Effects of the novel angiotensin II receptor type I antagonist, fimasartan on myocardial ischemia/reperfusion injury

Han, J.,Park, S.J.,Thu, V.T.,Lee, S.R.,Long, L.T.,Kim, H.K.,Kim, N.,Park, S.W.,Jeon, E.S.,Kim, E.J.,Yoon, C.H.,Cho, G.Y.,Choi, D.J. Elsevier/North-Holland Biomedical Press 2013 INTERNATIONAL JOURNAL OF CARDIOLOGY Vol.168 No.3

Background: The aim of this study was to investigate the cardioprotective effect of fimasartan, a newly developed angiotensin II receptor type I blocker (ARB), against myocardial ischemia/reperfusion (I/R) injury and to identify the mechanism by which it reduces mitochondrial damage. Methods: Fimasartan was administered intravenously to Sprague-Dawley rats (3mg/kg), cardiomyocytes (50μM), and H9c2 cells (50μM) before ischemia or hypoxia. Myocardial infarction (MI), echocardiograms, DNA fragmentation, terminal deoxynucleotidyl transferase-mediated dUTP in situ nick-end labeling, immunoblotting, oxygen consumption, confocal microscopic appearance, and L-type Ca<SUP>2+</SUP> current (I<SUB>Ca,L</SUB>) were then assessed. Results: Fimasartan pretreatment remarkably reduced the rate of MI and improved cardiac performance well after I/R (n=9/group). Fimasartan also reduced apoptotic cell death both in vivo and in hypoxia/reoxygenation (H/R)-treated H9c2 cells (n=5~8/group). H/R-induced mitochondrial O<SUB>2</SUB><SUP>-</SUP> production and collapse of membrane potential were markedly attenuated in fimasartan-treated cardiomyocytes (n=4~6/group). Additionally, mitochondrial Ca<SUP>2+</SUP> overload during reoxygenation was suppressed by fimasartan (n=4~6/group), and this was found to be possibly related to the inhibition of I<SUB>Ca,L</SUB> and mitochondrial Ca<SUP>2+</SUP> uniporter. Furthermore, fimasartan pretreatment increased phosphorylations of Akt and glycogen synthase kinase-3β (n=5~7/group), decreased pro-apoptotic p53 levels, and increased anti-apoptotic Bcl-2 levels (n=4) during reperfusion. Conclusions: Fimasartan preconditioning has the potential to modulate Bcl-2 and suppress I/R-induced Ca<SUP>2+</SUP> overload by inhibiting I<SUB>Ca,L</SUB> and MCU. These beneficial effects could prevent the mitochondrial dysfunction and apoptosis accompanied by I/R.

0.2% C강의 미세조직에 따른 3-body 연삭마멸 특성 연구

윤나래(N. R. Yoon),김종철(J. C. Kim),정영중(J. -Y. Jeong),권혁우(H. W. Gwon),김용석(Y. -S. Kim) 한국소성가공학회 2011 한국소성가공학회 학술대회 논문집 Vol.2011 No.5

Abrasive wear behavior of 0.2 wt. % C steel with different microstructures was studied. The steel was heat treated to obtain various microstructures under different conditions. Three-body abrasive wear tests were carried out using a ball-cratering abrasive wear tester at fixed load of 0.2 N. Sliding speed and wear distance adopted were 0.05 m/sec and 50 m, respectively. A bearing steel ball was utilized as a counterpart. SiC particles of size approximately 4 ㎛ were used as the abrasive medium. The slurry concentration and feed rate were 0.75 g/ml and 1.15 g/min, respectively. The wear crater was examined using SEM, FESEM, and a surface profilometer to investigate the wear mechanism of the steel. It was found that the abrasive wear resistance was proportional to initial hardness of the heat treated steel.

Crystal structure of Rv2258c from Mycobacterium tuberculosis H37Rv, an S-adenosyl-l-methionine-dependent methyltransferase

Im, H.N.,Kim, H.S.,An, D.R.,Jang, J.Y.,Kim, J.,Yoon, H.J.,Yang, J.K.,Suh, S.W. Academic Press 2016 Journal of structural biology Vol.193 No.3

<P>The Mycobacterium tuberculosis Rv2258c protein is an S-adenosyl-L-methionine (SAM)-dependent methyltransferase (MTase). Here, we have determined its crystal structure in three forms: a ligand-unbound form, a binary complex with sinefungin (SFG), and a binary complex with S-adenosyl-L-homocysteine (SAH). The monomer structure of Rv2258c consists of two domains which are linked by a long alpha-helix. The N-terminal domain is essential for dimerization and the C-terminal domain has the Class I MTase fold. Rv2258c forms a homodimer in the crystal, with the N-terminal domains facing each other. It also exists as a homodimer in solution. A DALI structural similarity search with Rv2258c reveals that the overall structure of Rv2258c is very similar to small-molecule SAM -dependent MTases. Rv2258c interacts with the bound SFG (or SAH) in an extended conformation maintained by a network of hydrogen bonds and stacking interactions. Rv2258c has a relatively large hydrophobic cavity for binding of the methyl-accepting substrate, suggesting that bulky nonpolar molecules with aromatic rings might be targeted for methylation by Rv2258c in M. tuberculosis. However, the ligand-binding specificity and the biological role of Rv2258c remain to be elucidated due to high variability of the amino acid residues defining the substrate-binding site. (C) 2016 Elsevier Inc. All rights reserved.</P>

Jacobi–Stirling numbers, Jacobi polynomials, and the left-definite analysis of the classical Jacobi differential expression

Everitt, W.N.,Kwon, K.H.,Littlejohn, L.L.,Wellman, R.,Yoon, G.J. Koninklijke Vlaamse Ingenieursvereniging 2007 Journal of computational and applied mathematics Vol.208 No.1

<P><B>Abstract</B></P><P>We develop the left-definite analysis associated with the self-adjoint Jacobi operator Ak(α,β), generated from the classical second-order Jacobi differential expression<SUB>ℓα,β,k</SUB>[y](t)=1<SUB>wα,β</SUB>(t)((-(1-t<SUP>)α+1</SUP>(1+t<SUP>)β+1</SUP><SUP>y′</SUP>(t)<SUP>)′</SUP>+k(1-t<SUP>)α</SUP>(1+t<SUP>)β</SUP>y(t))(t∈(-1,1)),in the Hilbert space Lα,β2(-1,1)≔<SUP>L2</SUP>((-1,1);<SUB>wα,β</SUB>(t)), where <SUB>wα,β</SUB>(t)=(1-t<SUP>)α</SUP>(1+t<SUP>)β</SUP>, that has the Jacobi polynomials {Pm(α,β)}m=0∞ as eigenfunctions; here, α,β>-1 and <I>k</I> is a fixed, non-negative constant. More specifically, for each n∈N, we explicitly determine the unique left-definite Hilbert–Sobolev space Wn,k(α,β)(-1,1) and the corresponding unique left-definite self-adjoint operator Bn,k(α,β) in Wn,k(α,β)(-1,1) associated with the pair (Lα,β2(-1,1),Ak(α,β)). The Jacobi polynomials {Pm(α,β)}m=0∞ form a complete orthogonal set in each left-definite space Wn,k(α,β)(-1,1) and are the eigenfunctions of each Bn,k(α,β). Moreover, in this paper, we explicitly determine the domain of each Bn,k(α,β) as well as each integral power of Ak(α,β). The key to determining these spaces and operators is in finding the explicit Lagrangian symmetric form of the integral composite powers of <SUB>ℓα,β,k</SUB>[·]. In turn, the key to determining these powers is a double sequence of numbers which we introduce in this paper as the <I>Jacobi–Stirling numbers</I>. Some properties of these numbers, which in some ways behave like the classical Stirling numbers of the second kind, are established including a remarkable, and yet somewhat mysterious, identity involving these numbers and the eigenvalues of Ak(α,β).</P>

Structural basis for differential activities of enantiomeric PPARγ agonists: Binding of S35 to the alternate site

Jang, J.Y.,Koh, M.,Bae, H.,An, D.R.,Im, H.N.,Kim, H.S.,Yoon, J.Y.,Yoon, H.J.,Han, B.W.,Park, S.B.,Suh, S.W. Elsevier Science 2017 Biochimica et biophysica acta. Proteins and proteo Vol.1865 No.6

<P>Peroxisome proliferator-activated receptor gamma (PPAR gamma) is a member of the nuclear receptor superfamily. It functions as a ligand-activated transcription factor and plays important roles in the regulation of adipocyte differentiation, type 2 diabetes mellitus, and inflammation. Many PPAR gamma agonists bind to the canonical ligand-binding pocket near the activation function-2 (AF-2) helix (i.e., helix H12) of the ligand-binding domain (LBD). More recently, an alternate ligand-binding site was identified in PPAR gamma LBD; it is located beside the 52 loop between the helices H2 ' and H3. We reported previously that the chirality of two optimized enantiomeric PPAR gamma ligands (S35 and R35) differentiates their PPAR gamma transcriptional activity, binding affinity, and inhibitory activity toward Cdk5 (cyclin-dependent kinase 5)-mediated phosphorylation of PPAR gamma at Ser245 (in PPAR gamma 1 numbering; Ser273 in PPAR gamma 2 numbering). S35 is a PPAR gamma phosphorylation inhibitor with promising glucose uptake potential, whereas R35 behaves as a potent conventional PPAR gamma agonist. To provide a structural basis for understanding the differential activities of these enantiomeric ligands, we have determined crystal structures of the PPAR gamma LBD in complex with either S35 or R35. S35 and R35 bind to the PPAR gamma LBD in significantly different manners. The partial agonist S35 occupies the alternate site near the Omega loop, whereas the full agonist R35 binds entirely to the canonical LBP. Alternate site binding of S35 affects the PPAR gamma transactivation and the inhibitory effect on PPAR gamma Ser245 phosphorylation. This study provides a useful platform for the development of a new generation of PPAR gamma ligands as anti-diabetic drug candidates.</P>

Genetic dissection of the biosynthetic route to gentamicin A2 by heterologous expression of its minimal gene set

Park, J. W.,Hong, J. S. J.,Parajuli, N.,Jung, W. S.,Park, S. R.,Lim, S.-K.,Sohng, J. K.,Yoon, Y. J. Proceedings of the National Academy of Sciences 2008 PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF Vol.105 No.24

<P>Since the first use of streptomycin as an effective antibiotic drug in the treatment of tuberculosis, aminoglycoside antibiotics have been widely used against a variety of bacterial infections for over six decades. However, the pathways for aminoglycoside biosynthesis still remain unclear, mainly because of difficulty in genetic manipulation of actinomycetes producing this class of antibiotics. Gentamicin belongs to the group of 4,6-disubstituted aminoglycosides containing a characteristic core aminocyclitol moiety, 2-deoxystreptamine (2-DOS), and the recent discovery of its biosynthetic gene cluster in Micromonospora echinospora has enabled us to decipher its biosynthetic pathway. To determine the minimal set of genes and their functions for the generation of gentamicin A(2), the first pseudotrisaccharide intermediate in the biosynthetic pathway for the gentamicin complex, various sets of candidate genes from M. echinospora and other related aminoglycoside-producing strains were introduced into a nonaminoglycoside producing strain of Streptomyces venezuelae. Heterologous expression of different combinations of putative 2-DOS biosynthetic genes revealed that a subset, gtmB-gtmA-gacH, is responsible for the biosynthesis of this core aminocyclitol moiety of gentamicin. Expression of gtmG together with gtmB-gtmA-gacH led to production of 2'-N-acetylparomamine, demonstrating that GtmG acts as a glycosyltransferase that adds N-acetyl-d-glucosamine (GLcNA) to 2-DOS. Expression of gtmM in a 2'-N-acetylparomamine-producing recombinant S. venezuelae strain generated paromamine. Expression of gtmE in an engineered paromamine-producing strain of S. venezuelae successfully generated gentamicin A(2), indicating that GtmE is another glycosyltransferase that attaches d-xylose to paromamine. These results represent in vivo evidence elucidating the complete biosynthetic pathway of the pseudotrisaccharide aminoglycoside.</P>

Fentanyl Transdermal System의 약물사용평가

심릿다,윤혜영,오지영,강진숙,김옥녀 한국병원약사회 1997 병원약사회지 Vol.14 No.1

DUROESIC^(R) is a transdermal patch providing continuous systemic delivery of fentanyl, a potent opioid analgesic for 72 hours. A retrospective Drug Use (DUE) study on fentanyl Transdermal Therapeutic System(TTS) was conducted. The charts of 50 patients, hospitalized at St. Mary's Hospital from March 1. 1996 to May 31. 1996 and applied fentanyl TTS, were reviewed. The procedure collaborated DUS criteria for fentanyl TTS established by American Journal of health-system pharmacists(AJHP) and manufacturer's guideline. The following information was gathered for patient; indication for use, initial dosage, and dosage interval. As a result, 46 patients(96%) met the criteria for indication of use, 30 patients met the criteria for initial dosage conforms, and 42 patients met criteria for dosage interval. Adverse effects, constipation(44%), nausea/vomiting(23%), respiratory depression (13%), etc, were observed. This study suggests the education for TTS dosage form needs to be provided to medical team.

Genome-wide Structural Analysis Reveals Novel Membrane Binding Properties of AP180 N-terminal Homology (ANTH) Domains

Silkov, A.,Yoon, Y.,Lee, H.,Gokhale, N.,Adu-Gyamfi, E.,Stahelin, R.V.,Cho, W.,Murray, D. The American Society for Biochemistry and Molecula 2011 The Journal of biological chemistry Vol.286 No.39

Comprehensive identification of LMW-GS genes and their protein products in a common wheat variety

Lee, J. Y.,Beom, H. R.,Altenbach, S. B.,Lim, S. H.,Kim, Y. T.,Kang, C. S.,Yoon, U. H.,Gupta, R.,Kim, S. T.,Ahn, S. N. Springer Science + Business Media 2016 Functional & integrative genomics Vol.16 No.3

<P>Although it is well known that low-molecular-weight glutenin subunits (LMW-GS) from wheat affect bread and noodle processing quality, the function of specific LMW-GS proteins remains unclear. It is important to find the genes that correspond to individual LMW-GS proteins in order to understand the functions of specific proteins. The objective of this study was to link LMW-GS genes and haplotypes characterized using well known Glu-A3, Glu-B3, and Glu-D3 gene-specific primers to their protein products in a single wheat variety. A total of 36 LMW-GS genes and pseudogenes were amplified from the Korean cultivar Keumkang. These include 11 Glu-3 gene haplotypes, two from the Glu-A3 locus, two from the Glu-B3 locus, and seven from the Glu-D3 locus. To establish relationships between gene haplotypes and their protein products, a glutenin protein fraction was separated by two-dimensional gel electrophoresis (2-DGE) and 17 protein spots were analyzed by N-terminal amino acid sequencing and tandem mass spectrometry (MS/MS). LMW-GS proteins were identified that corresponded to all Glu-3 gene haplotypes except the pseudogenes. This is the first report of the comprehensive characterization of LMW-GS genes and their corresponding proteins in a single wheat cultivar. Our approach will be useful to understand the contributions of individual LMW-GS to the end-use quality of flour.</P>

21C 프론티어사업에서의 미활용에너지 연구과제 현황(하천수열원이용 고효율 열펌프시스템 개발을 중심으로)

이영수(Y.S. Lee),장기창(K.C. Chang),박성룡(S.R. Park),윤형기(H.K. Yoon),이상남(S.N. Lee) 대한설비공학회 2003 대한설비공학회 학술발표대회논문집 Vol.2003 No.-