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      • Expression of Ang-2/Tie-2 and PI3K/AKT in Colorectal Cancer

        Zhang, Ji-Hong,Wang, Li-Hua,Li, Xiang-Jun,Wang, Ai-Ping,Reng, Li-Qun,Xia, Feng-Guo,Yang, Zhi-Ping,Jiang, Jing,Wang, Xiao-Dan,Wen, Chun-Yang Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.20

        Purpose: To study the expression of angiogenin-2 (Ang-2) and its receptor Tie-2 in colorectal cancer and discuss the possible mechanisms behind this process. Materials and Methods: Using the streptavidin-peroxidase (SP) immunohistochemical method, paraffin sections from 100 colorectal cancer samples and 10 samples from tumor-adjacent normal tissue (> 2 cm from the edge of the gross tumor) were tested for protein expression of Ang-2, Tie-2, PI3K, and AKT. Reverse transcription-polymerase chain reaction and Western blots were further used to measure expression of the 4 genes and proteins in 20 freshly-resected colorectal cancer samples and tumor-adjacent normal tissues. Results: In colorectal cancer tissues, the expression of the Ang-2, Tie-2, PI3K, and AKT genes and their proteins was significantly higher than in tumor-adjacent normal tissues. Protein expression in poorly-differentiated adenocarcinoma was higher than that in well and moderately differentiated adenocarcinoma. According to Duke's classification, the protein expression in Stages C and D was significantly higher than that in Stages A and B. In the group with lymphatic metastasis, the protein expression was higher than that without lymphatic metastasis. Conclusions: In colorectal cancer, the expression of the Ang-2, Tie-2, PI3K, and AKT genes and their proteins is markedly higher than those in tumor-adjacent normal tissues. No correlation was observed between protein expression and gender, location, or histologic type. Correlations did exist between protein expression and differentiation level, stage of Duke's classification, and lymphatic metastasis; in colorectal cancer tissues with lower differentiation levels, higher stages of Duke's classification, and lymphatic metastasis, the expression of all 4 proteins was higher. The study of their expression patterns and relationships with aggression and metastasis will provide a valuable experimental foundation for assessing prognosis and targeted therapy of colorectal cancer.

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        The role of ginsenoside Rb1, a potential natural glutathione reductase agonist, in preventing oxidative stress-induced apoptosis of H9C2 cells

        Hui-Jie Fan,Zhang-Bin Tan,Yu-Ting Wu,Xiao-Reng Feng,Yi-Ming Bi,Ling-Peng Xie,Wen-Tong Zhang,Zhi Ming,Bin Liu,Ying-Chun Zhou 고려인삼학회 2020 Journal of Ginseng Research Vol.44 No.2

        Background: Oxidative stress-induced cardiomyocytes apoptosis is a key pathological process inischemic heart disease. Glutathione reductase (GR) reduces glutathione disulfide to glutathione (GSH) toalleviate oxidative stress. Ginsenoside Rb1 (GRb1) prevents the apoptosis of cardiomyocytes; however,the role of GR in this process is unclear. Therefore, the effects of GRb1 on GR were investigated in thisstudy. Methods: The antiapoptotic effects of GRb1 were evaluated in H9C2 cells by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, annexin V/propidium iodide staining, and Western blotting. Theantioxidative effects were measured by a reactive oxygen species assay, and GSH levels and GR activitywere examined in the presence and absence of the GR inhibitor 1,3-bis-(2-chloroethyl)-1-nitrosourea. Molecular docking and molecular dynamics simulations were used to investigate the binding of GRb1 toGR. The direct influence of GRb1 on GR was confirmed by recombinant human GR protein. Results: GRb1 pretreatment caused dose-dependent inhibition of tert-butyl hydroperoxide-induced cellapoptosis, at a level comparable to that of the positive control N-acetyl-L-cysteine. The binding energybetween GRb1 and GR was positive ( 6.426 kcal/mol), and the binding was stable. GRb1 significantlyreduced reactive oxygen species production and increased GSH level and GR activity without altering GRprotein expression in H9C2 cells. Moreover, GRb1 enhanced the recombinant human GR protein activityin vitro, with a half-maximal effective concentration of z2.317 mM. Conversely, 1,3-bis-(2-chloroethyl)-1-nitrosourea co-treatment significantly abolished the GRb1’s apoptotic and antioxidative effects of GRb1in H9C2 cells. Conclusion: GRb1 is a potential natural GR agonist that protects against oxidative stresseinducedapoptosis of H9C2 cells.

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        The role of ginsenoside Rb1, a potential natural glutathione reductase agonist, in preventing oxidative stress-induced apoptosis of H9C2 cells

        Fan, Hui-Jie,Tan, Zhang-Bin,Wu, Yu-Ting,Feng, Xiao-Reng,Bi, Yi-Ming,Xie, Ling-Peng,Zhang, Wen-Tong,Ming, Zhi,Liu, Bin,Zhou, Ying-Chun The Korean Society of Ginseng 2020 Journal of Ginseng Research Vol.44 No.2

        Background: Oxidative stress-induced cardiomyocytes apoptosis is a key pathological process in ischemic heart disease. Glutathione reductase (GR) reduces glutathione disulfide to glutathione (GSH) to alleviate oxidative stress. Ginsenoside Rb1 (GRb1) prevents the apoptosis of cardiomyocytes; however, the role of GR in this process is unclear. Therefore, the effects of GRb1 on GR were investigated in this study. Methods: The antiapoptotic effects of GRb1 were evaluated in H9C2 cells by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, annexin V/propidium iodide staining, and Western blotting. The antioxidative effects were measured by a reactive oxygen species assay, and GSH levels and GR activity were examined in the presence and absence of the GR inhibitor 1,3-bis-(2-chloroethyl)-1-nitrosourea. Molecular docking and molecular dynamics simulations were used to investigate the binding of GRb1 to GR. The direct influence of GRb1 on GR was confirmed by recombinant human GR protein. Results: GRb1 pretreatment caused dose-dependent inhibition of tert-butyl hydroperoxide-induced cell apoptosis, at a level comparable to that of the positive control N-acetyl-L-cysteine. The binding energy between GRb1 and GR was positive (-6.426 kcal/mol), and the binding was stable. GRb1 significantl reduced reactive oxygen species production and increased GSH level and GR activity without altering GR protein expression in H9C2 cells. Moreover, GRb1 enhanced the recombinant human GR protein activity in vitro, with a half-maximal effective concentration of ≈2.317 μM. Conversely, 1,3-bis-(2-chloroethyl)-1-nitrosourea co-treatment significantly abolished the GRb1's apoptotic and antioxidative effects of GRb1 in H9C2 cells. Conclusion: GRb1 is a potential natural GR agonist that protects against oxidative stress-induced apoptosis of H9C2 cells.

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