can reduce histone acetylation of MIEP. A certain concentration of BAI or GEN can inhibit the human astrocyte's IE1 and IE2 to some extent. The inhibiting mechanism may be that BAI and GEN can decrease the expression of IE1,IE2 genes and also inhibit histone acetylation of MIEP, thus decrease the expression of IE1,IE2 genes, which makes BAI and GEN inhibit viral proliferation.
Bone marrow mesenchymal stem cells(BMSCs) have great potential ability of multi-directional differentiation and reproductive activity. Recent studys have demonstrated that BMSCs can be induced into hepatocyte-like cells. However, the molecular mechanism of hepatocellular differentiation remains unknown. In this study, we investigated the nexus between p38 MAPK and NF-κB signaling pathway in the process of the hepatocellular differentiation. We isolated BMSCs from femurs and tibias of rats. The third generation were divided into three main groups: induction group, inhibition group and negative control group. Hepatic differentiation was induced by 10% fetal bovine serum with hepatocyte growth factor(HGF). The inhibitors of p38 (SB203580) and NF-κB(BAY 11-7082) were added to the differentiation medium for inhibition of signaling molecular activities.Morphological characteristics and transferring function of the differentiated cells were examined by indocyanine green (ICG) uptake assay. Immunohistochemical staining was used to evaluate the protein expression position of NF-кB. And western blot analysis was used to detect the protein expression of several markers, including the specifc markers of hepatocytes(AAT), phosphorylated-p38(p-p38) and NF-кB. NF-кB were observed transferred into nuclear in the induction group. The respective inhibitors inhibited the expressions of NF-кB and p-p38 effectively.Compared to the induction group, expressions of specifc marker, AAT, were decreased visibly in the p38 and NF-κB inhibitor-treated groups. Notably, expression of NF-κB were significantly lowered in the p38 inhibitor-treated group.These data suggest both NF-κB pathway and p38MAPK pathway participate in the hepatocellular differentiation of BMSCs, p38MAPK can affect the regulation of NF-κB to this process of differentiation.
More and more microorganisms have developed drug resistance with the use of antibiotics, and some microorganisms have multi-drug resistance. Therefore, bacterial resistant antibiotic is a serious problem to treating infectious diseases in recent years all over the world. This paper briefly reviews the research progress of bacterial resistance mechanisms all over the world, and provides theoretical basis for exploring effective prevention measures and rational use antibiotics in clinical.
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