海南地不容生物碱抑制肿瘤细胞增殖及构效关系解析

目的研究海南地不容(Stephania hainanensis H.S.Lo et Y.Tsoong)生物碱对人肝癌细胞Hep G-2、乳腺癌细胞MCF-7、胃癌细胞SGC-7901增殖的影响,筛选出有效的抗肿瘤化合物以及其敏感细胞株;分析其生物碱的构效关系。方法采用MTT法检测不同浓度的海南地不容生物碱对人肝癌细胞Hep G-2、乳腺癌细胞MCF-7、胃癌细胞SGC-7901增殖的抑制率;通过查阅国内外相关文献,分析海南地不容生物碱抗肿瘤活性的基本构效关系。结果MTT结果显示荷包牡丹碱、氧化克班宁、去甲荷包牡丹碱和克班宁对人肝癌Hep G-2、乳腺癌MCF-7和胃癌SGC-7901细胞的增值分别具有不同程度的剂量依赖性的抑制作用,各给药组分吸光度值与空白对照组比具有显著性差异(P<0.01),与阳性对照比较无明显统计学差异(P>0.05);海南地不容生物碱结构中的1,2-亚甲二氧基、N-亚甲基等取代基以及其化学结构的平面性对其抗肿瘤活性有重要影响。结论海南地不容中具有明显抗肿瘤作用的生物碱为荷包牡丹碱、氧化克班宁、去甲荷包牡丹碱和克班宁,其敏感细胞株均为乳腺癌细胞MCF-7;通过分析海南地不容生物碱的结构和抗肿瘤活性的关系,初步明确了其抗肿瘤活性可能与其结构易于抑制DNA拓扑异构酶和诱导细胞凋亡有关。     

醒脑开窍针刺法治疗血管性痴呆患者的疗效

目的:探究醒脑开窍针刺法对血管性痴呆(VD)患者的简易智能状态量表(MMSE)评分、Barthel指数及基质金属蛋白酶(MMP)的影响。方法:选取2017年1月至2018年1月湖南省脑科医院收治的血管性痴呆患者共110例作为研究对象,随机分为观察组和对照组,每组55例。对照组采用常规针刺疗法;观察组采用醒脑开窍针刺疗法,2组疗程均为4周。比较2组患者治疗后治疗有效率及治疗前后MMSE、Barthel指数及MMP水平。结果:观察组、对照组的治疗有效率分别为92.72%和78.18%,差异有统计学意义(P<0.05);治疗后2组患者MMSE和Barthel指数均显著升高,差异有统计学意义(P<0.05),且观察组高于对照组,差异有统计学意义(P<0.05);治疗后2组患者的MMP-2和MMP-9值均下降,差异有统计学意义(P<0.05),且观察者组患者的MMP-2和MMP-9低于对照组,差异有统计学意义(P<0.05)。结论:醒脑开窍针刺法对VD患者疗效显著,能够有效缓解痴呆症状。     

不同镇静方案在无痛人工流产术中的应用及对认知的影响

  目的  比较丙泊酚和依托咪酯单用或合用在无痛人工流产术中的麻醉效果及对认知的影响。  方法  选取2019年1—4月在安徽医科大学第一附属医院妇科门诊进行无痛人工流产术的患者180例,采用随机数字法分为丙泊酚组(P组,53例)、依托咪酯组(E组,57例)和混合组(EP组,55例)。采用北京版蒙特利尔认知测评量表(MoCA)评估术后认知水平。记录术前、诱导后、术中、术毕的SBP、DBP、平均动脉压(MAP)、心率(HR)、脉搏血氧饱和度(SpO₂)以及麻醉效果、用药总量、手术时间、唤醒时间、离室时间和不良反应。  结果  3组间术后MoCA总分和各认知域分比较差异均无统计学意义(均P＞0.05)。P组和EP组镇静效果较好,但E组有4例效果欠佳。组间SBP、DBP、MAP、HR比较差异无统计学意义(均P＞0.05),各时点间比较差异有统计学意义(均P＜0.05),组别和时间对SBP、DBP和MAP有交互效应(均P＜0.05)。不同干预和不同时点对SpO₂均有显著效应,且存在交互作用(均P＜0.05)。P组注射痛的发生率高于EP组和E组(均P＜0.017),P组和EP组低氧血症的发生率高于E组(均P＜0.017),E组肌阵挛和恶心呕吐的发生率高于P组和EP组(均P＜0.017)。  结论  依托咪酯和丙泊酚单药或合用对于行无痛人工流产术的患者短期认知水平无不同影响,合用效果最优,但依托咪酯单用安全性最好。      

TRAIL联合化疗药物对人宫颈癌Hela细胞增殖与凋亡的影响

目的探讨肿瘤坏死因子相关诱导凋亡配体 (TRAIL)对人宫颈癌Hela细胞的作用 ,以及与化疗药物的协同作用。方法将Hela细胞接种至 96孔培养板后分别加入浓度为l.0、10 .0、10 0 .0 μl/L的TRAIL、0 .1、1.0、10 .0mg/L的阿霉素 (ADM )和丝裂霉素 (MMC) ,及不同匹配的TRAIL MMC和TRAIL ADM ,采用四甲基偶氮唑盐 (MTT)比色法分别检测肿瘤细胞的生存率 ;将Hela细胞接种至 12孔板 ,培育 2 4h后加入不同浓度的TRAIL、ADM、MMC、TRAIL ADM、TRAL MMC ,用流式细胞术检测不同处理组肿瘤细胞的凋亡率和死亡率。结果 10 0 μg/LTRAIL引起细胞的凋亡率为 2 0 .1% ,与无药物组 1.1%的凋亡率有非常显著性差异 (P <0 .0 1) ;单独采用 10mg/LMMC、ADM对细胞的抑制率为 3 6.0 %和 44 .1% ,而 10 0 μg/LTRAIL与 10mg/LMMC、ADM联合后对细胞的抑制率分别达到 5 8.4%和 73 .7% ,两者有协同作用 (P <0 .0 5 )。结论在体外实验中 ,TRAIL可通过诱导宫颈癌Hela细胞的凋亡而产生抗肿瘤作用 ;TRAIL与化疗药物ADM、MMC有协同抗肿瘤作用。     

中药汤剂口服联合玻璃体内注射曲安奈德治疗非增生性糖尿病视网膜病变弥漫性黄斑水肿30例临床观察

目的观察益气养阴、活血利水中药汤剂口服联合曲安奈德玻璃体内注射治疗非增生性糖尿病视网膜病变弥漫性黄斑水肿的疗效及安全性。方法将60例(92眼)非增生性糖尿病视网膜病变弥漫性黄斑水肿患者随机分为治疗组(30例,47眼)和对照组(30例,45眼)。两组患者于治疗第1天均行患眼玻璃体内注射曲安奈德4 mg。治疗组同时予以益气养阴活血利水中药汤剂口服,每日1剂,服药3个月。观察治疗前和注射后3、6个月患眼视力、视网膜厚度及黄斑区渗漏情况。注射后第1、3、7天及3、6个月分别测量眼压、眼前节、眼后节。结果注射后3、6个月,治疗组临床疗效有效率分别为89.36%和87.23%,对照组分别为73.33%和62.22%,治疗组临床有效率优于对照组(P0.05或P0.01)。治疗组注射后3、6个月视力、视网膜厚度均较治疗前显著改善,且显著优于对照组(P0.05或P0.01)。治疗组未见明显不良反应,对照组1例患者6个月时发现晶状体后囊下呈锅底样混浊,严重影响视力。结论益气养阴、活血利水中药汤剂口服联合玻璃体内注射曲安奈德治疗非增生性糖尿病视网膜病变弥漫性黄斑水肿,能够明显提高患者的视功能,减轻视网膜水肿和黄斑区渗漏,疗效稳定,安全性良好。     

Berberine Induces Cell Apoptosis through Cytochrome C/Apoptotic Protease-Activating Factor 1/Caspase-3 and Apoptosis Inducing Factor Pathway in Mouse Insulinoma Cells

Objective: To investigate apoptotic effects of berberine, a significant alkaloids component existing in Rhizoma coptidis, and its possible acting mechanism in insulinoma cells. Methods: Different concentrations of berberine were used to treat mouse insulinoma(MIN6) cells for various period of time. The viability and apoptosis of the cells were analyzed using methylthiazolyldiphenvl-tetrazolium bromide assay, flow cytometry and enzyme-linked immuno sorbent assay. Changes in the relating pro-and anti-apoptosis proteins were detected by western-blotting. Results: The half-maximal inhibitory concentration(IC50) of berberine was 5.7 μmol/L on MIN6 cells viability for 16 h. Berberine caused a 20% reduction(P0.05) in cell number after only 4-h incubation; which reached 50% after 24 h(P0.01). Berberine treatment for 16 h significantly increased the level of DNA fragmentation. The flow cytometry showed the apoptotic rate increased 2.9-and 4.6-fold after treating with berberine(5 μmol/L) for 8 and 16 h, while 3-and 8.7-fold after 10 μmol/L treatment for 8 and 16 h(P0.01). Berberine treatment dramatically elevated the expression ratio of Bax to Bcl-2. Meanwhile, berberine notably increased the apoptosis-inducing factors and cytochrome C transforming from the mitochondria to the cytoplasm. Apoptotic protease-activating factor 1(Apaf-1) was subsequently activated after cytochrome C release. Furthermore, caspase-3 and poly adenosine diphosphate-ribose polymerase were also activated to trigger apoptosis cascade. Conclusion: High concentration(5 and 10 μmol/L) of berberine could induce the apoptosis of MIN6 cells through cytochrome C/Apaf-1/caspase-3 and apoptosis inducing factor(AIF) pathway.     

Phenotypic changes caused by melatonin increased sensitivity of prostate cancer cells to cytokine‐induced apoptosis

Abstract: Melatonin has antiproliferative properties in prostate cancer cells. Melatonin reduces proliferation without increasing apoptosis, and it promotes cell differentiation into a neuroendocrine phenotype. Because neuroendocrine cells displayed an androgen‐independent growth and high resistance to radiotherapy and chemotherapy, the role of molecules that induce neuroendocrine differentiation was questioned in terms of their usefulness as oncostatic agents. By using human epithelial androgen‐dependent and androgen‐independent prostate cancer cells, the role of melatonin in drug‐induced apoptosis was studied after acute treatments. In addition to cytokines such as hrTNF‐alpha and TRAIL, chemotherapeutic compounds, including doxorubicin, docetaxel, or etoposide, were employed in combination with melatonin to promote cell death. Melatonin promotes cell toxicity caused by cytokines without influencing the actions of chemotherapeutic agents. In addition, antioxidant properties of melatonin were confirmed in prostate cancer cells. However, its ability to increase cell death caused by cytokines was independent of the redox changes. Finally, phenotypic changes caused by chronic treatment with the indole, that is, neuroendocrine differentiation, make cells significantly more sensitive to cytokines and slightly more sensitive to some chemotherapeutic compounds. Thus, melatonin is a good inhibitor of the proliferation of prostate cancer cells, promoting phenotypic changes that do not increase survival mechanisms and make cells more sensitive to cytokines such as TNF‐alpha or TRAIL.