Induction of apoptotic cell death in human bladder cancer cells by ethanol extract of Zanthoxylum schinifolium leaf,through ROS-dependent inactivation of the PI3K/Akt signaling pathway

BACKGROUND/OBJECTIVESZanthoxylum schinifolium is traditionally used as a spice for cooking in East Asian countries. This study was undertaken to evaluate the anti-proliferative potential of ethanol extracts of Z. schinifolium leaves (EEZS) against human bladder cancer T24 cells.MATERIALS/METHODSSubsequent to measuring the cytotoxicity of EEZS, the anti-cancer activity was measured by assessing apoptosis induction, reactive oxygen species (ROS) generation, and mitochondrial membrane potential (MMP). In addition, we determined the underlying mechanism of EEZS-induced apoptosis through various assays, including Western blot analysis.RESULTSEEZS treatment concentration-dependently inhibited T24 cell survival, which is associated with apoptosis induction. Exposure to EEZS induced the expression of Fas and Fas-ligand, activated caspases, and subsequently resulted to cleavage of poly (ADP-ribose) polymerase. EEZS also enhanced the expression of cytochrome c in the cytoplasm by suppressing MMP, following increase in the ratio of Bax:Bcl-2 expression and truncation of Bid. However, EEZS-mediated growth inhibition and apoptosis were significantly diminished by a pan-caspase inhibitor. Moreover, EEZS inhibited activation of the phosphoinositide 3-kinase (PI3K)/Akt pathway, and the apoptosis-inducing potential of EEZS was promoted in the presence of PI3K/Akt inhibitor. In addition, EEZS enhanced the production of ROS, whereas N-acetyl cysteine (NAC), a ROS scavenger, markedly suppressed growth inhibition and inactivation of the PI3K/Akt signaling pathway induced by EEZS. Furthermore, NAC significantly attenuated the EEZS-induced apoptosis and reduction of cell viability.CONCLUSIONSTaken together, our results indicate that exposure to EEZS exhibits anti-cancer activity in T24 bladder cancer cells through ROS-dependent induction of apoptosis and inactivation of the PI3K/Akt signaling pathway.     

扶正消瘤液对肿瘤化疗增敏作用的临床研究

观察中药复方在肿瘤化疗增敏方面的作用。将 6 9例晚期肿瘤患者随机分为治疗组和对照组 ,治疗组用中药复方扶正消瘤液配合化疗进行临床治疗 ,并与单纯化疗组进行对照。两组化疗方法相同。结果 ,治疗组有效率为 31.5 8% ,对照组有效率为 2 2 .5 8% ,统计学处理差异明显 (P<0 .0 5 )。治疗组治疗前后 TL c TR、NKc A、s IL-2 R及对照组治疗后相比均有显著性差异。结论 ,中药复方扶正消瘤液对晚期肿瘤化疗有一定的增敏作用。     

麝香酮对氰化钠加缺糖致PC12细胞缺血损伤的保护作用

目的:研究麝香酮对PC12细胞缺血损伤的影响。方法:在离体培养的PC12细胞,用NaCN加缺糖造成拟缺血损伤模型,通过细胞形态学观察、MTT微量比色、培养介质LDH活力测定,研究了麝香酮对该模型的保护作用。结果:10-7~510-5mol/L范围内,麝香酮呈浓度依赖性地降低NaCN加缺糖造成拟缺血损伤模型培养介质内LDH的释放,其IC50为:43.33μmol/L。在10-7~510-5mol/L范围内,麝香酮呈浓度依赖性地增加NaCN加缺糖造成拟缺血损伤模型培养介质的MTT比色值,其IC50为30.62μmol/L。结论:麝香酮对PC12细胞缺血损伤具有保护作用。     

细胞共培养技术在医药研究中的应用

细胞共培养由于能更好地模拟体内环境,便于更好的观察细胞与细胞、细胞与培养环境之间的相互作用以及探讨药物的作用机制和可能的作用靶点,填补了单层细胞培养与整体动物实验研究的鸿沟,近年来倍受医药领域的关注,成为药物研发、生物制药领域的研究热点.细胞共培养方法包括直接共培养和间接共培养,主要用于疾病病理基础、新型治疗手段以及药物活性筛选的研究.现有的细胞共培养技术主要用于单一药物的药效学研究,用于联合药物相互作用的研究甚少.中药复方之间协同配伍,减毒增效.细胞共培养技术符合中药多成分、多靶点的作用特点,这对于未来探讨中药联合用药对机体的作用及机制的研究具有一定参考价值,为中药及复方研究提供了一种新的手段.该文就细胞共培养技术的方法与运用进行了概述,并对该技术运用于中药及复方的研究进行了展望.     

中药复方研发与专利保护协调发展之积极影响分析

中药复方研发成果与日俱增,而成果的专利保护状况却不容乐观.中药复方专利保护与中药新药研发、产业发展、中药国际化等诸多领域息息相关,促成中药复方研发与专利保护的协调发展对于国内乃至国际社会影响深远.     

盐酸头孢吡肟中N-甲基吡咯烷的离子色谱-电导检测法测定

建立了直接进样离子色谱电导检测法测定盐酸头孢吡肟中的N-甲基吡咯烷.选用高容量阳离子交换柱,进样量25 μl,流动相为9 mmol/L硝酸(含15%乙腈),流速0.9 ml/min,35 min内洗脱所有成分.N-甲基吡咯烷在0.9～25μg/ml浓度范围内线性关系良好(r=0.999 7),检出限为0.095μg/ml,回收率为95.3%.     

Development of cyclosporin A-loaded hyaluronic microsphere with enhanced oral bioavailability

To develop a hyaluronic microsphere with the improved oral bioavailability of poorly water-soluble cyclosporin A (CsA), the microspheres were prepared with varying ratios of sodium hyaluronate (HA)/sodium lauryl sulfate (SLS)/CsA using a spray-drying technique. The effects of HA and SLS on the dissolution and solubility of CsA in microspheres were investigated. The CsA-microsphere prepared with HA/SLS/CsA at the ratio of 4/2/1 gave the highest solubility and dissolution rate of CsA among those formulae tested. As solubility and dissolution rate of CsA were increased about 17- and 2-fold compared to CsA powder, respectively, this CsA-microsphere was selected as an optimal formula for oral delivery in rats. The CsA-microsphere and Sandimmun neoral sol gave significantly higher blood levels compared with CsA powder alone. Moreover, the AUC, T(max) and C(max) values of CsA in CsA-microsphere were not significantly different from those in Sandimmun neoral sol in rats, indicating that CsA-microsphere was bioequivalent to the commercial product in rats. Our results demonstrated that the CsA-microsphere prepared with HA and SLS, with improved bioavailability of CsA, might have been useful to deliver a poorly water-soluble CsA.     

脂质体肺部给药的研究

由于脂质体肺部给药具有刺激性小、吸收迅速、生物利用度高、安全性好、可实现持续缓慢释药等独特优势而成为近年来制剂领域的研究热点之一。本文论述脂质体肺部给药的特点、稳定性以及在药代动力学、药效学和安全性等方面的最新研究进展。