In this study, an Alzheimer's disease model was established in rats through stereotactic injection of condensed amyloid beta 1-40 into the bilateral hippocampus, and the changes of gene expression profile in the hipp...In this study, an Alzheimer's disease model was established in rats through stereotactic injection of condensed amyloid beta 1-40 into the bilateral hippocampus, and the changes of gene expression profile in the hippocampus of rat models and sham-operated rats were compared by genome expression profiling analysis. Results showed that the expression of 50 genes was significantly up-regulated (fold change 〉 2), while 21 genes were significantly down-regulated in the hippocampus of Alzheimer's disease model rats (fold change 〈 0.5) compared with the sham-operation group. The differentially expressed genes are involved in many functions, such as brain nerve system development, neuronal differentiation and functional regulation, cellular growth, differentiation and apoptosis, synaptogenesis and plasticity, inflammatory and immune responses, ion channels/transporters, signal transduction, cell material/energy metabolism. Our findings indicate that several genes were abnormally expressed in the metabolic and signal transduction pathways in the hippocampus of amyloid beta 1 40-induced rat model of Alzheimer's disease, thereby affecting the hippocampal and brain functions.展开更多
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
Mammary glands undergo functional and metabolic changes during virgin,lactation and dry periods.A total of 122 genes were identified as differentially expressed,including 79 up-regulated and 43 down-regulated genes du...Mammary glands undergo functional and metabolic changes during virgin,lactation and dry periods.A total of 122 genes were identified as differentially expressed,including 79 up-regulated and 43 down-regulated genes during lactation compared with virgin and dry periods.Gene ontology analysis showed the functional classification of the up-regulated genes in lactation,including transport,biosynthetic process,signal transduction,catalytic activity,immune system process,cell death,and positive regulation of the developmental process.Microarray data clarified molecular events in bovine mammary gland lactation.展开更多
Objective: To study the effect of Tiantai No. 1 (天泰1号) on gene expression profile in hippocampus of Alzheimer's disease (AD) rat, molecular genetic target points of the effect of this drug were defined, its m...Objective: To study the effect of Tiantai No. 1 (天泰1号) on gene expression profile in hippocampus of Alzheimer's disease (AD) rat, molecular genetic target points of the effect of this drug were defined, its molecular genetic pharmacodynamic mechanism of anti-AD was further explored at molecular gene level, and a scientific basis was provided for its clinical availability and promotion. Methods: Thirty male Sprague- Dawley rats were divided into three groups with 10 rats per group: sham-operation group, model group and Tiantai No. 1 group. Sterile surgical procedure was applied, the model group with bilateral hippocampal injection of Aβ21-40 was established, and normal saline was used instead of Aβ1-40 in the sham-operation group. One week after the models was made, rats were administered by gastric lavage once every day for three consecutive weeks. The rats of the sham-operation group and the model group were daily fed with purified water by lavage; the rats of the Tiantai No.1 group treated group were administered with Tiantai No.1 by lavage. Total RNAs of hippocampus tissues were extracted with Trizol, the changes of hippocampus gene expression profiles in the above throe groups were analyzed by using Affymetrix rat whole genome expression profile microarray. Results: Microarray analysis showed that, compared with the sham-operation group, the hippocampus of the model group had 50 up-regulated genes with significant difference (fold change 〉2), and 21 down-rogulated genes with significant difference (fold change 〈0.5); compared with the hippocampus of the model group, the hippocampus of the Tiantai No. 1 group was found to have 5 up-regulated genes with significant difference (fold change 〉2) and 20 down-regulated genes with significant difference (fold change 〈0.5). The functions of differonUally expressed genes of the groups were involved in nervous system's development, neuronic differentiation and function-regulation, cellular growth and differentiation and apoptosis, synaptic occurrence and plasticity, inflammation and immune response, ion channels/transporters, cellular signal transduction, cellular material/energy metabolism and so on. Conclusion: Tiantai No. 1 can regulate hippocampal function, and further regulate the brain function of animals in multiple gene target points by a number of ways.展开更多
Since genetic engineering of pigs can benefit both biomedicine and agriculture,selecting a suitable gene promoter is critically important.The cytomegalovirus(CMV)promoter,which can robustly drive ubiquitous transgene ...Since genetic engineering of pigs can benefit both biomedicine and agriculture,selecting a suitable gene promoter is critically important.The cytomegalovirus(CMV)promoter,which can robustly drive ubiquitous transgene expression,is commonly used at present,yet recent reports suggest tissue-specific activity in the pig.The objective of this study was to quantify ZsGreen1 protein(in lieu of CMV promoter activity)in tissues from pigs harboring a CMV-ZsGreen1 transgene with a single integration site.Tissue samples(n=35)were collected from neonatal hemizygous(n=3)and homozygous(n=3)piglets and ZsGreen1 abundance was determined via immunoblotting.ZsGreen1 was detected in all tissues,except hypothalamus,kidney cortex and oviduct.The expression patterns of homozygous and hemizygous piglets were similar(P>0.05).However,quantification revealed that ZsGreen1 protein levels were tissue-specific.Within neural/endocrine tissues,ZsGreen1 abundance was highest in the anterior pituitary gland,intermediate in the cerebellum and lowest in the cerebrum,spinal cord and posterior pituitary(P<0.05).In the digestive system,ZsGreen1 was more abundant in the salivary gland than esophagus,stomach,pancreas,duodenum,jejunum,ileum,spleen,colon,gallbladder and liver(P<0.05).Interestingly,ZsGreen1 amounts also differed within an organ(i.e.,the right ventricle had 3-fold higher levels than the other heart chambers;P<0.05).These results provide useful information for the use of the CMV promoter to drive transgene expression in the pig.Moreover,this swine model represents a novel resource of ZsGreen1-labeled organs and a valuable tool to advance genome editing research.展开更多
Biochip is a kind of minimized and integrated analyzer for molecular biology and biochemistry. Advances in biochip technology enable massive parallel mining of biological data, with biochips providing hybridizationbas...Biochip is a kind of minimized and integrated analyzer for molecular biology and biochemistry. Advances in biochip technology enable massive parallel mining of biological data, with biochips providing hybridizationbased expression monitoring, polymorphism detection and genotyping on a genomic scale. Microarrays may soon permit the expression analysis of the entire human genome in a single reaction. These ’genome chips’ will provide access to key areas of human health, including disease diagnosis, drug discovery, toxicology, etc. Microarray technology is rapidly becoming a central platform for functional genomics. Development of biochips is to immigrate the eatire analysis process of biochemical reactions and establish the micro total analytical system or lab-on-a-chip.展开更多
基金sponsored by the National Natural Science Foundation of China,No. 30973779
文摘In this study, an Alzheimer's disease model was established in rats through stereotactic injection of condensed amyloid beta 1-40 into the bilateral hippocampus, and the changes of gene expression profile in the hippocampus of rat models and sham-operated rats were compared by genome expression profiling analysis. Results showed that the expression of 50 genes was significantly up-regulated (fold change 〉 2), while 21 genes were significantly down-regulated in the hippocampus of Alzheimer's disease model rats (fold change 〈 0.5) compared with the sham-operation group. The differentially expressed genes are involved in many functions, such as brain nerve system development, neuronal differentiation and functional regulation, cellular growth, differentiation and apoptosis, synaptogenesis and plasticity, inflammatory and immune responses, ion channels/transporters, signal transduction, cell material/energy metabolism. Our findings indicate that several genes were abnormally expressed in the metabolic and signal transduction pathways in the hippocampus of amyloid beta 1 40-induced rat model of Alzheimer's disease, thereby affecting the hippocampal and brain functions.
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.
基金supported by the National High Technology Research and Development Program of China (Grant No. 2006AA10Z1A4)the Innovation Team of the Northeast Agricultural University (Grant No. LXT005-1-1)
文摘Mammary glands undergo functional and metabolic changes during virgin,lactation and dry periods.A total of 122 genes were identified as differentially expressed,including 79 up-regulated and 43 down-regulated genes during lactation compared with virgin and dry periods.Gene ontology analysis showed the functional classification of the up-regulated genes in lactation,including transport,biosynthetic process,signal transduction,catalytic activity,immune system process,cell death,and positive regulation of the developmental process.Microarray data clarified molecular events in bovine mammary gland lactation.
基金Supported by the National Natural Science Foundation of China(No.39770890)Shenzhen Major Project of Science and Technology Planning,China(No.JCYJ20130401115231337)
文摘Objective: To study the effect of Tiantai No. 1 (天泰1号) on gene expression profile in hippocampus of Alzheimer's disease (AD) rat, molecular genetic target points of the effect of this drug were defined, its molecular genetic pharmacodynamic mechanism of anti-AD was further explored at molecular gene level, and a scientific basis was provided for its clinical availability and promotion. Methods: Thirty male Sprague- Dawley rats were divided into three groups with 10 rats per group: sham-operation group, model group and Tiantai No. 1 group. Sterile surgical procedure was applied, the model group with bilateral hippocampal injection of Aβ21-40 was established, and normal saline was used instead of Aβ1-40 in the sham-operation group. One week after the models was made, rats were administered by gastric lavage once every day for three consecutive weeks. The rats of the sham-operation group and the model group were daily fed with purified water by lavage; the rats of the Tiantai No.1 group treated group were administered with Tiantai No.1 by lavage. Total RNAs of hippocampus tissues were extracted with Trizol, the changes of hippocampus gene expression profiles in the above throe groups were analyzed by using Affymetrix rat whole genome expression profile microarray. Results: Microarray analysis showed that, compared with the sham-operation group, the hippocampus of the model group had 50 up-regulated genes with significant difference (fold change 〉2), and 21 down-rogulated genes with significant difference (fold change 〈0.5); compared with the hippocampus of the model group, the hippocampus of the Tiantai No. 1 group was found to have 5 up-regulated genes with significant difference (fold change 〉2) and 20 down-regulated genes with significant difference (fold change 〈0.5). The functions of differonUally expressed genes of the groups were involved in nervous system's development, neuronic differentiation and function-regulation, cellular growth and differentiation and apoptosis, synaptic occurrence and plasticity, inflammation and immune response, ion channels/transporters, cellular signal transduction, cellular material/energy metabolism and so on. Conclusion: Tiantai No. 1 can regulate hippocampal function, and further regulate the brain function of animals in multiple gene target points by a number of ways.
基金This project was partially supported by the Nebraska Agricultural Experiment Station with funding from the Hatch Multistate Research capacity funding program(Accession No.1011129 to BRW)an Agriculture and Food Research Initiative(AFRI)Competitive Grant(2017-67015-26508 to BRW)aan AFRI ELI predoctoral fellowship(2017-67011-26036 to ATD)from the USDA National Institute of Food and Agriculture.The funding agency had no role in study design,data collection,interpretation,or manuscript generation.The authors wish to thank Ginger Mills for pig husbandry as well as Scott Kurz,Guilherme Cezar,Kyle Regan and Amanda Lambrecht for technical assistance.The authors would also like to express gratitude to Lelanya Yates for aiding in the dissections.
文摘Since genetic engineering of pigs can benefit both biomedicine and agriculture,selecting a suitable gene promoter is critically important.The cytomegalovirus(CMV)promoter,which can robustly drive ubiquitous transgene expression,is commonly used at present,yet recent reports suggest tissue-specific activity in the pig.The objective of this study was to quantify ZsGreen1 protein(in lieu of CMV promoter activity)in tissues from pigs harboring a CMV-ZsGreen1 transgene with a single integration site.Tissue samples(n=35)were collected from neonatal hemizygous(n=3)and homozygous(n=3)piglets and ZsGreen1 abundance was determined via immunoblotting.ZsGreen1 was detected in all tissues,except hypothalamus,kidney cortex and oviduct.The expression patterns of homozygous and hemizygous piglets were similar(P>0.05).However,quantification revealed that ZsGreen1 protein levels were tissue-specific.Within neural/endocrine tissues,ZsGreen1 abundance was highest in the anterior pituitary gland,intermediate in the cerebellum and lowest in the cerebrum,spinal cord and posterior pituitary(P<0.05).In the digestive system,ZsGreen1 was more abundant in the salivary gland than esophagus,stomach,pancreas,duodenum,jejunum,ileum,spleen,colon,gallbladder and liver(P<0.05).Interestingly,ZsGreen1 amounts also differed within an organ(i.e.,the right ventricle had 3-fold higher levels than the other heart chambers;P<0.05).These results provide useful information for the use of the CMV promoter to drive transgene expression in the pig.Moreover,this swine model represents a novel resource of ZsGreen1-labeled organs and a valuable tool to advance genome editing research.
文摘Biochip is a kind of minimized and integrated analyzer for molecular biology and biochemistry. Advances in biochip technology enable massive parallel mining of biological data, with biochips providing hybridizationbased expression monitoring, polymorphism detection and genotyping on a genomic scale. Microarrays may soon permit the expression analysis of the entire human genome in a single reaction. These ’genome chips’ will provide access to key areas of human health, including disease diagnosis, drug discovery, toxicology, etc. Microarray technology is rapidly becoming a central platform for functional genomics. Development of biochips is to immigrate the eatire analysis process of biochemical reactions and establish the micro total analytical system or lab-on-a-chip.