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| 1 | p53 upregulated by HIF-la promotes hypoxiainduced G2/M arrest and renal fibrosis in vitro and in vivo显示文摘Hypoxia plays an important role in the genesis and progression of renal fibrosis.The underlying mechanisms, however, have not been sufficiently elucidated. We examined the role of p53 in hypoxia-induced renal fibrosis in cell culture (human and rat renal tubular epithelial cells) and a mouse unilateral ureteral obstruction (UUO) model. Cell cycle of tubular cells was determined by flow cytometry, and the expression of profibrogenic factors was determined by RT-PCR, immunohistochemistry, and western blotting. Chromatin immunoprecipitation and luciferase reporter experiments were performed to explore the effect of HIF-lα on p53 expression. We showed that, in hypoxic tubular cells, p53 upregulation suppressed the expression of CDK1 and cyclins Bl and DI, leading to cell cycle (G2/M) arrest (or delay) and higher expression of TGF-β, CTGF, collagens, and fibronectin. p53 suppression by siRNA or by a specific p53 inhibitor (PIF-α) triggered opposite effects preventing the G2/M arrest and profibrotic changes. In vivo experiments in the UUO model revealed similar antifibrotic results following intraperitoneal administration of PIF-α(2.2 mg/kg). Using gain-of-function, loss-of-function, and luciferase assays, we further identified an HRE3 region on the p53 promoter as the HIF-lα-binding site. The HIF-la-HRE3 binding resulted in a sharp transcriptional activation of p53. Collectively, we show the presence of a hypoxia-activated, p53-responsive profibrogenic pathway in the kidney. During hypoxia, p53 upregulation induced by HIF-la suppresses cell cycle progression, leading to the accumulation of G2/M cells, and activates profibrotic TGF-β and CTGF-mediated signaling pathways, causing extracellular matrix production and renal fibrosis. | Limin Liu Peng Zhang Ming Bai Lijie He Lei Zhang Ting Liu Zhen Yang Menglu Duan Minna Liu Baojian Liu Rui Du Qi Qian Shiren Sun | 2019 | Journal of Molecular Cell Biology2019，11，5： | 18 |
| 2 | ADMETNet:The knowledge base of pharmacokinetics and toxicology network显示文摘A good drug or drug candidate should not only interact with its target molecule effectively and specifically,but also be absorbed into the body,distributed to the right location,metabolized into right compounds,and eliminated out of the body in proper manner.The processes of drug getting into and out of the body involve Absorption,Distribution,Metabolism,and Excretion(ADME),which | Quan Xu Ke Liu Xingming Lin Yangmei Qin Linshan Chen Jiao Cheng Mindong Zhong Qiushun He Yinbo Li Tingwu Wang Jianbo Pan Menglu Peng Lixia Yao Zhiliang Ji | 2017 | Journal of Genetics and Genomics2017，44，5： | 2 |
| 3 | Signal generation in an isotropic medium in scanning electron acoustic microscope显示文摘在裁判员基于研究。[5 ][ 材料科学和工程, 1989; A122:57-63 ],热来源的一个改进模型被建立,在一根砍的电子横梁在频率 f 产生的一件各向同性的样品的兰姆波浪的不同模式与不可分的变换和正常功能扩大方法被获得,并且在样品的背表面联合的 PZT 的输出信号被发现。缝接(扫描电子声学的显微镜学) 的产生机制信号被讨论。它证明 SEAM 是有高空间的分辨率的一种近的领域成像技术,它的最好的侧面的空间分辨率关于 22a (一是集中的电子横梁的半径)缝接图象的试验性的结果的 .Some 在论文被介绍,它出现缝接的空间分辨率比 0.5 m 好、比样品的热散开长度小。因此,在缝接的近的领域成像的特性也试验性地被证明。 | QIAN Menglu PENG Ruolong | 2008 | Chinese Journal of Acoustics2008，27，2： | 1 |
| 4 | Next-generation finely controlled graded porous antibacterial bioceramics for high-efficiency vascularization in orbital reconstruction显示文摘Eyeball loss due to severe ocular trauma,intraocular malignancy or infection often requires surgical treatment called orbital implant reconstruction to rehabilitate the orbital volume and restore the aesthetic appearance.However,it remains a challenge to minimize the postoperative exposure and infection complications due to the inert nature of conventional orbital implants.Herein,we developed a novel Ca-Zn-silicate bioceramic implant with multi-functions to achieve the expected outcomes.The porous hardystonite(Ca2ZnSi2O7)scaffolds with triply periodic minimal surfaces(TPMS)-based pore architecture and graded pore size distribution from center to periphery(from 500 to 800μm or vice versa)were fabricated through the digital light processing(DLP)technique,and the scaffolds with homogeneous pores(500 or 800μm)were fabricated as control.The graded porous scaffolds exhibited a controlled bio-dissolving behavior and intermediate mechanical strength in comparison with the homogeneous counterparts,although all of porous implants presented significant antibacterial potential against S.aureus and E.coli.Meanwhile,the pore size-increasing scaffolds indicated more substantial cell adhesion,cell viability and angiogenesis-related gene expression in vitro.Furthermore,the gradually increasing pore feature exhibited a stronger blood vessel infiltrating potential in the dorsal muscle embedding model,and the spherical implants with such pore structure could achieve complete vascularization within 4 weeks in the eyeball enucleation rabbit models.Overall,our results suggested that the novel antibacterial hardystonite bioceramic with graded pore design has excellent potential as a next-generation orbital implant,and the pore topological features offer an opportunity for the improvement of biological performances in orbital reconstruction. | Jingyi Wang Yiyu Peng Menglu Chen Xizhe Dai Lixia Lou Changjun Wang Zhaonan Bao Xianyan Yang Zhongru Gou Juan Ye | 2022 | Bioactive Materials2022，7，10： | 0 |
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