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        The 4–1BB ligand and 4–1BB expressed on osteoclast precursors enhance RANKL-induced osteoclastogenesis via bi-directional signaling

        Yang, Jihyun,Park, Ok Jin,Lee, Yeon Ju,Jung, Hong-Moon,Woo, Kyung Mi,Choi, Youngnim WILEY-VCH Verlag 2008 European journal of immunology Vol.38 No.6

        <P>The 4–1BB is a costimulatory molecule similar to the receptor activator of NF-&kgr;B ligand (RANKL), both of which are key factors for the differentiation of osteoclasts and are expressed mainly by activated T cells. The 4–1BB shares common signaling pathways with RANK, suggesting a potential role in osteoclastogenesis. In this study, the role of 4–1BB and 4–1BB ligand (4–1BBL) in osteoclastogenesis was investigated using 4–1BB<SUP>–/–</SUP> and 4–1BB<SUP>+/+</SUP> mice. Osteoclast precursors normally express 4–1BB and 4–1BBL after exposure to RANKL, which was confirmed by semi-quantitative RT-PCR and flow cytometry. The 4–1BB<SUP>–/– </SUP>mice had a slightly increased bone mass accompanied by a reduced osteoclastogenic ability of 4–1BB<SUP>–/–</SUP> bone marrow-derived macrophages (BMM) ex vivo. In addition, 4–1BB<SUP>–/–</SUP> BMM demonstrated hypophosphorylation of JNK and p38 and decreased induction of c-Fos in response to RANKL stimulation. Retroviral transduction of wild-type as well as partial-length 4–1BB, which lacks TNF receptor-associated factor 2-binding sites for signaling, restored the osteoclastogenic ability of 4–1BB<SUP>–/–</SUP> BMM. Furthermore, both recombinant 4–1BB and 4–1BBL enhanced RANKL-induced osteoclastogenesis by 4–1BB<SUP>+/+</SUP> BMM and the induction of c-Fos and NFATc1.Together, these results indicate that 4–1BBL and 4–1BB expressed on osteoclast precursors enhance RANKL-induced osteoclastogenesis via bi–directional signaling, findings that may delineate the complex nature of the 4–1BBL and 4–1BB interaction.</P><P>Supporting Information for this article is available at www.wiley-vch.de/contents/jc_2040/2008/37650_s.pdf</P>

      • Impaired osteoclastogenesis by staphylococcal lipoteichoic acid through Toll-like receptor 2 with partial involvement of MyD88

        Yang, Jihyun,Ryu, Young Hee,Yun, Cheol-Heui,Han, Seung Hyun Wiley (John WileySons) 2009 Journal of leukocyte biology Vol.86 No.4

        <P>Degenerative bone disease, marked by excessive loss of calcified matrix, is often associated with bacterial infections. Osteoclasts, which mediate the bone-resorptive process, are derived mainly from myeloid precursor cells of the monocyte/macrophage lineage, from which cells with phagocytic and inflammatory capacities may alternatively arise. Here, we investigated the effect of LTA, a major cell-wall virulence factor of Gram-positive bacteria, on osteoclast differentiation. Osteoclast precursors were prepared from C57BL/6 mouse BM using M-CSF and RANKL. When osteoclastogenesis was induced in the presence of staphylococcal LTA, LTA dose-dependently inhibited the differentiation of osteoclast precursors to mature osteoclasts. A corresponding inhibition of bone-resorptive function was observed in the reduced resorption area on calcium phosphate-coated culture plates. In contrast, the phagocytic and inflammatory potential of the osteoclast precursors increased in the presence of LTA. TLR2, known to recognize LTA, might be essential for the LTA inhibition of osteoclastogenesis, as the inhibition did not occur in the precursors from TLR2-deficient mice. Importantly, MyD88-dependent and MyD88-independent pathways would participate in the inhibition, as determined using MyD88-deficient cells. Moreover, LTA inhibited phosphorylation of ERK and JNK in osteoclast precursors stimulated with M-CSF and RANKL, concomitantly with a decreased DNA-binding activity of AP-1. These results suggest that staphylococcal LTA inhibits osteoclast differentiation primarily through TLR2 but also in part through MyD88 signaling, which in turn, inhibits activation of ERK, JNK, and AP-1.</P>

      • SCOPUSKCI등재

        Risk factors and outcomes of acute renal infarction

        ( Jihyun Yang ),( Jun Yong Lee ),( Young Ju Na ),( Sung Yoon Lim ),( Myung Gyu Kim ),( Sang Kyung Jo ),( Wonyong Cho ) 대한신장학회 2016 Kidney Research and Clinical Practice Vol.35 No.2

        Background: Renal infarction (RI) is an uncommon disease that is difficult to diagnose. As little is known about clinical characteristics of this disease, we investigated its underlying risk factors and outcomes. Methods: We performed a retrospective single-center study of 89 patients newly diagnosed with acute RI between January 2002 and March 2015 using imaging modalities. Clinical features, possible etiologies, and long-term renal outcome data were reviewed. Results: The patients`` mean age was 63.5 ± 15.42 years; 23.6% had diabetes and 56.2% had hypertension. Unilateral and bilateral involvements were shown in 80.9% and 19.1% of patients, respectively; proteinuria and hematuria were reported in 40.4% and 41.6%, respectively. Cardiovascular disease was the most common underlying disease, followed by renal vascular injury and hypercoagulability disorder. Fourteen patients had no specific underlying disease. At the time of diagnosis, acute kidney injury (AKI) was found in 34.8% of patients. Univariate analysis revealed diabetes mellitus (DM), leukocytosis, and high C-reactive protein (CRP) as significant risk factors for the development of AKI. On multivariate analysis, DM and high CRP levels were independent predictors for AKI. During follow-up, chronic kidney disease developed in 27.4% of patients. Univariate and multivariate Cox regression analyses showed old age to be an independent risk factor for this disease, whereas AKI history was a negative risk factor. Conclusion: DM patients or those with high CRP levels should be observed for renal function deterioration. Clinicians should also monitor for RI in elderly patients.

      • SCOPUSKCI등재

        Probiotics partially attenuate the severity of acute kidney injury through an immunomodulatory effect

        ( Jihyun Yang ),( Geun Eog Ji ),( Myeong Soo Park ),( Yeong-je Seong ),( Yoon Sook Go ),( Hee Young Lee ),( Yina Fang ),( Myung-gyu Kim ),( Se Won Oh ),( Won Yong Cho ),( Sang-kyung Jo ) 대한신장학회 2021 Kidney Research and Clinical Practice Vol.40 No.4

        Background: A healthy microbiome helps maintain the gut barrier and mucosal immune tolerance. Previously, we demonstrated that acute kidney injury (AKI) provoked dysbiosis, gut inflammation, and increased permeability. Here, we investigated the renoprotective effects of the probiotic Bifidobacterium bifidum BGN4 and the underlying mechanisms thereof. Methods: C57BL/6 mice were subjected to bilateral renal ischemia-reperfusion injury (IRI) or sham operation. In the probiotic-treated group, BGN4 was administered by gavage once daily, starting 2 weeks before injury. Results: Administration of BGN4 significantly increased gut microbiome diversity and prevented expansion of the Enterobacteriaceae and Bacteroidetes that were the hallmarks of AKI-induced dysbiosis. Further, BGN4 administration also significantly reduced other IRI-induced changes in the colon microenvironment, including effects on permeability, apoptosis of colon epithelial cells, and neutrophil and proinflammatory macrophage infiltration. Mononuclear cells co-cultured with BGN4 expressed significantly increased proportions of CD103<sup>+</sup>/ CD11c<sup>+</sup> and CD4<sup>+</sup> CD25<sup>+</sup> Treg cells, suggesting a direct immunomodulatory effect. BGN4 induced Treg expansion in colon, mesenteric lymph nodes (MNL), and kidney. BGN4 also reduced CX<sub>3</sub>CR<sub>1</sub><sup>intermediate</sup>Ly6C<sup>high</sup> monocyte infiltration and interleukin (IL)-17A suppression in the small intestine, which may have attenuated AKI severity, kidney IL-6 messenger RNA expression, and AKI-induced liver injury. Conclusion: Prior supplementation with BGN4 significantly attenuated the severity of IRI and secondary liver injury. This renoprotective effect was associated with increased Foxp3 and reduced IL-17A expression in the colon, MNL, and kidney, suggesting that BGN4-induced immunomodulation might contribute to its renoprotective effects. Probiotics may therefore be a promising strategy to reduce AKI severity and/or remote organ injury.

      • Transfer-Free Growth of Multilayer Graphene Using Self-Assembled Monolayers

        Yang, Gwangseok,Kim, Hong-Yeol,Jang, Soohwan,Kim, Jihyun American Chemical Society 2016 ACS APPLIED MATERIALS & INTERFACES Vol.8 No.40

        <P>Large-area graphene needs to be directly synthesized on the desired substrates without using a transfer process so that it can easily be used in industrial applications. However, the development of a direct method for graphene growth on an arbitrary substrate remains challenging. Here, we demonstrate a bottom-up and transfer-free growth method for preparing multilayer graphene using a self-assembled monolayer (trimethoxy phenylsilane) as the carbon source. Graphene was directly grown on various substrates such as SiO2/Si, quartz, GaN, and textured Si by a simple thermal annealing process employing catalytic metal encapsulation. To determine the optimal growth conditions, experimental parameters such as the choice of catalytic metal, growth temperatures, and gas flow rate were investigated. The optical transmittance at 550 nm and the sheet resistance of the prepared transfer-free graphene are 84.3% and 3500 Omega/square, respectively. The synthesized graphene samples were fabricated into chemical sensors. High and fast responses to both NO2 and NH3 gas molecules were observed. The transfer-free graphene growth method proposed in this study is highly compatible with previously established fabrication systems;. thereby opening up new possibilities for using graphene in versatile applications.</P>

      • Influence of High-Energy Proton Irradiation on β-Ga<sub>2</sub>O<sub>3</sub> Nanobelt Field-Effect Transistors

        Yang, Gwangseok,Jang, Soohwan,Ren, Fan,Pearton, Stephen J.,Kim, Jihyun American Chemical Society 2017 ACS APPLIED MATERIALS & INTERFACES Vol.9 No.46

        <P>The robust radiation resistance of wide-band gap materials is advantageous for space applications, where the high-energy particle irradiation deteriorates the performance of electronic devices. We report on the effects of proton irradiation of beta-Ga2O3 nanobelts, whose energy band gap is similar to 4.85 eV at room temperature. Back-gated field-effect transistor (FET) based on exfoliated quasi-two-dimensional beta-Ga2O3 nanobelts were exposed to a 10 MeV proton beam. The proton-dose- and time-dependent characteristics of the radiation-damaged FETs were systematically analyzed. A 73% decrease in the field-effect mobility and a positive shift of the threshold voltage were observed after proton irradiation at a fluence of 2 x 10(15) cm(-2). Greater radiation-induced degradation occurs in the conductive channel of the beta-Ga2O3 nanobelt than at the contact between the metal and beta-Ga2O3. The on/off ratio of the exfoliated beta-Ga2O3 FETs was maintained even after proton doses up to 2 x 10(15) cm(-2). The radiation -induced damage in the beta-Ga2O3-based FETs was significantly recovered after rapid thermal annealing at 500 degrees C. The outstanding radiation durability of beta-Ga2O3 renders it a promising building block for space applications.</P>

      • Self-aligned growth of CdTe photodetectors using a graphene seed layer.

        Yang, Gwangseok,Kim, Donghwan,Kim, Jihyun Optical Society of America 2015 Optics express Vol.23 No.19

        <P>We demonstrate the self-aligned growth of CdTe photodetectors using graphene as a pre-defined seed layer. Defects were generated in the graphene prior to growth to act as CdTe nucleation sites. Self-aligned CdTe structures were grown selectively on the pre-defined graphene region. The electrical and optoelectrical properties of the photodetectors were systematically analyzed. Our CdTe devices displayed Ohmic behavior with a low sheet resistance of 1.24 ?? 10<sup>8</sup> 곽/sq. Excellent photodetecting performances were achieved, including a high on-off ratio (~2.8), fast response time (10.4 s), and highly reproducible photoresponses. The fabrication method proposed here for these self-aligned device structures proves valuable for the development of next-generation graphene-semiconductor hybrid devices.</P>

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