Death following situations of intense emotional stress has been linked to the cardiac pathology described as stress cardiomyopathy, whose pathomechanism is still not clear. In this study, we sought to determine, via a...Death following situations of intense emotional stress has been linked to the cardiac pathology described as stress cardiomyopathy, whose pathomechanism is still not clear. In this study, we sought to determine, via an animal model, whether the transcriptional coactivator peroxisome proliferator-activated receptor γ coactivator-1alpha (PGC-1α) and the amino peptide neuropeptide Y (NPY) play a role in the pathogenesis of this cardiac entity. Male Sprague-Dawley rats in the experimental group were subjected to immobilization in a plexy glass box for 1 h, which was followed by low voltage elec-tric foot shock for about 1h at 10s intervals in a cage fitted with metallic rods. After 25 days the rats were sacrificed and sections of their hearts were processed. Hematoxylin-eosin staining of cardiac tissues revealed the characteristic cardiac lesions of stress cardiomyopathy such as contraction band necrosis, inflammatory cell infiltration and fibrosis. The semi-quantitative RT-PCR analysis for PGC-1α mRNA expression showed significant overexpression of PGC1-α in the stress-subjected rats (P<0.05). Fluorescence immunohistochemistry revealed a higher production of NPY in the stress-subjected rats as compared to the control rats (P=0.0027). Thus, we are led to conclude that following periods of intense stress, an increased expression of PGC1-α in the heart and an overflow of NPY may lead to stress car-diomyopathy and even death in susceptible victims. Moreover, these markers can be used to identify stress cardiomyopathy as the cause of sudden death in specific cases.展开更多
目的探讨功能性消化不良(functional dyspepsia,FD)患者血浆中神经肽S受体1(neuropeptide S receptor 1,NPSR1)、降钙素基因相关肽(calcitonin gene related peptide,CGRP)及白介素-6(interleukin-6,IL-6)的表达水平及其临床意义。方法...目的探讨功能性消化不良(functional dyspepsia,FD)患者血浆中神经肽S受体1(neuropeptide S receptor 1,NPSR1)、降钙素基因相关肽(calcitonin gene related peptide,CGRP)及白介素-6(interleukin-6,IL-6)的表达水平及其临床意义。方法选取2012年4月至2015年10月就诊于本院的143例FD患者纳入FD组,其中,上腹痛综合征(epigastric pain syndrome,EPS)70例(EPS组),餐后不适综合征(postprandial distress syndrome,PDS)73例(PDS组)。选取同期于本院体检的健康者80例纳入对照组,采用酶联免疫吸附测定(ELISA)检测所有研究对象血浆中NPSR1、CGRP及IL-6的表达水平,并进行统计学分析。结果 FD组患者最主要的临床症状为消化不良或胀气(82.52%),其次为嗳气(79.72%)、疲乏(76.22%)及腹痛(75.52%)。FD组患者血浆中NPSR1、CGRP、IL-6的表达水平分别为(170.25±16.40)、(117.43±15.58)、(92.75±6.80)pg/ml,对照组分别为(207.10±14.42)、(172.55±8.90)、(65.60±7.35)pg/ml,两组比较差异具有显著性(P<0.05)。PDS组患者血浆中NPSR1、CGRP、IL-6水平分别为(158.55±17.43)、(106.72±14.65)、(88.42±7.15)pg/ml,EPS组分别为(182.00±16.66)、(128.54±16.64)、(97.50±6.75)pg/ml,两组比较差异显著(P<0.05)。结论FD患者血浆中NPSR1、CGRP表达水平下降,而IL-6表达水平升高,提示NPSR1、CGRP及IL-6的表达水平与FD的发生密切相关。展开更多
BACKGROUND Ulcerative colitis(UC)is an inflammatory bowel disease that is difficult to diagnose and treat.To date,the degree of inflammation in patients with UC has mainly been determined by measuring the levels of no...BACKGROUND Ulcerative colitis(UC)is an inflammatory bowel disease that is difficult to diagnose and treat.To date,the degree of inflammation in patients with UC has mainly been determined by measuring the levels of nonspecific indicators,such as C-reactive protein and the erythrocyte sedimentation rate,but these indicators have an unsatisfactory specificity.In this study,we performed bioinformatics analysis using data from the National Center for Biotechnology Information-Gene Expression Omnibus(NCBI-GEO)databases and verified the selected core genes in a mouse model of dextran sulfate sodium(DSS)-induced colitis.AIM To identify UC-related differentially expressed genes(DEGs)using a bioinformatics analysis and verify them in vivo and to identify novel biomarkers and the underlying mechanisms of UC.METHODS Two microarray datasets from the NCBI-GEO database were used,and DEGs between patients with UC and healthy controls were analyzed using GEO2R and Venn diagrams.We annotated these genes based on their functions and signaling pathways,and then protein-protein interactions(PPIs)were identified using the Search Tool for the Retrieval of Interacting Genes.The data were further analyzed with Cytoscape software and the Molecular Complex Detection(MCODE)app.The core genes were selected and a Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis was performed.Finally,colitis model mice were established by administering DSS,and the top three core genes were verified in colitis mice using real-time polymerase chain reaction(PCR).RESULTS One hundred and seventy-seven DEGs,118 upregulated and 59 downregulated,were initially identified from the GEO2R analysis and predominantly participated in inflammation-related pathways.Seven clusters with close interactions in UC formed:Seventeen core genes were upregulated[C-X-C motif chemokine ligand 13(CXCL13),C-X-C motif chemokine receptor 2(CXCR2),CXCL9,CXCL5,C-C motif chemokine ligand 18,interleukin 1 beta,matrix metallopeptidase 9,CXCL3,formyl peptide receptor 1,complement component 3,CXCL8,CXCL1,CXCL10,CXCL2,CXCL6,CXCL11 and hydroxycarboxylic acid receptor 3]and one was downregulated[neuropeptide Y receptor Y1(NYP1R)]in the top cluster according to the PPI and MCODE analyses.These genes were substantially enriched in the cytokinecytokine receptor interaction and chemokine signaling pathways.The top three core genes(CXCL13,NYP1R,and CXCR2)were selected and verified in a mouse model of colitis using real-time PCR Increased expression was observed compared with the control mice,but only CXCR2 expression was significantly different.CONCLUSION Core DEGs identified in UC are related to inflammation and immunity inflammation,indicating that these reactions are core features of the pathogenesis of UC.CXCR2 may reflect the degree of inflammation in patients with UC.展开更多
Early studies from several independent laboratories demonstrated that acupoints possess the characteristics of low electrical resistance.New devices are developing to increase the reliability of electrical skin impeda...Early studies from several independent laboratories demonstrated that acupoints possess the characteristics of low electrical resistance.New devices are developing to increase the reliability of electrical skin impedance measurements for counteracting the factors including skin dryness,skin thickness,size of the sensing electrode,pressure applied on the electrode,interelectrode distance,room temperature,and humidity.Morphological studies have identified that blood vessels,hair follicles,and nervous components are enhanced in the meridians/acupoints,which represent areas of potentially high neuronal activity.Recent evidence shows that nitric oxide(NO)concentrations are enhanced in skin acupoints/meridians.L-arginine-derived NO synthesis modifies skin norepinephrine(NE)synthesis/release in acupoints/meridians,and NO-NE activations play an important role in mediating the skin conductance responses to electrical stimulation.NOergic signaling molecules interact with gap junction and transient receptor potential vanilloid type-1.Other studies reported that the high conductance at acupoints is a result of the release of the neuropeptides substance P and calcitonin gene-related peptide during neurogenic inflammation in the referred pain area.Pathological body conditions caused considerable changes in skin conductance or impedance at acupoints.Although systematic research with an improved equipment and research design to avoid the influencing factors are requested for a definite answer in this field,the results from anatomical and biochemical studies consistently show that acupoints exist higher levels of nervous components,and NOergic signaling molecules and neuropeptides involved in the skin low resistance at acupoints.The increased interest in the acupoints/meridians has led to an open-minded attitude towards understanding this system,which is fundamental important to establish the valid aspects of scientific basis of Chinese medicine mechanisms and therapies.展开更多
目的探讨神经肽S受体1(neuropeptide S receptor 1,NPSR1)和消极应对在慢性心理应激反应中的中介效应。方法采用分层随机整群抽样方法在广西南丹县抽取366名当地普通居民对其进行生活事件量表(the life eventss cale,LES)、简化症状自...目的探讨神经肽S受体1(neuropeptide S receptor 1,NPSR1)和消极应对在慢性心理应激反应中的中介效应。方法采用分层随机整群抽样方法在广西南丹县抽取366名当地普通居民对其进行生活事件量表(the life eventss cale,LES)、简化症状自评量表、简易应对方式量表(the simplified coping style questionnaire,SCSQ)的测试,采用酶联免疫吸附测定检测调查对象血浆中的NPSR1表达水平,利用SPSS21.0和AMOS21.0统计学软件进行统计分析。结果慢性心理应激水平为(25.24±29.26)分,消极应对(14.84±4.35)分,躯体因子、焦虑因子、抑郁因子、敌对因子分别为(1.58±0.58)分,(1.43±0.56)分,(1.44±0.55)分,(1.23±0.37)分。生活事件总分与消极应对、躯体因子、焦虑因子、抑郁因子、敌对因子呈正相关(r=0.23~0.46,P<0.05),与NPSR1水平呈负相关(r=-0.26,P<0.05);NPSR1水平与躯体因子、焦虑因子、抑郁因子、敌对因子呈负相关(r=-0.18^-0.61,P<0.05);消极应对与躯体因子、焦虑因子、抑郁因子、敌对因子呈正相关(r=0.12~0.27,P<0.05)。在结构方程的中介模型中,拟合指标均达到理想值(χ2=0.349,GFI=0.993,AGFI=0.979,RMSEA=0.018,CFI=0.998),神经肽S受体1与消极应对对慢性心理应激引起的情绪反应的中介效应均显著(P<0.05),效应值分别为-0.08,0.05。根据Bootstrapping法检验中介模型的结果显示:Bias-Corrected的标准化总效应、标准化间接效应、标准化直接效应的95%CI均不与0相交。结论NPSR1和消极应对在由应激引起的应激性情绪反应中起到双重中介效应。展开更多
基金supported by a grant from the National Natural Science Foundation of China(No.81172898)
文摘Death following situations of intense emotional stress has been linked to the cardiac pathology described as stress cardiomyopathy, whose pathomechanism is still not clear. In this study, we sought to determine, via an animal model, whether the transcriptional coactivator peroxisome proliferator-activated receptor γ coactivator-1alpha (PGC-1α) and the amino peptide neuropeptide Y (NPY) play a role in the pathogenesis of this cardiac entity. Male Sprague-Dawley rats in the experimental group were subjected to immobilization in a plexy glass box for 1 h, which was followed by low voltage elec-tric foot shock for about 1h at 10s intervals in a cage fitted with metallic rods. After 25 days the rats were sacrificed and sections of their hearts were processed. Hematoxylin-eosin staining of cardiac tissues revealed the characteristic cardiac lesions of stress cardiomyopathy such as contraction band necrosis, inflammatory cell infiltration and fibrosis. The semi-quantitative RT-PCR analysis for PGC-1α mRNA expression showed significant overexpression of PGC1-α in the stress-subjected rats (P<0.05). Fluorescence immunohistochemistry revealed a higher production of NPY in the stress-subjected rats as compared to the control rats (P=0.0027). Thus, we are led to conclude that following periods of intense stress, an increased expression of PGC1-α in the heart and an overflow of NPY may lead to stress car-diomyopathy and even death in susceptible victims. Moreover, these markers can be used to identify stress cardiomyopathy as the cause of sudden death in specific cases.
基金Chinese Medicine Inheritance and Innovation“One Hundred Million”Talent Project Qihuang Scholar(to Li JX)The National Key R&D Program of China during the 13th Five-Year Plan Period,No.2018YFC1705405and The 66th China Postdoctoral Science Foundation,No.2019M660575.
文摘BACKGROUND Ulcerative colitis(UC)is an inflammatory bowel disease that is difficult to diagnose and treat.To date,the degree of inflammation in patients with UC has mainly been determined by measuring the levels of nonspecific indicators,such as C-reactive protein and the erythrocyte sedimentation rate,but these indicators have an unsatisfactory specificity.In this study,we performed bioinformatics analysis using data from the National Center for Biotechnology Information-Gene Expression Omnibus(NCBI-GEO)databases and verified the selected core genes in a mouse model of dextran sulfate sodium(DSS)-induced colitis.AIM To identify UC-related differentially expressed genes(DEGs)using a bioinformatics analysis and verify them in vivo and to identify novel biomarkers and the underlying mechanisms of UC.METHODS Two microarray datasets from the NCBI-GEO database were used,and DEGs between patients with UC and healthy controls were analyzed using GEO2R and Venn diagrams.We annotated these genes based on their functions and signaling pathways,and then protein-protein interactions(PPIs)were identified using the Search Tool for the Retrieval of Interacting Genes.The data were further analyzed with Cytoscape software and the Molecular Complex Detection(MCODE)app.The core genes were selected and a Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis was performed.Finally,colitis model mice were established by administering DSS,and the top three core genes were verified in colitis mice using real-time polymerase chain reaction(PCR).RESULTS One hundred and seventy-seven DEGs,118 upregulated and 59 downregulated,were initially identified from the GEO2R analysis and predominantly participated in inflammation-related pathways.Seven clusters with close interactions in UC formed:Seventeen core genes were upregulated[C-X-C motif chemokine ligand 13(CXCL13),C-X-C motif chemokine receptor 2(CXCR2),CXCL9,CXCL5,C-C motif chemokine ligand 18,interleukin 1 beta,matrix metallopeptidase 9,CXCL3,formyl peptide receptor 1,complement component 3,CXCL8,CXCL1,CXCL10,CXCL2,CXCL6,CXCL11 and hydroxycarboxylic acid receptor 3]and one was downregulated[neuropeptide Y receptor Y1(NYP1R)]in the top cluster according to the PPI and MCODE analyses.These genes were substantially enriched in the cytokinecytokine receptor interaction and chemokine signaling pathways.The top three core genes(CXCL13,NYP1R,and CXCR2)were selected and verified in a mouse model of colitis using real-time PCR Increased expression was observed compared with the control mice,but only CXCR2 expression was significantly different.CONCLUSION Core DEGs identified in UC are related to inflammation and immunity inflammation,indicating that these reactions are core features of the pathogenesis of UC.CXCR2 may reflect the degree of inflammation in patients with UC.
基金Supported by NIH Grant(No.AT002478,AT004620,and AT004504)from the National Center for Complementary and Integrative Health。
文摘Early studies from several independent laboratories demonstrated that acupoints possess the characteristics of low electrical resistance.New devices are developing to increase the reliability of electrical skin impedance measurements for counteracting the factors including skin dryness,skin thickness,size of the sensing electrode,pressure applied on the electrode,interelectrode distance,room temperature,and humidity.Morphological studies have identified that blood vessels,hair follicles,and nervous components are enhanced in the meridians/acupoints,which represent areas of potentially high neuronal activity.Recent evidence shows that nitric oxide(NO)concentrations are enhanced in skin acupoints/meridians.L-arginine-derived NO synthesis modifies skin norepinephrine(NE)synthesis/release in acupoints/meridians,and NO-NE activations play an important role in mediating the skin conductance responses to electrical stimulation.NOergic signaling molecules interact with gap junction and transient receptor potential vanilloid type-1.Other studies reported that the high conductance at acupoints is a result of the release of the neuropeptides substance P and calcitonin gene-related peptide during neurogenic inflammation in the referred pain area.Pathological body conditions caused considerable changes in skin conductance or impedance at acupoints.Although systematic research with an improved equipment and research design to avoid the influencing factors are requested for a definite answer in this field,the results from anatomical and biochemical studies consistently show that acupoints exist higher levels of nervous components,and NOergic signaling molecules and neuropeptides involved in the skin low resistance at acupoints.The increased interest in the acupoints/meridians has led to an open-minded attitude towards understanding this system,which is fundamental important to establish the valid aspects of scientific basis of Chinese medicine mechanisms and therapies.
