Microenvironment mesenchymal cells protect ovarian cancer cell lines from apoptosis by inhibiting XIAP inactivation

Epithelial ovarian carcinoma is characterized by high frequency of recurrence (70% of patients) and carboplatin resistance acquisition. Carcinoma-associated mesenchymal stem cells (CA-MSC) have been shown to induce ovarian cancer chemoresistance through trogocytosis. Here we examined CA-MSC properties to protect ovarian cancer cells from carboplatin-induced apoptosis. Apoptosis was determined by Propidium Iodide and Annexin-V-FITC labelling and poly-ADP-ribose polymerase cleavage analysis. We showed a significant increase of inhibitory concentration 50 and a 30% decrease of carboplatin-induced apoptosis in ovarian cancer cells incubated in the presence of CA-MSC-conditioned medium (CM). A molecular analysis of apoptosis signalling pathway in response to carboplatin revealed that the presence of CA-MSC CM induced a 30% decrease of effector caspases-3 and -7 activation and proteolysis activity. CA-MSC secretions promoted Akt and X-linked inhibitor of apoptosis protein (XIAP; caspase inhibitor from inhibitor of apoptosis protein (IAP) family) phosphorylation. XIAP depletion by siRNA strategy permitted to restore apoptosis in ovarian cancer cells stimulated by CA-MSC CM. The factors secreted by CA-MSC are able to confer chemoresistance to carboplatin in ovarian cancer cells through the inhibition of effector caspases activation and apoptosis blockade. Activation of the phosphatidylinositol 3-kinase (PI3K)/Akt signalling pathway and the phosphorylation of its downstream target XIAP underlined the implication of this signalling pathway in ovarian cancer chemoresistance. This study reveals the potentialities of targeting XIAP in ovarian cancer therapy.     

The G-protein-coupled estrogen receptor agonist G-1 suppresses proliferation of ovarian cancer cells by blocking tubulin polymerization

The G-protein-coupled estrogen receptor 1 (GPER) has recently been reported to mediate the non-genomic action of estrogen in different types of cells and tissues. G-1 (1-[4-(6-bromobenzo[1,3] dioxol-5yl)-3a,4,5,9b-tetrahydro-3H-cyclopenta[c]quinolin-8-yl]-ethanone) was developed as a potent and selective agonist for GPER. G-1 has been shown to induce the expression of genes and activate pathways that facilitate cancer cell proliferation by activating GPER. Here we demonstrate that G-1 has an anticancer potential with a mechanism similar to vinca alkaloids, the commonly used chemotherapy drugs. We found that G-1 blocks tubulin polymerization and thereby interrupts microtubule assembly in ovarian cancer cells leading to the arrest of cell cycle in the prophase of mitosis and the suppression of ovarian cancer cell proliferation. G-1 treatment also induces apoptosis of ovarian cancer cells. The ability of G-1 to target microtubules to suppress ovarian cancer cell proliferation makes it a promising candidate drug for treatment of ovarian cancer.     

胎膜早破新生儿口腔分泌物细菌培养与药敏分析

【摘 要】 目的 分析胎膜早破新生儿口腔分泌物细菌的分布特点、耐药情况以及不同分娩方式的影响,为临床合理的预防性使用抗生素提供科学的指导。方法 对2011年1月至2012年12月广东省妇幼保健院新生儿科送检的116份胎膜早破新生儿口腔分泌物标本进行细菌培养,并以法国梅里埃的全自动细菌鉴定药敏系统(VITEK-2 compact)对分离出的纯菌株进行鉴定和药敏试验,统计不同分娩方式的阳性率。结果 116份口腔分泌物标本中,共分离出细菌33株/31例,总检出率为26.7%,其中G-菌28株,占84.8%,G+菌5株,占15.2%,检出率最高的病原菌是大肠埃希菌17株(51.5%),其除了对丁胺卡那霉素、头孢替坦和亚胺培南全部敏感以外,对其他的抗生素均有不同程度的耐药,两种分娩方式的细菌培养阳性率差异无统计学意义。结论 胎膜早破新生儿口腔分泌物培养以G-菌为主且耐药性较高,临床应根据药敏结果合理选用抗生素进行预防用药;在无医学指针的情况下,推荐阴道分娩。     

微生态制剂对慢性肝衰竭患者肠道菌群的影响

目的探讨微生态调节剂双歧杆菌三联活菌对慢性肝衰竭患者肠道菌群的影响。方法根据治疗方法不同将46例慢性肝衰竭患者随机分为治疗组和对照组各23例,两组均给予慢性肝衰竭常规治疗,治疗组在上述基础上给予双歧杆菌三联活菌胶囊,210mg／粒,每次2粒,2次／d,疗程2周。观察治疗前后两组患者的肠道菌群菌落计数变化及血清总胆红素（TBiL）、凝血酶原时间（PT）变化。结果两组患者在实验前肠道菌群、TBiL、PT比较差异均无统计学意义（P〉0．05）。治疗2周后,对照组患者治疗前后肠道菌群无明显变化（P〉0．05）,TBiL、PT有所下降但不显著,治疗组患者的肠球菌、双歧杆菌、乳杆菌以及酵母样真菌的菌落数均较治疗前明显增加,TBiL、PT较前明显好转（P〈0．05）。结论口服双歧杆菌三联活菌制剂可以促进慢性肝衰竭患者肠道正常菌群的恢复及改善肝功能。     

卵巢早衰动物模型制备研究进展

卵巢早衰是一种典型异质性疾病,病因复杂多样。近年来,卵巢早衰的发病率有明显上升趋势,严重影响妇女身心健康和生活质量。建立一种理想可靠的卵巢早衰动物模型对研究卵巢早衰有着重要的临床意义。本文就国内外学者建立的卵巢早衰动物模型作一综述,讨论比较各种方法的优缺点。     

Características y resultados tras un año en pacientes ancianos ingresados con insuficiencia cardiaca y fracción de eyección reducida,intermedia o conservada

IntroductionThe latest European Society of Cardiology Heart Failure (HF) guidelines define three types of HF according to the ejection fraction (EF): HF with reduced EF (HFrEF) when EF < 40%, HF with mid-range EF (HFmrEF), when EF 40-49%, and HF with preserved EF (HFpEF) when EF ≥ 50%. The objective of this study was to analyse the characteristics and results of elderly patients hospitalised with HF according to the new classification using EF.MethodsA prospective study was carried out with 531 HF patients aged ≥ 75 years classified according to EF, and admitted in the geriatric wards of 6 hospitals in Spain. An analysis was performed on the demographic and clinical characteristics, as well as well as the morbidity and mortality at one year of follow-up.ResultsAs regards EF, 17.1% had HFrEF, 10% had HFmrEF, and 72.9% had HFpEF. Patients with HFmrEF were more similar to those with HFrEF in terms of a younger age, predominance of men, and previous admission due to HF. This was also the case with the use of drugs for neurohormonal blockade. Patients with HFrEF (compared to those with HFmrEF and HFpEF), had higher mortality (35.2%, 24.5%, and 25.6%, respectively), more readmissions for HF (17.6%, 15.1%, and 14.5%, respectively), and more events (61.5%, 45.3%, and 52.5%, respectively), although there were no significant differences. There were also no differences observed in the survival analysis between the EF groups and the time-dependent outcome variables.ConclusionsIn elderly patients hospitalised with HF, those classified as HFmrEF did not show any clear differences with respect to those with HFrEF or HFpEF. There were no differences in terms of morbidity and mortality.     

诺欣妥对射血分数降低的心力衰竭患者血管内皮损伤及生活质量的影响

目的:探讨诺欣妥对射血分数降低的心力衰竭(heart failure patients with reduced ejection fraction,HFrEF)患者血管内皮损伤及生活质量的影响。方法:将复旦大学附属闵行医院心内科2017年9月～2018年6月收治的170例HFrEF患者随机分为两组,每组各85例。对照组均给予心衰(heart failure,HF)标准化治疗,研究组在此基础上给予诺欣妥治疗,起始剂量50 mg/次,2次/d,每隔2-4周增加1倍剂量,逐步调整至200 mg/次并作为维持剂量,2次/d。所有患者均连续治疗10周。比较两组患者治疗前后血管内皮功能指标、生活质量评分的变化,住院及随访期间的预后转归。结果:治疗后,两组血清一氧化氮(nitric oxide,NO)、降钙素基因相关肽(calcitonin gene-related peptide,CGRP)水平均较治疗前明显升高,血清内皮素-1(endothelin 1,ET-1)水平较治疗前明显下降,且研究组上述指标水平明显优于对照组(P0.05)。两组治疗后躯体、情绪、其他领域及总分均较治疗前明显降低,且研究组除其他领域评分外其余维度评分及总分均明显低于对照组(P0.05)。与对照组比较,研究组住院期间全因死亡率、30 d内HF再住院率及随访期间不良心血管事件(adverse cardiovascular events,MACEs)发生率均显著降低(P0.05)。结论:诺欣妥治疗可使HFrEF患者明显获益,在改善血管内皮损伤、生活质量及近期预后方面效果显著优于心衰标准化治疗。