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        Valproic acid enforces the priming effect of sphingosine-1 phosphate on human mesenchymal stem cells

        Lim, Jisun,Lee, Seungun,Ju, Hyein,Kim, Yonghwan,Heo, Jinbeom,Lee, Hye-Yeon,Choi, Kyung-Chul,Son, Jaekyoung,Oh, Yeon-Mok,Kim, In-Gyu,Shin, Dong-Myung UNKNOWN 2017 INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE Vol.40 No.3

        <P>Engraftment and homing of mesenchymal stem cells (MSCs) are modulated by priming factors including the bioactive lipid sphingosine-1-phosphate (S1P), by stimulating CXCR4 receptor signaling cascades. However, limited <I>in vivo</I> efficacy and the remaining priming molecules prior to administration of MSCs can provoke concerns regarding the efficiency and safety of MSC priming. Here, we showed that valproic acid (VPA), a histone deacetylase inhibitor, enforced the priming effect of S1P at a low dosage for human umbilical cord-derived MSCs (UC-MSCs). A DNA-methylation inhibitor, 5-azacytidine (5-Aza), and VPA increased the expression of <I>CXCR4</I> in UC-MSCs. In particular, UC-MSCs primed with a suboptimal dose (50 nM) of S1P in combination with 0.5 mM VPA (VPA+S1P priming), but not 1 <I>µ</I>M 5-Aza, significantly improved the migration activity in response to stromal cell-derived factor 1 (SDF-1) concomitant with the activation of both MAPK<SUP>p42/44</SUP> and AKT signaling cascades. Both epigenetic regulatory compounds had little influence on cell surface marker phenotypes and the multi-potency of UC-MSCs. In contrast, VPA+S1P priming of UC-MSCs potentiated the proliferation, colony forming unit-fibroblast, and anti-inflammatory activities, which were severely inhibited in the case of 5-Aza treatment. Accordingly, the VPA+S1P-primed UC-MSCs exhibited upregulation of a subset of genes related to stem cell migration and anti-inflammation response. Thus, the present study demonstrated that VPA enables MSC priming with S1P at a low dosage by enhancing their migration and other therapeutic beneficial activities. This priming strategy for MSCs may provide a more efficient and safe application of MSCs for treating a variety of intractable disorders.</P>

      • KCI등재
      • KCI등재

        건축물 외부 마감 재료의 실대형 화재안전성 시험방법 적용을 위한 비교 실험 연구

        조경숙(Cho, Kyungsuk),채승언(Chae, Seungun),최지훈(Choi, Jihun),김흥열(Kim, Heungyoul) 한국방재학회 2017 한국방재학회논문집 Vol.17 No.3

        The fire at Haeundae Wooshin Golden Suite in Busan and Daebong Green Apartment in Euijeongbu reminded us of the high risk of fire spreading througth the claddings. But institutional standard to evaluate the risk of flame spread through claddings has yet to be established. Current building code suggests the test method and evaluation standard using a model specimen and thus the test method using a full-scale model to evaluate the whole cladding system has yet to be made available. Thus this study is intended to compare the test methods using BS 8414-1 and ISO 13785-2 among various full-scale tests adoped internationally, with same material, so as to use the result as the basic data in introducing the appropriate test method to the local sites. Consequently, the test results were found different because of some difference in size of speciemen and fire source. 부산 해운대 우신 골든 스위트 화재와 의정부 대봉 그린 아파트 화재사고는 외장재를 통한 화재 확산의 위험성을 알려준 계기가 되었다. 그러나 현행 규정에서는 이러한 외장재의 화염전파에 의한 위험성을 평가할 수 있는 제도적인 기준이 미흡한 상태이다. 건축법에서는 소형시험편을 이용한 시험방법과 평가기준을 제시하고 있으나 실제 규모에서 외장재 시스템 전체를 평가할 수 있는 시험방법이 부재한 상태이다. 따라서 본 연구에서는 국외에서 시행하고 있는 외장재의 실대형 시험방법 중 BS 8414-1과 ISO 13785-2의 시험방법을 동일 외장재를 시공하여 시험방법의 비교를 통해 국내에 시험방법을 도입하는데 있어 기초자료로 사용하고자 하였다. 시험결과 두 시험방법은 시험체의 크기, 화원의 크기 등에 있어 다소 차이가 있어 시험 결과에서도 차이가 발생하였다.

      • KCI등재

        Clinical Implications of Focal Mineral Deposition in the Globus Pallidus on CT and Quantitative Susceptibility Mapping of MRI

        Kim Hyojin,Jang Jinhee,Kang Junghwa,Jang Seungun,Nam Yoonho,Choi Yangsean,Shin Na-young,Ahn Kook-Jin,Kim Bum-soo 대한영상의학회 2022 Korean Journal of Radiology Vol.23 No.7

        Objective: To assess focal mineral deposition in the globus pallidus (GP) by CT and quantitative susceptibility mapping (QSM) of MRI scans and evaluate its clinical significance, particularly cerebrovascular degeneration. Materials and Methods: This study included 105 patients (66.1 ± 13.7 years; 40 male and 65 female) who underwent both CT and MRI with available QSM data between January 2017 and December 2019. The presence of focal mineral deposition in the GP on QSM (GPQSM) and CT (GPCT) was assessed visually using a three-point scale. Cerebrovascular risk factors and small vessel disease (SVD) imaging markers were also assessed. The clinical and radiological findings were compared between the different grades of GPQSM and GPCT. The relationship between GP grades and cerebrovascular risk factors and SVD imaging markers was assessed using univariable and multivariable linear regression analyses. Results: GPCT and GPQSM were significantly associated (p < 0.001) but were not identical. Higher GPCT and GPQSM grades showed smaller gray matter (p = 0.030 and p = 0.025, respectively) and white matter (p = 0.013 and p = 0.019, respectively) volumes, as well as larger GP volumes (p < 0.001 for both). Among SVD markers, white matter hyperintensity was significantly associated with GPCT (p = 0.006) and brain atrophy was significantly associated with GPQSM (p = 0.032) in at univariable analysis. In multivariable analysis, the normalized volume of the GP was independently positively associated with GPCT (p < 0.001) and GPQSM (p = 0.002), while the normalized volume of the GM was independently negatively associated with GPCT (p = 0.040) and GPQSM (p = 0.035). Conclusion: Focal mineral deposition in the GP on CT and QSM might be a potential imaging marker of cerebral vascular degeneration. Both were associated with increased GP volume.

      • SCIESCOPUSKCI등재

        The Therapeutic Effect of Human Embryonic Stem Cell-Derived Multipotent Mesenchymal Stem Cells on Chemical-Induced Cystitis in Rats

        Lee, Sang Wook,Ryu, Chae-Min,Shin, Jung-Hyun,Choi, Daeheon,Kim, Aram,Yu, Hwan Yeul,Han, Ju-Young,Lee, Hye-Yeon,Lim, Jisun,Kim, Yong Hwan,Heo, Jinbeom,Lee, Seungun,Ju, Hyein,Kim, Sujin,Hong, Ki-Sung,Ha Korean Continence Society 2018 International Neurourology Journal Vol.22 No.S1

        <P><B>Purpose</B></P><P>To evaluate the therapeutic effect of human embryonic stem cell (hESC)-derived multipotent mesenchymal stem cells (M-MSCs) on ketamine-induced cystitis (KC) in rats.</P><P><B>Methods</B></P><P>To induce KC, 10-week-old female rats were injected with 25-mg/kg ketamine hydrochloride twice weekly for 12 weeks. In the sham group, phosphate buffered saline (PBS) was injected instead of ketamine. One week after the final injection of ketamine, the indicated doses (0.25, 0.5, and 1×10<SUP>6</SUP> cells) of M-MSCs (KC+M-MSC group) or PBS vehicle (KC group) were directly injected into the bladder wall. One week after M-MSC injection, the therapeutic outcomes were evaluated via cystometry, histological analyses, and measurement of gene expression. Next, we compared the efficacy of M-MSCs at a low dose (1×10<SUP>5</SUP> cells) to that of an identical dose of adult bone marrow (BM)-derived MSCs.</P><P><B>Results</B></P><P>Rats in the KC group exhibited increased voiding frequency and reduced bladder capacity compared to rats of the sham group. However, these parameters recovered after transplantation of M-MSCs at all doses tested. KC bladders exhibited markedly increased mast cell infiltration, apoptosis, and tissue fibrosis. Administration of M-MSCs significantly reversed these characteristic histological alterations. Gene expression analyses indicated that several genes associated with tissue fibrosis were markedly upregulated in KC bladders. However the expression of these genes was significantly suppressed by the administration of M-MSCs. Importantly, M-MSCs ameliorated bladder deterioration in KC rats after injection of a low dose (1×10<SUP>5</SUP>) of cells, at which point BM-derived MSCs did not substantially improve bladder function.</P><P><B>Conclusions</B></P><P>This study demonstrates for the first time the therapeutic efficacy of hESC-derived M-MSCs on KC in rats. M-MSCs restored bladder function more effectively than did BM-derived MSCs, protecting against abnormal changes including mast cell infiltration, apoptosis and fibrotic damage.</P>

      • Estimation of ground-level particulate matter concentrations through the synergistic use of satellite observations and process-based models over South Korea

        Park, Seohui,Shin, Minso,Im, Jungho,Song, Chang-Keun,Choi, Myungje,Kim, Jhoon,Lee, Seungun,Park, Rokjin,Kim, Jiyoung,Lee, Dong-Won,Kim, Sang-Kyun Copernicus GmbH 2019 Atmospheric Chemistry and Physics Vol.19 No.2

        <P><p><strong>Abstract.</strong> Long-term exposure to particulate matter (PM) with aerodynamic diameters &lt;<span class='thinspace'></span>10 (PM<span class='inline-formula'><sub>10</sub></span>) and 2.5<span class='thinspace'></span><span class='inline-formula'>µ</span>m (PM<span class='inline-formula'><sub>2.5</sub></span>) has negative effects on human health. Although station-based PM monitoring has been conducted around the world, it is still challenging to provide spatially continuous PM information for vast areas at high spatial resolution. Satellite-derived aerosol information such as aerosol optical depth (AOD) has been frequently used to investigate ground-level PM concentrations. In this study, we combined multiple satellite-derived products including AOD with model-based meteorological parameters (i.e., dew-point temperature, wind speed, surface pressure, planetary boundary layer height, and relative humidity) and emission parameters (i.e., NO, <span class='inline-formula'>NH<sub>3</sub></span>, <span class='inline-formula'>SO<sub>2</sub></span>, primary organic aerosol (POA), and HCHO) to estimate surface PM concentrations over South Korea. Random forest (RF) machine learning was used to estimate both PM<span class='inline-formula'><sub>10</sub></span> and PM<span class='inline-formula'><sub>2.5</sub></span> concentrations with a total of 32 parameters for 2015-2016. The results show that the RF-based models produced good performance resulting in <span class='inline-formula'><i>R</i><sup>2</sup></span> values of 0.78 and 0.73 and root mean square errors (RMSEs) of 17.08 and 8.25<span class='thinspace'></span><span class='inline-formula'>µ</span>g<span class='thinspace'></span>m<span class='inline-formula'><sup>−3</sup></span> for PM<span class='inline-formula'><sub>10</sub></span> and PM<span class='inline-formula'><sub>2.5</sub></span>, respectively. In particular, the proposed models successfully estimated high PM concentrations. AOD was identified as the most significant for estimating ground-level PM concentrations, followed by wind speed, solar radiation, and dew-point temperature. The use of aerosol information derived from a geostationary satellite sensor (i.e., Geostationary Ocean Color Imager, GOCI) resulted in slightly higher accuracy for estimating PM concentrations than that from a polar-orbiting sensor system (i.e., the Moderate Resolution Imaging Spectroradiometer, MODIS). The proposed RF models yielded better performance than the process-based approaches, particularly in improving on the underestimation of the process-based models (i.e., GEOS-Chem and the Community Multiscale Air Quality Modeling System, CMAQ).</p> </P>

      • Small hypoxia-primed mesenchymal stem cells attenuate graft-versus-host disease

        Kim, YongHwan,Jin, Hye Jin,Heo, Jinbeom,Ju, Hyein,Lee, Hye-Yeon,Kim, Sujin,Lee, Seungun,Lim, Jisun,Jeong, Sang Young,Kwon, JiHye,Kim, Miyeon,Choi, Soo Jin,Oh, Wonil,Yang, Yoon Sun,Hwang, Hyun Ho,Yu, H Nature Publishing Group UK 2018 Leukemia Vol.32 No.12

        <P>Mesenchymal stem cells (MSCs) are of particular interest for the treatment of immune-related diseases due to their immunosuppressive capacity. Here, we show that Small MSCs primed with Hypoxia and Calcium ions (SHC-MSCs) exhibit enhanced stemness and immunomodulatory functions for treating allogeneic conflicts. Compared with naïve cultured human umbilical cord blood-derived MSCs, SHC-MSCs were resistant to passage-dependent senescence mediated via the monocyte chemoattractant protein-1 and p53/p21 cascade and secreted large amounts of pro-angiogenic and immunomodulatory factors, resulting in suppression of T-cell proliferation. SHC-MSCs showed DNA demethylation in pluripotency, germline, and imprinted genes similarly to very small embryonic-like stem cells, suggesting a potential mutual relationship. Genome-wide DNA methylome and transcriptome analyses indicated that genes related to immune modulation, cell adhesion, and the cell cycle were up-regulated in SHC-MSCs. Particularly, polo-like kinase-1 (<I>PLK1</I>), zinc-finger protein-143, dehydrogenase/reductase-3, and friend-of-GATA2 play a key role in the beneficial effects of SHC-MSCs. Administration of SHC-MSCs or <I>PLK1</I>-overexpressing MSCs significantly ameliorated symptoms of graft-versus-host disease (GVHD) in a humanized mouse model, resulting in significantly improved survival, less weight loss, and reduced histopathologic injuries in GVHD target organs compared with naïve MSC-infused mice. Collectively, our findings suggest that SHC-MSCs can improve the clinical treatment of allogeneic conflicts, including GVHD.</P>

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