Although the liver has a high regenerative capacity,as a result of massive hepatocyte death,liver failure occurs. In addition to liver failure,for acute,chronic and hereditary diseases of the liver,cell transplantatio...Although the liver has a high regenerative capacity,as a result of massive hepatocyte death,liver failure occurs. In addition to liver failure,for acute,chronic and hereditary diseases of the liver,cell transplantation therapies can stimulate regeneration or at least ensure sufficient function until liver transplantation can be performed. The lack of donor organs and the risks of rejection have prompted extensive experimental and clinical research in the field of cellular transplantation. Transplantation of cell lineages involved in liver regeneration,including mature hepatocytes,fetal hepatocytes,fetal liver progenitor cells,fetal stem cells,hepatic progenitor cells,hepatic stem cells,mesenchymal stem cells,hematopoietic stem cells,and peripheral blood and umbilical cord blood stem cells,have been found to be beneficial in the treatment of liver failure.In this article,the results of experimental and clinical cell transplantation trials for liver failure are reviewed,with an emphasis on regeneration.展开更多
Oxidative stress has been shown to play an important role in the pathogenesis of acute pancreatitis (AP). Antioxidants, alone or in combination with conventional therapy, should improve oxidative-stress-induced organ ...Oxidative stress has been shown to play an important role in the pathogenesis of acute pancreatitis (AP). Antioxidants, alone or in combination with conventional therapy, should improve oxidative-stress-induced organ damage and therefore accelerate the rate of recovery. In recent years, substantial amounts of data about the efficiency of antioxidants against oxidative damage have been obtained from experiments with rodents. Some of these antioxidants have been found beneficial in the treatment of AP in humans; however, at present there is insufficient clinical data to support the benefits of antioxidants, alone or in combination with conven-tional therapy, in the management of AP in humans. Conflicting results obtained from experimental animals and humans may represent distinct pathophysiological mechanisms mediating tissue injury in different species. Further detailed studies should be done to clarify the exact mechanisms of tissue injury in human AP. Herein I tried to review the existing experimental and clinical studies on AP in order to determine the efficiency of antioxidants. The use of antioxidant enriched nutrition is a potential direction of clinical research in AP given the lack of clues about the efficiency and safety of antioxidant usage in patients with AP.展开更多
AIM: To investigate the role of oxidative injury and the effect of exogenous melatonin administration on liver damage induced by bile duct ligation (BDL), and second, to evaluate the role of nitric oxide (NO), a free ...AIM: To investigate the role of oxidative injury and the effect of exogenous melatonin administration on liver damage induced by bile duct ligation (BDL), and second, to evaluate the role of nitric oxide (NO), a free oxygen radical, in oxidative injury. METHODS: Thirty-two Sprague-Dawley rats were assigned to four groups: sham operation (SO), BDL, BDL+melatonin, and BDL+vehicle. Cholestasis was achieved by double ligature of the common bile duct. Melatonin was injected intraperitoneally 500 μg/(kg·d) for 8 d. Hepatic oxidative stress markers were evaluated by changes in the amount of lipid peroxides, measured as malondialdehyde (MDA), and reduced GSH. Total nitrite (NOx) concentrations were determined in hepatic homogenates. Histopathological examination was performed using a histological scoring system. RESULTS: The histopathological changes including portal inflammation, necrosis,apoptosis, focal inflammation and fibrosis were severe in the BDL and BDL+vehicle groups. There were numerous large areas of coagulation necrosis. Histological Activity Index scores of these groups were significantly higher than that of the SO group. Treatment with melatonin reduced these alterations significantly. The degree of necro-inflammation and fibrosis showed significant difference between the BDL and BDL+melatonin groups. BDL was accompanied by a significant increase in MDA and NOx, and a significant decrease in GSH levels. Mean±SE values of MDA, GSH and NOx levels of SO group were 147.47±6.69, 0.88±0.33 μmol/g and 180.70±6.58 nm/g, respectively. The values of BDL group were 200.14±21.30, 0.65±0.02 μmol/g, and 400.46±48.89 nm/g, respectively, whereas the values of BDL+melatonin group were 115.93±6.8,0.74±0.02 μmol/g, and 290.38±32.32 nm/g, respectively. Melatonin treatment was associated with a significant recovery of MDA, GSH and NOx levels. CONCLUSION: We have concluded that oxidative stress is associated with the pathogenesis of cholestatic liver damage and NO contributes to oxidative damage. Melatonin, even at low dose, is an efficient agent in reducing negative parameters of cholestasis.展开更多
Autophagy,a conserved cellular degradation process,is crucial for various cellular processes such as immune responses,inflammation,metabolic and oxidative stress adaptation,cell proliferation,development,and tissue re...Autophagy,a conserved cellular degradation process,is crucial for various cellular processes such as immune responses,inflammation,metabolic and oxidative stress adaptation,cell proliferation,development,and tissue repair and remodeling.Dysregulation of autophagy is suspected in numerous diseases,including cancer,neurodegenerative diseases,digestive disorders,metabolic syndromes,and infectious and inflammatory diseases.If autophagy is disrupted,for example,this can have serious consequences and lead to chronic inflammation and tissue damage,as occurs in diseases such as Chron's disease and ulcerative colitis.On the other hand,the influence of autophagy on the development and progression of cancer is not clear.Autophagy can both suppress and promote the progression and metastasis of cancer at various stages.From inflammatory bowel diseases to gastrointestinal cancer,researchers are discovering the intricate role of autophagy in maintaining gut health and its potential as a therapeutic target.Researchers should carefully consider the nature and progression of diseases such as cancer when trying to determine whether inhibiting or stimulating autophagy is likely to be beneficial.Multidisciplinary approaches that combine cutting-edge research with clinical expertise are key to unlocking the full therapeutic potential of autophagy in digestive diseases.展开更多
文摘Although the liver has a high regenerative capacity,as a result of massive hepatocyte death,liver failure occurs. In addition to liver failure,for acute,chronic and hereditary diseases of the liver,cell transplantation therapies can stimulate regeneration or at least ensure sufficient function until liver transplantation can be performed. The lack of donor organs and the risks of rejection have prompted extensive experimental and clinical research in the field of cellular transplantation. Transplantation of cell lineages involved in liver regeneration,including mature hepatocytes,fetal hepatocytes,fetal liver progenitor cells,fetal stem cells,hepatic progenitor cells,hepatic stem cells,mesenchymal stem cells,hematopoietic stem cells,and peripheral blood and umbilical cord blood stem cells,have been found to be beneficial in the treatment of liver failure.In this article,the results of experimental and clinical cell transplantation trials for liver failure are reviewed,with an emphasis on regeneration.
文摘Oxidative stress has been shown to play an important role in the pathogenesis of acute pancreatitis (AP). Antioxidants, alone or in combination with conventional therapy, should improve oxidative-stress-induced organ damage and therefore accelerate the rate of recovery. In recent years, substantial amounts of data about the efficiency of antioxidants against oxidative damage have been obtained from experiments with rodents. Some of these antioxidants have been found beneficial in the treatment of AP in humans; however, at present there is insufficient clinical data to support the benefits of antioxidants, alone or in combination with conven-tional therapy, in the management of AP in humans. Conflicting results obtained from experimental animals and humans may represent distinct pathophysiological mechanisms mediating tissue injury in different species. Further detailed studies should be done to clarify the exact mechanisms of tissue injury in human AP. Herein I tried to review the existing experimental and clinical studies on AP in order to determine the efficiency of antioxidants. The use of antioxidant enriched nutrition is a potential direction of clinical research in AP given the lack of clues about the efficiency and safety of antioxidant usage in patients with AP.
文摘AIM: To investigate the role of oxidative injury and the effect of exogenous melatonin administration on liver damage induced by bile duct ligation (BDL), and second, to evaluate the role of nitric oxide (NO), a free oxygen radical, in oxidative injury. METHODS: Thirty-two Sprague-Dawley rats were assigned to four groups: sham operation (SO), BDL, BDL+melatonin, and BDL+vehicle. Cholestasis was achieved by double ligature of the common bile duct. Melatonin was injected intraperitoneally 500 μg/(kg·d) for 8 d. Hepatic oxidative stress markers were evaluated by changes in the amount of lipid peroxides, measured as malondialdehyde (MDA), and reduced GSH. Total nitrite (NOx) concentrations were determined in hepatic homogenates. Histopathological examination was performed using a histological scoring system. RESULTS: The histopathological changes including portal inflammation, necrosis,apoptosis, focal inflammation and fibrosis were severe in the BDL and BDL+vehicle groups. There were numerous large areas of coagulation necrosis. Histological Activity Index scores of these groups were significantly higher than that of the SO group. Treatment with melatonin reduced these alterations significantly. The degree of necro-inflammation and fibrosis showed significant difference between the BDL and BDL+melatonin groups. BDL was accompanied by a significant increase in MDA and NOx, and a significant decrease in GSH levels. Mean±SE values of MDA, GSH and NOx levels of SO group were 147.47±6.69, 0.88±0.33 μmol/g and 180.70±6.58 nm/g, respectively. The values of BDL group were 200.14±21.30, 0.65±0.02 μmol/g, and 400.46±48.89 nm/g, respectively, whereas the values of BDL+melatonin group were 115.93±6.8,0.74±0.02 μmol/g, and 290.38±32.32 nm/g, respectively. Melatonin treatment was associated with a significant recovery of MDA, GSH and NOx levels. CONCLUSION: We have concluded that oxidative stress is associated with the pathogenesis of cholestatic liver damage and NO contributes to oxidative damage. Melatonin, even at low dose, is an efficient agent in reducing negative parameters of cholestasis.
文摘Autophagy,a conserved cellular degradation process,is crucial for various cellular processes such as immune responses,inflammation,metabolic and oxidative stress adaptation,cell proliferation,development,and tissue repair and remodeling.Dysregulation of autophagy is suspected in numerous diseases,including cancer,neurodegenerative diseases,digestive disorders,metabolic syndromes,and infectious and inflammatory diseases.If autophagy is disrupted,for example,this can have serious consequences and lead to chronic inflammation and tissue damage,as occurs in diseases such as Chron's disease and ulcerative colitis.On the other hand,the influence of autophagy on the development and progression of cancer is not clear.Autophagy can both suppress and promote the progression and metastasis of cancer at various stages.From inflammatory bowel diseases to gastrointestinal cancer,researchers are discovering the intricate role of autophagy in maintaining gut health and its potential as a therapeutic target.Researchers should carefully consider the nature and progression of diseases such as cancer when trying to determine whether inhibiting or stimulating autophagy is likely to be beneficial.Multidisciplinary approaches that combine cutting-edge research with clinical expertise are key to unlocking the full therapeutic potential of autophagy in digestive diseases.
