定振丸对帕金森病大鼠神经递质及黑质多巴胺能神经元氧化应激的改善作用

目的探讨定振丸对帕金森病大鼠儿茶酚胺类神经递质及黑质多巴胺能神经元氧化应激的改善作用。方法利用6-羟多巴胺建立帕金森病大鼠模型,大鼠随机分为假手术组,模型组,定振丸低、中、高剂量组(11.03、22.05、44.10 mg/kg)及阳性组(美多芭1.67 mg/kg),1次/d,连续灌胃给药15 d。ELISA法检测脑黑质中DA、DOPAC、HVA、5-HT水平;应用硫代巴比妥那比色法、邻苯三酚自氧化法和二硫代二硝基苯甲酸直接法分别检测脑黑质匀浆上清液中MDA、SOD及GSH-Px水平;免疫组化法检测TH阳性率;TUNEL染色检测多巴胺能神经元细胞凋亡率;Western blot法检测Bax、Bcl-2、caspase-3蛋白表达。结果与模型组比较,定振丸组DA、DOPAC、HVA、5-HT、SOD、GSH-Px水平,TH阳性率及Bcl-2蛋白表达均升高(P<0.05);MDA水平、多巴胺能神经元凋亡率、Bax及caspase-3蛋白表达降低(P<0.05)。结论定振丸能改善帕金森大鼠儿茶酚胺类神经递质及黑质多巴胺能神经元氧化应激的作用,下调Bax、caspase-3蛋白表达,上调Bcl-2蛋白表达,从而促进TH表达、抑制多巴胺能神经元凋亡。     

下调FAM111B对乳腺癌细胞增殖和凋亡的影响

目的:探讨下调FAM111B对乳腺癌细胞系MDA-MB-231和MCF7细胞增殖和凋亡的影响及其机制。方法:构建siR-FAM111B慢病毒载体,转染乳腺癌MDA-MB-231和MCF7细胞,qRT-PCR检查转染组与对照组FAM111B mRNA表达,Western blotting法检测各组细胞FAM111B蛋白表达。用CCK-8法检测细胞的增殖能力。流式细胞术检测Annexin-V/PI双染各组细胞的凋亡情况。Western blotting法检测凋亡相关蛋白Bax和Bcl-2的表达。结果:siR-FAM111B成功转染MDA-MB-231和MCF7细胞,转染后应用qRT-PCR和Western blotting检测,结果显示,FAM111B mRNA与蛋白水平均下调。siR-FAM111B能抑制两种细胞的增殖。Annexin-V/PI双染结果显示,下调FAM111B诱导两种细胞凋亡。Western blotting结果显示,下调FAM111B可以促进两种细胞Bax的表达,抑制Bcl-2的表达。结论:下调FAM111B能够抑制乳腺癌细胞的增殖,通过调节线粒体凋亡通路诱导细胞凋亡。     

不同焦油释放量卷烟全烟气气-液界面暴露致细胞毒性、炎症因子释放和细胞凋亡的研究

目的:探讨两种不同焦油释放量卷烟对人支气管上皮细胞的细胞毒性、炎症因子释放水平和细胞凋亡的影响。方法:选取国际标准化组织(ISO)规定抽吸参数下焦油释放量分别为每支9.4 mg的卷烟样品1和每支14.0 mg的卷烟样品2作为研究对象。实验分为洁净空气对照组和烟气染毒组。利用VITROCELL系统产生的洁净空气或稀释的主流烟气以气-液界面方式暴露染毒Beas-2b细胞,经计算洁净空气对照组剂量为0支卷烟产生的主流烟气,烟气染毒组剂量分别为0.12%支、0.27%支、0.57%支、1%支卷烟产生的主流烟气;利用中性红细胞毒性试验检测细胞存活率;ELISA法检测细胞培养液中的IL-6、IL-8释放水平;Annexin V-FITC/PI流式细胞分析法检测细胞凋亡水平。结果:样品1和样品2产生的主流烟气均可引起Beas-2b细胞存活率降低,炎症因子IL-6、IL-8的释放水平和细胞凋亡率显著增加。在0.12%支的烟气剂量下,样品1与样品2烟气引起的细胞毒性、炎症因子释放水平和细胞凋亡率的差异无统计学意义;在0.57%和1%支的烟气剂量下,样品2的细胞毒性高于样品1。结论:两种不同焦油释放量卷烟样品均可引起细胞毒性、促炎症因子释放和细胞凋亡。在0.57%支~1%支烟气剂量范围内,具有高焦油释放量的卷烟烟气引起的细胞毒性强于低焦油释放量的卷烟烟气。     

Melatonin activates cell death programs for the suppression of uterine leiomyoma cell proliferation

The circadian nature of melatonin has a protective effect on the progression of female reproductive cancers, including breast and ovarian cancers. However, the effect of melatonin on the growth of uterine leiomyoma is still unclear. In this study, we found that the growth of uterine leiomyoma ELT3 cells was reduced by treatment with melatonin. Treatment with melatonin increased the distribution of sub-G1 phase and increased DNA condensation in ELT3 cells. Melatonin-induced apoptosis and autophagy cell death progression were observed in ELT3 cells. Melatonin exerts a highly selective effect on primary normal human uterine smooth muscle (UtSMC) cells. The UtSMC cell cycle was arrested by melatonin treatment through up-regulation of p21, p27, and PTEN protein expression, but melatonin did not further promote apoptosis program activation. Melatonin reduced cell proliferation in ELT3 cells underlying the activation of melatonin MT1 and MT2 receptors, which in turn down-regulated the Akt-ERK1/2-NFκB signaling pathway. Melatonin reduced ELT3 tumor growth in both xenograft and orthotopic uterine tumor mice models. The extracellular matrix of the tumor was also reduced by melatonin treatment. Taken together, these results suggest that melatonin potentially plays a role in suppression of uterine leiomyoma growth.     

LncRNA XIST acts as a MicroRNA-520 sponge to regulate the Cisplatin resistance in NSCLC cells by mediating BAX through CeRNA network

Background: In recent years, LncRNA acts as a member of competing endogenous RNA (ceRNA), playing an important role in drug resistance of lung cancer. The aim of this study was to identify potential biomarkers about cisplatin resistant lung cancer cells using a comprehensive ceRNA network.Methods: {"type":"entrez-geo","attrs":{"text":"GSE6410","term_id":"6410"}}GSE6410 (GPL-201) analyzed gene expression changes about cisplatin resistance in A549 NSCLC cells. {"type":"entrez-geo","attrs":{"text":"GSE43249","term_id":"43249"}}GSE43249 (GPL-14613) included noncoding RNA expression profiling derived from the cisplatin resistant A549 lung cells. GEO2R, an online analysis tool, analyzed the differentially expressed mRNAs and miRNAs (DEmRNAs and DEmiRNAs). To explore the functional enrichment implication of differentially expressed mRNAs, we used the GO (Gene ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway analysis. Through miRDB, Targetscan, Starbase and miRWalk, we found targeted miRNAs. The Kaplan-Meier curve method was used to show clinical survival analysis of targeted RNAs (P<0.05). The Starbase database predicted potential lncRNAs mediated targeted miRNAs. Eventually, the novel ceRNA network of lncRNAs, miRNAs, mRNA was constructed by cytoscape3.7.2.Results: 118 differentially expressed mRNAs were the basis of the mediated ceRNA network. DAVID and Kaplan-Meier picked out BAX, an apoptosis regulator. Venn diagram demonstrated 8 miRNAs commonly regulating BAX. Starbase predicted lncRNA XIST mediated miRNAs. Finally, lncRNA XIST may be a useful biomarker regulating cisplatin resistance in lung cancer cells and further, we explored the BAX may effect tumor-infiltrating immune cells.Conclusions: LncRNA XIST competitively bound to miRNA 520 in the regulation of cisplatin resistance by BAX, participating apoptosis in the p53 signaling pathway.     

葫芦素抗肿瘤作用研究进展

癌症是全球主要的公共卫生问题，中国国家癌症中心的统计数据也表明癌症以逐年提升的发病率和死亡率成为威胁人类健康的重大疾病。癌症的发生发展机制复杂，涉及多阶段、多个基因及多条信号通路的异常，常规的放化疗及新兴的靶向治疗方法是肿瘤治疗的主要方式，但由于其毒副作用和耐药性的产生严重影响了患者的生活质量和持续有效的治疗效果，因此寻找安全有效的抗癌药物是全球关注的焦点。抗肿瘤植物药紫杉醇类、长春碱类、鬼臼素类、人参皂苷和多糖等的研发与应用给肿瘤治疗带来了新的希望。葫芦素是一种来源于中药葫芦科植物的高度氧化的四环三萜类化合物，药理作用广泛且机制复杂，在葫芦素家族中，目前针对葫芦素B，D，E，I抗肿瘤作用研究最多，已有大量研究证实，葫芦素B，D，E，I在治疗消化系统、呼吸系统、生殖系统、血液系统、泌尿系统等肿瘤疾病中发挥了重要作用，能够显著抑制肿瘤细胞增殖，而且在阻滞细胞周期、诱导细胞凋亡和自噬性死亡、抑制细胞迁移和侵袭、抑制肿瘤血管生成、调节活性氧的水平、调节免疫等方面作用显著，有望开发成为抗癌新药。基于当前国内外针对葫芦素抗多种肿瘤的作用及机制研究成果，笔者对葫芦素抗肿瘤作用研究进展进行了全方面综述，以期为葫芦素类抗肿瘤药物新药研发提供参考。     

CircKIF4A靶向调控miR-384表达对卵巢癌SKOV3细胞增殖和凋亡的影响

Objective?To explore the effect of circKIF4A on the proliferation and apoptosis of ovarian cancer SKOV3 cells and its regulatory mechanism on miR-384. Methods?The qRT-PCR method was used to detect the expression of circKIF4A and miR-384 in ovarian cancer tissues and adjacent tissues. si-NC, si-circKIF4A, miR-NC, miR-384 mimics, si-circKIF4A and anti-miR-NC, si-circKIF4A and anti-miR-384 were transfected into SKOV3 cells respectively. The qRT-PCR method was used to detect the expression of circKIF4A and miR-384 in SKOV3 cells. MTT experiment and flow cytometry experiment were used to detect cell proliferation and apoptosis respectively. The dual luciferase reporter experiment was used to detect the targeting relationship between circKIF4A and miR-384. Results?Compared with adjacent tissues, the expression level of circKIF4A in ovarian cancer tissues was increased [(1.00±0.06), (4.28±0.32)] (t=62.915, P＜0.05), and the expression level of miR-384 was decreased [(1.00± 0.05), (0.43±0.03)] (t=61.047, P<0.05). After transfection with si-circKIF4A, the OD value of SKOV3 cells was decreased [(0.75±0.05), (0.41±0.03)] (t=17.493, P＜0.05), and the apoptosis rate was increased [(6.36±0.53)%, (23.19± 2.21)%] (t=22.216, P<0.05). After transfection of miR-384 mimics, the OD value of SKOV3 cells was decreased [(0.73±0.05), (0.47±0.04)] (t=12.182, P＜0.05), and the apoptosis rate was increased [(7.53±0.41)%, (19.11)±1.06)%] (t=30.567, P<0.05). The dual luciferase report experiment confirmed that circKIF4A could adsorb miR-384 and can act as a sponge molecule for miR-384. After co-transfection with si-circKIF4A and anti-miR-384, the OD value of SKOV3 cells was increased [(0.40±0.04), (0.65±0.03)] (t=15.000, P＜0.05), and the apoptosis rate was decreased [(25.20± 2.21)%, (10.37±0.86)%] (t=18.761, P＜0.05). Conclusion?Inhibition of circKIF4A expression could negatively regulate the expression of miR-384, thereby inhibiting the proliferation of ovarian cancer cells and inducing apoptosis.