Although glycogen synthase kinase-3 （GSK-3） might act as a tumor suppressor since its inhibition is expected to mimic the activation of Wnt-signaling pathway, GSK-3β may contribute to NF-κB activation in cancer ce...Although glycogen synthase kinase-3 （GSK-3） might act as a tumor suppressor since its inhibition is expected to mimic the activation of Wnt-signaling pathway, GSK-3β may contribute to NF-κB activation in cancer cells leading to increased cancer cell proliferation and survival. Here we report that GSK-3β activity was involved in the proliferation of human ovarian cancer cell both in vitro and in vivo. Inhibition of GSK-3 activity by pharmacological inhibitors suppressed proliferation of the ovarian cancer cells. Overexpressing constitutively active form of GSK-3β induced entry into the S phase, increased cyclin D1 expression and facilitated the proliferation of ovarian cancer cells. Furthermore, GSK-3 inhibition prevented the formation of the tumor in nude mice generated by the inoculation of human ovarian cancer cells. Our findings thus suggest that GSK-3β activity is important for the proliferation of ovarian cancer cells, implicating this kinase as a potential therapeutic target in ovarian cancer.展开更多
AIM： To investigate the regulatory mechanism of glycogen synthase kinase 3β（GSK3β） in epithelialmesenchymal transition（EMT） process after proliferative vitreoretinopathy（PVR） induction. METHODS： Experimenta...AIM： To investigate the regulatory mechanism of glycogen synthase kinase 3β（GSK3β） in epithelialmesenchymal transition（EMT） process after proliferative vitreoretinopathy（PVR） induction. METHODS： Experimental PVR was induced by intravitreal injection of retinal pigment epithelium（RPE） cells in the eyes of rabbits. A PI3 K/Akt inhibitor（wortmannin） and a GSK3β inhibitor（Li Cl） were also injected at different time during PVR progress. Electroretinogram（ERG）, ocular fundus photographs, and B-scan ultrasonography were used to observe the PVR progress. Western blot test on the extracted retina were performed at 1, 2, 4 wk. The expression of the mesenchymal marker vimentin was determined by immunohistochemistry. Toxicity of wortmannin and Li Cl were evaluated by ERG and Td Tmediated d UTP nick-end labeling（TUNEL） assay. The vitreous was also collected for metabolomic analysis. RESULTS： Experimental PVR could significantly lead to EMT, along with the suppressed expression of GSK3β and the activation of Wnt/β-catenin and PI3 K/Akt pathways. It was verified that upregulating the expression of GSK3β could effectively inhibit EMT process by suppressing Wnt/β-catenin and PI3 K/Akt pathways. CONCLUSION： GSK3β effectively inhibits EMT via the Wnt/β-catenin and PI3 K/Akt pathways. GSK3β may be regarded as a promising target of experimental PVR inhibition.展开更多
From the fruit of Rosa davidii Crep., eleven compounds were isolated and identified by spectral evidence, viz. 2 alpha, 3 beta, 19 beta -trihydroxyl-olean-12-en-28-oic acid (1), 2 alpha, 3 beta -dihydroxyl-urs-28 (13)...From the fruit of Rosa davidii Crep., eleven compounds were isolated and identified by spectral evidence, viz. 2 alpha, 3 beta, 19 beta -trihydroxyl-olean-12-en-28-oic acid (1), 2 alpha, 3 beta -dihydroxyl-urs-28 (13)-lactone (2), arjunic acid (3), euscaphic acid (4), 2 alpha, 3 beta -dihydroxyl-urs-12-en-28-oic acid (5), oleanolic acid (6), kaempferol (7), tiliroside (8), quercetin (9), daucosterol (10) and beta -sitosterol (11). Among them, 1 and 2 were new compounds.展开更多
Three new triterpenes, 3β,21α-dihydroxylupen-18（19）-en （1）, 3β,25-dihydroxytirucalla- 7,23（24）-dien （2）, and 21α-hydroxy-19α-hydrogentaraxastero1-20（30）-en （3） were obtained from an ethyl acetate extr...Three new triterpenes, 3β,21α-dihydroxylupen-18（19）-en （1）, 3β,25-dihydroxytirucalla- 7,23（24）-dien （2）, and 21α-hydroxy-19α-hydrogentaraxastero1-20（30）-en （3） were obtained from an ethyl acetate extract of the whole plant of Siyekucai （Ixeris chinensis）. The structures of 1-3 were determined by spectroscopic methods （EIMS, IR, 1D and 2D NMR）.展开更多
Background:Alzheimer’s disease(AD)is an age-related and progressive neurodegenerative disease that causes substantial public health care burdens.Intensive efforts have been made to find effective and safe treatment a...Background:Alzheimer’s disease(AD)is an age-related and progressive neurodegenerative disease that causes substantial public health care burdens.Intensive efforts have been made to find effective and safe treatment against AD.Salidroside(Sal)is the main effective component of Rhodiola rosea L.,which has several pharmacological activities.The objective of this study was to investigate the efficacy of Sal in the treatment of AD transgenic Drosophila and the associated mechanisms.Methods:We used tau transgenic Drosophila line(TAU)in which tau protein is expressed in the central nervous system and eyes by the Gal4/UAS system.After feeding flies with Sal,the lifespan and locomotor activity were recorded.We further examined the appearance of vacuoles in the mushroom body using immunohistochemistry,and detected the levels of total glycogen synthase kinase 3β(t-GSK-3β),phosphorylated GSK-3β(p-GSK-3β),t-tau and p-tau in the brain by western blot analysis.Results:Our results showed that the longevity was improved in salidroside-fed Drosophila groups as well as the locomotor activity.We also observed less vacuoles in the mushroom body,upregulated level of p-GSK-3βand downregulated p-tau following Sal treatment.Conclusion:Our data presented the evidence that Sal was capable of reducing the neurodegeneration in tau transgenic Drosophila and inhibiting neuronal loss.The neuroprotective effects of Sal were associated with its up-regulation of the p-GSK-3βand down-regulation of the p-tau.展开更多
A new sterol, ergosta-8(9),22-diene-3,5,6,7-tetraol(3β,5α,6β,7α,22E)(A) together with three known sterols: 3β, 5α,6β-trihydroxyergosta-7,22-diene (B), 3β-hydroxy-5α,8α- epidioxyer-gosta-6,22-diene (C) and er...A new sterol, ergosta-8(9),22-diene-3,5,6,7-tetraol(3β,5α,6β,7α,22E)(A) together with three known sterols: 3β, 5α,6β-trihydroxyergosta-7,22-diene (B), 3β-hydroxy-5α,8α- epidioxyer-gosta-6,22-diene (C) and ergosterol (D) were isolated from the mycelia of an unidentified endophytic fungus separated from Castaniopsis fissa (chestnut tree). Compound A exhibited potent selective cytotoxicity against Bel-7402, NCI4460 and L-02 cell lines with IC50 values 8.445, 5.03, 13.621 μg/mL, respectively.展开更多
文摘Although glycogen synthase kinase-3 （GSK-3） might act as a tumor suppressor since its inhibition is expected to mimic the activation of Wnt-signaling pathway, GSK-3β may contribute to NF-κB activation in cancer cells leading to increased cancer cell proliferation and survival. Here we report that GSK-3β activity was involved in the proliferation of human ovarian cancer cell both in vitro and in vivo. Inhibition of GSK-3 activity by pharmacological inhibitors suppressed proliferation of the ovarian cancer cells. Overexpressing constitutively active form of GSK-3β induced entry into the S phase, increased cyclin D1 expression and facilitated the proliferation of ovarian cancer cells. Furthermore, GSK-3 inhibition prevented the formation of the tumor in nude mice generated by the inoculation of human ovarian cancer cells. Our findings thus suggest that GSK-3β activity is important for the proliferation of ovarian cancer cells, implicating this kinase as a potential therapeutic target in ovarian cancer.
基金Supported by the National Natural Science Foundation of China(No.81371039)Shanghai Natural Science Foundation(No.18ZR1440200)
文摘AIM： To investigate the regulatory mechanism of glycogen synthase kinase 3β（GSK3β） in epithelialmesenchymal transition（EMT） process after proliferative vitreoretinopathy（PVR） induction. METHODS： Experimental PVR was induced by intravitreal injection of retinal pigment epithelium（RPE） cells in the eyes of rabbits. A PI3 K/Akt inhibitor（wortmannin） and a GSK3β inhibitor（Li Cl） were also injected at different time during PVR progress. Electroretinogram（ERG）, ocular fundus photographs, and B-scan ultrasonography were used to observe the PVR progress. Western blot test on the extracted retina were performed at 1, 2, 4 wk. The expression of the mesenchymal marker vimentin was determined by immunohistochemistry. Toxicity of wortmannin and Li Cl were evaluated by ERG and Td Tmediated d UTP nick-end labeling（TUNEL） assay. The vitreous was also collected for metabolomic analysis. RESULTS： Experimental PVR could significantly lead to EMT, along with the suppressed expression of GSK3β and the activation of Wnt/β-catenin and PI3 K/Akt pathways. It was verified that upregulating the expression of GSK3β could effectively inhibit EMT process by suppressing Wnt/β-catenin and PI3 K/Akt pathways. CONCLUSION： GSK3β effectively inhibits EMT via the Wnt/β-catenin and PI3 K/Akt pathways. GSK3β may be regarded as a promising target of experimental PVR inhibition.
文摘Three new triterpenes, 3β,21α-dihydroxylupen-18（19）-en （1）, 3β,25-dihydroxytirucalla- 7,23（24）-dien （2）, and 21α-hydroxy-19α-hydrogentaraxastero1-20（30）-en （3） were obtained from an ethyl acetate extract of the whole plant of Siyekucai （Ixeris chinensis）. The structures of 1-3 were determined by spectroscopic methods （EIMS, IR, 1D and 2D NMR）.
基金This work was supported by grants from the National Natural Science Fund(91332107,81430022,81371407).
文摘Background:Alzheimer’s disease(AD)is an age-related and progressive neurodegenerative disease that causes substantial public health care burdens.Intensive efforts have been made to find effective and safe treatment against AD.Salidroside(Sal)is the main effective component of Rhodiola rosea L.,which has several pharmacological activities.The objective of this study was to investigate the efficacy of Sal in the treatment of AD transgenic Drosophila and the associated mechanisms.Methods:We used tau transgenic Drosophila line(TAU)in which tau protein is expressed in the central nervous system and eyes by the Gal4/UAS system.After feeding flies with Sal,the lifespan and locomotor activity were recorded.We further examined the appearance of vacuoles in the mushroom body using immunohistochemistry,and detected the levels of total glycogen synthase kinase 3β(t-GSK-3β),phosphorylated GSK-3β(p-GSK-3β),t-tau and p-tau in the brain by western blot analysis.Results:Our results showed that the longevity was improved in salidroside-fed Drosophila groups as well as the locomotor activity.We also observed less vacuoles in the mushroom body,upregulated level of p-GSK-3βand downregulated p-tau following Sal treatment.Conclusion:Our data presented the evidence that Sal was capable of reducing the neurodegeneration in tau transgenic Drosophila and inhibiting neuronal loss.The neuroprotective effects of Sal were associated with its up-regulation of the p-GSK-3βand down-regulation of the p-tau.
文摘A new sterol, ergosta-8(9),22-diene-3,5,6,7-tetraol(3β,5α,6β,7α,22E)(A) together with three known sterols: 3β, 5α,6β-trihydroxyergosta-7,22-diene (B), 3β-hydroxy-5α,8α- epidioxyer-gosta-6,22-diene (C) and ergosterol (D) were isolated from the mycelia of an unidentified endophytic fungus separated from Castaniopsis fissa (chestnut tree). Compound A exhibited potent selective cytotoxicity against Bel-7402, NCI4460 and L-02 cell lines with IC50 values 8.445, 5.03, 13.621 μg/mL, respectively.
