目的综合评估胱硫醚β-合成酶（CBS）基因 G919A 多态性与原发性高血压（EH）发生风险的关系。方法全面检索 PubMed 、Embase 、Medline 、万方数据库、中国知网（CNKI）、维普资讯，收集 CBS 基因 G919A 多态性与 EH 发生关系的病例对...目的综合评估胱硫醚β-合成酶（CBS）基因 G919A 多态性与原发性高血压（EH）发生风险的关系。方法全面检索 PubMed 、Embase 、Medline 、万方数据库、中国知网（CNKI）、维普资讯，收集 CBS 基因 G919A 多态性与 EH 发生关系的病例对照研究，优势比（OR）及95％可信区间（CI）评估关联强度，应用 RevMan5.3软件对纳入研究进行异质性检验和效应值 OR 合并，漏斗图评价发表性偏倚；敏感度分析过程，分别以固定效应模型和随机效应模型合并 OR 值，以评估结果的稳定性。结果共纳入4篇文献6组病例－对照研究，共累计 EH 组患者1147例，健康对照组1138例，根据异质性检验结果选取固定效应模型或随机效应模型合并数据。 Meta 分析结果显示：CBS 基因919纯合子模型（AA vs GG）、杂合子模型（GA vs GG）、显性模型（AA ＋ GA vs GG）、隐性模型（AA vs GG ＋ GA）和基因频率（A vs G）与 EH 关系的合并 OR（95％ CI）分别为3.03（1.95～4.72）、1.49（1.10～2.02）、1.61（1.23～2.10）、2.65（1.26～5.57）和1.55（1.35～1.79），均 P＜0.01。漏斗图未检测出显著的发表性偏倚。结论目前 Meta 分析表明 CBS 基因 G919A 多态性与 EH 发病相关联，尤其是在中国人群。展开更多
Hydrogen sulfide(H2S)is a gasotransmitter that acts as an antioxidant and exhibits a wide variety of cytoprotective and physiological functions in age-associated diseases.One of the major causes of age-related disease...Hydrogen sulfide(H2S)is a gasotransmitter that acts as an antioxidant and exhibits a wide variety of cytoprotective and physiological functions in age-associated diseases.One of the major causes of age-related diseases is oxidative stress.In recent years,the importance of H2S has become clear,although its antioxidant function has not yet been fully explored.The enzymes cystathionineβ-synthase,cystathionineγ-lya-se,and 3-mercaptopyruvate sulfurtransferase are involved in the enzymatic production of H2S.Previously,H2S was considered a neuromodulator,given its role in long-term hippocampal potentiation,but it is now also recognized as an antioxidant in age-related neurodegeneration.Due to aerobic metabolism,the central nervous system is vulnerable to oxidative stress in brain aging,resulting in age-associated degenerative diseases.H2S exerts its antioxidant effect by limiting free radical reactions through the activation of antioxidant enzymes,including superoxide dismutase,catalase,and glutathione peroxidase,which protect against the effects of aging by regulating apoptosis-related genes,including p53,Bax,and Bcl-2.This review explores the implications and mechanisms of H2S as an antioxidant in age-associated neurodegenerative diseases,including Alzheimer’s disease,Parkinson’s disease,Huntington’s disease,and Down syndrome.展开更多
This study aimed to observe changes in the hydrogen sulfide（H_2S） system in the blood and liver tissue of rats with hepatic cirrhosis at different stages by studying the effect of H_2S on the course of hyperdynamic ...This study aimed to observe changes in the hydrogen sulfide（H_2S） system in the blood and liver tissue of rats with hepatic cirrhosis at different stages by studying the effect of H_2S on the course of hyperdynamic circulation in rats with hepatic cirrhosis. H_2S concentration in the blood from the portal vein and inferior vena cava of hepatic cirrhosis rat model induced with carbon tetrachloride was detected on the 15 th, 30 th, and 52 nd day. The expression of cystathionine β-synthase（CBS） and cystathionine γ-lyase（CSE） protein, and CBS and CSE mRNA in the liver was detected by immunohistochemistry and reverse transcriptase polymerase chain reaction（RT-PCR）, respectively. The results indicated that H_2S concentration in the blood from the portal vein and inferior vena cava of rats with hepatic cirrhosis was significantly lower than that in the control group. H_2S was gradually decreased with the development of the disease and significantly lower in the blood from portal vein than in the blood of inferior vena cava at the mid-stage and the late stage groups. The expression levels of CBS and CSE protein, and CBS and CSE mR NA in the livers with hepatic cirrhosis at different stages were all higher than those in the control group, and the expression gradually increased with the development of the disease. The expression of CBS was lower than CSE in the same stages. The results indicated that the CSE mRNA was expressed predominantly in the cirrhosis groups as compared with CBS mRNA. Among experimental rats, the H_2S system has an important effect on the occurrence and development of hyperdynamic circulation in rats with hepatic cirrhosis. This finding adds to the literature by demonstrating that H_2S protects vascular remodelling in the liver, and that CSE is indispensable in this process.展开更多
We investigated the expression of hydrogen sulphide （H2S） in human and rat lower urinary tract （including bladder, prostate and urethra） tissues, and we sought to determine whether H2S induces relaxation of human ...We investigated the expression of hydrogen sulphide （H2S） in human and rat lower urinary tract （including bladder, prostate and urethra） tissues, and we sought to determine whether H2S induces relaxation of human and Sprague-Dawley （SD） rat bladder strips. Human normal lower urinary tract tissue was obtained for the evaluation of endogenous H2S productivity using a sulphide-sensitive electrode and for the analysis of the expression levels of all three synthases of endogenous H2S, cystathionine β-synthase （CBS）, cystathionine y lyase （CSE） and 3-mercaptopyruvate sulphur transferase （MPST, as known as 3-MST） by Western blot assay. CBS, CSE and MPST were located in human sample slides by immunohistochemistry. Human and male adult SD rat bladder strips were tested for H2S function with a transducer and recorded. All experiments were repeated six times. The endogenous H2S productivity and the H2S synthases had various distributions in the human and rat lower urinary tract tissues and were located in both epithelial and stromal sections. L-cysteine （L-Cys, a substrate of CBS, CSE and MPST） elicited relaxation in a dose-dependent manner on human bladder strips ere-contracted by acetylcholine chloride. This effect could be diminished by the ATe-sensitive potassium ion （KATe） channel blocker glibenclamide （GLB）, the CSE inhibitor DL-propargylglycine （PEG） and the CBS inhibitor hydroxylamine （HA）. H2S and its three synthases were present in the human and rat lower urinary tract tissues and relaxed human and rat bladder strips, which implied that endogenous H2S might play a role in physiological function and pathological disorders of the lower urinary tract symptoms （LUTS） or overactive bladder （OAB）.展开更多
Hyperhomocysteinemia(HHcy)contributes to the incidence of many cardiovascular diseases(CVD).Our group have previously established crucial roles of eicosanoids and homocysteine in the incidence of vascular injury in di...Hyperhomocysteinemia(HHcy)contributes to the incidence of many cardiovascular diseases(CVD).Our group have previously established crucial roles of eicosanoids and homocysteine in the incidence of vascular injury in diabetic retinopathy and renal injury.Using cystathionine-β-synthase heterozygous mice(cβs^(+/-))as a model of HHcy,the current study was designed to determine the impact of homocysteine on circulating levels of lipid mediators derived from polyunsaturated fatty acids(PUFA).Plasma samples were isolated from wild-type(WT)and cβs^(+/-)mice for the assessment of eicosanoids levels using LC/MS.Plasma 12/15-lipoxygenase(12/15-LOX)activity significantly decreased in cβs^(+/-)vs.WT control mice.LOX-derived metabolites from both omega-3 and omega-6 PUFA were also reduced in cβs^(+/-)mice compared to WT control(P<0.05).Contrary to LOX metabolites,cytochrome P450(CYP)metabolites from omega-3 and omega-6 PUFA were significantly elevated in cβs^(+/-)mice compared to WT control.Epoxyeicosatrienoic acids(EETs)are epoxides derived from arachidonic acid(AA)metabolism by CYP with anti-inflammatory properties and are known to limit vascular injury,however their physiological role is limited by their rapid degradation by soluble epoxide hydrolase(sEH)to their corresponding diols(DiHETrEs).In cβs^(+/-)mice,a significant decrease in the plasma EETs bioavailability was obvious as evident by the decrease in EETs/DiHETrEs ratio relative to WT control mice.Cyclooxygenase(COX)metabolites were also significantly decreased in cβs^(+/-)vs.WT control mice.These data suggest that HHcy impacts eicosanoids metabolism through decreasing LOX and COX metabolic activities while increasing CYP metabolic activity.The increase in AA metabolism by CYP was also associated with increase in sEH activity and decrease in EETs bioavailability.Dysregulation of eicosanoids metabolism could be a contributing factor to the incidence and progression of HHcy-induced CVD.展开更多
文摘目的综合评估胱硫醚β-合成酶（CBS）基因 G919A 多态性与原发性高血压（EH）发生风险的关系。方法全面检索 PubMed 、Embase 、Medline 、万方数据库、中国知网（CNKI）、维普资讯，收集 CBS 基因 G919A 多态性与 EH 发生关系的病例对照研究，优势比（OR）及95％可信区间（CI）评估关联强度，应用 RevMan5.3软件对纳入研究进行异质性检验和效应值 OR 合并，漏斗图评价发表性偏倚；敏感度分析过程，分别以固定效应模型和随机效应模型合并 OR 值，以评估结果的稳定性。结果共纳入4篇文献6组病例－对照研究，共累计 EH 组患者1147例，健康对照组1138例，根据异质性检验结果选取固定效应模型或随机效应模型合并数据。 Meta 分析结果显示：CBS 基因919纯合子模型（AA vs GG）、杂合子模型（GA vs GG）、显性模型（AA ＋ GA vs GG）、隐性模型（AA vs GG ＋ GA）和基因频率（A vs G）与 EH 关系的合并 OR（95％ CI）分别为3.03（1.95～4.72）、1.49（1.10～2.02）、1.61（1.23～2.10）、2.65（1.26～5.57）和1.55（1.35～1.79），均 P＜0.01。漏斗图未检测出显著的发表性偏倚。结论目前 Meta 分析表明 CBS 基因 G919A 多态性与 EH 发病相关联，尤其是在中国人群。
基金supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT and Future Planning, No. 2018R1A2B6001123 (to NYJ), No. 2018R1D1A1B07040282 (to JJ)
文摘Hydrogen sulfide(H2S)is a gasotransmitter that acts as an antioxidant and exhibits a wide variety of cytoprotective and physiological functions in age-associated diseases.One of the major causes of age-related diseases is oxidative stress.In recent years,the importance of H2S has become clear,although its antioxidant function has not yet been fully explored.The enzymes cystathionineβ-synthase,cystathionineγ-lya-se,and 3-mercaptopyruvate sulfurtransferase are involved in the enzymatic production of H2S.Previously,H2S was considered a neuromodulator,given its role in long-term hippocampal potentiation,but it is now also recognized as an antioxidant in age-related neurodegeneration.Due to aerobic metabolism,the central nervous system is vulnerable to oxidative stress in brain aging,resulting in age-associated degenerative diseases.H2S exerts its antioxidant effect by limiting free radical reactions through the activation of antioxidant enzymes,including superoxide dismutase,catalase,and glutathione peroxidase,which protect against the effects of aging by regulating apoptosis-related genes,including p53,Bax,and Bcl-2.This review explores the implications and mechanisms of H2S as an antioxidant in age-associated neurodegenerative diseases,including Alzheimer’s disease,Parkinson’s disease,Huntington’s disease,and Down syndrome.
基金supported by grants from the National Natural Science Foundation of China(No.30850004 and No.81170402)
文摘This study aimed to observe changes in the hydrogen sulfide（H_2S） system in the blood and liver tissue of rats with hepatic cirrhosis at different stages by studying the effect of H_2S on the course of hyperdynamic circulation in rats with hepatic cirrhosis. H_2S concentration in the blood from the portal vein and inferior vena cava of hepatic cirrhosis rat model induced with carbon tetrachloride was detected on the 15 th, 30 th, and 52 nd day. The expression of cystathionine β-synthase（CBS） and cystathionine γ-lyase（CSE） protein, and CBS and CSE mRNA in the liver was detected by immunohistochemistry and reverse transcriptase polymerase chain reaction（RT-PCR）, respectively. The results indicated that H_2S concentration in the blood from the portal vein and inferior vena cava of rats with hepatic cirrhosis was significantly lower than that in the control group. H_2S was gradually decreased with the development of the disease and significantly lower in the blood from portal vein than in the blood of inferior vena cava at the mid-stage and the late stage groups. The expression levels of CBS and CSE protein, and CBS and CSE mR NA in the livers with hepatic cirrhosis at different stages were all higher than those in the control group, and the expression gradually increased with the development of the disease. The expression of CBS was lower than CSE in the same stages. The results indicated that the CSE mRNA was expressed predominantly in the cirrhosis groups as compared with CBS mRNA. Among experimental rats, the H_2S system has an important effect on the occurrence and development of hyperdynamic circulation in rats with hepatic cirrhosis. This finding adds to the literature by demonstrating that H_2S protects vascular remodelling in the liver, and that CSE is indispensable in this process.
基金We thank Professor Jun-Bao Du for providing experimental suggestions and advice, and our study was supported by the National Natural Science Foundation of China （No. 30571851 to Jie Jill, No. 81201527 to Hui Guo）.
文摘We investigated the expression of hydrogen sulphide （H2S） in human and rat lower urinary tract （including bladder, prostate and urethra） tissues, and we sought to determine whether H2S induces relaxation of human and Sprague-Dawley （SD） rat bladder strips. Human normal lower urinary tract tissue was obtained for the evaluation of endogenous H2S productivity using a sulphide-sensitive electrode and for the analysis of the expression levels of all three synthases of endogenous H2S, cystathionine β-synthase （CBS）, cystathionine y lyase （CSE） and 3-mercaptopyruvate sulphur transferase （MPST, as known as 3-MST） by Western blot assay. CBS, CSE and MPST were located in human sample slides by immunohistochemistry. Human and male adult SD rat bladder strips were tested for H2S function with a transducer and recorded. All experiments were repeated six times. The endogenous H2S productivity and the H2S synthases had various distributions in the human and rat lower urinary tract tissues and were located in both epithelial and stromal sections. L-cysteine （L-Cys, a substrate of CBS, CSE and MPST） elicited relaxation in a dose-dependent manner on human bladder strips ere-contracted by acetylcholine chloride. This effect could be diminished by the ATe-sensitive potassium ion （KATe） channel blocker glibenclamide （GLB）, the CSE inhibitor DL-propargylglycine （PEG） and the CBS inhibitor hydroxylamine （HA）. H2S and its three synthases were present in the human and rat lower urinary tract tissues and relaxed human and rat bladder strips, which implied that endogenous H2S might play a role in physiological function and pathological disorders of the lower urinary tract symptoms （LUTS） or overactive bladder （OAB）.
基金supported by1R01EY030054(MA),NIH-1R01EY029751(AT)supported in part by National Center for Research Resources,National Institutes of Health Grant S10RR027926.
文摘Hyperhomocysteinemia(HHcy)contributes to the incidence of many cardiovascular diseases(CVD).Our group have previously established crucial roles of eicosanoids and homocysteine in the incidence of vascular injury in diabetic retinopathy and renal injury.Using cystathionine-β-synthase heterozygous mice(cβs^(+/-))as a model of HHcy,the current study was designed to determine the impact of homocysteine on circulating levels of lipid mediators derived from polyunsaturated fatty acids(PUFA).Plasma samples were isolated from wild-type(WT)and cβs^(+/-)mice for the assessment of eicosanoids levels using LC/MS.Plasma 12/15-lipoxygenase(12/15-LOX)activity significantly decreased in cβs^(+/-)vs.WT control mice.LOX-derived metabolites from both omega-3 and omega-6 PUFA were also reduced in cβs^(+/-)mice compared to WT control(P<0.05).Contrary to LOX metabolites,cytochrome P450(CYP)metabolites from omega-3 and omega-6 PUFA were significantly elevated in cβs^(+/-)mice compared to WT control.Epoxyeicosatrienoic acids(EETs)are epoxides derived from arachidonic acid(AA)metabolism by CYP with anti-inflammatory properties and are known to limit vascular injury,however their physiological role is limited by their rapid degradation by soluble epoxide hydrolase(sEH)to their corresponding diols(DiHETrEs).In cβs^(+/-)mice,a significant decrease in the plasma EETs bioavailability was obvious as evident by the decrease in EETs/DiHETrEs ratio relative to WT control mice.Cyclooxygenase(COX)metabolites were also significantly decreased in cβs^(+/-)vs.WT control mice.These data suggest that HHcy impacts eicosanoids metabolism through decreasing LOX and COX metabolic activities while increasing CYP metabolic activity.The increase in AA metabolism by CYP was also associated with increase in sEH activity and decrease in EETs bioavailability.Dysregulation of eicosanoids metabolism could be a contributing factor to the incidence and progression of HHcy-induced CVD.
