AIM To identify punitive transcriptional factor binding sites(TFBS) from regulatory single nucleotide polymorphisms(rS NPs) that are significantly associated with disease.METHODS The genome-wide association studies ha...AIM To identify punitive transcriptional factor binding sites(TFBS) from regulatory single nucleotide polymorphisms(rS NPs) that are significantly associated with disease.METHODS The genome-wide association studies have provided us with nearly 6500 disease or trait-predisposing SNPs where 93% are located within non-coding regions such as gene regulatory or intergenic areas of the genome. In the regulatory region of a gene, a SNP can change the DNA sequence of a transcriptional factor(TF) motif and in turn may affect the process of gene regulation. SNP changes that affect gene expression and impact gene regulatory sequences such as promoters, enhancers, and silencers are known as rS NPs. Computational tools can be used to identify unique punitive TFBS created by rS NPs that are associated with disease or sickness. Computational analysis was used to identify punitive TFBS generated by the alleles of these rS NPs.RESULTS r SNPs within nine genes that have been significantly associated with disease or sickness were used to illustrate the tremendous diversity of punitive unique TFBS that can be generated by their alleles. The genes studied are the adrenergic, beta, receptor kinase 1, the v-akt murine thymoma viral oncogene homolog 3, the activating transcription factor 3, the type 2 demodkinase gene, the endothetal Per-Arnt-Sim domain protein 1, the lysosomal acid lipase A, the signal Transducer and Activator of Transcription 4, the thromboxane A2 receptor and the vascular endothelial growth factor A. From this sampling of SNPs among the nine genes, there are 73 potential unique TFBS generated by the common alleles comparedto 124 generated by the minor alleles indicating the tremendous diversity of potential TFs that are capable of regulating these genes.CONCLUSION From the diversity of unique punitive binding sites for TFs, it was found that some TFs play a role in the disease or sickness being studied.展开更多
Nucleotide-binding oligomerization domain 1(NOD1) is an intracellular innate immune sensor for small molecules derived from bacterial cell components. NOD1 activation by its ligands leads to robust production of pro-i...Nucleotide-binding oligomerization domain 1(NOD1) is an intracellular innate immune sensor for small molecules derived from bacterial cell components. NOD1 activation by its ligands leads to robust production of pro-inflammatory cytokines and chemokines by innate immune cells, thereby mediating mucosal host defense systems against microbes. Chronic gastric infection due to Helicobacter pylori(H. pylori) causes various upper gastrointestinal diseases, including atrophic gastritis, peptic ulcers, and gastric cancer. It is now generally accepted that detection of H. pylori by NOD1 expressed in gastric epithelial cells plays an indispensable role in mucosal host defense systems against this organism. Recent studies have revealed the molecular mechanism by which NOD1 activation caused by H. pylori infection is involved in the development of chronic gastritis and gastric cancer. In this review, we have discussed and summarized how sensing of H. pylori by NOD1 mediates the prevention of chronic gastritis and gastric cancer.展开更多
BACKGROUND： The pharmacological action of opioid drugs is related to signal transduction of inhibitory guanine nucleotide binding protein. OBJECTIVE： To quantitatively and qualitatively analyze the influence of morp...BACKGROUND： The pharmacological action of opioid drugs is related to signal transduction of inhibitory guanine nucleotide binding protein. OBJECTIVE： To quantitatively and qualitatively analyze the influence of morphine on levels of type Ⅱ inhibitory guanine nucleotide binding protein （Gi2 protein） in primary cultured hippocampal neurons at different time points. DESIGN, TIME AND SETTING： A randomized controlled study, which was performed at the Department of Neurobiology, Changzheng Hospital, Second Military Medical University of Chinese PLA between September 2002 and March 2004. MATERIALS： Cerebral hippocampal neurons were obtained from newborn SD rats at 1 2 days of age. Biotin-antibody Ⅱ-avidin fluorescein isothiocyanate （Avidin-FITC） was purchased from Sigma Company （USA） and the Gi2 protein polyclonal antibody from Santa Cruz Biochemistry Company （USA）. METHODS： Seven days after culture, mature hippocampal neurons were randomly divided into six groups： 4-, 8-, 16-, 24-, and 48-hour morphine groups, and a blank control group. Neurons in the morphine groups received morphine （10 μ mol/L）, which could cause alterations of G-protein mRNA and cAMP expression in the prefrontal cortex. Neurons in the blank control group were given the same volume of saline. MAIN OUTCOME MEASURES： Gi2 protein levels were detected by an immunofluorescence technique, and were analyzed by the image analytic system with the use of green fluorescence intensity. RESULTS： Gi2 protein levels in hippocampal neurons gradually decreased in the 4-, 8-, 16-, 24-, and 48-hour morphine groups. In particular, Gi2 protein levels in the 16-, 24-, and 48-hour morphine groups were significantly lower than that in the blank control group （P 〈 0.05 0.01）. CONCLUSION： Morphine may decrease Gi2 protein level in primary hippocampal neurons, and the decreasing trend is positively related to morphine-induced time.展开更多
BACKGROUND： Drug addiction involves two main central nervous systems, namely the dopamine and noradrenaline systems. These systems are primarily distributed in five brain regions： the ventral tegmental area, the nuc...BACKGROUND： Drug addiction involves two main central nervous systems, namely the dopamine and noradrenaline systems. These systems are primarily distributed in five brain regions： the ventral tegmental area, the nucleus accumbens, the prefrontal cortex, the hippocampus, and the locus coeruleus. OBJECTIVE： To investigate regional changes of guanine nucleotide binding protein-inhabitant 2 （Gi2） in dopaminergic and noradrenergic neurons in brains of morphine-tolerant and -dependent rats. DESIGN, TIME, AND SETTING： A randomized control study was performed at the Department of Neurobiology in the Second Military Medical University of Chinese PLA （Shanghai, China） between September 2002 and March 2004. MATERIALS： Thirty-six, healthy, male, Sprague-Dawley （SD） rats were used to establish morphine-dependent models. Morphine hydrochloride was a product of Shenyang First Pharmaceutical Factory （China）; naloxone hydrochloride was a product of Beijing Four-Ring Pharmaceutical Factory （China）; and α subunit of Gi2 antibody was offered by Santa Cruz Biotechnology, lnc （USA）. METHODS： Thirty-six SD rats were randomly divided into six groups （n = 6）： （1） acute morphine-dependent group, （2） acute abstinent group, （3） acute control group, （4） chronic morphine-dependent group, （5） chronic abstinent group, and （6） chronic control group. Rats in the acute morphine-dependent and the acute groups were injected with morphine （5 mg/kg）, one injection every two hours, for a total of eight injections. In the acute and chronic morphine-dependent rat models, morphine withdrawal syndrome was precipitated by an injection of naloxone （5 mg/kg）. Rats in the acute control group were given a peritoneal injection of physiological saline at the same administration time as the above two groups. Rats in the chronic morphine-dependent and chronic abstinent groups were injected with morphine three times per day. The administration dose on day 1 was initially 5 mg/kg at 20：00, which increased by 5 mg/kg at 8：00, 12：00, and 20：00 until day 7. On day 13, the dose continuously increased by 10 mg/kg until a chronic morphine-dependent rat model was successfully induced. Afterwards, the rats presented with withdrawal syndromes on naloxone （5 mg/kg） at 8：00 on the same day. Rats in the chronic control group were injected with physiological saline at the same time of the two chronic groups. MAIN OUTCOME MEASURES： The concentration of Gi2 protein in the five brain regions （ventral tegmental area, nucleus accumbens, prefrontal cortex, locus coeruleus, and hippocampus） was detected by immunohistochemistry. RESULTS： In the acute morphine-dependent and acute abstinent groups, Gi2 protein concentration was significantly decreased in the nucleus accumbens, compared to the acute control group （P 〈 0.01）, while no obvious changes were detected in other brain regions. In the chronic morphine-dependent and chronic abstinent groups, Gi2 protein concentration was significantly decreased in the nucleus accumbens, but significantly increased in the locus coeruleus （P 〈 0.01 ） compared to the chronic control group. CONCLUSION： Morphine dependence and tolerance may induce obvious reductions of Gi2 protein levels in the nucleus accumbens of rats. Chronic morphine dependence desensitizes the homologous neurons.展开更多
文摘AIM To identify punitive transcriptional factor binding sites(TFBS) from regulatory single nucleotide polymorphisms(rS NPs) that are significantly associated with disease.METHODS The genome-wide association studies have provided us with nearly 6500 disease or trait-predisposing SNPs where 93% are located within non-coding regions such as gene regulatory or intergenic areas of the genome. In the regulatory region of a gene, a SNP can change the DNA sequence of a transcriptional factor(TF) motif and in turn may affect the process of gene regulation. SNP changes that affect gene expression and impact gene regulatory sequences such as promoters, enhancers, and silencers are known as rS NPs. Computational tools can be used to identify unique punitive TFBS created by rS NPs that are associated with disease or sickness. Computational analysis was used to identify punitive TFBS generated by the alleles of these rS NPs.RESULTS r SNPs within nine genes that have been significantly associated with disease or sickness were used to illustrate the tremendous diversity of punitive unique TFBS that can be generated by their alleles. The genes studied are the adrenergic, beta, receptor kinase 1, the v-akt murine thymoma viral oncogene homolog 3, the activating transcription factor 3, the type 2 demodkinase gene, the endothetal Per-Arnt-Sim domain protein 1, the lysosomal acid lipase A, the signal Transducer and Activator of Transcription 4, the thromboxane A2 receptor and the vascular endothelial growth factor A. From this sampling of SNPs among the nine genes, there are 73 potential unique TFBS generated by the common alleles comparedto 124 generated by the minor alleles indicating the tremendous diversity of potential TFs that are capable of regulating these genes.CONCLUSION From the diversity of unique punitive binding sites for TFs, it was found that some TFs play a role in the disease or sickness being studied.
文摘Nucleotide-binding oligomerization domain 1(NOD1) is an intracellular innate immune sensor for small molecules derived from bacterial cell components. NOD1 activation by its ligands leads to robust production of pro-inflammatory cytokines and chemokines by innate immune cells, thereby mediating mucosal host defense systems against microbes. Chronic gastric infection due to Helicobacter pylori(H. pylori) causes various upper gastrointestinal diseases, including atrophic gastritis, peptic ulcers, and gastric cancer. It is now generally accepted that detection of H. pylori by NOD1 expressed in gastric epithelial cells plays an indispensable role in mucosal host defense systems against this organism. Recent studies have revealed the molecular mechanism by which NOD1 activation caused by H. pylori infection is involved in the development of chronic gastritis and gastric cancer. In this review, we have discussed and summarized how sensing of H. pylori by NOD1 mediates the prevention of chronic gastritis and gastric cancer.
文摘BACKGROUND： The pharmacological action of opioid drugs is related to signal transduction of inhibitory guanine nucleotide binding protein. OBJECTIVE： To quantitatively and qualitatively analyze the influence of morphine on levels of type Ⅱ inhibitory guanine nucleotide binding protein （Gi2 protein） in primary cultured hippocampal neurons at different time points. DESIGN, TIME AND SETTING： A randomized controlled study, which was performed at the Department of Neurobiology, Changzheng Hospital, Second Military Medical University of Chinese PLA between September 2002 and March 2004. MATERIALS： Cerebral hippocampal neurons were obtained from newborn SD rats at 1 2 days of age. Biotin-antibody Ⅱ-avidin fluorescein isothiocyanate （Avidin-FITC） was purchased from Sigma Company （USA） and the Gi2 protein polyclonal antibody from Santa Cruz Biochemistry Company （USA）. METHODS： Seven days after culture, mature hippocampal neurons were randomly divided into six groups： 4-, 8-, 16-, 24-, and 48-hour morphine groups, and a blank control group. Neurons in the morphine groups received morphine （10 μ mol/L）, which could cause alterations of G-protein mRNA and cAMP expression in the prefrontal cortex. Neurons in the blank control group were given the same volume of saline. MAIN OUTCOME MEASURES： Gi2 protein levels were detected by an immunofluorescence technique, and were analyzed by the image analytic system with the use of green fluorescence intensity. RESULTS： Gi2 protein levels in hippocampal neurons gradually decreased in the 4-, 8-, 16-, 24-, and 48-hour morphine groups. In particular, Gi2 protein levels in the 16-, 24-, and 48-hour morphine groups were significantly lower than that in the blank control group （P 〈 0.05 0.01）. CONCLUSION： Morphine may decrease Gi2 protein level in primary hippocampal neurons, and the decreasing trend is positively related to morphine-induced time.
文摘BACKGROUND： Drug addiction involves two main central nervous systems, namely the dopamine and noradrenaline systems. These systems are primarily distributed in five brain regions： the ventral tegmental area, the nucleus accumbens, the prefrontal cortex, the hippocampus, and the locus coeruleus. OBJECTIVE： To investigate regional changes of guanine nucleotide binding protein-inhabitant 2 （Gi2） in dopaminergic and noradrenergic neurons in brains of morphine-tolerant and -dependent rats. DESIGN, TIME, AND SETTING： A randomized control study was performed at the Department of Neurobiology in the Second Military Medical University of Chinese PLA （Shanghai, China） between September 2002 and March 2004. MATERIALS： Thirty-six, healthy, male, Sprague-Dawley （SD） rats were used to establish morphine-dependent models. Morphine hydrochloride was a product of Shenyang First Pharmaceutical Factory （China）; naloxone hydrochloride was a product of Beijing Four-Ring Pharmaceutical Factory （China）; and α subunit of Gi2 antibody was offered by Santa Cruz Biotechnology, lnc （USA）. METHODS： Thirty-six SD rats were randomly divided into six groups （n = 6）： （1） acute morphine-dependent group, （2） acute abstinent group, （3） acute control group, （4） chronic morphine-dependent group, （5） chronic abstinent group, and （6） chronic control group. Rats in the acute morphine-dependent and the acute groups were injected with morphine （5 mg/kg）, one injection every two hours, for a total of eight injections. In the acute and chronic morphine-dependent rat models, morphine withdrawal syndrome was precipitated by an injection of naloxone （5 mg/kg）. Rats in the acute control group were given a peritoneal injection of physiological saline at the same administration time as the above two groups. Rats in the chronic morphine-dependent and chronic abstinent groups were injected with morphine three times per day. The administration dose on day 1 was initially 5 mg/kg at 20：00, which increased by 5 mg/kg at 8：00, 12：00, and 20：00 until day 7. On day 13, the dose continuously increased by 10 mg/kg until a chronic morphine-dependent rat model was successfully induced. Afterwards, the rats presented with withdrawal syndromes on naloxone （5 mg/kg） at 8：00 on the same day. Rats in the chronic control group were injected with physiological saline at the same time of the two chronic groups. MAIN OUTCOME MEASURES： The concentration of Gi2 protein in the five brain regions （ventral tegmental area, nucleus accumbens, prefrontal cortex, locus coeruleus, and hippocampus） was detected by immunohistochemistry. RESULTS： In the acute morphine-dependent and acute abstinent groups, Gi2 protein concentration was significantly decreased in the nucleus accumbens, compared to the acute control group （P 〈 0.01）, while no obvious changes were detected in other brain regions. In the chronic morphine-dependent and chronic abstinent groups, Gi2 protein concentration was significantly decreased in the nucleus accumbens, but significantly increased in the locus coeruleus （P 〈 0.01 ） compared to the chronic control group. CONCLUSION： Morphine dependence and tolerance may induce obvious reductions of Gi2 protein levels in the nucleus accumbens of rats. Chronic morphine dependence desensitizes the homologous neurons.
