Objective. To investigate the relationship of plasma homocysteine (Hcy) level to stroke and genetic factor to elevated plasma Hcy level.Methods. The plasma Hcy level was measured by capillary electrophoresis- ultravio...Objective. To investigate the relationship of plasma homocysteine (Hcy) level to stroke and genetic factor to elevated plasma Hcy level.Methods. The plasma Hcy level was measured by capillary electrophoresis- ultraviolet detection and the gene polymorphism of N5, N10 - methylenetetrahydrofolate reductase (MTHFR) was studied with PCR - RFLP assay in 43 patients with cortical cerebral infarction and 42 healthy controls.Results. The plasma Hcy level of the patients ( 19. 3 + 6. 0 μ mol/L) was markedly higher than that of the controls (13.7 + 5.4 μ mol/L) ( t = 4. 16, P ＜ 0. 001). There are 3 genotypes, C/C, C/T and T/T, about base - variation of MTHFR gene at locus 677. The plasma Hcy level of the subjects with T/T genotype was higher than that of subjects with other genotypes. However, the frequencies of each genotype and allele were not significantly different between the patients and the controls.Conclusions. The elevated plasma Hcy level is a risk factor for atherothrombotic cerebral infarction, and is related to the C→T mutation at locus 677 of MTHFR gene.展开更多
目的:通过研究银屑病患者皮损处真皮间充质干细胞(DMSCs)中磷脂酶C-β4(PLCB4)和视黄醇脱氢酶(RDH)10mRNA的表达水平,进一步探讨银屑病发病的细胞及分子机制。方法:对24例寻常性银屑病(PV)患者和22例正常人皮肤DMSCs进行分离培养,流式...目的:通过研究银屑病患者皮损处真皮间充质干细胞(DMSCs)中磷脂酶C-β4(PLCB4)和视黄醇脱氢酶(RDH)10mRNA的表达水平,进一步探讨银屑病发病的细胞及分子机制。方法:对24例寻常性银屑病(PV)患者和22例正常人皮肤DMSCs进行分离培养,流式细胞术进行细胞表型鉴定,实时荧光定量聚合酶链式反应(PCR)测定PLCB4和RDH10 mRNA表达水平。结果:PV组与正常对照组DMSCs形态无差异。PV组患者DMSCs中PLCB4 m RNA的表达水平是正常对照组的3.35倍,RDH10 mRNA的表达水平是正常对照组的1.17倍。结论:银屑病患者DMSCs中PLCB4和RDH10 m RNA表达均增高,可能影响相关信号通路,进而对银屑病发病产生影响。展开更多
Background The 5,10-methylenetetrahydrofolate reductase （MTHFR） and methionine synthase （MS） are attractive candidates for screening for risk of neural tube defects （NTDs）. The aim of the current study was to in...Background The 5,10-methylenetetrahydrofolate reductase （MTHFR） and methionine synthase （MS） are attractive candidates for screening for risk of neural tube defects （NTDs）. The aim of the current study was to investigate maternal MTHFR and MS polymorphisms and the interaction between them and their influence on children with NTDs in the Shanxi Province of northern China. Methods Fifty-one mothers who previously had children with NTDs constituted the case group and 51 age-matched mothers with children that were unaffected by any birth defects constituted the control group. All subjects were genotyped for MTHFR C677T and MS A2756G polymorphisms. SPSS 11.5 software package was used for all analyses. Results There was a significant difference for MTHFR genotype distribution for one site （C677T） between the case and control groups. The T allele frequencies were significantly higher in the case group than in the control group （55.9% vs. 35.3%, P 〈0.05）. A lack of association was observed for the MS A2756G polymorphism. There was an interaction between the maternal MTHFR C677T genotype and MS A2756G genotype. Conclusion Genetic interaction between MTHFR and MS genes raises the probability of neural tube defects.展开更多
Interleukin-10(IL-10)is the most potent anti-inflammatory cytokine in the body and plays an essential role in determining outcomes of many inflammatory diseases.Cellular metabolism is a critical determinant of immune ...Interleukin-10(IL-10)is the most potent anti-inflammatory cytokine in the body and plays an essential role in determining outcomes of many inflammatory diseases.Cellular metabolism is a critical determinant of immune cell function;however,it is currently unclear whether metabolic processes are specifically involved in IL-10 production.In this study,we aimed to find the central metabolic molecule regulating IL-10 production of macrophages,which are the main producers of IL-10.Transcriptomic analysis identified that metabolic changes were predominantly enriched in Kupffer cells at the early inflammatory phase of a mouse endotoxemia model.Among them,pyruvate dehydrogenase kinase(PDK)-dependent acute glycolysis was negatively involved in IL-10 production.Inhibition or knockdown of PDK selectively increased macrophage IL-10 expression.Mechanistically,PDK inhibition increased IL-10 production via profound phosphorylation of adenosine monophosphate(AMP)-activated protein kinase alpha 1(AMPKα1)by restricting glucose uptake in lipopolysaccharide-stimulated macrophages.AMPKα1 consequently activated p38 mitogen-activated protein kinase,c-Jun N-terminal kinase,and cyclic AMP-responsive element-binding protein to regulate IL-10 production.Our study uncovers a previously unknown regulatory mechanism of IL-10 in activated macrophages involving an immunometabolic function of PDK.展开更多
本实验分析了受异丙基肾上腺素损伤的心肌线粒体琥珀酸脱氢酶和细胞色素 C 氧化酶的活性,辅酶 Q_(10)的含量,以及全血中的 ATP 含量,结果表明,心肌线粒体辅酶 Q_(10)和全血中ATP,ADP 含量及线粒体上清中琥珀酸脱氢酶活性降低,说明损伤...本实验分析了受异丙基肾上腺素损伤的心肌线粒体琥珀酸脱氢酶和细胞色素 C 氧化酶的活性,辅酶 Q_(10)的含量,以及全血中的 ATP 含量,结果表明,心肌线粒体辅酶 Q_(10)和全血中ATP,ADP 含量及线粒体上清中琥珀酸脱氢酶活性降低,说明损伤心肌组织的能量代谢发生障碍。我们也开展了复方丹参和辅酶 Q_(10)对心肌保护作用的研究,结果发现这两种药物对心肌有明显的保护作用。展开更多
Objective To investigate the relationship of plasma homocysteine (Hcy) levels and the gene polymorphisms of N5, N10-methylenetetrahydrofolate reductase (MTHFR), cystathionine β-synthase (CBS) with Alzheimer’s diseas...Objective To investigate the relationship of plasma homocysteine (Hcy) levels and the gene polymorphisms of N5, N10-methylenetetrahydrofolate reductase (MTHFR), cystathionine β-synthase (CBS) with Alzheimer’s disease (AD). Methods Plasma Hcy levels were measured by means of high voltage capillary electrophoresis with ultra-violet detection, the polymorphisms of C677T in exon 4 of MTHFR gene and 844ins68 in exon 8 of CBS gene were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in 105 AD patients and 102 non-AD controls. All controls were excluded from cardiocerebrovascular disorders and other diseases. Results The plasma Hcy level in AD patients (16.04 ± 3.84 μmol/L) was significantly higher than that in the controls(11.94 ± 3.87 μmol/L, P < 0.001). There were no significant differences of the genotype and allele frequencies of MTHFR C677T mutation and CBS 844ins68 mutation between the patients and controls. However, the T allele of MTHFR gene was found to relate with the plasma Hcy level increase in all subjects. Conclusion The elevated plasma Hcy level in AD patients is probably involved in the pathogenesis of AD, which may be due to the environmental factor rather than genetic factors of the mutations of MTHFR and CBS.展开更多
目的分析17β-羟类固醇脱氢酶10(17β-hydroxysteroid dehydrogenase type 10,HSD17B10)缺乏症的临床及基因特点。方法对四川大学华西第二医院新生儿科诊治的1例病情进展迅速的HSD17B10缺乏症患儿临床资料进行分析,并以"17β-羟类...目的分析17β-羟类固醇脱氢酶10(17β-hydroxysteroid dehydrogenase type 10,HSD17B10)缺乏症的临床及基因特点。方法对四川大学华西第二医院新生儿科诊治的1例病情进展迅速的HSD17B10缺乏症患儿临床资料进行分析,并以"17β-羟类固醇脱氢酶"、"17β-HSD"、"17β-羟类固醇脱氢酶10"、"HSD17B10"、"2-甲基-3-羟基丁酰辅酶A脱氢酶"、"2-甲基-3-羟基丁酰辅酶A脱氢酶缺乏症"、"MHBD"、"MHBDD"为关键词在中国期刊全文数据库、维普数据库、万方数据库中检索国内文献,以"17β-hydroxysteroid dehydrogenase type 10 disease"、"HSD10"、"HSD17B10"和"2-methyl-3-hydroxybutyryl-CoA dehydrogenase deficiency"、"2M3HBDD"、"MHBD"、"MHBDD"为关键词在PubMed、Embase检索相关文献。复习已报道的HSD17B10缺乏症患者资料,总结HSD17B10缺乏症的临床特点及基因突变情况。结果患儿男,以生后反应差为首发临床症状,伴有严重代谢性酸中毒、心肌损伤、高氨血症,家属放弃治疗后死亡,基因检测提示HSD17B10外显子6发生c.740A>G(p.N247S)突变。文献检索共收集38篇文献40例患儿资料,包括本例在内共41例,均存在HSD17B10基因突变,共报道16种基因突变类型。男性38例(92.7%),明显多于女性,且病情多较女性严重;表现为神经系统异常37例(90.2%),伴有代谢性酸中毒13例(31.7%)、低血糖8例(19.5%)、视网膜病变7例(17.1%)、心肌病6例(14.6%)、眼球震颤4例(9.8%)。新生儿期发病者常表现为严重代谢性酸中毒,发病年龄越小,病死率越高,预后越差,通过HSD17B10基因突变分析可确诊。结论HSD17B10缺乏症基因突变类型较多,男性患儿病情相对严重,预后差,目前尚无有效治疗方法,若有该疾病家族史,需早期行产前咨询、产前诊断。展开更多
基金This study was supported by"333 Talent Project " funds of Jiangsu Province in 1999.
文摘Objective. To investigate the relationship of plasma homocysteine (Hcy) level to stroke and genetic factor to elevated plasma Hcy level.Methods. The plasma Hcy level was measured by capillary electrophoresis- ultraviolet detection and the gene polymorphism of N5, N10 - methylenetetrahydrofolate reductase (MTHFR) was studied with PCR - RFLP assay in 43 patients with cortical cerebral infarction and 42 healthy controls.Results. The plasma Hcy level of the patients ( 19. 3 + 6. 0 μ mol/L) was markedly higher than that of the controls (13.7 + 5.4 μ mol/L) ( t = 4. 16, P ＜ 0. 001). There are 3 genotypes, C/C, C/T and T/T, about base - variation of MTHFR gene at locus 677. The plasma Hcy level of the subjects with T/T genotype was higher than that of subjects with other genotypes. However, the frequencies of each genotype and allele were not significantly different between the patients and the controls.Conclusions. The elevated plasma Hcy level is a risk factor for atherothrombotic cerebral infarction, and is related to the C→T mutation at locus 677 of MTHFR gene.
文摘目的:通过研究银屑病患者皮损处真皮间充质干细胞(DMSCs)中磷脂酶C-β4(PLCB4)和视黄醇脱氢酶(RDH)10mRNA的表达水平,进一步探讨银屑病发病的细胞及分子机制。方法:对24例寻常性银屑病(PV)患者和22例正常人皮肤DMSCs进行分离培养,流式细胞术进行细胞表型鉴定,实时荧光定量聚合酶链式反应(PCR)测定PLCB4和RDH10 mRNA表达水平。结果:PV组与正常对照组DMSCs形态无差异。PV组患者DMSCs中PLCB4 m RNA的表达水平是正常对照组的3.35倍,RDH10 mRNA的表达水平是正常对照组的1.17倍。结论:银屑病患者DMSCs中PLCB4和RDH10 m RNA表达均增高,可能影响相关信号通路,进而对银屑病发病产生影响。
基金This research was supported by the grants from the National Natural Science Foundation of China （No. 31140012, and No. 31040056） the Natural Science Foundation of Shanxi Province （No. 200611113） and Shanxi Scholarship Council of China （No. 2010-52）.
文摘Background The 5,10-methylenetetrahydrofolate reductase （MTHFR） and methionine synthase （MS） are attractive candidates for screening for risk of neural tube defects （NTDs）. The aim of the current study was to investigate maternal MTHFR and MS polymorphisms and the interaction between them and their influence on children with NTDs in the Shanxi Province of northern China. Methods Fifty-one mothers who previously had children with NTDs constituted the case group and 51 age-matched mothers with children that were unaffected by any birth defects constituted the control group. All subjects were genotyped for MTHFR C677T and MS A2756G polymorphisms. SPSS 11.5 software package was used for all analyses. Results There was a significant difference for MTHFR genotype distribution for one site （C677T） between the case and control groups. The T allele frequencies were significantly higher in the case group than in the control group （55.9% vs. 35.3%, P 〈0.05）. A lack of association was observed for the MS A2756G polymorphism. There was an interaction between the maternal MTHFR C677T genotype and MS A2756G genotype. Conclusion Genetic interaction between MTHFR and MS genes raises the probability of neural tube defects.
基金supported by Basic Science Research Program through the National Research Foundation of Korea(NRF)funded by the Ministry of Science,ICT&Future Planning(NRF-2015R1D1A1A02061958 and NRF-2017R1D1A1B04031161)J.-W.P.was supported by a grant from the National Research Found ation of Korea(2017R1AAA1015015)S.H.S.and j.J.H.were supported by the Korea Research Institute of Bioscience and Biotechnology Research Initiative Program(KGM 4571922).
文摘Interleukin-10(IL-10)is the most potent anti-inflammatory cytokine in the body and plays an essential role in determining outcomes of many inflammatory diseases.Cellular metabolism is a critical determinant of immune cell function;however,it is currently unclear whether metabolic processes are specifically involved in IL-10 production.In this study,we aimed to find the central metabolic molecule regulating IL-10 production of macrophages,which are the main producers of IL-10.Transcriptomic analysis identified that metabolic changes were predominantly enriched in Kupffer cells at the early inflammatory phase of a mouse endotoxemia model.Among them,pyruvate dehydrogenase kinase(PDK)-dependent acute glycolysis was negatively involved in IL-10 production.Inhibition or knockdown of PDK selectively increased macrophage IL-10 expression.Mechanistically,PDK inhibition increased IL-10 production via profound phosphorylation of adenosine monophosphate(AMP)-activated protein kinase alpha 1(AMPKα1)by restricting glucose uptake in lipopolysaccharide-stimulated macrophages.AMPKα1 consequently activated p38 mitogen-activated protein kinase,c-Jun N-terminal kinase,and cyclic AMP-responsive element-binding protein to regulate IL-10 production.Our study uncovers a previously unknown regulatory mechanism of IL-10 in activated macrophages involving an immunometabolic function of PDK.
文摘本实验分析了受异丙基肾上腺素损伤的心肌线粒体琥珀酸脱氢酶和细胞色素 C 氧化酶的活性,辅酶 Q_(10)的含量,以及全血中的 ATP 含量,结果表明,心肌线粒体辅酶 Q_(10)和全血中ATP,ADP 含量及线粒体上清中琥珀酸脱氢酶活性降低,说明损伤心肌组织的能量代谢发生障碍。我们也开展了复方丹参和辅酶 Q_(10)对心肌保护作用的研究,结果发现这两种药物对心肌有明显的保护作用。
文摘Objective To investigate the relationship of plasma homocysteine (Hcy) levels and the gene polymorphisms of N5, N10-methylenetetrahydrofolate reductase (MTHFR), cystathionine β-synthase (CBS) with Alzheimer’s disease (AD). Methods Plasma Hcy levels were measured by means of high voltage capillary electrophoresis with ultra-violet detection, the polymorphisms of C677T in exon 4 of MTHFR gene and 844ins68 in exon 8 of CBS gene were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in 105 AD patients and 102 non-AD controls. All controls were excluded from cardiocerebrovascular disorders and other diseases. Results The plasma Hcy level in AD patients (16.04 ± 3.84 μmol/L) was significantly higher than that in the controls(11.94 ± 3.87 μmol/L, P < 0.001). There were no significant differences of the genotype and allele frequencies of MTHFR C677T mutation and CBS 844ins68 mutation between the patients and controls. However, the T allele of MTHFR gene was found to relate with the plasma Hcy level increase in all subjects. Conclusion The elevated plasma Hcy level in AD patients is probably involved in the pathogenesis of AD, which may be due to the environmental factor rather than genetic factors of the mutations of MTHFR and CBS.
文摘目的分析17β-羟类固醇脱氢酶10(17β-hydroxysteroid dehydrogenase type 10,HSD17B10)缺乏症的临床及基因特点。方法对四川大学华西第二医院新生儿科诊治的1例病情进展迅速的HSD17B10缺乏症患儿临床资料进行分析,并以"17β-羟类固醇脱氢酶"、"17β-HSD"、"17β-羟类固醇脱氢酶10"、"HSD17B10"、"2-甲基-3-羟基丁酰辅酶A脱氢酶"、"2-甲基-3-羟基丁酰辅酶A脱氢酶缺乏症"、"MHBD"、"MHBDD"为关键词在中国期刊全文数据库、维普数据库、万方数据库中检索国内文献,以"17β-hydroxysteroid dehydrogenase type 10 disease"、"HSD10"、"HSD17B10"和"2-methyl-3-hydroxybutyryl-CoA dehydrogenase deficiency"、"2M3HBDD"、"MHBD"、"MHBDD"为关键词在PubMed、Embase检索相关文献。复习已报道的HSD17B10缺乏症患者资料,总结HSD17B10缺乏症的临床特点及基因突变情况。结果患儿男,以生后反应差为首发临床症状,伴有严重代谢性酸中毒、心肌损伤、高氨血症,家属放弃治疗后死亡,基因检测提示HSD17B10外显子6发生c.740A>G(p.N247S)突变。文献检索共收集38篇文献40例患儿资料,包括本例在内共41例,均存在HSD17B10基因突变,共报道16种基因突变类型。男性38例(92.7%),明显多于女性,且病情多较女性严重;表现为神经系统异常37例(90.2%),伴有代谢性酸中毒13例(31.7%)、低血糖8例(19.5%)、视网膜病变7例(17.1%)、心肌病6例(14.6%)、眼球震颤4例(9.8%)。新生儿期发病者常表现为严重代谢性酸中毒,发病年龄越小,病死率越高,预后越差,通过HSD17B10基因突变分析可确诊。结论HSD17B10缺乏症基因突变类型较多,男性患儿病情相对严重,预后差,目前尚无有效治疗方法,若有该疾病家族史,需早期行产前咨询、产前诊断。
