Improved Synthesis of Biotinol-5′-AMP: Implications for Antibacterial Discovery

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Structure-Based Design of Type II Inhibitors Applied to Maternal Embryonic Leucine Zipper Kinase

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Biological activity of bevacizumab,a humanized anti-VEGF antibody <Emphasis Type="Italic">in vitro</Emphasis>

Bevacizumab (Avastin, Genentech) is a humanized monoclonal antibody targeting vascular endothelial growth factor (VEGF), a critical angiogenic factor involved in both physiological and pathological conditions. It has been recently approved by the US FDA as a first-line therapy for widespread metastatic colorectal cancer. This report is a detailed biological characterization of bevacizumab in a variety of in vitro models. It is shown that bevacizumab potently neutralizes VEGF and blocks its signal transduction through both the VEGFR-1 and VEGFR-2 receptors, as demonstrated by the inhibition of VEGF-induced cell proliferation, survival, permeability, nitric oxide production, as well as migration and tissue factor production. Although bevacizumab retains the ability to bind to human Fc receptors and complement protein C1q, it does not demonstrate cell or complement-mediated cytotoxicity in either VEGF producing or targeting cells. Thus the mechanism of anti-tumor activity of bevacizumab is most likely due to its anti-angiogenesis effect through binding and neutralization of secreted VEGF.     

天然产物对毛发色素的调节作用研究进展

毛发的颜色不仅受年龄、环境因素的影响,还受到众多因子的调控,其中主要有阿黑皮素原(POMC)、黑色素细胞刺激素(α-MSH)、黑色素1受体(MCIR)、小眼畸形相关蛋白因子(MITF)、酪氨酸酶(TYR)、酪氨酸相关蛋白酶1(TRP-1)、酪氨酸相关蛋白酶2(TRP-2)、刺鼠信号蛋白(ASIP)等。毛发颜色的异常常被认为是衰老的特征,给患者带来巨大的心理压力,但相关的治疗药物目前尚属空白。总结了天然药物对毛发颜色的影响程度和作用方式,以期阐明天然药物在治疗须发早白方面可能的作用途径及靶点,为从天然产物中寻找发掘新的药物奠定基础。     

基于全国中药资源普查的中药基本药物供应预警方法探讨

中药和中药饮片是基本药物目录的重要组成,是我国基本药物制度中医药特色的集中体现。然而以"安全、必需、有效、价廉"著称的基本药物,常常出现供不应求的情况。通常认为中成药多为复方组成,药味多样,相互之间价格可以互补,加之中药价格是波动的,短期上涨也会回落,所以短缺情况不十分严重。但中药价格暴涨暴跌现象普遍,由此造成的厂家停止中成药生产的情况时有发生,短期上涨对投料质量的影响也不容忽视。探讨了通过全国中药资源普查建立中药基本药物供应预警方法的必要性和可行性,并且以复方丹参片为实例进行了说明和演示。     

Recent trends in preclinical drug–drug interaction studies of flavonoids — Review of case studies,issues and perspectives

Because of health benefits that are manifested across various disease areas, the consumption of herbal products and/or health supplements containing different kinds of flavonoids has been on the rise. While the drug–drug interaction potential between flavonoids and co‐ingested drugs still remain an issue, opportunities exist for the combination of flavonoids with suitable anti‐cancer drugs to enhance the bioavailability of anti‐cancer drugs and thereby reduce the dose size of the anti‐cancer drugs and improve its therapeutic index. In recent years, scores of flavonoids have undergone preclinical investigation with variety of drugs encompassing therapeutic areas such as oncology (etoposide, doxorubicin, paclitaxel, tamoxifen etc.), immunosuppression (cyclosporine) and hypertension (losartan, felodipine, nitrendipine etc.). The review provides examples of the recent trends in the preclinical investigation of 14 flavonoids (morin, quercetin, silibinin, kaempferol etc.) with various co‐administered drugs. The relevance of combination of flavonoids with anti‐cancer drugs and a framework to help design the in vitro and in vivo preclinical studies to gain better mechanistic insights are discussed. Also, concise discussions on the various physiological factors that contribute for the reduced bioavailability of flavonoids along with the significant challenges in the data interpretation are provided. Copyright © 2015 John Wiley & Sons, Ltd.     

常用抗心律失常药对实验性心室晚电位的影响

本文采用常用抗心律失常药(AAD)对33条犬进行46次实验,观察AAD对实验性急性心肌梗塞(AMI)心室晚电位(VLP)的影响。结果表明;普鲁卡因酰胺、利多卡因、心律平、美多心安和乙胺碘呋+酮的VLP转阴率分别为44.4％、22.2％、0％、44.4％和42.8％(P>0.05);AAD抗室性心律失常(VA)疗效与VLP转阴无关,不能根据AAD对于VLP的影响与否,预测其抗VA的疗效。     

中药药物质量精准预期的相关性思考

从中药本质及其用药形式与质量控制水平进行关联分析, 阐述中药理论精准理念及其中药药物质量的优势与特色, 并论述探究实现中药理想药物与中药药物质量精准预期的路经。基于中药药物本质, 应用自然药学观药物体系理念构架中药有效物质基础及其药物组成, 结合整体观与还原论关联分析,可破解自然药物原及其药物质量的不确定性难题,从宏观到微观构架药物体系而实现中药药物质量精准预期与推进中药产业质量升级。     

药用亲缘学论纲——知识谱系,认识论和范式转换

中药资源是我国中医药事业发展的基础,采用创新的理论和方法寻找和发现中药新资源是中药资源可持续利用研究的热点和重点。药用亲缘学研究药用生物(特别是药用植物)的生物亲缘关系,化学成分和疗效(传统疗效和药理活性)间的相关性,该学科的建立对于开发中药植物资源具有重要指导意义;系统发育基因组学方法可用于药物发现和开发的相关问题研究,在组学水平拓展了药用亲缘学的领域,由此衍生出药用基因组亲缘学的新概念。该文简述药用亲缘学的知识谱系,研究方法和范式转换,凸显药用基因组亲缘学的理论和实践价值,建议选择《中国药典》2010年版收录最多的毛茛科为例,对药用基因组亲缘学进行深入的实证研究。在基因组,转录组和代谢组水平探讨毛茛科及其重要族属系统发育和进化关系,揭示药用植物基因型和代谢表型,以及近缘种遗传多样性和化学多样性的内在关联。通过毛茛科示范研究,丰富药用亲缘学研究的内涵,扩展其外延,将药用基因组亲缘学视为药用亲缘学的升级版,开放地吸收有关领域的新知识和新技术,促进中药资源学科的成长,推动中药植物资源的开发和可持续利用。     

土家药天珠散防治血管性痴呆的有效成分与作用机制研究

采用双侧颈总动脉永久结扎复制慢性低灌注型血管性痴呆大鼠模型,常规饲养60 d后灌胃给予天珠散0.1 g·kg^-1,给药体积0.02 mL·g^-1,连续3 d,制备含药血清;采用UPLC检测天珠散入血成分并推测其结构;使用Discovery Studio 3.5软件进行反向找靶,并将获得的潜在靶标基因在线提交DAVID数据库进行基因富集分析。该文共推断获得天珠散5个入血成分,鉴定其中4个成分为parishin B,parishin C,parishin,偏诺皂苷元-3-O-α-L-吡喃鼠李糖基-(1→2)-β-D-葡萄糖苷;经反向找靶,获得Fit value≥0.6的药效团模型861个,从KEGG,BIOCARTA获得经文献验证的信号通路Cytokine-cytokine receptor interaction,Apoptosis等 9条,提示天珠散改善血管性痴呆的药理作用与机制可能与上述入血成分及相关信号通路有关。对于少数民族传统经验方,在药效验证的前提下,综合采用血清药物化学、计算机辅助药物设计、系统生物学等技术,将有益于民族效验方物质基础、作用机制的快速发现。