Molecular Targets of TRAIL-Sensitizing Agents in Colorectal Cancer

Tumor necrosis factor (TNF)-related apoptosis inducing ligand (TRAIL), a member of the TNF superfamily, interacts with its functional death receptors (DRs) and induces apoptosis in a wide range of cancer cell types. Therefore, TRAIL has been considered as an attractive agent for cancer therapy. However, many cancers are resistant to TRAIL-based therapies mainly due to the reduced expression of DRs and/or up-regulation of TRAIL pathway-related anti-apoptotic proteins. Compounds that revert such defects restore the sensitivity of cancer cells to TRAIL, suggesting that combined therapies could help manage neoplastic patients. In this article, we will focus on the TRAIL-sensitizing effects of natural products and synthetic compounds in colorectal cancer (CRC) cells and discuss the molecular mechanisms by which such agents enhance the response of CRC cells to TRAIL.     

Metal-Sulfate Induced Generation of ROS in Human Brain Cells: Detection Using an Isomeric Mixture of 5- and 6-Carboxy-2',7'-Dichlorofluorescein Diacetate (Carboxy-DCFDA) as a Cell Permeant Tracer

Evolution of reactive oxygen species (ROS), generated during the patho-physiological stress of nervous tissue, has been implicated in the etiology of several progressive human neurological disorders including Alzheimer's disease (AD) and amylotrophic lateral sclerosis (ALS). In this brief communication we used mixed isomers of 5-(and-6)-carboxy-2',7'-dichlorofluorescein diacetate (carboxy-DCFDA; C(25)H(14)C(l2)O(9); MW 529.3), a novel fluorescent indicator, to assess ROS generation within human neuronal-glial (HNG) cells in primary co-culture. We introduced pathological stress using the sulfates of 12 environmentally-, industrially- and agriculturally-relevant divalent and trivalent metals including Al, Cd, Cu, Fe, Hg, Ga, Mg, Mn, Ni, Pb, Sn and Zn. In this experimental test system, of all the metal sulfates analyzed, aluminum sulfate showed by far the greatest ability to induce intracellular ROS. These studies indicate the utility of using isomeric mixtures of carboxy-H(2)DCFDA diacetates as novel and highly sensitive, long-lasting, cell-permeant, fluorescein-based tracers for quantifying ROS generation in intact, metabolizing human brain cells, and in analyzing the potential epigenetic contribution of different metal sulfates to ROS-generation and ROS-mediated neurological dysfunction.     

由CPVA-g-PSSS功能接枝微球构建pH依赖型5-ASA结肠定位释药体系

采用铈盐-羟基氧化还原引发体系,在交联聚乙烯醇(CPVA)微球表面引发接枝聚合对苯乙烯磺酸钠(SSS),制备了接枝聚阴离子的功能接枝微球CPVA-g-PSSS,研究了其对5-氨基水杨酸(5-ASA)的吸附(载药)性能、机理和释放行为. 结果表明,在酸性介质中,受强静电相互作用驱动,CPVA-g-PSSS对5-ASA分子表现出很强的吸附能力,吸附容量达39.1 mg/g,可实现有效载药. 载药微球的释药行为具有强烈的pH值依赖性, 在pH=1的介质中基本不释药,而在pH=7.4的介质中发生突释,释放率可达86%,表现出良好的结肠定位释放行为.     

改性HZSM-5分子筛催化剂芳构化性能研究

制备Ni改性及水热改性HZSM-5分子筛催化剂,并在固定床连续微型反应装置上考察对正辛烷芳构化反应的催化性能。采用低温氮吸附、NH₃-TPD和FT-IR等方法对催化剂进行表征。结果表明,随着Ni含量的增加,催化剂B酸逐渐减少,L酸逐渐增多,总酸呈现出先减少后增多的趋势,适宜的Ni含量能够促进芳构化反应。随着水热温度的提高,B酸减少,总酸增多,催化剂的芳构化活性逐渐降低。催化剂活性与表面酸性有关,尤其是与强酸量有关,强酸量下降,芳构化能力下降。     

预处理温度对SAPO-11催化丁烯骨架异构化性能的影响

采用水热合成法合成的SAPO-11分子筛,经酸洗、干燥和焙烧处理得H-SAPO-11分子筛,考察了预处理温度对催化剂物化性能的影响,采用XRD、XRF、IR和NH₃-TPD等手段对催化剂进行表征。实验证明,500 ℃预处理后H-SAPO-11分子筛的结构缺陷较少,B酸位较多,骨架更完美;将其成型制成催化剂,对丁烯骨架异构化反应显示更优良的催化活性、选择性和稳定性。     

SmCo5垂直磁记录薄膜的研究进展

SmCo5垂直磁化膜具有极高的单轴磁晶各异性,能有效克服当前垂直磁记录介质所面临的超顺磁效应问题,是未来超高密度磁记录介质的候选材料。本文叙述了SmCo5垂直磁记录薄膜制备的国内外发展现状,着重介绍了底层材料和结构对SmCo5垂直磁化膜微观结构和磁性能的影响,同时对今后SmCo5垂直磁记录薄膜的研究方向作了展望。     

3-乙基-5-吡唑羧酸乙酯的合成研究

3-乙基-5-吡唑羧酸乙酯是新型杀螨剂吡螨胺的关键中间体,传统的合成方法副反应多、产率低、反应速率慢,探索了用乙酸做催化剂,高效方便地合成了目标产物。同时研究了乙酸做催化剂时合成目标产物的最佳条件。实验结果表明,在丙酰丙酮酸乙酯、乙酸与水合肼的物质的量比为1∶2∶1.2,反应时间4 h,反应温度0～5℃时,收率达到98.53%,纯度达到96.2%。     

1-(5-(4-氯苯基)-1-(2,4-二氯苯基)-4-甲基-1H-吡唑-3-基)-3-(吡啶-3-基甲基)脲的合成

以5-(4-氯苯基)-1-(2,4-二氯苯基)-4-甲基-1H-吡唑-3-甲酸与二氯亚砜为起始原料,经酰氯化反应、酰胺反应、霍夫曼重排以及水解反应生成中间体5-(4-氯苯基)-1-(2,4-二氯苯基)-3-氨基-4-甲基-1H-吡唑,再经过与氯甲酸苯酯反应、胺酯交换反应得到标题化合物,其结构经1HNMR、MS谱确证,总收率26.9%。     

5-溴苊的合成研究

以苊为原料,采用两种氧化溴化体系合成5-溴苊,确定较佳的溴化体系及溴化工艺条件。考察了溶剂种类、物料配比、反应温度及时间对反应收率的影响。实验结果表明:在乙酸乙酯溶剂中,反应温度20℃,反应时间为1h,n(溴酸钠)∶n(亚硫酸氢钠)∶n(苊)=1.2∶1.2∶1,产品收率为85.8%,纯度﹥98%(HPLC)。产品结构经IR和1 H NMR表征。