Insulin Promotes Glucose Consumption via Regulation of miR-99a/mTOR/PKM2 Pathway

Insulin is known to regulate multiple cellular functions and is used for the treatment of diabetes. MicroRNAs have been demonstrated to be involved in many human diseases, including Type 2 diabetes. In this study, we showed that insulin decreased miR-99a expression levels, but induced glucose consumption and lactate production, and increased the expression of mTOR, HIF-1α and PKM2 in HepG2 and HL7702 cells. Forced expression of miR-99a or rapamycin treatment blocked insulin-induced PKM2 and HIF-1α expression, and glucose consumption and lactate production. Meanwhile, knockdown of HIF-1α inhibited PKM2 expression and insulin-induced glucose consumption. Taken together, these findings will reveal the role and mechanism ofinsulin in regulating glycolytic activities via miR-99a/mTOR.     

Regulation of survivin by PI3K/Akt/p70S6K1 pathway

PI3K activation is commonly observed in many human cancer cells. Survivin expression is elevated in cancer cells, and induced by some growth factors through PI3K activation. However, it is not clear whether PI3K activation is sufficient to induce survivin expression. To investigate the role of PI3K pathway in the regulation of survivin, we expressed an active form of PI3K, v-P3k in chicken embryonic fibroblast cells (CEF), and found that overexpression of PI3K-induced survivin mRNA expression. Forced expression of wild-type but not mutant tumor suppressor PTEN in CEF decreased survivin mRNA levels. PI3K regulates survivin expression through Akt activation. To further investigate downstream target of PI3K and Akt in regulating the expression of survivin mRNA, we found that PI3K and Akt-induced p70S6K1 activation and that overexpression of p70S6K1 alone was sufficient to induce survivin expression. The treatment of CEF cells by rapamycin decreased the survivin mRNA expression. This result demonstrated that p70S6K1 is an important target downstream of PI3K and Akt in regulating suvivin mRNA expression. The knockdown of survivin mRNA expression by its specific siRNA induced apoptosis of cancer cells when the cells were treated with LY294002 or taxol. Taken together, these results demonstrated that PI3K/Akt/p70S6K1 pathway is essential for regulating survivin mRNA expression.     

对新型农村合作医疗满意度的调查分析

目的:通过采取随机抽样法对湖南省5个市20个乡2500名农民进行问卷调查,调查其对新型农村合作医疗满意度,对新型农村合作医疗制度的认识程度以及该政策在实践运行中存在的不足,并针对问题提出相应建议.方法:抽样的2500名调查对象来自湘乡市、衡阳市、益阳市、邵阳市和怀化市,调查内容有对新型农村合作医疗制度的满意度,对新农合执行过程的满意度,对政策的意见看法,采用卡方检验方法.结果:对新农合制度的满意度为94%,对新型农村合作医疗制度执行过程的满意度57.5%,集中反映了10个问题.结论:为了提高农民对新型农村合作医疗制度执行过程的满意度,缓解农民"因病返贫,因病致贫"现象,改变农民"看病难,看病贵"现状,政府部门应加大对医疗卫生服务财政支持力度与监管力度,规范医疗行为,同时医务人员加强自身医德修养,减少农民不必要的医疗卫生经济支出并减轻农民负担.     

Molecular mechanisms underlying function of hair bundle: study on genetic deafness in mouse models

Although the basic principles for the function of peripheral auditory system have been known for many years, the molecular mechanisms which affect deafness are not clear. In recent years, the study of hereditary deafness associated mouse models has revealed the molecular basis which is related with the formation and function of the hair bundle and the mechanosensory organelle of hair cell. This review focused on the role of protein network, which is formed by the proteins encoded by the Usher syndrome type 1 genes, in hair-bundle development and mechanotransducer channel gating. And the review also showed how the stereocilia rootlets contribute to the hair bundle's mechanical properties and how the hair bundle produces suppressive masking. Finally, the review revealed multiple roles of the tectorial membrane and extracellular matrix in the hair bundles stimulating in the cochlea.     

Identification of Regulators of Polyploidization Presents Therapeutic Targets for Treatment of AMKL

The mechanism by which cells decide to skip mitosis to become polyploid is largely undefined. Here we used a high-content image-based screen to identify small-molecule probes that induce polyploidization of megakaryocytic leukemia cells and serve as perturbagens to help understand this process. Our?study implicates five networks of kinases that?regulate the switch to polyploidy. Moreover, we find that dimethylfasudil (diMF, H-1152P) selectively increased polyploidization, mature cell-surface marker expression, and apoptosis of malignant megakaryocytes. An integrated target identification approach employing proteomic and shRNA screening revealed that a major target of diMF is Aurora kinase A (AURKA). We further find that MLN8237 (Alisertib), a selective inhibitor of AURKA, induced polyploidization and expression of mature megakaryocyte markers in acute megakaryocytic leukemia (AMKL) blasts and displayed potent anti-AMKL activity in?vivo. Our findings provide a rationale to support clinical trials of MLN8237 and other inducers of polyploidization and differentiation in AMKL.     

抗肿瘤海绵放线菌的分离及菌株HA01184的鉴定

目的：对采自海南、湛江等海域的海绵样品进行放线菌选择性分离,采用其发酵液进行抗肿瘤活性筛选,并对活性较好的菌株进行鉴定。方法：用含50μg／mL重铬酸钾为抑制剂的海水高氏一号合成培养基分离培养海绵放线菌;以MTT法进行菌株的抗肿瘤活性筛选;通过培养特征、形态特征、生理生化特征、16S rDNA序列测定及系统发育分析,对菌株HA01184进行鉴定。结果与结论：海水高氏一号合成培养基用于海绵放线菌分离培养具有很好的选择性,从海绵样品中共分离得到放线菌165株,细胞毒活性达80％以上的阳性菌株有10株,其中菌株HA01184的发酵液细胞毒活性为90％。结合形态观察、生理生化特征和16S rDNA序列比对分析,将HA01184归于链霉菌属,可能是来自海洋环境的一个潜在新种。     

PI3K/PTEN signaling in tumorigenesis and angiogenesis

The phosphatidyl inositol 3-kinase (PI3K) can be activated by a variety of extracellular signals and involved in a number of cellular processes including cell proliferation, survival, protein synthesis, and tumor growth. Phosphatase and tensin homologue deleted on chromosome 10 (PTEN) is an antagonist of PI3K. The alterations of PI3K pathway such as activation of oncogenes, gene amplification, and inactivation of tumor suppressors, commonly occur in many human cancers. Angiogenesis is required for tumor growth and metastasis when the tumor reaches more than 1 mm in diameter. Recent studies have shown that PI3K and Akt play an important role in regulating tumor growth and angiogenesis through VEGF and HIF-1 expression. PI3K regulates the expression of these two proteins through HDM2 and p70S6K1 in human cancer cells. The frequent dysregulation of the PI3K/PTEN pathway in human cancer demonstrates that this pathway is an appropriate target for cancer therapeutics. In this review, we describe the recent advances in understanding the PI3K/PTEN pathway, the role and mechanism of PI3K in regulating tumor growth and angiogenesis, and the potential therapeutic opportunities for targeting this pathway for cancer treatment.     

Neurotoxicity of 25-OH-Cholesterol on NGF-Differentiated PC12 Cells

PC12 cells induced to differentiate with nerve growth factor were used to study the neurotoxicity of 25-OH-cholesterol. This agent induced a dose- and time-dependent cell death in neuronal PC12 cells. Cells treated with this agent showed condensed nuclei, a morphology similar to that of cells dying of programmed cell death. However, agents known to prevent neuronal programmed cell death (cyclic AMP, KCl, aurintricarboxylic acid, and cycloheximide) failed to prevent the 25-OH-cholesterol-mediated cytotoxicity. On the other hand, cell death induced by 25-OH-cholesterol was prevented by treatment with vitamin E and methyl-beta-cyclodextrin. In contrast to observations made in other cell types, whole-cell patch clamp recording of neuronal PC12 cells revealed that treatment with 25-OH-cholesterol did not significantly alter calcium influx through voltage-dependent channels. These results provide the first characterization of the toxicity of cholesterol oxides toward neuronal PC12 cells, which should be useful in future studies on the interactions between cholesterol oxides and cells from the nervous system.     

Minocycline ameliorates <Emphasis Type="SmallCaps">d</Emphasis>-galactose-induced memory deficits and loss of Arc/Arg3.1 expression

Dysfunction of learning and memory is widely found in many neurological diseases. Understanding how to preserve the normal function of learning and memory will be extremely beneficial for the treatment of these diseases. However, the possible protective effect of minocycline in memory impairment is unknown. We used the well-established d-galactose rat amnesia model and two behavioral tasks, the Morris water maze and the step-down task, for memory evaluation. Western blot and PCR were used to examine the protein and mRNA levels of Arc/Arg3.1. We report that minocycline supplementation ameliorates both the spatial and fear memory deficits caused by d-galactose. We also found that Arc/Arg3.1, c-fos, and brain-derived neurotrophic factor levels are decreased in the d-galactose animal model, and that minocycline reverses the protein and mRNA levels of Arc in the hippocampus, suggesting the potential role of Arc/Arg3.1 in minocycline’s neuroprotective mechanism. Our study strongly suggests that minocycline can be used as a novel treatment for memory impairment in neurological diseases.