AIM： To study the effects of extract from Ginkgo biloba （EGb） containing 22% flavonoid and 5% terpenoid on chronic liver injury and liver fibrosis of rats induced by carbon tetrachloride （CCh）. METHODS： All rats...AIM： To study the effects of extract from Ginkgo biloba （EGb） containing 22% flavonoid and 5% terpenoid on chronic liver injury and liver fibrosis of rats induced by carbon tetrachloride （CCh）. METHODS： All rats were randomly divided into control group, CCl4-treated group, colchicine-treated group and EGb-protected group. Chronic liver injury was induced in experimental groups by subcutaneous injection of CCh and fed with chows premixed with 79.5% corn powder, 20% lard and 0.5% cholesterol （v/v）. EGb-protected group was treated with EGb （0.5 g/kg body weight per day） for 7 wk. At the end of wk 8, all the rats were killed. Liver function, liver fibrosis, oxidative stress and expression of transforming growth factor β1 （TGF-β1） a-smooth muscle actin （α-SMA） and type I collagens in liver were determined. In addition, pathology changes of liver tissue were observed under light microscope. RESULTS： The levels of alanine aminotransferase （ALT）, aspartate aminotransferase （AST） and albumin （AIb） in EGb-protected group were notably improved as compared with the CCL4-treated group （P 〈 0.01）. The contents of serum hyaluronic acid （HA）, type III procollagen （PCⅢ）, type IV collagen （CIV） and the expression of hepatic tissue TGF-β1, α-SMA and type I collagen in EGb-protected group were significantly lower than those in CCL4-treated groups （P 〈 0.05, P 〈 0.01）. The degrees of liver fibrosis in EGb-protected groups were lower than those in CCL4-treated groups （6.58 ±1.25 vs 9.52 ± 2.06, P 〈 0.05）. Compared to the CCL4-treated group, the levels of plasma glutathoine peroxidase （Se-GSH-Px）, superoxide dismutase （SOD） and malondialdehyde （MDA） were strikingly improved also in EGb-protected group （P 〈 0.05, P 〈 0.01）. CONCLUSION： EGb resists oxidative stress and thereby reduces chronic liver injury and liver fibrosis in rats with liver injury induced by CCl4.展开更多
AIM： To investigate the precise roles of CAR in CCI4- induced acute hepatotoxicity. METHODS： To prepare an acute liver injury model, CCI4 was intraperitoneally injected in CAR＋/＋ and CAR-/- mice. RESULTS： Elevati...AIM： To investigate the precise roles of CAR in CCI4- induced acute hepatotoxicity. METHODS： To prepare an acute liver injury model, CCI4 was intraperitoneally injected in CAR＋/＋ and CAR-/- mice. RESULTS： Elevation of serum alanine aminotransferase and extension of centrilobular necrosis were slightly inhibited in CAR-/- mice compared to CAR＋/＋ mice without PB. Administration of a CAR inducer, PB, revealed that CCl4-induced liver toxicity was partially inhibited in CAR-/- mice compared with CAR＋/＋ mice. On the other hand, androstanol, an inverse agonist ligand, inhibited hepatotoxicity in CAR＋/＋ but not in CAR./. mice. Thus, CAR activation caused CCl4 hepatotoxicity while CAR inhibition resulted in partial protection against CCl4-induced hepatotoxicity.There were no differences in the expression of CYP2E1, the main metabolizing enzyme for CCl4, between CAR＋/＋ and CAR./. mice. However, the expression of other CCI4-metabolizing enzymes, such as CYP2B10 and 3All, was induced by PB in CAR＋/＋ but not in CAR-/- mice. Although the main pathway of CCl4-induced acute liver injury is mediated by CYP2E1, CAR modulates its pathway via induction of CYP2B10 and 3All in the presence of activator or inhibitor. CONCLUSION： The nuclear receptor CAR modulates CCl4- induced liver injury via induction of CCl4-metabolizing enzymes in the presence of an activator. Our results suggest that drugs interacting with nuclear receptors such as PB might play critical roles in drug-induced liver injury or drug- drug interaction even though such drugs themselves are not hepatotoxic.展开更多
AIM： To study the effect of WeiJia on chronic liver injury using carbon tetrachloride （CCh） induced liver injury animal model. METHODS： Wistar rats weighing 180-220g were randomly divided into three groups： norma...AIM： To study the effect of WeiJia on chronic liver injury using carbon tetrachloride （CCh） induced liver injury animal model. METHODS： Wistar rats weighing 180-220g were randomly divided into three groups： normal control group （Group A）, CCh induced liver injury control group （Group B） and CCI4 induction with WeiJia treatment group （Group C）. Each group consisted of 14 rats. Liver damage and fibrosis was induced by subcutaneous injection with 40% CCh in olive oil at 3 mL/kg body weight twice a week for eight weeks for Groups B and C rats whereas olive oil was used for Group A rats. Starting from the third week, Group C rats also received daily intraperitoneal injection of Wei.lia at a dose of 1.25 μg/kg body weight. Animals were sacrificed at the fifth week （4 male, 3 female）, and eighth week （4 male, 3 female） respectively. Degree of fibrosis were measured and serological markers for liver fibrosis and function including hyaluronic acid （HA）, type Ⅳ collagen （CIV）, γ-glutamyl transferase （γ-GT）, alanine aminotransferase （ALT） and aspartate aminotransferase （AST） were determined. Alpha smooth muscle actin （α-SMA） and proliferating cell nuclear antigen （PCNA） immunohistochemistry were also performed. RESULTS： CCl4 induction led to the damage of liver and development of fibrosis in Group B and Group C rats when compared to Group A rats. The treatment of WeiJia in Group C rats could reduce the fibrosis condition significantly compared to Group B rats. The effect could be observed after three weeks of treatment and was more obvious after eight weeks of treatment. Serum HA, CIV,ALT, AST and γ-GT levels after eight weeks of treatment for Group C rats were 58±22 μg/L （P〈0.01）, 57±21 μg/L （P〈0.01）, 47±10 U/L （P〈0.01）, 139±13 U/L （P〈0.05） and 52±21 U/L （P〉0.05） respectively, similar to normal control group （Group A）, but significantly different from CCh induced liver injury control group （Group B）. An increase in PCNA and decrease in α-SMA expression level was also observed. CONCLUSION： WeiJia could improve liver function and reduce liver fibrosis which might be through the inhibition of stellate cell activity.展开更多
The occurrence of massive CD4+ T cell depletion is one of the most prominent characteristics of human immunodeficiency virus type 1 (HIV-1) infection during acute phase, resulting in unrestorable destruction to the im...The occurrence of massive CD4+ T cell depletion is one of the most prominent characteristics of human immunodeficiency virus type 1 (HIV-1) infection during acute phase, resulting in unrestorable destruction to the immune system. The infected host undergoes an asymptomatic period lasting several years with low viral load and ostensibly healthy status, which is presumably due to virus-specific adaptive immune responses. In the absence of therapy, an overwhelming majority of cases develop to AIDS within 8-10 years of latent infection. In this review, we discuss the roles in AIDS pathogenesis played by massive CD4+ T lymphocytes depletion in gut-associated lymphoid tissue (GALT) during acute infection and abnormal immune activation emerging in the later part of chronic phase.展开更多
A theoretical study is carried out on Gaunt＇s palladium-catalyzed selective C（sp3）-H activation of unprotected aliphatic amines. In this reaction, the methyl group is proposed to be activated through a four-membere...A theoretical study is carried out on Gaunt＇s palladium-catalyzed selective C（sp3）-H activation of unprotected aliphatic amines. In this reaction, the methyl group is proposed to be activated through a four-membered cyclometallation pathway even though an ethyl group is present in the substrate. Our calculation shows that the methyl and ethyl activation processes proceed in nitrogen-atom-directed pathway rather than carbonyl-directed one. More important, methyl activation is more favorable than ethyl activation with nitrogen atom as the directing group. Further studies on the structural parameters show that the lactone structure in cyclic substrate is the origin of the selective methyl activation. When the lactone moiety is changed to ketone, ether or alkyl, the selectivity could be reversed so that the ethyl activation becomes more favorable. This result validates the pro- oosal that lactone structure is key to selective methyl activation.展开更多
文摘AIM： To study the effects of extract from Ginkgo biloba （EGb） containing 22% flavonoid and 5% terpenoid on chronic liver injury and liver fibrosis of rats induced by carbon tetrachloride （CCh）. METHODS： All rats were randomly divided into control group, CCl4-treated group, colchicine-treated group and EGb-protected group. Chronic liver injury was induced in experimental groups by subcutaneous injection of CCh and fed with chows premixed with 79.5% corn powder, 20% lard and 0.5% cholesterol （v/v）. EGb-protected group was treated with EGb （0.5 g/kg body weight per day） for 7 wk. At the end of wk 8, all the rats were killed. Liver function, liver fibrosis, oxidative stress and expression of transforming growth factor β1 （TGF-β1） a-smooth muscle actin （α-SMA） and type I collagens in liver were determined. In addition, pathology changes of liver tissue were observed under light microscope. RESULTS： The levels of alanine aminotransferase （ALT）, aspartate aminotransferase （AST） and albumin （AIb） in EGb-protected group were notably improved as compared with the CCL4-treated group （P 〈 0.01）. The contents of serum hyaluronic acid （HA）, type III procollagen （PCⅢ）, type IV collagen （CIV） and the expression of hepatic tissue TGF-β1, α-SMA and type I collagen in EGb-protected group were significantly lower than those in CCL4-treated groups （P 〈 0.05, P 〈 0.01）. The degrees of liver fibrosis in EGb-protected groups were lower than those in CCL4-treated groups （6.58 ±1.25 vs 9.52 ± 2.06, P 〈 0.05）. Compared to the CCL4-treated group, the levels of plasma glutathoine peroxidase （Se-GSH-Px）, superoxide dismutase （SOD） and malondialdehyde （MDA） were strikingly improved also in EGb-protected group （P 〈 0.05, P 〈 0.01）. CONCLUSION： EGb resists oxidative stress and thereby reduces chronic liver injury and liver fibrosis in rats with liver injury induced by CCl4.
基金Supported by a Grant-in Aid for Scientific Research, No. 15790337from the Ministry of Education, Science, Sports and Culture of the Japanese Government
文摘AIM： To investigate the precise roles of CAR in CCI4- induced acute hepatotoxicity. METHODS： To prepare an acute liver injury model, CCI4 was intraperitoneally injected in CAR＋/＋ and CAR-/- mice. RESULTS： Elevation of serum alanine aminotransferase and extension of centrilobular necrosis were slightly inhibited in CAR-/- mice compared to CAR＋/＋ mice without PB. Administration of a CAR inducer, PB, revealed that CCl4-induced liver toxicity was partially inhibited in CAR-/- mice compared with CAR＋/＋ mice. On the other hand, androstanol, an inverse agonist ligand, inhibited hepatotoxicity in CAR＋/＋ but not in CAR./. mice. Thus, CAR activation caused CCl4 hepatotoxicity while CAR inhibition resulted in partial protection against CCl4-induced hepatotoxicity.There were no differences in the expression of CYP2E1, the main metabolizing enzyme for CCl4, between CAR＋/＋ and CAR./. mice. However, the expression of other CCI4-metabolizing enzymes, such as CYP2B10 and 3All, was induced by PB in CAR＋/＋ but not in CAR-/- mice. Although the main pathway of CCl4-induced acute liver injury is mediated by CYP2E1, CAR modulates its pathway via induction of CYP2B10 and 3All in the presence of activator or inhibitor. CONCLUSION： The nuclear receptor CAR modulates CCl4- induced liver injury via induction of CCl4-metabolizing enzymes in the presence of an activator. Our results suggest that drugs interacting with nuclear receptors such as PB might play critical roles in drug-induced liver injury or drug- drug interaction even though such drugs themselves are not hepatotoxic.
基金Supported by Innovation and Technology Fund of the Hong Kong SAR Government(UIM/101)the National Hi-Tech 863 Program of the Ministry of Science and Technology of China,2003AA2Z2052
文摘AIM： To study the effect of WeiJia on chronic liver injury using carbon tetrachloride （CCh） induced liver injury animal model. METHODS： Wistar rats weighing 180-220g were randomly divided into three groups： normal control group （Group A）, CCh induced liver injury control group （Group B） and CCI4 induction with WeiJia treatment group （Group C）. Each group consisted of 14 rats. Liver damage and fibrosis was induced by subcutaneous injection with 40% CCh in olive oil at 3 mL/kg body weight twice a week for eight weeks for Groups B and C rats whereas olive oil was used for Group A rats. Starting from the third week, Group C rats also received daily intraperitoneal injection of Wei.lia at a dose of 1.25 μg/kg body weight. Animals were sacrificed at the fifth week （4 male, 3 female）, and eighth week （4 male, 3 female） respectively. Degree of fibrosis were measured and serological markers for liver fibrosis and function including hyaluronic acid （HA）, type Ⅳ collagen （CIV）, γ-glutamyl transferase （γ-GT）, alanine aminotransferase （ALT） and aspartate aminotransferase （AST） were determined. Alpha smooth muscle actin （α-SMA） and proliferating cell nuclear antigen （PCNA） immunohistochemistry were also performed. RESULTS： CCl4 induction led to the damage of liver and development of fibrosis in Group B and Group C rats when compared to Group A rats. The treatment of WeiJia in Group C rats could reduce the fibrosis condition significantly compared to Group B rats. The effect could be observed after three weeks of treatment and was more obvious after eight weeks of treatment. Serum HA, CIV,ALT, AST and γ-GT levels after eight weeks of treatment for Group C rats were 58±22 μg/L （P〈0.01）, 57±21 μg/L （P〈0.01）, 47±10 U/L （P〈0.01）, 139±13 U/L （P〈0.05） and 52±21 U/L （P〉0.05） respectively, similar to normal control group （Group A）, but significantly different from CCh induced liver injury control group （Group B）. An increase in PCNA and decrease in α-SMA expression level was also observed. CONCLUSION： WeiJia could improve liver function and reduce liver fibrosis which might be through the inhibition of stellate cell activity.
文摘The occurrence of massive CD4+ T cell depletion is one of the most prominent characteristics of human immunodeficiency virus type 1 (HIV-1) infection during acute phase, resulting in unrestorable destruction to the immune system. The infected host undergoes an asymptomatic period lasting several years with low viral load and ostensibly healthy status, which is presumably due to virus-specific adaptive immune responses. In the absence of therapy, an overwhelming majority of cases develop to AIDS within 8-10 years of latent infection. In this review, we discuss the roles in AIDS pathogenesis played by massive CD4+ T lymphocytes depletion in gut-associated lymphoid tissue (GALT) during acute infection and abnormal immune activation emerging in the later part of chronic phase.
基金supported by the National Natural Science Foundation of China(21325208,21172209,21361140372,21202006)the National Basic Research Program of China(2012CB215306)+2 种基金Financial Resources Federal Credit Union(WK2060190025,WK2060190040,FRF-TP-14-015A2)Chinese Academy of Sciences(KJCX2-EW-J02)Program for Changjiang Scholars and Innovative Research Team and the supercomputer center of Shanghai and USTC
文摘A theoretical study is carried out on Gaunt＇s palladium-catalyzed selective C（sp3）-H activation of unprotected aliphatic amines. In this reaction, the methyl group is proposed to be activated through a four-membered cyclometallation pathway even though an ethyl group is present in the substrate. Our calculation shows that the methyl and ethyl activation processes proceed in nitrogen-atom-directed pathway rather than carbonyl-directed one. More important, methyl activation is more favorable than ethyl activation with nitrogen atom as the directing group. Further studies on the structural parameters show that the lactone structure in cyclic substrate is the origin of the selective methyl activation. When the lactone moiety is changed to ketone, ether or alkyl, the selectivity could be reversed so that the ethyl activation becomes more favorable. This result validates the pro- oosal that lactone structure is key to selective methyl activation.
