目的探究Tim-3/Galectin-9负性信号通路在亲缘HLA单倍体相合外周血造血干细胞移植中的变化特点及其临床意义。方法以行单倍体造血干细胞移植的36例患者和20例健康者为研究对象,通过FCM监测患者及健康对照组外周血中CD4^(+)T细胞和Tim-3...目的探究Tim-3/Galectin-9负性信号通路在亲缘HLA单倍体相合外周血造血干细胞移植中的变化特点及其临床意义。方法以行单倍体造血干细胞移植的36例患者和20例健康者为研究对象,通过FCM监测患者及健康对照组外周血中CD4^(+)T细胞和Tim-3分子的表达情况,ELISA法检测移植后患者细胞因子Galectin-9、IFN-γ、IL-4、TGF-β和IL-17的动态变化。结果根据西雅图国际诊断标准,移植术后有14例患者发生aGVHD,22例患者未发生aGVHD。①未发生aGVHD患者移植后30~90 d CD4^(+)T细胞百分比均低于健康对照组(P<0.05);未发生aGVHD患者移植后血清中细胞因子Galectin-9、TGF-β、IFN-γ、IL-4和IL-17水平呈现逐渐增高的趋势,Galectin-9和TGF-β水平在移植后60 d达到正常值(P>0.05),IFN-γ、IL-4和IL-17在移植后第90天恢复到正常水平(P>0.05)。Spearman相关分析结果显示Galectin-9与TGF-β变化水平呈正相关(r=0.651,P=0.001);②发生aGVHD患者外周血中Tim-3^(+)CD4^(+)T细胞的百分比和IFN-γ、IL-17水平明显高于不发生aGVHD患者(P<0.01);不发生aGVHD患者的Galectin-9和TGF-β水平更高(P<0.05)。Spearman相关分析结果显示Tim-3^(+)CD4^(+)T细胞的百分比与IFN-γ水平呈正相关(r=0.631,P=0.015)。结论单倍体相合外周血造血干细胞移植后细胞因子Galectin-9和TGF-β的早期快速重建可以避免或减缓aGVHD的发生,移植后动态监测Tim-3^(+)CD4^(+)T细胞持续较多而血清中Galectin-9水平下降可能预示着aGVHD的发生。展开更多
Objective To investigate effect of pinacidil, an ATP sensitive potassium channel （KATP） opener, on the neuronal apoptosis and its signaling transduction mechanism following focal cerebral ischemia-reperfusion in rat...Objective To investigate effect of pinacidil, an ATP sensitive potassium channel （KATP） opener, on the neuronal apoptosis and its signaling transduction mechanism following focal cerebral ischemia-reperfusion in rats. Methods One hundred male Wistar rats were randomly divided into four groups： A, sham-operated group; B, ischemia-reperfusion group; C, KATe opener treatment group; and D, KATe opener and blocker treatment group. The middle cerebral artery occlusion （MCAO） model was established by using the intraluminal suture occlusion method, neuronal apoptosis was determined by TUNEL staining, and expressions of caspase-8, caspase-9 and caspase-3 mRNA were detected by in situ hybridization. Results （1） The numbers of apoptotic neurons at 12 h, 24 h, 48 h, and 72 h were significantly less in group C than in groups B and D （P 〈 0.01 or P 〈 0.05）; and there was no difference between groups B and D at all time points （P 〉 0.05）. （2） The expressions of caspase-3 mRNA and caspase-8 mRNA at all times and the expressions of caspase-9 mRNA at 12 h, 24 h, 48 h, 72 h were significantly lower in group C than in groups B and D （P 〈 0.01 or P 〈 0.05）; and there were no differences between groups B and D at all time points （P 〉 0.05）. Conclusions KATP opener can significantly decrease the neuronal apoptosis and the expressions of caspase-3, caspase-8 and caspase-9 mRNAs following cerebral ischemiareperfusion. The neuronal apoptosis may be decreased by the inhibition of both mitochondrial and death-receptor signal pathways.展开更多
Decidual natural killer （dNK） cells actively participate in the establishment and maintenance of maternal-fetal immune tolerance and act as local guardians against infection. However, how dNK cells maintain the immu...Decidual natural killer （dNK） cells actively participate in the establishment and maintenance of maternal-fetal immune tolerance and act as local guardians against infection. However, how dNK cells maintain the immune balance between tolerance and anti-infection immune responses during pregnancy remains unknown. Here, we demonstrated that the inhibitory molecule T-cell immunoglobulin domain and mucin domain-containing molecule-3 （Tim-3） are expressed on over 60% of dNK cells. Tim-3^＋ dNK cells display higher interleukin （IL）-4 and lower tumor necrosis factor （TNF）-α and perforin production. Human trophoblast cells can induce the transformation of peripheral NK cells into a dNK-like phenotype via the secretion of galectin-9 （Gal-9） and the interaction between Gal-9 and Tim-3. In addition, trophoblasts inhibit lipopolysaccharide （LPS）-induced pro-inflammatory cytokine and perforin production by dNK cells, which can be attenuated by Tim-3 neutralizing antibodies. Interestingly, a decreased percentage of Tim-3-expressing dNK cells were observed in human miscarriages and murine abortion-prone models. Moreover, T helper （Th）2-type cytokines were decreased and Thl-type cytokines were increased in Tim-3^＋ but not Tim-3- dNK cells from human and mouse miscarriages. Therefore, our results suggest that the Gal-9/Tim-3 signal is important for the regulation of dNK cell function, which is beneficial for the maintenance of a normal pregnancy.展开更多
文摘目的探究Tim-3/Galectin-9负性信号通路在亲缘HLA单倍体相合外周血造血干细胞移植中的变化特点及其临床意义。方法以行单倍体造血干细胞移植的36例患者和20例健康者为研究对象,通过FCM监测患者及健康对照组外周血中CD4^(+)T细胞和Tim-3分子的表达情况,ELISA法检测移植后患者细胞因子Galectin-9、IFN-γ、IL-4、TGF-β和IL-17的动态变化。结果根据西雅图国际诊断标准,移植术后有14例患者发生aGVHD,22例患者未发生aGVHD。①未发生aGVHD患者移植后30~90 d CD4^(+)T细胞百分比均低于健康对照组(P<0.05);未发生aGVHD患者移植后血清中细胞因子Galectin-9、TGF-β、IFN-γ、IL-4和IL-17水平呈现逐渐增高的趋势,Galectin-9和TGF-β水平在移植后60 d达到正常值(P>0.05),IFN-γ、IL-4和IL-17在移植后第90天恢复到正常水平(P>0.05)。Spearman相关分析结果显示Galectin-9与TGF-β变化水平呈正相关(r=0.651,P=0.001);②发生aGVHD患者外周血中Tim-3^(+)CD4^(+)T细胞的百分比和IFN-γ、IL-17水平明显高于不发生aGVHD患者(P<0.01);不发生aGVHD患者的Galectin-9和TGF-β水平更高(P<0.05)。Spearman相关分析结果显示Tim-3^(+)CD4^(+)T细胞的百分比与IFN-γ水平呈正相关(r=0.631,P=0.015)。结论单倍体相合外周血造血干细胞移植后细胞因子Galectin-9和TGF-β的早期快速重建可以避免或减缓aGVHD的发生,移植后动态监测Tim-3^(+)CD4^(+)T细胞持续较多而血清中Galectin-9水平下降可能预示着aGVHD的发生。
文摘Objective To investigate effect of pinacidil, an ATP sensitive potassium channel （KATP） opener, on the neuronal apoptosis and its signaling transduction mechanism following focal cerebral ischemia-reperfusion in rats. Methods One hundred male Wistar rats were randomly divided into four groups： A, sham-operated group; B, ischemia-reperfusion group; C, KATe opener treatment group; and D, KATe opener and blocker treatment group. The middle cerebral artery occlusion （MCAO） model was established by using the intraluminal suture occlusion method, neuronal apoptosis was determined by TUNEL staining, and expressions of caspase-8, caspase-9 and caspase-3 mRNA were detected by in situ hybridization. Results （1） The numbers of apoptotic neurons at 12 h, 24 h, 48 h, and 72 h were significantly less in group C than in groups B and D （P 〈 0.01 or P 〈 0.05）; and there was no difference between groups B and D at all time points （P 〉 0.05）. （2） The expressions of caspase-3 mRNA and caspase-8 mRNA at all times and the expressions of caspase-9 mRNA at 12 h, 24 h, 48 h, 72 h were significantly lower in group C than in groups B and D （P 〈 0.01 or P 〈 0.05）; and there were no differences between groups B and D at all time points （P 〉 0.05）. Conclusions KATP opener can significantly decrease the neuronal apoptosis and the expressions of caspase-3, caspase-8 and caspase-9 mRNAs following cerebral ischemiareperfusion. The neuronal apoptosis may be decreased by the inhibition of both mitochondrial and death-receptor signal pathways.
文摘Decidual natural killer （dNK） cells actively participate in the establishment and maintenance of maternal-fetal immune tolerance and act as local guardians against infection. However, how dNK cells maintain the immune balance between tolerance and anti-infection immune responses during pregnancy remains unknown. Here, we demonstrated that the inhibitory molecule T-cell immunoglobulin domain and mucin domain-containing molecule-3 （Tim-3） are expressed on over 60% of dNK cells. Tim-3^＋ dNK cells display higher interleukin （IL）-4 and lower tumor necrosis factor （TNF）-α and perforin production. Human trophoblast cells can induce the transformation of peripheral NK cells into a dNK-like phenotype via the secretion of galectin-9 （Gal-9） and the interaction between Gal-9 and Tim-3. In addition, trophoblasts inhibit lipopolysaccharide （LPS）-induced pro-inflammatory cytokine and perforin production by dNK cells, which can be attenuated by Tim-3 neutralizing antibodies. Interestingly, a decreased percentage of Tim-3-expressing dNK cells were observed in human miscarriages and murine abortion-prone models. Moreover, T helper （Th）2-type cytokines were decreased and Thl-type cytokines were increased in Tim-3^＋ but not Tim-3- dNK cells from human and mouse miscarriages. Therefore, our results suggest that the Gal-9/Tim-3 signal is important for the regulation of dNK cell function, which is beneficial for the maintenance of a normal pregnancy.
