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Juan Feng,Xiang Li,Xiaolan Yang,Chun Zhang,Yonghua Yuan,Jun Pu,Yunsheng Zhao,Yanling Xie,Huidong Yuan,Youquan Bu,Fei Liao 대한약학회 2010 Archives of Pharmacal Research Vol.33 No.11
The use of uricase-deficient mammals to screen formulations of engineered uricases as potential drugs for hyperuricemia involves heavy costs and presents a technical bottleneck. Herein, a new practical system was investigated to evaluate the pharmacological significance of a bacterial uricase based on its ability to eliminate uric acid in plasma in vitro, its pharmacokinetics in vivo in healthy rats, and the modeled pharmacodynamics in vivo. This uricase, before and after modification with the monomethyl ether of poly(ethylene glycol)-5000, effectively eliminated uric acid in vitro in rabbit plasma, but its action was susceptible to xanthine inhibition. After intravenous injection of the modified uricase without purification, a bi-exponential model fit well to uricase activities in vivo in the plasma of healthy rats; the half-life of the modified uricase was estimated without interference from the unmodified uricase leftover in the sample and was nearly 100-fold longer than that of the unmodified uricase. Using a model of the elimination of uric acid in vivo taking into account of uricase pharmacokinetics and xanthine inhibition, modeled pharmacodynamics supported that the half-life of uricase and its susceptibility to xanthine are crucial for the pharmacological significance of uricase. Hence,this practical system is desirable for doing preliminary screening of formulations of engineered uricases as potential drugs for hyperuricemia.
Jingang Xiong,Moqiang Xiong,Youquan Liu,Xiang Li,Shujun Hu 대한토목학회 2024 KSCE Journal of Civil Engineering Vol.28 No.2
A novel self-centering frame with Y-eccentrically braced structure (SC-YEBFs) has been proposed in this paper to solve the problem that the storey drift of structure may exceed the specified limit in standards when self-centering beam-column joints are applied in high-rise and larger spans buildings, and the SC-YEBFs not only has the self-centering performance of self-centering frame system, but also has the high lateral stiffness and energy dissipating capacity of Y-Eccentrically braced frame. To study the lateral load behavior and influencing factors of SC-YEBFs, cyclic loading tests of two scaled specimens of SC-YEBFs substructure (SCS) were conducted, and seven finite element models corrected by the experiment were established to perform parametric analysis. The experiment and finite element analysis results indicated that the shear link has greatly increased the lateral stiffness and energy dissipating capacity of the self-centering structure, at the same time, it has maintained a good self-centering performance and replace ability. With an increase in the cross-sectional area and initial prestress of post-tensioned steel strands, the lateral load capacity and self-centering performance can be improved. The self-centering performance can be effectively improved by reducing the friction coefficient at the rotation connections. SC-YEBFs further extending the application field of self-centering structural systems, and making it possible to be applied to high-rise and larger spans structures.
PRR11 and SKA2 gene pair is overexpressed and regulated by p53 in breast cancer
Wang, Yitao,Zhang, Chunxue,Mai, Li,Niu, Yulong,Wang, Yingxiong,Bu, Youquan Korean Society for Biochemistry and Molecular Biol 2019 BMB Reports Vol.52 No.2
Our previous study found that two novel cancer-related genes, PRR11 and SKA2, constituted a classic gene pair that was regulated by p53 and NF-Y in lung cancer. However, their role and regulatory mechanism in breast cancer remain elusive. In this study, we found that the expression levels of PRR11 and SKA2 were upregulated and have a negative prognotic value in breast cancer. Loss-of-function experiments showed that RNAi-mediated knockdown of PRR11 and/or SKA2 inhibited proliferation, migration, and invasion of breast cancer cells. Mechanistic experiments revealed that knockdown of PRR11 and/or SKA2 caused dysregulation of several downstream genes, including CDK6, TPM3, and USP12, etc. Luciferase reporter assays demonstrated that wild type p53 significantly repressed the PRR11-SKA2 bidirectional promoter activity, but not NF-Y. Interestingly, NF-Y was only essential for and correlated with the expression of PRR11, but not SKA2. Consistently, adriamycin-induced (ADR) activation of endogenous p53 also caused significant repression of the PRR11 and SKA2 gene pair expression. Notably, breast cancer patients with lower expression levels of either PRR11 or SKA2, along with wild type p53, exhibited better disease-free survival compared to others with p53 mutations and/or higher expression levels of either PRR11 or SKA2. Collectively, our study indicates that the PRR11 and SKA2 transcription unit might be an oncogenic contributor and might serve as a novel diagnostic and therapeutic target in breast cancer.