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>

C3, C4 의 Nephelometric 측정 경험

조병철 ( B C Cho ),검덕희 ( D H Kim ),김민숙 ( M S Kim ),서덕규 ( D K Seo ) 대한임상검사과학회 1990 대한임상검사과학회지(KJCLS) Vol.22 No.1

RIA has been used to measure accurately a minute quantity of Ags, such as proteins. hormones, enzymes or drugs. However, due to the presence of a radication hazard and the increment of having to pool test specimens. RIA is gradually being replaced by other immunoassay that have a comparable sensitivity but do not require radiocative meterial. Turbidimetric immunoassay, latex immunoassay and fluorescence immunoassay are such examples. We at the department of clinical pathology, Asan medical center, compared CH 50 activity with C3 , C4 quantity by nephelometric method.

T_c and J_c distribution in in situ processed MgB₂ bulk superconductors with/without C doping

Kim, C.J.,Kim, Y.J.,Lim, C.Y.,Jun, B.H.,Park, S.D.,Choo, K.N. The Korea Institute of Applied Superconductivity a 2014 한국초전도저온공학회논문지 Vol.16 No.2

Temperature dependence of magnetic moment (m-T) and the magnetization (M-H) at 5 K and 20 K of the in situ processed $MgB_2$ bulk pellets with/without carbon (C) doping were examined. The superconducting critical temperature ($T_c$), the superconducting transition width (${\delta}T$) and the critical current density ($J_c$) were estimated for ten test samples taken from the $MgB_2$ bulk pellets. The reliable m-T characteristics associated with the uniform $MgB_2$ formation were obtained for both $MgB_2$ pellets. The $T_cs$ and ${\delta}Ts$ of all test samples of the undoped $MgB_2$ were the same each other as 37.5 K and 1.5 K, respectively. The $T_cs$ and ${\delta}Ts$ of the C-doped $MgB_2$ were 36.5 K and 2.5 K, respectively. Unlike the m-T characteristics, there existed the difference among the M-H curves of the test samples, which might be caused by the microstructure variation. In spite of the slight $T_c$ decrease, the C doping was effective in enhancing the $J_c$ at 5 K.

Ex-situ catalytic pyrolysis of citrus fruit peels over mesoporous MFI and Al-MCM-41

Kim, Y.M.,Jae, J.,Lee, H.W.,Han, T.U.,Lee, H.,Park, S.H.,Kim, S.,Watanabe, C.,Park, Y.K. Pergamon ; Elsevier Science Ltd 2016 Energy conversion and management Vol.125 No.-

The thermal and ex-situ catalytic pyrolysis of different citrus peels, Citrus paradisi peel, Citrus sinensis peel, Citrus unshiu peel, and Citrus limon peel, were studied by thermogravimetric, evolved gas analysis-mass spectrometry and tandem micro-reactor-gas chromatograph/mass spectrometry analyses. Kinetic analysis revealed more complicated reaction steps and a wider range of activation energies of citrus peels than those of wood powder due to the presence of pectin in the citrus peels. Large amounts of methanol formation from each citrus peel were also recorded by evolved gas analysis-mass spectrometry and fast pyrolysis-gas chromatograph/mass spectrometry analyses at the main decomposition temperature of pectin, between 150 and 250<SUP>o</SUP>C. Mesoporous MFI was found to be a more effective catalyst for the production of mono aromatic compounds (benzene, toluene, ethylbenzene, and xylene; 3.06-4.17C%) and light olefins (ethene, propene, butene, and butadiene; 8.13-9.13C%) than Al-MCM-41 (mono aromatic compounds 0.67-0.93C% and light olefins 3.61-4.58C%) because of its higher catalytic activity in deoxygenation and aromatization due to the stronger acidity of mesoporous MFI. The yield of mono aromatic compounds over mesoporous MFI was highest from C. paradisi peel (4.17C%), followed in order by C. sinensis peel (3.83C%), C. unshiu peel (3.61C%), and C. limon peel (3.06C%), due mainly to the different contents and properties of pectin in each citrus peel. The higher activities of mesoporous MFI than Al-MCM-41 were also maintained during the 7 times sequential catalytic pyrolysis of C. paradisi peel, demonstrating the stability of mesoporous MFI catalyst.

Mechanical properties of (W,Ti)C and (W,Ti)C-NiAl₃ cermet consolidated by the high-frequency induction-heating method

Kim, W.,Suh, C.Y.,Roh, K.M.,Cho, S.W.,Na, K.I.,Shon, I.J. Elsevier Sequoia 2013 Journal of alloys and compounds Vol.568 No.-

In the case of cemented (W,Ti)C, Co is added as a binder for the formation of composite structures. However, the high cost of Co and the low corrosion resistance of the (W,Ti)C-Co cermet have generated interest in recent years for alternative binder phases. In this study, NiAl<SUB>3</SUB> was used as a binder and consolidated by the high-frequency induction heated sintering (HFIHS) method. The densification of both monolithic (W,Ti)C and (W,Ti)C-NiAl<SUB>3</SUB> cermet was accomplished within 3min. Highly dense (W,Ti)C and (W,Ti)C-NiAl<SUB>3</SUB> with a relative density of upto 99% were obtained within 3min by HFIHS under a pressure of 80MPa. The method was found to enable not only the rapid densification but also the prohibition of grain growth preserving the nano-scale microstructure. The average grain sizes of the sintered (W,Ti)C and (W,Ti)C-NiAl<SUB>3</SUB> were lower than 100nm. The addition of NiAl<SUB>3</SUB> to (W,Ti)C enhanced the toughness at the expense of the slight decrease in hardness. The hardness of (W,Ti)C and (W,Ti)C-NiAl<SUB>3</SUB> was significantly higher than that of (W,Ti)C-Co or (W,Ti)C-Ni. The fracture toughness and hardness values of (W,Ti)C, (W,Ti)C-5vol.%NiAl<SUB>3</SUB>, and (W,Ti)C-10vol.%NiAl<SUB>3</SUB> consolidated by HFIHS with a pressure of 80MPa and a induced current were 7.6+/-0.4MPam<SUP>½</SUP> and 2850+/-35kg/mm<SUP>2</SUP>, 8.5+/-0.3MPam<SUP>½</SUP> and 2610+/-37kg/mm<SUP>2</SUP>, 9.7+/-0.5MPam<SUP>½</SUP> and 2520+/-26kg/mm<SUP>2</SUP>, respectively.

TmSR-C, scavenger receptor class C, plays a pivotal role in antifungal and antibacterial immunity in the coleopteran insect Tenebrio molitor

Kim, S.G.,Jo, Y.H.,Seong, J.H.,Park, K.B.,Noh, M.Y.,Cho, J.H.,Ko, H.J.,Kim, C.E.,Tindwa, H.,Patnaik, B.B.,Bang, I.S.,Lee, Y.S.,Han, Y.S. Pergamon Press ; Elsevier Science Ltd 2017 Insect biochemistry and molecular biology Vol.89 No.-

Scavenger receptors (SRs) constitute a family of membrane-bound receptors that bind to multiple ligands. The SR family of proteins is involved in removing cellular debris, oxidized low-density lipoproteins, and pathogens. Specifically, class C scavenger receptors (SR-C) have also been reported to be involved in phagocytosis of gram-positive and -negative bacteria in Drosophila and viruses in shrimp. However, reports are unavailable regarding the role of SR-C in antifungal immune mechanisms in insects. In this study, a full-length Tenebrio molitor SR-C (TmSR-C) sequence was obtained by 5'- and 3'-Rapid amplification of cDNA ends-polymerase chain reaction (RACE-PCR). The TmSR-C full-length cDNA comprised 1671 bp with 5'- and 3'-untranslated regions of 23- and 107-bp, respectively. TmSR-C encodes a putative protein of 556 amino acid residues that is constitutively expressed in all tissues of late instar larvae and 2-day-old adults, with the highest transcript levels observed in hemocytes of larvae and adults. TmSR-C mRNA showed a 2.5-fold and 3-fold increase at 24 and 6 h after infection with Candida albicans and β-glucan, respectively. Immunoassay with TmSR-C polyclonal antibody showed induction of the putative protein in the cytosols of hemocytes at 3 h after inoculation of C. albicans. RNA interference (RNAi)-based gene silencing and phagocytosis assays were used to understand the role of TmSR-C in antifungal immunity. Silencing of TmSR-C transcripts reduced the survivability of late instar larvae at 2 days post-inoculation of C. albicans, Escherichia coli, or Staphylococcus aureus. Furthermore, in TmSR-C-silenced larvae, there was a decline in the rate of microorganism phagocytosis. Taken together, results of this study suggest that TmSR-C plays a pivotal role in phagocytosing not only fungi but also gram-negative and -positive bacteria in T. molitor.

Regulation of cancer cell death by a novel compound, C604, in a c-Myc-overexpressing cellular environment

Jo, M.J.,Paek, A.R.,Choi, J.S.,Ok, C.Y.,Jeong, K.C.,Lim, J.H.,Kim, S.H.,You, H.J. North-Holland ; Elsevier Science Ltd 2015 european journal of pharmacology Vol.769 No.-

<P>The proto-oncogene c-Myc has been implicated in a variety of cellular processes, such as proliferation, differentiation and apoptosis. Several c-Myc targets have been studied; however, selective regulation of c-Myc is not easy in cancer cells. Herein, we attempt to identify chemical compounds that induce cell death in c-Myc-overexpressing cells (STF-cMyc and STF-Control) by conducting MTS assays on approximately 4000 chemical compounds. One compound, C604, induced cell death in STF-cMyc cells but not STF-Control cells. Apoptotic proteins, including caspase-3 and poly(ADP-ribose) polymerase (PAPP), were cleaved in C604-treated STF-cMyc cells. In addition, 5W620, HCT116 and NCI-H23 cells, which exhibit higher basal levels of c-Myc, underwent apoptotic cell death in response to C604, suggesting a role for C604 as an inducer of apoptosis in cancer cells with c-Myc amplification. C604 induced cell cycle arrest at the G2/M phase in cells, which was not affected by apoptotic inhibitors. Interestingly, C604 induced accumulation of c-Myc and Cdc25A proteins. In summary, a chemical compound was identified that may induce cell death in cancer cells with c-Myc amplification specifically through an apoptotic pathway. (C) 2015 Elsevier B.V. All rights reserved.</P>

한우 비육에 관한 연구 1 . Methylthiouracil 첨가 및 Estradiol 17β - Cypionate 주사가 약령 모우 비육에 미치는 효과

김창기 ( C K Kim ),이택원 ( T W Lee ),김종욱 ( J W Kim ),배대식 ( D S Bae ),오선균 ( S K Oh ),조지훈 ( C H Cho ),김법회 ( B H Kim ),김상렬 ( S Y Kim ),배신석 ( S S Bae ) 한국축산학회 1971 한국축산학회지 Vol.13 No.1

This study was performed to affirm any effects of methylthiouracil and estradiol 17β-cypionate administered to young bulls for short term fattening. Eighteen bulls of Korean native breed, approximately 1.5 to 2 years of age and 260㎏ to 360㎏ in weight, were used in this study. All bulls had received a basal ration of soiling corn and concentrate made up of 55% grains, 40% brans and 5% others, in a period of 40 days. Bulls were divided into six groups as follows: group C was not treated, group M-2 received 2g of methylthiouracil per day, group M-3 received 3g of methylthiouracil per day, group EM-0 was injected intramusculary with 25㎎ of estradiol 17β-cypionate in the neck region 10 days after the beginning of the fattening period, group EM-2 was injected with estradiol 17β-cypionate as above mentioned and simultaneously received 2g of methylthiouracil per day, and group EM-3 was injected with estradiol 17β-cypionate as above mentioned and simultaneously received 3g of methylthiouracil per day. The results obtained were summarized as follows. 1. The average daily gain was for group C: 0.83㎏, group M-2: 1.07㎏, group M-3: 1.40㎏, group EM-0, 0.93㎏, group EM-2: 0.95㎏, and group EM-3: 1.18㎏. The M-3 group gained significantly(P$lt;0.05) more weight than C and EM-0 group. There were no significant differences in the average daily gain between the groups injected with estradiol 17β-eypionate and the control group. 2. The average daily concentrate intake was as follows: group C: 5.47㎏, group M-2: 5.00㎏, group M-3: 4.52㎏, group EM-0: 5.21㎏, group EM-2: 4.35㎏, and group EM-3: 4.61㎏. The consumption of concentrate was decreased by 17% in the M-3 group compared with the C group. There was no significant difference in the soiling corn intake among these groups. 3. Feed consumed for 1㎏ gain were decreased by the supplementation of methylthiouracil. The consumption of DCP for 1㎏ gain was in group C: 0.82㎏, group M-2: 0.59㎏, group M-3: 0.41㎏, group EM-0: 0.70㎏, group EM-2: 0.59㎏, and group EM-3: 0.50㎏. The amounts of TDN required were; group C: 6.57㎏, group M-2: 4.76㎏, group M-3: 3.39㎏, group EM-0: 5.67㎏, group EM-Z: 4.87㎏, and group EM-3: 4.08㎏. The consumption of DCP and TDN for 1㎏ gain in the M-3 group was about a half of that in the C group. 4. There was not any significant difference in the increase in body measurements among the various groups. 5. The average margins in the fattening period of 40 days were for group C: 2,950won, group M-2: 5,327won, group M-3: 9,158won, group EM-0: 3,310won, group EM-2: 3,623won, and group EM-3: 5,575won. The margin of group M-3 was about three times higher than that of group C. In short, this experiment demonstrated that methylthiouracil when fed to young native Korean bulls at the proper level 40 days before slaughter would bring a noticeable effect on weight gain, feed efficiency and economic advantage. There were no advantages from the simultaneous injecting estradiol 17β-cypionate with methylthiouracil. The proper supplementation level of methylthiouracil would appear to be 3g per head per day in this experiment.

Fabrication of ex situ processed MgB₂ wires using nano carbon doped powder

Lee, C.M.,Park, J.H.,Hwang, S.M.,Lim, J.H.,Joo, J.,Kang, W.N.,Kim, C.J. North-Holland 2009 Physica. C, Superconductivity Vol.469 No.15

We fabricated ex situ MgB<SUB>2</SUB> wires using C-doped MgB<SUB>2</SUB> powder as a precursor in order to improve the core density of the wires and their C doping content. The C-doped powder was prepared with Mg, B, and nano carbon (NC) powders by the in situ technique and then MgB<SUB>2-x</SUB>C<SUB>x</SUB> (x=0, 0.01, and 0.03) wires were fabricated by the ex situ technique using the powder-in-tube method. The phase formation, lattice change, and microstructure were characterized and correlated with the T<SUB>c</SUB> and J<SUB>c</SUB> variations. We observed that the ex situ wire had a higher core density than the in situ wire, however its morphology consisted of agglomerated particles, indicating that sintering and grain growth did not occur completely, even though the sintering was conducted at high temperature (1000<SUP>o</SUP>C). As the C content increased, T<SUB>c</SUB> decreased, while the decrease of J<SUB>c</SUB> with increasing magnetic field became smaller. The J<SUB>c</SUB> of MgB<SUB>1.97</SUB>C<SUB>0.03</SUB> wire made by the ex situ technique was 3.34kA/cm<SUP>2</SUP> at 6.6T and 5K which is comparable to that of the in situ wire (4.81kA/cm<SUP>2</SUP> at 6.6T and 5K).

소 c-KIT Receptor 유전자의 다형성에 관한 연구

장요순,김태헌,윤두학,박응우,이혜원,이학교,정일정 한국동물자원과학회 2002 한국축산학회지 Vol.44 No.6

소의 흰 반점 관련 후보유전자로 c-KIT receptor 유전자를 선정하여, c-KIT receptor 유전자내의 변이를 탐색하고 변이가 흰반점 표현형과 연관성이 있는지를 분석하였다. 한우, Angus, Brown Swiss, Charolais, Hereford, Holstein, Limousin 및 Simmental 등 8개 품종의 DNA 시료를 사용하여 c-KIT receptor 유전자의 intron 6번 영역에서 다형성을 조사하고 분석하였다. c-KIT receptor 유전자의 intron 6번 영역에서는 4개의 염기치환이 발견되어, MspⅠ, BsrBⅠ 및 NdeⅠ 제한효소를 이용하여 PCR-RFLP 분석을 실시하였다. Intron 6번을 포함하는 영역의 PCR 산물 크기는 2,440 bp 이었다. MspⅠ다형성은 PCR-RFLP 분석 결과 3개의 대립유전자가 존재하였으며, 한우품종에서는 3개의 대립유전자 모두가 발견되었고, CC 형태이 유전자형을 제외한 5개의 유전자형 (AA, AB, AC, BC 및 BB)을 확인하였다. Angus, Brown Swiss, Hereford, Holstein 및 Simmental 품종에서는 A 대립유전자만을 갖는 것으로 조사되었고, 한우는 44%만 AA 유전자형을 나타내었다. BsrBⅠ 다형성은 2개의 대립유전자로서 3개의 유전자형이 나타나는 것을 확인하였으며, Charolais 및 Hereford 품종이 다른 소 품종에 비하여 A 대립유전자의 빈도가 높게 나타났다. NdeⅠ 다형성을 분석한 결과 Brown Swiss 품종에서는 NdeⅠ에 의해 절단되는 형태인 A 대립유전자만 관찰되었으며, Holstein 품종은 92%, Simmental 품종은 72%가 절단되는 형태를 나타내어, 모색이 흰색을 띠는 소 품종에서 절단되는 형태가 많았다. 소 c-KIT receptor 유전자의 intron 6번 영역에서 확인된 4개의 염기치환은 품종에 따라 다른 빈도를 보였으나, 이들 염기치환과 흰 반점과의 연관성에 대한 증거는 발견하지 못하였다. 그러므로 소의 흰 반점과 c-KIT receptor 유전자 내의 변이와의 관련성은 다른 영역에 대한 추가적인 분석과, 이미 보고된 다른 모색관련 유전자의 다형성과의 연관성 분석 등과 같은 연구가 필요한 것으로 판단된다. We considered KIT gene as a candidate gene for the white-spotting pattern in cattle. This study was carried out to detect genetic variation of c-KIT receptor gene and to investigate association between the mutation and the white-spotting pattern in cattle. PCR-RFLP analysis within intron 6 of c-KIT receptor gene were performed with 8 cattle breeds including Hanwoo, Angus, Brown Swiss, Charolais, Hereford, Holstein, Limousin and Simmental. When PCR product of approximately 2,440 bp including intron 6 of c-KIT receptor gene was sequenced, four nucleotide substitutions were found within intron 6 of the bovine c-KIT receptor gene. In PCR-RFLP analysis, three alleles (A, B and C), two alleles (A and B) and two alleles (A and B) at each locus were identified by Msp Ⅰ, BsrBⅠ and NdeⅠ, respectively. Although frequencies of allele at each locus were different among cattle breeds, we could not get any evidence related with white or white spotting phenotypes in these mutations on intron 6 of c-KIT receptor gene. However, we can not entirely exclude the possibility that c-KIT receptor gene is responsible for white spotting phenotype in cattle. Thus, further studies need to detect other mutations in c-KIT receptor gene and to test association of those mutations and coat color phenotypes in cattle.