颅内动脉瘤破裂出血术后血清HIF-1α、miR-210表达与脑血管痉挛的关系

目的检测颅内动脉瘤破裂出血术后血清缺氧诱导因子1α（HIF-1α）、miR-210表达情况，并探讨其与脑血管痉挛（CVS）的关系。 方法选取禹城市人民医院神经外科自2015年1月至2018年12月收治的87例颅内动脉瘤破裂急诊自发性蛛网膜下腔出血（SAH）并接受介入栓塞或开颅夹闭治疗的患者为研究对象，采用头颅X线、CT及全脑数字减影血管造影（DSA）检查判断CVS的发生情况，并评估其严重程度。术后3、7 d采用ELISA法检测血清HIF-1α表达情况，采用qRT-PCR法检测血清miR-210表达情况。分析颅内动脉瘤破裂出血患者术后血清HIF-1α、miR-210表达的关系，采用ROC曲线分析颅内动脉瘤破裂出血患者术后3 d血清HIF-1α、miR-210水平对CVS的诊断价值。 结果87例颅内动脉瘤破裂出血患者出现术后CVS者37例（42.53%），其中轻度CVS 10例（11.49%），中度19例（21.84%），重度8例（90.20%）；术后3、7 d，与无CVS组患者相比，不同程度CVS患者血清中的HIF-1α、miR-210水平均显著升高（P<0.05），且CVS程度越重，血清HIF-1α、miR-210表达水平越高，不同程度CVS患者术后3、7 d时血清HIF-1α、miR-210水平均显著高于术前（P<0.05），术后7 d时血清HIF-1α、miR-210水平均显著低于术后3 d，差异有统计学意义（P<0.05）；颅内动脉瘤破裂出血术后3、7 d患者血清HIF-1α水平与miR-210水平均呈正相关（r=0.381、0.631，P<0.05）；术后3 d血清HIF-1α、miR-210水平及HIF-1α+miR-210联合诊断颅内动脉瘤破裂出血患者CVS的曲线下面积分别为0.834、0.769、0.900，二者联合诊断CVS的敏感度为93.06%，准确度为87.36%，均高于单项指标检测。 结论颅内动脉瘤破裂出血术后血清HIF-1α、miR-210水平可有效预示CVS的发生，二者可能成为CVS发生、发展的重要生物学指标。     

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.     

lncRNA CYTOR靶向调控miR-503/CCNE1信号轴促进上皮性卵巢癌细胞增殖北大核心

目的:探讨细胞骨架调节剂(lncRNA cytoskeleton regulator,CYTOR)是否通过靶向调控miR-503来促进细胞周期蛋白E1(cyclin E1,CCNE1)影响上皮性卵巢癌增殖。方法:实时定量聚合酶链反应(RT-qPCR)检测CYTOR在不同临床分期、病理分级和有无淋巴结转移患者人上皮性卵巢癌组织、癌旁组织和正常组织以及不同卵巢癌细胞中的表达;starBase数据库(网址:http://starbase.sysu.edu.cn/)预测分析CYTOR和miR-503以及miR-503与CCNE1之间的关系,同时荧光素酶实验进行验证;RT-qPCR和免疫荧光分别检测miR-503与CCNE1在人上皮性卵巢癌组织、癌旁组织和正常组织以及不同卵巢癌细胞中的表达;RNA转染技术在A2780中细胞分别沉默CYTOR、过表达miR-503和沉默CCNE1表达,CCK-8检测各组细胞增殖能力变化;RT-qPCR和免疫荧光检测沉默CYTOR后miR-503和CCNE1的表达以及过表达miR-503后CCNE1的表达。结果:CYTOR和CCNE1在上皮性卵巢癌组织中表达增加,同时在临床分期III-IV期、病理分级G_(3)级、淋巴结转移阳性患者肿瘤组织中表达同样显著增加且导致卵巢癌患者术后预后较差;通过数据库分析CYTOR可直接靶向抑制miR-503,而miR-503可直接靶向抑制CCNE1表达,双荧光素酶实验结果与之相同;CYTOR和CCNE1促进上皮性卵巢癌增殖,而miR-503抑制上皮性卵巢癌增殖作用。结论:lncRNA CYTOR通过调控miR-503/CCNE1轴促进上皮性卵巢癌的增殖。     

miR-372 inhibits p62 in head and neck squamous cell carcinoma in vitro and in vivo

Here we showed that exogenous miR-372 expression and knockdown of p62 (sequestosome1 or SQSTM1), both increased migration of head and neck squamous cell carcinoma (HNSCC) cells. p62 induced phase II detoxification enzyme NADPH quinone oxidoreductase 1 (NQO1), which decreased ROS levels and cell migration. Also, miR-372 decreased p62 during hypoxia, thus increasing cell migration. Levels of miR-372 and p62 inversely correlated in human HNSCC tissues. Plasma levels of miR-372 was associated with advanced tumor stage and patient mortality. Both plasma and salivary miR-372 levels were decreased after tumor resection. We conclude that miR-372 decreases p62, thus increasing ROS and motility in HNSCC cells.     

微小RNA在人类压疮组织中的异常表达

目的建立人类压疮组织微小RNA表达谱。方法收集本院24例压疮组织临床样本,选取其中4例用于压疮微小RNA芯片制备。采用生物信息学算法比较压疮组织与正常组织中差异表达的微小RNA,获得压疮微小RNA表达谱。进一步利用20例测试样本,采用实时荧光定量-逆转录-聚合酶链反应对所鉴定的表达谱进行验证。结果获得了12个差异表达的微小RNA,其中包括5个表达水平上调和7个表达水平下调的微小RNA,其中表达水平下调的miR-17差异表达水平最显著。结论作者建立了一组由12个微小RNA组成的压疮组织微小RNA表达谱,为压疮发生及发展分子调控机制研究提供了丰富的素材。     

Mir-192 suppresses apoptosis and promotes proliferation in esophageal aquamous cell caicinoma by targeting Bim

MicroRNAs (miRNAs) are small, non-coding RNAs of endogenous origin. Accumulating studies have shown aberrant miRNA expression plays an important role in many tumor types. However, the mechanisms by which miRNAs regulate esophageal squamous cell carcinoma (ESCC) development remain poorly understood. In the present study, we assayed expression level of miR-192 in ESCC tissues and cell lines by real-time PCR, and defined the target gene and biological function by luciferase reporter assay, Western blot and apoptosis assay. We first verified that the expression level of miR-192 was significantly increased in ESCC tissues and cancer cells. Moreover, miR-192 over-expression inhibited cells apoptosis and promoted ESCC cells proliferation. We further demonstrated that miR-192 directly targeted 3’-UTR of Bim gene, and inhibited its protein expression. Importantly, Bim could reduce ESCC cells apoptosis ability induced by miR-192. These data suggest an important role of miR-192 in the molecular etiology of ESCC and implicate the potential application of miR-192 in ESCC therapy.     

MicroRNA-137 inhibits cell migration and invasion by targeting bone morphogenetic protein-7 (BMP7) in non-small cell lung cancer cells

MicroRNA-137 (miR-137) was reported to be dysregulated in several human cancers. However, the function and mechanism of miR-137 in non-small cell lung cancer (NSCLC) is still unclear. In the current study, we explored the role of miR-137 in NSCLC progression. Using qRT-PCR, our data showed that miR-137 was significantly down-regulated in NSCLC tissues and cell lines. In vitro functional assay, we found that over-expression of miR-137 suppressed NSCLC cells proliferation, migration and invasion, indicating that miR-137 could act as a tumor suppressor in NSCLC progression. In addition, bone morphogenetic protein-7 (BMP7) was identified as a target of miR-137 in NSCLC cells, Luciferase reporter assay suggested that miR-137 directly targeted 3’-UTR of BMP7, and correlation analysis revealed that BMP7 inversely correlated with miR-137 in NSCLC tissues. Furthermore, Restoration of BMP7 remarkably reversed the tumor suppressive effects of miR-137 on NSCLC cell proliferation, migration, and invasion. Taken together, our findings suggested that miR-137/BMP7 axis could contribute to the progression of NSCLC, suggesting miR-137 as a potential therapeutic target for the treatment of NSCLC.     

Paediatric prescribing: why children are not small adults

Paracetamol (acetaminophen) overdose is one of the most common causes of acute liver injury in the Western world. To improve patient care and reduce pressure on already stretched health care providers new biomarkers are needed that identify or exclude liver injury soon after an overdose of paracetamol is ingested. This review highlights the current state of paracetamol poisoning management and how novel biomarkers could improve patient care and save healthcare providers money. Based on the widely used concept of defining a target product profile, a target biomarker profile is proposed that identifies desirable and acceptable key properties for a biomarker in development to enable the improved treatment of this patient population. The current biomarker candidates, with improved hepatic specificity and based on the fundamental mechanistic basis of paracetamol-induced liver injury, are reviewed and their performance compared with our target profile.     

膀胱癌中miR-9对CBX7表达的调控作用

目的研究mi R-9在膀胱癌中对CBX7基因表达的调控作用及机制。方法应用荧光定量PCR方法检测膀胱癌及癌旁组织中mi R-9及CBX7基因的表达。培养膀胱癌T24细胞,转染mi R-9的前体pre-mi R-9,Western blot检测CBX7蛋白的表达。荧光素酶报告基因表达分析明确mi R-9与CBX7基因3'非翻译区(3'UTR)的结合。结果 mi R-9在膀胱癌组织中的表达较癌旁组织呈现显著的上调,而CBX7的表达则下调明显,二者的表达呈显著负相关。在转染后膀胱癌T24细胞中,pre-mi R-9能够分别下调T24细胞中CBX7蛋白的表达。荧光素酶报告基因表达分析明确mi R-9能够与CBX7基因的3'UTR结合并负性调节其表达。结论 mi R-9与CBX7基因的表达改变与膀胱癌相关,mi R-9能够在膀胱癌细胞中靶向负性调节CBX7基因的表达。