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      • The association of disease activity, pro-inflammatory cytokines, and neurotrophic factors with depression in patients with rheumatoid arthritis

        Cheon, Yun-Hong,Lee, Seung-Geun,Kim, Mingyo,Kim, Hyun-Ok,Sun Suh, Young,Park, Ki-Soo,Kim, Rock Bum,Yang, Hyun-Su,Kim, Ji-Min,Son, Chang-Nam,Kyoung Park, Eun,Kim, Sang-Hyon,Lee, Sang-Il Elsevier 2018 Brain, behavior, and immunity Vol.73 No.-

        <P><B>Abstract</B></P> <P>Inflammation and trophic factors (brain-derived neurotrophic factor [BDNF], vascular endothelial growth factor, glial cell line-derived neurotrophic factor, and insulin-like growth factor-1) are associated with depression in the general population. Rheumatoid arthritis (RA) is a chronic representative inflammatory autoimmune disease; however, the association of disease activity, pro-inflammatory cytokines, and neurotrophic factors with depression has not been sufficiently investigated. Therefore, we determined the prevalence of depression and risk factors for depression and deterioration of depressive symptoms in RA patients. In addition, we analyzed the association between disease activity, pro-inflammatory cytokines, trophic factors, and depression in RA (N = 474). Demographic and laboratory data were examined, and routine assessment of patient index data 3 (RAPID 3) and disease activity score 28-joint count C-reactive protein (DAS 28-CRP) was performed to assess disease activity of RA. Depression was measured using the Korean version of the Beck Depression Inventory-second edition (K-BDI II). A K-BDI score ≥18 was considered the cut-off for depression in accordance with a previous validation study. The serum level of pro-inflammatory cytokines and neurotrophic factors was assessed by enzyme-linked immune sorbent assay. The prevalence of depression was 32.4% in patients with RA. The severity of disease activity of RA (RAPID 3 score [OR 2.34; 95% confidence interval, CI 1.22–4.51], DAS 28-CRP [≥3.2] [OR 1.60, 95% CI 1.01–2.53]) and severity of fatigue (OR 1.26 95% CI 1.15–1.38) were associated with depression and deterioration of depressive symptoms in the multivariate analysis. Among the components of RAPID 3 and DAS 28-CRP, patient assessment for global health and abilities for daily performance were more related to depression. The level of pro-inflammatory cytokines (IL-1β, IL-6, TNF-alpha) was not related to depression. The level of BDNF was significantly lower in RA patients with depression and was negatively correlated with K-BDI II score. Depression was related with the level of fatigue, low expression of BDNF, and high RA disease activity, which was associated with impaired ability to perform activities of daily life. Strict control of fatigue and disease activity to improve one’s capacity to perform daily life activities would be important to regulate depression. The level of BDNF might be one of the possible biomarkers to predict or monitor depression in patients with RA.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Prevalence of depression in patients with rheumatoid arthritis (RA) was analyzed. </LI> <LI> Risk factors for depression and deterioration of depressive symptoms and were analyzed. </LI> <LI> Depression was related with disease activity in RA. </LI> <LI> Depression in RA was associated with impaired ability to perform activities of daily life. </LI> <LI> Among neurotrophic factors, the level of BDNF was related with depression in RA patients. </LI> <LI> The level of pro-inflammatory cytokines were not related with depression in RA patients. </LI> </UL> </P>

      • KCI등재
      • Neutrophils disturb pulmonary microcirculation in sepsis-induced acute lung injury

        Park, Inwon,Kim, Mingyo,Choe, Kibaek,Song, Eunjoo,Seo, Howon,Hwang, Yoonha,Ahn, Jinhyo,Lee, Seung-Hyo,Lee, Jae Hyuk,Jo, You Hwan,Kim, Kyuseok,Koh, Gou Young,Kim, Pilhan European Respiratory Society 2019 The European respiratory journal Vol.53 No.3

        <▼1><P>The lung is highly vulnerable during sepsis, yet its functional deterioration accompanied by disturbances in the pulmonary microcirculation is poorly understood. This study aimed to investigate how the pulmonary microcirculation is distorted in sepsis-induced acute lung injury (ALI) and reveal the underlying cellular pathophysiologic mechanism.</P><P>Using a custom-made intravital lung microscopic imaging system in a murine model of sepsis-induced ALI, we achieved direct real-time visualisation of the pulmonary microcirculation and circulating cells <I>in vivo</I>. We derived the functional capillary ratio (FCR) as a quantitative parameter for assessing the fraction of functional microvasculature in the pulmonary microcirculation and dead space.</P><P>We identified that the FCR rapidly decreases in the early stage of sepsis-induced ALI. The intravital imaging revealed that this decrease resulted from the generation of dead space, which was induced by prolonged neutrophil entrapment within the capillaries. We further showed that the neutrophils had an extended sequestration time and an arrest-like dynamic behaviour, both of which triggered neutrophil aggregates inside the capillaries and arterioles. Finally, we found that Mac-1 (CD11b/CD18) was upregulated in the sequestered neutrophils and that a Mac-1 inhibitor restored the FCR and improved hypoxaemia.</P><P>Using the intravital lung imaging system, we observed that Mac-1-upregulated neutrophil aggregates led to the generation of dead space in the pulmonary microcirculation that was recovered by a Mac-1 inhibitor in sepsis-induced ALI.</P></▼1><▼2><P><B>Neutrophils induce dead space in the pulmonary microcirculation in sepsis-induced ALI, recovered by a Mac-1 inhibitor</B>http://ow.ly/vUzO30nbUyU</P></▼2>

      • SCOPUSKCI등재SCIE

        Promising Therapeutic Effects of Embryonic Stem Cells-Origin Mesenchymal Stem Cells in Experimental Pulmonary Fibrosis Models: Immunomodulatory and Anti-Apoptotic Mechanisms

        Hanna Lee,Ok-Yi Jeong,Hee Jin Park,Sung-Lim Lee,Eun-yeong Bok,Mingyo Kim,Young Sun Suh,Yun-Hong Cheon,Hyun-Ok Kim,Suhee Kim,Sung Hak Chun,Jung Min Park,Young Jin Lee,Sang-Il Lee 대한면역학회 2023 Immune Network Vol.23 No.6

        Interstitial lung disease (ILD) involves persistent inflammation and fibrosis, leading to respiratory failure and even death. Adult tissue-derived mesenchymal stem cells (MSCs) show potential in ILD therapeutics but obtaining an adequate quantity of cells for drug application is difficult. Daewoong Pharmaceutical’s MSCs (DW-MSCs) derived from embryonic stem cells sustain a high proliferative capacity following long-term culture and expansion. The aim of this study was to investigate the therapeutic potential of DW-MSCs in experimental mouse models of ILD. DW-MSCs were expanded up to 12 passages for in vivo application in bleomycin-induced pulmonary fibrosis and collagen-induced connective tissue disease- ILD mouse models. We assessed lung inflammation and fibrosis, lung tissue immune cells, fibrosis-related gene/protein expression, apoptosis and mitochondrial function of alveolar epithelial cells, and mitochondrial transfer ability. Intravenous administration of DWMSCs consistently improved lung fibrosis and reduced inflammatory and fibrotic markers expression in both models across various disease stages. The therapeutic effect of DW-MSCs was comparable to that following daily oral administration of nintedanib or pirfenidone. Mechanistically, DW-MSCs exhibited immunomodulatory effects by reducing the number of B cells during the early phase and increasing the ratio of Tregs to Th17 cells during the late phase of bleomycin-induced pulmonary fibrosis. Furthermore, DW-MSCs exhibited antiapoptotic effects, increased cell viability, and improved mitochondrial respiration in alveolar epithelial cells by transferring their mitochondria to alveolar epithelial cells. Our findings indicate the strong potential of DW-MSCs in the treatment of ILD owing to their high efficacy and immunomodulatory and anti-apoptotic effects.

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