AIM:To investigate the protective role of ghrelin against diabetic retinopathy(DR),focusing on its anti-ferroptotic mechanism in high glucose-induced retinal endothelial injury.METHODS:First,small interfering RNA(siRN...AIM:To investigate the protective role of ghrelin against diabetic retinopathy(DR),focusing on its anti-ferroptotic mechanism in high glucose-induced retinal endothelial injury.METHODS:First,small interfering RNA(siRNA)-mediated interference was conducted to knockdown nuclear factor erythroid 2-related factor 2(Nrf2).Using reverse transcription-polymerase chain reaction(RT-PCR),the expression level of Nrf2 was determined from human retinal microvascular endothelial cells(HRMECs)transfected with either si-NC or si-Nrf2.After that,cells were treated with 10 nmol/L ghrelin and then cultured in a high glucose(30 mmol/L)environment.EdU assay was utilized to assess cell proliferation,while transmission electron microscopy was employed to observe mitochondrial morphology.Flow cytometry was used to measure the level of intracellular reactive oxygen species(ROS),and biochemical assays were conducted to detect malondialdehyde(MDA),glutathione(GSH),superoxide dismutase(SOD),and ferrous iron(Fe2+).Western blotting was used to identify the presence of ferroptosis-related proteins such as glutathione peroxidase 4(GPX4),solute carrier family 7 member 11(SLC7A11),Nrf2,and haem oxygenase-1(HO-1).RESULTS:Under a high glucose environment,ghrelin could significantly promote the proliferation of HRMECs and mitochondrial status,remarkably decrease the levels of intracellular ROS and MDA,and up-regulate the level of GSH and SOD.Besides,ghrelin greatly reduced Fe2+level in the cells while increased protein levels of GPX4 and SLC7A11.Subsequently,we found that high glucose induced inactivation of Nrf2/HO-1 axis and the protein expression profile were significantly promoted by ghrelin.Moreover,silencing of Nrf2 by siRNA delivery markedly diminished the changes induced by ghrelin in high glucose-induced HRMECs,shown as reduced cell proliferation and increased mitochondrial malformation,up-regulated ROS,MDA,Fe^(2+),GPX4 and SLC7A11,as well as down-regulated GSH,SOD,Nrf2 and HO-1.CONCLUSION:Ghrelin attenuates high glucose-induced injury of retinal endothelial cells via inhibiting ferroptosis,and activation of Nrf2/HO-1 pathway may be one of the mechanisms involved in this effect of ghrelin.展开更多
目的分析首发精神分裂症患者认知水平与血清高迁移率族蛋白B1(high mobil ity group protein B1,HMGB1)、胃饥饿素(Ghrelin)、程序性细胞死亡因子4(programmed cell death factor 4,PDCD4)的相关性。方法选定乌鲁木齐市第四人民医院2021...目的分析首发精神分裂症患者认知水平与血清高迁移率族蛋白B1(high mobil ity group protein B1,HMGB1)、胃饥饿素(Ghrelin)、程序性细胞死亡因子4(programmed cell death factor 4,PDCD4)的相关性。方法选定乌鲁木齐市第四人民医院2021年6月~2023年6月就诊的60例首发精神分裂症患者为研究对象,以MATRICS公认认知成套测验(MATRICS consensus cognitive battery,MCCB)量表对患者进行认知功能评价,以MCCB量表评价患者认知功能并分组,比较认知功能正常组(39例)、认知功能障碍组(21例)阳性阴性症状评定量表(PANSS)评分、血清HMGB1、Ghrelin、PDCD4水平的差异,Pearson分析血清HMGB1、Ghrelin、PDCD4与MCCB评分、PANSS评分的相关性。结果认知功能障碍组MCCB评分、血清Ghrelin、PDCD4水平均低于认知功能正常组(P<0.05);认知功能障碍组PANSS评分、血清HMGB1均高于认知功能正常组(P<0.05);血清HMGB1与MCCB评分呈负相关性(P<0.05,r值=-0.394),与PANSS评分呈正相关性(P<0.05,r值=0.405),血清Ghrelin、PDCD4与MCCB评分均呈正相关性(P均<0.05,r值=0.386、0.412),血清Ghrelin、PDCD4与PANSS评分均呈负相关性(P<0.05,r值=-0.392、-0.402)。结论首发精神分裂症患者血清Ghrelin、PDCD4水平较低,血清HMGB1水平较高,血清HMGB1、Ghrelin、PDCD4与首发精神分裂症患者认知功能具有相关性。展开更多
基金Supported by the Scientific Research Development Project of North Sichuan Medical College(No.CBY24-QDA01)Science and Technology Program of Shaanxi Province(No.2024SF-YBXM-324,No.2024SFYBXM-341).
文摘AIM:To investigate the protective role of ghrelin against diabetic retinopathy(DR),focusing on its anti-ferroptotic mechanism in high glucose-induced retinal endothelial injury.METHODS:First,small interfering RNA(siRNA)-mediated interference was conducted to knockdown nuclear factor erythroid 2-related factor 2(Nrf2).Using reverse transcription-polymerase chain reaction(RT-PCR),the expression level of Nrf2 was determined from human retinal microvascular endothelial cells(HRMECs)transfected with either si-NC or si-Nrf2.After that,cells were treated with 10 nmol/L ghrelin and then cultured in a high glucose(30 mmol/L)environment.EdU assay was utilized to assess cell proliferation,while transmission electron microscopy was employed to observe mitochondrial morphology.Flow cytometry was used to measure the level of intracellular reactive oxygen species(ROS),and biochemical assays were conducted to detect malondialdehyde(MDA),glutathione(GSH),superoxide dismutase(SOD),and ferrous iron(Fe2+).Western blotting was used to identify the presence of ferroptosis-related proteins such as glutathione peroxidase 4(GPX4),solute carrier family 7 member 11(SLC7A11),Nrf2,and haem oxygenase-1(HO-1).RESULTS:Under a high glucose environment,ghrelin could significantly promote the proliferation of HRMECs and mitochondrial status,remarkably decrease the levels of intracellular ROS and MDA,and up-regulate the level of GSH and SOD.Besides,ghrelin greatly reduced Fe2+level in the cells while increased protein levels of GPX4 and SLC7A11.Subsequently,we found that high glucose induced inactivation of Nrf2/HO-1 axis and the protein expression profile were significantly promoted by ghrelin.Moreover,silencing of Nrf2 by siRNA delivery markedly diminished the changes induced by ghrelin in high glucose-induced HRMECs,shown as reduced cell proliferation and increased mitochondrial malformation,up-regulated ROS,MDA,Fe^(2+),GPX4 and SLC7A11,as well as down-regulated GSH,SOD,Nrf2 and HO-1.CONCLUSION:Ghrelin attenuates high glucose-induced injury of retinal endothelial cells via inhibiting ferroptosis,and activation of Nrf2/HO-1 pathway may be one of the mechanisms involved in this effect of ghrelin.
文摘目的分析首发精神分裂症患者认知水平与血清高迁移率族蛋白B1(high mobil ity group protein B1,HMGB1)、胃饥饿素(Ghrelin)、程序性细胞死亡因子4(programmed cell death factor 4,PDCD4)的相关性。方法选定乌鲁木齐市第四人民医院2021年6月~2023年6月就诊的60例首发精神分裂症患者为研究对象,以MATRICS公认认知成套测验(MATRICS consensus cognitive battery,MCCB)量表对患者进行认知功能评价,以MCCB量表评价患者认知功能并分组,比较认知功能正常组(39例)、认知功能障碍组(21例)阳性阴性症状评定量表(PANSS)评分、血清HMGB1、Ghrelin、PDCD4水平的差异,Pearson分析血清HMGB1、Ghrelin、PDCD4与MCCB评分、PANSS评分的相关性。结果认知功能障碍组MCCB评分、血清Ghrelin、PDCD4水平均低于认知功能正常组(P<0.05);认知功能障碍组PANSS评分、血清HMGB1均高于认知功能正常组(P<0.05);血清HMGB1与MCCB评分呈负相关性(P<0.05,r值=-0.394),与PANSS评分呈正相关性(P<0.05,r值=0.405),血清Ghrelin、PDCD4与MCCB评分均呈正相关性(P均<0.05,r值=0.386、0.412),血清Ghrelin、PDCD4与PANSS评分均呈负相关性(P<0.05,r值=-0.392、-0.402)。结论首发精神分裂症患者血清Ghrelin、PDCD4水平较低,血清HMGB1水平较高,血清HMGB1、Ghrelin、PDCD4与首发精神分裂症患者认知功能具有相关性。
