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 dynamin-r...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 m A, 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 d UTP-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
Necroptosis is a non-apoptotic programmed cell death pathway,which causes necrosislike morphologic changes and triggers inflammation in the surrounding tissues.Accumulating evidence has demonstrated that necroptosis i...Necroptosis is a non-apoptotic programmed cell death pathway,which causes necrosislike morphologic changes and triggers inflammation in the surrounding tissues.Accumulating evidence has demonstrated that necroptosis is involved in a number of pathological processes that lead to cardiovascular diseases.However,the exact molecular pathways linking them remain unknown.Herein,this review summarizes the necroptosis-related pathways involved in the development of various cardiovascular diseases,including atherosclerosis,cardiac ischemia-reperfusion injury,cardiac hypertrophy,dilated cardiomyopathy and myocardial infarction,and may shed light on the diagnosis and treatment of these diseases.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 m A, 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 d UTP-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.
基金This work was supported by grants from the Natural Science Foundation of Jiangxi Province (No.20161bab215222Educational Commission of Jiangxi Province of China (No.gjjl50147)Cultivation Scientific Research Fund for the Junior Teachers of Medicine in Nanchang University (No.py201826).
文摘Necroptosis is a non-apoptotic programmed cell death pathway,which causes necrosislike morphologic changes and triggers inflammation in the surrounding tissues.Accumulating evidence has demonstrated that necroptosis is involved in a number of pathological processes that lead to cardiovascular diseases.However,the exact molecular pathways linking them remain unknown.Herein,this review summarizes the necroptosis-related pathways involved in the development of various cardiovascular diseases,including atherosclerosis,cardiac ischemia-reperfusion injury,cardiac hypertrophy,dilated cardiomyopathy and myocardial infarction,and may shed light on the diagnosis and treatment of these diseases.
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.
