Amyotrophic lateral sclerosis(ALS) is a rapidly progressing neurodegenerative disease that leads to death. No effective treatments are currently available. Based on data from epidemiological, etiological, laboratory, ...Amyotrophic lateral sclerosis(ALS) is a rapidly progressing neurodegenerative disease that leads to death. No effective treatments are currently available. Based on data from epidemiological, etiological, laboratory, and clinical studies, I offer a new way of thinking about ALS and its treatment. This paper describes a host of extrinsic factors, including the exposome, that disrupt the extracellular matrix and protein function such that a spreading, prionlike disease leads to neurodegeneration in the motor tracts. A treatment regimen is described using the stem cell released molecules from a number of types of adult stem cells to provide tissue dependent molecules that restore homeostasis, including proteostasis, in the ALS patient. Because stem cells themselves as a therapeutic are cumbersome and expensive, and when implanted in a host cause aging of the host tissue and often fail to engraft or remain viable, only the S2 RM molecules are used. Rebuilding of the extracellular matrix and repair of the dysfunctional proteins in the ALS patient ensues.展开更多
目的:探讨艾灸对幽门螺杆菌(Helicobacter pylori,H.pylori)胃炎大鼠胃黏膜HE染色镜检胃黏膜炎症积分值和单核细胞核因子-B(nuclear factor-B,NF-B)、I B含量的影响,初步揭示艾灸干预H.pylori胃黏膜炎性损伤,保护胃黏膜的机制.方法:50...目的:探讨艾灸对幽门螺杆菌(Helicobacter pylori,H.pylori)胃炎大鼠胃黏膜HE染色镜检胃黏膜炎症积分值和单核细胞核因子-B(nuclear factor-B,NF-B)、I B含量的影响,初步揭示艾灸干预H.pylori胃黏膜炎性损伤,保护胃黏膜的机制.方法:50只健康大鼠随机分为5组,即A空白组、B模型组、C艾灸组、D艾灸非穴点组和E电针组,每组10只.采用H.pylori灌胃造模,蛋白免疫印记法检测大鼠外周血单核细胞NFB、I B的含量.结果:与A组比较,B组大鼠胃黏膜HE染色镜检胃黏膜炎症积分值和单核细胞NF-B含量显著升高(0±2.0 vs 2.5±2.5,0.54±0.11/-actinvs 0.36±0.13/-actin,P<0.01),I B含量显著降低(0.21±0.03/-actin vs 0.65±0.18/-actin,P<0.01);与B组比较,C组大鼠胃黏膜H E染色镜检胃黏膜炎症积分值和单核细胞NF-B含量显著减低(2.5±2.5 vs 0±2.00,0.36±0.13/-actin vs 0.50±0.04/-actin,P<0.01),I B含量显著升高(0.65±0.18/-actin vs 0.24±0.06/-actin,P<0.01);与D组相比,C组大鼠胃黏膜HE染色镜检胃黏膜炎症积分值和单核细胞NF-B含量明显升高(3.00±2.5 vs 0±2.00,0.36±0.12/-actin vs 0.50±0.04/-actin,P<0.01),I B含量显著降低(0.64±0.19/-actin vs 0.24±0.06/-actin,P<0.01);与E组相比,C组大鼠胃黏膜HE染色镜检胃黏膜炎症积分值和单核细胞NF-B含量明显升高(3±2.75 vs 0±2.00,0.35±0.10/-actin vs 0.50±0.04/-actin,P<0.01),I B含量显著降低(0.52±0.17/-actinvs 0.24±0.06/-actin,P<0.01).结论:艾灸穴位可减轻H.pylori胃炎胃黏膜炎性损伤,此作用可能与艾灸诱导单核细胞I B大量表达,抑制NF-B表达,减少炎性细胞因子的释放,减轻胃黏膜炎症损伤有关.展开更多
目的探讨PKC介导的ERK1/2信号通路在臭氧(ozone,O_(3))预处理大鼠肝缺血再灌注中的作用。方法60只大鼠随机分成6组:对照组、缺血再灌注组、O_(3)预处理组、O_(3)预处理+ERK抑制剂组(O_(3)+PD98059组)、O_(3)预处理+PKC抑制剂组(O_(3)+CH...目的探讨PKC介导的ERK1/2信号通路在臭氧(ozone,O_(3))预处理大鼠肝缺血再灌注中的作用。方法60只大鼠随机分成6组:对照组、缺血再灌注组、O_(3)预处理组、O_(3)预处理+ERK抑制剂组(O_(3)+PD98059组)、O_(3)预处理+PKC抑制剂组(O_(3)+CHE组)、缺血再灌注+PKC激活剂组(IR+PMA组)。除对照组外,其余各组均进行肝缺血再灌注手术。O_(3)相关组予O_(3)预处理,调节剂组予相应的调节剂。分别检测各组的血清中丙氨酸氨基转移酶、天冬氨酸氨基转氨酶水平,进行病理学观察,Western blotting检测肝组织中的热休克蛋白70(heat shock protein 70,HSP70)、蛋白激酶C(protein kinase C,PKC)和细胞外调节蛋白激酶1/2(extracellular regulated protein kinases,ERK1/2)的表达水平。结果与对照组相比,缺血再灌注组肝组织细胞损伤明显加重(P<0.05),肝组织中PKC、ERK1/2的磷酸化和HSP70的表达水平明显升高(P<0.05)。与缺血再灌注组相比,O_(3)相关组肝组织细胞损伤明显减轻(P<0.05),肝组织中PKC、ERK1/2的磷酸化和HSP70的表达水平明显升高(P<0.05)。与O_(3)预处理组相比,当使用PKC和ERK1/2抑制剂后,肝组织细胞损伤明显加重(P<0.05),肝组织中PKC、ERK1/2的磷酸化和HSP70的表达水平明显降低(P<0.05)。结论O_(3)氧化预处理可通过激活PKC介导的ERK1/2信号通路,使HSP70的表达水平明显增加,使大鼠肝脏缺血再灌注损伤明显减轻。展开更多
文摘Amyotrophic lateral sclerosis(ALS) is a rapidly progressing neurodegenerative disease that leads to death. No effective treatments are currently available. Based on data from epidemiological, etiological, laboratory, and clinical studies, I offer a new way of thinking about ALS and its treatment. This paper describes a host of extrinsic factors, including the exposome, that disrupt the extracellular matrix and protein function such that a spreading, prionlike disease leads to neurodegeneration in the motor tracts. A treatment regimen is described using the stem cell released molecules from a number of types of adult stem cells to provide tissue dependent molecules that restore homeostasis, including proteostasis, in the ALS patient. Because stem cells themselves as a therapeutic are cumbersome and expensive, and when implanted in a host cause aging of the host tissue and often fail to engraft or remain viable, only the S2 RM molecules are used. Rebuilding of the extracellular matrix and repair of the dysfunctional proteins in the ALS patient ensues.
文摘目的:探讨艾灸对幽门螺杆菌(Helicobacter pylori,H.pylori)胃炎大鼠胃黏膜HE染色镜检胃黏膜炎症积分值和单核细胞核因子-B(nuclear factor-B,NF-B)、I B含量的影响,初步揭示艾灸干预H.pylori胃黏膜炎性损伤,保护胃黏膜的机制.方法:50只健康大鼠随机分为5组,即A空白组、B模型组、C艾灸组、D艾灸非穴点组和E电针组,每组10只.采用H.pylori灌胃造模,蛋白免疫印记法检测大鼠外周血单核细胞NFB、I B的含量.结果:与A组比较,B组大鼠胃黏膜HE染色镜检胃黏膜炎症积分值和单核细胞NF-B含量显著升高(0±2.0 vs 2.5±2.5,0.54±0.11/-actinvs 0.36±0.13/-actin,P<0.01),I B含量显著降低(0.21±0.03/-actin vs 0.65±0.18/-actin,P<0.01);与B组比较,C组大鼠胃黏膜H E染色镜检胃黏膜炎症积分值和单核细胞NF-B含量显著减低(2.5±2.5 vs 0±2.00,0.36±0.13/-actin vs 0.50±0.04/-actin,P<0.01),I B含量显著升高(0.65±0.18/-actin vs 0.24±0.06/-actin,P<0.01);与D组相比,C组大鼠胃黏膜HE染色镜检胃黏膜炎症积分值和单核细胞NF-B含量明显升高(3.00±2.5 vs 0±2.00,0.36±0.12/-actin vs 0.50±0.04/-actin,P<0.01),I B含量显著降低(0.64±0.19/-actin vs 0.24±0.06/-actin,P<0.01);与E组相比,C组大鼠胃黏膜HE染色镜检胃黏膜炎症积分值和单核细胞NF-B含量明显升高(3±2.75 vs 0±2.00,0.35±0.10/-actin vs 0.50±0.04/-actin,P<0.01),I B含量显著降低(0.52±0.17/-actinvs 0.24±0.06/-actin,P<0.01).结论:艾灸穴位可减轻H.pylori胃炎胃黏膜炎性损伤,此作用可能与艾灸诱导单核细胞I B大量表达,抑制NF-B表达,减少炎性细胞因子的释放,减轻胃黏膜炎症损伤有关.
文摘目的探讨PKC介导的ERK1/2信号通路在臭氧(ozone,O_(3))预处理大鼠肝缺血再灌注中的作用。方法60只大鼠随机分成6组:对照组、缺血再灌注组、O_(3)预处理组、O_(3)预处理+ERK抑制剂组(O_(3)+PD98059组)、O_(3)预处理+PKC抑制剂组(O_(3)+CHE组)、缺血再灌注+PKC激活剂组(IR+PMA组)。除对照组外,其余各组均进行肝缺血再灌注手术。O_(3)相关组予O_(3)预处理,调节剂组予相应的调节剂。分别检测各组的血清中丙氨酸氨基转移酶、天冬氨酸氨基转氨酶水平,进行病理学观察,Western blotting检测肝组织中的热休克蛋白70(heat shock protein 70,HSP70)、蛋白激酶C(protein kinase C,PKC)和细胞外调节蛋白激酶1/2(extracellular regulated protein kinases,ERK1/2)的表达水平。结果与对照组相比,缺血再灌注组肝组织细胞损伤明显加重(P<0.05),肝组织中PKC、ERK1/2的磷酸化和HSP70的表达水平明显升高(P<0.05)。与缺血再灌注组相比,O_(3)相关组肝组织细胞损伤明显减轻(P<0.05),肝组织中PKC、ERK1/2的磷酸化和HSP70的表达水平明显升高(P<0.05)。与O_(3)预处理组相比,当使用PKC和ERK1/2抑制剂后,肝组织细胞损伤明显加重(P<0.05),肝组织中PKC、ERK1/2的磷酸化和HSP70的表达水平明显降低(P<0.05)。结论O_(3)氧化预处理可通过激活PKC介导的ERK1/2信号通路,使HSP70的表达水平明显增加,使大鼠肝脏缺血再灌注损伤明显减轻。
