pJAK2 polypeptide,an antagonist of suppressors of cytokine signaling-1,can enhance the antitumor effect of dendritic cells

目的:探讨细胞因子信号转导抑制因子-1(SuPPrESSOrS Of CyTOkInE SIgnAlIng1,SOCS1)拮抗物PJAk2多肽(氨基酸序列号为1001-1013)参与树突状细胞(dEndrITIC CEllS,dCS)的体外诱导培养后对dCS抗肿瘤作用的影响。方法:采集健康人外周血,离心获得单个核细胞,用重组人粒细胞巨噬细胞集落刺激因子(rECOMbInAnT HuMAn grAnulOCyTE-MACrOPHAgE COlOny STIMulATIng fACTOr,rHgM-CSf)及重组人白细胞介素-4(rECOMbInAnT HuMAn InTErlEukIn-4,rHIl-4)诱导dCS,第5天分为4组:单纯dCS培养(对照)组、抗原负载(lySATE-dCS)组、多肽修饰(PJAk2-dCS)组和抗原与多肽共培养(lySATE+PJAk2-dCS)组,第6天各组加入肿瘤坏死因子-α(TuMOr nECrOSIS fACTOr-AlPHA,Tnf-α)促成熟。倒置显微镜下观察dCS形态;fCM法检测dCS表型;乳酸脱氢酶(lACTATE dEHydrOgEnASE,ldH)细胞毒实验检测各组细胞毒性T淋巴细胞(CyTOTOXIC T lyMPHOCyTE,CTl)对胃癌细胞bgC-823的靶向杀伤作用;ElISA法检测白细胞介素-12(InTErlEukIn-12,Il-12)和γ干扰素(InTErfErOn-γ,Ifn-γ)的水平。结果:与未加入诱导剂组相比,各组均成功诱导出成熟dCS,均高表达Cd80、Cd83、Cd86和人类白细胞dr抗原(HuMAn lEukOCyTE AnTIgEn dr,HlA-dr),但以lySATE+PJAk2-dCS组的表达水平最高。在10:1~30:1的效靶比范围内,CTl杀伤作用与效靶比呈正相关。当效靶比为30:1时,对照组的CTl杀伤率达(19.77±2.34)%,低于其他3组(P<0.01),而lySATE+PJAk2-dCS组较lySATE-dCS组及PJAk2-dCS组都高(P<0.05)。lySATE+PJAk2-dCS组培养上清液中Il-12及Ifn-γ的分泌水平明显高于对照组(P<0.01)。结论:SOCS1拮抗物PJAk2多肽(1001-1013)可增强dCS对胃癌细胞的抗原递呈及特异性抗肿瘤作用。Objective:To investigate the effect of pJAK2 polypeptide,an antagonist of SOCS1(suppressors of cytokine signaling 1),on antitumor effect of in vitro cultivation-induced DCs(dendritic cells).Methods:Peripheral blood was collected from the healthy volunteers,and the PBMCs(peripheral blood mononuclear cells)were isolated.DCs were induced by rhGM-CSF(recombinant human granulocyte-macrophage colony-stimulating factor)and rhIL-4(recombinant human interleukin-4).On the fifth day,DCs were divided into four groups:control group,Lysate-DCs group,pJAK2-DCs group,and Lysate + pJAK2 DCs group.On the sixth day,TNF-α(tumor necrosis factor-alpha)was added into each group.The morphological features of DCs were observed under an inverted microscope;the phenotypes were detected by FCM(flow cytometry);the killing effect of CTLs(cytotoxic T lymphocytes)on gastric cancer BGC-823 cells was evaluated by LDH(lactate dehydrogenase)cytotoxicity test;the concentrations of IL-12(interleukin-12)and IFN-γ(interferon-γ)were detected by ELISA(enzyme-linked immuno sorbent assay).Results:Mature DCs presented typically morphological and phenotypic features;the DCs in Lysate + pJAK2-DCs group had the highest expression levels of CD80,CD83,CD86 and HLA-DR(human leukocyte antigen DR).When the ratio of effectors to target cells ranged from 10:1 to 30:1,the killing activity of CTLs had a positive correlation with the ratio.When the ratio of effectors to target cells was 30:1,the killing activity of CTLs in the control group was(19.77±2.34)%,which was lowest as compared with the other groups(P < 0.01),meanwhile the killing activity of CTLs in Lysate + pJAK2-DCs group was higher than those in Lysate-DCs and pJAK2-DCs groups(P < 0.05).The levels of IL-12 and IFN-γ secretion in Lysate + pJAK2-DCs group were apparently higher than those in the control group(P < 0.01).Conclusion:An antagonist of SOCS1,pJAK2 polypeptide,can enhance the ability of antigen presentation and specific antitumor effect of DCs on gastric cancer cells.南京军区医学科技创新课题资助项目(编号:10MA068); 福建省自然科学基金面上项目(编号:2010D013); 厦门市科技计划创新项目(编号:3502z20104014

Effect of Helicobacter pylori on the function of peripheral blood monocyte-derived dendritic cells in gastric cancer patients

分析HP阳性和HP阴性的胃癌患者外周血单核细胞来源树突状细胞(MOdCS)功能的差异性及其临床意义。方法:用尿素14C呼气试验对解放军第一七四医院2011年1月至2012年10月收治的84例胃癌患者进行HP感染状态鉴定,分别采集HP阳性和阴性胃癌患者外周血,分离外周血单个核细胞,采用经典方法(rHgM-CSf、rHIl-4联合rHTnf-α)诱导产生dCS,采用流式细胞仪检测dCS表型,采用ldH释放法检测dCS致敏T细胞对胃癌细胞的毒性杀伤作用,采用ElISA方法检测细胞因子Il-12、Ifn-γ的分泌水平。结果:两组MOdCS成熟过程形态变化无差异,HP阳性组MOdCS表面标记分子Cd1A、Cd80、Cd83、Cd86和HlA-dr平均表达百分率均高于HP阴性组,其中Cd80、Cd83、Cd86的表达水平差异有统计学意义,Cd1A、HlA-dr差异无统计学意义。HP阳性组dCS致敏T淋巴细胞对胃癌细胞杀伤率和Il-12、Ifn-γ的分泌水平均高于HP阴性组(P<0.05)。结论:HP感染状态不影响胃癌患者外周血MOdCS成熟过程形态变化,HP感染的胃癌患者MOdCS成熟和活化水平更高。Objective:This study aimed to compare and analyze the functional differences between peripheral blood monocyte-derived dendritic cells(DCs) of Helicobacter pylori-positive and H.pylori-negative patients with gastric cancer.Methods:H.pylori infection was detected in 84 patients with gastric cancer in our hospital from January 2011 to October 2012 by the14C-urea breath test.DCs were generated from monocytes isolated by an adherent method from the two groups of patients and cultured in the presence of rhIL-4,rhGM-CSF,and rhTNF-α.Furthermore,the expression of surface marker molecules was determined by fluorescence-activated cell sorting analysis.The cytotoxicity of DCs pulsed T cells against gastric carcinoma cell was assessed by the lactate dehydrogenase-releasing assay.The secretion of IL-12 and IFN-γ in the supernatant was determined by enzyme-linked immunosorbent assay.Results:No difference was observed in the morphological change of the maturation process.The mean expression of CD1a,CD80,CD83,CD86,and HLA-DR molecules in DCs of H.pylori-infected patients was higher than that in DCs of H.pylori-negative group,and the differences were statistically significant except for CD1a and HLA-DR.The cytotoxicity activities,IL-12 release,and IFN-γ release in the H.pylori-positive group were significantly higher than those in the H.pylori-negative group(P<0.05).Conclusion:H.pylori infection has no effect on the morphological change of the maturation process of monocyte-derived DCs.These data clearly demonstrate that monocyte-derived DCs of H.pylori-infected patients with gastric cancer can induce stronger maturation and activation than those of H.pylori-negative patients.南京军区医学科技创新课题(编号:10MA068); 福建省自然科学基金资助项目(编号:2010D013); 厦门市科技计划创新项目(编号:3502z20104014)资助~

萨拉乌苏河流域MGS5层段CaCO3记录的末次间冰期东亚季风与沙漠环境演化

毛乌素沙漠萨拉乌苏河流域米浪沟湾剖面时代上属末次间冰期的MGS5层段可以进一步划分为5a-5e亚段.其中5a,5c和5e亚段以河湖相和古土壤为主要特征,其CaCO3含量主体呈现峰态;5b和5d亚段以风成沙丘砂沉积为主,CaCO3含量主体呈现谷态.研究表明,末次间冰期毛乌素沙漠冬季风盛行时期,沙丘砂强烈堆积,CaCO3大量迁移;夏季风盛行时期河湖相和古土壤发育,CaCO3大量聚集.研究还发现,MGS5各个亚段CaCO3记录的冬夏季风环境与格陵兰冰芯氧同位素5a-5e亚段在时间-气候性质上的变化节奏相当一致.这可能说明,末次间冰期毛乌素沙漠的演化主要受北半球冰量增减导致的东亚冬、夏季风强弱所控制.link_to_OA_fulltex

新疆极端水文事件的时空分布特征[J]

利用1901-2010年的资料,采用传统统计方法及通过衡量极端水文事件的集中度、集中指数,分析了新疆极端水文事件的空间分布特征和时间变化规律。结果表明:新疆极端水文事件在空间分布上主要集中在伊犁和阿克苏地区,吐鲁番、和田为少灾区;时间上主要发生在夏半年,而冬半年相对较少,但北疆的阿勒泰地区冬半年较多;吐鲁番地区年内分布非常集中,乌鲁木齐、奎屯-石河子、阿克苏地区次之,阿勒泰地区集中度最小

不同产地厚叶岩白菜花部特征变化及其结实性差异研究/Study on Floral Characteristic Changes and Fecundity Differences of Bergenia crassifolia (L.) Fritsch in Different Places[J]

于2012年4～8月分别以喀纳斯湖旁的野生居群和阿勒泰市、奎屯市及乌鲁木齐市人工栽培居群的厚叶岩白菜为试材,进行开花物候过程观测,研究不同产地厚叶岩白菜花部形态特征、结实特性以及环境变化对其开花生物学特性的影响.结果表明:引种厚叶岩白菜的花期为4月初～5月中旬,野生的花期为5月中旬～6月底至7月初；引种厚叶岩白菜的花葶较矮、花朵较大、花萼也较大,但雄蕊花药较短,且花葶高及花瓣长差异极显著；通过显著性相关分析得知,引种与野生厚叶岩白菜在花期以及花部综合特征上的差异主要与海拔、年均温、年降水量及年蒸发量有关；引种厚叶岩白菜的果实相对于野生的较小,但种子却较重,且败育率也最高.该结果对于深入探索厚叶岩白菜的繁殖生态学特性和其园林绿化和园艺栽培提供了重要的理论依据