Jang H.-U.,Kyungpook National University |
Park K.-S.,Gyeongsang National University |
Cheon S.-M.,Dong - A University |
Lee H.-W.,Brain Science and Engineering Institute |
And 3 more authors.
Clinical and Experimental Otorhinolaryngology | Year: 2014
Objectives. Obstructive sleep apnea (OSA) is a disorder characterized by repetitive partial or complete occlusion of the upper airway during sleep that affects quality of life. The aim of this study was to develop the Korean version of the sleep apnea quality of life index (K-SAQLI) and apply it in Korean patients with OSA. Methods. Ninety-three patients with OSA completed the K-SAQLI. Its construct validity and responsiveness were tested by comparing the baseline and change scores obtained in each domain (i.e., daily functioning, social interactions, emotional functioning, and symptoms) using the medical outcome survey-short form 36 (SF-36). Results. The Cronbach α coefficients of internal reliability exceeded 0.60 in all the domains (daily functioning, 0.89; social interactions, 0.88; emotional functioning, 0.92; symptoms, 0.67; and total, 0.94). The K-SAQLI had a high test-retest correlation coefficient of 0.73 in the 20 randomized selected patients. The construct validity was confirmed by significant correlations with SF-36 subscale scores. Conclusion. The results of this study demonstrate that the K-SAQLI may be applicable for clinical purposes. © 2014 by Korean Society of Otorhinolaryngology-Head and Neck Surgery.
Lee S.-H.,Kyungpook National University |
Lee J.H.,Chungnam National University |
Kim E.-J.,Kyungpook National University |
Kim W.-J.,Kyungpook National University |
And 4 more authors.
Cell Biology International | Year: 2012
Decursin and related coumarin compounds in herbal extracts have a number of biological activities against inflammation, angiogenesis and cancer. We have analysed a derivative of decursin (CSL-32) for activity against inflammatory activation of cancer cells, such as migration, invasion and expression of pro-inflammatory mediators. The human fibrosarcoma cell line, HT1080, was treated with TNFα (tumour necrosis factor α) in the presence or absence of CSL-32. The cellular responses and modification of signalling adapters were analysed with respect to the production of pro-inflammatory mediators, as also migration, adhesion and invasion. Treatment of HT1080 cells with CSL-32 inhibited their proliferation, without affecting cell viability, and TNFα-induced expression of pro-inflammatory mediators, such as MMP-9 (matrix metalloproteinase-9) and IL-8 (interleukin-8). CSL-32 also suppressed phosphorylation and degradation of IkB (inhibitory κB), phosphorylation of p65 subunit of NF-κB (nuclear factor-κB) and nuclear translocation of NF-κB, which are required for the expression of pro-inflammatory mediators. In addition, CSL-32 inhibited invasion and migration of HT1080 cells, as also cellular adhesion to fibronectin, an ECM (extracellular matrix) protein. CSL-32 treatment resulted in a dose-dependent inhibition of PI3K (phosphoinositide 3-kinase) activity, required for the cellular migration. The analyses show that CSL-32 inhibits processes associated with inflammation, such as the production of pro-inflammatory mediators, as well as adhesion, migration and invasion in HT1080 cells. © The Author(s) Journal compilation © 2012 International Federation for Cell Biology.
Seo M.,Brain Science and Engineering Institute |
Seo M.,Dongguk University |
Lee S.,Brain Science and Engineering Institute |
Lee S.,Korea Brain Research Institute |
And 5 more authors.
Nature Communications | Year: 2014
Lentiviral short hairpin RNA (shRNA)-mediated genetic screening is a powerful tool for identifying loss-of-function phenotype in mammalian cells. Here, we report the identification of 91 cell migration-regulating genes using unbiased genome-wide functional genetic selection. Individual knockdown or cDNA overexpression of a set of 10 candidates reveals that most of these cell migration determinants are strongly dependent on the PI3K/PTEN/AKT pathway and on their downstream signals, such as FOXO1 and p70S6K1. ALK, one of the cell migration promoting genes, uniquely uses p55Î 3 regulatory subunit of PI3K, rather than more common p85 subunit, to trigger the activation of the PI3K-AKT pathway. Our method enables the rapid and cost-effective genome-wide selection of cell migration regulators. Our results emphasize the importance of the PI3K/PTEN/AKT pathway as a point of convergence for multiple regulators of cell migration. © 2014 Macmillan Publishers Limited.
Nam Y.S.,Chonnam National University |
Kim Y.,Chonnam National University |
Joung H.,Chonnam National University |
Kwon D.-H.,Chonnam National University |
And 15 more authors.
Circulation Research | Year: 2014
RATIONALE:: Small heterodimer partner (SHP; NR0B2) is an atypical orphan nuclear receptor that lacks a conventional DNA-binding domain. Through interactions with other transcription factors, SHP regulates diverse biological events, including glucose metabolism in liver. However, the role of SHP in adult heart diseases has not yet been demonstrated. OBJECTIVE:: We aimed to investigate the role of SHP in adult heart in association with cardiac hypertrophy. METHODS AND RESULTS:: The roles of SHP in cardiac hypertrophy were tested in primary cultured cardiomyocytes and in animal models. SHP-null mice showed a hypertrophic phenotype. Hypertrophic stresses repressed the expression of SHP, whereas forced expression of SHP blocked the development of hypertrophy in cardiomyocytes. SHP reduced the protein amount of Gata6 and, by direct physical interaction with Gata6, interfered with the binding of Gata6 to GATA-binding elements in the promoter regions of natriuretic peptide precursor type A. Metformin, an antidiabetic agent, induced SHP and suppressed cardiac hypertrophy. The metformin-induced antihypertrophic effect was attenuated either by SHP small interfering RNA in cardiomyocytes or in SHP-null mice. CONCLUSIONS:: These results establish SHP as a novel antihypertrophic regulator that acts by interfering with GATA6 signaling. SHP may participate in the metformin-induced antihypertrophic response. © 2014 American Heart Association, Inc.
Ock J.,Brain Science and Engineering Institute |
Kim S.,Brain Science and Engineering Institute |
Yi K.-Y.,Korea Research Institute of Chemical Technology |
Kim N.-J.,Korea Research Institute of Chemical Technology |
And 3 more authors.
Biochemical Pharmacology | Year: 2010
Excessive microglial activation with overexpression of proinflammatory cytokines and oxidative stress products is linked to the progression of several neurodegenerative diseases; therefore, suppression of microglial activation is a potential therapeutic approach against these diseases. Since nitric oxide (NO) is one of the major inflammatory mediators that are produced by activated microglia, inhibitory effects of novel synthetic compounds on microglial NO production were investigated. From the mouse microglia cell-based assays, an imidazo [4,5-b] pyridine compound KR-31360 was identified as an inhibitor of microglial NO production with an IC50 value of 2 μM. Structure-activity relationship study indicated that 5-position of imidazo [4,5-b] pyridine ring is critical for the activity. KR-31360 also inhibited lipopolysaccharide (LPS)-induced secretion of tumor necrosis factor alpha (TNF-α) and transcription of TNF-α, interleukin-1 beta, and inducible nitric oxide synthase as well as activation of nuclear factor kappa B and mitogen-activated protein kinases. KR-31360 was neuroprotective by suppressing microglial neurotoxicity in a microglia-neuron coculture. The neuroprotective activity of the compound was most effective when microglia were pretreated with the compound prior to LPS challenge. The inhibitory effect of KR-31360 on microglial activation was further demonstrated in a mouse neuroinflammation model in vivo: compared to vehicle-injected animals, KR-31360 injection attenuated LPS-induced microglial activation as evidenced by isolectin B4 staining and proinflammatory gene expression of brain sections. DNA microarray analysis supported that KR-31360 targeted Toll-like receptor 4 pathways. In addition to being a new drug candidate against neuroinflammatory diseases, the compound may be a powerful tool for the better understanding of microglia biology and neuroinflammation. © 2009 Elsevier Inc. All rights reserved.