Simvastatin, a semisynthetic derivertive of lovastatin, is an important drug for the treatment of hypercholesteromia, and is traditionally prepared by direct alkylation of lovastatin. Chemical reaction conditons are very rigid, and the final product is difficult to purify, also the pressure of labor protection and environment protection is very high. Recently, with the devolpement in the research of lovastatin biosynthesis, more and more attention has been paid to simvastatin biosynthesis. This paper compared the chemical and biological routes in simvastatin production. Simvastatin could be produced by direct fermentation with combinational biosynthesis method, and could also be synthesized from monacolin J with acyltransferase LovD.
Acyltransferases ; genetics ; metabolism ; Anticholesteremic Agents ; metabolism ; Catalysis ; Escherichia coli ; genetics ; metabolism ; Fermentation ; Lovastatin ; analogs & derivatives ; biosynthesis ; Naphthalenes ; metabolism ; Simvastatin ; metabolism ; Transformation, Bacterial

Objective To study the effect and mechanism of bone marrow mesenchymal stem cells (BMSCs) on autologous peripheral blood lymphocyte proliferation in vitro in patients with hepatitis B virus related decompensated cirrhosis.Methods MSCs were isolated and expanded from human bone marrow blood of nine patients with decompensated cirrhosis,four groups were designed for experiment:①BMSCs + lymphocytes + PHA (contact co-culture) ; ② BMSCs + lymphocytes + PHA (non-contact co-culture) ; ③lymphocytes + PHA (positive control) ; ④lymphocytes alone (negative control).Lymphocytes proliferation rate were detected by flow cytometry.The mRNA expression levels of interleukin-10 (IL-10)and transforming growth factor-β1 (TGF-β1)in BMSCs were detected by using reverse transcription-polymerase chain reaction (RT-PCR).Results Cell proliferation of contact and non-contact co-culture groups significantly declined when compared with that of positive control group (all P ＜ 0.01),The relative expression levels of IL-10 mRNA and TGF-βlmRNA in BMSCs of contact and non-contact co-culture group raised up significantly after culture (all P ＜ 0.01).Besides,there was no significant difference on lymphocyte proliferation rate or expression levels of IL-10mRNA and TGF-β1 mRNA between contact co-culture group and non-contact coculture group (all P ＞ 0.05).Conclusion BMSCs from cirrhotic patients can inhibit proliferation of autologous peripheral blood lymphocytes,the mechanism may be associated with the secretion of inhibitory cytokine IL-10 and TGF-β1 in BMSCs.

ObjectiveTo investigate the feasibility of apical sodium-dependent bile salt transporter (ASBT) and asialoglycoprotein receptor (ASGPR) in the design of oral liver-targeting preparations for the treatment of hepatic alveolar echinococcosis (HAE) by measuring the expression of ASBT and ASGPR. MethodsA total of 18 male Sprague-Dawley rats were selected, among which 10 were used to establish a model of HAE (HAE group) and 8 were used as controls (normal group). Immunofluorescence assay, Western blotting, and quantitative real-time PCR were used to measure the expression distribution, protein expression level, and mRNA expression level of ASBT in the ileal tissue of HAE model rats and normal rats; the same methods were used to measure the expression level of ASGPR in the non-diseased liver tissue and the marginal zone of liver tissue lesion of HAE model rats and the liver tissue of normal rats. The t-test was used for comparison of normally distributed continuous data between two groups; a one-way analysis of variance was used for comparison between three groups, and the least significant difference t-test was used for comparison between two groups. ResultsThe results of immunofluorescence assay, Western blotting, and quantitative real-time PCR showed that compared with the normal group, the HAE group had significantly upregulated expression of ASBT in the ileal tissue (t=5309, 4.110, and 28.060, all P＜0.05) and a significantly higher expression level of ASGPR (the closer to the lesion, the higher the expression) (F=110666, 128.201, and 143.879, all P＜0.001). ConclusionASBT and ASGPR can be used as potential mediated receptors for oral liver-targeting preparations for HAE, which provides a theoretical basis for the design of oral liver-targeting preparations for the treatment of HAE.

Objective To study the effect of bone marrow mesenchymal stem cells (BMSCs) on autologous peripheral blood lymphocyte proliferation and regulatory T cells (Tregs)subsets in vitro in patients with hepatitis B virus related decompensated cirrhosis.Methods MSCs were isolated and expanded from human bone marrow blood of eight patients with decompensated cirrhosis.The purity of MSCs was identified by flow cytometry.lymphocytes were isolated from the peripheral blood of patients and stained with carboxy fluoresce indiacetate succinimidyl ester (CFDA SE).The BMSCs and peripheral blood lymphocytes from patients were added into wells containing autologous serum in the presence of phytohemagglutinin (PHA).lymphocytes proliferation rate and CD4 + CD25 + CD127-Tregs frequency were detected by flow cytometry.Results Flowcytometric analysis showed that lymphocyte proliferation in contact co-culture group and noncontact co-culture group were much lower than positive control (all P ＜ 0.01),and significantly higher than negative control (all P ＜ 0.01),while CD4+ CD25+ CD127-Tregs in contact co-culture group and noncontact co-culture group were much higher than positive control and negative control (all P ＜ 0.01).Besides,there was no significant difference on lymphocyte proliferation rate or Tregs frequency between contact co-culture group and non-contact co-culture group(all P ＞ 0.05).Conclusion BMSCs can inhibit proliferation of autologous peripheral blood lymphocytes and increase expression of CD4 + CD25 + CD127-Tregsin patients with decompensated cirrhosis.