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      • SCIESCOPUSKCI등재

        Profiling of remote skeletal muscle gene changes resulting from stimulation of atopic dermatitis disease in NC/Nga mouse model

        Donghee Lee,Yelim Seo,Young-Won Kim,Seongtae Kim,Jeongyoon Choi,Sung-Hee Moon,Hyemi Bae,Hui-sok Kim,Hangyeol Kim,Jae-Hyun Kim,Tae-Young Kim,Eunho Kim,Suemin Yim,Inja Lim,Hyoweon Bang,Jung-Ha Kim,Jae-H 대한약리학회 2019 The Korean Journal of Physiology & Pharmacology Vol.23 No.5

        Although atopic dermatitis (AD) is known to be a representative skin disorder, it also affects the systemic immune response. In a recent study, myoblasts were shown to be involved in the immune regulation, but the roles of muscle cells in AD are poorly understood. We aimed to identify the relationship between mitochondria and atopy by genome-wide analysis of skeletal muscles in mice. We induced AD-like symptoms using house dust mite (HDM) extract in NC/Nga mice. The transcriptional profiles of the untreated group and HDM-induced AD-like group were analyzed and compared using microarray, differentially expressed gene and functional pathway analyses, and protein interaction network construction. Our microarray analysis demonstrated that immune response-, calcium handling-, and mitochondrial metabolism-related genes were differentially expressed. In the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology pathway analyses, immune response pathways involved in cytokine interaction, nuclear factor-kappa B, and T-cell receptor signaling, calcium handling pathways, and mitochondria metabolism pathways involved in the citrate cycle were significantly upregulated. In protein interaction network analysis, chemokine family-, muscle contraction process-, and immune response-related genes were identified as hub genes with many interactions. In addition, mitochondrial pathways involved in calcium signaling, cardiac muscle contraction, tricarboxylic acid cycle, oxidation-reduction process, and calcium-mediated signaling were significantly stimulated in KEGG and Gene Ontology analyses. Our results provide a comprehensive understanding of the genome-wide transcriptional changes of HDM-induced AD-like symptoms and the indicated genes that could be used as AD clinical biomarkers.

      • SCIESCOPUSKCI등재

        Profiling of remote skeletal muscle gene changes resulting from stimulation of atopic dermatitis disease in NC/Nga mouse model

        Lee, Donghee,Seo, Yelim,Kim, Young-Won,Kim, Seongtae,Choi, Jeongyoon,Moon, Sung-Hee,Bae, Hyemi,Kim, Hui-sok,Kim, Hangyeol,Kim, Jae-Hyun,Kim, Tae-Young,Kim, Eunho,Yim, Suemin,Lim, Inja,Bang, Hyoweon,Ki The Korean Society of Pharmacology 2019 The Korean Journal of Physiology & Pharmacology Vol.23 No.5

        Although atopic dermatitis (AD) is known to be a representative skin disorder, it also affects the systemic immune response. In a recent study, myoblasts were shown to be involved in the immune regulation, but the roles of muscle cells in AD are poorly understood. We aimed to identify the relationship between mitochondria and atopy by genome-wide analysis of skeletal muscles in mice. We induced AD-like symptoms using house dust mite (HDM) extract in NC/Nga mice. The transcriptional profiles of the untreated group and HDM-induced AD-like group were analyzed and compared using microarray, differentially expressed gene and functional pathway analyses, and protein interaction network construction. Our microarray analysis demonstrated that immune response-, calcium handling-, and mitochondrial metabolism-related genes were differentially expressed. In the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology pathway analyses, immune response pathways involved in cytokine interaction, nuclear factor-kappa B, and T-cell receptor signaling, calcium handling pathways, and mitochondria metabolism pathways involved in the citrate cycle were significantly upregulated. In protein interaction network analysis, chemokine family-, muscle contraction process-, and immune response-related genes were identified as hub genes with many interactions. In addition, mitochondrial pathways involved in calcium signaling, cardiac muscle contraction, tricarboxylic acid cycle, oxidation-reduction process, and calcium-mediated signaling were significantly stimulated in KEGG and Gene Ontology analyses. Our results provide a comprehensive understanding of the genome-wide transcriptional changes of HDM-induced AD-like symptoms and the indicated genes that could be used as AD clinical biomarkers.

      • Effects of modulators of AMP-activated protein kinase on TASK-1/3 and intracellular Ca(2+) concentration in rat carotid body glomus cells.

        Kim, Donghee,Kang, Dawon,Martin, Elizabeth A,Kim, Insook,Carroll, John L Elsevier Science 2014 Respiratory physiology & neurobiology Vol.195 No.-

        <P>Acute hypoxia depolarizes carotid body chemoreceptor (glomus) cells and elevates intracellular Ca(2+) concentration ([Ca(2+)]i). Recent studies suggest that AMP-activated protein kinase (AMPK) mediates these effects of hypoxia by inhibiting the background K(+) channels such as TASK. Here we studied the effects of modulators of AMPK on TASK activity in cell-attached patches. Activators of AMPK (1mM AICAR and 0.1-0.5mM A769662) did not inhibit TASK activity or cause depolarization during acute (10min) or prolonged (2-3h) exposure. Hypoxia inhibited TASK activity by 70% in cells pretreated with AICAR or A769662. Both AICAR and A769662 (15-40min) failed to increase [Ca(2+)]i in glomus cells. Compound C (40μM), an inhibitor of AMPK, showed no effect on hypoxia-induced inhibition of TASK. AICAR and A769662 phosphorylated AMPKα in PC12 cells, and Compound C blocked the phosphorylation. Our results suggest that AMPK does not affect TASK activity and is not involved in hypoxia-induced elevation of intracellular [Ca(2+)] in isolated rat carotid body glomus cells.</P>

      • KCI등재후보

        Factors associated with rebleeding after coil embolization in patients with aneurysmal subarachnoid hemorrhage

        Kim Donghee,Pyen Jinsu,Whang Kum,Cho Sungmin,Jang Yeongyu,Kim Jongyeon,Koo Younmoo,Choi Jongwook 대한뇌혈관외과학회 2022 Journal of Cerebrovascular and Endovascular Neuros Vol.24 No.1

        Objective: Aneurysmal subarachnoid hemorrhage (aSAH) has a high mortality rate, and hemorrhage amounts and perioperative rebleeding importantly determines prognosis. However, despite adequate treatment, prognosis is poor in many ruptured aneurysm cases. In this study, we identified and evaluated factors related to perioperative rebleeding in patients with aSAH. Methods: The medical and surgical records of 166 patients that underwent endovascular embolization for a ruptured cerebral aneurysm at a single institution from 2014 to 2016 were retrospectively analyzed to identify risk factors of rebleeding. All patients were examined for risk factors and evaluated for increased hemorrhage by brain computed tomography at 3 days after surgery. Results: This series included 54 men (32.5%) and 112 women (67.5%) of mean age 58.3±14.3 years. After procedures, 26 patients (15.7%) experienced rebleeding, and 1 of these (0.6%) experienced an intraoperative aneurysmal rupture. External ventricular drainage (EVD) (odds ratio [OR] 5.389, [95% confidence interval (CI) 1.171- 24.801]) and modified Fisher grade (OR 2.037, [95% CI 1.077-3.853]) were found to be independent risk factors of rebleeding, and perioperative rebleeding was strongly associated with patient outcomes (p<0.001). Conclusions: We concluded the rebleeding risk after aSAH is greater in patients with large hemorrhage amounts and a high pre-operative modified Fisher grade, and thus, we caution neurosurgeons should take care in such cases. Objective: Aneurysmal subarachnoid hemorrhage (aSAH) has a high mortality rate, and hemorrhage amounts and perioperative rebleeding importantly determines prognosis. However, despite adequate treatment, prognosis is poor in many ruptured aneurysm cases. In this study, we identified and evaluated factors related to perioperative rebleeding in patients with aSAH. Methods: The medical and surgical records of 166 patients that underwent endovascular embolization for a ruptured cerebral aneurysm at a single institution from 2014 to 2016 were retrospectively analyzed to identify risk factors of rebleeding. All patients were examined for risk factors and evaluated for increased hemorrhage by brain computed tomography at 3 days after surgery. Results: This series included 54 men (32.5%) and 112 women (67.5%) of mean age 58.3±14.3 years. After procedures, 26 patients (15.7%) experienced rebleeding, and 1 of these (0.6%) experienced an intraoperative aneurysmal rupture. External ventricular drainage (EVD) (odds ratio [OR] 5.389, [95% confidence interval (CI) 1.171- 24.801]) and modified Fisher grade (OR 2.037, [95% CI 1.077-3.853]) were found to be independent risk factors of rebleeding, and perioperative rebleeding was strongly associated with patient outcomes (p<0.001). Conclusions: We concluded the rebleeding risk after aSAH is greater in patients with large hemorrhage amounts and a high pre-operative modified Fisher grade, and thus, we caution neurosurgeons should take care in such cases.

      • SCISCIESCOPUS

        Palladium(II)-Catalyzed Direct Intermolecular Alkenylation of Chromones

        Kim, Donghee,Hong, Sungwoo American Chemical Society 2011 ORGANIC LETTERS Vol.13 No.16

        <P>A new efficient method for the direct alkenylation of chromones via a palladium(II)-catalyzed C–H functionalization reaction was developed. The use of pivalic acid with Cu(OAc)<SUB>3</SUB>/Ag<SUB>2</SUB>CO<SUB>3</SUB> provided superior reactivity in the cross-coupling of chromones with alkene partners. This approach represents a significant advance over the existing two-step method and afforded various 3-vinylchromone derivatives, which are privileged structures in many biologically active compounds and versatile synthetic building blocks.</P><P><B>Graphic Abstract</B> <IMG SRC='http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/orlef7/2011/orlef7.2011.13.issue-16/ol2018278/production/images/medium/ol-2011-018278_0001.gif'></P><P><A href='http://pubs.acs.org/doi/suppl/10.1021/ol2018278'>ACS Electronic Supporting Info</A></P>

      • Subclinical Hypothyroidism and Low-Normal Thyroid Function Are Associated With Nonalcoholic Steatohepatitis and Fibrosis

        Kim, Donghee,Kim, Won,Joo, Sae Kyung,Bae, Jeong Mo,Kim, Jung Ho,Ahmed, Aijaz Elsevier 2018 Clinical gastroenterology and hepatology Vol.16 No.1

        <P><B>Background & Aims</B></P> <P>Variations in level of thyroid-stimulating hormone (TSH) within the reference range of thyroid hormone could have negative health effects. We evaluated the effect of plasma TSH levels within the euthyroid range on the severity of histological damage associated with nonalcoholic fatty liver disease (NAFLD).</P> <P><B>Methods</B></P> <P>We performed a cross-sectional study of 425 subjects with biopsy-proven NAFLD (mean age, 53 years; 52% male) who participated in the Boramae NAFLD study from January 2013 to January 2017. Each subject underwent an anthropometric assessment and laboratory and clinical evaluations. Of the subjects, 282 were assigned to a strict-normal thyroid function group (plasma level of TSH, 0.4 to 2.5 mIU/L). Patients with low thyroid function were assigned to groups of subclinical hypothyroidism (plasma level of TSH above 4.5 mIU/L with a normal thyroid hormone level; n = 59) or low-normal thyroid function (higher plasma TSH level [2.5 to 4.5 mIU/L] with a normal thyroid hormone level; n = 84). Multivariate logistic regression analysis was used to identify factors independently associated with nonalcoholic steatohepatitis (NASH) and advanced fibrosis.</P> <P><B>Results</B></P> <P>NASH and advanced fibrosis were found in higher percentages of subjects with low thyroid function vs strict-normal thyroid function (52.4% vs 37.2% for NASH and 21.0% vs 10.6% for advanced fibrosis; <I>P</I> < .01). Among subjects with low thyroid function, a higher proportion of patients with subclinical hypothyroidism had NASH and associated advanced fibrosis vs patients with low-normal thyroid function (57.6% vs 48.8% for NASH and 25.4% vs 17.9% for advanced fibrosis; <I>P</I> < .01). Subjects with low thyroid function had more extensive hepatic steatosis with greater severity of balloon degeneration and fibrosis. In multivariate analyses, low thyroid function was significantly associated with NASH (odds ratio, 1.61; 95% CI, 1.04–2.50; <I>P</I> = .035) and advanced fibrosis (odds ratio, 2.23; 95% CI, 1.18–4.23; <I>P</I> = .014). Risks of NASH and advanced fibrosis increased significantly with plasma concentration of TSH (<I>P</I>trend <.05 for each).</P> <P><B>Conclusions</B></P> <P>Subclinical hypothyroidism and low-normal thyroid function are independent predictors of NASH and advanced fibrosis, confirming the relationship between these diseases. ClinicalTrials.gov, Number: NCT02206841.</P>

      • SCIESCOPUSKCI등재

        Prediction of itching diagnostic marker through RNA sequencing of contact hypersensitivity and skin scratching stimulation mice models

        Kim, Young-Won,Zhou, Tong,Ko, Eun-A,Kim, Seongtae,Lee, Donghee,Seo, Yelim,Kwon, Nahee,Choi, Taeyeon,Lim, Heejung,Cho, Sungvin,Bae, Gwanhui,Hwang, Yuseong,Kim, Dojin,Park, Hyewon,Lee, Minjae,Jang, Eunk The Korean Society of Pharmacology 2019 The Korean Journal of Physiology & Pharmacology Vol.23 No.2

        Pruritus (itching) is classically defined as an unpleasant cutaneous sensation that leads to scratching behavior. Although the scientific criteria of classification for pruritic diseases are not clear, it can be divided as acute or chronic by duration of symptoms. In this study, we investigated whether skin injury caused by chemical (contact hypersensitivity, CHS) or physical (skin-scratching stimulation, SSS) stimuli causes initial pruritus and analyzed gene expression profiles systemically to determine how changes in skin gene expression in the affected area are related to itching. In both CHS and SSS, we ranked the Gene Ontology Biological Process terms that are generally associated with changes. The factors associated with upregulation were keratinization, inflammatory response and neutrophil chemotaxis. The Kyoto Encyclopedia of Genes and Genomes pathway shows the difference of immune system, cell growth and death, signaling molecules and interactions, and signal transduction pathways. Il1a, Il1b and Il22 were upregulated in the CHS, and Tnf, Tnfrsf1b, Il1b, Il1r1 and Il6 were upregulated in the SSS. Trpc1 channel genes were observed in representative itching-related candidate genes. By comparing and analyzing RNA-sequencing data obtained from the skin tissue of each animal model in these characteristic stages, it is possible to find useful diagnostic markers for the treatment of itching, to diagnose itching causes and to apply customized treatment.

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