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        Ginsenoside compound K inhibits nuclear factor-kappa B by targeting Annexin A2

        Yushi Wang,Hongyan Zhu,He Liu,Yang Li,Bing Zhao,Ying-Hua Jin 고려인삼학회 2019 Journal of Ginseng Research Vol.43 No.3

        Background: Ginsenoside compound K(C-K), a major metabolite of ginsenoside, exhibits anticancer activityin various cancer cells and animal models. A cell signaling study has shown that C-K inhibitednuclear factor-kappa B (NF-kB) pathway in human astroglial cells and liver cancer cells. However, themolecular targets of C-K and the initiating events were not elucidated. Methods: Interaction between C-K and Annexin A2 was determined by molecular docking and thermalshift assay. HepG2 cells were treated with C-K, followed by a luciferase reporter assay for NF-lB,immunofluorescence imaging for the subcellular localization of Annexin A2 and NF-lB p50 subunit,coimmunoprecipitation of Annexin A2 and NF-lB p50 subunit, and both cell viability assay and plateclone formation assay to determine the cell viability. Results: Both molecular docking and thermal shift assay positively confirmed the interaction betweenAnnexin A2 and C-K. This interaction prevented the interaction between Annexin A2 and NF-lB p50subunit and their nuclear colocalization, which attenuated the activation of NF-lB and the expression ofits downstream genes, followed by the activation of caspase 9 and 3. In addition, the overexpression ofAnnexin A2-K320A, a C-K binding-deficient mutant of Annexin A2, rendered cells to resist C-K treatment,indicating that C-K exerts its cytotoxic activity mainly by targeting Annexin A2. Conclusion: This study for the first time revealed a cellular target of C-K and the molecular mechanismfor its anticancer activity.

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        Betulin induces reactive oxygen species-dependent apoptosis in human gastric cancer SGC7901 cells

        Yang Li,Xiaokang Liu,Dan Jiang,Yingjia Lin,Yushi Wang,Qing Li,Linlin Liu,Ying-Hua Jin 대한약학회 2016 Archives of Pharmacal Research Vol.39 No.9

        Betulin, an abundant natural compound, significantly inhibited the cell viability of advanced human gastric cancer SGC7901 cells. Mechanism study demonstrated that betulin induced apoptosis through mitochondrial Bax and Bak accumulation-mediated intrinsic apoptosis pathway. Downregulation of the anti-apoptosis proteins Bcl-2 and XIAP was involved during betulin-induced cell apoptosis. Reactive oxygen species (ROS) was generated in cells after betulin treatment in a time- and dose-dependent manner. Addition of antioxidant N-acetyl-L-cysteine (NAC) significantly attenuated betulin-induced ROS generation as well as Bcl-2 and XIAP downregulation. The mitochondrial accumulation of Bax and Bak, as well as caspase activity, was also remarkably inhibited by NAC treatment, indicating that ROS are important signaling intermediates that lead to betulin-induced apoptosis by modulating multiple apoptosis-regulating proteins in SGC7901 cells.

      • KCI등재

        Finite-time Incremental Stability Analysis for Nonlinear Switched Systems With Unstable Subsystems

        Lijuan Wang,Yuanhong Ren,Yushi Yang,Lin Guan 제어·로봇·시스템학회 2023 International Journal of Control, Automation, and Vol.21 No.10

        In this paper, finite-time incremental stability (FTIS) and finite-time incremental boundedness (FTIB) are investigated for nonlinear switched systems (NSS) with unstable systems. Firstly, based on the reverse modedependent average dwell time (MDADT) method, we propose some sufficient conditions for FTIS of NSS. Secondly, the sufficient conditions for NSS to be FTIB with an incremental performance index are given by the multiple incremental Lyapunov functions. Finally, a distinctive advantage of reverse MDADT method is that each subsystems satisfies FTIB in the activation interval. A example has been provided to show the effectiveness of the theoretic results developed.

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        Overexpression of the Cytokinin Oxidase/dehydrogenase (CKX) from Medicago sativa Enhanced Salt Stress Tolerance of Arabidopsis

        Shuxia Li,Yunru An,Shaya Hailati,Jing Zhang,Yuman Cao,Yushi Liu,Jincai Geng,Tianming Hu,Peizhi Yang 한국식물학회 2019 Journal of Plant Biology Vol.62 No.5

        Cytokinin oxidase/dehydrogenase (CKXs) areinvolved in various physiological processes, includingcytokinins (CKs) catabolism, root system architecture andresponse to abiotic stresses in plants. Alfalfa (Medicagosativa) is a widely cultivated forage which is frequentlythreatened by high salinity, and the potential role of CKXs inalleviating the salt stress in alfalfa lacked attention. In thisstudy, we isolated a CKX gene from alfalfa, MsCKX(MK177192), and identified its biological functions byoverexpressing it in Arabidopsis. MsCKX shares high sequenceidentity with CKX from other legume plants, especiallyMedicago truncatula (98%). MsCKX was clearly tissuespecific,and it was mainly expressed in roots. In addition,the expression of MsCKX increased under salt stress andabscisic acid (ABA) treatment. Overexpression of MsCKXgene increased the activity of CKX, which led to an enlargedroot system in transgenic Arabidopsis plants. Overexpressionof MsCKX gene enhanced salt tolerance of transgenic plantsby maintaining a higher K+/Na+ ratio, enhancing the activities ofantioxidant enzymes to scavenge ROS and increasing theexpression levels of stress-related genes (P5CS1, DREB2,ion transporters and H+ pumps). Taken together, these resultsshed light on the roles of MsCKX involved in salt toleranceand may have applications in salt-resistant breeding ofalfalfa.

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