BACKGROUND Diabetic retinopathy(DR)is the primary cause of visual problems in patients with diabetes.The Heyingwuzi formulation(HYWZF)is effective against DR.AIM To determine the HYWZF prevention mechanisms,especially...BACKGROUND Diabetic retinopathy(DR)is the primary cause of visual problems in patients with diabetes.The Heyingwuzi formulation(HYWZF)is effective against DR.AIM To determine the HYWZF prevention mechanisms,especially those underlying mitophagy.METHODS Human retinal capillary endothelial cells(HRCECs)were treated with high glucose(hg),HYWZF serum,PX-478,or Mdivi-1 in vitro.Then,cell counting kit-8,transwell,and tube formation assays were used to evaluate HRCEC proliferation,invasion,and tube formation,respectively.Transmission electron microscopy was used to assess mitochondrial morphology,and Western blotting was used to determine the protein levels.Flow cytometry was used to assess cell apoptosis,reactive oxygen species(ROS)production,and mitochondrial membrane potential.Moreover,C57BL/6 mice were established in vivo using streptozotocin and treated with HYWZF for four weeks.Blood glucose levels and body weight were monitored continuously.Changes in retinal characteristics were evaluated using hematoxylin and eosin,tar violet,and periodic acid-Schiff staining.Protein levels in retinal tissues were determined via Western blotting,immunohistochemistry,and immunostaining.RESULTS HYWZF inhibited excessive ROS production,apoptosis,tube formation,and invasion in hg-induced HRCECs via mitochondrial autophagy in vitro.It increased the mRNA expression levels of BCL2-interacting protein 3(BNIP3),FUN14 domain-containing 1,BNIP3-like(BNIP3L,also known as NIX),PARKIN,PTEN-induced kinase 1,and hypoxia-inducible factor(HIF)-1α.Moreover,it downregulated the protein levels of vascular endothelial cell growth factor and increased the light chain 3-II/I ratio.However,PX-478 and Mdivi-1 reversed these effects.Additionally,PX-478 and Mdivi-1 rescued the effects of HYWZF by decreasing oxidative stress and apoptosis and increasing mitophagy.HYWZF intervention improved the symptoms of diabetes,tissue damage,number of acellular capillaries,and oxidative stress in vivo.Furthermore,in vivo experiments confirmed the results of in vitro experiments.CONCLUSION HYWZF alleviated DR and associated damage by promoting mitophagy via the HIF-1α/BNIP3/NIX axis.展开更多
Spinal cord ischemia-reperfusion injury,a severe form of spinal cord damage,can lead to sensory and motor dysfunction.This injury often occurs after traumatic events,spinal cord surgeries,or thoracoabdominal aortic su...Spinal cord ischemia-reperfusion injury,a severe form of spinal cord damage,can lead to sensory and motor dysfunction.This injury often occurs after traumatic events,spinal cord surgeries,or thoracoabdominal aortic surgeries.The unpredictable nature of this condition,combined with limited treatment options,poses a significant burden on patients,their families,and society.Spinal cord ischemia-reperfusion injury leads to reduced neuronal regenerative capacity and complex pathological processes.In contrast,mitophagy is crucial for degrading damaged mitochondria,thereby supporting neuronal metabolism and energy supply.However,while moderate mitophagy can be beneficial in the context of spinal cord ischemia-reperfusion injury,excessive mitophagy may be detrimental.Therefore,this review aims to investigate the potential mechanisms and regulators of mitophagy involved in the pathological processes of spinal cord ischemia-reperfusion injury.The goal is to provide a comprehensive understanding of recent advancements in mitophagy related to spinal cord ischemia-reperfusion injury and clarify its potential clinical applications.展开更多
基金Supported by the National Key Research and Development Project of China,No.2019YFC1711605National Natural Science Foundation of China,No.81904257Medical Innovation Research Project of Science and Technology Commission of Shanghai Municipality,No.21Y11923100.
文摘BACKGROUND Diabetic retinopathy(DR)is the primary cause of visual problems in patients with diabetes.The Heyingwuzi formulation(HYWZF)is effective against DR.AIM To determine the HYWZF prevention mechanisms,especially those underlying mitophagy.METHODS Human retinal capillary endothelial cells(HRCECs)were treated with high glucose(hg),HYWZF serum,PX-478,or Mdivi-1 in vitro.Then,cell counting kit-8,transwell,and tube formation assays were used to evaluate HRCEC proliferation,invasion,and tube formation,respectively.Transmission electron microscopy was used to assess mitochondrial morphology,and Western blotting was used to determine the protein levels.Flow cytometry was used to assess cell apoptosis,reactive oxygen species(ROS)production,and mitochondrial membrane potential.Moreover,C57BL/6 mice were established in vivo using streptozotocin and treated with HYWZF for four weeks.Blood glucose levels and body weight were monitored continuously.Changes in retinal characteristics were evaluated using hematoxylin and eosin,tar violet,and periodic acid-Schiff staining.Protein levels in retinal tissues were determined via Western blotting,immunohistochemistry,and immunostaining.RESULTS HYWZF inhibited excessive ROS production,apoptosis,tube formation,and invasion in hg-induced HRCECs via mitochondrial autophagy in vitro.It increased the mRNA expression levels of BCL2-interacting protein 3(BNIP3),FUN14 domain-containing 1,BNIP3-like(BNIP3L,also known as NIX),PARKIN,PTEN-induced kinase 1,and hypoxia-inducible factor(HIF)-1α.Moreover,it downregulated the protein levels of vascular endothelial cell growth factor and increased the light chain 3-II/I ratio.However,PX-478 and Mdivi-1 reversed these effects.Additionally,PX-478 and Mdivi-1 rescued the effects of HYWZF by decreasing oxidative stress and apoptosis and increasing mitophagy.HYWZF intervention improved the symptoms of diabetes,tissue damage,number of acellular capillaries,and oxidative stress in vivo.Furthermore,in vivo experiments confirmed the results of in vitro experiments.CONCLUSION HYWZF alleviated DR and associated damage by promoting mitophagy via the HIF-1α/BNIP3/NIX axis.
基金supported by Cuiying Scientific and Technological Innovation Program of Second Hospital of Lanzhou University,Nos.CY2023-QN-B18(to YD),2020QN-16(to YZ)the Natural Science Foundation of Gansu Province,No.22JR11RA082(to YZ)Key R&D Plan of Gansu Provincial Department of Science and Technology-Social Development Projects,No.23YFFA0043(to XK).
文摘Spinal cord ischemia-reperfusion injury,a severe form of spinal cord damage,can lead to sensory and motor dysfunction.This injury often occurs after traumatic events,spinal cord surgeries,or thoracoabdominal aortic surgeries.The unpredictable nature of this condition,combined with limited treatment options,poses a significant burden on patients,their families,and society.Spinal cord ischemia-reperfusion injury leads to reduced neuronal regenerative capacity and complex pathological processes.In contrast,mitophagy is crucial for degrading damaged mitochondria,thereby supporting neuronal metabolism and energy supply.However,while moderate mitophagy can be beneficial in the context of spinal cord ischemia-reperfusion injury,excessive mitophagy may be detrimental.Therefore,this review aims to investigate the potential mechanisms and regulators of mitophagy involved in the pathological processes of spinal cord ischemia-reperfusion injury.The goal is to provide a comprehensive understanding of recent advancements in mitophagy related to spinal cord ischemia-reperfusion injury and clarify its potential clinical applications.
