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
Interleukin-1βis a potent proinflammatory cytokine that plays a key role in the pathogenesis of the brain aging and diverse range of neurological diseases including Alzheimer’s disease,Parkinson’s disease,stroke an...Interleukin-1βis a potent proinflammatory cytokine that plays a key role in the pathogenesis of the brain aging and diverse range of neurological diseases including Alzheimer’s disease,Parkinson’s disease,stroke and persistent pain.Activated microglia are the main cellular source of interleukin-1βin the brain.Cathepsin B is associated with the production and secretion of interleukin-1βthrough pyrin domain-containing protein 3 inflammasome-independent processing of procaspase-3 in the phagolysosomes.The leakage of cathepsin B from the endosomal-lysosomal system during aging is associated with the proteolytic degradation of mitochondrial transcription factor A,which can stabilize mitochondrial DNA.Therefore,microglial cathepsin B could function as a major driver for inflammatory brain diseases and brain aging.Orally active and blood-brain barrier-permeable specific inhibitors for cathepsin B can be potentially effective new pharmaceutical interventions against inflammatory brain diseases and brain aging.展开更多
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
基金founded by JSPS KAKENHI,No.24390416,JP15H05015,15K15684 and JP16H01304(all to HN)
文摘Interleukin-1βis a potent proinflammatory cytokine that plays a key role in the pathogenesis of the brain aging and diverse range of neurological diseases including Alzheimer’s disease,Parkinson’s disease,stroke and persistent pain.Activated microglia are the main cellular source of interleukin-1βin the brain.Cathepsin B is associated with the production and secretion of interleukin-1βthrough pyrin domain-containing protein 3 inflammasome-independent processing of procaspase-3 in the phagolysosomes.The leakage of cathepsin B from the endosomal-lysosomal system during aging is associated with the proteolytic degradation of mitochondrial transcription factor A,which can stabilize mitochondrial DNA.Therefore,microglial cathepsin B could function as a major driver for inflammatory brain diseases and brain aging.Orally active and blood-brain barrier-permeable specific inhibitors for cathepsin B can be potentially effective new pharmaceutical interventions against inflammatory brain diseases and brain aging.
