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1.
NKG2D ligand RAE1ε induces generation and enhances the inhibitor function of myeloid‐derived suppressor cells in mice 下载免费PDF全文
Li Qian Weijuan Gong Xiaoqin Jia Lu Liu Feng Ye Jingjuan Ding Yuwei Xu Yi Fu Fang Tian 《Journal of cellular and molecular medicine》2017,21(9):2046-2054
Expression of surface NKG2D ligands on tumour cells, which activates nature killer (NK) cells and CD8+ T cells, is crucial in antitumour immunity. Some types of tumours have evolved mechanisms to suppress NKG2D‐mediated immune cell activation, such as tumour‐derived soluble NKG2D ligands or sustained NKG2D ligands produced by tumours down‐regulate the expression of NKG2D on NK cells and CD8+ T cells. Here, we report that surface NKG2D ligand RAE1ε on tumour cells induces CD11b+Gr‐1+ myeloid‐derived suppressor cell (MDSC) via NKG2D in vitro and in vivo. MDSCs induced by RAE1ε display a robust induction of IL‐10 and arginase, and these MDSCs show greater suppressive activity by inhibiting antigen‐non‐specific CD8+ T‐cell proliferation. Consistently, upon adoptive transfer, MDSCs induced by RAE1ε significantly promote CT26 tumour growth in IL‐10‐ and arginase‐dependent manners. RAE1ε moves cytokine balance towards Th2 but not Th1 in vivo. Furthermore, RAE1ε enhances inhibitory function of CT26‐derived MDSCs and promotes IL‐4 rather than IFN‐γ production from CT26‐derived MDSCs through NKG2D in vitro. Our study has demonstrated a novel mechanism for NKG2D ligand+ tumour cells escaping from immunosurveillance by facilitating the proliferation and the inhibitory function of MDSCs. 相似文献
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Li Liu Jingang Cui Qinbo Yang Chenglin Jia Minqi Xiong Bingbing Ning Xiaoye Du Peiwei Wang Xintong Yu Li Li Wenjian Wang Yu Chen Teng Zhang 《Biochemical and biophysical research communications》2014
Oxidative stress is mechanistically implicated in the pathogenesis of myocardial injury and the subsequent fibrogenic tissue remodeling. Therapies targeting oxidative stress in the process of myocardial fibrogenesis are still lacking and thus remain as an active research area in myocardial injury management. The current study evaluated the effects of a NADPH oxidase inhibitor, apocynin, on the production of reactive oxygen species and the development of myocardial fibrogenesis in isoproterenol (ISO)-induced myocardial injury mouse model. The results revealed a remarkable effect of apocynin on attenuating the development of myocardial necrotic lesions, inflammation and fibrogenesis. Additionally, the protective effects of apocynin against myocardial injuries were associated with suppressed expression of an array of genes implicated in inflammatory and fibrogenic responses. Our study thus provided for the first time the histopathological and molecular evidence supporting the therapeutic value of apocynin against the development of myocardial injuries, in particular, myocardial fibrogenesis, which will benefit the mechanism-based drug development targeting oxidative stress in preventing and/or treating related myocardial disorders. 相似文献
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Spectroscopic and in silico study of binding mechanism of cynidine‐3‐O‐glucoside with human serum albumin and glycated human serum albumin 下载免费PDF全文
The drug–serum albumin interaction plays a dominant role in drug efficacy and disposition. The glycation of serum albumin that occurs during diabetes may affect its drug‐binding properties in vivo. In order to evaluate the interactivity characteristics of cyanidin‐3‐O‐glucoside (C3G) with human serum albumin (HSA) and glycated human serum albumin (gHSA), this study was undertaken using multiple spectroscopic techniques and molecular modeling analysis. Time‐resolved fluorescence and the thermodynamic parameters indicated that the quenching mechanism was static quenching, and hydrogen bonding and Van der Waals force were the main forces. The protein fluorescence could be quenched by C3G, whereas the polarity of the fluorophore was not obviously changed. C3G significantly altered the secondary structure of the proteins. Furthermore, the interaction force that existed in the HSA–C3G system was greater than that in the gHSA–C3G system. Fluorescence excitation emission matrix spectra, red edge excitation shift, Fourier transform infrared spectroscopy and circular dichroism spectra provided further evidence that glycation could inhibit the binding between C3G and proteins. In addition, molecular modeling analysis supported the experimental results. The results provided more details for the application of C3G in the treatment of diabetes. 相似文献
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Bst DNA聚合酶大片段作为一种常用的DNA聚合酶,因其独特的特点:能引发链置换反应、高保真、耐高温等,而成为一种重要的DNA多重置换扩增酶。目的:为减少成本,设计一种高产,方便且扩增活性高的Bst DNA聚合酶大片段表达体系;探究该酶应用于胃癌石蜡包埋组织基因组DNA的扩增条件。方法:采用p TWIN1质粒作为载体克隆表达Bst DNA聚合酶大片段,应用几丁质亲和层析柱纯化该酶,使用该酶对人类基因组DNA进行不同温度下扩增,探究其最适反应温度,并据此对胃癌石蜡包埋组织基因组DNA进行扩增。结果:由此得到的Bst DNA聚合酶大片段能运用于胃癌石蜡包埋组织基因组DNA的扩增,扩增效率可达200倍,并能应用于a CGH芯片。结论:扩增得到保真性高,覆盖基因组范围大的DNA扩增产物。该应用与a CGH结合,使得对少量的癌症石蜡包埋组织DNA样本进行全基因组扩增,并进行其基因拷贝数变异研究成为可能。 相似文献
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Jia Liu Aihua Yang Jie Liu Xiaofan Ding Liming Liu Zhongping Shi 《Biotechnology letters》2014,36(7):1469-1477
Escherichia coli K4 synthesizes a capsular polysaccharide (CPS) consisting of a fructose-branched chondroitin (GalNAc-GlcA(fructose)n), which is a biosynthetic precursor of chondroitin sulfate. Here, the role of kfoE in the modification of the chondroitin backbone was investigated using knock-out and recombinant complementation experiments. kfoE disruption and complementation had no significant effect on cell growth. CPS production was increased by 15 % in the knock-out strain, and decreased by 21 % in the knock-out strain complemented with recombinant kfoE. CPS extracted from the knock-out strain was chondroitin, whereas CPS extracted from the complemented strain was a fructose-branched chondroitin. The results demonstrated that the kfoE gene product altered the fructose group at the C3 position of the GlcA residue during production of K4CPS. 相似文献
10.
黄皮种子发育过程中脱水敏感性与细胞膜透性的关系 总被引:3,自引:0,他引:3
黄皮(Clausena lansium (Lour.) Skeels)胚轴与完整种子的发育模式以及发育中电解质渗漏率变化有些不同. 种子生理成熟前、后的胚轴对脱水的反应也不同,前者经轻微脱水可提高萌发率和活力指数,后者不耐任何程度的脱水.活力指数的急剧下降伴随着电解质渗漏率的迅速上升.实验表明,黄皮种子在发育过程中没有形成耐脱水性. 细胞膜透性变化可反映脱水对种子的伤害程度 相似文献