Ganoderma lucidum is a traditional Chinese medicine, which has been shown to have both an-tioxidative and anti-inflammatory effects, and noticeably decreases both the infarct area and neuronal apoptosis of the ischemi...Ganoderma lucidum is a traditional Chinese medicine, which has been shown to have both an-tioxidative and anti-inflammatory effects, and noticeably decreases both the infarct area and neuronal apoptosis of the ischemic cortex. This study aimed to investigate the protective effects and mechanisms of pretreatment with ganoderma lucidum （by intragastric administration） in cerebral ischemia/reperfusion injury in rats. Our results showed that pretreatment with ganoderma lucidum for 3 and 7 days reduced neuronal loss in the hippocampus, diminished the content of malondialdehyde in the hippocampus and serum, decreased the levels of tumor necrosis factor-a and interleukin-8 in the hippocampus, and increased the activity of superoxide dismutase in the hippocampus and serum. These results suggest that pretreatment with ganoderma lucidum was protective against cerebral ischemia/reperfusion injury through its anti-oxidative and an-tiinflammatory actions.展开更多
BACKGROUND： Subsequent to cerebral ischemic injury, endogenous neural stem cells are activated, but ischemia-induced neuronal loss is not compensated by ischemic injury-induced neural regeneration. Salvia （S.） milt...BACKGROUND： Subsequent to cerebral ischemic injury, endogenous neural stem cells are activated, but ischemia-induced neuronal loss is not compensated by ischemic injury-induced neural regeneration. Salvia （S.） miltiorrhiza Bge.f.alba （Baihua Danshen, a Chinese herbal medicine） could enhance learning and memory functions, as well as promote neural regeneration. OBJECTIVE： To observe the effects of S. miltiorrhiza Bge.f.alba on recovery from cerebral ischemia-reperfusion injury, and the influence on neuronal regeneration and differentiation. DESIGN, TIME AND SETTING： Randomized, controlled, animal experiments were performed at the Experimental Animal Center and Neurobiology Laboratory of Taishan Medical College in September of 2006. MATERIALS： S. miltiorrhiza Bge.f.alba was provided by Taishan Medical College Botanic Garden, Taian, China; dl-3n-butylphthalide （NBP） soft capsule was purchased from NBP Pharmaceutical, Shijiazhuang, China; mouse anti-bromodeoxyuridine antibody, rabbit anti-NF200 antibody, and bromodeoxyuridine were purchased from Sigma, Louis, MO, USA; Annexin V-fluorescein isothiocyanate/PI apoptosis kit was purchased from Nanjing Comissariado Biological Technology Development, Nanjing, China. METHODS： Adult Sprague Dawley rats were randomly assigned to sham surgery, model （cerebral ischemia and reperfusion, without administration）, S. miltiorrhiza Bge.f.alba, and NBP groups. Following establishment of the cerebral ischemia/reperfusion model, S. miltiorrhiza Bge.f.alba or NBP （1 mL/100 g） was respectively perfused at 30 minutes following cerebral ischemia/reperfusion. MAIN OUTCOME MEASURES： Alterations in cerebral blood flow before and after ischemia/reperfusion, NF200- and bromodeoxyuridine-double positive cells in striatum of affected tissues, as well as neuronal apoptosis rate at days 5 and 7 following cerebral ischemia/reperfusion. RESULTS： Subsequent to cerebral ischemia reperfusion, cerebral blood flow was reduced. Following treatment with S. miltiorrhiza Bge.f.alba, cerebral blood flow significantly increased （P 〈 0.05）. NBP treatment was inferior to S. miltiorrhiza Bge.f.alba with regard to stabilization of cerebral blood flow （P 〈 0.05）. S. miltiorrhiza Bge.f.alba significantly increased the number of newly formed neurons in rats following cerebral ischemia （P 〈 0.05） and significantly reduced neuronal apoptosis （P 〈 0.05）, with no significant difference compared with NBP treatment （P 〉 0.05）. CONCLUSION： S. miltiorrhiza Bge.f.alba significantly increased cerebral blood flow, reduced neuronal apoptosis, and promoted neuronal regeneration in rats with cerebral ischemia/reperfusion impairment.展开更多
The liver is an important metabolic and detoxification organ and hence demands a large amount of energy,which is mainly produced by the mitochondria.Liver tissues of pa-tients with alcohol-related or non-alcohol-relat...The liver is an important metabolic and detoxification organ and hence demands a large amount of energy,which is mainly produced by the mitochondria.Liver tissues of pa-tients with alcohol-related or non-alcohol-related liver diseases contain ultrastructural mito-chondrial lesions,mitochondrial DNA damage,disturbed mitochondrial dynamics,and compromised ATP production.Overproduction of mitochondrial reactive oxygen species in-duces oxidative damage to mitochondrial proteins and mitochondrial DNA,decreases mito-chondrial membrane potential,triggers hepatocyte inflammation,and promotes programmed cell death,all of which impair liver function.Mitochondrial DNA may be a poten-tial novel non-invasive biomarker of the risk of progression to liver cirrhosis and hepatocellular carcinoma in patients infected with the hepatitis B virus.We herein present a review of the mechanisms of mitochondrial dysfunction in the development of acute liver injury and chronic liver diseases,such as hepatocellular carcinoma,viral hepatitis,drug-induced liver injury,alcoholic liver disease,and non-alcoholic fatty liver disease.This review also discusses mito-chondrion-centric therapies for treating liver diseases.展开更多
Background and Aims:Liver cirrhosis can lead to liver failure and eventually death.Macrophages are the main contributors to cirrhosis and have a bidirectional role in regulating matrix deposition and degradation.Macro...Background and Aims:Liver cirrhosis can lead to liver failure and eventually death.Macrophages are the main contributors to cirrhosis and have a bidirectional role in regulating matrix deposition and degradation.Macrophage-based cell therapy has been developed as an alternative to liver transplantation.However,there is insufficient evidence regarding its safety and efficacy.In this study,we aimed to explore the effect of combining insulin-like growth factor 2(IGF2)with bone marrow-derived macrophages(BMDMs)to treat mice with liver cirrhosis.Methods:We assessed liver inflammation,fibrosis regression,liver function,and liver regeneration in mice with CCl4-induced cirrhosis and treated with BMDM only or IGF2+BMDM.We performed in vitro experiments in which activated hepatic stellate cells(HSCs)were co-cultured with macrophages in the presence or absence of IGF2.The polarity of macrophages and the degree of inhibition of HSCs were examined.The effect of IGF2 on macrophages was also verified by the overexpression of IGF2.Results:Combining IGF2 with BMDM reduced liver inflammation and fibrosis and increased hepatocyte proliferation.Combining IGF2 with BMDM was more effective than using BMDM alone.In vitro experiments demonstrated that IGF2 inhibited HSCs activation by upregulating NR4A2 to promote the anti-inflammatory macrophages phenotype.IGF2 also increased the synthesis of matrix metalloproteinases(MMPs)by macrophages,which may explain why administering IGF2 combined with BMDM was more effective than administering BMDM only.Conclusions:Our study provides a theoretical basis for the future use of BMDM-based cell therapy to treat liver cirrhosis.展开更多
基金supported by the Natural Science Foundation of Taishan Medical University in China,No.2007.ZR-087
文摘Ganoderma lucidum is a traditional Chinese medicine, which has been shown to have both an-tioxidative and anti-inflammatory effects, and noticeably decreases both the infarct area and neuronal apoptosis of the ischemic cortex. This study aimed to investigate the protective effects and mechanisms of pretreatment with ganoderma lucidum （by intragastric administration） in cerebral ischemia/reperfusion injury in rats. Our results showed that pretreatment with ganoderma lucidum for 3 and 7 days reduced neuronal loss in the hippocampus, diminished the content of malondialdehyde in the hippocampus and serum, decreased the levels of tumor necrosis factor-a and interleukin-8 in the hippocampus, and increased the activity of superoxide dismutase in the hippocampus and serum. These results suggest that pretreatment with ganoderma lucidum was protective against cerebral ischemia/reperfusion injury through its anti-oxidative and an-tiinflammatory actions.
基金Key Scientific and Technological Project of Shandong Province,No.2006GG2202037a fund by Shandong Province Ministry of Education,No.J06L20
文摘BACKGROUND： Subsequent to cerebral ischemic injury, endogenous neural stem cells are activated, but ischemia-induced neuronal loss is not compensated by ischemic injury-induced neural regeneration. Salvia （S.） miltiorrhiza Bge.f.alba （Baihua Danshen, a Chinese herbal medicine） could enhance learning and memory functions, as well as promote neural regeneration. OBJECTIVE： To observe the effects of S. miltiorrhiza Bge.f.alba on recovery from cerebral ischemia-reperfusion injury, and the influence on neuronal regeneration and differentiation. DESIGN, TIME AND SETTING： Randomized, controlled, animal experiments were performed at the Experimental Animal Center and Neurobiology Laboratory of Taishan Medical College in September of 2006. MATERIALS： S. miltiorrhiza Bge.f.alba was provided by Taishan Medical College Botanic Garden, Taian, China; dl-3n-butylphthalide （NBP） soft capsule was purchased from NBP Pharmaceutical, Shijiazhuang, China; mouse anti-bromodeoxyuridine antibody, rabbit anti-NF200 antibody, and bromodeoxyuridine were purchased from Sigma, Louis, MO, USA; Annexin V-fluorescein isothiocyanate/PI apoptosis kit was purchased from Nanjing Comissariado Biological Technology Development, Nanjing, China. METHODS： Adult Sprague Dawley rats were randomly assigned to sham surgery, model （cerebral ischemia and reperfusion, without administration）, S. miltiorrhiza Bge.f.alba, and NBP groups. Following establishment of the cerebral ischemia/reperfusion model, S. miltiorrhiza Bge.f.alba or NBP （1 mL/100 g） was respectively perfused at 30 minutes following cerebral ischemia/reperfusion. MAIN OUTCOME MEASURES： Alterations in cerebral blood flow before and after ischemia/reperfusion, NF200- and bromodeoxyuridine-double positive cells in striatum of affected tissues, as well as neuronal apoptosis rate at days 5 and 7 following cerebral ischemia/reperfusion. RESULTS： Subsequent to cerebral ischemia reperfusion, cerebral blood flow was reduced. Following treatment with S. miltiorrhiza Bge.f.alba, cerebral blood flow significantly increased （P 〈 0.05）. NBP treatment was inferior to S. miltiorrhiza Bge.f.alba with regard to stabilization of cerebral blood flow （P 〈 0.05）. S. miltiorrhiza Bge.f.alba significantly increased the number of newly formed neurons in rats following cerebral ischemia （P 〈 0.05） and significantly reduced neuronal apoptosis （P 〈 0.05）, with no significant difference compared with NBP treatment （P 〉 0.05）. CONCLUSION： S. miltiorrhiza Bge.f.alba significantly increased cerebral blood flow, reduced neuronal apoptosis, and promoted neuronal regeneration in rats with cerebral ischemia/reperfusion impairment.
基金funded by the Anti-aging Research Center of Wuhan University Education Development Foundation,Hubei,China(No.2002330)the National Stem Cell Clinical Research Project of China(China Medical Biotechnology Association 2019,No.007).
文摘The liver is an important metabolic and detoxification organ and hence demands a large amount of energy,which is mainly produced by the mitochondria.Liver tissues of pa-tients with alcohol-related or non-alcohol-related liver diseases contain ultrastructural mito-chondrial lesions,mitochondrial DNA damage,disturbed mitochondrial dynamics,and compromised ATP production.Overproduction of mitochondrial reactive oxygen species in-duces oxidative damage to mitochondrial proteins and mitochondrial DNA,decreases mito-chondrial membrane potential,triggers hepatocyte inflammation,and promotes programmed cell death,all of which impair liver function.Mitochondrial DNA may be a poten-tial novel non-invasive biomarker of the risk of progression to liver cirrhosis and hepatocellular carcinoma in patients infected with the hepatitis B virus.We herein present a review of the mechanisms of mitochondrial dysfunction in the development of acute liver injury and chronic liver diseases,such as hepatocellular carcinoma,viral hepatitis,drug-induced liver injury,alcoholic liver disease,and non-alcoholic fatty liver disease.This review also discusses mito-chondrion-centric therapies for treating liver diseases.
基金This work was supported by the National Natural Science Foundation of China(no.81972673)the Wuhan University Education and Development Foundation(no.2002330).
文摘Background and Aims:Liver cirrhosis can lead to liver failure and eventually death.Macrophages are the main contributors to cirrhosis and have a bidirectional role in regulating matrix deposition and degradation.Macrophage-based cell therapy has been developed as an alternative to liver transplantation.However,there is insufficient evidence regarding its safety and efficacy.In this study,we aimed to explore the effect of combining insulin-like growth factor 2(IGF2)with bone marrow-derived macrophages(BMDMs)to treat mice with liver cirrhosis.Methods:We assessed liver inflammation,fibrosis regression,liver function,and liver regeneration in mice with CCl4-induced cirrhosis and treated with BMDM only or IGF2+BMDM.We performed in vitro experiments in which activated hepatic stellate cells(HSCs)were co-cultured with macrophages in the presence or absence of IGF2.The polarity of macrophages and the degree of inhibition of HSCs were examined.The effect of IGF2 on macrophages was also verified by the overexpression of IGF2.Results:Combining IGF2 with BMDM reduced liver inflammation and fibrosis and increased hepatocyte proliferation.Combining IGF2 with BMDM was more effective than using BMDM alone.In vitro experiments demonstrated that IGF2 inhibited HSCs activation by upregulating NR4A2 to promote the anti-inflammatory macrophages phenotype.IGF2 also increased the synthesis of matrix metalloproteinases(MMPs)by macrophages,which may explain why administering IGF2 combined with BMDM was more effective than administering BMDM only.Conclusions:Our study provides a theoretical basis for the future use of BMDM-based cell therapy to treat liver cirrhosis.
