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( Jiejie Dong ),( Bo Zhai ),( Weihua Sun ),( Fengli Hu ),( Hao Cheng ),( Lishan Xu ),( Jun Xu ) 대한간학회 2017 춘·추계 학술대회 (KASL) Vol.2017 No.1
Aims: Sorafenib, an orally available kinase inhibitor, is the standard first-line systemic drug for advanced hepatocellular carcinoma (HCC), and it exerts potent inhibitory activity against epithelial-mesenchymal transition (EMT) and multidrug resistance (MDR) by inhibiting mitogen- activated protein kinase (MAPK) signalling in HCC. However, after long-term exposure to sorafenib, HCC cells exhibit EMT and resistance to sorafenib. The activation of AKT by sorafenib is thought to be responsible for the development of these characteristics. The present study aims to examine the underlying mechanism and seek potential strategies to reverse this resistance and the progression to EMT. Methods: Cell viability assay; Transfection of siRNA; Construction of the pCDNA3.1-Snail eukaryotic expression vector and transfection; Cell migration and invasion assays; Western blot analysis; Real-time reverse transcription PCR. Results: Sorafenib-resistant cells showed increased metastatic and invasive ability, with a higher expression of P-glycoprotein (P-gp), compared with the parental cells. This phenomenon was at least partially due to EMT and the appearance of MDR in sorafenib-resistant HCC cells. Moreover, MDR was a downstream molecular event of EMT. Silencing Snail with siRNA blocked EMT and partially reversed the MDR, thereby markedly abolishing invasion and metastasis in sorafenib- resistant HCC cells, but silencing of MDR1 had no effect on the EMT phenotype. Additionally, HCC parental cells that were stably transfected with pCDNA3.1-Snail exhibited EMT and MDR. Two sorafenib- resistant HCC cell lines, established from human HCC HepG2 and Huh7 cells, were refractory to sorafenib-induced growth inhibition but were sensitive to MK-2206, a novel allosteric AKT inhibitor. Thus, the combination of sorafenib and MK-2206 led to significant reversion of the EMT phenotype and P-gp-mediated MDR by downregulating phosphorylated AKT. Conclusions: These findings underscore the significance of EMT, MDR and enhanced PI3K/AKT signalling in sorafenib-resistant HCC cells.
Stability of a Class of Switched Stochastic Nonlinear Systems under Asynchronous Switching
Yu Kang,Dihua Zhai,Ping Zhao,Yun-Bo Zhao 제어·로봇·시스템학회 2012 International Journal of Control, Automation, and Vol.10 No.6
The stability of a class of switched stochastic nonlinear retarded systems with asynchronous switching controller is investigated. By constructing a virtual switching signal and using the average dwell time approach incorporated with Razumikhin-type theorem, the sufficient criteria for pth moment exponential stability and global asymptotic stability in probability are given. It is shown that the stability of the asynchronous stochastic systems can be guaranteed provided that the average dwell time is sufficiently large and the mismatched time between the controller and the systems is suffi-ciently small. This result is then applied to a class of switched stochastic nonlinear delay systems where the controller is designed with both state and switching delays. A numerical example illustrates the effectiveness of the obtained results.
Stratum corneun decontamination: Overview & clinical perspective
( Heidi P. Chan ),( Hong Bo Zhai ),( Howard I. Maibach ) 한국피부장벽학회 2008 한국피부장벽학회지 Vol.10 No.2
The stratum corneum(SC), being the outermost layer of the skin and constantly exposed to the environment, is always at risk for contamination. SC decontamination models & methods and their implications as well as variables influencing the effectiveness of decontamination such as timing of decontamination and chemical nature of decontaminating solutions are analyzed. These models offer promise of an enhanced understanding of mechanisms involved and development of more effective interventions.
Xi-xiang Ying,Hai-bo Li,Zheng-yun Chu,Yan-jun Zhai,Ai-jing Leng,Xun Liu,Wen-jie Zhang,Ting-guo Kang,Chun Xin 대한약학회 2008 Archives of Pharmacal Research Vol.31 No.7
To investigate the antioxidant effect of vitexin-4"-O-glucoside, a flavone glycoside, isolated from the leaves of Crataegus pinnatifida Bge. var. major, we developed a simple and sensitive high-performance liquid chromatography (HPLC) method to determine levels of malondialdehyde (MDA) in ECV304 cell culture medium after induction by tert-butyl-hydroperoxide (TBHP). The preparation of analyzed samples involved a one-step derivatization with thiobarbituric acid (TBA). HPLC analysis was performed on a SynergiTM Hydro-RP, a polar end-capped C18 column (250×4.6 mm, 4 μm), using an acetonitrile-ammonium acetate aqueous solution (10 mM, pH 6.8) as the mobile phase under linear gradient conditions with UV detection at 532 nm. The calibration curve was linear over 0.0125-1.25 μM MDA (r = 0.9951). Relative standard deviations (RSDs) of intra-day and inter-day precision were less than 6.1% and 5.0%, respectively. The mean recovery was 96.9 ± 1.6%. The lower limit of quantification (LLOQ) of MDA was 0.0125 μM. This chromatographic method was successfully applied to investigating the in vitro antioxidant effect of vitexin-4"-O-glucoside. Vitexin-4"-O-glucoside (120 M) protected ECV304 cells from peroxidation induced by TBHP.