Objective Schizophrenia(SZ)is associated with cognitive impairment,and it is known that the activity of cAMP response element binding protein(CREB)decreases in the brain of SZ patients.The previous study conducted by ...Objective Schizophrenia(SZ)is associated with cognitive impairment,and it is known that the activity of cAMP response element binding protein(CREB)decreases in the brain of SZ patients.The previous study conducted by the investigators revealed that the upregulation of CREB improves the MK801-related SZ cognitive deficit.The present study further investigates the mechanism on how CREB deficiency is associated with SZ-related cognitive impairment.Methods MK-801 was used to induce SZ in rats.Western blotting and immunofluorescence were performed to investigate CREB and the CREB-related pathway implicated in MK801 rats.The long-term potentiation and behavioral tests were performed to assess the synaptic plasticity and cognitive impairment,respectively.Results The phosphorylation of CREB at Ser133 decreased in the hippocampus of SZ rats.Interestingly,among the upstream kinases of CREB,merely ERK1/2 was downregulated,while CaMKII and PKA remained unchanged in the brain of MK801-related SZ rats.The inhibition of ERK1/2 by PD98059 reduced the phosphorylation of CREB-Ser133,and induced synaptic dysfunction in primary hippocampal neurons.Conversely,the activation of CREB attenuated the ERK1/2 inhibitor-induced synaptic and cognitive impairment.Conclusion These present findings partially suggest that the deficiency of the ERK1/2-CREB pathway is involved in MK801-related SZ cognitive impairment.The activation of the ERK1/2-CREB pathway may be therapeutically useful for treating SZ cognitive deficits.展开更多
数控铣床是数字控制机床(Computer numerical which control of machine tools)的简称,是用程序来控制系统的自动化机床,该控制系统能够逻辑地处理具有控制编码或其他符号指令规定的程序,并将其译码,从而使铣床动作。正常的数控铣床并...数控铣床是数字控制机床(Computer numerical which control of machine tools)的简称,是用程序来控制系统的自动化机床,该控制系统能够逻辑地处理具有控制编码或其他符号指令规定的程序,并将其译码,从而使铣床动作。正常的数控铣床并不适用于学生们的课堂学习实验,因为一般铣床价格昂贵、拥有巨大的体积、软件硬件也相对比较封闭,故专门为此设计了一套教学型数控铣床,不仅功能多样符合一般铣床教学要求,而且软硬件结构都十分开放、成本不高、结构简单且具有代表性。展开更多
目的:观察5-脂氧合酶活化蛋白(5-lipoxygenase activating protein,FLAP)抑制剂MK886对人结肠癌细胞株SW480、Caco-2增殖和凋亡的影响.方法:噻唑蓝(MTT)比色法检测6.25、12.5、25、50、100、200μmol/L MK886作用24、48、72 h对S W480和...目的:观察5-脂氧合酶活化蛋白(5-lipoxygenase activating protein,FLAP)抑制剂MK886对人结肠癌细胞株SW480、Caco-2增殖和凋亡的影响.方法:噻唑蓝(MTT)比色法检测6.25、12.5、25、50、100、200μmol/L MK886作用24、48、72 h对S W480和C a c o-2细胞的抑制率;A n n e x i n V-F I T C/P I双染流式细胞术检测12.5、25、50、100μmol/L MK886作用72 h的结肠癌细胞凋亡率;流式细胞仪检测12.5、25、50μmol/L MK886作用72 h的结肠癌细胞周期.结果:50μmol/L到200μmol/L的MK886对结肠癌SW480细胞有抑制作用,且存在时效和量效依赖性;而12.5μmol/L到25μmol/L浓度的MK886处理24 h后,对SW480细胞无明显作用,延长时间至48、72 h后,作用有统计学意义,且同样存在时效和量效依赖性;6.25μmol/L的MK886对SW480细胞无抑制作用.25μmol/L到200μmol/L的MK886对结肠癌Caco-2细胞有抑制作用,且存在时效和量效依赖性;而6.25μmol/L到12.5μmol/L浓度的MK886对Caco-2细胞无抑制作用.200μmol/L MK886作用24h即可明显抑制SW480、Caco-2两种结肠癌细胞株的增殖,抑制率接近90%.12.5μmol/L到100μmol/L浓度的MK886对两种结肠癌SW480和Caco-2细胞有凋亡作用,且存在时效和量效依赖性;12.5μmol/L到50μmol/L浓度的MK886可以增加两种结肠癌SW480和Caco-2细胞G0/G1期比例,降低S期比例.结论:MK886具有显著的抑制人结肠癌SW48-0、Caco-2细胞株增殖的作用,该作用可能是通过阻滞细胞于G0/G1期,并诱导肿瘤细胞凋亡所致.展开更多
基金supported in part by grants from National Natural Science Foundation of China(No.31929002,No.82201326 No.82071440 and No.92049107)Science,Technology and Innovation Commission of Shenzhen Municipality(No.JCYJ20210324141405014)+1 种基金Guangdong Basic and Applied Basic Research Foundation(No.2020B1515120017)the Academic Frontier Youth Team Project to Xiao-chuan WANG from Huazhong University of Science and Technology.
文摘Objective Schizophrenia(SZ)is associated with cognitive impairment,and it is known that the activity of cAMP response element binding protein(CREB)decreases in the brain of SZ patients.The previous study conducted by the investigators revealed that the upregulation of CREB improves the MK801-related SZ cognitive deficit.The present study further investigates the mechanism on how CREB deficiency is associated with SZ-related cognitive impairment.Methods MK-801 was used to induce SZ in rats.Western blotting and immunofluorescence were performed to investigate CREB and the CREB-related pathway implicated in MK801 rats.The long-term potentiation and behavioral tests were performed to assess the synaptic plasticity and cognitive impairment,respectively.Results The phosphorylation of CREB at Ser133 decreased in the hippocampus of SZ rats.Interestingly,among the upstream kinases of CREB,merely ERK1/2 was downregulated,while CaMKII and PKA remained unchanged in the brain of MK801-related SZ rats.The inhibition of ERK1/2 by PD98059 reduced the phosphorylation of CREB-Ser133,and induced synaptic dysfunction in primary hippocampal neurons.Conversely,the activation of CREB attenuated the ERK1/2 inhibitor-induced synaptic and cognitive impairment.Conclusion These present findings partially suggest that the deficiency of the ERK1/2-CREB pathway is involved in MK801-related SZ cognitive impairment.The activation of the ERK1/2-CREB pathway may be therapeutically useful for treating SZ cognitive deficits.
文摘数控铣床是数字控制机床(Computer numerical which control of machine tools)的简称,是用程序来控制系统的自动化机床,该控制系统能够逻辑地处理具有控制编码或其他符号指令规定的程序,并将其译码,从而使铣床动作。正常的数控铣床并不适用于学生们的课堂学习实验,因为一般铣床价格昂贵、拥有巨大的体积、软件硬件也相对比较封闭,故专门为此设计了一套教学型数控铣床,不仅功能多样符合一般铣床教学要求,而且软硬件结构都十分开放、成本不高、结构简单且具有代表性。
文摘目的:观察5-脂氧合酶活化蛋白(5-lipoxygenase activating protein,FLAP)抑制剂MK886对人结肠癌细胞株SW480、Caco-2增殖和凋亡的影响.方法:噻唑蓝(MTT)比色法检测6.25、12.5、25、50、100、200μmol/L MK886作用24、48、72 h对S W480和C a c o-2细胞的抑制率;A n n e x i n V-F I T C/P I双染流式细胞术检测12.5、25、50、100μmol/L MK886作用72 h的结肠癌细胞凋亡率;流式细胞仪检测12.5、25、50μmol/L MK886作用72 h的结肠癌细胞周期.结果:50μmol/L到200μmol/L的MK886对结肠癌SW480细胞有抑制作用,且存在时效和量效依赖性;而12.5μmol/L到25μmol/L浓度的MK886处理24 h后,对SW480细胞无明显作用,延长时间至48、72 h后,作用有统计学意义,且同样存在时效和量效依赖性;6.25μmol/L的MK886对SW480细胞无抑制作用.25μmol/L到200μmol/L的MK886对结肠癌Caco-2细胞有抑制作用,且存在时效和量效依赖性;而6.25μmol/L到12.5μmol/L浓度的MK886对Caco-2细胞无抑制作用.200μmol/L MK886作用24h即可明显抑制SW480、Caco-2两种结肠癌细胞株的增殖,抑制率接近90%.12.5μmol/L到100μmol/L浓度的MK886对两种结肠癌SW480和Caco-2细胞有凋亡作用,且存在时效和量效依赖性;12.5μmol/L到50μmol/L浓度的MK886可以增加两种结肠癌SW480和Caco-2细胞G0/G1期比例,降低S期比例.结论:MK886具有显著的抑制人结肠癌SW48-0、Caco-2细胞株增殖的作用,该作用可能是通过阻滞细胞于G0/G1期,并诱导肿瘤细胞凋亡所致.
