Background Oxidative stress,caused by an imbalance in the production and elimination of intracellular reactive oxygen species(ROS),has been recognized for its detrimental effects on mammalian embryonic development.Lut...Background Oxidative stress,caused by an imbalance in the production and elimination of intracellular reactive oxygen species(ROS),has been recognized for its detrimental effects on mammalian embryonic development.Luteolin(Lut)has been documented for its protective effects against oxidative stress in various studies.However,its specific role in embryonic development remains unexplored.This study aims to investigate the influence of Lut on porcine embryonic development and to elucidate the underlying mechanism.Results After undergoing parthenogenetic activation(PA)or in vitro fertilization,embryos supplemented with 0.5μmol/L Lut displayed a significant enhancement in cleavage and blastocyst formation rates,with an increase in total cell numbers and a decrease in the apoptosis rate compared to the control.Measurements on D2 and D6 revealed that embryos with Lut supplementation had lower ROS levels and higher glutathione levels compared to the control.Moreover,Lut supplementation significantly augmented mitochondrial content and membrane potential.Intriguingly,activation of the Nrf2/Keap1 signaling pathway was observed in embryos supplemented with Lut,leading to the upregulation of antioxidant-related gene transcription levels.To further validate the relationship between the Nrf2/Keap1 signaling pathway and effects of Lut in porcine embryonic development,we cultured PA embryos in a medium supplemented with brusatol,with or without the inclusion of Lut.The positive effects of Lut on developmental competence were negated by brusatol treatment.Conclusions Our findings indicate that Lut-mediated activation of the Nrf2/Keap1 signaling pathway contributes to the enhanced production of porcine embryos with high developmental competence,and offers insight into the mechanisms regulating early embryonic development.展开更多
目的观察达格列净通过Nrf2/Keap1信号通路对成人1型糖尿病患者血糖波动及尿酸的影响。方法选择2019年1月—2020年12月长沙市第四医院(湖南师范大学附属长沙医院)内分泌科收治成人1型糖尿病患者66例作为研究对象,随机数字表法分为对照组(...目的观察达格列净通过Nrf2/Keap1信号通路对成人1型糖尿病患者血糖波动及尿酸的影响。方法选择2019年1月—2020年12月长沙市第四医院(湖南师范大学附属长沙医院)内分泌科收治成人1型糖尿病患者66例作为研究对象,随机数字表法分为对照组(n=33)和观察组(n=33)。对照组给予胰岛素治疗,观察组给予胰岛素加达格列净治疗。治疗3个月,比较2组患者治疗前后血清Nrf2、Keap1水平的变化、动态血糖监测指标、胰岛β细胞功能及不良反应发生情况。结果与治疗前比较,治疗后2组患者血清Nrf2、Keap1水平及平均血糖波动幅度(MAGE)、血糖标准差(SDBG)、血糖平均水平(MBG)、最大血糖波动幅度(LAGE)、尿酸(UA)、每日胰岛素值均降低,空腹C肽(FC-P)、餐后2 h C肽(2 h C-P)均明显升高,且观察组各项指标改善较对照组更显著(t/P=4.838/<0.001、6.345/<0.001、4.742/<0.001、10.196/<0.001、4.555/<0.001、6.632/<0.001、11.598/<0.001、14.688/<0.001、12.196/<0.001、15.729/<0.001)。2组患者不良反应发生率比较差异无统计学意义(P>0.05)。结论达格列净治疗成人1型糖尿病,可有效控制血糖,改善胰岛β细胞功能,降低血清Nrf2、Keap1及尿酸水平,改善机体氧化应激反应,安全性高。展开更多
基金supported by the Korea Research Institute of Bioscience and Biotechnology(KRIBB)Research Initiative Program(KGM4252331,KGM5382322),Republic of Korea.
文摘Background Oxidative stress,caused by an imbalance in the production and elimination of intracellular reactive oxygen species(ROS),has been recognized for its detrimental effects on mammalian embryonic development.Luteolin(Lut)has been documented for its protective effects against oxidative stress in various studies.However,its specific role in embryonic development remains unexplored.This study aims to investigate the influence of Lut on porcine embryonic development and to elucidate the underlying mechanism.Results After undergoing parthenogenetic activation(PA)or in vitro fertilization,embryos supplemented with 0.5μmol/L Lut displayed a significant enhancement in cleavage and blastocyst formation rates,with an increase in total cell numbers and a decrease in the apoptosis rate compared to the control.Measurements on D2 and D6 revealed that embryos with Lut supplementation had lower ROS levels and higher glutathione levels compared to the control.Moreover,Lut supplementation significantly augmented mitochondrial content and membrane potential.Intriguingly,activation of the Nrf2/Keap1 signaling pathway was observed in embryos supplemented with Lut,leading to the upregulation of antioxidant-related gene transcription levels.To further validate the relationship between the Nrf2/Keap1 signaling pathway and effects of Lut in porcine embryonic development,we cultured PA embryos in a medium supplemented with brusatol,with or without the inclusion of Lut.The positive effects of Lut on developmental competence were negated by brusatol treatment.Conclusions Our findings indicate that Lut-mediated activation of the Nrf2/Keap1 signaling pathway contributes to the enhanced production of porcine embryos with high developmental competence,and offers insight into the mechanisms regulating early embryonic development.
文摘目的观察达格列净通过Nrf2/Keap1信号通路对成人1型糖尿病患者血糖波动及尿酸的影响。方法选择2019年1月—2020年12月长沙市第四医院(湖南师范大学附属长沙医院)内分泌科收治成人1型糖尿病患者66例作为研究对象,随机数字表法分为对照组(n=33)和观察组(n=33)。对照组给予胰岛素治疗,观察组给予胰岛素加达格列净治疗。治疗3个月,比较2组患者治疗前后血清Nrf2、Keap1水平的变化、动态血糖监测指标、胰岛β细胞功能及不良反应发生情况。结果与治疗前比较,治疗后2组患者血清Nrf2、Keap1水平及平均血糖波动幅度(MAGE)、血糖标准差(SDBG)、血糖平均水平(MBG)、最大血糖波动幅度(LAGE)、尿酸(UA)、每日胰岛素值均降低,空腹C肽(FC-P)、餐后2 h C肽(2 h C-P)均明显升高,且观察组各项指标改善较对照组更显著(t/P=4.838/<0.001、6.345/<0.001、4.742/<0.001、10.196/<0.001、4.555/<0.001、6.632/<0.001、11.598/<0.001、14.688/<0.001、12.196/<0.001、15.729/<0.001)。2组患者不良反应发生率比较差异无统计学意义(P>0.05)。结论达格列净治疗成人1型糖尿病,可有效控制血糖,改善胰岛β细胞功能,降低血清Nrf2、Keap1及尿酸水平,改善机体氧化应激反应,安全性高。
