Effect of stromal cell-derived factor-1/CXCR4 axis in neural stem cell transplantation for Parkinson’s disease

Previous studies have shown that neural stem cell transplantation has the potential to treat Parkinson’s disease,but its specific mechanism of action is still unclear.Stromal cell-derived factor-1 and its receptor,chemokine receptor 4(CXCR4),are important regulators of cell migration.We speculated that the CXCR4/stromal cell-derived factor 1 axis may be involved in the therapeutic effect of neural stem cell transplantation in the treatment of Parkinson’s disease.A Parkinson’s disease rat model was injected with 6-hydroxydopamine via the right ascending nigrostriatal dopaminergic pathway,and then treated with 5μL of neural stem cell suspension(1.5×104/L)in the right substantia nigra.Rats were intraperitoneally injected once daily for 3 days with 1.25 mL/kg of the CXCR4 antagonist AMD3100 to observe changes after neural stem cell transplantation.Parkinson-like behavior in rats was detected using apomorphine-induced rotation.Immunofluorescence staining was used to determine the immunoreactivity of tyrosine hydroxylase,CXCR4,and stromal cell-derived factor-1 in the brain.Using quantitative real-time polymerase chain reaction,the mRNA expression of stromal cell-derived factor-1 and CXCR4 in the right substantia nigra were measured.In addition,western blot assays were performed to analyze the protein expression of stromal cell-derived factor-1 and CXCR4.Our results demonstrated that neural stem cell transplantation noticeably reduced apomorphine-induced rotation,increased the mRNA and protein expression of stromal cell-derived factor-1 and CXCR4 in the right substantia nigra,and enhanced the immunoreactivity of tyrosine hydroxylase,CXCR4,and stromal cell-derived factor-1 in the brain.Injection of AMD3100 inhibited the aforementioned effects.These findings suggest that the stromal cell-derived factor-1/CXCR4 axis may play a significant role in the therapeutic effect of neural stem cell transplantation in a rat model of Parkinson’s disease.This study was approved by the Animal Care and Use Committee of Kunming Medical University,China(approval No.SYXKK2015-0002)on April 1,2014.     

急性白血病医院感染病原学分析及HIF-1α、VEGF和Bcl-2表达研究

目的 探讨急性白血病医院感染病原学分析及缺氧诱导因子1α(HIF-1α)、血管内皮生长因子(VEGF)和B细胞淋巴瘤/白血病-2(Bcl-2)表达研究。 方法 选择舟山市普陀区人民医院和浙江省人民医院于2014年1月—2017年12月收治的急性白血病患者171例,分析医院感染发生率、病原菌分布及主要病原菌耐药情况。取患者骨髓组织病理切片,采用免疫组化染色法测定HIF-1α、VEGF和Bcl-2表达,以平均光密度值进行定量分析。 结果 急性白血病住院患者171例,发生医院感染患者54例(医院感染率为31.58%);感染部位以呼吸道、口腔和胃肠道为主,分别占35.19%、24.07%和16.67%;共分离病原菌71株,革兰阴性菌39株占54.93%;71株病原菌中,肺炎克雷伯菌15株占21.13%、金黄色葡萄球菌12株占16.90%、铜绿假单胞菌10株占14.08%、凝固酶阴性葡萄球菌9株占12.68%。分离的革兰阴性菌中,肺炎克雷伯菌对头孢哌酮耐药率较高,耐药率为53.33%;铜绿假单胞菌对哌拉西林耐药率较高,耐药率为60.00%。分离的革兰阳性菌中,金黄色葡萄球菌对红霉素耐药率较高,耐药率为75.00%;凝固酶阴性葡萄球菌对红霉素耐药率较高,耐药率为66.67%。感染组骨髓组织中HIF-1α和VEGF平均光密度值高于未感染组而Bcl-2平均光密度值低于未感染组,且差异有统计学意义(均P<0.05)。 结论 急性白血病住院患者医院感染率较高,病原菌以革兰阴性菌为主,且感染患者骨髓组织中HIF-1α和VEGF呈高表达而Bcl-2呈低表达,具有重要研究意义。      

吉西他滨联合顺铂对晚期非小细胞肺癌的效果分析

目的探讨吉西他滨联合顺铂对晚期非小细胞肺癌的临床疗效。方法随机将2015年1月至2018年6月本院收治的84例晚期非小细胞肺癌患者分到A组(n=42例)和B组(n=42例),A组患者予以吉西他滨联合顺铂治疗,B组患者予以长春瑞滨联合顺铂治疗,对比两组患者的治疗效果。结果 A组中,完全缓解4例,部分缓解15例,稳定17例,进展6例,有效率为45.24%(19/42);B组中,完全缓解4例,部分缓解14例,稳定17例,进展7例,有效率为42.86%(18/42);两组比较,差异无统计学意义,P> 0.05。随访6个月～2年,A组及B组的中位生存期分别为(9.16±1.06)个月、(8.98±1.12)个月;两组比较,差异无统计学意义,P> 0.05。A组Ⅲ/Ⅳ度白细胞下降8例(19.05%)、皮疹1例(2.38%)、恶心呕吐2例(4.76%);B组出现Ⅲ/Ⅳ度白细胞下降2例(4.76%)、皮疹9例(21.43%)、恶心呕吐10例(23.81%);两组比较,P <0.05。经对症处理后,症状均缓解。结论吉西他滨联合顺铂治疗与长春瑞滨联合顺铂对晚期非小细胞肺癌的临床疗效相当,均出现不同的药物不良反应,在临床应用中应根据患者药物的耐受情况选择适当的化疗方案,从而有效提高患者的生存质量。     

多囊卵巢综合征患者血清miR-206和IGF-1的表达水平及临床意义

目的探讨多囊卵巢综合征(PCOS)患者血清miR-206和胰岛素样生长因子-1 (IGF-1)表达水平及临床意义。方法选取2016年4月-2017年4月漯河市中心医院收治的79例PCOS患者为研究对象,同期选取60例月经规律健康女性为对照组,利用全自动生化分析仪检测血糖、血脂,采用放射免疫法检测空腹胰岛素(FINS)水平,计算胰岛素抵抗指数(HOMAIR),采用化学发光免疫分析法检测催乳素(PRL)、雌二醇(E2)、促卵泡刺激素(FSH)、黄体生成素(LH)、总睾酮(TT)、硫酸脱氢表雄酮(DHEAS)及雄激素结合球蛋白(SHBG)。采用实时荧光定量PCR (qRT-PCR)检测血清miR-206水平,采用酶联免疫吸附试验(ELISA)检测血清IGF-1水平。结果 (1)与对照组比较,PCOS组总胆固醇(TC)、低密度脂蛋白(LDL)、高密度脂蛋白(HDL)水平无明显异常(P0. 05),甘油三酯(TG)、空腹血糖(FBG)、FINS及HOMA-IR水平明显升高(P0. 05)。与对照组比较,PCOS组PRL、E2、LH/FSH、TT及DHEAS水平明显升高(P0. 05),SHBG水平明显下降(P0. 05)。(2)与对照组比较,PCOS组血清miR-206水平明显降低,血清IGF-1水平明显升高(P0. 05)。(3)相关分析结果显示,血清miR-206水平与PCOS患者FINS、HOMA-IR呈明显负相关(P0. 05),血清IGF-1水平与PCOS患者TG、FINS及HOMA-IR呈明显正相关(P0. 05)。多元逐步分析结果显示,HOMA-IR是PCOS组血清miR-206、IGF-1表达的独立影响因素。血清miR-206表达与IGF-1呈明显负相关(P0. 05)。结论 miR-206在PCOS患者血清中明显低表达,IGF-1呈高表达,二者与PCOS患者胰岛素抵抗有关。     

可溶性髓样细胞触发受体-1在化脓性关节炎诊断及疗效评价分析

目的分析可溶性髓样细胞触发受体-1(sTREM-1)在化脓性关节炎诊断及疗效评价中的价值,为感染性疾病诊断和治疗工作提供研究依据。方法选取2015年2月-2017年2月医院收治的50例化脓性关节炎患者作为化脓性关节炎组,选取同期35例单纯骨关节炎患者作为骨关节炎组,选取同期30名健康体检者作为对照组。检测研究对象血液中sTREM-1、C-反应蛋白(CRP)、红细胞沉降率(ESR)水平,对化脓性关节炎组和骨关节炎组患者关节液中sTREM-1水平进行检测和比较;分析患者sTREM-1、CRP及ESR水平在化脓性关节炎诊断中的价值,观察化脓性关节炎组患者的临床疗效。结果三组研究对象血液sTREM-1水平、血液CRP水平、ESR水平比较差异有统计学意义(P<0.05),其中化脓性关节炎组患者指标水平最高;化脓性关节炎组患者关节液sTREM-1水平为(82.05±62.97)ng/L高于骨关节炎组的(43.36±7.48)ng/L,两组比较差异有统计学意义(t=9.628,P<0.001);关节液sTREM-1、血液sTREM-1、CRP水平诊断化脓性关节炎患者的受试者工作特征曲线下面积(AUC)分别为0.913、0.841、0.785;关节液sTREM-1水平较低的化脓性关节炎患者的疗效分布优于关节液sTREM-1水平较高的患者(Z=2.260,P=0.024)。结论化脓性关节炎表现为关节液和血液sTREM-1表达水平的上调,可作为诊断化脓性关节炎的辅助指导,术前检测关节液sTREM-1水平也有助于预测手术治疗的效果。     

Microinjection of a growth factor cocktail affects activated microglia in the neocortex of adult rats

Microglia, as the resident immune cells in the central nervous system, play important roles in regulating neuronal processes, such as neural excitability, synaptic activity, and apoptotic cell clearance. Growth factors can activate multiple signaling pathways in central nervous system microglia and can regulate their immune effects, but whether growth factors can affect the morphological characteristics and ultrastructure of microglia has not been reported. After microinjecting 300 nL of a growth factor cocktail, including 10 μg/mL epidermal growth factor, 10 μg/mL basic fibroblast growth factor, 10 μg/mL hepatocyte growth factor and 10 μg/mL insulin-like growth factor into adult rat cortex, we found that the number of IBA1-positive microglia around the injection area increased significantly, indicating local activation of microglia. All CD68-positive labeling co-localized with IBA1 in microglia. Cell bodies and protrusions of CD68-positive cells were strongly attached to or were engulfing neurons. Characteristic huge phagosomes were observed in activated phagocytes by electron microscopy. The phagosomes generally included non-degraded neuronal protrusions and mitochondria, yet they contained no myelin membrane or remnants, which might indicate selective phagocytosis by the phagocytes. The remnant myelin sheath after phagocytosis still had regenerative ability and formed "myelin-like" structures around phagocytes. These results show that microinjection of a growth factor cocktail into the cerebral cortex of rodents can locally activate microglia and induce selective phagocytosis of neural structures by phagocytes. The study was approved by the Institute of Laboratory Animal Science, Beijing Institute of Basic Medical Sciences(approval No. IACUC-AMMS-2014-501) on June 30, 2014.     

miR-138介导ERK和AKT对NSCLC细胞株A549增殖和迁移的作用机制研究

目的探讨miR-138介导ERK和AKT对非小细胞肺癌(NSCLC)细胞株A549增殖和迁移的作用机制。方法选取NSCLC细胞株A549分成Az组、Am组和Ay组,Az组A549细胞转染空载体,Am组转染miR-138-mimics,Ay组转染miR-138-inhibitions,采用RT-PCR法检测miR-138、ERK和AKT mRNA水平变化,Westernblot法检测ERK和AKT蛋白,分别用Transwell法和MTT法检测A459细胞的迁移和增殖情况,流式细胞仪检测A549细胞凋亡程度。结果 RT-PCR检测三组miR-138、ERK和AKT mRNA水平变化:Ay组ERK和AKT mRNA水平变化最高,Az组其次,Am组最低; Am组miR-138水平变化最高,Az组其次,Ay组最低(均P <0. 05)。Westernblot法检测三组ERK和AKT蛋白表达:Ay组ERK和AKT蛋白表达最高,Az组其次,Am组最低(均P <0. 05)。流式细胞仪检测三组A549细胞凋亡程度:Am组A549细胞凋亡最多,Az组其次,Ay组最低,Am组A549细胞凋亡数量较Ay组多,说明A549细胞凋亡随miR-138水平增加而上升(均P <0. 05)。Transwell检测三组A549细胞迁移能力:Ay组癌细胞迁移能力强,显微镜下细胞数量多,Am组癌细胞数量较Az组少,迁移能力较弱(均P <0. 05)。MTT检测三组A549细胞增殖能力:Ay组细胞增殖能力最高,Az组其次,Am组最弱(均P <0. 05)。结论 miR-138在NSCLC细胞株A549的迁移和增殖中发挥重要作用,其过表达可调控ERK和AKT信号,抑制细胞迁移和增殖,促进细胞凋亡。