<i>S100A9</i> and <i>EGFR</i> gene signatures predict disease progression in muscle invasive bladder cancer patients after chemotherapy

Kim, W. T.,Kim, J.,Yan, C.,Jeong, P.,Choi, S. Y.,Lee, O. J.,Chae, Y. B.,Yun, S. J.,Lee, S. C.,Kim, W. J. Oxford University Press 2014 Annals of Oncology Vol.25 No.5

<P>In our previous gene expression profile analysis, IL1B, S100A8, S100A9, and EGFR were shown to be important mediators of muscle invasive bladder cancer (MIBC) progression. The aim of the present study was to investigate the ability of these gene signatures to predict disease progression after chemotherapy in patients with locally recurrent or metastatic MIBC. Patients with locally advanced MIBC who received chemotherapy were enrolled. The expression signatures of four genes were measured and carried out further functional analysis to confirm our findings. Two of the four genes, S100A9 and EGFR, were determined to significantly influence disease progression (P = 0.023, 0.045, respectively). Based on a receiver operating characteristic curve, a cut-off value for disease progression was determined. Patients with the good-prognostic signature group had a significantly longer time to progression and cancer-specific survival time than those with the poor-prognostic signature group (P < 0.001, 0.042, respectively). In the multivariate Cox regression analysis, gene signature was the only factor that significantly influenced disease progression [hazard ratio: 4.726, confidence interval: 1.623-13.763, P = 0.004]. In immunohistochemical analysis, S100A9 and EGFR positivity were associated with disease progression after chemotherapy. Protein expression of S100A9/EGFR showed modest correlation with gene expression of S100A9/EGFR (r = 0.395, P = 0.014 and r = 0.453, P = 0.004). Our functional analysis provided the evidence demonstrating that expression of S100A9 and EGFR closely associated chemoresistance, and that inhibition of S100A9 and EGFR may sensitize bladder tumor cells to the cisplatin-based chemotherapy. The S100A9/EGFR level is a novel prognostic marker to predict the chemoresponsiveness of patients with locally recurrent or metastatic MIBC.</P>

Production of (S)-3-hydroxybutyrate by metabolically engineered Saccharomyces cerevisiae

Yun, E.J.,Kwak, S.,Kim, S.R.,Park, Y.C.,Jin, Y.S.,Kim, K.H. Elsevier Science Publishers 2015 Journal of biotechnology Vol.209 No.-

(S)-3-Hydroxybutyrate (S-3HB) can be used as a precursor for the synthesis of biodegradable polymers such as polyhydroxyalkanoate and stereo-specific fine chemicals such as antibiotics, pheromones, and drugs. For the production of S-3HB in yeast, the biosynthetic pathway of S-3HB from acetyl-CoA, consisting of the three enzymes, acetyl-CoA C-acetyltransferase (ACCT), acetoacetyl-CoA reductase (ACR), and 3-hydroxybutyryl-CoA thioesterase (HBT), was introduced into Saccharomyces cerevisiae. An engineered yeast strain overexpressing ERG10, hbd, and tesB genes not only exhibited enzyme activities of AACT, ACR, and HBT, but also produced S-3HB from ethanol. In order to increase the titer of S-3HB, a fed-batch fermentation based on pulse feeding of ethanol as a carbon source was performed, and a final S-3HB titer of 12.0g/L was achieved. This is the first report on the production of 3HB by engineered yeast, utilizing ethanol as the carbon source, suggesting that the industrially preferred S. cerevisiae can be a promising host for producing S-3HB.

Strategy for enhancing the solar-driven water splitting performance of TiO₂ nanorod arrays with thin Zn(O,S) passivated layer by atomic layer deposition

Shin, S.W.,Suryawanshi, M.P.,Hong, H.K.,Yun, G.,Lim, D.,Heo, J.,Kang, S.H.,Kim, J.H. Pergamon Press 2016 ELECTROCHIMICA ACTA Vol.219 No.-

An array of one dimensional (1D) TiO<SUB>2</SUB> nanorods (TONRs) has been regarded as an attractive candidate for electrochemical energy conversion and as storage device due to its large surface area, effiective light scattering, and undisturbed charge transport pathway. However, the high defect/trap densities on surface of the nanostructured morphology and architecture may generally hinder the performance enhancement by providing electron-hole recombination sites. Hence, the surface passivation of nanoarchitectures based photoelectrodes has recently received much attention as an effective strategy to enhance the charge-separation and charge-transfer processes in photoelectrochemical (PEC) water splitting devices. In particular, a coating layer with narrowing band gap materials can promote enhanced light harvesting in the UV-vis region as well as surface passivation, directly supplying a driving force for charge separation and charge transfer due to band alignment. In this paper, the surface of TONRs were passivated by 10 and 30nm thick Zn(O,S) layers with a relatively narrow band gap using an atomic layer deposition technique to modulate the thickness exactly. The 10nm Zn(O,S)/TONR array exhibits a significantly enhanced photocurrent density (J<SUB>sc</SUB>) of 5.94mA/cm<SUP>2</SUP> at 1.23eV vs NHE and an incident photon-to-electron conversion efficiency (IPCE) of 49% at 374nm compared with that of TONR arrays (J<SUB>sc</SUB> of 1.99mA/cm<SUP>2</SUP> at 1.23eV vs NHE and an IPCE of 20% at 380nm). However, the PEC performance is worse in the 30nm Zn(O,S)/TONR arrays, showing a J<SUB>sc</SUB> of 3.09mA/cm<SUP>2</SUP> at 1.23eV vs NHE and an IPCE of 29% at 374nm. To clearly demonstrate these PEC behaviors, the TONR and Zn(O,S)/TONR arrays were characterized by electrochemical impedance spectroscopy (EIS), open circuit voltage decay (OCV) measurement, and X-ray photoelectron spectroscopy (XPS). The above mentioned characterizations indicate that the enhanced PEC performance of the 10nm Zn(O,S)/TONR array resulted from the (i) increased light harvesting in the UV-vis region, (ii) lower charge transfer resistance and (iii) high value of valence band offset (VBO, -1.44eV) and conduction band offset (CBO, -1.2eV) than those of the TONR. However, the deterioration of J<SUB>sc</SUB> in the 30nm Zn(O,S)/TONR array is attributed to the negative value of VBO (-0.13eV) and positive value of CBO (+0.27eV), as well as the higher charge transfer resistance to the electrolyte than that of the TONR arrays, despite of the improved light absorption in the visible region. The photocurrent densities of 10nm Zn(O,S)/TONR and 30nm Zn(O,S)/TONR photocathodes decay to 4.718mA/cm<SUP>2</SUP> (5.90mA/cm<SUP>2</SUP> at 0min) and 2.212mA/cm<SUP>2</SUP> (3.03mA/cm<SUP>2</SUP> at 0min) after 90min, respectively, they retain of about~80% and 70% of its original values. These experimental results and discussions not only provide the physical insights into the surface passivation effect and band alignment but also can open a promising route to design the thin passivation layer having the narrowing band gap energy (1.0eV~2.5eV) on the 1D TiO<SUB>2</SUB> nanostructure for further enhanced performance and realization of a TiO<SUB>2</SUB> based PEC system.

Induction of bone formation by <i>Escherichia coli</i>‐expressed recombinant human bone morphogenetic protein‐2 using block‐type macroporous biphasic calcium phosphate in orthotopic and ectopic rat models

Park, J‐,C.,So, S‐,S.,Jung, I‐,H.,Yun, J‐,H.,Choi, S‐,H.,Cho, K‐,S.,Kim, C‐,S. Blackwell Publishing Ltd 2011 Journal of periodontal research Vol.46 No.6

<P><I>Park J‐C, So S‐S, Jung I‐H, Yun J‐H, Choi S‐H, Cho K‐S, Kim C‐S. Induction of bone formation by</I> Escherichia coli<I>‐expressed recombinant human bone morphogenetic protein‐2 using block‐type macroporous biphasic calcium phosphate in orthotopic and ectopic rat models. J Periodont Res 2011; 46: 682–690. © 2011 John Wiley & Sons A/S</I></P><P><B>Background and Objective: </B> The potential of the <I>Escherichia coli</I>‐expressed recombinant human bone morphogenetic protein‐2 (ErhBMP‐2) to support new bone formation/maturation using a block‐type of macroporous biphasic calcium phosphate (bMBCP) carrier was evaluated in an orthotopic and ectopic rat model.</P><P><B>Material and Methods: </B> Critical‐size (Φ 8 mm) calvarial defects and subcutaneous pockets in 32 Sprague–Dawley rats received implants of rhBMP‐2 (2.5 μg) in a bMBCP carrier or bMBCP alone (control). Implant sites were evaluated using histological and histometric analysis following 2‐ and 8‐wk healing intervals (eight animals/group/interval).</P><P><B>Results: </B> ErhBMP‐2/bMBCP supported significantly greater bone formation at 2 and 8 wk (10.8% and 25.4%, respectively) than the control at 2 and 8 wk (5.3% and 14.0%, respectively) in calvarial defects (<I>p</I> < 0.01). Bone formation was only observed for the ErhBMP‐2/bMBCP ectopic sites and was significantly greater at 8 wk (7.5%) than at 2 wk (4.5%) (<I>p</I> < 0.01). Appositional and endochondral bone formation was usually associated with a significant increase in fatty marrow at 8 wk. The bMBCP carrier showed no evidence of bioresorption.</P><P><B>Conclusion: </B> ErhBMP‐2/bMBCP induced significant bone formation in both calvarial and ectopic sites. Further study appears to be required to evaluate the relevance of the bMBCP carrier.</P>

濟州道 原乳의 季節別, 飼育規模別 成分 變化에 關한 硏究

李賢鐘,梁昇柱,朴喜錫,尹瑛斌 濟州大學校 새마을硏究所 1988 새마을硏究論文集 Vol.5 No.-

The study was conducted to analyze components of raw milk, seasonal variation and correlation between components, and to obtain fundamental data in developing the quaity of raw milk and of feeding management, surveying 3 districts by milk-collecting area and 4 groups farm size between March of 1986 to February of 1987, and the results obtained are as follows; 1. Fat and T.S. were low in spring and summer and S.N.F. was low in summer, protein and lactose showed however, no significant seasonal variation. 2. The correlations between fat and T. S.(r= + 0.599004 in spring (r=+ 0.877195 in winter) fat and S. N. F. (r=+ 0.206696 in winter, r = + 0.829499 in spring) and S. N. F. and T. S. ( r= + 0.286247 in spring, r = + 0.812476 in winter) were significant in components by season. 3. On component veriation by from size, fat component highest in the group of 6-10 head, and the larger the farm size was, the higher the fat component was, and T. S. showed the same pattern as this, lactose and protein were not signigicant by farm size. 4. Fat component was 3.73-3.83%, protein 3.17-3.23%, lactose 4.54-4.63%, S.N.F. 8.66-8.71%, and T. S. 12.41-12.56% by area, and there was no variation between areas.

Wall teichoic acid is an essential component of Staphylococcus aureus for the induction of human dendritic cell maturation

Hong, S.J.,Kim, S.K.,Ko, E.B.,Yun, C.H.,Han, S.H. Pergamon Press 2017 Molecular immunology Vol.81 No.-

<P>Staphylococcus aureus is a Gram-positive pathogen that can cause chronic skin inflammation, pneumonia, and septic shock. The immunomodulatory functions of wall teichoic acid (WTA), a glycopolymer abundantly expressed on the Gram-positive bacterial cell wall, are poorly understood. Here, we investigated the role of WTA in the phenotypic and functional activation of human monocyte-derived dendritic cells (DCs) treated with ethanol-killed S. aureus. WTA-deficient S. aureus mutant (Delta tagO) exhibited attenuated binding and internalization to DCs compared to the wild-type. Delta tagO induced lower expression of maturation markers on and cytokines in DCs than the wild-type S. aureus. Furthermore, autologous human peripheral blood mononuclear cells cocultured with Delta tagO-treated DCs exhibited a marked reduction in T cell proliferative activity, the expression of activation markers, and the production of cytokines compared to the wild-type S. aureus-stimulated DCs. Collectively, these results suggest that WTA is an important cell wall component of S. aureus for the induction of DC maturation and activation. (C) 2016 Elsevier Ltd. All rights reserved.</P>

Biochemical analysis of recombinant CYP4A11 allelic variant enzymes: W126R, K276T and S353G

Han, S.,Cha, G.S.,Chun, Y.J.,Lee, C.H.,Kim, D.,Yun, C.H. JAPANESE SOCIETY FOR THE STUDY OF XENOBIOTICS 2016 DRUG METABOLISM AND PHARMACOKINETICS Vol.31 No.6

Human CYP4A11 is the major ω-hydroxylase of fatty acids in the liver and kidneys. It produces 20-hydroxyeicosatetraenoic acid as well as hydroxylates fatty acids. In this study, we investigated the biochemical properties of three alleles of CYP4A11: W126R, K276T, and S353G. Site-directed mutagenesis of the wild type CYP4A11 was performed, to construct the W126R, K276T, and S353G variant clones. The CYP4A11 wild type and variant constructs were heterologously expressed in Escherichia coli. CO-binding spectra showed the expression of the wild type, K276T and S353G variants, indicating the functional P450 holoenzyme. The W126R variant was not expressed in E. coli. Binding affinities of lauric acid in K276T and S353G variants were stronger than that of wild type. Steady-state kinetics in the hydroxylation reaction of fatty acids were studied. The catalytic efficiencies (k<SUB>cat</SUB>/K<SUB>m</SUB>) of K276T and S353G variants in the reactions without cytochrome b<SUB>5</SUB> were approximately 2- and 4-fold higher, respectively, than that of wild type, and in the reactions with cytochrome b<SUB>5</SUB> they were approximately 2- and 3-fold higher, respectively. These results suggest that individuals carrying the alleles, K276T and S353G, might exhibit higher catalysis of CYP4A11, which may affect the endogenous metabolic products associated with regulation of blood pressure.

High lipid composition of particulate organic matter in the northern Chukchi Sea, 2011

Kim, B.K.,Lee, J.H.,Yun, M.S.,Joo, H.,Song, H.J.,Yang, E.J.,Chung, K.H.,Kang, S.H.,Lee, S.H. Pergamon Press 2015 Deep-sea research. Part II, Topical studies in oce Vol.120 No.-

We investigated the biochemical compositions (lipids, proteins, and carbohydrates) of particulate organic matter (POM) as a potential food source in the northern Chukchi Sea. We aimed to understand physiological status of phytoplankton, determine important controlling factors, and estimate the energetic contents of POM. The major inorganic nutrients were generally depleted at upper mixed-layer depth (>20m). The average chlorophyll a (chl-a) concentration was 31.9mgm<SUP>-2</SUP> (S.D.=+/-31.3mgm<SUP>-2</SUP>) in this study, significantly higher than that reported previously in the northern Chukchi Sea. Small phytoplankton (0.7-5@?m) accounted for 65.9% of total chl-a concentration. The overall average compositions of lipids, carbohydrates, and proteins were 50% (S.D.=+/-10.7%), 35% (S.D.=+/-11.0%), and 15% (S.D.=+/-11.2%) for POM, respectively. Along with other evidence (e.g., low N:P and protein-carbohydrate ratios), the high lipid and low protein compositions of POM in this study suggests that phytoplankton might have had a nitrogen limitation and/or stationary growth phase in the northern Chukchi Sea during the cruise period, 2011. The overall average calorific content of food material (FM) was 149.2μgL<SUP>-1</SUP> (S.D.=+/-36.5μgL<SUP>-1</SUP>) or 1.0Kcalm<SUP>-3</SUP> (S.D.=+/-0.2Kcalm<SUP>-3</SUP>). The relatively higher calorific contents in the northern Chukchi Sea were due to high lipid contributions and the considerably high calorific content of FM per POC.

Streptococcus gordonii induces nitric oxide production through its lipoproteins stimulating Toll-like receptor 2 in murine macrophages

Kim, H.Y.,Baik, J.E.,Ahn, K.B.,Seo, H.S.,Yun, C.H.,Han, S.H. Pergamon Press 2017 Molecular immunology Vol.82 No.-

<P>Streptococcus gordonii, a Gram-positive commensal in the oral cavity, is an opportunistic pathogen that can cause endodontic and systemic infections resulting in infective endocarditis. Lipoteichoic acid (LTA) and lipoprotein are major virulence factors of Gram-positive bacteria that are preferentially recognized by Toll-like receptor 2 (TLR2) on immune cells. In the present study, we investigated the effect of S. gordonii LTA and lipoprotein on the production of the representative inflammatory mediator nitric oxide (NO) by the mouse macrophages. Heat-killed S. gordonii wild-type and an LTA-deficient mutant (Delta ltaS) but not a lipoprotein-deficient mutant (Delta lgt) induced NO production in mouse primary macrophages and the cell line, RAW 264.7.S. gordonii wild-type and Delta ItaS also induced the expression of inducible NO synthase (iNOS) at the mRNA and protein levels. In contrast, the Delta lgt mutant showed little effect under the same condition. Furthermore, S. gordonii wild-type and Delta ItaS induced NF-kappa B activation, STAT1 phosphorylation, and IFN-beta expression, which are important for the induction of iNOS gene expression, with little activation by Delta lgt. S. gordonii wild-type and Delta ltaS showed an increased adherence and internalization to RAW 264.7 cells compared to Delta lgt. In addition, S. gordonii wild-type and AIMS, but not Delta lgt, substantially increased TLR2 activation while none of these induced NO production in TLR2-deficient macrophages. Triton X-114-extracted lipoproteins from S. gordonii were sufficient to induce NO production. Collectively, we suggest that lipoprotein is an essential cell wall component of S. gordonii to induce NO production in macrophages through TLR2 triggering NF-kappa B and STAT1 activation. (C) 2016 Elsevier Ltd. All rights reserved.</P>

消化性 潰瘍에 對한 sulfated glycopeptide(Glide^(�))의 治療效果

尹鎬周,高允錫,安明洙,孫周鉉,安光武,奇椿錫 최신의학사 1987 最新醫學 Vol.30 No.9