The Forkhead box O(FoxO) family has recently been highlighted as an important transcriptional regulator of crucial proteins associated with the many diverse functions of cells. So far, FoxO1, FoxO3 a, FoxO4 and FoxO6 ...The Forkhead box O(FoxO) family has recently been highlighted as an important transcriptional regulator of crucial proteins associated with the many diverse functions of cells. So far, FoxO1, FoxO3 a, FoxO4 and FoxO6 proteins have been identified in humans. Although each FoxO family member has its own role, unlike the other FoxO families, FoxO3 a has been extensively studied because of its rather unique and pivotal regulation of cell proliferation, apoptosis, metabolism, stress management and longevity. FoxO3 a alteration is closely linked to the progression of several types of cancers, fibrosis and other types of diseases. In this review, we will examine the function of FoxO3 a in disease progression and also explore FoxO3a's regulatory mechanisms. We will also discuss FoxO3 a as a potential target for the treatment of several types of disease.展开更多
AIM:To evaluate human gastric submucosal vascular dysfunction and its mechanism during the aging process.METHODS:Twenty male patients undergoing subtotal gastrectomy were enrolled in this study.Young and elderly patie...AIM:To evaluate human gastric submucosal vascular dysfunction and its mechanism during the aging process.METHODS:Twenty male patients undergoing subtotal gastrectomy were enrolled in this study.Young and elderly patient groups aged 25-40 years and 60-85 years,respectively,were included.Inclusion criteria were:no clinical evidence of cardiovascular,renal or diabetic diseases.Conventional clinical examinations were carried out.After surgery,gastric submucosal arteries were immediately dissected free of fat and connective tissue.Vascular responses to acetylcholine(ACh)and sodium nitroprusside(SNP)were measured by isolated vascular perfusion.Morphological changes in the gastric mucosal vessels were observed by hematoxylin and eosin(HE)staining and Verhoeff van Gieson(EVG)staining.The expression of xanthine oxidase(XO)and manganese-superoxide dismutase(Mn-SOD)was assessed by Western blotting analysis.The malondialdehyde(MDA)and hydrogen peroxide(H2O2)content and the activities of superoxide dismutase(SOD)and glutathione peroxidase(GSH-Px)were determined according to commercial kits.RESULTS:The overall structure of vessel walls was shown by HE and EVG staining,respectively.Disruption of the internal elastic lamina or neointimal layers was not observed in vessels from young or elderly patients;however,cell layer number in the vessel wall increased significantly in the elderly group.Compared with submucosal arteries in young patients,the amount of vascular collagen fibers,lumen diameter and media cross-sectional area were significantly increased in elderly patients.Ach-and SNP-induced vasodilatation in elderly arterioles was significantly decreased compared with that of gastric submucosal arterioles from young patients.Compared with the young group,the expression of XO and the contents of MDA and H2O2in gastric submucosal arterioles were increased in the elderly group.In addition,the expression of Mn-SOD and the activities of SOD and GSH-Px in the elderly group decreased significantly compared with those in the young gro展开更多
基金Supported by the National Institutes of Health R01 HL 114662 to Nho R
文摘The Forkhead box O(FoxO) family has recently been highlighted as an important transcriptional regulator of crucial proteins associated with the many diverse functions of cells. So far, FoxO1, FoxO3 a, FoxO4 and FoxO6 proteins have been identified in humans. Although each FoxO family member has its own role, unlike the other FoxO families, FoxO3 a has been extensively studied because of its rather unique and pivotal regulation of cell proliferation, apoptosis, metabolism, stress management and longevity. FoxO3 a alteration is closely linked to the progression of several types of cancers, fibrosis and other types of diseases. In this review, we will examine the function of FoxO3 a in disease progression and also explore FoxO3a's regulatory mechanisms. We will also discuss FoxO3 a as a potential target for the treatment of several types of disease.
基金Supported by The Natural Science Foundation of Jiangsu Province,China,No.BK2009088the Natural Science Fund for Colleges and Universities in Jiangsu Province,No.10KJB310015
文摘AIM:To evaluate human gastric submucosal vascular dysfunction and its mechanism during the aging process.METHODS:Twenty male patients undergoing subtotal gastrectomy were enrolled in this study.Young and elderly patient groups aged 25-40 years and 60-85 years,respectively,were included.Inclusion criteria were:no clinical evidence of cardiovascular,renal or diabetic diseases.Conventional clinical examinations were carried out.After surgery,gastric submucosal arteries were immediately dissected free of fat and connective tissue.Vascular responses to acetylcholine(ACh)and sodium nitroprusside(SNP)were measured by isolated vascular perfusion.Morphological changes in the gastric mucosal vessels were observed by hematoxylin and eosin(HE)staining and Verhoeff van Gieson(EVG)staining.The expression of xanthine oxidase(XO)and manganese-superoxide dismutase(Mn-SOD)was assessed by Western blotting analysis.The malondialdehyde(MDA)and hydrogen peroxide(H2O2)content and the activities of superoxide dismutase(SOD)and glutathione peroxidase(GSH-Px)were determined according to commercial kits.RESULTS:The overall structure of vessel walls was shown by HE and EVG staining,respectively.Disruption of the internal elastic lamina or neointimal layers was not observed in vessels from young or elderly patients;however,cell layer number in the vessel wall increased significantly in the elderly group.Compared with submucosal arteries in young patients,the amount of vascular collagen fibers,lumen diameter and media cross-sectional area were significantly increased in elderly patients.Ach-and SNP-induced vasodilatation in elderly arterioles was significantly decreased compared with that of gastric submucosal arterioles from young patients.Compared with the young group,the expression of XO and the contents of MDA and H2O2in gastric submucosal arterioles were increased in the elderly group.In addition,the expression of Mn-SOD and the activities of SOD and GSH-Px in the elderly group decreased significantly compared with those in the young gro
