依那普利预防阵发房颤复发的临床疗效

[目的]观察胺碘酮联合依那普利预防阵发房颤复发的疗效及对P波离散度(Pd)的影响.[方法]将52例阵发房颤病人随机分成A、B两组(每组26例),A组口服依那普利加胺碘酮,B组单服胺碘酮,随访6个月,每3个月作1次心电图(ECG)检测Pd及统计房颤发作情况.[结果]治疗3个月后两组Pd值与治疗前相比均明显降低(P＜0.01),两组间的Pd值无统计学差异,6个月后两组病例的Pd值均进一步降低,A组下降程度较B组明显,两组间差异有显著性(P＜0.01).后3个月两组病例平均每人房颤发作次数及持续时间与前3个月相比均明显减少(P＜0.01),A组减少程度较B组明显,两组间有显著性差异(P＜0.01).[结论]依那普利可能有预防阵发房颤复发的作用.     

Partial cystectomy for muscle-invasive bladder cancer: a review of the literature

The radical cystectomy (RC) for muscle-invasive bladder cancer is one of the most morbid and complex urologic procedures performed today. To avoid these complications, the partial cystectomy (PC) has been offered as an alternative in carefully selected patients as a means of achieving equal oncologic efficacy with less morbidity. Selection criteria should include solitary tumors without concomitant carcinoma in situ (CIS) and amenable to resection with 1–2 cm margins in a normally functioning bladder. In addition to the standard work-up, random bladder and prostatic biopsies may be performed. The PC can be performed through an open, laparoscopic, or robot-assisted approach, each with acceptable outcomes. A number of techniques have been developed to identify and resect the tumor completely with negative margins, while preventing tumor spillage within the abdomen. While there are no randomized trials, single institution series have demonstrated acceptable oncologic outcomes in appropriately selected patients. Therefore, offering PC in the appropriate candidate, including those patients who do not accept or are unfit for the associated morbidity of a RC, represents an acceptable alternative.     

Anticancer properties of green-synthesised zinc oxide nanoparticles using Hyssopus officinalis extract on prostate carcinoma cells and its effects on testicular damage and spermatogenesis in Balb/C mice

The unclear bio-safety issue and potential risk of nanoparticles (NPs) on various organelles can be considered as a major challenge. In the present study, we have assessed the green synthesis of ZnO nanoparticles using Hyssop (Hyssopus officinalis) extract and their effects on PC3 cell line and BALB/c mice model. The cytotoxicity of the ZnO-NPs was assessed on PC3 cell line by MTT test after characterisation. Apoptotic effect of ZnO-NPs was determined by in vitro AO/PI staining. The histopathological assessments and determination of LH and FSH levels carried out as in vivo analysis in BALB/c adult male mice. The expression of major genes involved in spermatogenesis and sperm maturation (Adam3, Prm1, Spata19, Tnp2, Gpx5) were also analysed. The obtained result demonstrated that the IC₅₀ for PC3 cell line treated with green-synthesised ZnO-NPs during 24 and 48 hr was reported 8.07 and 5 µg/ml respectively. Meanwhile, the induced apoptosis was recorded 26.6% ± 0.05, 44% ± 0.12 and 80% ± 0.07 of PC3 cells. The results of gene expression analysis revealed that the increase in the concentration of ZnO-NPs significantly (p < .05) down-regulated the Adam3, Prm1, Spata-19, Tnp2 and Gpx5 genes. The overall results of this research elucidated that ZnO-NPs impaired spermatogenesis, sperm maturation process and sperm motility.     

Aspartame-induced apoptosis in PC12 cells

Aspartame is an artificial sweetner added to many low-calorie foods. The safety of aspartame remains controversial even though there are many studies on its risks. In this study, to understand the physiological effects of trace amounts of artificial sweetners on cells, the effects of aspartame on apoptosis were investigated using a PC12 cell system. In addition, the mechanism of apoptosis induced by aspartame in PC12 cells and effects on apoptotic factors such as cytochrome c, apoptosis-inducing factor, and caspase family proteins were studied by Western blotting and RT-PCR.Aspartame-induced apoptosis in PC12 cells in a dose-dependent manner. In addition, aspartame exposure increased the expressions of caspases 8 and 9, and cytochrome c. These results indicate that aspartame induces apoptosis mainly via mitochondrial pathway involved in apoptosis due to oxigen toxicity.     

Bornyl caffeate induces apoptosis in human breast cancer cells in vitro via the ROS- and JNK-mediated pathways

Aim： To investigate the effects of bornyl caffeate discovered in several species of plant on human breast cancer cells in vitro and the underlying mechanisms.
Methods： Human breast cancer cell line MCF-7 and other tumor cell lines （T47D, HepG2, HeLa, and PC12） were tested. Cell viability was determined using MTT assay, and apoptosis was defined by monitoring the morphology of the nuclei and staining with Annexin V-FITC. Mitochondrial membrane potential （MMP） was measured using JC-1 under fluorescence microscopy. Intracellular reactive oxygen species （ROS） were assessed by flow cytometry. The expression of apoptosis-associated proteins was determined by Western blotting analysis.

Results： Bornyl caffeate （10, 25, and 50 μmol/L） suppressed the viability of MCF-7 cells in dose- and time-dependent manners, but neither caffeic acid nor borneol showed cytotoxicity at a concentration of 50 μmol/L. Bornyl caffeate also exerted cytotoxicity to HepG2, Hela, T47D, and PC12 cells. Bornyl caffeate dose-dependently induced apoptosis of MCF-7 cells, increased the expression of Bax and decreased the expression of Bcl-xl, resulting in the disruption of MMP and subsequent activation of caspase-3. Moreover, bornyl caffeate triggered the formation of ROS and activated p38 and c-Jun JNK. In MCF-7 cells, the cytotoxicity of bornyl caffeate was significantly attenuated by SB203580 （p38 inhibitor）, SP600125 （JNK inhibitor）, z-VAD （pan-caspase inhibitor） or the thiol antioxidant L-NAC.

Conclusion： Bornyl caffeate exerts non-selective cytotoxicity against cancer cells of different origin in vitro. The compound induces apoptosis in human breast cancer MCF-7 cells via the ROS- and JNK-mediated pathways.     

IGF-1通过PI3K/Akt通路抑制MPP~+诱导PC12细胞凋亡机制的研究

目的探讨胰岛素样生长因子-1(insulin-like growth factor-1,IGF-1)对1-甲基-4-苯基吡啶离子(1-methyl-4-phenylpyridinium,MPP+)诱导的PC12细胞凋亡的抑制作用及其潜在的作用机制。方法以250μmol/L的MPP+损伤PC12细胞作为帕金森病(Parkinson disease,PD)细胞模型。实验分组如下:空白对照组、MPP+组、IGF-1组、IGF-1+MPP+组、IGF-1+MPP++LY294002组。孵育24 h后采用AO-EB法检测细胞凋亡率;采用MTT法检测细胞存活率;孵育4 h之后采用Western blot免疫印迹法检测Akt、磷酸化-Akt(phospho-Akt,p-Akt)蛋白表达。结果 (1)100 nmol的IGF-1能够显著抑制MPP+所致的细胞凋亡,对PC12细胞具有保护作用;(2)总Akt含量蛋白表达水平各处理组之间差别无统计学意义(P>0.05),但磷酸化的Akt在IGF-1+MPP+组表达高于MPP+单独处理组(P<0.05)。结论 IGF-1可减少MPP+所致的细胞凋亡,其保护作用与上调磷酸化的Akt的表达相关。     

小剂量左旋多巴上调pCREB及CD39蛋白表达发挥抗氧化应激损伤作用的研究

目的明确左旋多巴对PC12细胞生长及应激状态下存活的影响,探讨其抗氧化应激损伤的机制。方法不同浓度左旋多巴处理PC12细胞,用MTT法检测PC12细胞增长率及加入过氧化氢后细胞存活率;免疫荧光、Western blot方法测定磷酸化环单磷酸腺苷反应元件结合蛋白(pCREB)及CD39蛋白表达。结果低浓度左旋多巴(20μmol·L-1)促进PC12细胞生长,且可抗氧化应激损伤,而蛋白激酶抑制剂减弱此保护作用。免疫荧光及Western blot结果显示CD39及pCREB表达升高。结论低浓度左旋多巴可通过上调CD39及pCREB表达发挥抗氧化应激神经保护作用。     

Evidences of endocytosis via caveolae following blood–brain barrier breakdown by Phoneutria nigriventer spider venom

Spider venoms contain neurotoxic peptides aimed at paralyzing prey or for defense against predators; that is why they represent valuable tools for studies in neuroscience field. The present study aimed at identifying the process of internalization that occurs during the increased trafficking of vesicles caused by Phoneutria nigriventer spider venom (PNV)-induced blood–brain barrier (BBB) breakdown. Herein, we found that caveolin-1α is up-regulated in the cerebellar capillaries and Purkinje neurons of PNV-administered P14 (neonate) and 8- to 10-week-old (adult) rats. The white matter and granular layers were regions where caveolin-1α showed major upregulation. The variable age played a role in this effect. Caveolin-1 is the central protein that controls caveolae formation. Caveolar-specialized cholesterol- and sphingolipid-rich membrane sub-domains are involved in endocytosis, transcytosis, mechano-sensing, synapse formation and stabilization, signal transduction, intercellular communication, apoptosis, and various signaling events, including those related to calcium handling. PNV is extremely rich in neurotoxic peptides that affect glutamate handling and interferes with ion channels physiology. We suggest that the PNV-induced BBB opening is associated with a high expression of caveolae frame-forming caveolin-1α, and therefore in the process of internalization and enhanced transcytosis. Caveolin-1α up-regulation in Purkinje neurons could be related to a way of neurons to preserve, restore, and enhance function following PNV-induced excitotoxicity. The findings disclose interesting perspectives for further molecular studies of the interaction between PNV and caveolar specialized membrane domains. It proves PNV to be excellent tool for studies of transcytosis, the most common form of BBB-enhanced permeability.