Lipoteichoic acid of Streptococcus mutans interacts with Toll-like receptor 2 through the lipid moiety for induction of inflammatory mediators in murine macrophages

Hong, S.W.,Baik, J.E.,Kang, S.S.,Yun, C.H.,Seo, D.G.,Han, S.H. Pergamon Press 2014 Molecular immunology Vol.57 No.2

Streptococcus mutans is a pathogenic Gram-positive bacterium that is closely associated with dental caries and subsequent pulpal inflammation. Although lipoteichoic acid (LTA) is considered a major virulence factor of Gram-positive bacteria, little is known about the innate immunity to S. mutans LTA. In this study, we purified LTA from S. mutans (Sm.LTA) through n-butanol extraction, hydrophobic interaction column chromatography, and ion-exchange column chromatography to investigate its immunological properties using murine macrophages. The Sm.LTA preparation had no detectable contamination with endotoxins, proteins, or nucleic acids. Upon exposure to Sm.LTA, the murine macrophage cell-line RAW 264.7 cells produced TNF-α and nitric oxide (NO) in a dose-dependent manner. Sm.LTA preferentially bound to and activated CHO/CD14/TLR2 cells rather than CHO/CD14/TLR4 cells, which are stable transfectants expressing CD14 and TLR2 or CD14 and TLR4, respectively. Sm.LTA could not induce TNF-α or NO production in macrophages derived from TLR2-deficient mice whereas it dose-dependently induced those inflammatory mediators in wild-type macrophages. TLR2-dependent induction of NO by Sm.LTA was also confirmed in RAW 264.7 cells using specific antibodies blocking TLR2. Furthermore, Sm.LTA deacylated by alkaline hydrolysis neither stimulated TLR2 nor induced TNF-α or NO production, suggesting that Sm.LTA lipid moieties are crucial for the immuno-stimulatory activity of Sm.LTA. Unlike Staphylococcus aureus LTA, which has potent immuno-stimulating activity, Sm.LTA showed a modest induction of NO production comparable to LTAs of other oral bacteria Enterococcus faecalis and Lactobacillus plantarum. In conclusion, our results suggest that the Sm.LTA interacts with TLR2 through the lipid moiety for the induction of inflammatory mediators in macrophages.

CO OBSERVATIONS AND STABILITY ANALYSIS OF B133 AND B134

Hong, S.S.,Kim, H.G.,Park, S.H.,Park, Y.S.,Imaoka, K. The Korean Astronomical Society 1991 Journal of The Korean Astronomical Society Vol.24 No.1

With the 14 m radio telescope at DRAO and the 4 m at Nagoya University, we have made detailed maps of $^{12}CO$ and $^{13}CO$ emissions from two Barnard objects B133 and B134 in the $J=1{\rightarrow}O$ rotational transition lines. Usual LTE analyses of the CO observations led us to determine the distribution of column densities over an entire area encompassing both globules. Total gas masses estimated from the column density map are $90\;M_{\odot}$ and $20\;M_{\odot}$ for B133 and B134, respectively. The radial velocity of B133 is red shifted with respect to B134 by $0.8\;km\;s^{-1}$, which is too lagre to bind the two clouds as a binary system. We have shown that the usual stability analysis based on the simplified version of virial theorem with the second time-derivative of the moment of inertia term $\ddot{I}$ being ignored could mislead us in determining whether a given cloud eventually collapses or not. The lull version of the scalar virial theorem with the $\ddot{I}$ term is shown to be useful in following up the time-dependent variations of the cloud size R and its streaming velocity $\dot{R}$ as functions of time. Results of our stability analysis suggest that B133 will eventually collapse in $(2{\sim}4){\times}10^6$ years.

Characterization of a G11,P[4] Strain of Human Rotavirus Isolated in South Korea

Hong, S.-K.,Lee, S.-G.,Lee, S.-A,Kang, J.-H.,Lee, J.-H.,Kim, J.-H.,Kim, D.-S.,Kim, H.-M.,Jang, Y.-T.,Ma, S.-H.,Kim, S.-Y.,Paik, S.-Y. American Society for Microbiology 2007 Journal of clinical microbiology Vol.45 No.11

Experimental Approach to Explosive Nucloeosynthesis with RI Beams

S. Kubono,Y. Yamaguchi,G. Amadio,S. Hayakawa,Y. Wakabayashi,Y. Kurihara,J. J. He,A. Saito,H. Fujikawa,Le Hong Khiem,M. Niikura,T. Teranishi,N. Iwasa,S. Kato,S. Nishimura,C. S. Lee,Y. K. Kwon,I. S. Hah 한국물리학회 2009 THE JOURNAL OF THE KOREAN PHYSICAL SOCIETY Vol.54 No.1

Experimental efforts to investigate stellar reactions under high-temperature and high density conditions have been made as a major program using the RI beams from the Center for Nuclear Study (CNS) low-energy in-flight RI beam separator (CRIB) at University of Tokyo in order to understand the evolution of the universe, as well as various stellar phenomena. Specically, two subjects of hydrogen burning are discussed here. One is a reaction study of the pp-chain and the second is of the explosive hydrogen burning, the rp-process. Some s-wave resonances have been identified by the thick target method in the crucial reaction processes in the hydrogen burning. The resonant scattering with the thick target method also succeeded in identifying inelastic resonant scattering, giving proton widths for the first excited state of the target nucleus. This provided very efficiently the reaction rate estimate for the process under high-temperature equilibrium conditions. Possibilities of the CRIB facility in near future are also briey discussed. Experimental efforts to investigate stellar reactions under high-temperature and high density conditions have been made as a major program using the RI beams from the Center for Nuclear Study (CNS) low-energy in-flight RI beam separator (CRIB) at University of Tokyo in order to understand the evolution of the universe, as well as various stellar phenomena. Specically, two subjects of hydrogen burning are discussed here. One is a reaction study of the pp-chain and the second is of the explosive hydrogen burning, the rp-process. Some s-wave resonances have been identified by the thick target method in the crucial reaction processes in the hydrogen burning. The resonant scattering with the thick target method also succeeded in identifying inelastic resonant scattering, giving proton widths for the first excited state of the target nucleus. This provided very efficiently the reaction rate estimate for the process under high-temperature equilibrium conditions. Possibilities of the CRIB facility in near future are also briey discussed.

A genetic variation in microRNA target site of <i>KRT81</i> gene is associated with survival in early-stage non-small-cell lung cancer

Lee, S. Y.,Choi, J. E.,Jeon, H. S.,Hong, M. J.,Choi, Y. Y.,Kang, H. G.,Yoo, S. S.,Lee, E. B.,Jeong, J. Y.,Lee, W. K.,Lee, J.,Cha, S. I.,Kim, C. H.,Kim, Y. T.,Jheon, S.,Son, J. W.,Park, J. Y. Oxford University Press 2015 ANNALS OF ONCOLOGY Vol.26 No.6

<P>In this study, <I>KRT81</I> rs3660G>C was associated with survival of patients with NSCLC after surgical resection. Mechanistic study suggested that the G-to-C change caused reduced binding efficiency of miRNA, leading to decreased translational repression, thereby increased <I>KRT81</I> expression. The <I>KRT81</I> rs3660G>C may be a useful prognostic biomarker in early-stage NSCLC patients.</P><P><B>Background</B></P><P>MicroRNAs (miRNAs) have a key role in carcinogenesis through negative regulation of their target genes. Therefore, genetic variations in miRNAs or their target sites may affect miRNA–mRNA interactions, thereby result in altered expression of target genes. This study was conducted to investigate the associations between single-nucleotide polymorphisms (SNP) located in the miRNA target sites (poly-miRTSs) and survival of patients with early-stage non-small-cell lung cancer (NSCLC).</P><P><B>Methods</B></P><P>Using public SNP database and miRNA target sites prediction program, 354 poly-miRTSs were selected for genotyping. Among these, 154 SNPs applicable to Sequenom's MassARRAY platform were investigated in 357 patients. A replication study was carried out on an independent patient population (<I>n</I> = 479). <I>Renilla</I> luciferase assay and reverse transcription-polymerase chain reaction were conducted to examine functional relevance of potentially functional poly-miRTSs.</P><P><B>Results</B></P><P>Of the 154 SNPs analyzed in a discovery set, 14 SNPs were significantly associated with survival outcomes. Among these, <I>KRT81</I> rs3660G>C was found to be associated with survival outcomes in the validation cohort. In the combined analysis, patients with the rs3660 GC + CC genotype had a significantly better overall survival compared with those with GG genotype [adjusted hazard ratio (aHR) for OS, 0.65; 95% confidence interval (CI) 0.50–0.85; <I>P</I> = 0.001]. An increased expression of the reporter gene for the C allele of rs3660 compared with the G allele was observed by luciferase assay. Consistently, the C allele was associated with higher relative expression level of <I>KRT81</I> in tumor tissues.</P><P><B>Conclusion</B></P><P>The rs3660G>C affects KRT81 expression and thus influences survival in early-stage NSCLC. The analysis of the rs3660G>C polymorphism may be useful to identify patients at high risk of a poor disease outcome.</P>

A novel imidazopyridine derivative, HS-106, induces apoptosis of breast cancer cells and represses angiogenesis by targeting the PI3K/mTOR pathway

Li, G.Y.,Jung, K.H.,Lee, H.,Son, M.K.,Seo, J.,Hong, S.W.,Jeong, Y.,Hong, S.,Hong, S.S. Elsevier Science Ireland 2013 Cancer letters Vol.329 No.1

Abnormal activation of the phosphatidylinositol 3-kinase (PI3K)/Akt pathway is an essential step for the formation and growth of tumors in humans. HS-106 is an imidazopyridine derivative that inhibits the kinase activity of PI3K by binding to the ATP-binding cleft. We found that this compound suppressed breast cancer cell proliferation and induced apoptosis by specifically inhibiting the activity of target proteins in the PI3K/Akt/mTOR signaling pathway. Cell cycle analysis revealed that treatment with HS-106 resulted in cell cycle arrest at the G<SUB>2</SUB>/M phase due to up-regulation of p-cdc25 and down-regulation of cyclin B1. Also, HS-106 induced apoptosis by increasing the levels of cleaved caspase-3 and cleaved PARP. In addition, chromatin condensation and apoptotic bodies were detected in HS-106-treated breast cancer cells. Furthermore, HS-106 decreased the expression of hypoxia-inducible factor 1α (HIF-1α), and inhibited tube formation and migration of human umbilical vein endothelial cells (HUVECs) in vitro and blood vessel formation in an in vivo Matrigel plug assay. These results show that HS-106 may be an effective novel therapeutic candidate in clinical trials as a potential treatment for human breast cancers or other advanced malignancies with aberrant PI3K/Akt/mTOR signaling.

Neuroprotective Effect of Human Adipose Stem Cell-Derived Extract in Amyotrophic Lateral Sclerosis

Jeon, G. S.,Im, W.,Shim, Y. M.,Lee, M.,Kim, M. J.,Hong, Y. H.,Seong, S. Y.,Kim, M.,Sung, J. J. Springer Science + Business Media 2016 Neurochem Res Vol.41 No.4

<P>Amyotrophic lateral sclerosis (ALS) is a devastating human neurodegenerative disease. The precise pathogenic mechanisms of the disease remain uncertain, and as of yet, there is no effective cure. Human adipose stem cells (hASC) can be easily obtained during operative procedures. hASC have a clinically feasible potential to treat neurodegenerative disorders, since cytosolic extract of hASC contain a number of essential neurotrophic factors. In this study, we investigated effects of hASC extract on the SOD1 G93A mouse model of ALS and in vitro test. Administration of hASC extract improved motor function and prolonged the time until symptom onset, rotarod failure, and death in ALS mice. In the hASC extracts group, choline acetyltransferase immunostaining in the ventral horn of the lumbar spinal cord showed a large number of motor neurons, suggesting normal morphology. The neuroprotective effect of hASC extract in ALS mice was also suggested by western blot analysis of spinal cord extract from ALS mice and in vitro test. hASC extract treatment significantly increased expression of p-Akt, p-CREB, and PGC-1 alpha in SOD1 G93A mouse model and in vitro test. Our results indicated that hASC extract reduced apoptotic cell death and recovered mutant SOD1-induced mitochondrial dysfunction. Moreover, hASC extract reduced mitochondrial membrane potential. In conclusion, we have demonstrated, for the first time, that hASC extract exert a potential therapeutic action in the SOD1 G93A mouse model of ALS and in vitro test. These findings suggest that hASC hold promise as a novel therapeutic strategy for treating ALS.</P>

Production of transgenic cloned minipig expressing HLA-G1 and DAF gene by nuclear transfer

Park K.W.,G.S.Han,K.M. Choi,S.P. Hong,J.Y. Yoo,E.J. Kim,S.H. Kim,Y.C. Park,W.K. Lee,C.G. Park,S.J. Kim,J.G. Seol 한국동물생명공학회(구 한국동물번식학회) 2007 발생공학 국제심포지엄 및 학술대회 Vol.2007 No.1

점진성형기술을 이용한 건축용 작업 발판의 개발

홍성훈(S. H. Hong),이승욱(S. J. Lee),누엑늑뚜안(D. T. Nguyen),김갑득(G. D. Kim),송성훈(S. H. Song),김영석(Y. S. Kim) 한국소성가공학회 2010 한국소성가공학회 학술대회 논문집 Vol.2010 No.5

The incremental sheet forming (ISF) method is known as valuable tools to make a rapid prototype which can be observed the forming shape and also able to re-design the part based on the requirements. In this study, we have applied the ISF to prototype of walkway and stair step used in factories and architecture fields. CAD model of walkway and stair step is initially designed and imported to CAM software to model and generate G-code files. These files are imported to CNC machine to make a female die and subsequently producing the prototype of walkway and stair step by using the ISF. The major safety requirement is to avoid permanent deflection due to low stiffness and the slip of passenger while walking on the metal walkway. If the part is not able to satisfy given requirements, then the design should be modified. After we got experience with more trial, the best shape, which was obtained by incremental sheet forming process, will be applied to actual manufacturing of walkway and stair step by punching and stamping process.

Limiting Concentrate during Growing Period Affect Performance and Gene Expression of Hepatic Gluconeogenic Enzymes and Visfatin in Korean Native Beef Calves

Chang, S.S.,Lohakare, J.D.,Singh, N.K.,Kwon, E.G.,Nejad, J.G.,Sung, K.I.,Hong, S.K. Asian Australasian Association of Animal Productio 2013 Animal Bioscience Vol.26 No.2

This study elucidated the effects of limited concentrate feeding on growth, plasma profile, and gene expression of gluconeogenic enzymes and visfatin in the liver of Hanwoo beef calves. The purpose of this study was to test that reducing the amount of concentrate would partially be compensated by increasing the intake of forage and by altering the metabolic status. The study utilized 20 Korean native beef calves (Hanwoo; 60 to 70 d of age) divided into two groups of 10 calves each for 158 d. Control group calves received the amount of concentrate as per the established Korean feeding standards for Hanwoo, whereas calves in the restricted group only received half the amount of concentrate as per standard requirements. Good quality forage (Timothy hay) was available for ad libitum consumption to both groups. Since calves were with their dam until 4 months of age in breeding pens before weaning, the intake of milk before weaning was not recorded, however, the concentrate and forage intakes were recorded daily. Body weights (BW) were recorded at start and on 10 d interval. Blood samples were collected at start and at 50 d interval. On the final day of the experiment, liver biopsies were collected from all animals in each group. The BW was not different between the groups at all times, but tended to be higher (p = 0.061) only at final BW in control than restricted group. Total BW gain in the control group was 116.2 kg as opposed to 84.1 kg in restricted group that led to average BW gain of 736 g/d and 532 g/d in respective groups, and the differences were significant (p<0.01). As planned, the calves in the control group had higher concentrate and lower forage intake than the restricted group. The plasma variables like total protein and urea were higher (p<0.05) in control than restricted group. The mRNA expressions for the gluconeogenic enzymes such as cytosolic phosphoenol pyruvate carboxykinase (EC 4.1.1.32) and pyruvate carboxylase (EC 6.4.1.1), and visfatin measured by quantitative real-time PCR in liver biopsies showed higher expression (p<0.05) in restricted group than control. Overall, restricting concentrate severely reduced the growth intensity and affected few plasma indices, and gene expression in liver was increased indicating that restricting concentrate in the feeding schemes during early growth for beef calves is not advocated.