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Lee, D.H.,Han, D.H.,Nam, K.T.,Park, J.S.,Kim, S.H.,Lee, M.,Kim, G.,Min, B.S.,Cha, B.S.,Lee, Y.S.,Sung, S.H.,Jeong, H.,Ji, H.W.,Lee, M.J.,Lee, J.S.,Lee, H.Y.,Chun, Y.,Kim, J.,Komatsu, M.,Lee, Y.h.,Bae, Pergamon ; Elsevier Science Ltd 2016 FREE RADICAL BIOLOGY AND MEDICINE Vol.99 No.-
Oxidative stress is important for the pathogenesis of nonalcoholic fatty liver disease (NAFLD), a chronic disease that ranges from hepatic steatosis to nonalcoholic steatohepatitis (NASH). The nuclear factor erythroid 2-related factor 2-Kelch-like ECH associated protein 1 (Nrf2-Keap1) pathway is essential for cytoprotection against oxidative stress. In this study, we found that oxidative stress or inflammatory biomarkers and TUNEL positive cells were markedly increased in NASH patients compared to normal or simple steatosis. In addition, we identified that the hepatic mRNA levels of Nrf2 target genes such as Nqo-1 and GSTA-1 were significantly increased in NASH patients. Ezetimibe, a drug approved by the Food and Drug Administration for the treatment of hypercholesterolemia, improves NAFLD and alleviates oxidative stress. However, the precise mechanism of its antioxidant function remains largely unknown. We now demonstrate that ezetimibe activates Nrf2-Keap1 pathway which was dependent of autophagy adaptor protein p62, without causing cytotoxicity. Ezetimibe activates AMP-activated protein kinase (AMPK), which in turn phosphorylates p62 (p-S351) via their direct interaction. Correspondingly, Ezetimibe protected liver cells from saturated fatty acid-induced apoptotic cell death through p62-dependent Nrf2 activation. Furthermore, its role as an Nrf2 activator was supported by methione- and choline- deficient (MCD) diet-induced NASH mouse model, showing that ezetimibe decreased the susceptibility of the liver to oxidative injury. These data demonstrate that the molecular mechanisms underlying ezetimibe's antioxidant role in the pathogenesis of NASH.
Analysis of Fifty Hotspot Mutations of Lung Squamous Cell Carcinoma in Never-smokers
Lee, Ha Youn,Lee, Se-Hoon,Won, Jae-Kyung,Lee, Dong Soo,Kwon, Nak-Jung,Choi, Sun Mi,Lee, Jinwoo,Lee, Chang-Hoon,Lee, Sang-Min,Yim, Jae-Joon,Yoo, Chul-Gyu,Kim, Young Whan,Han, Sung Koo,Park, Young Sik KOREAN ACADEMY OF MEDICAL SCIENCE 2017 JOURNAL OF KOREAN MEDICAL SCIENCE Vol.32 No.3
<P>Smoking is the major risk factor for lung squamous cell carcinoma (SCC), although a small number of lung SCCs occurs in never-smokers. The purpose of this study was to compare 50 hotspot mutations of lung SCCs between never-smokers and smokers. We retrospectively reviewed the medical records of patients newly diagnosed with lung SCC between January 1, 2011 and December 31, 2013 in the Seoul National University Hospital. Formalin-fixed, paraffin-embedded tumor samples were used for analysis of hotspot mutations. Fifty cancer-related genes in never-smokers were compared to those in ever-smokers. Of 379 lung SCC patients, 19 (5.0%) were never-smokers. The median age of these 19 patients was 67 years (interquartile range 57–73 years), and 10 of these patients were women (52.5%). The incidence rates of stage I, II, III, and IV disease in this group were 26.4%, 5.3%, 31.6%, and 36.8%, respectively, and sequencing was performed successfully in 14 cases. In the 26 lung SCC tumor samples (12 from never-smokers and 14 from ever-smokers) sequenced using personal genome machine, the most common mutations were in <I>TP53</I> (75.0%), <I>RAS</I> (66.7%), and <I>STK11</I> (33.3%), but mutations were also found in <I>EGFR</I>, <I>KIT</I>, and <I>PTEN</I>. The distribution of hotspot mutations in never-smokers was similar to that in ever-smokers. There was no significant difference in overall survival between the 2 groups. The 50 hotspot mutations of lung SCC in never-smokers were similar to those of ever-smokers.</P>
Coenzyme Q10 Inhibits Th17 and STAT3 Signaling Pathways to Ameliorate Colitis in Mice
Lee, Seon-Yeong,Lee, Seung Hoon,Yang, Eun-Ji,Kim, Jae-Kyung,Kim, Eun-Kyung,Jung, KyungAh,Jung, Hongsoon,Lee, Kyungjin,Lee, Han Hee,Lee, Bo-In,Park, Sung-Hwan,Shin, Dong Yun,Cho, Mi-La Mary Ann Liebert, Inc. Publishers 2017 Journal of Medicinal Food Vol. No.
<P>Coenzyme Q10 (CoQ10) is a powerful antioxidant substance synthesized in the body. The current study aimed to determine whether CoQ10 suppresses inflammation and inhibits p-STAT3 expression in an experimental colitis mouse model. The mice were orally fed with CoQ10 once a day for 13 days. Histological analysis of the colons was performed by immunohistochemistry. Expression of IL-17, FOXP3, p53, AMPK, and mTOR and activation of p-STAT3 and p-STAT5 in lymph node and spleen tissues were detected by confocal microscopy of stained tissue sections. The relative mRNA expression was measured with real-time PCR, and protein levels were examined by western blot. CoQ10 reduced the disease activity index score and the colon histological score. It also reduced inflammatory mediators in the colon and increased the colon length. The expression of IL-17 and p-STAT3 was decreased with CoQ10 treatment. In contrast, CoQ10 treatment increased the expression of p-AMPK and FOXP3. Expression of anti-inflammatory cytokines was shown to increase in colitis mice treated with CoQ10. These results suggested that CoQ10 may reduce the severity of colitis and suppress inflammation through the inhibition of p-STAT3 and IL-17. These results support the use of CoQ10 as a potential targeted therapy for the treatment of colitis.</P>
Methylpiperate Derivatives from Piper longum and Their Inhibition of Monoamine Oxidase
Lee, Seon-A,Hwang, Ji-Sang,Han, Xiang Hua,Lee, Chul,Lee, Min-Hee,Choe, Sang-Gil,Hong, Seong-Su,Lee, Dong-Ho,Lee, Myung-Koo,Hwang, Bang-Yeon 대한약학회 2008 Archives of Pharmacal Research Vol.31 No.6
We have previously reported that piperine, a known piperidine alkaloid from Piper longum, competitively inhibited mouse brain MAO-A and MAO-B activities. Piperine also showed in vivo antidepressant-like activity against the tail suspension test. In the present study, we further expanded on the identification of MAO inhibitors from the fruit of P. longum. Activity-guided fractionation of a methylene chloride soluble extract led to the isolation of three known piperine-related compounds, methylpiperate (1), guineensine (2), and piperlonguminine (3). Of these, methylpiperate (1) and guineensine (2) showed significant MAO inhibitory activities with $IC_{50}$ values of 3.6 and $139.2\;{\mu}M$, respectively. Furthermore, methylpiperate (1) exhibited a selective inhibitory effect against MAO-B ($IC_{50}$ value: $1.6\;{\mu}M$) than MAO-A ($IC_{50}$ value: $27.1\;{\mu}M$). The kinetic study using the Lineweaver-Burk plots analysis suggested that methylpiperate (1) competitively inhibits MAO-A and MAO-B activities with the Ki values of 23.5 and $1.3\;{\mu}M$, respectively.
Adverse Events With Sustained-Release Donepezil in Alzheimer Disease: Relation to Body Mass Index
Lee, Chunsoo,Lee, Kyungsang,Yu, Hyewon,Ryu, Seung-Ho,Moon, Seok Woo,Han, Changsu,Lee, Jun-Young,Lee, Young Min,Kim, Shin-Gyeom,Kim, Ki Woong,Lee, Dong Woo,Kim, Seong Yoon,Lee, Sang-Yeol,Bae, Jae Nam,J Wolters Kluwer Health, Inc. All rights reserved. 2017 JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY Vol.37 No.4
<P>Implications/Conclusions In Korean patients with moderate to severe AD receiving high-dose donepezil over 24 weeks, TEAEs were significantly more common in those with lower BMI (not clinically overweight), especially nausea. This finding may inform clinical practice for Asian patients.</P>
A User-Oriented Interactive Model for the Conceptual Design of Bulk Cargo Ships
Lee, Dong-Kon,Lee, Kyung-Ho,Han, Soon-Hung,Lee, Soon-Sub,Lee, Kyu-Yeul,Shin, Soo-Chol,Shin, Dong-Won,Lee, Jong-Chol,Kwon, Sung-Chil The Society of Naval Architects of Korea 1994 Selected papers of the society of naval architects Vol.2 No.1
This paper describes a design model for the conceptual design of ships. Existing design models have problems such that their operating mode of batch versions cannot reflect the design procedures in reality. Reliability of the results is low because the performance estimations are based mainly on empirical formulas. To improve the problems of existing design models, a new design model has been developed. The new model consists of an interactive user interface, a database of main engines, a database of particulars of existing ships, and ten modules for performance estimations. To develop such a user-oriented system, the concept of graphical user interface (GUI) is adopted.
Lee, Han-Byoel,Kang, Un-Beom,Moon, Hyeong-Gon,Lee, Jiwoo,Lee, Kyung-Min,Yi, Minju,Park, Yong Sun,Lee, Jong Won,Yu, Jong-Han,Choi, Seung Ho,Cho, Sang Heon,Lee, Cheolju,Han, Wonshik,Noh, Dong-Young Potamitis Press 2015 Anticancer research Vol.35 No.11
<P>We aimed to develop a plasma protein signature for breast cancer diagnosis by using multiple reaction monitoring (MRM)-based mass spectrometry.</P>
Korean National Emissions Inventory System and 2007 Air Pollutant Emissions
Lee, Dae-Gyun,Lee, Yong-Mi,Jang, Kee-Won,Yoo, Chul,Kang, Kyoung-Hee,Lee, Ju-Hyoung,Jung, Sung-Woon,Park, Jung-Min,Lee, Sang-Bo,Han, Jong-Soo,Hong, Ji-Hyung,Lee, Suk-Jo Korean Society for Atmospheric Environment 2011 Asian Journal of Atmospheric Environment (AJAE) Vol.5 No.4
Korea has experienced dramatic development and has become highly industrialized and urbanized during the past 40 years, which has resulted in rapid economic growth. Due to the industrialization and urbanization, however, air pollutant emission sources have increased substantially. Rapid increases in emission sources have caused Korea to suffer from serious air pollution. An air pollutant emissions inventory is one set of essential data to help policymakers understand the current status of air pollution levels, to establish air pollution control policies and to analyze the impacts of implementation of policies, as well as for air quality studies. To accurately and realistically estimate administrative district level air pollutant emissions of Korea, we developed a Korean Emissions Inventory System named the Clean Air Policy Support System (CAPSS). In CAPSS, emissions sources are classified into four levels. Emission factors for each classification category are collected from various domestic and international research reports, and the CAPSS utilizes various national, regional and local level statistical data, compiled by approximately 150 Korean organizations. In this paper, we introduced for the first time, a Korean national emissions inventory system and release Korea's official 2007 air pollutant emissions for five regulated air pollutants.
Lee, Sun Hwa,Lee, Eun Yong,Yoo, Dong-Woo,Hong, Sung Jin,Lee, Jung Hwan,Kwak, Han,Lee, Young Min,Kim, Jinheung,Kim, Cheal,Lee, Jin-Kyu Royal Society of Chemistry 2007 NEW JOURNAL OF CHEMISTRY Vol.31 No.9
<P>Polymer-supported metal (Fe or Ru) complexes for epoxide ring opening reactions were successfully prepared by anchoring the bis(2-picolyl)amine ligand onto the polymer poly(chloromethylstyrene-co-divinylbenzene) (PCD); the catalysts showed heterogeneous catalytic activity and easy recyclability in the ring opening reactions of various epoxide substrates with methanol or H<SUB>2</SUB>O at room temperature under mild and neutral conditions.</P> <P>Graphic Abstract</P><P>Polymer-supported metal catalysts showed efficient heterogeneous catalytic activity and easy recyclability in epoxide ring opening reactions under mild conditions. <IMG SRC='http://pubs.rsc.org/services/images/RSCpubs.ePlatform.Service.FreeContent.ImageService.svc/ImageService/image/GA?id=b707028d'> </P>
Lee, Sun Hwa,Han, Jung Hee,Kwak, Han,Lee, Sung Jea,Lee, Eun Yong,Kim, Hee Jin,Lee, Jung Hwan,Bae, Cheolbeom,Lee, Soo No,Kim, Youngmee,Kim, Cheal WILEY-VCH Verlag 2007 Chemistry Vol.13 No.33
<P>Mononuclear nonheme iron(III) complexes of tetradentate ligands containing two deprotonated amide moieties, [Fe(Me<SUB>2</SUB>bpb)Cl(H<SUB>2</SUB>O)] (3 a) and [Fe(bpc)Cl(H<SUB>2</SUB>O)] (4 a), were prepared by substitution reactions involving the previously synthesized iron(III) complexes [Et<SUB>3</SUB>NH][Fe(Me<SUB>2</SUB>bpb)Cl<SUB>2</SUB>] (3) and [Et<SUB>3</SUB>NH][Fe(bpc)Cl<SUB>2</SUB>] (4). Complexes 3 a and 4 a were characterized by IR and elemental analysis, and complex 3 a also by X-ray crystallography. Nonheme iron(III) complexes 3, 3 a, 4, and 4 a catalyze olefin epoxidation and alcohol oxidation on treatment with m-chloroperbenzoic acid. Pairwise comparisons of the reactivity of these complexes revealed that the nature of the axial ligand (Cl<SUP>−</SUP> versus H<SUB>2</SUB>O) influences the yield of oxidation products, whereas an electronic change in the supporting chelate ligand has little effect. Hydrocarbon oxidation by these catalysts was proposed to involve an iron(V) oxo species which is formed on heterolytic O&n.bond;O bond cleavage of an iron acylperoxo intermediate (FeOOC(O)R). Evidence for this iron(V) oxo species was derived from KIE (k<SUB>H</SUB>/k<SUB>D</SUB>) values, H<SUB>2</SUB><SUP>18</SUP>O exchange experiments, and the use of peroxyphenylacetic acid (PPAA) as the peracid. Our results suggest that an Fe<SUP>V</SUP>&n.dbond;O moiety can form in a system wherein the supporting chelate ligand comprises a mixture of neutral and anionic nitrogen donors. This work is relevant to the chemistry of mononuclear nonheme iron enzymes that are proposed to oxidize organic substrates via reaction pathways involving high-valent iron oxo species.</P> <B>Graphic Abstract</B> <P>High-valent iron–oxo species Fe<SUP>V</SUP>&n.dbond;O, generated by reaction of mononuclear nonheme iron(III) complexes with peracids, are capable of performing olefin epoxidation and alcohol oxidation (see scheme, Sub=olefin or alcohol substrate). The nature of the high-valent species was evidenced by means of mechanistic probes. These results suggest that Fe<SUP>V</SUP>&n.dbond;O species could be generated in many mononuclear nonheme iron enzymes. <img src='wiley_img/09476539-2007-13-33-CHEM200700513-content.gif' alt='wiley_img/09476539-2007-13-33-CHEM200700513-content'> </P>