Objective To investigate the effects and underlying mechanisms of Panax quinquefolium saponin(PQS)on energy deficiency in hypoxia-reperfusion(H/R)induced cardiomyocytes.Methods The H/R injury involved hypoxia for 3 h ...Objective To investigate the effects and underlying mechanisms of Panax quinquefolium saponin(PQS)on energy deficiency in hypoxia-reperfusion(H/R)induced cardiomyocytes.Methods The H/R injury involved hypoxia for 3 h and then reperfusion for 2 h.Cardiomyocytes recruited from neonatal rat ventricular myocytes(NRVMs)were randomly divided into control,H/R,H/R+compound C(C.C),H/R+PQS,and H/R+C.C+PQS groups.BrdU assay,lactase dehydrogenase(LDH)leakage and early apoptosis rate were evaluated to assess cell damages.Contents of high energy phosphate compounds were conducted to detect the energy production.Protein expression levels of adenosine monophosphate-activated protein kinase a(AMPKα),glucose transporter 4(GLUT4),phosphate fructose kinase 2(PFK2),fatty acid translocase/cluster of differentiation 36(FAT/CD36),and acetyl CoA carboxylase 2(ACC2)in the regulatory pathways were measured by Western blotting.Immunofluorescence staining of GLUT4 and FAT/CD36 was used to observe the mobilization of metabolic transporters.Results PQS(50 mg/L)pretreatment significantly alleviated H/R-induced inhibition of NRVMs viability,up-regulation of LDH leakage,acceleration of early apoptosis,and reduction of energy production(P<0.05).Compared with the H/R group,up-regulated expression of AMPKα,GLUT4,PFK2,FAT/CD36 and ACC2 were observed,and more GLUT4 and FAT/CD36 expressions were detected on the membrane in the H/R+PQS group(P<0.05).These effects of PQS on H/R-induced NRVMs were eliminated in the H/R+C.C+PQS group(P<0.05).Conclusion PQS has prominent advantages in protecting NRVMs from H/R-induced cell damages and energy metabolic disorders,by activation of AMPKα-mediated GLUT4-PFK2 and FAT/CD36-ACC2 pathways.展开更多
为筛选高产胆盐水解酶的乳杆菌,探究其对新生儿黄疸的防治作用。采用添加了25 U/mL制霉菌素的LBS选择性培养基,从健康新生儿粪便和母乳中筛选乳杆菌并鉴定种类;以鼠李糖乳杆菌LGG为阳性对照,体外评估菌株的益生菌特性;利用盐酸苯肼诱导...为筛选高产胆盐水解酶的乳杆菌,探究其对新生儿黄疸的防治作用。采用添加了25 U/mL制霉菌素的LBS选择性培养基,从健康新生儿粪便和母乳中筛选乳杆菌并鉴定种类;以鼠李糖乳杆菌LGG为阳性对照,体外评估菌株的益生菌特性;利用盐酸苯肼诱导新生SD大鼠黄疸模型,通过分析血清胆红素水平和肝脏组织的损伤情况,以及肝脏炎症因子、核转录因子的相对表达水平,探究高产胆盐水解酶乳杆菌对新生大鼠黄疸的防治作用及机制。结果表明,来自婴儿粪便的格氏乳杆菌FWJL-5在体外具良好的益生特性,并且产胆盐水解酶能力优于LGG,能够显著缓解新生大鼠胆红素水平升高、肝脏组织肿胀和溶血症状,减少肝脏损伤中肝酶的释放,抑制促炎因子的分泌,促进UGt1A1和上游核转录因子孕烷X受体(pregnane X receptor,pXR)、法尼醇X受体(farnesol X receptor,FXR)的表达。综上所述,婴儿粪便来源的格氏乳杆菌FWJL-5可通过上调核受体FXR/pXR促进UGt1A1表达以调节肝脏胆红素代谢,从而减轻新生大鼠黄疸症状,本研究可为格氏乳杆菌防治新生儿黄疸提供新思路。展开更多
The brain injury associated with neonatal hypoxia ischemia（HI）is a major contributor to neonatal mortality and neurodevelopment retardation.Approximately 30-40%of infants with brain injury will die and 20-40%of surv...The brain injury associated with neonatal hypoxia ischemia（HI）is a major contributor to neonatal mortality and neurodevelopment retardation.Approximately 30-40%of infants with brain injury will die and 20-40%of survivors will develop significant neurological disorders and lifelong disability.展开更多
Function of lactate:Lactate is a three-carbon molecule produced by glycolytic metabolism that is a metabolic waste product with no known use in clinical therapy.Conversely,it is a metabolite that the body should quick...Function of lactate:Lactate is a three-carbon molecule produced by glycolytic metabolism that is a metabolic waste product with no known use in clinical therapy.Conversely,it is a metabolite that the body should quickly guarantee the clearance.However,lactate is now recognized as a potential energy substrate,as well as an anti-inflammatory signaling molecule.These actions were first reported in adult animal models with a brain injury,including a traumatic brain injury and cerebral ischemia,and have also been observed in human patients(Magistretti and Allaman,2018).Recently,however,two studies by independent research groups described promising n euro p rotective results from the use of lactate in animal models with neonatal hypoxia-ischemia(Roumes et al.,2021;Tassinari et al.,2020).展开更多
Application of TMS technology in newborn screening has resulted in major expansion of disorder panel for metabolic diseases in recent years. This automated, multiplex testing methodology detects multiple analytes from...Application of TMS technology in newborn screening has resulted in major expansion of disorder panel for metabolic diseases in recent years. This automated, multiplex testing methodology detects multiple analytes from single analysis of one blood spot, which leads to detection of 30-35 disorders of amino acids, organic acids, and fatty acids metabolism. The early identification of persons affected with inborn errors of metabolism has led to unexpected discoveries related to the natural history of the disorder or options for therapy. This article summarized (1) the basic principles of this technology and methodology. (2) Current status of application of this methodology in the United States, European countries and in China. (3) The positive impacts on the public health and advances in medical genetics. Finally (4) Challenges, issues and possible solutions. The purpose of this article aimed at introducing new technology and exploring the possibilities of implementing into developing countries where medical genetics is not developed and foreseeing the possible problems and obstacles.展开更多
基金Supported by the National Natural Science Foundation of China(No.81273934 and No.81874410)。
文摘Objective To investigate the effects and underlying mechanisms of Panax quinquefolium saponin(PQS)on energy deficiency in hypoxia-reperfusion(H/R)induced cardiomyocytes.Methods The H/R injury involved hypoxia for 3 h and then reperfusion for 2 h.Cardiomyocytes recruited from neonatal rat ventricular myocytes(NRVMs)were randomly divided into control,H/R,H/R+compound C(C.C),H/R+PQS,and H/R+C.C+PQS groups.BrdU assay,lactase dehydrogenase(LDH)leakage and early apoptosis rate were evaluated to assess cell damages.Contents of high energy phosphate compounds were conducted to detect the energy production.Protein expression levels of adenosine monophosphate-activated protein kinase a(AMPKα),glucose transporter 4(GLUT4),phosphate fructose kinase 2(PFK2),fatty acid translocase/cluster of differentiation 36(FAT/CD36),and acetyl CoA carboxylase 2(ACC2)in the regulatory pathways were measured by Western blotting.Immunofluorescence staining of GLUT4 and FAT/CD36 was used to observe the mobilization of metabolic transporters.Results PQS(50 mg/L)pretreatment significantly alleviated H/R-induced inhibition of NRVMs viability,up-regulation of LDH leakage,acceleration of early apoptosis,and reduction of energy production(P<0.05).Compared with the H/R group,up-regulated expression of AMPKα,GLUT4,PFK2,FAT/CD36 and ACC2 were observed,and more GLUT4 and FAT/CD36 expressions were detected on the membrane in the H/R+PQS group(P<0.05).These effects of PQS on H/R-induced NRVMs were eliminated in the H/R+C.C+PQS group(P<0.05).Conclusion PQS has prominent advantages in protecting NRVMs from H/R-induced cell damages and energy metabolic disorders,by activation of AMPKα-mediated GLUT4-PFK2 and FAT/CD36-ACC2 pathways.
文摘为筛选高产胆盐水解酶的乳杆菌,探究其对新生儿黄疸的防治作用。采用添加了25 U/mL制霉菌素的LBS选择性培养基,从健康新生儿粪便和母乳中筛选乳杆菌并鉴定种类;以鼠李糖乳杆菌LGG为阳性对照,体外评估菌株的益生菌特性;利用盐酸苯肼诱导新生SD大鼠黄疸模型,通过分析血清胆红素水平和肝脏组织的损伤情况,以及肝脏炎症因子、核转录因子的相对表达水平,探究高产胆盐水解酶乳杆菌对新生大鼠黄疸的防治作用及机制。结果表明,来自婴儿粪便的格氏乳杆菌FWJL-5在体外具良好的益生特性,并且产胆盐水解酶能力优于LGG,能够显著缓解新生大鼠胆红素水平升高、肝脏组织肿胀和溶血症状,减少肝脏损伤中肝酶的释放,抑制促炎因子的分泌,促进UGt1A1和上游核转录因子孕烷X受体(pregnane X receptor,pXR)、法尼醇X受体(farnesol X receptor,FXR)的表达。综上所述,婴儿粪便来源的格氏乳杆菌FWJL-5可通过上调核受体FXR/pXR促进UGt1A1表达以调节肝脏胆红素代谢,从而减轻新生大鼠黄疸症状,本研究可为格氏乳杆菌防治新生儿黄疸提供新思路。
基金supported in part by National Institutes of Health grants(HL60190,HL67841,and P01HL0101902)
文摘The brain injury associated with neonatal hypoxia ischemia（HI）is a major contributor to neonatal mortality and neurodevelopment retardation.Approximately 30-40%of infants with brain injury will die and 20-40%of survivors will develop significant neurological disorders and lifelong disability.
基金funding from Conselho Nacional de Desenvolvimento Científico e Tecnológico(CNPq-Brazil)Coordenacao de Aperfeicoamento de Pessoal de Nível Superior(CAPES-Brazil)+1 种基金Fundacao de AmparoàPesquisa do Estado do Rio Grande do Sul(FAPERGS-Brazil)Fundo de IncentivoàPesquisa e Eventos do Hospital de Clínicas de Porto Alegre(FIPE/HCPA-Brazil)(to LSdeF)。
文摘Function of lactate:Lactate is a three-carbon molecule produced by glycolytic metabolism that is a metabolic waste product with no known use in clinical therapy.Conversely,it is a metabolite that the body should quickly guarantee the clearance.However,lactate is now recognized as a potential energy substrate,as well as an anti-inflammatory signaling molecule.These actions were first reported in adult animal models with a brain injury,including a traumatic brain injury and cerebral ischemia,and have also been observed in human patients(Magistretti and Allaman,2018).Recently,however,two studies by independent research groups described promising n euro p rotective results from the use of lactate in animal models with neonatal hypoxia-ischemia(Roumes et al.,2021;Tassinari et al.,2020).
文摘Application of TMS technology in newborn screening has resulted in major expansion of disorder panel for metabolic diseases in recent years. This automated, multiplex testing methodology detects multiple analytes from single analysis of one blood spot, which leads to detection of 30-35 disorders of amino acids, organic acids, and fatty acids metabolism. The early identification of persons affected with inborn errors of metabolism has led to unexpected discoveries related to the natural history of the disorder or options for therapy. This article summarized (1) the basic principles of this technology and methodology. (2) Current status of application of this methodology in the United States, European countries and in China. (3) The positive impacts on the public health and advances in medical genetics. Finally (4) Challenges, issues and possible solutions. The purpose of this article aimed at introducing new technology and exploring the possibilities of implementing into developing countries where medical genetics is not developed and foreseeing the possible problems and obstacles.
