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        Dang-Gui-Liu-Huang Tang a traditional herbal formula, ameliorates imiquimod-induced psoriasis-like skin inflammation in mice by inhibiting IL-22 production

        Nguyen, Ly Thi Huong,Ahn, Sang-Hyun,Nguyen, Uy Thai,Yang, In-Jun Elsevier 2018 Phytomedicine Vol.47 No.-

        <P><B>Abstract</B></P> <P><B>Background</B></P> <P>The traditional herbal formula, Dang-Gui-Liu-Huang Tang (DGLHT) has been previously shown to inhibit T lymphocyte proliferation and suppress dendritic cell function. Hypothesis/Purpose: To assess the therapeutic value of DGLHT for the treatment of psoriasis, a Th1 and/or Th17 cell-mediated inflammatory skin disease, and to investigate the underlying molecular mechanisms.</P> <P><B>Methods</B></P> <P>An <I>in vivo</I> mouse model of imiquimod (IMQ)-induced psoriasis-like inflammation was used to investigate the effect of DGLHT. The anti-inflammatory effects of an ethanolic extract of DGLHT (DGLHT-E) and the mechanism responsible were examined in an <I>in vitro</I> model using IL-1α, IL-17A, IL-22, oncostatin M, plus TNF-α (M5) stimulated HaCaT cells. The anti-proliferative effect of DGLHT-E was examined by analyzing the expression levels of K16, K17 and Ki67 in IL-22 stimulated HaCaT cells. <I>Results:</I> Topical application of 1% DGLHT-E significantly reduced psoriasis-like symptoms including scaling and epidermal hyperplasia in IMQ-treated mice. Immunohistochemical studies showed that DGLHT-E exerted potent anti-inflammatory effects by inhibiting IL-22 production in local skin lesions. DGLHT-E also attenuated the productions of CXCL10 and CCL20 in M5-stimulated HaCaT cells by suppressing the ERK1/2, JNK and STAT3 signaling pathways. Furthermore, berberine hydrochloride, a primary constituent of DGLHT-E inhibited the expressions of the proliferation markers K16 and K17 in IL-22 stimulated HaCaT cells.</P> <P><B>Conclusion</B></P> <P>These results suggested that DGLHT-E offers a possible treatment for psoriasis, and that berberine hydrochloride might be a useful component of ointment-based treatments for psoriatic lesions.</P> <P><B>Graphical <B>abstract</B> </B></P> <P>[DISPLAY OMISSION]</P>

      • Astragali Radix and its compound formononetin ameliorate diesel particulate matter-induced skin barrier disruption by regulation of keratinocyte proliferation and apoptosis

        Nguyen, Ly Thi Huong,Nguyen, Uy Thai,Kim, Yeoun-Hee,Shin, Heung-Mook,Yang, In-Jun Elsevier 2019 Journal of Ethnopharmacology Vol.228 No.-

        <P><B>Abstract</B></P> <P><B>Ethnopharmacological relevance</B></P> <P>Astragali Radix (AR), the root of <I>Astragalus mongholicus</I> Bunge, is widely applied in traditional medicine to promote skin health and tissue regeneration.</P> <P><B>Aim of the study</B></P> <P>This study investigated the effects of AR and its active compound, formononetin (FMT), on skin barrier defects in keratinocytes exposed to diesel particulate matter (PM).</P> <P><B>Materials and methods</B></P> <P>HaCaT cells and three-dimensional (3D) human skin reconstructed model were pre-treated with AR (50, 100 μg/ml) and FMT (30, 50 μM), then treated with PM (200 μg/ml).</P> <P><B>Results</B></P> <P>AR and FMT significantly enhanced the expression of Keratin (KRT) 16 in PM stimulated HaCaT cells. PM increased p53 and Bax expression as well as the subsequent cleavage of caspase 3 and PARP in HaCaT cells, while this was inhibited by AR and FMT treatment. <I>In vitro</I> studies using the PM stimulated 3D human skin reconstructed model revealed that AR and FMT increased the expression of KRT 16 and KRT 17. Histological examination of the 3D human skin reconstructed model showed that AR and FMT up-regulated the expression of Ki67, but down-regulated the expression of cleaved caspase 3. Both AR and FMT significantly inhibited phosphorylation of ERK, but not JNK and p38 MAPK in PM stimulated HaCaT cells.</P> <P><B>Conclusions</B></P> <P>These results suggest that AR and FMT act as anti-pollution agents and alleviate PM induced skin barrier defects through regulation of apoptosis and proliferation in keratinocytes.</P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

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        Functional Analysis of CXCR3 Splicing Variants and Their Ligands Using NanoBiT-Based Molecular Interaction Assays

        황종익,Huong Thi Nguyen,Sunghoon Hurh,Lan Phuong Nguyen,Thai Uy Nguyen,Hee-Kyung Park,Jae Young Seong,Cheol Soon Lee,Byung-Joo Ham 한국분자세포생물학회 2023 Molecules and cells Vol.46 No.5

        CXCR3 regulates leukocyte trafficking, maturation, and various pathophysiological conditions. Alternative splicing generates three CXCR3 isoforms in humans. Previous studies investigated the roles of CXCR3 isoforms, and some biochemical data are not correlated with biological relevance analyses. RT-PCR analyses indicate that most cells express all three splicing variants, suggesting that they may mutually affect the chemokine binding and cellular responses of other splicing variants. Here, we performed an integrative analysis of the functional relations among CXCR3 splicing variants and their chemokine-dependent signaling using NanoBiT live cell protein interaction assays. The results indicated that the CXCR3 N-terminal region affected cell surface expression levels and ligand-dependent activation. CXCR3A was efficiently expressed in the plasma membrane and responded to I-TAC, IP-10, and MIG chemokines. By contrast, CXCR3B had low plasma membrane expression and mediated I-TAC–stimulated cellular responses. CXCR3Alt was rarely expressed on the cell surface and did not mediate any cell responses to the tested chemokines; however, CXCR3Alt negatively affected the plasma membrane expression of CXCR3A and CXCR3B and their chemokine-stimulated cellular responses. Jurkat cells express endogenous CXCR3, and exogenous CXCR3A expression enhanced chemotactic activity in response to I-TAC, IP-10, and MIG. By contrast, exogenous expression of CXCR3B and CXCR3Alt eliminated or reduced the CXCR3A-induced chemotactic activity. The PF-4 chemokine did not activate any CXCR3-mediated cellular responses. NanoBiT technology are useful to integrative studies of CXCR3-mediated cell signaling, and expand our knowledge of the cellular responses mediated by molecular interactions among the splicing variants, including cell surface expression, ligand-dependent receptor activation, and chemotaxis.

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