BACKGROUND： Natural cerebrolysin （NC）, a Chinese herbal drug for the treatment of Alzheimer＇s disease （AD）, induces mesenchymal stem cell （MSC） differentiation into neuron-like cells, with low toxicity. But th...BACKGROUND： Natural cerebrolysin （NC）, a Chinese herbal drug for the treatment of Alzheimer＇s disease （AD）, induces mesenchymal stem cell （MSC） differentiation into neuron-like cells, with low toxicity. But the mechanisms involved in NC effects on MSCs remain poorly understood. OBJECTIVE： We used a whole genome microarray technique to further investigate the molecular, genetic, and pharmacodynamic mechanisms of NC on MSC gene expression profiles. DESIGN, TIME AND SETTING： A parallel, controlled, in vitro experiment was performed at the First Affiliated Hospital of Shenzhen University, Shenzhen Institute of Integrated Chinese and Western Medicine, China, between September 2006 and October 2008. MATERIALS： NC was provided by Shenzhen Institute of Integrated Chinese and Western Medicine China. It was predominantly composed of Renshen （Radix Ginseng）, Tianma （Rhizoma Gastrodiae） and Yinxingye （Ginkgo Leaf） and prepared by conventional water extractJon technology. Twelve adult, male, New Zealand rabbits were included, six of which underwent intragastric administration of NC extract for 1 month to create NC-containing serum. METHODS： Bone marrow was collected from the tibia and femur of Sprague Dawley rats, aged 6 8 months old. Rat MSCs were isolated and purified by the whole bone marrow adherence method. After in vitro culture, MSCs from passage 4 were treated with NC-containing serum for 48 hours, and total RNA was extracted. Gene expression in MSCs was analyzed using Affymetrix whole genome microarray analysis. MAIN OUTCOME MEASURES： Differentially expressed genes in NC serum-treated MSCs. RESULTS： NC treated MSCs displayed 46 differentially expressed genes, 22 with upregulated expression （fold change 〉 2） and 24 with downregulated expression （fold change 〈 -2）. Differentially expressed genes participated in neuronal growth, differentiation, and function, cell growth, differentiation, proliferation, apoptosis, signal transduction, substance/energy metabolism, ion transport, and immune responses. NC treatment changed levels of transforming growth factor β/ bone morphogenetic proteins, Hedgehog, Bmp, and Wntsignaling pathways, which regulate nerve cell differentiation, development and function, as well as learning and memory; Ras, G protein- coupled receptor signal pathways that are related to cell growth, proliferation, and apoptosis; and mitogen-activated protein kinase kinase kinase signaling cascades. CONCLUSION： NC can regulate gene expression for many signal transduction pathways related to nerve cell differentiation, development and function, learning and memory function, as well as regulation of cell growth, differentiation, proliferation, or apoptosis to mediate the genetic effects of NC treatment on AD.展开更多
为解决集成电路的全芯片静电防护设计中寄生电阻导致的防护空间压缩问题,提出了一种实用的能够在版图设计过程中提高集成电路静电放电(ESD)防护能力的仿真方法,用于评估和控制ESD电流通路上的寄生电阻,辅助ESD防护设计,预估器件静电防...为解决集成电路的全芯片静电防护设计中寄生电阻导致的防护空间压缩问题,提出了一种实用的能够在版图设计过程中提高集成电路静电放电(ESD)防护能力的仿真方法,用于评估和控制ESD电流通路上的寄生电阻,辅助ESD防护设计,预估器件静电防护等级。详细介绍了仿真方法的原理和流程,以0.18μm SOI CMOS工艺制造的静态随机存储器电路为仿真和实验对象,应用此仿真方法,统计寄生电阻值,优化ESD防护设计,并进行ESD测试,记录未优化样品和优化样品的失效电压。通过对比寄生电阻和失效电压,证明降低寄生电阻可获得更好的ESD防护性能,而且器件失效电压和关键寄生电阻值R Vdd之间存在近似线性反比关系。展开更多
基金Scientific and Technological Foundation of the National Administration of Traditional Chinese Medicine of China,No.02-03LP41the Scientific and Techno-logical Key Project of Guangdong Province,No.2006B35630007
文摘BACKGROUND： Natural cerebrolysin （NC）, a Chinese herbal drug for the treatment of Alzheimer＇s disease （AD）, induces mesenchymal stem cell （MSC） differentiation into neuron-like cells, with low toxicity. But the mechanisms involved in NC effects on MSCs remain poorly understood. OBJECTIVE： We used a whole genome microarray technique to further investigate the molecular, genetic, and pharmacodynamic mechanisms of NC on MSC gene expression profiles. DESIGN, TIME AND SETTING： A parallel, controlled, in vitro experiment was performed at the First Affiliated Hospital of Shenzhen University, Shenzhen Institute of Integrated Chinese and Western Medicine, China, between September 2006 and October 2008. MATERIALS： NC was provided by Shenzhen Institute of Integrated Chinese and Western Medicine China. It was predominantly composed of Renshen （Radix Ginseng）, Tianma （Rhizoma Gastrodiae） and Yinxingye （Ginkgo Leaf） and prepared by conventional water extractJon technology. Twelve adult, male, New Zealand rabbits were included, six of which underwent intragastric administration of NC extract for 1 month to create NC-containing serum. METHODS： Bone marrow was collected from the tibia and femur of Sprague Dawley rats, aged 6 8 months old. Rat MSCs were isolated and purified by the whole bone marrow adherence method. After in vitro culture, MSCs from passage 4 were treated with NC-containing serum for 48 hours, and total RNA was extracted. Gene expression in MSCs was analyzed using Affymetrix whole genome microarray analysis. MAIN OUTCOME MEASURES： Differentially expressed genes in NC serum-treated MSCs. RESULTS： NC treated MSCs displayed 46 differentially expressed genes, 22 with upregulated expression （fold change 〉 2） and 24 with downregulated expression （fold change 〈 -2）. Differentially expressed genes participated in neuronal growth, differentiation, and function, cell growth, differentiation, proliferation, apoptosis, signal transduction, substance/energy metabolism, ion transport, and immune responses. NC treatment changed levels of transforming growth factor β/ bone morphogenetic proteins, Hedgehog, Bmp, and Wntsignaling pathways, which regulate nerve cell differentiation, development and function, as well as learning and memory; Ras, G protein- coupled receptor signal pathways that are related to cell growth, proliferation, and apoptosis; and mitogen-activated protein kinase kinase kinase signaling cascades. CONCLUSION： NC can regulate gene expression for many signal transduction pathways related to nerve cell differentiation, development and function, learning and memory function, as well as regulation of cell growth, differentiation, proliferation, or apoptosis to mediate the genetic effects of NC treatment on AD.
文摘为解决集成电路的全芯片静电防护设计中寄生电阻导致的防护空间压缩问题,提出了一种实用的能够在版图设计过程中提高集成电路静电放电(ESD)防护能力的仿真方法,用于评估和控制ESD电流通路上的寄生电阻,辅助ESD防护设计,预估器件静电防护等级。详细介绍了仿真方法的原理和流程,以0.18μm SOI CMOS工艺制造的静态随机存储器电路为仿真和实验对象,应用此仿真方法,统计寄生电阻值,优化ESD防护设计,并进行ESD测试,记录未优化样品和优化样品的失效电压。通过对比寄生电阻和失效电压,证明降低寄生电阻可获得更好的ESD防护性能,而且器件失效电压和关键寄生电阻值R Vdd之间存在近似线性反比关系。
