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Mechanistic Analysis of Taxol-induced Multidrug Resistance in an Ovarian Cancer Cell Line
Wang, Ning-Ning,Zhao, Li-Jun,Wu, Li-Nan,He, Ming-Feng,Qu, Jun-Wei,Zhao, Yi-Bing,Zhao, Wan-Zhou,Li, Jie-Shou,Wang, Jin-Hua Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.9
Objectives: To establish a taxol-resistant cell line of human ovarian carcinoma (A2780/Taxol) and investigate its biological features. Methods: The drug-resistant cell line (A2780/Taxol) was established by continuous stepwise selection with increasing concentrations of Taxol. Cell morphology was assessed by microscopy and growth curves were generated with in vitro and in vivo tumor xenograft models. With rhodamine123 (Rh123) assays, cell cycle distribution and the apoptotic rate were analyzed by flow cytometry (FCM). Drug resistance-related and signal associated proteins, including P-gp, MRPs, caveolin-1, PKC-${\alpha}$, Akt, ERK1/2, were detected by Western blotting. Results: A2780/Taxol cells were established with stable resistance to taxol. The drug resistance index (RI) was 430.7. Cross-resistance to other drugs was also shown, but there was no significant change to radioresistance. Compared with parental cells, A2780/Taxol cells were significantly heteromorphous, with a significant delay in population doubling time and reduced uptake of Rh123 (p<0.01). In vivo, tumor take by A2780 cells was 80%, and tumor volume increased gradually. In contrast, with A2780/Taxol cells in xenograft models there was no tumor development. FCM analysis revealed that A2780/Taxol cells had a higher percentage of G0/G1 and lower S phase, but no changes of G2 phase and the apoptosis rate. Expression of P-gp, MRP1, MRP2, BCRP, LRP, caveolin-1, PKC-${\alpha}$, Phospho-ERK1/2 and Phospho-JNK protein was significantly up-regulated, while Akt and p38 MARK protein expression was not changed in A2780/Taxol cells. Conclusion: The A2780/Taxol cell line is an ideal model to investigate the mechanism of muti-drug resistance related to overexpression of drug-resistance associated proteins and activation of the PKC-${\alpha}/ERK$ (JNK) signaling pathway.
Zhi-Ning Huang,Han Liang,Hong Qiao,Bao-Rui Wang,Ning Qu,Hua Li,Run-Run Zhou,Li-Juan Wang,Shan-Hua Li,Fu-Nan Li 대한약학회 2018 Archives of Pharmacal Research Vol.41 No.12
Guided by bioisosterism and pharmacokinetic parameters, we designed and synthesized a series of novel benzamide derivatives. Preliminary in vitro studies indicated that compounds 10b and 10j show significant inhibitory bioactivity in HepG2 cells (IC50 values of 0.12 and 0.13 μM, respectively). Compounds 10b and 10j induced the expression of HIF-1α protein and downstream target gene p21, and upregulated the expression of cleaved caspase-3 to promote tumor cells apoptosis.
Finite element generalized tooth contact analysis of double circular arc helical gears
Qu, Wentao,Peng, Xiongqi,Zhao, Ning,Guo, Hui Techno-Press 2012 Structural Engineering and Mechanics, An Int'l Jou Vol.43 No.4
This paper investigates the load sharing of double circular arc helical gears considering the influence of assembly errors. Based on a load sharing formulae, a three-dimensional finite element tooth contact analysis (TCA) is implemented with commercial software package ANSYS. The finite element grid for the double circular arc gear contact model is automatically generated by using the APDL (ANSYS Parameter Design Language) embedded in ANSYS. The realistic rotation of gears is achieved by using a coupling degree-of-freedom method. Numerical simulations are carried out to exemplify the proposed approach. The distribution of contact stress and bending stress under specific loading conditions are computed and compared with those obtained from Hertz contact theory and empirical formulae to demonstrate the efficiency of the proposed load sharing calculation formulae and TCA approach.
Lower Antibody Response in Chickens Homozygous for the Mx Resistant Allele to Avian Influenza
Qu, L.J.,Li, X.Y.,Xu, G.Y.,Ning, Z.H.,Yang, N. Asian Australasian Association of Animal Productio 2009 Animal Bioscience Vol.22 No.4
The chicken Mx gene has been regarded as a candidate gene for resistance to avian influenza virus (AIV). In this study, three groups of chickens with homozygotes (AA, GG) and heterozygotes (AG) of the resistant (A) and susceptible alleles (G) to AIV of the Mx gene were constructed from a line of dwarf egg-type chickens. These chickens were not examined for their resistant activities to AIV because the differential resistance had only been detected in vitro. The birds of the three groups were vaccinated with inactivated H5N2 AIV vaccine and the level of hemagglutination inhibition (HI) antibody to AIV was detected. The association between disease resistant activity to AIV and antibody response to AIV vaccination in the three groups was analyzed. The chickens with homozygous resistant allele A showed the lowest antibody levels, whereas the heterozygous chickens (AG) presented the highest antibody level after the boosting vaccination, which indicates that the efficiency of artificial selection on the resistant allele of Mx gene will be compromised since the homozygotes of the allele presented the weakest antibody response to the corresponding vaccine.
Finite element generalized tooth contact analysis of double circular arc helical gears
Wentao Qu,Xiongqi Peng,Ning Zhao,Hui Guo 국제구조공학회 2012 Structural Engineering and Mechanics, An Int'l Jou Vol.43 No.4
This paper investigates the load sharing of double circular arc helical gears considering the influence of assembly errors. Based on a load sharing formulae, a three-dimensional finite element tooth contact analysis (TCA) is implemented with commercial software package ANSYS. The finite element grid for the double circular arc gear contact model is automatically generated by using the APDL (ANSYS Parameter Design Language) embedded in ANSYS. The realistic rotation of gears is achieved by using a coupling degree-of-freedom method. Numerical simulations are carried out to exemplify the proposed approach. The distribution of contact stress and bending stress under specific loading conditions are computed and compared with those obtained from Hertz contact theory and empirical formulae to demonstrate the efficiency of the proposed load sharing calculation formulae and TCA approach.
Research on Discontinuous Pulse Width Modulation Algorithm for Single-phase Voltage Source Rectifier
Yang, Xi-Jun,Qu, Hao,Tang, Hou-Jun,Yao, Chen,Zhang, Ning-Yun,Blaabjerg, Frede Journal of International Conference on Electrical 2014 Journal of international Conference on Electrical Vol.3 No.4
Single phase voltage source converter (VSC) is an important power electronic converter (PEC), including single-phase voltage source inverter (VSI), single-phase voltage source rectifier (VSR), single-phase active power filter (APF) and single-phase grid-connection inverter (GCI). As the fundamental part of large scale PECs, single-phase VSC has a wide range of applications. In the paper, as first, on the basis of the concept of the discontinuous pulse-width modulation (DPWM) for three-phase VSC, a new DPWM of single-phase VSR is presented by means of zero-sequence component injection. Then, the transformation from stationary frame (abc) to rotating frame (dq) is designed after reconstructing the other orthogonal current by means of one order all-pass filter. Finally, the presented DPWM based single-phase VSR is established analyzed and simulated by means of MATLAB/SIMULINK. In addition, the DPWMs presented by D. Grahame Holmes and Thomas Lipo are discussed and simulated in brief. Obviously, the presented DPWM can also be used for single-phase VSI, GCI and APF. The simulation results show the validation of the above modulation algorithm, and the DPWM based single-phase VSR has reduced power loss and increased efficiency.
Jia-Yu Lv,Ning-Ning Zhang,Ya-Wei Du,Ying Wu,Tian-Qiang Song,Ya-Min Zhang,Yan Qu,Yu-Xin Liu,Jie Gu,Ze-Yu Wang,Yi-Bo Qiu,Bing Yang,Da-Zhi Tian,Qing-Jun Guo,Li Zhang,Ji-San Sun,Yan Xie,Zheng-Lu Wang,Xin 연세대학교의과대학 2021 Yonsei medical journal Vol.62 No.1
Purpose: The aim of this study was to compare the efficacy of liver transplantation (LT) and liver resection (LR) for hepatocellularcarcinoma (HCC) patients with portal vein tumor thrombus (PVTT) and to investigate risk factors affecting prognosis. Materials and Methods: A total of 94 HCC patients with PVTT type I (segmental PVTT) and PVTT type II (lobar PVTT) were involvedand divided into LR (n=47) and LT groups (n=47). Recurrence-free survival (RFS) and overall survival (OS) were comparedbefore and after inverse probability of treatment weighting (IPTW). Prognostic factors for RFS and OS were explored. Results: Two treatment groups were well-balanced using IPTW. In the entire cohort, LT provided a better prognosis than LR. Among patients with PVTT type I, RFS was better with LT (p=0.039); OS was not different significantly between LT and LR(p=0.093). In subgroup analysis of PVTT type I patients with α-fetoprotein (AFP) levels >200 ng/mL, LT elicited significantly longermedian RFS (18.0 months vs. 2.1 months, p=0.022) and relatively longer median OS time (23.6 months vs. 9.8 months, p=0.065). Among patients with PVTT type II, no significant differences in RFS and OS were found between LT and LR (p=0.115 and 0.335,respectively). Multivariate analyses showed treatment allocation (LR), tumor size (>5 cm), AFP and aspartate aminotransferase(AST) levels to be risk factors of RFS and treatment allocation (LR), AFP and AST as risk factors for OS. Conclusion: LT appeared to afford a better prognosis for HCC with PVTT type I than LR, especially in patients with AFP levels>200 ng/mL.
Wang, Xinxin,Ma, Shanshan,Meng, Nan,Yao, Ning,Zhang, Kun,Li, Qinghua,Zhang, Yanting,Xing, Qu,Han, Kang,Song, Jishi,Yang, Bo,Guan, Fangxia Korean Society for Molecular and Cellular Biology 2016 Molecules and cells Vol.39 No.5
Resveratrol (RES) plays a critical role in the fate of cells and longevity of animals via activation of the sirtuins1 (SIRT1) gene. In the present study, we intend to investigate whether RES could promote the self-renewal and neural-lineage differentiation in human umbilical cord derived MSCs (hUC-MSCs) in vitro at concentrations ranging from 0.1 to $10{\mu}M$, and whether it exerts the effects by modulating the SIRT1 signaling. Herein, we demonstrated that RES at the concentrations of 0.1, 1 and $2.5{\mu}M$ could promote cell viability and proliferation, mitigate senescence and induce expression of SIRT1 and Proliferating Cell Nuclear Antigen (PCNA) while inhibit the expression of p53 and p16. However, the effects were reversed by 5 and $10{\mu}M$ of RES. Furthermore, RES could promote neural differentiation in a dose-dependent manner as evidenced by morphological changes and expression of neural markers (Nestin, ${\beta}III-tubulin$ and NSE), as well as pro-neural transcription factors Neurogenin (Ngn)1, Ngn2 and Mash1. Taken together, RES exerts a dosage-dependent effect on the self-renewal and neural differentiation of hUC-MSCs via SIRT1 signaling. The current study provides a new strategy to regulate the fate of hUC-MSCs and suggests a more favorable in vitro cell culture conditions for hUCMSCs-based therapies for some intractable neurological disorders.
Fangxia Guan,Xinxin Wang,Shanshan Ma,Nan Meng,Ning Yao,Kun Zhang,Qinghua Li,Yanting Zhang,Qu Xing,Kang Han,Jishi Song,Bo Yang 한국분자세포생물학회 2016 Molecules and cells Vol.39 No.5
Resveratrol (RES) plays a critical role in the fate of cells and longevity of animals via activation of the sirtuins1 (SIRT1) gene. In the present study, we intend to investigate whether RES could promote the self-renewal and neural-lineage differentiation in human umbilical cord derived MSCs (hUC-MSCs) in vitro at concentrations ranging from 0.1 to 10 M, and whether it exerts the effects by modulating the SIRT1 signaling. Herein, we demonstrated that RES at the concentrations of 0.1, 1 and 2.5 M could promote cell viability and proliferation, mitigate senescence and induce expression of SIRT1 and Proliferating Cell Nuclear Antigen (PCNA) while inhibit the expression of p53 and p16. However, the effects were reversed by 5 and 10 M of RES. Furthermore, RES could promote neural differentiation in a dose-dependent manner as evidenced by morphological changes and expression of neural markers (Nestin, Ⅲ-tubulin and NSE), as well as pro-neural transcription factors Neurogenin (Ngn)1, Ngn2 and Mash1. Taken together, RES exerts a dosage-dependent effect on the self-renewal and neural differentiation of hUC-MSCs via SIRT1 signaling. The current study provides a new strategy to regulate the fate of hUC-MSCs and suggests a more favorable in vitro cell culture conditions for hUC-MSCs-based therapies for some intractable neurological disorders.