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| 1 | Small Interfering RNA-mediated Caveolin-1 Knockout on Plasminogen Activator Inhibitor-1 Expression in Insulin-stimulated Human Vascular Endothelial Cells显示文摘把人的脉管的 endothelial 房间(ECV304 ) 用作目标,我们学习了 caveolin (CAV ) 的效果在 plasminogen 的刺激胰岛素的表示期间的 -1 禁止者(白族)-1。代表 RNAi CAV-1 基因的适当搁浅单人赛的 oligonucleotides 被 Ambion 软件分析。在退火产生双 stranded oligonucleotides (dsoligo ) 以后,它被克隆进由 T4 DNA 连接酶包含 RNA 聚合酶 III 表示元素的 pENTR/U6 入口向量。从 pENTR/U6 入口转移的短发卡(shRNA ) 序列与 LR 再结合反应被克隆进 pLenti6/BLOCK-iT-DEST 向量。由定序的 Afteridentification,我们成功地用网关技术构造了 CAV-1 RNAi lentiviral 表达式系统。Silencing 效率是由即时 reversetranscription 聚合酶链反应,免疫荧光染色并且西方的弄污的 assayed。ECV304cells 在包含胰岛素的不同集中的媒介是有教养的(1x10 ^( 有 CAV-1 基因 silenced 的 -9)to1x10^(-7) M ) 。表示水平和潜水艇 PAI-1 和 CAV-1 的细胞的本地化用反向的抄写聚合酶链反应,免疫荧光染色和蛋白质印迹试金被比较。结果证明有势力抑制 ofCAV-1 表示能到达 85% ,并且它对 CAV-1-derived shRNA,不是导出 theS100A13 的 shRNA 特定。在蛋白质确实在房间膜下面积累了的在与生理的胰岛素,而是 PAI-1 孵化的 RNAi^+andRNAi^- ECV304 房间之间的 PAI-1 表示没有戏剧的差别。当胰岛素的集中增加了, PAI-1 的表示是起来调整的,而 CAV-1 的表示稀释了。而且, PAI-1 清楚地在 CAV-1knockdown 以后扩充了。这些结果显示 hyperinsulinism 能由 inhibitingCAV-1 支持 PAI-1 表示,并且稳定或在 endothelial 房间的起来调整的 CAV-1 表示可能在糖尿病减少大容器和毛状的容器的复杂并发症。 | Huiling YANG Shuya HE Zhihua QUAN Weixia PENG Bin YAN Jianghua LIU Fang WEN Renxian CAO Yangyan XU Gebo WEN Weixin HU | 2007 | Acta Biochimica et Biophysica Sinica2007，39，3： | 7 |
| 2 | The Notch pathway attenuates burn-induced acute lung injury in rats by repressing reactive oxygen species显示文摘Background:Acute lung injury(ALI)is a common complication following severe burns.The underlying mechanisms of ALI are incompletely understood;thus,available treatments are not sufficient to repair the lung tissue after ALI.Methods:To investigate the relationship between the Notch pathway and burn-induced lung injury,we established a rat burn injury model by scalding and verified lung injury via lung injury evaluations,including hematoxylin and eosin(H&E)staining,lung injury scoring,bronchoalveolar lavage fluid and wet/dry ratio analyses,myeloperoxidase immunohistochemical staining and reac-tive oxygen species(ROS)accumulation analysis.To explore whether burn injury affects Notch1 expression,we detected the expression of Notch1 and Hes1 after burn injury.Then,we extracted pulmonary microvascular endothelial cells(PMVECs)and conducted Notch pathway inhibition and activation experiments,via aγ-secretase inhibitor(GSI)and OP9-DLL1 coculture,respectively,to verify the regulatory effect of the Notch pathway on ROS accumulation and apoptosis in burn-serum-stimulated PMVECs.To investigate the regulatory effect of the Notch pathway on ROS accumulation,we detected the expression of oxidative-stress-related molecules such as superoxide dismutase,nicotinamide adenine dinucleotide phosphate(NADPH)oxidase(NOX)2,NOX4 and cleaved caspase-3.NOX4-specific small interfering RNA(siRNA)and the inhibitor GKT137831 were used to verify the regulatory effect of the Notch pathway on ROS via NOX4.Results:We successfully established a burn model and revealed that lung injury,excessive ROS accumulation and an inflammatory response occurred.Notch1 detection showed that the expression of Notch1 was significantly increased after burn injury.In PMVECs challenged with burn serum,ROS and cell death were elevated.Moreover,when the Notch pathway was suppressed by GSI,ROS and cell apoptosis levels were significantly increased.Conversely,these parameters were reduced when the Notch pathway was activated by OP9-DLL1.Mechanistically,the inhibition of NOX4 by siRNA and GKT137831 showed that the Notch pathway reduced ROS production and cell apoptosis by downregulating the expression of NOX4 in PMVECs.Conclusions:The Notch pathway reduced ROS production and apoptosis by downregulating the expression of NOX4 in burn-stimulated PMVECs.The Notch-NOX4 pathway may be a novel therapeutic target to treat burn-induced ALI. | Weixia Cai Kuo Shen Peng Ji Yanhui Jia Shichao Han Wanfu Zhang Xiaolong Hu Xuekang Yang Juntao Han Dahai Hu | 2022 | Burns & Trauma2022，10，1： | 2 |
| 3 | α/Sulfono-γ-AA peptide hybrids agonist of GLP-1R with prolonged action both in vitro and in vivo显示文摘Peptides are increasingly important resources for biological and therapeutic development,however,their intrinsic susceptibility to proteolytic degradation represents a big hurdle.As a natural agonist for GLP-1R,glucagon-like peptide 1(GLP-1)is of significant clinical interest for the treatment of type-2 diabetes mellitus,but its in vivo instability and short half-life have largely prevented its therapeutic application.Here,we describe the rational design of a series of a/sulfono-γ-AA peptide hybrid analogues of GLP-1 as the GLP-1R agonists.Certain GLP-1 hybrid analogues exhibited enhanced stability(t_(1/2)>14 days)compared to t_(1/2)(<1 day)of GLP-1 in the blood plasma and in vivo.These newly developed peptide hybrids may be viable alternative of semaglutide for type-2 diabetes treatment.Additionally,our findings suggest that sulfono-γ-AA residues could be adopted to substitute canonical amino acids residues to improve the pharmacological activity of peptide-based drugs. | Yan Shi Candy Lee Peng Sang Zaid Amso David Huang Weixia Zhong Meng Gu Lulu Wei Vân T.B.Nguyen-Tran Jingyao Zhang Weijun Shen Jianfeng Cai | 2023 | Acta Pharmaceutica Sinica B2023，13，4： | 0 |
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