Multiple heterologous M2 extracellular domains presented on virus-like particles confer broader and stronger M2 immunity than live influenza A virus infection

Kim, M.C.,Lee, J.S.,Kwon, Y.M.,O, E.,Lee, Y.J.,Choi, J.G.,Wang, B.Z.,Compans, R.W.,Kang, S.M. Elsevier/North-Holland 2013 Antiviral research Vol.99 No.3

The influenza M2 ectodomain (M2e) is poorly immunogenic and has some amino acid changes among isolates from different host species. We expressed a tandem repeat construct of heterologous M2e sequences (M2e5x) derived from human, swine, and avian origin influenza A viruses on virus-like particles (M2e5x VLPs) in a membrane-anchored form. Immunization of mice with M2e5x VLPs induced protective antibodies cross-reactive to antigenically different influenza A viruses and conferred cross protection. Anti-M2e antibodies induced by heterologous M2e5x VLPs showed a wider range of cross reactivity to influenza A viruses at higher levels than those by live virus infection, homologous M2e VLPs, or M2e monoclonal antibody 14C2. Fc receptors were found to be important for mediating protection by immune sera from M2e5x VLP vaccination. The present study provides evidence that heterologous recombinant M2e5x VLPs can be more effective in inducing protective M2e immunity than natural virus infection and further supports an approach for developing an effective universal influenza vaccine.

Microneedle patch delivery to the skin of virus-like particles containing heterologous M2e extracellular domains of influenza virus induces broad heterosubtypic cross-protection

Kim, M.C.,Lee, J.W.,Choi, H.J.,Lee, Y.N.,Hwang, H.S.,Lee, J.,Kim, C.,Lee, J.S.,Montemagno, C.,Prausnitz, M.R.,Kang, S.M. Elsevier Science Publishers 2015 Journal of controlled release Vol.210 No.-

A broadly cross-protective influenza vaccine that can be administrated by a painless self-immunization method would be a value as a potential universal mass vaccination strategy. This study developed a minimally-invasive microneedle (MN) patch for skin vaccination with virus-like particles containing influenza virus heterologous M2 extracellular (M2e) domains (M2e5x VLPs) as a universal vaccine candidate without adjuvants. The stability of M2e5x VLP-coated microneedles was maintained for 8weeks at room temperature without losing M2e antigenicity and immunogenicity. MN skin immunization induced strong humoral and mucosal M2e antibody responses and conferred cross-protection against heterosubtypic H1N1, H3N2, and H5N1 influenza virus challenges. In addition, M2e5x VLP MN skin vaccination induced T-helper type 1 responses such as IgG2a isotype antibodies and IFN-γ producing cells at higher levels than those by conventional intramuscular injection. These potential immunological and logistic advantages for skin delivery of M2e5x VLP MN vaccines could offer a promising approach to develop an easy-to-administer universal influenza vaccine.

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>

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>

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).

Supplemented vaccination with tandem repeat M2e virus-like particles enhances protection against homologous and heterologous HPAI H5 viruses in chickens

Song, B.M.,Kang, H.M.,Lee, E.K.,Jung, S.C.,Kim, M.C.,Lee, Y.N.,Kang, S.M.,Lee, Y.J. Butterworths ; Elsevier Science Ltd 2016 Vaccine Vol.34 No.5

Highly pathogenic avian influenza (HPAI) H5 viruses derived from A/Goose/Guangdong/1/96 have been continuously circulating globally, severely affecting the public health and poultry industries. The matrix 2 protein ectodomain (M2e) is considered a promising candidate for a universal cross-protective influenza vaccine that provides more effective control over HPAI H5 viruses harboring variant hemagglutinin (HA)-antigens. Here, we evaluated the protective efficacy of a tandem repeat construct of heterologous M2e presented on virus-like particles (M2e5x VLPs) either alone or as a supplement against HPAI H5 viruses in a chicken model. Chickens immunized with M2e5x VLPs alone induced M2e-specific antibodies but were not protected against HPAI H5. The homo- and cross-protective efficacy of M2e5x VLP-supplemented vaccination of chickens was also examined. Importantly, supplementation with M2e5x VLPs induced significantly higher levels of antibodies specific for M2e and different viruses as well as provided improved protection against homologous and heterologous HPAI H5 viruses. Considering the limited efficacy of inactivated vaccines, supplement vaccination with M2e5x VLPs may be an effective measure for preventing outbreaks of HPAI viruses that have the ability to constantly change their antigenic properties in poultry.

Shewanella marina sp. nov., isolated from seawater

Park, S. C.,Baik, K. S.,Kim, M. S.,Kim, D.,Seong, C. N. Microbiology Society 2009 International journal of systematic and evolutiona Vol.59 No.8

<P>A motile, rod-shaped, pale-brown-pigmented bacterium, designated strain C4T, was isolated from seawater collected from the South Sea (Republic of Korea). Cells were Gram-negative, facultatively anaerobic, and catalase- and oxidase-positive. The major fatty acids were summed feature 3 (C16:1omega7c and/or iso-C15:0 2-OH; 19.4%), C16:0 (16.3%), C17:1omega8c (9.5%) and iso-C15:0 (7.7%). The DNA G+C content was 40.8 mol%. A phylogenetic tree based on 16S rRNA gene sequences showed that strain C4T formed a lineage within the genus Shewanella (92.7-96.1% sequence similarity to representative strains of the genus Shewanella) and was part of a distinct branch with the clade comprising Shewanella haliotis DW01T and Shewanella algae ATCC 51192T. Phenotypic characteristics enabled strain C4T to be distinguished from S. haliotis and S. algae. On the basis of the data presented in this study, strain C4T represents a novel species, for which the name Shewanella marina sp. nov. is proposed. The type strain is C4T (=KCTC 22185T=JCM 15074T).</P>