Supplementation of oil-based inactivated H9N2 vaccine with M2e antigen enhances resistance against heterologous H9N2 avian influenza virus infection

Park, J.K.,Lee, D.H.,Cho, C.H.,Yuk, S.S.,To, E.O.,Kwon, J.H.,Noh, J.Y.,Kim, B.Y.,Choi, S.W.,Shim, B.S.,Song, M.K.,Lee, J.B.,Park, S.Y.,Choi, I.S.,Song, C.S. Elsevier Scientific Pub. Co 2014 Veterinary microbiology Vol.169 No.3

Avian influenza virus (AIV) subtype H9N2 has been evolving rapidly and vaccine escape variants have been reported to cause circulation of infections and economic losses. In the present study, we developed and evaluated ectodomain of the AIV matrix 2 (M2e) protein as a supplementing antigen for oil-based inactivated H9N2 vaccine to increase resistance against vaccine escape variants. AIV H9N2 M2e antigen was expressed in Escherichia coli and supplemented to inactivated H9N2 oil emulsion vaccine. Specific pathogen-free chickens received a single injection of inactivated H9N2 oil emulsion vaccines with or without M2e supplementation. At three weeks post vaccination, hemagglutination inhibition tests and enzyme-linked immunosorbent assays were performed to determine serological immune responses. Challenge study using a vaccine escape H9N2 variant was performed to evaluate the efficacy of M2e supplementation. M2e antigen supplemented in oil emulsion vaccine was highly immunogenic, and a single M2e-supplemented vaccination reduced challenge virus replication and shedding more effectively than non-supplemented vaccination.

A phase II study of S-1 monotherapy administered for 2 weeks of a 3-week cycle in advanced gastric cancer patients with poor performance status

Jeung, H-C,Rha, S Y,Shin, S J,Ahn, J B,Noh, S H,Roh, J K,Chung, H C Nature Publishing Group 2007 The British journal of cancer Vol.97 No.4

<P>Systemic chemotherapy for gastric cancer is often associated with treatment-related toxicity, which is particularly severe in patients with a poor performance status. In this paper, we describe the first study to evaluate S-1 monotherapy as an option for advanced gastric cancer patients who are not candidates for combination chemotherapy due to poor clinical condition. Fifty-two patients with Eastern Cooperative Oncology Group (ECOG) performance scale 2–3, whose general condition had made use of combination chemotherapy impossible, were enrolled. S-1 was administered to 30 patients as second- or third-line therapy. The initial dose of S-1 was 35 mg m<SUP>−2</SUP>, administered b.i.d for 14 days every 3 weeks. With a median follow-up period of 33 weeks, the median progression-free survival, and overall survival were 11 weeks (95% CI, 8–14) and 33 weeks (95% CI, 19–47), respectively. The overall 1-year survival rate was 29% by intent-to-treat analysis. The overall response rate was 12% (95% CI, 3–21), and the percentage of stable disease was 35%, resulting in the disease control rate of 47% (95% CI, 32–60). Significant drug-related toxicity included grade 3 diarrhoea (14%), anorexia (14%), fatigue (10%), neutropenia (10%), and leucopenia (6%). In conclusion, this study indicated the modest activity of S-1 in gastric cancer patients with poor performance status.</P>

Two S-wave gap symmetry for single crystals of the superconductor BaFe_1.8Co_0.2As₂

Choi, K.Y.,Kim, S.H.,Choi, C.,Jung, M.H.,Wang, X.F.,Chen, X.H.,Noh, J.D.,Lee, S.I. North-Holland 2010 Physica. C, Superconductivity Vol.470 No.suppl1

To clarify the gap structure of the iron-pnictide superconductors, we synthesized optimally doped single crystals of BaFe<SUB>1.8</SUB>Co<SUB>0.2</SUB>As<SUB>2</SUB>, which had a critical temperature, T<SUB>c</SUB>, of 23.6K. The initial M-H curve was used to find the lower critical field, H<SUB>c1</SUB>. The full range of the temperature dependence of H<SUB>c1</SUB> was explained by using a two S-wave gap symmetry. We estimate the two gap as Δ<SUB>1</SUB>(0)=1.64+/-0.2meV for the small gap and Δ<SUB>2</SUB>(0)=6.20+/-0.2meV for the large gap.

Efficacy of clade 2.3.2 H5 commercial vaccines in protecting chickens from clade 2.3.4.4 H5N8 highly pathogenic avian influenza infection

Yuk, S.s.,Erdene-Ochir, T.O.,Kwon, J.H.,Noh, J.Y.,Hong, W.t.,Jeong, J.H.,Jeong, S.,Gwon, G.B.,Shin, J.i.,Sur, J.H.,Song, C.S. Butterworths ; Elsevier Science Ltd 2017 Vaccine Vol.35 No.9

Emerging clade 2.3.4.4 of the highly pathogenic avian influenza (HPAI) virus strain H5N8, which had been detected sporadically in domestic poultry in China, started to affect wild birds and poultry in South Korea in 2014. The virus was spread to Germany, Italy, the Netherlands, United Kingdom, and even United States by migratory birds. Here, we tested currently used commercial clade 2.3.2 H5 vaccines to evaluate mortality, clinical signs, virus shedding, and histological damage after experimental infection of chickens with the clade 2.3.4.4 HPAI H5N8 virus. Although the vaccination protected chickens from death, it failed to prevent chickens from shedding the virus and from tissue damage according to histological examination. These results suggest that the use of appropriate vaccines that match the currently epidemic HPAI virus is recommended, and continuous HPAI surveillance and testing of currently used commercial vaccines should be performed.

Genetic identification of a novel locus, ACCELERATED FLOWERING 1 that controls chromatin modification associated with histone H3 lysine 27 trimethylation in Arabidopsis thaliana

Lee, S.,Shin, K.,Lee, I.,Song, H.R.,Noh, Y.S.,Lee, R.A.,Lee, S.,Kim, S.Y.,Park, S.K.,Lee, S.,Soh, M.S. Elsevier Scientific Publishers Ireland Ltd 2013 Plant science Vol.208 No.-

Flowering on time is a critically important for successful reproduction of plants. Here we report an early-flowering mutant in Arabidopsis thaliana, accelerated flowering 1-1D (afl1-1D) that exhibited pleiotropic developmental defects including semi-dwarfism, curly leaf, and increased branching. Genetic analysis showed that afl1-1D mutant is a single, dominant mutant. Chromosomal mapping indicates that AFL1 resides at the middle of chromosome 4, around which no known flowering-related genes have been characterized. Expression analysis and double mutant studies with late flowering mutants in various floral pathways indicated that elevated FT is responsible for the early-flowering of afl1-1D mutant. Interestingly, not only flowering-related genes, but also several floral homeotic genes were ectopically overexpressed in the afl1-1D mutants in both FT-dependent and -independent manner. The degree of histone H3 Lys27-trimethylation (H3K27me3) was reduced in several chromatin including FT, FLC, AG and SEP3 in the afl1-1D, suggesting that afl1-1D might be involved in chromatin modification. In support, double mutant analysis of afl1-1D and lhp1-4 revealed epistatic interaction between afl1-1D and lhp1-4 in regard to flowering control. Taken together, we propose that AFL1 regulate various aspect of development through chromatin modification, particularly associated with H3K27me3 in A. thaliana.

Therapeutic potential of compound K as an IKK inhibitor with implications for osteoarthritis prevention: an in silico and in vitro study

Kang, S.,Siddiqi, M. H.,Yoon, S. J.,Ahn, S.,Noh, H. Y.,Kumar, N. S.,Kim, Y. J.,Yang, D. C. Springer Science + Business Media 2016 In vitro cellular & developmental biology Animal Vol.52 No.9

<P>Ginsenosides have been used traditionally as an oriental medicine. However, the anti-osteoarthritic effect of ginsenoside compound K (hereafter referred to as CK) has not been reported. Therefore, in this study, the protective effects of CK were evaluated in silico and in vitro using H2O2-stimulated MC3T3-E1 cells by measuring the levels of proinflammatory cytokines responsible for articular cartilage degradation. In silico results demonstrated that, among the selected ginsenosides, CK is a non-toxic drug-like molecule with strong binding affinity for selected cytokine-activated kinase such as IkB alpha kinase (IKK). The molecular binding energy of CK with the active sites of IKK suggests anti-osteoarthritic functions. Cultured H2O2-stimulated MC3T3-E1 cells that were exposed to CK showed dramatically increased expression of osteoblast differentiation markers such as alkaline phosphatase (ALP) activity, type I collagen (Col-I) content, and mineralization. During aging, H2O2 also leads to the production of reactive oxygen species (ROS) and nitric oxide (NO), which play important roles in the development of osteoarthritis (OA). Therefore, the effect of CK on ROS and NO generation was also examined. Our results showed that CK dose-dependently inhibited H2O2-induced ROS and NO production in MC3T3-E1 cells. Moreover, qRT-PCR data showed that CK increased expression of osteogenic markers such as ALP and Col-I but decreased expression of inflammatory-related genes including IKK and interleukin 1 beta (IL-1 beta) in a dose-dependent manner in H2O2-stimulated MC3T3-E1 cells. The findings of this study suggest the use of CK as a novel protective and therapeutic agent in AO.</P>

Melatonin enhances arsenic trioxide-induced cell death via sustained upregulation of Redd1 expression in breast cancer cells

Yun, S.M.,Woo, S.H.,Oh, S.T.,Hong, S.E.,Choe, T.B.,Ye, S.K.,Kim, E.K.,Seong, M.K.,Kim, H.A.,Noh, W.C.,Lee, J.K.,Jin, H.O.,Lee, Y.H.,Park, I.C. North-Holland 2016 Molecular and cellular endocrinology Vol.422 No.-

Melatonin is implicated in various physiological functions, including anticancer activity. However, the mechanism(s) of its anticancer activity is not well understood. In the present study, we investigated the combined effects of melatonin and arsenic trioxide (ATO) on cell death in human breast cancer cells. Melatonin enhanced the ATO-induced apoptotic cell death via changes in the protein levels of Survivin, Bcl-2, and Bax, thus affecting cytochrome c release from the mitochondria to the cytosol. Interestingly, we found that the cell death induced by co-treatment with melatonin and ATO was mediated by sustained upregulation of Redd1, which was associated with increased production of reactive oxygen species (ROS). Combined treatment with melatonin and ATO induced the phosphorylation of JNK and p38 MAP kinase downstream from Redd1 expression. Rapamycin and S6K1 siRNA enhanced, while activation of mTORC1 by transfection with TSC2 siRNA suppressed the cell death induced by melatonin and ATO treatment. Taken together, our findings suggest that melatonin enhances ATO-induced apoptotic cell death via sustained upregulation of Redd1 expression and inhibition of mTORC1 upstream of the activation of the p38/JNK pathways in human breast cancer cells.

CK2α/CSNK2A1 Phosphorylates SIRT6 and Is Involved in the Progression of Breast Carcinoma and Predicts Shorter Survival of Diagnosed Patients

Bae, J.S.,Park, S.H.,Jamiyandorj, U.,Kim, K.M.,Noh, S.J.,Kim, J.R.,Park, H.J.,Kwon, K.S.,Jung, S.H.,Park, H.S.,Park, B.H.,Lee, H.,Moon, W.S.,Sylvester, K.G.,Jang, K.Y. American Association of Pathologists and Bacteriol 2016 The American journal of pathology Vol.186 No.12

<P>Recently, the roles of sirtuins (SIRTs) in tumorigenesis have been of interest to oncologists, and protein kinase CK2 alpha 1 (CSNK2A1) has been shown to be involved in tumorigenesis by phosphorylating various proteins, including SIRT1. Therefore, we evaluated the roles of CSNK2A1, SIRT6, and phosphorylated SIRT6 and their relationships in breast carcinoma. Nuclear expression of CSNK2A1 and SIRT6 predicted shorter overall survival and relapse-free survival by multivariate analysis. Inhibition of CSNK2A1 decreased the proliferative and invasive activity of cancer cells. In addition, CSNK2A1 was bound to SIRT6 and phosphorylated SIRT6; evidence for this is provided from immunofluorescence staining, co-immunoprecipitation of CSNK2A1 and SIRT6, a glutathione S-transferase pull-down assay, an in vitro kinase assay, and transfection of mutant CSNK2A1. Knockdown of SIRT6 decreased the proliferation and invasiveness of cancer cells. Overexpression of SIRT6 increased proliferation, but mutation at the Ser338 phosphorylation site of SIRT6 inhibited the proliferation of MCF7 cells. Moreover, both knockdown of SIRT6 and a mutation at the phosphorylation site of SIRT6 decreased expression of matrix metallopeptidase 9, beta-catenin, cyclin D1, and NF-kappa B. Especially, SIRT6 expression was associated with the nuclear localization of B-catenin. This study demonstrates that CSNK2A1 and SIRT6 are indicators of poor prognosis for breast carcinomas and that CSNK2A1-mediated phosphorylation of SIRT6 might be involved in the progression of breast carcinoma.</P>

In₂O₃:Sn/TiO₂/CdS heterojunction nanowire array photoanode in photoelectrochemical cells

Kim, J.S.,Han, H.S.,Shin, S.,Han, G.S.,Jung, H.S.,Hong, K.S.,Noh, J.H. Pergamon Press ; Elsevier Science Ltd 2014 International journal of hydrogen energy Vol.39 No.30

The design of photoanode with highly efficient light harvesting and charge collection properties is important in photoelectrochemical (PEC) cell performance for hydrogen production. Here, we report the hierarchical In<SUB>2</SUB>O<SUB>3</SUB>:Sn/TiO<SUB>2</SUB>/CdS heterojunction nanowire array photoanode (ITO/TiO<SUB>2</SUB>/CdS-nanowire array photoanode) as it provides a short travel distance for charge carrier and long light absorption pathway by scattering effect. In addition, optical properties and device performance of the ITO/TiO<SUB>2</SUB>/CdS-nanowire array photoanode were compared with the TiO<SUB>2</SUB> nanoparticle/CdS photoanode. The photocatalytic properties for water splitting were measured in the presence of sacrificial agent such as SO<SUB>3</SUB><SUP>2-</SUP> and S<SUP>2-</SUP> ions. Under illumination (AM 1.5G, 100 mW/cm<SUP>2</SUP>), ITO/TiO<SUB>2</SUB>/CdS-nanowire array photoanode exhibits a photocurrent density of 8.36 mA/cm<SUP>2</SUP> at 0 V versus Ag/AgCl, which is four times higher than the TiO<SUB>2</SUB> nanoparticle/CdS photoanode. The maximum applied bias photon-to-current efficiency for the ITO/TiO<SUB>2</SUB>/CdS-nanowire array and the TiO<SUB>2</SUB> nanoparticle/CdS photoanode were 3.33% and 2.09%, respectively. The improved light harvesting and the charge collection properties due to the increased light absorption pathway and reduced electron travel distance by ITO nanowire lead to enhancement of PEC performance.

Simultaneous subtyping and pathotyping of the novel reassortant influenza A (H5N8) virus from clinical samples using a diagnostic microarray

Kwon, J. H.,Kim, J. H.,Lee, D. h.,Cho, H.,Hwang, S. Y.,Yuk, S. S.,Erdene-Ochir, T. O.,Noh, J. Y.,Hong, W. T.,Jeong, J. H. Springer Science + Business Media 2016 BioChip Journal Vol.10 No.3

<P>Highly pathogenic avian influenza (HPAI) viruses cause economic losses in the poultry industry and pose a severe threat to human health. Rapid and accurate diagnostic methods are important because they can help prevent further spread of the virus and reduce the time required for eradication of the virus. We developed a low-density microarray for the rapid detection and identification of avian influenza virus subtypes H5, H7, and H9 and their pathotypes in a previous study. In the present study, we report the development of updated probe sets and evaluation of the diagnostic microarray using H5N8 clade 2.3.4.4 HPAI viruses including clinical samples, without the need for egg propagation. Cy3-labeled DNA targets were obtained by reverse transcription polymerase chain reaction using Cy3-labeled universal primers, and labeled amplicons were hybridized to the microarray. All positive samples from RT-PCR showed H5-specific and highly pathogenic pattern in the microarray, without purification of PCR products. Furthermore, it allowed for specific detection of the subtype and pathotype from low DNA concentration samples that did not allow direct sequence analysis. Therefore, this diagnostic microarray has enormous potential for the rapid subtyping and pathotyping from clinical samples without the need for culture.</P>