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        Hyperglycemia-Suppressed SMARCA5 Disrupts Transcriptional Homeostasis to Facilitate Endothelial Dysfunction in Diabetes

        Ju Wang,Hui Zhou,Jinhua Shao,Shu Zhang,Jing Jin 대한당뇨병학회 2023 Diabetes and Metabolism Journal Vol.47 No.3

        Background: Dysfunction of vascular endothelial cells (ECs) plays a central role in the pathogenesis of cardiovascular complications in diabetes. SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A member 5 (SMARCA5) is a key regulator of chromatin structure and DNA repair, but its role in ECs remains surprisingly unexplored. The current study was designed to elucidate the regulated expression and function of SMARCA5 in diabetic ECs.Methods: SMARCA5 expression was evaluated in ECs from diabetic mouse and human circulating CD34<sup>+</sup> cells using quantitative reverse transcription polymerase chain reaction and Western blot. Effects of SMARCA5 manipulation on ECs function were evaluated using cell migration, <i>in vitro</i> tube formation and <i>in vivo</i> wound healing assays. Interaction among oxidative stress, SMARCA5 and transcriptional reprogramming was elucidated using luciferase reporter assay, electrophoretic mobility shift assay and chromatin immunoprecipitation.Results: Endothelial SMARCA5 expression was significantly decreased in diabetic rodents and humans. Hyperglycemia-suppressed SMARCA5 impaired EC migration and tube formation <i>in vitro</i>, and blunted vasculogenesis <i>in vivo</i>. Contrarily, overexpression of SMARCA5 <i>in situ</i> by a SMARCA5 adenovirus-incorporated hydrogel effectively promoted the rate of wound healing in a dorsal skin punch injury model of diabetic mice. Mechanistically, hyperglycemia-elicited oxidative stress suppressed <i>SMARCA5</i> transactivation in a signal transducer and activator of transcription 3 (STAT3)-dependent manner. Moreover, SMARCA5 maintained transcriptional homeostasis of several pro-angiogenic factors through both direct and indirect chromatin-remodeling mechanisms. In contrast, depletion of SMARCA5 disrupted transcriptional homeostasis to render ECs unresponsive to established angiogenic factors, which ultimately resulted in endothelial dysfunction in diabetes.Conclusion: Suppression of endothelial SMARCA5 contributes to, at least in part, multiple aspects of endothelial dysfunction, which may thereby exacerbate cardiovascular complications in diabetes.

      • KCI등재

        Cordycepsmilitaris polysaccharide triggers apoptosis and G0/G1 cell arrest in cancer cells

        Cheng Chen,Mei-LinWang,Chao Jin,Huijuan Chen,Shao-Hui Li,Shu-Ying Li,Xing-Fan Dou,Jun-Qiang Jia,Zhong-Zheng Gui 한국응용곤충학회 2015 Journal of Asia-Pacific Entomology Vol.18 No.3

        Although many studies have shown the antitumor properties of Cordyceps militaris (artificial cultivated from Bombyx mori pupa) polysaccharides, little is known regarding the mechanism of its effects. This study was conducted to determine the mechanism of antitumor effects of C. militaris polysaccharide extract by evaluating apoptosis rate and cell cycle progression status in human liver cancer cell SMMC-7721, stomach cancer cell BGC-823 and breast cancer cell MCF-7. Results showed that C. militaris polysaccharides inhibited proliferation of SMMC-7721, BGC-823 and MCF-7 cells with an IC50 of 192 ± 23.2 μg/mL, 237 ± 12.7 μg/mL and 165 ± 16.3 μg/mL, respectively. We also found that C. militaris polysaccharides at increasing concentrations induced apoptosis dose dependently in those cancer cells: apoptosis rates were 48.3%, 59.4% and 70.9% for SMMC-7721, 41.3% and 57.0%, 72.2% for BGC-823 and 61.3%, 66.9% and 80.6% for MCF-7 at 110, 156 and 323 mg/mL of C. militaris polysaccharides, respectively. C. militaris polysaccharides arrested SMMC-7721, BGC-823 and MCF-7 cells at G0/G1 and G2/M phases with corresponding decrease in S-phase. This study suggests that C. militaris polysaccharides may exert its antitumor effects in those cancer cells by suppressing its growth, arresting the G0/G1-phase, reducing DNA synthesis and inducing apoptosis.

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        Schisandrin B Improves the Hypothermic Preservation of Celsior Solution in Human Umbilical Cord Mesenchymal Stem Cells

        Zhang Ying,Wang Peng,Jin Mei-xian,Zhou Ying-qi,Ye Liang,Zhu Xiao-juan,Li Hui-fang,Zhou Ming,Li Yang,Li Shao,Liang Kang-yan,Wang Yi,Gao Yi,Pan Ming-xin,Zhou Shu-qin,Peng Qing 한국조직공학과 재생의학회 2023 조직공학과 재생의학 Vol.20 No.3

        BACKGROUND: Human umbilical cord mesenchymal stem cells (hUCMSCs) have emerged as promising therapy for immune and inflammatory diseases. However, how to maintain the activity and unique properties during cold storage and transportation is one of the key factors affecting the therapeutic efficiency of hUCMSCs. Schisandrin B (SchB) has many functions in cell protection as a natural medicine. In this study, we investigated the protective effects of SchB on the hypothermic preservation of hUCMSCs. METHODS: hUCMSCs were isolated from Wharton’s jelly. Subsequently, hUCMSCs were exposed to cold storage (4 C) and 24-h re-warming. After that, cells viability, surface markers, immunomodulatory effects, reactive oxygen species (ROS), mitochondrial integrity, apoptosis-related and antioxidant proteins expression level were evaluated. RESULTS: SchB significantly alleviated the cells injury and maintained unique properties such as differentiation potential, level of surface markers and immunomodulatory effects of hUCMSCs. The protective effects of SchB on hUCMSCs after hypothermic storage seemed associated with its inhibition of apoptosis and the anti-oxidative stress effect mediated by nuclear factor erythroid 2–related factor 2 signaling. CONCLUSION: These results demonstrate SchB could be used as an agent for hypothermic preservation of hUCMSCs.

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