Selectivity determinants of the aldose and aldehyde reductase inhibitor-binding sites

Aldose reductase and aldehyde reductase belong to the aldo-keto reductase superfamily of enzymes whose members are responsible for a wide variety of biological functions. Aldose reductase has been identified as the first enzyme involved in the polyol pathway of glucose metabolism which converts glucose into sorbitol. Glucose over-utilization through the polyol pathway has been linked to tissue-based pathologies associated with diabetes complications, which make the development of a potent aldose reductase inhibitor an obvious and attractive strategy to prevent or delay the onset and progression of the complications. Structural studies of aldose reductase and the homologous aldehyde reductase in complex with inhibitor were carried out to explain the difference in the potency of enzyme inhibition. The aim of this review is to provide a comprehensive summary of previous studies to aid the development of aldose reductase inhibitors that may have less toxicity problems than the currently available ones. Received 4 December 2006; received after revision 12 February 2007; accepted 20 April 2007     

Modulation of protein biophysical properties by chemical glycosylation: biochemical insights and biomedical implications

Glycosylation constitutes one of the most important posttranslational modifications employed by biological systems to modulate protein biophysical properties. Due to the direct biochemical and biomedical implications of achieving control over protein stability and function by chemical means, there has been great interest in recent years towards the development of chemical strategies for protein glycosylation. Since current knowledge about glycoprotein biophysics has been mainly derived from the study of naturally glycosylated proteins, chemical glycosylation provides novel insights into its mechanistic understanding by affording control over glycosylation parameters. This review presents a survey of the effects that natural and chemical glycosylation have on the fundamental biophysical properties of proteins (structure, dynamics, stability, and function). This is complemented by a mechanistic discussion of how glycans achieve such effects and discussion of the implications of employing chemical glycosylation as a tool to exert control over protein biophysical properties within biochemical and biomedical applications. Received 15 December 2006; received after revision 28 March 2007; accepted 25 April 2007     

邻苯二甲酸丁基苄酯对雄性大鼠生殖系统影响

研究邻苯二甲酸丁基苄酯(BBP)对雄性生殖内分泌系统的损害作用及其机制．将不同剂量的BBP(0、0．45、0．9、1．8 mL/kg),每日对Wistar雄性大鼠连续灌胃,染毒30 d、60 d,测定大鼠血清中FSH、LH、T和睾丸匀浆中T的水平及睾丸标志酶ACP、γ-GT的活性．随着BBP染毒剂量的增加及时间的延长血清中及睾丸匀浆中T的水平显著下降(P＜0．01),血清中LH、FSH呈上升趋势(P＜0．05),睾丸中ACP水平先升后降,γ-GT的活性则明显下降(P＜0．01)．BBP对雄性失鼠有明显的生殖毒性,影响其血清及睾丸性激素水平和酶活性,这可能与BBP对支持细胞和生精上皮的损害有关．     

温敏性水凝胶作为固定化酶载体的研究

提出水凝胶载体材料优化模型,根据优化结果制备出了两种性能相异的载体材料即聚丙烯酰胺/2-甲基丙烯酸羟基乙酯和聚N-异丙基丙烯酰胺/2-甲基丙烯酸羟基乙酯,并用其包埋α-胰凝乳蛋白酶,利用载体材料的温敏性可实现固定化酶活力的可控及连续可调,两种固定化酶经连续催化8次,固定化酶活力并无明显下降.     

腹部消化器官病变部位与两类腹痛部位的关系

目的:探讨腹部消化器官疾病所致内脏痛及腹膜痛的部位与病变部位的关系.方法:收集1226例有腹痛表现的腹部消化器官疾病患者的临床资料,分别统计分析内脏痛部位及腹膜痛部位与内脏病变部位的关系.结果:内脏痛平面与病变内脏起源的原肠的平面呈正相关(rs=0.87,P<0.01).腹膜痛最先出现或最明显的部位与病变内脏的解剖部位一致(=0.96,P<0.01).结论:腹部消化器官疾病所致内脏痛及腹膜痛的部位均与病变部位显著相关.依据腹痛部位定位诊断,需要分清腹痛类型,分别根据内脏痛及腹膜痛部位推测病变内脏的胚胎起源及解剖部位.     

亚麻纤维的酶处理

亚麻纤维织物具有优良的吸湿、透气、滑爽等特点,但因其刺痒感和抗皱性差而大大影响了服用性能.针对亚麻纤维织物的这一缺陷概括介绍了生物酶的种类、特性及作用机理,特别对纺织用果胶酶和纤维素酶的使用情况进行了论述.探讨了亚麻纤维的各种酶处理方法及作用,以便改善其服用性能.     

外源性H2S通过调节β-位淀粉样前体蛋白裂解酶1表达对PC12细胞APP／Aβ代谢的影响

目的观察外源性硫化氢对嗜铬细胞瘤细胞β-位淀粉样前体蛋白裂解酶1（BACE1）的调节作用,进而探讨其对淀粉样前体蛋白／β-位淀粉样蛋白代谢途径的影响。方法用硫氢化钠作外源性H2s供体,实验设空白对照组、NaHs50μmol／L组、NaHS100μmol／L组和NariS200μmol／L组,按分组浓度处理PC12细胞24h后,RT-PCR和Western blot法检测细胞内BACE1 mRNA及蛋白表达,并用Western blot法继而检测APP代谢过程中关键蛋白APP、C99、C83表达变化,EusA法检测细胞培养液中AB40和AB42水平。结果NaHS在实验浓度范围内从基因与蛋白两个水平上呈剂量依赖性下调BACE1表达,并下调C99、Ap40和Ap42蛋白表达,上调C83蛋白,各NaHS组分别与对照组比较,差别均有统计学意义（P〈0．05）,而对APP蛋白表达没有影响,各组间比较差别无显著性（P〉0．05）。结论外源性H2s具有通过调节PC12细胞BACE1表达下调APP／Aβ代谢的作用。     

胰岛素信号通路PI3K／Akt对海马神经元β-淀粉样前体蛋白裂解酶1mRNA水平的影晌

目的通过胰岛素和磷脂酰肌醇-3激酶（P13K）抑制剂渥曼青霉素（wortmannin）对P13K／丝氨酸苏氨酸蛋白激酶（P13K／Akt）信号通路的激活和抑制作用,观察P13K／Akt信号通路对海马神经元β-淀粉样前体蛋白裂解酶1（BACEl）mRNA水平表达的影响。方法20只sD大鼠随机分为空白对照组、假手术组、胰岛素组和渥曼青霉素组,海马立体定向注射胰岛素和P13K抑制剂渥曼青霉素。逆转录一聚合酶链反应（RT-PCR）检测P13K／Akt信号传导下游蛋白Akt以及BACEImRNA水平。结果注射胰岛素的海马P13K信号通路下游信号分子：AktmRNA表达上调（分别较空白和阴性对照组P=0．047,P=0．002）,而BACElmRNA表达下调（分别较空白和阴性对照组P=0．004,P=0．01）。渥曼青霉素组的P13K下游信号分子AktmRNA表达明显被抑制（分别较空白和阴性对照组P=0．002,P=0．039）,同时BACEImRNA的表达较对照组上调（分别较空白和阴性对照组P=0．039,P=0．018）。结论胰岛素信号通路P13K／AM可以调节BACEl的转录水平参与阿尔茨海默病的发病机制。     

Sugar-mimicking glycosidase inhibitors: bioactivity and application

A large number of compounds mimicking the structures of monosaccharides or oligosaccharides have been discovered from natural sources. Such sugar mimics inhibit carbohydrate-degrading enzymes because of a structural resemblance to the sugar moiety of the natural substrate. Carbohydrate-degrading enzymes are involved in a wide range of important biological processes, such as intestinal digestion, posttranslational processing of the sugar chain of glycoproteins, their quality control mechanisms, lysosomal catabolism of glycoconjugates, and some viral infections. It has now been realized that inhibitors of the enzymes have enormous therapeutic potential in diabetes and lysosomal storage disorders. In this review, the general bioactivity, current applications, and the prospects for new therapeutic applications are described. Received 27 August 2008; received after revision 08 November 2008; accepted 03 December 2008     

酶化苏云金芽孢杆菌固态发酵培养基研究

在生物农药生产过程中，粉碎能耗占据了生产成本的10％以上。采用纤维素酶对苏云金芽孢杆菌固体发酵的培养基进行前处理，得到一种易粉碎的培养基，用该培养基发酵所得产品后处理能耗明显降低，且和原培养基发酵产品的效价相当，证明纤维素酶的加入没有影响菌种的生长。