Browsing by Author "Chen, Kai"

Now showing 1 - 4 of 4
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    Attenuation of epigenetic regulator SMARCA4 and ERK-ETS signaling suppresses aging-related dopaminergic degeneration
    (Wiley, 2020-08-04) Sun, Ling; Zhang, Jie; Chen, Wenfeng; Chen, Yun; Zhang, Xiaohui; Yang, Mingjuan; Xiao, Min; Ma, Fujun; Yao, Yizhou; Ye, Meina; Zhang, Zhenkun; Chen, Kai; Chen, Fei; Ren, Yujun; Ni, Shiwei; Zhang, Xi; Yan, Zhangming; Sun, Zhi-Rong; Zhou, Hai-Meng; Yang, Hongqin; Xie, Shusen; Haque, M. Emdadul; Huang, Kun; Yang, Yufeng; Medical and Molecular Genetics, School of Medicine
    How complex interactions of genetic, environmental factors and aging jointly contribute to dopaminergic degeneration in Parkinson's disease (PD) is largely unclear. Here, we applied frequent gene co‐expression analysis on human patient substantia nigra‐specific microarray datasets to identify potential novel disease‐related genes. In vivo Drosophila studies validated two of 32 candidate genes, a chromatin‐remodeling factor SMARCA4 and a biliverdin reductase BLVRA. Inhibition of SMARCA4 was able to prevent aging‐dependent dopaminergic degeneration not only caused by overexpression of BLVRA but also in four most common Drosophila PD models. Furthermore, down‐regulation of SMARCA4 specifically in the dopaminergic neurons prevented shortening of life span caused by α‐synuclein and LRRK2. Mechanistically, aberrant SMARCA4 and BLVRA converged on elevated ERK‐ETS activity, attenuation of which by either genetic or pharmacological manipulation effectively suppressed dopaminergic degeneration in Drosophila in vivo. Down‐regulation of SMARCA4 or drug inhibition of MEK/ERK also mitigated mitochondrial defects in PINK1 (a PD‐associated gene)‐deficient human cells. Our findings underscore the important role of epigenetic regulators and implicate a common signaling axis for therapeutic intervention in normal aging and a broad range of age‐related disorders including PD.
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    Preparation of PVA-GO Composite Hydrogel and Effect of Ionic Coordination on Its Properties
    (IOP, 2020-07) Wu, Xiaofang; Xie, Yingying; Xue, Chao; Chen, Kai; Yang, Xuehui; Xu, Linmin; Qi, Jianwei; Zhang, Dekun; Mechanical and Energy Engineering, School of Engineering and Technology
    This paper adopts a method combining hybrid self-assembly, cyclic freezing-thawing and annealing treatment to prepare polyvinyl alcohol (PVA) and graphene oxide (GO) composite hydrogel. Then, the PVA-GO composite hydrogels are re-swelled in different ionic solutions (NaCl, MgCl2, CaCl2 and AlCl3) to improve mechanical strength, toughness and wear resistance by the ionic coordination bonds. The microstructure and morphology are characterized by Fourier transforms infrared spectroscopy (FTIR), x-ray diffraction (XRD) and Scanning electron microscopy (SEM), finding that the internal structure is porous three-dimensional network. Mechanical experiments indicate that the composite hydrogel with GO content of 0.05 wt% immersed in MgCl2 solution displays the best mechanical properties overall. Its tensile strength can reach 11.10 MPa and the elastic modulus reaches 1.72 MPa, which is 175% and 85% higher than the pure PVA, respectively. Sliding friction experiments illustrate that the composite hydrogel immersed in AlCl3 solution exhibits the lowest friction coefficient, and the higher the valence state of metal cation is, the better the wear reduction effect is. We expect to enrich the development of PVA-GO hydrogels in tissue engineering through synergy of hydrogen bonds and ionic coordination bonds.
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    Rab23 negatively regulates Gli1 transcriptional factor in a Su(Fu)-dependent manner
    (Elsevier, 2012) Chi, Sumin; Xie, Guorui; Liu, Hailan; Chen, Kai; Zhang, Xiaoli; Li, Chengxin; Xie, Jingwu; Pediatrics, School of Medicine
    Hedgehog (Hh) signaling, via the key signal transducer Smoothened (SMO) and Gli transcription factors, is essential for embryonic development and carcinogenesis. While the biological relevance of hedgehog signaling to cancer is well established, very little is known about the molecular mechanisms by which signaling transduction of this pathway occurs. Rab23 was discovered as a negative regulator of the Hh pathway through a mouse genetic study. Here we report that Rab23 directly associates with Su(Fu) and inhibits Gli1 function in a Su(Fu)-dependent manner. By confocal microscope and immunoprecipitation, we detected interaction between Rab23 and Su(Fu). Using Gli1-mediated reporter gene analysis, we found that Rab23 can suppress Gli1 transcriptional activity in wild type but not Su(Fu) null fibroblasts. Similarly, Rab23 expression reduced the nuclear localization of Gli1 in wild type but not Su(Fu) null fibroblast cells. Consistent with the GTPase motif in the protein, we showed that Rab23 has GTPase activity. The dominant negative form of Rab23 was unable to suppress Gli1-mediated transcriptional activity. Taken together, these data provide evidence to support that Rab23 negatively regulates Gli1 activity in a Su(Fu)-dependent manner.
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    Study on the technology and properties of 3D bioprinting SF/GT/n-HA composite scaffolds
    (Elsevier, 2019-03) Wu, Xiaofang; Chen, Kai; Zhang, Dekun; Xu, Linmin; Yang, Xuehui; Mechanical and Energy Engineering, School of Engineering and Technology
    In this paper, three kinds of natural polymer materials, silk fibroin (SF), gelatin (GT), and nano-hydroxyapatite (n-HA), are mixed as 3D printing bioink to mimic protein polysaccharide and collagen fibers in natural articular cartilage. By changing the SF content, SF/GT/n-HA composite scaffolds with different ratios are prepared using 3D bioprinting technology. The microstructure and morphology, biological properties and mechanical properties of composite scaffolds are characterized. The results show that the printing precision of the bioink with 10% SF is best, and the composite scaffold with 10% SF also exhibits better mechanical properties, whose tensile elastic modulus is 10.60 ± 0.32 MPa and the compression elastic modulus is 1.22 ± 0.06 MPa. These studies are helpful to understand the interaction between SF, GT and n-HA, and provide a theoretical basis for the preparation of better silk fibroin-based composite scaffolds.