Araplysillins-I and-II: Biologically active dibromotyrosine derivatives from the spongePsammaplysilla arabica

Summary Araplysillins-I and-II, two novel dibromotyrosine derivatives, were isolated fromPsammaplysilla arabica and their structure was elucidated by spectroscopic methods. They proved to be inhibitors of Na⁺/K⁺ ATPase and to have antimicrobial activity.     

Interaction of mitochondrial porin with cytosolic proteins

Summary Intracellular phosphorylation is an important step in active uptake and utilization of carbohydrates. For example glucose and glycerol enter the liver, cell along the extra intracellular gradient by facilitated diffusion through specific carriers and are concentrated inside the cell by phosphorylation via hexokinase or glycerol kinase. Depending on the function of the respective tissue the uptake of carbohydrates serves different metabolic purposes. In brain and kidney medulla cells which depend on carbohydrates, glucose and glycerol are taken up according to the energy demand. However, in tissues such as muscle which synthesize glycogen or like liver which additionally produce fat from glucose, the uptake of carbohydrates has to be regulated according to the availability of glucose and glycerol. How the reversible coupling of the kinases to the outer membrane pore and the mitochondrial ATP serves to fulfil these specific requirements will be explained as well as how this regulates the carbohydrate uptake in brain according to the activity of the oxidative phosphorylation and how this allows glucose uptake in liver, and muscle to persist in the presence of high glucose 6-phosphate without activating the rate of glycolysis.     

6-氮杂甾醇类Ⅱ型5-α还原酶抑制剂的三维定量构效关系研究和虚拟筛选

采用Topomer CoMFA对37个6-氮杂甾醇类抑制剂进行三维定量构效关系分析,新建模型的交互验证和拟合相关系数为q2=0.774,r2=0.965,结果表明模型具有良好的可信度和预测能力.将基于配体的Topomer search虚拟筛选、基于受体的分子对接虚拟筛选和基于3D-QSAR模型的分子活性预测等方法运用到新抑制剂的分级筛选,最终获得4个高活性的新抑制剂分子.新抑制剂的Surflex-dock结果显示6-氮杂甾醇类抑制剂与5AR-Ⅱ靶点的作用模式主要是氢键作用.MTT法生物学活性测试结果显示新抑制剂能显著抑制BPH-1细胞增殖,且抑制程度呈浓度依赖性.通过分子对接机理解释和细胞学实验的抑制前列腺增生活性测试,这两种研究方式相互验证,证明此虚拟筛选方法能够为治疗良性前列腺增生的新药设计提供有效候选化合物.     

肿瘤血管生成抑制剂临床应用进展

血管生成抑制剂已被证明是一类有效的肿瘤治疗药物.概述了从单靶点、多靶点,到广谱血管生成抑制剂在临床上的应用;介绍了单克隆抗体、小分子和内源性的血管生成抑制剂及其相应靶点,讨论了新的靶点及有前景的新型血管生成抑制剂,希望为未来临床治疗提供切实的帮助.     

从兔骨骼肌综合提取ALD等五种酶的研究

采用一种组合５’－ＡＭＰ亲和层析、离子交换层析、分子筛层析以及重结晶的方法，从经硫酸铵沉淀初步分离的四个兔骨骼肌酶组分中逐步分离和纯化出醛缩酶等五种医用酶。本方法提取的五种酶均具有高比活和高纯度。本方法提取成本低，操作简便，酶活回收率高，因此具有应用价值     

Alzheimer's disease: fundamental and therapeutic aspects

Alzheimer's disease is the most common type of progressive and debilitating dementia affecting aged people. In some early — as well as late-onset familial cases, a genetic linkage with chromosomes 14, 21 (early-onset) or 19 (late-onset) has been indicated. Furthermore, a direct or indirect role has been attributed to normal or structurally altered amyloid -protein (concentrated in senile plaques) and/or excessively phosphorylated tau protein (located in neurofibrillary tangles). Degeneration of cholinergic neurons and concomitant impairment of cortical and hippocampal neurotransmission lead to cognitive and memory deficits. Several compounds are being tested in attempts to prevent and/or cure Alzheimer's disease, including tacrine, which has very modest efficacy in a sub-group of patients, and new acetylcholinesterase inhibitors. Pilot experiments have also been launched using nerve growth factor (NGF) to prevent or stabilize the processes of cholinergic pathway degeneration. Alternatively, antioxidants, free radical scavengers and/or non steroidal anti-inflammatory agents may be screened as potential therapies for neurodegenerative diseases induced by multiple endogenous and/or exogenous factors. The recent use of transgenic mice, in parallel with other genetic, biochemical and neurobiological systems, in vivo and/or in vitro (cell cultures), should accelerate the discovery and development of specific drugs for the treatment of Alzheimer's disease.     

混合拥挤试剂对人肌肌酸激酶稳定性的影响作用研究

为了更加真实地模拟细胞内环境,在人肌肌酸激酶(HCK)的去折叠环境中同时加入了大分子拥挤试剂(葡聚糖)和小分子渗透剂(蔗糖),采用酶活性、荧光发射谱和溶液浊度检测等方法研究肌酸激酶在含有蔗糖和葡聚糖的混合拥挤环境中的稳定性,结果表明在肌酸激酶盐酸胍变性过程中,蔗糖不仅抑制肌酸激酶酶活性的丧失,还稳定肌酸激酶的构象,而葡聚糖对肌酸激酶保护能力相对较弱.对于热变性过程,相同质量浓度的蔗糖和葡聚糖能同等程度地减缓肌酸激酶活性的丧失,并抑制聚沉的产生.在葡聚糖和蔗糖同时存在的情况下,两者的保护作用可以累加,并共同维持肌酸激酶的稳定性.     

过量维甲酸对小鼠胚胎神经管RhoA和Rac1表达的影响

目的:探讨过量维甲酸(RA)对小鼠胚胎神经管Rho A、Rac 1蛋白表达的影响.方法:应用免疫组织化学染色和图像分析方法检测Rho A、Rac 1蛋白的表达,分析在正常对照组和实验组小鼠胚胎神经管上皮的分布状况和表达水平的变化.结果:在各正常对照组和实验组,Rho A在神经管腔面、神经上皮细胞的细胞膜以及胞质均呈不同程度的阳性着色;比较有趣的是,在两侧神经褶靠拢的部位,Rho A的表达水平较神经管其它部位要强.统计学显示:Rho A在正常神经管的表达有时间依赖性;而且与正常对照组相比,其在实验组的表达水平明显高于正常对照组.在正常对照组,Rac 1的表达随着孕龄的增加在减弱;在各实验组,Rac1的表达都是阴性的.结论:过量RA会导致胚胎神经管Rho A和Rac1的表达异常,这两种蛋白与过量维甲酸致神经管畸形有关.     

Albumin resuscitation protects against traumatic/hemorrhagic shock-induced lung apoptosis in rats

Objective： To determine the effects of albumin administration on lung injury and apoptosis in traumatic/hemorrhagic shock （T/HS） rats. Methods： Studies were performed on an in vivo model of spontaneously breathing rats with induced T/HS; the rats were subjected to femur fracture, ischemia for 30 min, and reperfusion for 20 min with Ringer＇s lactate solution （RS） or 5% （w/v） albumin （ALB）, and the left lower lobes of the lungs were resected. Results： Albumin administered during reperfusion markedly attenuated injury of the lung and decreased the concentration of lactic acid and the number of in situ TdT-mediated dUTP nick-end labelling （TUNEL）-positive cells. Moreover, immunohistochemistry performed 24 h after reperfusion revealed increases in the level of nuclear factor κB （NF-κB）, and phosphorylated p38 mitogen-activated protein kinase （MAPK） in the albumin-untreated group was down-regulated by albumin treatment when compared with the sham rats. Conclusion： Resuscitation with albumin attenuates tissue injury and inhibits T/HS-induced apoptosis in the lung via the p38 MAPK signal transduction pathway that functions to stimulate the activation of NF-κB.