OBJECTIVE Refractory wounds in diabetic patients constitute a serious complication that often leads to amputation with limited treatment regimens.Recent studies have shown that the imbalance of mitochondrial dynamics ...OBJECTIVE Refractory wounds in diabetic patients constitute a serious complication that often leads to amputation with limited treatment regimens.Recent studies have shown that the imbalance of mitochondrial dynamics was associated with the increased reactive oxygen species(ROS)production in endothelial cells,which is a significant contributor to the microvascular complications of diabetes.The present study was designed to determine the involvement of transcription factor FOXO1in diabetic wound healing and investigate underlying mechanisms.METHODS&RESULTS Impaired mitochondrial networks and increased phosphorylation of dynaminrelated protein-1(Drp1)at ser616,a protein required for mitochondrial fission,were observed in human umbilical vein endothelial cells(HUVECs)24 h after exposure to high concentrations of glucose.Inhibition of FOXO1 by si RNA or by FOXO1 selective inhibitor AS1842856 abrogated high glucos-induced alterations in mitochondrial networks and phosphorylation of Drp1.Treatment with AS1842856 or si RNA of FOXO1 could significantly increase the mitochondrial membrane potential and suppress the overproduction of ROS induced by high glucose.Addition of AS1842856 inhibited glucoseinduced apoptosis,ameliorated capillary tube formation in HUVECs.In vivo,AS1842856 dose-dependently rescued the delay of wound closure in diabetic mice,and5 mg·kg-1of AS1842856 treatment significantly increased the mean perfusion rate.CONCLUSION These findings suggested that FOXO1 is critical to preserve mitochondrial quantity and function in endothelial cells,inhibition of FOXO1 rescued the delayed wound healing and improved wound angiogenesis in diabetic mice.展开更多
The anisotropy of dipole-dipole interaction is revealed by energy band,tunneling dynamics and stabilities of a dipolar condensate in one-dimensional optical lattices.It is demonstrated that the Bloch band structure,th...The anisotropy of dipole-dipole interaction is revealed by energy band,tunneling dynamics and stabilities of a dipolar condensate in one-dimensional optical lattices.It is demonstrated that the Bloch band structure,the tunneling rate between Bloch bands and the stabilities of Bloch states can be controlled by adjusting the effective aspect ratio of the condensate and the dipolar orientation.展开更多
基金The project supported by National Natural Science Foundation of China(81373405,30901803)Beijing Higher Education Young Elite Teacher Project(YETP0053)
文摘OBJECTIVE Refractory wounds in diabetic patients constitute a serious complication that often leads to amputation with limited treatment regimens.Recent studies have shown that the imbalance of mitochondrial dynamics was associated with the increased reactive oxygen species(ROS)production in endothelial cells,which is a significant contributor to the microvascular complications of diabetes.The present study was designed to determine the involvement of transcription factor FOXO1in diabetic wound healing and investigate underlying mechanisms.METHODS&RESULTS Impaired mitochondrial networks and increased phosphorylation of dynaminrelated protein-1(Drp1)at ser616,a protein required for mitochondrial fission,were observed in human umbilical vein endothelial cells(HUVECs)24 h after exposure to high concentrations of glucose.Inhibition of FOXO1 by si RNA or by FOXO1 selective inhibitor AS1842856 abrogated high glucos-induced alterations in mitochondrial networks and phosphorylation of Drp1.Treatment with AS1842856 or si RNA of FOXO1 could significantly increase the mitochondrial membrane potential and suppress the overproduction of ROS induced by high glucose.Addition of AS1842856 inhibited glucoseinduced apoptosis,ameliorated capillary tube formation in HUVECs.In vivo,AS1842856 dose-dependently rescued the delay of wound closure in diabetic mice,and5 mg·kg-1of AS1842856 treatment significantly increased the mean perfusion rate.CONCLUSION These findings suggested that FOXO1 is critical to preserve mitochondrial quantity and function in endothelial cells,inhibition of FOXO1 rescued the delayed wound healing and improved wound angiogenesis in diabetic mice.
基金Supportrd by the National Natural Science Foundation of China under Grant Nos 10774120 and 10975114the Natural Science Foundation of Gansu Province under Grant No 1010RJZA012the Natural Science Foundation of Northwest Normal University(NWNU-KJCXGC-03-48).
文摘The anisotropy of dipole-dipole interaction is revealed by energy band,tunneling dynamics and stabilities of a dipolar condensate in one-dimensional optical lattices.It is demonstrated that the Bloch band structure,the tunneling rate between Bloch bands and the stabilities of Bloch states can be controlled by adjusting the effective aspect ratio of the condensate and the dipolar orientation.