Sulfated glycosaminoglycans and low-density lipoprotein receptor mediate the cellular entry of Clostridium novyi alpha-toxin

Dear Editor, Clostridium novyi(C.novyi)is a spore-forming anaerobic bacterium and opportunistic pathogen causing severe infectious diseases in humans and animal...     

大型水生植物对重金属的富集与转移

通过野外调查和室内分析,研究了云南阳宗海南北两区域自然生长的17种水生植物的生长状况及植物和对应水样、根区底泥中重金属(As、Zn、Cu、Cd、Pb)的含量。结果表明:植物长势良好,未发现受害症状。水体As严重污染,Pb轻度污染,Zn、Cu和Cd均未超标。9种沉水植物同时对As、Zn、Cu、Cd、Pb的富集系数(植物全株重金属含量与水中该元素含量的比值)远大于1,具有共富集特征。在平均含As0.175mg/L的水中,金鱼藻、黑藻、小眼子菜、八药水筛全株As平均含量分别为(150±7.3)、(179±35)、(92±31)、(265±21)mg/kg(干重),对As具有较强富集能力;对于8种湿生和挺水植物,北部采样点的喜旱莲子草、田栖稗、细叶小苦荬和长芒稗对As,长芒稗、细叶小苦荬、圆果雀稗、水蓼和风车草对Cd,海芋和圆果雀稗对Zn的富集系数(植物地上部重金属含量与底泥中该元素含量的比值)以及圆果雀稗对Cd和Zn转移系数(植物地上部重金属含量与根中该元素含量的比值)均大于1。聚类分析结果表明,金鱼藻、黑藻、八药水筛、小眼子菜、穗状狐尾藻5种水生植物同时对As、Zn、Cu、Cd、Pb具有较强的吸收和富集能力,在重金属复合污染水体修复中具有较大潜力。     

Lithocholic acid inhibits dendritic cell activation by reducing intracellular glutathione via TGR5 signaling

Dendritic cells (DCs) are the major antigen-presenting cells and play an important role in autoimmune uveitis. Emerging evidence suggests that bile acids (BAs) regulate DCs maturation. However, the underlying mechanisms by which BAs regulate the function of DCs still need to be clarified. Here, we demonstrate that lithocholic acid (LCA) inhibits the production of pro-inflammatory cytokines and the expression of surface molecules in bone marrow-derived dendritic cells (BMDCs). LCA attenuates the severity of EAU by modulating the maturation of splenic CD11C⁺MHCII^high DCs. Notably, Takeda G-protein coupled receptor 5 (TGR5) deficiency partially reverses the inhibitory effect of LCA on DCs in vitro and in vivo. TGR5 activation also downregulates the NF-κB and MAPK pathways by inhibiting glutathione production and inducing oxidative stress in DCs, which leads to apoptosis and autophagy in DCs. In addition, LCA or INT-777 treatment increases the TGR5 expression in monocyte-derived dendritic cells (MD-DCs) of patients with active BD, whereas both LCA and TGR5 agonists inhibit the activation of MD-DCs. These results suggest that LCA and TGR5 agonists might be potential therapeutic drugs for the treatment of autoimmune uveitis.     

Design,synthesis, and biological evaluation of novel carbazole derivatives as potent DNMT1 inhibitors with reasonable PK properties

The DNA methyltransferases (DNMTs) were found in mammals to maintain DNA methylation. Among them, DNMT1 was the first identified, and it is an attractive target for tumour chemotherapy. DC_05 and DC_517 have been reported in our previous work, which is non-nucleoside DNMT1 inhibitor with low micromolar IC₅₀ values and significant selectivity towards other S-adenosyl-_L-methionine (SAM)-dependent protein methyltransferases. In this study, through a process of similarity-based analog searching, a series of DNMT1 inhibitors were designed, synthesized, and evaluated as anticancer agents. SAR studies were conducted based on enzymatic assays. And most of the compounds showed strong inhibitory activity on human DNMT1, especially WK-23 displayed a good inhibitory effect on human DNMT1 with an IC₅₀ value of 5.0 µM. Importantly, the pharmacokinetic (PK) profile of WK-23 was obtained with quite satisfying oral bioavailability and elimination half-life. Taken together, WK-23 is worth developing as DNMT1-selective therapy for the treatment of malignant tumour.     

银合欢基因文库的构建和种子贮藏蛋白基因的分离

本文以λEMBL_3为载体,构建了银合欢(Leucaena leucocephala)的基因文库,所得重组子为3.5×10~6pfu。以大豆种子贮藏蛋白α′亚基基因为探针,从基因文库中分离得到了4个阳性克隆,并初步绘制了其中3个重组子的物理图谱。结果表明在这3个重组子的基因内部有一致的酶切位点。亚克隆的部分核苷酸序列与 GenBank 中的基因序列比较,表明与大豆种子贮藏蛋白α′亚基基因高度同源。     

A new technique to expand human mesenchymal stem cells using basement membrane extracellular matrix

Mesenchymal stem cells (MSC) show a very short proliferative life span and readily lose the differentiation potential in culture. However, the growth rate and the proliferative life span of the stem cells markedly increased using tissue culture dishes coated with a basement membrane-like extracellular matrix, which was produced by PYS-2 cells or primary endothelial cells. Furthermore, the stem cells expanded on the extracellular matrix, but not those on plastic tissue culture dishes, retained the osteogenic, chondrogenic, and adipogenic potential throughout many mitotic divisions. The extracellular matrix had greater effects on the proliferation of MSC and the maintenance of the multi-lineage differentiation potential than basic fibroblast growth factor. Mesenchymal stem cells expanded on the extracellular matrix should be useful for regeneration of large tissue defects and repeated cell therapies, which require a large number of stem or progenitor cells.