Implication of CD38 gene in podocyte epithelial-to-mesenchymal transition and glomerular sclerosis

CD38 is a multifunctional protein involving in a number of signalling pathways. Given that the lack of CD38 is considered as a dedifferentiation marker of lymphocytes and other cells, we hypothesized that CD38 and its signalling pathway may participate in the epithelial-to-mesenchymal transition (EMT) process of podocytes and thereby regulates the integrity of glomerular structure and function. Western blot analysis and RT-PCR demonstrated that renal tissue CD38 expression was lacking in CD38(-/-) mice or substantially reduced in renal CD38 shRNA-transfected WT (CD38-shRNA) mice compared to CD38(+/+) littermates. Confocal fluorescent microscopy demonstrated the reduced expression of epithelial markers (P-Cadherin, ZO-1 and podocin) and increased expression of mesenchymal markers (FSP-1, α-SMA and desmin) in the glomeruli of CD38(-/-) and CD38-shRNA mice compared to CD38(+/+) mice. Morphological examinations showed profound injury in the glomeruli of CD38(-/-) or CD38-shRNA mice compared to CD38(+/+) mice. This enhanced glomerular injury in CD38(-/-) or CD38-shRNA mice was accompanied by increased albuminuria and proteinuria. DOCA/high salt treatment further decreased the expression of epithelial markers and increased the abundance of mesenchymal markers, which were accompanied by more increased glomerular damage index and mean arterial pressure in CD38(-/-) and CD38-shRNA mice than CD38(+/+) mice. In vitro studies showed that inhibition of CD38 enhances the EMT in podocytes. In conclusion, our observations reveal that the normal expression of CD38 importantly contributes to the differentiation and function of podocytes and the defect of this gene expression may be a critical mechanism inducing EMT and consequently resulting in glomerular injury and sclerosis.     

Modeling the interaction of seven bisphosphonates with the hydroxyapatite(100) face

The interaction of seven pamidronate bisphosphonate (Pami-BPs) and its analogs with the hydroxyapatite (HAP) (100) surface was studied using density functional theory (DFT) and molecular dynamic (MD) methods. Partial Mulliken oxygen atomic charges in protonated structures were calculated at the level of B3LYP/6-31G*. The MD simulation was performed using the Discover module of Material Studio by compass force field. The results indicate the abilities of donating electrons of the oxygen atoms of the phosphate groups that are closely associated with the antiresorptive potency. The binding energies, including vdw and electrostatic, are used to discuss the mechanism of antiresorption. The results of calculations show that the strength of interaction of the HAP (100) face with the bisphosphonates is N(4)?>?N(6)?>?N(7)?>?N(5)?>?N(3)?>?N(2)?>?N(1) according to their experimental pIC(50) values.     

Dissecting cell death with proteomic scalpels

Programmed cell deaths (PCD), including apoptosis, autophagy and programmed necrosis, are genetically determined, complex processes in multi-cellular organisms. Problems with the regulation of PCD have been implicated in a number of diseases including myocardial infarction, cancer and autoimmune disease. As a result, the investigation on PCD regulation has stirred considerable interest. In the past decades, many PCD-involved proteins had been identified as being modulated by post-translational mechanisms, including post-translational modification, protein-protein interactions and protein cleavage, which fall precisely within the range of proteomic analysis. Contemporary quantitative proteomics, interactomics, PTMomics, degradomics, chemical proteomics and pharmacoproteomics have been quickly applied in the field of PCD research, and possess the potential to be the driving forces of the field. This review attempts to highlight some of the major achievements in the application of proteomics in PCD research to trigger further thinking and application.     

家长因素对幼儿参与健身类课程的影响

以上海市28所幼儿园的204名幼儿为研究对象,从家长的视角探寻影响幼儿参与健身类课程的因素,运用文献资料法、问卷调查法和数理统计等方法对影响幼儿参与健身类课程的家长因素进行研究,寻求促进幼儿参与健身类课程的方法与措施,为帮助更多的幼儿运动起来,不再依赖电脑、电视和电子游戏等,从而为促使幼儿更加健康的发展奠定一定的理论基础.结果表明:(1)父母的健身经历及父亲受教育的程度能较显著地影响幼儿喜欢运动的程度.(2)父母对幼儿参与运动的消极观念会严重地影响幼儿参与运动的积极性.(3)母亲参与健身的经历对幼儿参加健身类课程的意向具有较显著性的影响,有健身经历的母亲越会让幼儿参与健身类课程.(4)父母受教育的程度对幼儿参加健身类课程的意向具有较显著的影响,父母的学历越高,幼儿参加健身类课程的意向越明显.     

The study on newly developed McAb NJ001 specific to non-small cell lung cancer and its biological characteristics

Monoclonal antibody (McAb) is the key tool for cancer immunodiagnosis and immunotherapy. McAb-based immunotherapy that targets tumor antigens has had great achivement. In this study, a cell clone which kept secreting high-titer IgG1-type McAb named NJ001 against human non-small cell lung cancer (NSCLC) cells was obtained. The titer of purified NJ001 was 2×10(6). The antigen named SP70 of NSCLC specifically identified by NJ001 was proved to be a protein with the relative molecular mass (Mr) of 70 kDa. The results of immunohistochemical staining indicated that NJ001 could positively react to NSCLC, but weak positively or negatively react to human small-cell lung cancer (SCLC), pulmonary pseudotumor and other epithelial tumors. In soft agar assay, the colony formation efficiency in NJ001 groups decreased in a dose-dependent manner. For the concentration of 100 μg/ml, 200 μg/ml and 400 μg/ml, the inhibition ratio of colony formation was 23.4%, 62.5% and 100% respectively. Meanwhile, NJ001 caused significant reduction in tumor volume and tumor weight compared to control mice in lung cancer xenograft model. The tumor growth inhibition ratio in 200 μg, 400 μg and 800 μg NJ001 groups was 10.44%, 37.29% and 44.04%, respectively. NJ001 also led to cytomorphological changes and induced the apoptosis of human lung adenocarcinoma cell line SPC-A1 significantly. The newly developed NJ001 selectively reacted to NSCLC and exhibited anti-tumor activity both in vitro and in vivo. NJ001 is of great value concerning immunodiagnostics and immunotherapy for NSCLC and holds promise for further research regarding the mechanism underlying tumor progression of NSCLC.     

Carcinogenesis or tumourigenicity testing of animal cell lines for vaccine preparation by colony formation on soft agar and by agglutination under plant lectins

The carcinogenic or tumourigenic testing of seven animal kidney cell lines (F-81, CRFK, MDCK, Vero, Vero-2 cell line, MA-104 and BHK-21) established in China, were carried out in more than 700 nude mice for colony formation in soft agar and for agglutination under different density of plant lectins. Tests showed that there were correlation between cell line chromosome number variations and anchorage independence in soft agar, agglutinability under lectins and tumour-forming ability in nude mice. Since testing in vitro was more economical, simpler and faster and thus thought to be more reliable, we recommend measuring agglutinability, followed by anchorage independence or analysis of karyotype as the initial means for monitoring tumourigenicity of animal cell lines in nude mice.     

Chemical synthesis of a core 2 branched pentasaccharide containing a carboxylate group

Design and synthesis of a carboxylate-containing pentasaccahride 1 with the Galbeta(1-4) (Fucalpha1-3)GlcNAcbeta(1-6)[3-[1-carboxymethyl]-Galbeta+ ++(1-3)]GalNAcalpha-OMe sequence, which is obtained through regioselective coupling of the 6-OH of a novel acceptor 9 with Lewis(x) donor 10 catalyzed by NIS-TfOH are described.