Chemical inhibitors of c-Met receptor tyrosine kinase stimulate osteoblast differentiation and bone regeneration

Kim, J.W.,Lee, M.N.,Jeong, B.C.,Oh, S.H.,Kook, M.S.,Koh, J.T. North-Holland 2017 European journal of pharmacology Vol.806 No.-

<P>The c-Met receptor tyrosine kinase and its ligand, hepatocyte growth factor (HGF), have been recently introduced to negatively regulate bone morphogenetic protein (BMP)-induced osteogenesis. However, the effect of chemical inhibitors of c-Met receptor on osteoblast differentiation process has not been examined, especially the applicability of c-Met chemical inhibitors on in vivo bone regeneration. In this study, we demonstrated that chemical inhibitors of c-Met receptor tyrosine kinase, SYN1143 and SGX523, could potentiate the differentiation of precursor cells to osteoblasts and stimulate regeneration in calvarial bone defects of mice. Treatment with SYN1143 or SGX523 inhibited HGF-induced c-Met phosphorylation in MC3T3-E1 and C3H10T1/2 cells. Cell proliferation of MC3T3-E1 or C3H10T1/2 was not significantly affected by the concentrations of these inhibitors. Co-treatment with chemical inhibitor of c-Met and osteogenic inducing media enhanced osteoblast-specific genes expression and calcium nodule formation accompanied by increased Runx2 expression via c-Met receptor-dependent but Erk-Smad signaling independent pathway. Notably, the administration of these c-Met inhibitors significantly repaired critical-sized calvarial bone defects. Collectively, our results suggest that chemical inhibitors of c-Met receptor tyrosine kinase might be used as novel therapeutics to induce bone regeneration.</P>

Validation of egg yolk antibody based C-ELISA for avian influenza surveillance in breeder duck

Jeong, O.M.,Kim, M.C.,Kang, H.M.,Ha, G.W.,Oh, J.S.,Yoo, J.E.,Park, C.H.,Kwon, J.S.,Pack, M.R.,Kim, H.R.,Kim, Y.J.,Kwon, J.H.,Lee, Y.J. Elsevier Scientific Pub. Co 2010 Veterinary microbiology Vol.144 No.3

Active surveillance for avian influenza virus (AIV) has expanded from chicken to various poultry species including duck. To further effective antibody screening in laying breeder ducks, we validated the egg yolk antibody as alternative source to serum for AIV antibody. Sera and eggs were collected at weekly intervals after two types of AIV vaccination, H5N3 and H9N2. The antibody levels were determined by an agar gel immunodiffusion (AGID) test, haemagglutination inhibition (HI) test and the competitive enzyme-linked immunosorbent assay (C-ELISA). AGID test did not detect antibodies in egg yolk, and the agreement between AGID test and either HI test or C-ELISA in serum was slight and fair based on kappa statistics (kappa value (κ)@?0.19 in H5N3 group and κ@?0.37 in H9N2 groups). However, there was almost perfect agreement between HI test and C-ELISA (κ>0.9 in all group). The C-ELISA was as sensitive and specific as the HI test, and could be used as a pre-screening test for the detection of type A avian influenza virus antibody. Comparison was made between egg yolk and serum antibody titers by a regression analysis. A high correlation was observed between serum and yolk antibody titers (r=0.8762 for H5N3 and 0.8914 for H9N2 in HI test; r=1 for H5N3 and 0.9686 for H9N2 in ELISA test), although egg yolk antibodies were detected later and remained lower levels than serum antibodies. In field trials involving 54 duck flocks, the positive rate of egg yolk and serum samples showed agreement for the detection of AIV antibody. We concluded that as an alternative to serum, antibody monitoring of laying breeder duck using egg yolk with C-ELISA is feasible and is recommended.

Two-step reduction process and spark plasma sintering for the synthesis of ultra fine SiC and ZrB₂ powder mixtures

Oh, H.C.,Lee, S.H.,Choi, S.C. MPR Pub. Services 2014 International journal of refractory metals & hard Vol.42 No.-

A novel two-step reduction process is proposed for the synthesis of homogeneously intermixed nano-SiC/ZrB<SUB>2</SUB> powder using ZrSiO<SUB>4</SUB>, B<SUB>4</SUB>C and C. During the conventional carbo-borothermal reduction process, B<SUB>4</SUB>C reacted with ZrSiO<SUB>4</SUB> to form borosilicate glass or B<SUB>2</SUB>O<SUB>3</SUB>. The reactions for the formation of B<SUB>2</SUB>O<SUB>3</SUB> had lower Gibbs free energy than those to synthesize ZrB<SUB>2</SUB> and SiC. The borosilicate glass also promoted the strong grain growth of ZrB<SUB>2</SUB> and inhibited the formation of SiC. In order to solve the problem, the synthesis process was divided into the carbothermal reduction of ZrSiO<SUB>4</SUB>, and subsequent conversion of the resultant ZrC into ZrB<SUB>2</SUB>. By the two-step reduction process, the formation of SiC was achieved and the grain growth of ZrB<SUB>2</SUB> could be effectively suppressed. Spark plasma sintering process also helped to minimize the grain growth of the synthesized powder by the fast heating/cooling rate of 100<SUP>o</SUP>C/min. The synthesized ZrB<SUB>2</SUB>-SiC powders were 10-40nm in size and were homogeneously inter-mixed.

Characterization of Phosphoinositide-3-kinase, Class 3 (PIK3C3) Gene and Association Tests with Quantitative Traits in Pigs

Kim, J.H.,Choi, B.H.,Lim, H.T.,Park, E.W.,Lee, S.H.,Seo, B.Y.,Cho, I.C.,Lee, J.G.,Oh, S.J.,Jeon, J.T. Asian Australasian Association of Animal Productio 2005 Animal Bioscience Vol.18 No.12

This study deals with the characterization of porcine PIK3C3 and association tests with quantitative traits. PIK3C3 belongs to the class 3 PI3Ks that participate in the regulation of hepatic glucose output, glycogen synthase, and antilipolysis in typical insulin target cells such as those in the such as liver, muscle system, and fat. On the analysis of full-length mRNA sequence, the length of the PIK3C3 CDS was recorded as 2,664 bps. As well, nucleotide and amino acid identities between human and pig subjects were 92% and 99%, respectively. Five SNPs were detected over 5 exons. We performed genotyping by using a SNP C2604T on exon24 for 145 F$_2$ animals (from a cross between Korean native boars and Landrace sows) by PCR-RFLP analysis with Hpy8I used to investigate the relationship between growth and fat depot traits. In the total association analysis, which doesn' consider transmission disequilibrium, the SNP showed a significant effect (p<0.05) on body weight and carcass fat at 30 weeks of age as well as a highly significant effect (p<0.01) on back fat. In an additional sib-pair analysis, C allele still showed positive and significant effects (p<0.05) on back fat thickness and carcass fat. Moreover, the effects of C allele on the means of within-family components for carcass fat and back fat were estimated as 2.76 kg and 5.07 mm, respectively. As a result, the SNP of porcine PIK3C3 discovered in this study could be utilized as a possible genetic marker for the selection of pigs that possess low levels of back fat and carcass fat at the slaughter weight.

Sol-Gel 법에 의한 Al2O3 제조시 침전제 (H2C2O4) 의 영향

오재현,원창환,천병선,이정원 대한금속재료학회(대한금속학회) 1991 대한금속·재료학회지 Vol.29 No.1

A new way of producing alumina from the alkoxide is reported. Aluminum oxalate is first synthesized by reactions which allow controlled precipitation. Alumina powder is obtained by subsequent thermal decomposition. 1) The addition of H₂C₂O₄, in the Boehmite Sol. was able to reduce the Geling time. 2) The first generated particles in the size of 10㎛ were agglomerated in chain type. 3) The recovery of A1₂O₃ was increased with increasing PH of solution and decreasing both the mole ratio of H₂C₂O₄/ Alkoxide and reaction temperature. 4) The grain size of the calcined products was increased with increasing PH of solution, mole ratio of H₂C₂O₄/ Alkoxide and reaction temperature, however, decreased significantly in the range of PH 1.

Preventive effect of fermented Maillard reaction products from milk proteins in cardiovascular health

Oh, N.S.,Kwon, H.S.,Lee, H.A.,Joung, J.Y.,Lee, J.Y.,Lee, K.B.,Shin, Y.K.,Baick, S.C.,Park, M.R.,Kim, Y.,Lee, K.W.,Kim, S.H. American Dairy Science Association 2014 Journal of dairy science Vol.97 No.6

The aim of this study was to determine the dual effect of Maillard reaction and fermentation on the preventive cardiovascular effects of milk proteins. Maillard reaction products (MRP) were prepared from the reaction between milk proteins, such as whey protein concentrates (WPC) and sodium caseinate (SC), and lactose. The hydrolysates of MRP were obtained from fermentation by lactic acid bacteria (LAB; i.e., Lactobacillus gasseri H10, L. gasseri H11, Lactobacillus fermentum H4, and L. fermentum H9, where human-isolated strains were designated H1 to H15), which had excellent proteolytic and 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activities (>20%). The antioxidant activity of MRP was greater than that of intact proteins in assays of the reaction with 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt and trivalent ferric ions; moreover, the effect of MRP was synergistically improved by fermentation. The Maillard reaction dramatically increased the level of antithrombotic activity and 3-hydroxy-3-methylglutaryl-CoA reductase (HMGR) inhibitory effect of milk proteins, but did not change the level of activity for micellar cholesterol solubility. Furthermore, specific biological properties were enhanced by fermentation. Lactobacillus gasseri H11 demonstrated the greatest activity for thrombin and HMGR inhibition in Maillard-reacted WPC, by 42 and 33%, respectively, whereas hydrolysates of Maillard-reacted SC fermented by L. fermentum H9 demonstrated the highest reduction rate for micellar cholesterol solubility, at 52%. In addition, the small compounds that were likely released by fermentation of MRP were identified by size-exclusion chromatography. Therefore, MRP and hydrolysates of fermented MRP could be used to reduce cardiovascular risks.

A potent and selective 11β-hydroxysteroid dehydrogenase type 1 inhibitor, SKI2852, ameliorates metabolic syndrome in diabetic mice models

Oh, H.,Jeong, K.H.,Han, H.Y.,Son, H.J.,Kim, S.S.,Lee, H.J.,Kim, S.,Sa, J.H.,Jun, H.S.,Ryu, J.H.,Choi, C.S. North-Holland ; Elsevier Science Ltd 2015 european journal of pharmacology Vol.768 No.-

11β-Hydroxysteroid dehydrogenase type 1 (11βHSD1) has been targeted for new drugs to treat type 2 diabetes and metabolic syndrome. In this study, we determined whether the inhibition of 11βHSD1 with a new selective inhibitor, SKI2852, could improve lipid profiles, glucose levels, and insulin sensitivity in type 2 diabetic and obese conditions. SKI2852 showed a potent inhibition of cortisone to cortisol conversion for over 80% in both liver and adipose tissue ex vivo from orally administered C57BL/6 mice, and in vivo analysis results were consistent with this. Repeated oral administrations of SKI2852 in diet-induced obesity (DIO) and ob/ob mice revealed a partially beneficial effect of SKI2852 in improving levels of cholesterols, triglycerides, free fatty acids, postprandial glucose, and/or blood hemoglobinA<SUB>1c</SUB>. SKI2852 significantly reduced body weight increase in ob/ob mice, and efficiently suppressed hepatic mRNA levels of gluconeogenic enzymes in DIO mice. Moreover, SKI2852 enhanced hepatic and whole body insulin sensitivities in hyperinsulinemic-euglycemic clamp experiment in DIO mice. In conclusion, these results indicate that selective and potent inhibition of 11βHSD1 by SKI2852, thus blockade of active glucocorticoid conversion, may improve many aspects of metabolic parameters in type 2 diabetes and metabolic diseases, mainly by inhibitions of hepatic gluconeogenesis and partial improvements of lipid profiles. Our study strongly support that SKI2852 may have a great potential as a novel candidate drug for the treatment of diabetes and metabolic diseases.

RNA expression analysis of efflux pump genes in clinical isolates of multidrug-resistant and extensively drug-resistant Mycobacterium tuberculosis in South Korea

Oh, T.S.,Kim, Y.J.,Kang, H.Y.,Kim, C.K.,Cho, S.Y.,Lee, H.J. Elsevier Science 2017 INFECTION GENETICS AND EVOLUTION Vol.49 No.-

<P>Tuberculosis (TB), caused by infection with Mycobacterium tuberculosis, is an important communicable disease. Various mechanisms of resistance to antituberculosis drugs have been reported; these are principally mutations in target genes. However, not all M. tuberculosis resistance can be explained by mutations in such genes. Other resistance mechanisms associated with drug transport, such as efflux pumps, have also been reported. In this study, we investigated the expression levels of three putative efflux pumps and mutations in target genes associatedwith injectable agents and fluoroquinoloneswith clinicalMDR and XDR-TB isolates. Thirty clinical isolates of M. tuberculosis that had been phenotypically characterized were obtained from the Korean Institute of Tuberculosis. Of these, 14 were MDR-TB isolates resistant to at least one injectable aminoglycoside (amikacin; AMK, kanamycin; KAN, and/or capreomycin; CPM) and 16 were XDR-TB isolates. M. tuberculosis H37Rv (ATCC 27249) was used as a reference strain. Five putative genes (Rv1258c, Rv2686c, Rv2687c, Rv2688c and pstB) were selected for analysis in this study. Sequencing was performed to detect mutations in rrs and eis genes. qRT-PCR was performed to investigate expression levels of five efflux pump genes. Of the 30 isolates, 25 strains hadmutations in rrs associated with resistance to KAN, CPMand AMK and two strains had eis mutations, as well as mutations in rrs. pstB (Rv0933) exhibited increased expression and Rv2687c and Rv2688c exhibited decreased expression compared to the reference strain. Increased expression of pstB in clinical drug-resistant tuberculosis isolates may contribute to drug resistance in M. tuberculosis. In our case, overexpression of Rv1258c may have been associated with resistance to kanamycin. No correlation was evident between Rv2686c, Rv2687c or Rv2688c expression and fluoroquinolone resistance. To explore the details of efflux pump drug-resistancemechanisms, further studies on efflux pump inhibitors, transcriptional regulators, such as whiB7, and additional efflux pump genes are needed. (C) 2017 Elsevier B. V. All rights reserved.</P>

Identification of Novel SNPs with Effect on Economic Traits in Uncoupling Protein Gene of Korean Native Chicken

Oh, J.D.,Kong, H.S.,Lee, J.H.,Choi, I.S.,Lee, S.J.,Lee, S.G.,Sang, B.D.,Choi, C.H.,Cho, B.W.,Jeon, G.J.,Lee, H.K. Asian Australasian Association of Animal Productio 2006 Animal Bioscience Vol.19 No.8

The avian uncoupling protein (avUCP) is a member of the mitochondrial transporter superfamily that uncouples proton entry in the mitochondrial matrix from ATP synthesis. The sequencing analysis method was used to identify nucleotide polymorphisms within the avUCP gene in Korean native chicken (KNC). This study identified ten single nucleotide polymorphisms (SNPs) in the avUCP gene. We analyzed the SNPs of the avUCP gene to investigate whether polymorphism in the gene might be responsible for quantitative variations in economic traits in KNC. Three significant polymorphic sites for economic traits were avUCP C+282T (mean body weight, p<0.05), avUCP C+433T (daily percent lay, p<0.05), and avUCP T+1316C (daily percent lay, p<0.05). The frequency of each SNP was 0.125 (C+282T in avUCP gene exon 1 region), 0.150 (C+433T in avUCP gene intron 1 region), and 0.15 (T+1316C in avUCP gene exon 3 region), respectively. Among the identified SNPs, one pair of SNPs (genotype CC, C+282T and TT, avUCP C+433T) showed the highest daily percent lay (p<0.05) and mean body weight (p<0.05) and the frequency was 0.067. This study of the avUCP gene could be useful for genetic studies of this gene and selection on economic traits for KNC.

Effects of Dietary Fermented Chlorella vulgaris (CBT^®) on Growth Performance, Relative Organ Weights, Cecal Microflora, Tibia Bone Characteristics, and Meat Qualities in Pekin Ducks

Oh, S.T.,Zheng, L.,Kwon, H.J.,Choo, Y.K.,Lee, K.W.,Kang, C.W.,An, Byoung-Ki Asian Australasian Association of Animal Productio 2015 Animal Bioscience Vol.28 No.1

Fermented Chlorella vulgaris was examined for its effects on growth performance, cecal microflora, tibia bone strength, and meat qualities in commercial Pekin ducks. A total of three hundred, day-old male Pekin ducks were divided into three groups with five replicates (n = 20 ducklings per replicate) and offered diets supplemented with commercial fermented C. vulgaris (CBT$^{(R)}$) at the level of 0, 1,000 or 2,000 mg/kg, respectively for 6 wks. The final body weight was linearly (p = 0.001) increased as the addition of fermented C. vulgaris into diets increased. Similarly, dietary C. vulgaris linearly increased body weight gain (p = 0.001) and feed intake (p = 0.001) especially at the later days of the feeding trial. However, there was no C. vulgaris effect on feed efficiency. Relative weights of liver were significantly lowered by dietary fermented C. vulgaris (linear effect at p = 0.044). Dietary fermented C. vulgaris did not affect total microbes, lactic acid bacteria, and coliforms in cecal contents. Finally, meat quality parameters such as meat color (i.e., yellowness), shear force, pH, or water holding capacity were altered by adding fermented C. vulgaris into the diet. In our knowledge, this is the first report to show that dietary fermented C. vulgaris enhanced meat qualities of duck meats. In conclusion, our study indicates that dietary fermented C. vulgaris exerted benefits on productivity and can be employed as a novel, nutrition-based strategy to produce value-added duck meats.