Objective To investigate the role of H1 and H2 receptors in the locus ceruleus （LC） in carotid sinus baroreceptor reflex （CSR） resetting induced by intracerebroventricular （i.c.v.） injection of histamine （HA）....Objective To investigate the role of H1 and H2 receptors in the locus ceruleus （LC） in carotid sinus baroreceptor reflex （CSR） resetting induced by intracerebroventricular （i.c.v.） injection of histamine （HA）. Methods The left and right carotid sinus regions were isolated from the systemic circulation in 18 male Sprague-Dawley rats anesthetized with pentobarbital sodium. The intracarotid sinus pressure （ISP） was altered in a stepwise manner in vivo. ISP-mean arterial pressure （MAP） relationship curve and its characteristic parameters were constructed by fitting to the logistic function with five parameters. The changes in CSR performance induced by i.c.v. HA and the effects of pretreatment with H1 or H2 receptors selective antagonist, chlorpheniramine （CHL） or cimetidine （CIM） into the LC, on the responses of CSR to HA were examined. Results I.c.v. HA （100 ng in 5 μl） significantly shifted the ISP-MAP relationship curve upwards （P 〈 0.05） and obviously decreased the value of the reflex parameters such as MAP range and maximum gain （P 〈 0.05）, but increased the threshold pressure, saturation pressure and ISP at maximum gain （P 〈 0.05）. The pretreatment with CHL （0.5 μg in 1 μl） or CIM （1.5 μg in 1 μl） into the LC could obviously attenuate the changes mentioned above in CSR performance induced by HA, but the alleviative effect of CIM was less remarkable than that of CHL （P 〈 0.05）. Respective microinjection of CHL or CIM alone into the LC with the corresponding dose and volume did not change CSR performance significantly （P 〉 0.05）. Conclusion Intracerebroventricular administration of HA results in a rapid resetting of CSR and a decrease in reflex sensitivity, and the responses of CSR to HA may be mediated, at least in part, by H1 and H2 receptors activities in the LC, especially by H1 receptors. Moreover, the effects of the central HA on CSR might be related to a histaminergic descending pathway from the hypothalamus to LC.展开更多
TPL2(tumor progression locus 2)为一种激酶,虽然最初是作为一种致癌基因被发现,但其在机体的炎症反应中也起重要作用。TPL2激酶可通过丝裂原激活蛋白激酶信号转导通路,介导多种细胞因子的信号转导,影响炎症反应和免疫过程的多个环节,...TPL2(tumor progression locus 2)为一种激酶,虽然最初是作为一种致癌基因被发现,但其在机体的炎症反应中也起重要作用。TPL2激酶可通过丝裂原激活蛋白激酶信号转导通路,介导多种细胞因子的信号转导,影响炎症反应和免疫过程的多个环节,参与多种炎症性相关疾病的发生。炎症性肠病(IBD)作为一种以肠道慢性炎症反应为特征的免疫性疾病,目前尚未有治愈药物。近年来,随着对IBD发病机制研究的不断深入,越来越多的相关发病因子、小分子抑制剂的研发备受关注。TPL2激酶通过其在炎症反应过程的作用,参与IBD的发病。未来,TPL2激酶可能成为IBD治疗药物研究的潜在靶点。展开更多
Type 2 diabetes(T2D) is a common metabolic disorder which is caused by multiple genetic perturbations affecting different biological pathways. Identifying genetic factors modulating the susceptibility of this complex ...Type 2 diabetes(T2D) is a common metabolic disorder which is caused by multiple genetic perturbations affecting different biological pathways. Identifying genetic factors modulating the susceptibility of this complex heterogeneous metabolic phenotype in different ethnic and racial groups remains challenging. Despite recent success, the functional role of the T2D susceptibility variants implicated by genome-wide association studies(GWAS) remains largely unknown. Genetic dissection of transcript abundance or expression quantitative trait(eQTL) analysis unravels the genomic architecture of regulatory variants. Availability of eQTL information from tissues relevant for glucose homeostasis in humans opens a new avenue to prioritize GWASimplicated variants that may be involved in triggering a causal chain of events leading to T2D. In this article, we review the progress made in the field of eQTL research and knowledge gained from those studies in understanding transcription regulatory mechanisms in human subjects. We highlight several novel approaches that can integrate eQTL analysis with multiple layers of biological information to identify ethnic-specific causal variants and gene-environment interactions relevant to T2D pathogenesis. Finally, we discuss how the eQTL analysis mediated search for "missing heritability" may lead us to novel biological and molecular mechanisms involved in susceptibility to T2D.展开更多
Purpose:To explore how perceptions of self-efficacy,health locus of control and outcome expectancy impact the adherence of adults with type 2 diabetes mellitus in Saudi Arabiato self-care activities.Methods:A descript...Purpose:To explore how perceptions of self-efficacy,health locus of control and outcome expectancy impact the adherence of adults with type 2 diabetes mellitus in Saudi Arabiato self-care activities.Methods:A descriptive correlation design was used to analyse self-report questionnaires completed by a convenience sample of Arabic-speaking individuals(n=30)with type 2 diabetes mellitus from King Abdulaziz Medical City in Riyadh.Results:More than half(53%)of participants reported high self-efficacy,and the majority(77%)valued health and believed that effective diabetes management was important.Although the vast majority(93%)of participants believed that their doctor influenced their diabetes management,90%and 80%also acknowledged themselves and God,respectively,as the health locus of control.Participants who perceived that they or their doctors were in control of their health condition were more likely to adhere to self-care activities,such as follow a specific diet and perform foot care(p<0.05).Furthermore,female participants reported significantly greater adherence to medication than male participants(6.91±0.29 vs 5.14±2.44;p=0.02),and unmarried participants reported greater adherence to exercise than married participants(4.15±2.22 vs 1.60±1.43;p=0.001).Finally,self-efficacy had a significant,positive correlation with participants'adherence to exercise(r=0.491;p=0.006)and performing their foot care(r=0.586;p=0.001).Conclusion:Patients'perceptions of their health should be considered by healthcare providers to maximize adherence to effective self-care management.展开更多
文摘Objective To investigate the role of H1 and H2 receptors in the locus ceruleus （LC） in carotid sinus baroreceptor reflex （CSR） resetting induced by intracerebroventricular （i.c.v.） injection of histamine （HA）. Methods The left and right carotid sinus regions were isolated from the systemic circulation in 18 male Sprague-Dawley rats anesthetized with pentobarbital sodium. The intracarotid sinus pressure （ISP） was altered in a stepwise manner in vivo. ISP-mean arterial pressure （MAP） relationship curve and its characteristic parameters were constructed by fitting to the logistic function with five parameters. The changes in CSR performance induced by i.c.v. HA and the effects of pretreatment with H1 or H2 receptors selective antagonist, chlorpheniramine （CHL） or cimetidine （CIM） into the LC, on the responses of CSR to HA were examined. Results I.c.v. HA （100 ng in 5 μl） significantly shifted the ISP-MAP relationship curve upwards （P 〈 0.05） and obviously decreased the value of the reflex parameters such as MAP range and maximum gain （P 〈 0.05）, but increased the threshold pressure, saturation pressure and ISP at maximum gain （P 〈 0.05）. The pretreatment with CHL （0.5 μg in 1 μl） or CIM （1.5 μg in 1 μl） into the LC could obviously attenuate the changes mentioned above in CSR performance induced by HA, but the alleviative effect of CIM was less remarkable than that of CHL （P 〈 0.05）. Respective microinjection of CHL or CIM alone into the LC with the corresponding dose and volume did not change CSR performance significantly （P 〉 0.05）. Conclusion Intracerebroventricular administration of HA results in a rapid resetting of CSR and a decrease in reflex sensitivity, and the responses of CSR to HA may be mediated, at least in part, by H1 and H2 receptors activities in the LC, especially by H1 receptors. Moreover, the effects of the central HA on CSR might be related to a histaminergic descending pathway from the hypothalamus to LC.
文摘TPL2(tumor progression locus 2)为一种激酶,虽然最初是作为一种致癌基因被发现,但其在机体的炎症反应中也起重要作用。TPL2激酶可通过丝裂原激活蛋白激酶信号转导通路,介导多种细胞因子的信号转导,影响炎症反应和免疫过程的多个环节,参与多种炎症性相关疾病的发生。炎症性肠病(IBD)作为一种以肠道慢性炎症反应为特征的免疫性疾病,目前尚未有治愈药物。近年来,随着对IBD发病机制研究的不断深入,越来越多的相关发病因子、小分子抑制剂的研发备受关注。TPL2激酶通过其在炎症反应过程的作用,参与IBD的发病。未来,TPL2激酶可能成为IBD治疗药物研究的潜在靶点。
基金Supported by National Institutes of Health(NIH/NIDDK),Nos.R01 DK090111 and DK039311
文摘Type 2 diabetes(T2D) is a common metabolic disorder which is caused by multiple genetic perturbations affecting different biological pathways. Identifying genetic factors modulating the susceptibility of this complex heterogeneous metabolic phenotype in different ethnic and racial groups remains challenging. Despite recent success, the functional role of the T2D susceptibility variants implicated by genome-wide association studies(GWAS) remains largely unknown. Genetic dissection of transcript abundance or expression quantitative trait(eQTL) analysis unravels the genomic architecture of regulatory variants. Availability of eQTL information from tissues relevant for glucose homeostasis in humans opens a new avenue to prioritize GWASimplicated variants that may be involved in triggering a causal chain of events leading to T2D. In this article, we review the progress made in the field of eQTL research and knowledge gained from those studies in understanding transcription regulatory mechanisms in human subjects. We highlight several novel approaches that can integrate eQTL analysis with multiple layers of biological information to identify ethnic-specific causal variants and gene-environment interactions relevant to T2D pathogenesis. Finally, we discuss how the eQTL analysis mediated search for "missing heritability" may lead us to novel biological and molecular mechanisms involved in susceptibility to T2D.
文摘Purpose:To explore how perceptions of self-efficacy,health locus of control and outcome expectancy impact the adherence of adults with type 2 diabetes mellitus in Saudi Arabiato self-care activities.Methods:A descriptive correlation design was used to analyse self-report questionnaires completed by a convenience sample of Arabic-speaking individuals(n=30)with type 2 diabetes mellitus from King Abdulaziz Medical City in Riyadh.Results:More than half(53%)of participants reported high self-efficacy,and the majority(77%)valued health and believed that effective diabetes management was important.Although the vast majority(93%)of participants believed that their doctor influenced their diabetes management,90%and 80%also acknowledged themselves and God,respectively,as the health locus of control.Participants who perceived that they or their doctors were in control of their health condition were more likely to adhere to self-care activities,such as follow a specific diet and perform foot care(p<0.05).Furthermore,female participants reported significantly greater adherence to medication than male participants(6.91±0.29 vs 5.14±2.44;p=0.02),and unmarried participants reported greater adherence to exercise than married participants(4.15±2.22 vs 1.60±1.43;p=0.001).Finally,self-efficacy had a significant,positive correlation with participants'adherence to exercise(r=0.491;p=0.006)and performing their foot care(r=0.586;p=0.001).Conclusion:Patients'perceptions of their health should be considered by healthcare providers to maximize adherence to effective self-care management.
