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      • Programmed Cell Death 1 (PD-1) and Cytotoxic T Lymphocyte-Associated Antigen 4 (CTLA-4) in Viral Hepatitis

        Cho, Hyosun,Kang, Hyojeung,Lee, Hwan Hee,Kim, Chang Wook MDPI AG 2017 INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES Vol.18 No.7

        <P>Virus-specific cluster of differentiation 8 (CD8+) cytotoxic T cells (CTL) recognize viral antigens presented on major histocompatibility complex (MHC) class I chains on infected hepatocytes, with help from CD4+ T cells. However, this CTL response is frequently weak or undetectable in patients with chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infection. Programmed cell death 1 (PD-1) and cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) are receptors in the CD28 family of costimulatory molecules, providing inhibitory signals to T cells. The overexpressions of PD-1 and CTLA-4 in patients with viral infection have been shown to associate with functional impairment of virus-specific T cells. In acute viral hepatitis, PD-1 and CTLA-4 are up-regulated during the symptomatic phase, and then down-regulated after recovery. These findings suggest that PD-1 and CTLA-4 have protective effects as inhibitory molecules to suppress cytotoxic T cells which induce harmful destruction of viral infected hepatocytes in self-limited viral hepatitis. In chronic viral hepatitis, the extended upregulations of PD-1 and CTLA-4 are associated with T cell exhaustion and persistent viral infection, suggesting positive correlations between expression of immune inhibitory factors and the chronicity of viral disease. In this review, we summarize recent literature relating to PD-1, CTLA-4, and other inhibitory receptors in antigen-specific T cell exhaustion in viral hepatitis, including hepatitis A, B, C, and others.</P>

      • SCIESCOPUSKCI등재

        Phenotypic Characteristics of PD-1 and CTLA-4 Expression in Symptomatic Acute Hepatitis A

        ( Hyosun Cho ),( Hyojeung Kang ),( Chang Wook Kim ),( Hee Yeon Kim ),( Jeong Won Jang ),( Seung Kew Yoon ),( Chang Don Lee ) 대한소화기학회 2016 Gut and Liver Vol.10 No.2

        Background/Aims: The immunoregulatory molecules programmed death 1 (PD-1) and cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) are associated with the dysfunction of antiviral effector T-cells, which leads to T-cell exhaustion and persistent viral infection in patients with chronic hepatitis C and chronic hepatitis B. Little is known about the role of PD-1 and CTLA-4 in patients with symptomatic acute hepatitis A (AHA). Methods: Peripheral blood mononuclear cells were isolated from seven patients with AHA and from six patients with nonviral acute toxic hepatitis (ATH) during the symptomatic and convalescent phases of the respective diseases; five healthy subjects acted as controls. The expression of PD-1 and CTLA-4 on T-cells was measured by flow cytometry. Results: PD-1 and CTLA-4 expression during the symptomatic phase was significantly higher in the Tcells of AHA patients than in those of ATH patients or healthy controls (PD-1: 18.3% vs 3.7% vs 1.6%, respectively, p<0.05; CTLA-4: 23.5% vs 6.1% vs 5.9%, respectively, p<0.05). The levels of both molecules decreased dramatically during the convalescent phase of AHA, whereas a similar pattern was not seen in ATH. Conclusions: Our findings are consistent with a viral-protective effect of PD-1 and CTLA-4 as inhibitory molecules that suppress cytotoxic T-cells and thereby prevent the destruction of virus-infected hepatocytes in AHA. (Gut Liver 2016;10:288-294)

      • Foxp3 and PD-1 Except CTLA-4 Are Decreased Significantly during 1 Year Tenofovir Therapy in Chronic Hepatitis B

        ( Hyosun Cho ),( Chang Wook Kim ),( Ji Young Kim ),( Yun Hui Kim ),( Seok Cheon Yeom ),( Su Gyeong Lee ),( Hee Yeon Kim ),( Si Hyun Bae ),( Jong Young Choi ),( Seung Kew Yoon ) 대한간학회 2016 춘·추계 학술대회 (KASL) Vol.2016 No.1

        Aims: Immune regulatory molecules such as forkhead box P3 (Foxp3) on CD4+ T cell and programmed death-1 (PD-1) and cytotoxic T lymphocyte- associated antigen 4 (CTLA-4) on CD8+ T cell are associated with antiviral effector T cell dysfunction, which influences on T cell exhaustion and persistent viral infection in patients with chronic hepatitis C and chronic hepatitis B, These Foxp3, PD-1 and CTLA-4 are up-regulated in chronic viral infection such as chronic hepatitis C, chronic hepatitis B and human immunodeficiency virus infection but there is few report about the role of Foxp3, PD-1 and CTLA-4 in patients with chronic hepatitis B during antiviral therapy with tenofovir. We investigated the expression of Foxp3, PD-1 and CTLA-4 during 1 year tenofovir treatment in patients with chronic hepatitis B. Methods: Thirty patients with chronic hepatitis B under tenofovir treatment were enrolled for detection of Foxp3, PD-1 and CTLA-4 on T cells. Peripheral blood mononuclear cells (PBMC) were isolated from these subjects before tenofovir treatment (T0), 1 month (T1), 3 month T3), 6 month (T6) and 12 month (T12) during tenofovir treatment. The expressions of Foxp3, PD-1 and CTLA-4 on T cells were monitored by flow cytometry. Results: T cells from patients with chronic hepatitis B under tenofovir treatment showed decreased expression of Foxp3 and PD-1 at T12 compared to T0 significantly but, the expression of CTLA-4 were decreased initially then increased at T12 compared to T0. Conclusions: In chronic hepatitis B, PD-1 as inhibitory T cell molecules and FoxP3 as regulatory T cell marker are down-regulated during 1 year tenofovir therapy, which could restore HBV-specific T cell function during tenofovir antiviral therapy. Interestingly, CTLA-4 may be up-regulated during 12 months tenofovir therapy in chronic hepatitis B, may play an important role in failing to eradicate HBV in spite of complete virologic response with tenofovir.

      • Cytokine-Modulated Natural Killer Cells Differentially Regulate the Activity of the Hepatitis C Virus

        Cho, Yoo Jin,Lee, Hwan Hee,Kang, Hyojeung,Cho, Hyosun MDPI 2018 INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES Vol.19 No.9

        <P>HCV genotype 2a strain JFH-1 replicates and produces viral particles efficiently in human hepatocellular carcinoma (huh) 7.5 cells, which provide a stable in vitro cell infection system for the hepatitis C virus (HCVcc system). Natural killer (NK) cells are large lymphoid cells that recognize and kill virus-infected cells. In this study, we investigated the interaction between NK cells and the HCVcc system. IL-10 is a typical immune regulatory cytokine that is produced mostly by NK cells and macrophages. IL-21 is one of the main cytokines that stimulate the activation of NK cells. First, we used anti-IL-10 to neutralize IL-10 in a coculture of NK cells and HCVcc. Anti-IL-10 treatment increased the maturation of NK cells by enhancing the frequency of the CD56<SUP>+dim</SUP> population in NK-92 cells. However, with anti-IL-10 treatment of NK cells in coculture with J6/JFH-1-huh 7.5 cells, there was a significant decrease in the expression of STAT1 and STAT5 proteins in NK-92 cells and an increase in the HCV Core and NS3 proteins. In addition, rIL-21 treatment increased the frequency of the CD56<SUP>+dim</SUP> population in NK-92 cells, Also, there was a dramatic increase in the expression of STAT1 and STAT5 proteins in rIL-21 pre-stimulated NK cells and a decrease in the expression of HCV Core protein in coculture with J6/JFH-1-huh 7.5 cells. In summary, we found that the functional activation of NK cells can be modulated by anti-IL-10 or rIL-21, which controls the expression of HCV proteins as well as HCV RNA replication.</P>

      • SCOPUSKCI등재
      • SCOPUSKCI등재
      • SCISCIESCOPUS

        Synthesis, structural characterization and MMA polymerization studies of dimeric 5-coordinate copper(II), cadmium(II), and monomeric 4-coordinate zinc(II) complexes supported by <i>N</i>-methyl-<i>N</i>-((pyridine-2-yl)methyl)benzeneamine

        Cho, Hyungwoo,Jung, Maeng Joon,Jeon, Jongho,Lee, Hyosun,Nayab, Saira Elsevier Sequoia [etc.] 2019 Inorganica chimica acta Vol.487 No.-

        <P><B>Abstract</B></P> <P>Copper(II), cadmium(II) and zinc(II) complexes containing <I>N</I>-methyl-<I>N</I>-((pyridine-2-yl)methyl)benzeneamine (<B>npmb</B>) ligand have been synthesized and characterized by X-ray crystallography. Molecular structures of Cu(II) and Cd(II) complexes revealed dimeric structures with square pyramidal and distorted trigonal bipyramidal geometries, respectively, involving two nitrogen atoms, two bridged and one terminal halogen ligands. However, the monomeric Zn(II) complex showed a distorted tetrahedral geometry around the Zn centre. <B>[(npmb)ZnCl<SUB>2</SUB>]</B> exhibited the higher catalytic activity (2.88 × 10<SUP>4</SUP> g PMMA/molZn·h) for the polymerization of methyl methacrylate (MMA) in the presence of modified methylaluminoxane (MMAO) at 60 °C and yielded high molecular weight (11.1 g/mol × 10<SUP>5</SUP>) syndiotactic-enriched poly(methylmethacrylate) (PMMA) compared to its Cu(II) and Cd(II) analogues.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Cu(II), Zn(II) and Cd(II) complexes with <I>N</I>-methyl-<I>N</I>-((pyridine-2-yl)methyl)benzeneamine. </LI> <LI> Dimeric Cu(II) and Cd(II) complexes showed distorted trigonal bipyramidal geometries. </LI> <LI> Monomeric Zn(II) complex adopted a distorted tetrahedral geometry around the Zn centre. </LI> <LI> <B>[(npmb)ZnCl<SUB>2</SUB>]</B> yielded high molecular weight (11.1 g/mol × 10<SUP>5</SUP>) syndio-enriched PMMA. </LI> <LI> Higher activities were observed for Zn(II) initiators compared to Cu(II) and Cd(II) analogous. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>Novel Cu(II), Zn(II) and Cd(II) complexes supported by <I>N</I>-methyl-<I>N</I>-((pyridine-2-yl)methyl)benzeneamine (<B>npmb</B>) have been synthesized and characterized by X-ray diffraction. <B>[(npmb)ZnCl<SUB>2</SUB>]</B> exhibited the higher catalytic activity for MMA polymerization in the presence of modified methylaluminoxane (MMAO) at 60 °C and resulted syndio-enriched poly(methylmethacrylate) (PMMA) compared to its Cu(II) and Cd(II) analogues.</P> <P>[DISPLAY OMISSION]</P>

      • TMED9 expression level as a biomarker of epithelial ovarian cancer progression and prognosis

        ( Hyosun Kim ),( Gwan Hee Han ),( Hee Yun ),( Jae-hoon Kim ),( Hanbyoul Cho ) 대한산부인과학회 2022 대한산부인과학회 학술대회 Vol.108 No.-

        Objective: Transmembrane emp24 domain-containing protein 9 (TMED9) belongs to the TMED/p24 family that transports, modifies, and packs proteins and lipids into vesicles for delivery to specific locations and is important in innate immune signaling via the endoplasmic reticulum-Golgi cargo pathway. TMED9 has been implicated in various cancers; however, its role in epithelial ovarian cancer (EOC) is unclear. In this study, we aimed to elucidate the role and clinical significance of TMED9 in EOC. Methods: mRNA and protein levels of TMED9 and their associations with clinicopathological features in EOCs were evaluated using RNA-sequencing and immunohistochemistry data. Functional studies assessing the tumorigenic role of TMED9 in EOC cell lines were also performed. Results: The mRNA expression of TMED9 was upregulated in EOC compared to that in normal ovarian epithelium. TMED9 protein expression eventually progressed to EOC from the normal ovarian epithelium (p < 0.001). Moreover, high expression of TMED9 was associated with advanced stage, serous cell type, poor grade histology in EOC and, both disease free survival (DFS) and overall survival (OS) in EOC demonstrated independent prognostic significance. Further functional studies showed that TMED9 knockdown decreased migration, and invasion, cell proliferation, colony formation of EOC cells. Conclusion: Overall, high TMED9 expression was associated with EOC development and progression with significancy and has an independent power for EOC progression.

      • Real-Time Underwater Object Detection Based on DC Resistivity Method

        Cho, Sung-Ho,Jung, Hyun-Key,Lee, Hyosun,Rim, Hyoungrea,Lee, Seong Kon IEEE 2016 IEEE transactions on geoscience and remote sensing Vol.54 No.11

        <P>A new real-time underwater object detection method adopting geophysical direct-current resistivity techniques is proposed. Our final goals are real-time detection and tracking of small submarines in water depths less than 100 m, under acoustically noisy conditions. The main features of our method are as follows: 1) a detection line, several kilometers long and semipermanently buried in the seabed, consisting of two current electrodes and multiple potential electrodes; 2) fixed current electrode configurations for high-speed real-time detection of the target object; 3) measurement of extremely low-level electric field signals, made possible by the shielding effect of the conductive seawater overburden; and 4) signals from a moving object such as a submarine are extracted by differential data analysis because the target object passes through the detection area for only a short time compared with the long-term drift change of the electrical properties of seawater. We verify our method and confirm real-time detection feasibility through numerical and physical scale experiments. For this purpose, a dedicated instrument and a background data update algorithm are developed, and a differential data analysis method is used. The background data update algorithm is used for counteracting the time-varying electrical characteristics of seawater. The differential data analysis method is exploited to extract disturbed signals by objects from complex background data. Through numerical experiments, we find that the x-coordinate value of a target object corresponds to the position of a peak data point, and this result is consistent with 1: 200 downscaled water tank experiments. We also confirm real-time detection feasibility using our instrument through an offshore experiment. We expect that our proposed method will complement conventional detection methods for harbor defense and surveillance systems in acoustically noisy environments.</P>

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