We previously showed that death-associated protein kinase 1(DAPK1)expression is increased in hippocampal tissue in a mouse model of major depressive disorde and is related to cognitive dysfunction in Alzheimer's d...We previously showed that death-associated protein kinase 1(DAPK1)expression is increased in hippocampal tissue in a mouse model of major depressive disorde and is related to cognitive dysfunction in Alzheimer's disease.In addition,depression is a risk factor for developing Alzheimer's disease,as well as an early clinical manifestation of Alzheimer's disease.Meanwhile,cognitive dysfunction is a distinctive feature of major depressive disorder.Therefore,DAPK1 may be related to cognitive dysfunction in major depressive disorder.In this study,we established a mouse model of major depressive disorder by housing mice individually and exposing them to chronic,mild,unpredictable stressors.We found that DAPK1 and tau protein levels were increased in the hippocampal CA3 area,and tau was hyperphosphorylated at Thr231,Ser262,and Ser396 in these mice.Furthermore,DAPK1 shifted from axonal expression to overexpression on the cell membrane.Exercise and treatment with the antidepressant drug citalopram decreased DAPK1 expression and tau protein phosphorylation in hippocampal tissue and improved both depressive symptoms and cognitive dysfunction.These results indicate that DAPK1 may be a potential reason and therapeutic target of cognitive dysfunction in major depressive disorder.展开更多
Electroacupuncture preconditioning at acupoint Baihui （GV20） can reduce focal cerebral ischemia/reperfusion injury. However, the precise protective mechanism remains unknown. Mitochondrial fission mediated by dynami...Electroacupuncture preconditioning at acupoint Baihui （GV20） can reduce focal cerebral ischemia/reperfusion injury. However, the precise protective mechanism remains unknown. Mitochondrial fission mediated by dynamin-related protein 1 （Drp1） can trigger neuronal apoptosis following cerebral ischemia/reperfusion injury. Herein, we examined the hypothesis that electroacupuncture pretreatment can regulate Drp1, and thus inhibit mitochondrial fission to provide cerebral protection. Rat models of focal cerebral ischemia/reperfusion injury were established by middle cerebral artery occlusion at 24 hours after 5 consecutive days of preconditioning with electroacupuncture at GV20 （depth 2 mm, intensity 1 mA, frequency 2/15 Hz, for 30 minutes, once a day）. Neurological function was assessed using the Longa neurological deficit score. Pathological changes in the ischemic penumbra on the injury side were assessed by hematoxylin-eosin staining. Cellular apoptosis in the ischemic penumbra on the injury side was assessed by terminal deoxyribonucleotidyl transferase-mediated dUTP-digoxigenin nick end labeling staining. Mitochondrial ultrastructure in the ischemic penumbra on the injury side was assessed by transmission electron microscopy. Drp1 and cytochrome c expression in the ischemic penumbra on the injury side were assessed by western blot assay. Results showed that electroacupuncture preconditioning decreased expression of total and mitochondrial Drp1, decreased expression of total and cytosolic cytochrome c, maintained mitochondrial morphology and reduced the proportion of apoptotic cells in the ischemic penumbra on the injury side, with associated improvements in neurological function. These data suggest that electroacupuncture preconditioning-induced neuronal protection involves inhibition of the expression and translocation of Drp1.展开更多
目的探讨mi R-183及丝裂原激活的蛋白激酶1(MAPK1)m RNA与蛋白在非小细胞肺癌(NSCLC)组织中的表达及意义。方法实时定量PCR方法检测NSCLC组织mi R-183及MAPK1 m RNA的表达水平,Western blot方法检测NSCLC组织MAPK1蛋白表达;统计分析mi R...目的探讨mi R-183及丝裂原激活的蛋白激酶1(MAPK1)m RNA与蛋白在非小细胞肺癌(NSCLC)组织中的表达及意义。方法实时定量PCR方法检测NSCLC组织mi R-183及MAPK1 m RNA的表达水平,Western blot方法检测NSCLC组织MAPK1蛋白表达;统计分析mi R-183与MAPK1蛋白的相关性。结果 mi R-183在非小细胞肺癌组织中的表达量较癌旁组织明显降低(P<0.01),MAPK1 m RNA与蛋白在癌组织中较癌旁组织表达明显增高(P<0.05);统计分析显示,mi R-183表达与MAPK1表达呈显著地负相关关系。结论 mi R-183在NSCLC组织中低表达,与MAPK1表达呈显著负相关关系。展开更多
目的联合应用抗血小板聚集(拜阿司匹林片)、和(或)抗凝(法安明)、和(或)降脂(辛伐他汀)和(或)溶栓(rt-PA)治疗急性脑梗死,同时观察血清死亡蛋白激酶1(death-associated protein kinase1,DAPK1)含量的变化,进一步探讨NMDA受体和死亡蛋白...目的联合应用抗血小板聚集(拜阿司匹林片)、和(或)抗凝(法安明)、和(或)降脂(辛伐他汀)和(或)溶栓(rt-PA)治疗急性脑梗死,同时观察血清死亡蛋白激酶1(death-associated protein kinase1,DAPK1)含量的变化,进一步探讨NMDA受体和死亡蛋白激酶(DAPK1)在脑梗死的相互作用,为缺血性脑血管疾病的防治提供临床依据。方法选择发病在72h以内住院急性脑梗死患者,分为溶栓组11例、常规治疗组56例,并选择我科因后循环缺血住院患者46例做为对照组。溶栓组除了给予rt-PA溶栓外,与常规治疗组均联合应用抗血小板聚集(阿司匹林肠溶片100mgqd)、和(或)抗凝(低分子肝素5000u皮下注射,每日2次)、和(或)降脂(辛伐他汀片20mgqN)及活血化瘀(奥扎格雷钠40mgqd)、清除自由基(依达拉奉30mg bid)等治疗,对照组仅给予常规的活血化瘀、营养神经等治疗,观察治疗前和治疗10d后患者的血清死亡蛋白激酶1(DAPK1)含量的变化,以及肝功能、血小板、凝血机制及临床神经功能缺损评分进行评定,进一步探讨NMDA受体和死亡蛋白激酶1(DAPK1)在缺血性脑血管疾病的相互作用机制。结果溶栓组及常规治疗组患者的死亡蛋白激酶1(DAPK1)含量均高于对照组,治疗10天后溶栓组及常规治疗组患者的死亡蛋白激酶1(DAPK1)含量均降低,常规治疗组更明显(P<0.05),溶栓组的神经功能缺损评分(NIHSS)明显降低(P<0.05),临床疗效明显优于常规治疗组(P<0.05),肝功能、血小板、凝血功能、血脂的指标均在正常范围内。结论死亡蛋白激酶1(DAPK1)通过与NMDA受体的NR2B亚型结合激活神经细胞死亡通路,激发神经细胞死亡,形成卒中[2],为缺血性脑血管病的防治提供临床依据。展开更多
AIM: To explore methylation of DAPK, THBS1, CDH-1, and p14 genes, and Helicobacter pylori(H. pylori) status in individuals harboring esophageal columnar metaplasia.METHODS: Distal esophageal mucosal samples obtained b...AIM: To explore methylation of DAPK, THBS1, CDH-1, and p14 genes, and Helicobacter pylori(H. pylori) status in individuals harboring esophageal columnar metaplasia.METHODS: Distal esophageal mucosal samples obtained by endoscopy and histologically diagnosed as gastric-type(non-specialized) columnar metaplasia, were studied thoroughly. DNA was extracted from paraffin blocks, and methylation status of deathassociated protein kinase(DAPK), thrombospondin-1(THBS1), cadherin-1(CDH1), and p14 genes, was examined using a methyl-sensitive polymerase chain reaction(MS-PCR) and sodium bisulfite modification protocol. H. pylori cag A status was determined by PCR.RESULTS: In total, 68 subjects(33 females and 35 males), with a mean age of 52 years, were included. H. pylori cag A positive was present in the esophageal gastric-type metaplastic mucosa of 18 individuals. DAPK, THSB1, CDH1, and p14 gene promoters were methylated by MS-PCR in 40(58.8%), 33(48.5%), 46(67.6%), and 23(33.8%) cases of the 68 esophageal samples. H. pyloristatus was associated with methylation of DAPK(P = 0.003) and THBS1(P = 0.019).CONCLUSION: DNA methylation occurs in cases of gastric-type(non-specialized) columnar metaplasia of the esophagus, and this modification is associated with H. pylori cag A positive infection.展开更多
Background: Posttraumatic Stress Disorder (PTSD) is a psychiatric disorder found in individuals afflicted by a traumatic event including the natural disaster. “Tsunami” occurred in Andaman coast of Thailand on Decem...Background: Posttraumatic Stress Disorder (PTSD) is a psychiatric disorder found in individuals afflicted by a traumatic event including the natural disaster. “Tsunami” occurred in Andaman coast of Thailand on December 26, 2004, in which 33.6% of survivors were diagnosed as PTSD. This study aimed to explore the single nucleotide polymorphism (SNP). rs267943 genotype is located on chromosome 5 in the intron of the death-associated protein 1 (DAP1) gene and psychosocial factors for PTSD. Methods: Participants (N = 1970) were recruited from volunteers who have complete data both of DAP1 gene and psychosocial factor. Results: Using a binary logistic regression model, significant gene-environment interactions were found for the single nucleotide polymorphism (SNP) rs267943 and psychosocial factors including depression (adj. OR = 6.0, 95% CI = 4.29 - 8.39), neurotic personality (adj. OR = 2.73, 95% CI = 2.18 - 3.42), planning (adj. OR = 1.52, 95% CI = 1.20 - 1.93), use of emotional support (adj. OR = 1.32, 95% CI = 1.21 - 1.94) with statistical significant p Conclusion: This study demonstrated that GxE studies can be utilized to shed light on the origins of PTSD.展开更多
Posttraumatic stress disorder (PTSD) is a psychiatric disorder found in individuals afflicted by a traumatic event. Multiple environmental and genetic factors can contribute to PTSD susceptibility. Since it is rare to...Posttraumatic stress disorder (PTSD) is a psychiatric disorder found in individuals afflicted by a traumatic event. Multiple environmental and genetic factors can contribute to PTSD susceptibility. Since it is rare to find members of the same family afflicted by the same catastrophic event, it is not practical to determine PTSD susceptibility genes by a gene linkage analysis. A natural disaster, such as the 2004 Tsunami, provided us with a rare chance for a genetic analysis of PTSD. To identify SNPs associated with PTSD susceptibility, we conducted a genome-association study (GWAS) in Thai-Tsunami survivors. Initial phase of the study with 396 chronic PTSD patients and 457 controls, we identified top ninety SNPs (P -4), which were further assessed in the second phase with 395 chronic PTSD patients and 798 controls. Two SNPs (rs267950 and rs954406), were identified in the second phase, and subjected to fine mapping using a data set from both phases. SNP rs267943 showed the strongest association with PTSD susceptibility and was in complete linkage disequilibrium with SNP rs267950 with P = 6.15 × 10-8, OR = 1.46 and 95% CI = 1.19 - 1.79, reaching genome-wide significance. SNP rs267943 is located on chromosome 5 in the intron of the death-associated protein 1 (DAP1) gene and, when linked to a synthetic promoter, could regulate transcription. To our knowledge, this is the first GWAS for PTSD susceptibility in an Asian population which could provide an important insight into the genetic contribution of PTSD and may lead to new treatment strategies for PTSD.展开更多
基金supported by the Department of Science and Technology of Henan Province,Nos.192102310084(to HCZ),222102310143(to DXD)the Youth Fund of School of Basic Medical Sciences of Zhengzhou University,No.JCYXY2017-YQ-07(to DXD)。
文摘We previously showed that death-associated protein kinase 1(DAPK1)expression is increased in hippocampal tissue in a mouse model of major depressive disorde and is related to cognitive dysfunction in Alzheimer's disease.In addition,depression is a risk factor for developing Alzheimer's disease,as well as an early clinical manifestation of Alzheimer's disease.Meanwhile,cognitive dysfunction is a distinctive feature of major depressive disorder.Therefore,DAPK1 may be related to cognitive dysfunction in major depressive disorder.In this study,we established a mouse model of major depressive disorder by housing mice individually and exposing them to chronic,mild,unpredictable stressors.We found that DAPK1 and tau protein levels were increased in the hippocampal CA3 area,and tau was hyperphosphorylated at Thr231,Ser262,and Ser396 in these mice.Furthermore,DAPK1 shifted from axonal expression to overexpression on the cell membrane.Exercise and treatment with the antidepressant drug citalopram decreased DAPK1 expression and tau protein phosphorylation in hippocampal tissue and improved both depressive symptoms and cognitive dysfunction.These results indicate that DAPK1 may be a potential reason and therapeutic target of cognitive dysfunction in major depressive disorder.
基金supported by the Natural Science Foundation of Shandong Province of China,No.ZR2015HM023a grant from the Science and Technology Plan Project of Shinan District of Qingdao City of China,No.2016-3-029-YY
文摘Electroacupuncture preconditioning at acupoint Baihui （GV20） can reduce focal cerebral ischemia/reperfusion injury. However, the precise protective mechanism remains unknown. Mitochondrial fission mediated by dynamin-related protein 1 （Drp1） can trigger neuronal apoptosis following cerebral ischemia/reperfusion injury. Herein, we examined the hypothesis that electroacupuncture pretreatment can regulate Drp1, and thus inhibit mitochondrial fission to provide cerebral protection. Rat models of focal cerebral ischemia/reperfusion injury were established by middle cerebral artery occlusion at 24 hours after 5 consecutive days of preconditioning with electroacupuncture at GV20 （depth 2 mm, intensity 1 mA, frequency 2/15 Hz, for 30 minutes, once a day）. Neurological function was assessed using the Longa neurological deficit score. Pathological changes in the ischemic penumbra on the injury side were assessed by hematoxylin-eosin staining. Cellular apoptosis in the ischemic penumbra on the injury side was assessed by terminal deoxyribonucleotidyl transferase-mediated dUTP-digoxigenin nick end labeling staining. Mitochondrial ultrastructure in the ischemic penumbra on the injury side was assessed by transmission electron microscopy. Drp1 and cytochrome c expression in the ischemic penumbra on the injury side were assessed by western blot assay. Results showed that electroacupuncture preconditioning decreased expression of total and mitochondrial Drp1, decreased expression of total and cytosolic cytochrome c, maintained mitochondrial morphology and reduced the proportion of apoptotic cells in the ischemic penumbra on the injury side, with associated improvements in neurological function. These data suggest that electroacupuncture preconditioning-induced neuronal protection involves inhibition of the expression and translocation of Drp1.
文摘目的探讨mi R-183及丝裂原激活的蛋白激酶1(MAPK1)m RNA与蛋白在非小细胞肺癌(NSCLC)组织中的表达及意义。方法实时定量PCR方法检测NSCLC组织mi R-183及MAPK1 m RNA的表达水平,Western blot方法检测NSCLC组织MAPK1蛋白表达;统计分析mi R-183与MAPK1蛋白的相关性。结果 mi R-183在非小细胞肺癌组织中的表达量较癌旁组织明显降低(P<0.01),MAPK1 m RNA与蛋白在癌组织中较癌旁组织表达明显增高(P<0.05);统计分析显示,mi R-183表达与MAPK1表达呈显著地负相关关系。结论 mi R-183在NSCLC组织中低表达,与MAPK1表达呈显著负相关关系。
文摘目的联合应用抗血小板聚集(拜阿司匹林片)、和(或)抗凝(法安明)、和(或)降脂(辛伐他汀)和(或)溶栓(rt-PA)治疗急性脑梗死,同时观察血清死亡蛋白激酶1(death-associated protein kinase1,DAPK1)含量的变化,进一步探讨NMDA受体和死亡蛋白激酶(DAPK1)在脑梗死的相互作用,为缺血性脑血管疾病的防治提供临床依据。方法选择发病在72h以内住院急性脑梗死患者,分为溶栓组11例、常规治疗组56例,并选择我科因后循环缺血住院患者46例做为对照组。溶栓组除了给予rt-PA溶栓外,与常规治疗组均联合应用抗血小板聚集(阿司匹林肠溶片100mgqd)、和(或)抗凝(低分子肝素5000u皮下注射,每日2次)、和(或)降脂(辛伐他汀片20mgqN)及活血化瘀(奥扎格雷钠40mgqd)、清除自由基(依达拉奉30mg bid)等治疗,对照组仅给予常规的活血化瘀、营养神经等治疗,观察治疗前和治疗10d后患者的血清死亡蛋白激酶1(DAPK1)含量的变化,以及肝功能、血小板、凝血机制及临床神经功能缺损评分进行评定,进一步探讨NMDA受体和死亡蛋白激酶1(DAPK1)在缺血性脑血管疾病的相互作用机制。结果溶栓组及常规治疗组患者的死亡蛋白激酶1(DAPK1)含量均高于对照组,治疗10天后溶栓组及常规治疗组患者的死亡蛋白激酶1(DAPK1)含量均降低,常规治疗组更明显(P<0.05),溶栓组的神经功能缺损评分(NIHSS)明显降低(P<0.05),临床疗效明显优于常规治疗组(P<0.05),肝功能、血小板、凝血功能、血脂的指标均在正常范围内。结论死亡蛋白激酶1(DAPK1)通过与NMDA受体的NR2B亚型结合激活神经细胞死亡通路,激发神经细胞死亡,形成卒中[2],为缺血性脑血管病的防治提供临床依据。
文摘AIM: To explore methylation of DAPK, THBS1, CDH-1, and p14 genes, and Helicobacter pylori(H. pylori) status in individuals harboring esophageal columnar metaplasia.METHODS: Distal esophageal mucosal samples obtained by endoscopy and histologically diagnosed as gastric-type(non-specialized) columnar metaplasia, were studied thoroughly. DNA was extracted from paraffin blocks, and methylation status of deathassociated protein kinase(DAPK), thrombospondin-1(THBS1), cadherin-1(CDH1), and p14 genes, was examined using a methyl-sensitive polymerase chain reaction(MS-PCR) and sodium bisulfite modification protocol. H. pylori cag A status was determined by PCR.RESULTS: In total, 68 subjects(33 females and 35 males), with a mean age of 52 years, were included. H. pylori cag A positive was present in the esophageal gastric-type metaplastic mucosa of 18 individuals. DAPK, THSB1, CDH1, and p14 gene promoters were methylated by MS-PCR in 40(58.8%), 33(48.5%), 46(67.6%), and 23(33.8%) cases of the 68 esophageal samples. H. pyloristatus was associated with methylation of DAPK(P = 0.003) and THBS1(P = 0.019).CONCLUSION: DNA methylation occurs in cases of gastric-type(non-specialized) columnar metaplasia of the esophagus, and this modification is associated with H. pylori cag A positive infection.
文摘Background: Posttraumatic Stress Disorder (PTSD) is a psychiatric disorder found in individuals afflicted by a traumatic event including the natural disaster. “Tsunami” occurred in Andaman coast of Thailand on December 26, 2004, in which 33.6% of survivors were diagnosed as PTSD. This study aimed to explore the single nucleotide polymorphism (SNP). rs267943 genotype is located on chromosome 5 in the intron of the death-associated protein 1 (DAP1) gene and psychosocial factors for PTSD. Methods: Participants (N = 1970) were recruited from volunteers who have complete data both of DAP1 gene and psychosocial factor. Results: Using a binary logistic regression model, significant gene-environment interactions were found for the single nucleotide polymorphism (SNP) rs267943 and psychosocial factors including depression (adj. OR = 6.0, 95% CI = 4.29 - 8.39), neurotic personality (adj. OR = 2.73, 95% CI = 2.18 - 3.42), planning (adj. OR = 1.52, 95% CI = 1.20 - 1.93), use of emotional support (adj. OR = 1.32, 95% CI = 1.21 - 1.94) with statistical significant p Conclusion: This study demonstrated that GxE studies can be utilized to shed light on the origins of PTSD.
文摘Posttraumatic stress disorder (PTSD) is a psychiatric disorder found in individuals afflicted by a traumatic event. Multiple environmental and genetic factors can contribute to PTSD susceptibility. Since it is rare to find members of the same family afflicted by the same catastrophic event, it is not practical to determine PTSD susceptibility genes by a gene linkage analysis. A natural disaster, such as the 2004 Tsunami, provided us with a rare chance for a genetic analysis of PTSD. To identify SNPs associated with PTSD susceptibility, we conducted a genome-association study (GWAS) in Thai-Tsunami survivors. Initial phase of the study with 396 chronic PTSD patients and 457 controls, we identified top ninety SNPs (P -4), which were further assessed in the second phase with 395 chronic PTSD patients and 798 controls. Two SNPs (rs267950 and rs954406), were identified in the second phase, and subjected to fine mapping using a data set from both phases. SNP rs267943 showed the strongest association with PTSD susceptibility and was in complete linkage disequilibrium with SNP rs267950 with P = 6.15 × 10-8, OR = 1.46 and 95% CI = 1.19 - 1.79, reaching genome-wide significance. SNP rs267943 is located on chromosome 5 in the intron of the death-associated protein 1 (DAP1) gene and, when linked to a synthetic promoter, could regulate transcription. To our knowledge, this is the first GWAS for PTSD susceptibility in an Asian population which could provide an important insight into the genetic contribution of PTSD and may lead to new treatment strategies for PTSD.
