系统药物学

系统药物学,是在系统水平认识药物,研究药物作用的系统性、多组分药物系统、和药物信息分子。系统药物学包括计算系统药物学、实验系统药物学及系统药物治疗学,需要引入新的思路、技术、算法与软件、设备等。中药现代化的方向是系统药物学,中药西化只是其组成部分之一。同时,要西药中化,西药中化与中药西化将成为构建系统药物学理论体系的重要组成部分。本文还讨论了系统药物学研究对药物发现和个性化治疗的意义。     

钙阻断剂与肿瘤治疗

抗药性是肿瘤化疗的最大障碍之一,具抗药性的肿瘤细胞药物外排功能很强,而钙阻断剂能抑制抗癌药物从抗药性肿癌细胞排出,导致细胞抗药性减弱,可用于肿囊化疗,有潜在的临床应用价值,但有副作用。故应寻求毒副作用小类似钙阻断剂的其他修饰物以促进肿癌化疗。     

中华鳖常见致病菌对13种抗菌药物的敏感性测定

本研究检测了13种抗菌药物对7株中华鳖致病菌的最小抑菌浓度（MIC），结果表明，从河南郑州的患病中华鳖体内分离的菌株较湖北武汉、湖北咸宁的病鳖体内分离的菌株对各类药物的敏感性强，而从武汉和咸宁产地的病鳖体内分离的菌株其对各类药物的敏感性也有很大差异，结果显示供试菌株对抗菌药物产生了不同程度的耐药性，推测滥用药物和用药方法不当是导致病原菌产生耐药性的原因。     

Multitasking with neurotensin in the central nervous system

The 13-amino acid peptide neurotensin (NT) was discovered over 30 years ago and has been implicated in a wide variety of neurotransmitter and endocrine functions. This review focuses on four areas where there has been substantial recent progress in understanding NT signaling and several functions of the endogenous peptide. The first area concerns the functional activation of the high-affinity NT receptor, NTR-1, including the delineation of the NT binding pocket and receptor domains involved in functional coupling to intracellular signaling pathways. The development of NT receptor antagonists and the application of genetic and molecular genetic approaches have accelerated progress in understanding NT function in several areas, including the involvement of NT in antipsychotic drug actions, psychostimulant sensitization and the modulation of pain, and these are reviewed in that order. There is now substantial evidence indicating that NT is required for certain antipsychotic drug actions and that the peptide plays a key role in stress-induced analgesia.Received 18 March 2005; received after revision 9 May 2005; accepted 23 May 2005     

Phosphodiesterase: overview of protein structures, potential therapeutic applications and recent progress in drug development

Phosphodiesterases (PDEs) are essential regulators of cyclic nucleotide signaling with diverse physiological functions. Because of their great market potential and therapeutic importance, PDE inhibitors became recognized as important therapeutic agents in the treatment of various diseases. Currently, there are seven PDE inhibitors on the market, and the pharmacological and safety evaluations of many drug candidates are in progress. Three-dimensional (3D) structures of catalytic domains of PDE 1, -3, -4, -5 and -9 in the presence of their inhibitors are now available, and can be utilized for rational drug design. Recent advances in molecular pharmacology of PDE isoenzymes resulted in identification of new potential applications of PDE inhibitors in various therapeutic areas, including dementia, depression and schizophrenia. This review will describe the latest advances in PDE research on 3D structural studies, the potential of therapeutic applications and the development of drug candidates.Received 30 November 2004; received after revision 24 January 2005; accepted 5 February 2005     

水溶性壳聚糖的热分解动力学研究

利用多重扫描速率法研究了商品水溶性壳聚糖(盐酸盐)的热分解反应动力学.主分解过程可以分为两个阶段,首先是高分子盐的分解,其次是高分子链的解聚合,两个阶段的反应活化能E和指前因子lnA值分别为173.99±2.63,128.97±1.87 kJ·mol-1和35.28±0.62,24.69±0.44 min-1.利用Achar微分法判定该物质两个阶段的热分解最概然机理函数相同,为f(α)＝ 1-α,该模型属于每个颗粒上只有一个核心的随机成核和随后生长机理.     

斑马鱼在人类疾病模型以及药物筛选中的应用

小鼠作为研究人类疾病的动物模型已被广泛使用,然而其在大规模遗传筛选和药物筛选方面受到诸多限制.斑马鱼作为典型的脊椎动物,在器官水平和细胞水平上与哺乳动物相似,而且胚胎和幼体的透明特性为实时观察提供了方便;其基因与人类有很高的同源性且易于进行基因操作,因而成为了研究人类疾病的理想动物模型.本文介绍了斑马鱼在人类疾病模型和药物 筛选中的研究概况.     

A pathway profile-based method for drug repositioning

Finding new applications for existing pharmaceuticals,known as drug repositioning,is a validated strategy for resolving the problem of high expenditure but low productivity in drug discovery.Currently,the prevalent computational methods for drug repositioning are focused mainly on the similarity or relevance between known drugs based on their "features",including chemical structure,side effects,gene expression profile,and/or chemical-protein interactome.However,such drug-oriented methods may constrain the newly predicted functions to the pharmacological functional space of the existing drugs.Clinically,many drugs have been found to bind "off-target"(i.e.to receptors other than their primary targets),which can lead to undesirable effects.In this study,which integrates known drug target information,we propose a disease-oriented strategy for evaluating the relationship between drugs and disease based on their pathway profile.The basic hypothesis of this method is that drugs exerting a therapeutic effect may not only directly target the disease-related proteins but also modulate the pathways involved in the pathological process.Upon testing eight of the global best-selling drugs in 2010(each with more than three targets),the FDA(Food and Drug Administration,USA)-approved therapeutic function of each was included in the top 10 predicted indications.On average,60% of predicted results made using our method are proved by literature.This approach could be used to complement existing methods and may provide a new perspective in drug repositioning and side effect evaluation.     

叶绿酸铁与环糊精包合性质的初步研究

探索环糊精改进叶绿酸铁性质的可行性.紫外法测定环糊精与叶绿酸铁的包合常数;研磨法制备包合物;测定包合物溶解速度和增溶度,测定溶液降解半衰期和固体样品热稳定性.实验结果表明系列环糊精中,叶绿酸铁与β-环糊精具有最大包合常数(Ka=2869.8 L/mol),β-环糊精包合物可加快叶绿酸铁的溶出度,提高溶解度,增强溶液及固体样品的光热稳定性.β-环糊精包合叶绿酸铁具有较好的技术效果.