In recent years,studies have shown that there is a correlation between sleep disorders and cancer,but at the present stage,the research on sleep disorders and tumor related animal models is relatively insufficient.Our...In recent years,studies have shown that there is a correlation between sleep disorders and cancer,but at the present stage,the research on sleep disorders and tumor related animal models is relatively insufficient.Our research will focus on mice bearing B16F10-luc-G5 melanoma tumor with sleep fragmentation,detecting promoting effect of sleep fragmentation(SF)on the metastasis of melanoma.At the same time,we used Ganoderma lucidum poly⁃saccharides peptide(GL-pp,80 mg·kg-1),a component of traditional Chinese medicine Ganoderma lucidum,which has long enjoyed a good reputation at home and abroad,to observe its anti-tumor metastasis effects on B16F10-luc-G5 mice with SF.Then we used whole proteomics to analyze the difference proteins expressed in lung tissue and compared between groups,includes mice bearing B16F10-luc-G5,mice bearing B16F10-luc-G5 with SF and GL-pp administered mice bearing B16F10-luc-G5 with SF.With the analysis using bioinformatics,we found several key proteins,their genes name are Adcy9,ptk2,Yap1 and Lpin2,Per1 and Tim.And several important clusters,they are,immune system,platelet aggres⁃sion,energy metabolism,cell cytoskeleton,cell adhesion and circadian rhythms.Moreover,we detected the TLR4 signal pathway and macrophage differentiation to reconfirm the results of proteomics and trying to elucidate the mechanism of SF on tumor growth and metastasis and the effects of GL-pp.展开更多
OBJECTIVE Ganoderma lucidum polysaccharide peptides(GLPP)have an anti-oxidant activity.The oxidative stress implicates in the pathogenesis of renal ischemia-reperfusion injury(RIRI).The objective of this study was to ...OBJECTIVE Ganoderma lucidum polysaccharide peptides(GLPP)have an anti-oxidant activity.The oxidative stress implicates in the pathogenesis of renal ischemia-reperfusion injury(RIRI).The objective of this study was to determine whether GLPP could attenuate RIRI via counteracting the oxidative stress.METHODS Mice subjected to uninephrectomy with the right kidney ischemia for 35 min and reperfusion for 24 hwere used to explore the protective activity of GLPP against RIRI.In GLPP-treated group,100mg·kg-1·d-1 of GLPP were intraperitoneally injected for 7dbefore the procedure.In vitro,NRK-52 Ecells subjected to hypoxia-reoxygenation(H/R)and tunicamycin were used to explore the protective effect of GLPP against oxidative stress.The mechanisms in which GLPP protected kidney from RIRI were studied using a series of physiological and molecular biological methods.RESULTS Kidneys undergone ischemia-reperfusion showed renal dysfunction and characteristic morphological changes including cellular necrosis,brush border loss,cast formation,vacuolization and tubular dilatation while these damages were significantly attenuated by GLPP treatment.The abnormal levels of MPO,MDA and SOD caused by renal ischemia-reperfusion were significantly reversed by GLPP treatment.More apoptotic cells were found in the renal ischemia-reperfusion group than the sham group whereas GLPP reduced apoptotic cells in the ischemia-reperfusion mice by21.75%(P<0.01).The GLPPs(25-1μg·mL)alleviated H/R induced cell viability loss by 20.12%(P<0.01)andΔφm dissipation by 27.3%(P<0.01)in vitro as well and its pretreatment dramatically reduced H/R and tunicamycin induced cell injury.CONCLUSION Our study found that GLPP had a protective effect on RIRI via its anti-oxidative capacity,which suggests that GLPP may be developed as a candidate drug for preventing acute kidney injury.展开更多
OBJECTIVE Ganoderma lucidum polysaccharide peptide(GLPP)is a group of extract from Ganoderma lucidum with a molecular mass of approximately 5×10^5,which ratio of polysaccharide to peptide is approximately 95%/5%....OBJECTIVE Ganoderma lucidum polysaccharide peptide(GLPP)is a group of extract from Ganoderma lucidum with a molecular mass of approximately 5×10^5,which ratio of polysaccharide to peptide is approximately 95%/5%.The purpose of this study was to determine whether GLPP has therapeutic effect on Non-alcoholic fatty liver disease(NAFLD).METHODS Ob/ob mouse model and ApoC3 transgenic mouse model were used for exploring the effect of GLPP on NAFLD.Key metabolic pathways and enzymes were identified by metabolomics combining with KEGG and PIUmet analyses and key enzymes were detected by Western blotting.Hepatosteatosis models of HepG2 cells and primary hepatocytes were used to further confirm the therapeutic effect of GLPP on NAFLD.RESULTS GLPP administrated for a month alleviated hepatosteatosis,dyslipidemia,liver dysfunction and liver insulin resistance.Pathways of glycerophos⁃pholipid metabolism,fatty acid metabolism and primary bile acid biosynthesis were involved in the therapeutic effect of GLPP on NAFLD.Detection of key enzymes revealed that GLPP reversed low expression of CYP7A1,CYP8B1,FXR,SHP and high expression of FGFR4 in ob/ob mice and ApoC3 mice.Besides,GLPP inhibited fatty acid synthesis by reducing the expression of SREBP1c,FAS and ACC via a FXR-SHP dependent mechanism.Additionally,GLPP reduced the accumulation of lipid droplets and the content of TG in HepG2 cells and primary hepatocytes induced by oleic acid and palmitic acid.CONCLUSION GLPP significantly improves NAFLD via regulating bile acid synthesis dependent on FXR-SHP/FGF pathway,which finally inhibits fatty acid synthesis,indicating that GLPP might be developed as a ther⁃apeutic drug for NAFLD.展开更多
The immune regulatory and antioxidant roles of Ganoderma lucidum were investigated using cyclophosphamide(CTX)-induced immunosuppressed mice. Mice were randomly divided into groups: untreated(groupⅠ), immunosuppresse...The immune regulatory and antioxidant roles of Ganoderma lucidum were investigated using cyclophosphamide(CTX)-induced immunosuppressed mice. Mice were randomly divided into groups: untreated(groupⅠ), immunosuppressed(groupⅡ), unfermented G. lucidum polysaccharide(groupⅢ) and fermented G. lucidum polysaccharide(group Ⅳ). After seven consecutive days of treatments, the serum concentration of IL-4, IFN-gamma, IgG, IgA and IgM and the liver activity of GSH-Px, SOD, CAT and MDA enzymes were analyzed. The contents of IL-4, IFN-γ in serum and GSH-Px, SOD and CAT in liver tissues were significantly reduced in groupⅡ compared with those in group I, indicating successful CTX-induced immunosuppression. Interestingly, the results showed that the above immune and antioxidant indicators were significantly improved after G. lucidum polysaccharide treatment, regardless of fermentation. However, fermentation caused changes in polysaccharide structure, which might have a significant impact on immune regulation and antioxidant functions in immunosuppressed mice.展开更多
OBJECTIVE Non-alcoholic fatty liver disease(NAFLD) encompasses a series of patho.logic changes ranging from steatosis to steatohepatitis,which may progress to cirrhosis and hepatocel.lular carcinoma.The purpose of thi...OBJECTIVE Non-alcoholic fatty liver disease(NAFLD) encompasses a series of patho.logic changes ranging from steatosis to steatohepatitis,which may progress to cirrhosis and hepatocel.lular carcinoma.The purpose of this study was to determine whether Ganoderma lucidum polysaccha.ride peptide(GLPP) has therapeutic effect on NAFLD.METHODS ob/ob mouse model and ApoC3 transgenic mouse model were used for exploring the effect of GLPP on NAFLD.Key metabolic path.ways and enzymes were identified by metabolomics combining with KEGG and PIUmet analyses and key enzymes were detected by Western blotting.Hepatosteatosis models of HepG2 cells and primary hepatocytes were used to further confirm the therapeutic effect of GLPP on NAFLD.RESULTS GLPP administrated for a month alleviated hepatosteatosis,dyslipidemia,liver dysfunction and liver insulin resistance.Pathways of glycerophospholipid metabolism,fatty acid metabolism and primary bile acid biosynthesis were involved in the therapeutic effect of GLPP on NAFLD.Detection of key enzymes revealed that GLPP reversed low expression of CYP7 A1,CYP8 B1,FXR,SHP and high expression of FGFR4 in ob/ob mice and ApoC3 mice.Besides,GLPP inhibited fatty acid synthesis by reducing the expression of SREBP1 c,FAS and ACC via a FXR-SHP dependent mechanism.Additionally,GLPP reduced the accumulation of lipid droplets and the content of TG in HepG2 cells and primary hepato.cytes induced by oleic acid and palmitic acid.CONCLUSION GLPP significantly improves NAFLD via regulating bile acid synthesis dependent on FXR-SHP/FGF pathway,which finally inhibits fatty acid synthesis,indicating that GLPP might be developed as a therapeutic drug for NAFLD.展开更多
文摘In recent years,studies have shown that there is a correlation between sleep disorders and cancer,but at the present stage,the research on sleep disorders and tumor related animal models is relatively insufficient.Our research will focus on mice bearing B16F10-luc-G5 melanoma tumor with sleep fragmentation,detecting promoting effect of sleep fragmentation(SF)on the metastasis of melanoma.At the same time,we used Ganoderma lucidum poly⁃saccharides peptide(GL-pp,80 mg·kg-1),a component of traditional Chinese medicine Ganoderma lucidum,which has long enjoyed a good reputation at home and abroad,to observe its anti-tumor metastasis effects on B16F10-luc-G5 mice with SF.Then we used whole proteomics to analyze the difference proteins expressed in lung tissue and compared between groups,includes mice bearing B16F10-luc-G5,mice bearing B16F10-luc-G5 with SF and GL-pp administered mice bearing B16F10-luc-G5 with SF.With the analysis using bioinformatics,we found several key proteins,their genes name are Adcy9,ptk2,Yap1 and Lpin2,Per1 and Tim.And several important clusters,they are,immune system,platelet aggres⁃sion,energy metabolism,cell cytoskeleton,cell adhesion and circadian rhythms.Moreover,we detected the TLR4 signal pathway and macrophage differentiation to reconfirm the results of proteomics and trying to elucidate the mechanism of SF on tumor growth and metastasis and the effects of GL-pp.
基金The project supported by National Natural Science Foundation of China(81330074,81261160507,81170632,81370783,41376166)the 111Project,and International Science&Technology Cooperation Program of China 2012DFA11070
文摘OBJECTIVE Ganoderma lucidum polysaccharide peptides(GLPP)have an anti-oxidant activity.The oxidative stress implicates in the pathogenesis of renal ischemia-reperfusion injury(RIRI).The objective of this study was to determine whether GLPP could attenuate RIRI via counteracting the oxidative stress.METHODS Mice subjected to uninephrectomy with the right kidney ischemia for 35 min and reperfusion for 24 hwere used to explore the protective activity of GLPP against RIRI.In GLPP-treated group,100mg·kg-1·d-1 of GLPP were intraperitoneally injected for 7dbefore the procedure.In vitro,NRK-52 Ecells subjected to hypoxia-reoxygenation(H/R)and tunicamycin were used to explore the protective effect of GLPP against oxidative stress.The mechanisms in which GLPP protected kidney from RIRI were studied using a series of physiological and molecular biological methods.RESULTS Kidneys undergone ischemia-reperfusion showed renal dysfunction and characteristic morphological changes including cellular necrosis,brush border loss,cast formation,vacuolization and tubular dilatation while these damages were significantly attenuated by GLPP treatment.The abnormal levels of MPO,MDA and SOD caused by renal ischemia-reperfusion were significantly reversed by GLPP treatment.More apoptotic cells were found in the renal ischemia-reperfusion group than the sham group whereas GLPP reduced apoptotic cells in the ischemia-reperfusion mice by21.75%(P<0.01).The GLPPs(25-1μg·mL)alleviated H/R induced cell viability loss by 20.12%(P<0.01)andΔφm dissipation by 27.3%(P<0.01)in vitro as well and its pretreatment dramatically reduced H/R and tunicamycin induced cell injury.CONCLUSION Our study found that GLPP had a protective effect on RIRI via its anti-oxidative capacity,which suggests that GLPP may be developed as a candidate drug for preventing acute kidney injury.
基金National Natural Science Foundation of China(8133007481620108029+1 种基金81261160507)Beijing Natural Science Foundation(7172113)
文摘OBJECTIVE Ganoderma lucidum polysaccharide peptide(GLPP)is a group of extract from Ganoderma lucidum with a molecular mass of approximately 5×10^5,which ratio of polysaccharide to peptide is approximately 95%/5%.The purpose of this study was to determine whether GLPP has therapeutic effect on Non-alcoholic fatty liver disease(NAFLD).METHODS Ob/ob mouse model and ApoC3 transgenic mouse model were used for exploring the effect of GLPP on NAFLD.Key metabolic pathways and enzymes were identified by metabolomics combining with KEGG and PIUmet analyses and key enzymes were detected by Western blotting.Hepatosteatosis models of HepG2 cells and primary hepatocytes were used to further confirm the therapeutic effect of GLPP on NAFLD.RESULTS GLPP administrated for a month alleviated hepatosteatosis,dyslipidemia,liver dysfunction and liver insulin resistance.Pathways of glycerophos⁃pholipid metabolism,fatty acid metabolism and primary bile acid biosynthesis were involved in the therapeutic effect of GLPP on NAFLD.Detection of key enzymes revealed that GLPP reversed low expression of CYP7A1,CYP8B1,FXR,SHP and high expression of FGFR4 in ob/ob mice and ApoC3 mice.Besides,GLPP inhibited fatty acid synthesis by reducing the expression of SREBP1c,FAS and ACC via a FXR-SHP dependent mechanism.Additionally,GLPP reduced the accumulation of lipid droplets and the content of TG in HepG2 cells and primary hepatocytes induced by oleic acid and palmitic acid.CONCLUSION GLPP significantly improves NAFLD via regulating bile acid synthesis dependent on FXR-SHP/FGF pathway,which finally inhibits fatty acid synthesis,indicating that GLPP might be developed as a ther⁃apeutic drug for NAFLD.
基金Supported by the "12th Five-year Plan" National Science and Technology(2011BAD34B01)
文摘The immune regulatory and antioxidant roles of Ganoderma lucidum were investigated using cyclophosphamide(CTX)-induced immunosuppressed mice. Mice were randomly divided into groups: untreated(groupⅠ), immunosuppressed(groupⅡ), unfermented G. lucidum polysaccharide(groupⅢ) and fermented G. lucidum polysaccharide(group Ⅳ). After seven consecutive days of treatments, the serum concentration of IL-4, IFN-gamma, IgG, IgA and IgM and the liver activity of GSH-Px, SOD, CAT and MDA enzymes were analyzed. The contents of IL-4, IFN-γ in serum and GSH-Px, SOD and CAT in liver tissues were significantly reduced in groupⅡ compared with those in group I, indicating successful CTX-induced immunosuppression. Interestingly, the results showed that the above immune and antioxidant indicators were significantly improved after G. lucidum polysaccharide treatment, regardless of fermentation. However, fermentation caused changes in polysaccharide structure, which might have a significant impact on immune regulation and antioxidant functions in immunosuppressed mice.
基金supported by National Natural Science Foundation of China(8133007481620108029+1 种基金81261160507) Beijing Natural Science Foundation(7172113)
文摘OBJECTIVE Non-alcoholic fatty liver disease(NAFLD) encompasses a series of patho.logic changes ranging from steatosis to steatohepatitis,which may progress to cirrhosis and hepatocel.lular carcinoma.The purpose of this study was to determine whether Ganoderma lucidum polysaccha.ride peptide(GLPP) has therapeutic effect on NAFLD.METHODS ob/ob mouse model and ApoC3 transgenic mouse model were used for exploring the effect of GLPP on NAFLD.Key metabolic path.ways and enzymes were identified by metabolomics combining with KEGG and PIUmet analyses and key enzymes were detected by Western blotting.Hepatosteatosis models of HepG2 cells and primary hepatocytes were used to further confirm the therapeutic effect of GLPP on NAFLD.RESULTS GLPP administrated for a month alleviated hepatosteatosis,dyslipidemia,liver dysfunction and liver insulin resistance.Pathways of glycerophospholipid metabolism,fatty acid metabolism and primary bile acid biosynthesis were involved in the therapeutic effect of GLPP on NAFLD.Detection of key enzymes revealed that GLPP reversed low expression of CYP7 A1,CYP8 B1,FXR,SHP and high expression of FGFR4 in ob/ob mice and ApoC3 mice.Besides,GLPP inhibited fatty acid synthesis by reducing the expression of SREBP1 c,FAS and ACC via a FXR-SHP dependent mechanism.Additionally,GLPP reduced the accumulation of lipid droplets and the content of TG in HepG2 cells and primary hepato.cytes induced by oleic acid and palmitic acid.CONCLUSION GLPP significantly improves NAFLD via regulating bile acid synthesis dependent on FXR-SHP/FGF pathway,which finally inhibits fatty acid synthesis,indicating that GLPP might be developed as a therapeutic drug for NAFLD.
