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
Objective:To investigate the mechanism of serum uric acid in Ankylosing spondylitis(AS)through the Kelch-like ECH-Associating protein 1(Keap1)-nuclear factor erythroid 2 related factor 2(Nrf2)signaling pathway.Methods...Objective:To investigate the mechanism of serum uric acid in Ankylosing spondylitis(AS)through the Kelch-like ECH-Associating protein 1(Keap1)-nuclear factor erythroid 2 related factor 2(Nrf2)signaling pathway.Methods:A total of 60 AS patients in our hospital from March 2018 to October 2019 were recruited and divided into the active group(>4 points,26 cases)and the inactive group(≤4 points,34 cases)according to the Bath Ankylosing Spondylitis Disease Activity Index(BASDAI).Keap1,Nrf2,catalase(CAT),superoxide dismutase(SOD),Malondialdehyde(MDA),reactive nitrogen species(RNS),reactive oxygen species(ROS)were detected by ELISA;furthermore,erythrocyte sedimentation rate(ESR),Uric acid(UA)and C-reactive protein(CRP)were tested.The relationship among UA,BASDAI and oxidative stress indicators were analyzed.Results:The expression levels of ESR,CRP,UA,ROS,RNS,MDA,and Keap1 in the active group were significantly higher than those in the inactive group(all P<0.001);the levels of Nrf2,CAT,and SOD in the active group were higher than those in the inactive group,markedly reduced(all P<0.001)in the inactive group.The Pearson's correlation coefficient showed that ROS,RNS,MDA,and Keap1 were notably positively correlated with blood UA and BASDAI in the active group with AS patients;while Nrf2,CAT,and SOD were negatively correlated with blood UA and BASDAI.Moreover,blood UA and BASDAI were found to be moderately positively correlated.Conclusion:The results in the study demonstrate that the UA level in blood is related to the AS disease activity,blood UA exerts the pro-inflammatory effects,increasing oxidative stress injury and reducing antioxidant capacity,possibly by activating the Keap1-Nrf2 pathway.展开更多
Age-related eye diseases,including cataract,glaucoma,diabetic retinopathy(DR),and age-related macular degeneration(AMD),are the leading causes of vision loss in the world.Several studies have shown that the occurrence...Age-related eye diseases,including cataract,glaucoma,diabetic retinopathy(DR),and age-related macular degeneration(AMD),are the leading causes of vision loss in the world.Several studies have shown that the occurrence and development of these diseases have an important relationship with oxidative stress in the eye.The Keap1-Nrf2-ARE pathway is a classical pathway that resists oxidative stress and inflammation in the body.This pathway is also active in the development of age-related eye diseases.A variety of drugs have been shown to treat agerelated eye diseases through the Keap1-Nrf2-ARE(Kelch-like ECH-Associating protein 1-nuclear factor erythroid 2 related factor 2-antioxidant response element)pathway.This review describes the role of oxidative stress in the development of age-related eye diseases,the function and regulation of the Keap1-Nrf2-ARE pathway,and the therapeutic effects of drugs associated with this pathway on age-related eye diseases.展开更多
Grape skin,one of the by-products of grape processing,is rich in oxyresveratrol and other bioactive compounds.Oxyresveratrol is a polyphenolic non-flavonoid with anti-inflammatory and anti-aging properties among other...Grape skin,one of the by-products of grape processing,is rich in oxyresveratrol and other bioactive compounds.Oxyresveratrol is a polyphenolic non-flavonoid with anti-inflammatory and anti-aging properties among other biological activities,but little research has been done on its antioxidant mechanism.This study aims to evaluate the regulation of oxyresveratrol on Keap1-Nrf2-ARE signaling pathway.Firstly,oxyresveratrol in grape skin was detected by HPLC-MS/MS,and then its interaction mechanism with Keap1 was investigated by molecular docking.The result of Western blot further confirmed that oxyresveratrol can bind with Nrf2 to induce its nuclear translocation.The Luciferase reporter gene analysis revealed the agonistic effects of oxyresveratrol on ARE.Oxyresveratrol increased not only the mRNA expression levels of ARE-mediated genes NQO1,HO-1,and GCLM,but also their protein expression levels,suggesting that oxyresveratrol inhibited H2 O2-induced oxidative damage.Therefore,oxyresveratrol can be applied as a potential antioxidant by activating the Keap-Nrf2-ARE signaling pathway.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.
基金Hainan health and family planning industry scientific research project (18A200018)
文摘Objective:To investigate the mechanism of serum uric acid in Ankylosing spondylitis(AS)through the Kelch-like ECH-Associating protein 1(Keap1)-nuclear factor erythroid 2 related factor 2(Nrf2)signaling pathway.Methods:A total of 60 AS patients in our hospital from March 2018 to October 2019 were recruited and divided into the active group(>4 points,26 cases)and the inactive group(≤4 points,34 cases)according to the Bath Ankylosing Spondylitis Disease Activity Index(BASDAI).Keap1,Nrf2,catalase(CAT),superoxide dismutase(SOD),Malondialdehyde(MDA),reactive nitrogen species(RNS),reactive oxygen species(ROS)were detected by ELISA;furthermore,erythrocyte sedimentation rate(ESR),Uric acid(UA)and C-reactive protein(CRP)were tested.The relationship among UA,BASDAI and oxidative stress indicators were analyzed.Results:The expression levels of ESR,CRP,UA,ROS,RNS,MDA,and Keap1 in the active group were significantly higher than those in the inactive group(all P<0.001);the levels of Nrf2,CAT,and SOD in the active group were higher than those in the inactive group,markedly reduced(all P<0.001)in the inactive group.The Pearson's correlation coefficient showed that ROS,RNS,MDA,and Keap1 were notably positively correlated with blood UA and BASDAI in the active group with AS patients;while Nrf2,CAT,and SOD were negatively correlated with blood UA and BASDAI.Moreover,blood UA and BASDAI were found to be moderately positively correlated.Conclusion:The results in the study demonstrate that the UA level in blood is related to the AS disease activity,blood UA exerts the pro-inflammatory effects,increasing oxidative stress injury and reducing antioxidant capacity,possibly by activating the Keap1-Nrf2 pathway.
基金Supported by National Natural Science Foundation of China(No.81970801No.81670859)+1 种基金Natural Science Foundation of Hunan Province(No.2019JJ40001)Key Project of Changsha Science and Technology Bureau(No.kh1801229)。
文摘Age-related eye diseases,including cataract,glaucoma,diabetic retinopathy(DR),and age-related macular degeneration(AMD),are the leading causes of vision loss in the world.Several studies have shown that the occurrence and development of these diseases have an important relationship with oxidative stress in the eye.The Keap1-Nrf2-ARE pathway is a classical pathway that resists oxidative stress and inflammation in the body.This pathway is also active in the development of age-related eye diseases.A variety of drugs have been shown to treat agerelated eye diseases through the Keap1-Nrf2-ARE(Kelch-like ECH-Associating protein 1-nuclear factor erythroid 2 related factor 2-antioxidant response element)pathway.This review describes the role of oxidative stress in the development of age-related eye diseases,the function and regulation of the Keap1-Nrf2-ARE pathway,and the therapeutic effects of drugs associated with this pathway on age-related eye diseases.
基金supported by the Agricultural Science and Technology Innovation Program of Jilin Province(KYJF2021JQ010,CXGC2021TD006 and CXGC2021RCY028)the Capital Construction Funds within the Provincial Budget in 2022(2022c043-12)+2 种基金the Science and Technology Development Project Foundation of Jilin Province(20210203182SF)the Administration of Traditional Chinese Medicine of Jilin Province(2021100)the National Key Research and Development Program(2021YFD1200103).
文摘Grape skin,one of the by-products of grape processing,is rich in oxyresveratrol and other bioactive compounds.Oxyresveratrol is a polyphenolic non-flavonoid with anti-inflammatory and anti-aging properties among other biological activities,but little research has been done on its antioxidant mechanism.This study aims to evaluate the regulation of oxyresveratrol on Keap1-Nrf2-ARE signaling pathway.Firstly,oxyresveratrol in grape skin was detected by HPLC-MS/MS,and then its interaction mechanism with Keap1 was investigated by molecular docking.The result of Western blot further confirmed that oxyresveratrol can bind with Nrf2 to induce its nuclear translocation.The Luciferase reporter gene analysis revealed the agonistic effects of oxyresveratrol on ARE.Oxyresveratrol increased not only the mRNA expression levels of ARE-mediated genes NQO1,HO-1,and GCLM,but also their protein expression levels,suggesting that oxyresveratrol inhibited H2 O2-induced oxidative damage.Therefore,oxyresveratrol can be applied as a potential antioxidant by activating the Keap-Nrf2-ARE signaling pathway.
