Netrin stimulates tyrosine phosphorylation of the UNC-5 family of netrin receptors and induces Shp2 binding to the RCM cytodomain

Caenorhabditis elegans UNC-5 and its mammalian homologues such as RCM are receptors for the secreted axon guidance cue UNC-6/netrin and are required to mediate the repulsive effects of UNC-6/netrin on growth cones. We find that C. elegans UNC-5 and mouse RCM are phosphorylated on tyrosine in vivo. C. elegans UNC-5 tyrosine phosphorylation is reduced in unc-6 null mutants, and RCM tyrosine phosphorylation is induced by netrin-1 in transfected HEK-293 cells, demonstrating that phosphorylation of UNC-5 proteins is enhanced by UNC-6/netrin stimulation in both worms and mammalian cells. An activated Src tyrosine kinase induces phosphorylation of RCM at multiple cytoplasmic tyrosine residues creating potential binding sites for cytoplasmic signaling proteins. Indeed, the NH2-terminal SH2 domain of the Shp2 tyrosine phosphatase bound specifically to a Tyr(568) RCM phosphopeptide. Furthermore, Shp2 associated with RCM in a netrin-dependent manner in transfected cells, and co-immunoprecipitated with RCM from an embryonic mouse brain lysate. A Y568F mutant RCM receptor failed to bind Shp2 and was more highly phosphorylated on tyrosine than the wild type receptor. These results suggest that netrin-stimulated phosphorylation of RCM Tyr(568) recruits Shp2 to the cell membrane where it can potentially modify RCM phosphorylation and function.     

Inhibition of miR-21-5p suppresses high glucose-induced proliferation and angiogenesis of human retinal microvascular endothelial cells by the regulation of AKT and ERK pathways via maspin

The aim of the present study is to investigate the role of miR-21-5p in angiogenesis of human retinal microvascular endothelial cells (HRMECs). HRMECs were incubated with 5 mM glucose, 30 mM glucose or 30 mM mannitol for 24 h, 48 h or 72 h. Then, HRMECs exposed to 30 mM glucose were transfected with miR-21-5p inhibitor. We found that high glucose increased the expression of miR-21-5p, VEGF, VEGFR2 and cell proliferation activity. Inhibition of miR-21-5p reduced high glucose-induced proliferation, migration, tube formation of HRMECs, and reversed the decreased expression of maspin as well as the abnormal activation of PI3K/AKT and ERK pathways. Down-regulation of maspin by siRNA significantly increased the activities of PI3K/AKT and ERK pathways. In conclusion, inhibition of miR-21-5p could suppress high glucose-induced proliferation and angiogenesis of HRMECs, and these effects may partly dependent on the regulation of PI3K/AKT and ERK pathways via its target protein maspin.     

Uncovering the pathogenesis and identifying novel targets of pancreatic cancer using bioinformatics approach

Pancreatic cancer is a uniformly lethal disease that can be difficult to diagnose at its early stage. Thus, our present study aimed to explore the underlying mechanism and identify new targets for this disease. The data GSE16515, including 36 tumor and 16 normal samples were available from Gene Expression Omnibus. Differentially expressed genes (DEGs) were screened out using Robust Multichip Averaging and LIMMA package. Moreover, gene ontology and pathway enrichment analyses were performed to DEGs. Followed with protein–protein interaction (PPI) network construction by STRING and Cytoscape, module analysis was conducted using ClusterONE. Finally, based on PubMed, text mining about these DEGs was carried out. Total 274 up-regulated and 93 down-regulated genes were identified as the common DEGs and these genes were discovered significantly enriched in cell adhesion and extracellular region terms, as well as ECM-receptor interaction pathway. In addition, five modules were screened out from the up-regulated PPI network with none in down-regulated network. Finally, the up-regulated genes, including MIA, MET and CEACAMS, and down-regulated genes, such as FGF, INS and LAPP, had the most references in text mining analysis. Our findings demonstrate that the up- and down-regulated genes play important roles in pancreatic cancer development and might be new targets for the therapy.     

人源乳酸菌对2型糖尿病小鼠的缓解效果

为考察人源乳酸菌(发酵乳杆菌Lactobacillus fermentum 11、305和植物乳杆菌Lactobacillus plantarum 22、25)对2型糖尿病的缓解效果,对2型糖尿病小鼠连续灌胃菌粉溶液12周.每周记录各组小鼠体重、进食量和血糖.实验结束前进行口服葡萄糖耐量试验和胰岛素抵抗试验.实验结束后...     

肺成体干细胞体外培养模型的研究进展北大核心CSCD

目前,肺体外培养模型有肺类器官和肺芯片两种主要手段。肺类器官是离体的肺上皮干细胞在体外特定的三维培养环境中生长,自发形成具有自我更新能力的干细胞簇并成功分化出功能细胞。肺芯片是利用人工活性膜为细胞提供组织分层结构,模拟微环境和机械力的仿生微流体芯片。由于原有二维培养模式缺乏精确的微结构和功能,组织体外培养模型作为模拟肺部发育、稳态、损伤和再生机制的研究工具,为肺部纤维化、癌症等疾病的探索提供了新的手段和可能。本文就肺成体干细胞两种体外培养模型的分类、研发历史、建立方法、实际应用、优缺点等方面进行综述,期望为器官移植和再生、药物筛选等应用提供参考。     

Knowledge Levels and Training Needs of Disaster Medicine among Health Professionals,Medical Students,and Local Residents in Shanghai,China

Background

Disaster is a serious public health issue. Health professionals and community residents are main players in disaster responses but their knowledge levels of disaster medicine are not readily available. This study aimed to evaluate knowledge levels and training needs of disaster medicine among potential disaster responders and presented a necessity to popularize disaster medicine education.

Methods

A self-reporting questionnaire survey on knowledge level and training needs of disaster medicine was conducted in Shanghai, China, in 2012. A total of randomly selected 547 health professionals, 456 medical students, and 1,526 local residents provided intact information. The total response rate was 93.7%.

Results

Overall, 1.3% of these participants have received systematic disaster medicine training. News media (87.1%) was the most common channel to acquire disaster medicine knowledge. Although health professionals were more knowledgeable than community residents, their knowledge structure of disaster medicine was not intact. Medical teachers were more knowledgeable than medical practitioners and health administrators (p = 0.002). Clinicians performed better than public health physicians (p<0.001), whereas public health students performed better than clinical medical students (p<0.001). In community residents, education background significantly affected the knowledge level on disaster medicine (p<0.001). Training needs of disaster medicine were generally high among the surveyed. ‘Lecture’ and ‘practical training’ were preferred teaching methods. The selected key and interested contents on disaster medicine training were similar between health professionals and medical students, while the priorities chosen by local residents were quite different from health professionals and medical students (p<0.001).

Conclusions

Traditional clinical-oriented medical education might lead to a huge gap between the knowledge level on disaster medicine and the current needs of disaster preparedness. Continuing medical education and public education plans on disaster medicine via media should be practice-oriented, and selectively applied to different populations and take the knowledge levels and training needs into consideration.