Dihydromyricetin increases endothelial nitric oxide production and inhibits atherosclerosis through microRNA-21 in apolipoprotein E-deficient mice

Natural products were extracted from traditional Chinese herbal emerging as potential therapeutic drugs for treating cardiovascular diseases. This study examines the role and underlying mechanism of dihydromyricetin (DMY), a natural compound extracted from Ampelopsis grossedentata, in atherosclerosis. DMY treatment significantly inhibits atherosclerotic lesion formation, proinflammatory gene expression and the influx of lesional macrophages and CD4-positive T cells in the vessel wall and hepatic inflammation, whereas increases nitric oxide (NO) production and improves lipid metabolism in apolipoprotein E-deficient (Apoe^−/−) mice. Yet, those protective effects are abrogated by using NOS inhibitor L-NAME in Apoe^−/− mice received DMY. Mechanistically, DMY decreases microRNA-21 (miR-21) and increases its target gene dimethylarginine dimethylaminohydrolase-1 (DDAH1) expression, an effect that reduces asymmetric aimethlarginine (ADMA) levels, and increases endothelial NO synthase (eNOS) phosphorylation and NO production in cultured HUVECs, vascular endothelium of atherosclerotic lesions and liver. In contrast, systemic delivery of miR-21 in Apoe^−/− mice or miR-21 overexpression in cultured HUVECs abrogates those DMY-mediated protective effects. These data demonstrate that endothelial miR-21-inhibited DDAH1-ADMA-eNOS-NO pathway promotes the pathogenesis of atherosclerosis which can be rescued by DMY. Thus, DMY may represent a potential therapeutic adjuvant in atherosclerosis management.     

内质网应激在乙型脑炎病毒诱导神经元细胞凋亡中的作用及机制研究

内质网应激(Endoplasmic reticulum stress,ERS)的激活与创伤、缺血再灌注等病理刺激引起的神经元凋亡有关,流行性乙型脑炎病毒(JEV)感染能够促进神经元凋亡、激活ERS,但ERS在JEV诱导神经元细胞凋亡中的作用尚不清楚.为了研究ERS在JEV诱导神经元细胞凋亡中的作用及机制,本研究以神经细胞株SH-SY5Y为对象,感染JEV并加用ERS激动剂、ERS抑制剂或转染阴性对照(NC) siRNA、蛋白激酶R样内质网激酶(PERK)siRNA,检测细胞存活率、凋亡率、ERS蛋白PERK、肌醇必需酶-1α(IRE1α)、活化转录因子6(ATF6)及凋亡蛋白C/EBP同源蛋白(CHOP)、含半胱氨酸的天冬氨酸蛋白水解酶12(Caspase-12)、Bcl-2相关X蛋白(Bax)的表达.结果 显示:JEV组SH-SY5Y细胞的凋亡率及PERK、CHOP、Caspase-12、Bax的表达水平高于对照组,存活率低于对照组(P＜0.05),IRE1α、ATF6的表达水平与对照组比较无显著差异(P＞0.05).与JEV组比较,激动剂组SH-SY5Y细胞的凋亡率及PERK、CHOP、Caspase-12、Bax的表达水平显著增加,存活率显著降低(P＜0.05);抑制剂组SH-SY5Y细胞的凋亡率及PERK、CHOP、Caspase-12、Bax的表达水平显著降低,存活率显著增加(P＜0.05);与si-NC+JEV组比较,si-PERK+JEV组SH-SY5Y细胞的凋亡率及PERK、CHOP、Caspase-12、Bax的表达水平P显著降低,存活率显著增加(P＜0.05).以上结果表明ERS的PERK通路激活与JEV诱导神经元凋亡有关.     

Cutaneous and Mucosal Phaeohyphomycosis Caused by Exophiala spinifera in a Pregnant Patient: Case Report and Literature Review

We report a case of mucocutaneous phaeohyphomycosis caused by Exophiala spinifera. Crusty plaques and nodules were major clinical features. Histological examination revealed brown yeast-like cells and hyphae. Mycological and molecular data identified E. spinifera as etiologic agent. Oral itraconazole was effective, which was in accordance with the results of in vitro susceptibility testing. We speculated that her pregnancy may play a role of risk factor in the infection by E. spinifera.     

Determination of the genetic architecture of seed size and shape via linkage and association analysis in soybean (Glycine max L. Merr.)

Seed-size traits, which are controlled by multiple genes in soybean, play an important role in determining seed yield, quality and appearance. However, the molecular mechanisms controlling the size of soybean seeds remain unclear, and little research has been done to investigate these mechanisms. In this study, we performed a genetic analysis to determine the genetic architecture of soybean seed size and shape via linkage and association analyses. We used 184 recombinant inbred lines (RILs) and 219 cultivated soybean accessions to evaluate seed length, seed width and seed height as seed-size traits, and their ratios of these values as seed-shape traits. Our results showed that all six traits had high heritability ranging from 92.46 to 98.47 %. Linkage analysis in the RILs identified 12 quantitative traits loci (QTLs), with five of these QTLs being associated with seed size, five with seed shape and two with the two first principal components of our principal component analysis (PCA). Association analysis in the 219 accessions detected 41 single nucleotide polymorphism (SNP)-trait associations, with 20 of these SNPs being associated with seed-size traits, seven with seed-shape traits and 14 with the two first principal components of our PCA. This analysis reveals that seed-size and seed-shape may be controlled by different genetic factors. Our results provide a greater understanding of phenotypic structure and genetic architecture of soybean seed, and the QTLs detected in this study form a basis for future fine mapping, quantitative trait gene cloning and molecular breeding in soybean.     

3D-QSAR studies on fluoropyrrolidine amides as dipeptidyl peptidase IV inhibitors by CoMFA and CoMSIA

Three-dimensional quantitative structure-activity relationship (3D-QSAR) analyses using CoMFA and CoMSIA methods were conducted on a series of fluoropyrrolidine amides as dipeptidyl peptidase IV (DP-IV) inhibitors. The selected ligands were docked into the binding site of the 3D model of DP-IV using the GOLD software, and the possible interaction models between DP-IV and the inhibitors were obtained. Based on the binding conformations of these fluoropyrrolidine amides and their alignment inside the binding pocket of DP-IV, predictive 3D-QSAR models were established by CoMFA and CoMSIA analyses, which had conventional r ² and cross-validated coefficient values () up to 0.982 and 0.555 for CoMFA and 0.953 and 0.613 for CoMSIA, respectively. The predictive ability of these models was validated by six compounds that were in the testing set. Structure-based investigations and the final 3D-QSAR results provide the guide for designing new potent inhibitors.     

Inhibitory mode of indole-2-carboxamide derivatives against HLGPa: molecular docking and 3D-QSAR analyses

The interaction of a series of indole-2-carboxamide compounds with human liver glycogen phosphorylase a (HLGPa) have been studied employing molecular docking and 3D-QSAR approaches. The Lamarckian Genetic Algorithm (LGA) of AutoDock 3.0 was employed to locate the binding orientations and conformations of the inhibitors interacting with HLGPa. The binding models were demonstrated in the aspects of inhibitor's conformation, subsite interaction, and hydrogen bonding. The very similar binding conformations of these inhibitors show that they interact with HLGPa in a very similar way. Good correlations between the calculated interaction free energies and experimental inhibitory activities suggest that the binding conformations of these inhibitors are reasonable. The structural and energetic differences in inhibitory potencies of indole-2-carboxamide compounds were reasonably explored. Using the binding conformations of indole-2-carboxamides, consistent and highly predictive 3D-QSAR models were developed by CoMFA and CoMSIA analyses. The q2 values are 0.697 and 0.622 for CoMFA and CoMSIA models, respectively. The predictive ability of these models was validated by four compounds that were not included in the training set. Mapping these models back to the topology of the active site of HLGPa leads to a better understanding of the vital indole-2-carboxamide-HLGPa interactions. Structure-based investigations and the final 3D-QSAR results provide clear guidelines and accurate activity predictions for novel inhibitor design.     

杨树基因工程进展

本文重点对杨树的遗传转化技术进行了概述,讨论了影响农杆菌转化效果的主要因素,并综述了杨树在抗除草剂、抗虫和抗病等方面基因工程进展状况。     

心阻抗图的弹性腔-边值问题理论模型

分析了造成Ｎｙｂｏｅｒ－Ｋｕｂｉｃｅｋ公式与用其它较可靠的方法测得的每搏心排量相差较大的五个主要原因,并针对其中前三个原因,修改了原有的物理模型,用弹性腔模型及解边值问题的方法得出了一种心阻抗图的新理论模型;最后对此新理论模型作了初步的讨论     

Pharmacophore modeling of human adenosine receptor A2A antagonists

Three-dimensional pharmacophore models of human adenosine receptor A_2A antagonists were developed based on 23 diverse compounds selected from a large number of A_2A antagonists. The best pharmacophore model, Hypo1, contained five features: one hydrogen bond donor , three hydrophobic points and one ring aromatic. Its correlation coefficient, root mean square deviation, and cost difference values were 0.955, 0.921 and 84.4, respectively, suggested that the Hypo1 model was reasonable and reliable. This model was validated by three methods: a test set of 106 diverse compounds, a simulated virtual screening, and superimposition with the crystal structure of A_2A receptor. The results showed that Hypo1 was not only in agreement with the A_2A crystal structure and literature reports, but also well identified active A_2A antagonists from the virtual database. This methodology provides helpful information and a robust tool for the discovery of potent A_2A antagonists.