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.

Cryopreservation induces macrophage colony stimulating factor from human periodontal ligament cells in vitro

Rhim, E.M.,Ahn, S.J.,Kim, J.Y.,Chang, Y.R.,Kim, K.H.,Lee, H.W.,Jung, S.H.,Kim, E.C.,Park, S.H. Academic Press 2013 Cryobiology Vol.67 No.2

Cryopreservation is used to protect vital periodontal ligaments during the transplantation of teeth. We investigated which gene products implicated in root resorption are upregulated in human periodontal ligament cells by cryopreservation, and whether cryopreservation affects the expression of macrophage-colony stimulating factor (M-CSF) in human periodontal ligament cells. We used customized microarrays to compare gene expression in human periodontal ligament cells cultured from teeth immediately after extraction and from cryopreserved teeth. Based on the result of these assays, we examined M-CSF expression in periodontal ligament cells from the immediately extracted tooth and cryopreserved teeth by real-time PCR, enzyme-linked immunosorbent assay (ELISA), Western blot analysis, and immunofluorescence. We also investigated whether human bone marrow cells differentiate into tartrate-resistant acid phosphatase (TRAP) positive osteoclasts when stimulated with RANKL (Receptor Activator for Nuclear Factor κ B Ligand) together with any secreted M-CSF present in the supernatants of the periodontal ligament cells cultured from the various groups of teeth. M-CSF was twofold higher in the periodontal ligament cells from the rapid freezing teeth than in those from the immediately extracted group (p<0.05). Cryopreservation increased M-CSF expression in the periodontal ligament cells when analyzed by real time PCR, ELISA, Western blotting, and immunofluorescence (p<0.05). TRAP positive osteoclasts were formed in response to RANKL and the secreted M-CSF present in the supernatants of all the experimental groups except negative control. These results demonstrate that cryopreservation promotes the production of M-CSF, which plays an important role in root resorption by periodontal ligament cells.

Additional effects of bisphenol A and paraben on the induction of calbindin-D(9K) and progesterone receptor via an estrogen receptor pathway in rat pituitary GH3 cells.

Kim, S M,Jung, E M,An, B S,Hwang, I,Vo, T T,Kim, S R,Lee, S M,Choi, K C,Jeung, E B The Society 2012 Journal of physiology and pharmacology Vol.63 No.5

<P>There are concerns about the combined estrogenic effects of chemicals since mixtures of these chemicals exist in our environment. This study investigated potential additional interactions between bisphenol A (BPA) and isobutylparaben (IBP), which are major xenoestrogens used in the manufacture of plastics, cosmetics, drugs, and other products. The combined effects of these two chemicals were analyzed by measuring the expression of calbindin-D(9k) (CaBP-9k) in rat pituitary cancer GH3 cells. GH3 cells were treated with single and combination doses of both chemicals (BPA single doses: 10(-7), 10(-6) and 10(-5) M; IBP single doses: 10(-7), 10(-6) and 10(-5) M, and each of the BPA and IBP doses combined). Prior to treatment, cells were temporarily transfected with a plasmid containing an ERE-luciferase reporter gene. Luciferase activity was measured as an indicator of ER activation by 17β-estradiol (E2), BPA, and IBP. BPA (10(-5) M) combined with IBP (10(-7) M and 10(-6) M) induced a significant increase in the luciferase activity. Twenty-four hours after treatment, dose-dependent effects were observed in both single and combined dose groups, and several combination doses induced significant increases in the expression of CaBP-9k and progesterone receptor (PR) at both transcriptional and translational levels. Pre-treatment with ICI 182,780, a pure estrogen antagonist, significantly reversed BPA- and IBP-induced CaBP-9k and PR upregulation in GH3 cells. Taken together, these results indicate that BPA and IBP may have additionally increased estrogenic potency via an estrogen receptor-mediated pathway.</P>

Electronic Band Structure and Photocatalytic Activity of M-Doped TiO2(M=Co and Fe)

M. G. Ha,H. G. Kim,B. H. Shon,E. D. Jeong,박혁규,J. H. Jung,이재성,M. S. Won,S. W. Bae 한국물리학회 2006 THE JOURNAL OF THE KOREAN PHYSICAL SOCIETY Vol.49 No.III

Cobalt- or iron-doped TiO2 nanocrystals were fabricated by the hydrothermal synthesis method. The electronic structure and optical properties of the materials were studied by using XRD, UVDRS, and the FP-LAPW (Full-Potential Linearized Augmented Plane Wave) method. The bandgap energy of Co- and Fe-doped TiO2 obtained by FP-LAPW and UV-DRS was ca. 2.6 and 2.5 eV, respectively. These doped materials absorbed visible light and exhibited photocatalytic activity for oxidative decomposition of CH3Cl to CO2 under visible light irradiation ( > 420 nm). However, only Fe-doped TiO2 showed the activity for CH3Cl degradation to CO2, probably due to its higher oxidation potential, as the FP-LAPW calculation indicated.

Rotational viscosity calculation method for liquid crystal mixture using molecular dynamics

Kim, J.S.,Jamil, M.,Jung, J.E.,Jang, J.E.,Lee, J.W.,Ahmad, F.,Woo, M.K.,Kwak, J.Y.,Jeon, Y.J. The Korean Infomation Display Society 2011 Journal of information display Vol.12 No.3

This paper presents the directly obtained rotational viscosity values of E7, which includes pentylcyanobiphenol, heptylcyanobiphenol, 4-cyano-4'-n-octyloxy-1,1'-biphenyl, and 4-cyano-4"-n-pentyl-1,1',1"-terphenyl, at various tempe using molecular dynamics computer simulation. The director mean squared displacement was achieved from the squared displacement of the mean director using the concept of the mean director of various nematic liquid crystals. The calculated values were compared with the experiment results that predicted a good agreement. Additional points that must be considered for further study are also discussed.

Quantitative Determination of Cyclosporine in Human Whole Blood by Ultra-Performance Liquid Chromatography with Triple Quadrupole Tandem Mass Spectrometry

Jung, H.J.,Gwon, M.-R.,Park, J.,Seo, J.J.,Seong, S.J.,Kim, E.H.,Suh, S.R.,Jeong, J.Y.,Lee, H.W.,Yoon, Y.-R. Japan Society for Analytical Chemistry 2014 Analytical sciences Vol.30 No.2

Cyclosporine is an immunosuppressant drug used in organ transplants or for the treatment of autoimmune diseases. We developed and validated a simple, sensitive, and specific method using UPLC-MS/MS to determine cyclosporine levels in human whole blood. MS/MS detection was performed in the positive electrospray ionization mode with multiple reaction monitoring. Cyclosporine was extracted from whole-blood samples using ascomycin as an internal standard. The mass transitions m/z 1203.49 -> 1185.53 and m/z 814.71 -> 796.67 were used to assay the analyte and IS. This method was validated with respect to linearity, specificity, accuracy, precision, recovery, and stability. The method exhibited a linear response from 10 to 1000 ng mL(-1) with correlation coefficient values >0.99. The precision and the accuracy values were within 15%, except at the lower limit of quatification (LLOQ). Cyclosporine was stable in whole blood with no evidence of degradation. This method was successfully applied to a pharmacokinetic study of cyclosporine in healthy volunteers following oral administration.

A clinical drug library screen identifies clobetasol propionate as an NRF2 inhibitor with potential therapeutic efficacy in KEAP1 mutant lung cancer

Choi, E-J,Jung, B-J,Lee, S-H,Yoo, H-S,Shin, E-A,Ko, H-J,Chang, S,Kim, S-Y,Jeon, S-M Macmillan Publishers Limited, part of Springer Nat 2017 Oncogene Vol.36 No.37

<P>The Kelch-like ECH-associated protein 1 (KEAP1)-nuclear factor E2-related factor 2 (NRF2) pathway has a central role in cellular antioxidant defense. NRF2 activation due to KEAP1 or NRF2 mutations occurs frequently in many cancers, suggesting that NRF2 inhibition could be a promising therapeutic strategy. However, no potent NRF2 inhibitors are clinically available to date. To develop potent NRF2 inhibitors for therapeutic purpose, we screened similar to 4000 clinical compounds and determined clobetasol propionate (CP) as the most potent NRF2 inhibitor. Mechanistically, CP prevented nuclear accumulation and promoted beta-TrCP-dependent degradation of NRF2 in a glucocorticoid receptor-and a glycogen synthase kinase 3 (GSK3)-dependent manner. As a result, CP induced oxidative stress and strongly suppressed the anchorage-independent growth of tumors with KEAP1 mutation, but not with the wild-type KEAP1. Further, CP alone or in combination with rapamycin strongly inhibited the in vitro and in vivo growth of tumors harboring mutations in KEAP1 or both KEAP1 and LKB1 that are frequently observed in lung cancer. Thus, CP could be a repurposed therapeutic agent for cancers with high NRF2 activity. We also proposed that the use CP and rapamycin in combination could be a potential therapeutic strategy for tumors harboring both KEAP1 and LKB1 mutations.</P>

Sorptive removal of selected emerging contaminants using biochar in aqueous solution

Kim, E.,Jung, C.,Han, J.,Her, N.,Park, C.M.,Jang, M.,Son, A.,Yoon, Y. Korean Society of Industrial and Engineering Chemi 2016 Journal of industrial and engineering chemistry Vol.36 No.-

<P>The adsorption of sunscreen compounds (benzophene [BZP] and benzotriazole [BZT]) and widely known endocrine-disrupting compounds (bisphenol A [BPA] and 17 p-estradiol [E2]) was investigated using commercially available powdered activated carbon (PAC) and activated biochar produced in the laboratory. The removal efficiency by biochar was approximately 5-30% higher than that by PAC depending on experimental conditions, presumably due to the higher surface area and pore volume of biochar. The removal of compounds followed the order E2 > BZP > BPA > BZT: K-f (mu g/g)/(mg/L)(1/n), Freundlich affinity coefficients, were as follows - 19.7, 19.7, 6.57, and 4.56 for PAC, and 30.2, 28.4, 9.22, and 6.79 for biochar. An increase in pH from 3.5 to 10.5 decreased the adsorption of BZP, BZT, BPZ, and E2 by 11.5, 11.4, 10.7, and 4.7% by biochar, respectively. Overall, biochar had a higher adsorption capacity for all chemicals tested compared with PAC. (C) 2016 The Korean Society of Industrial and Engineering Chemistry. Published by Elsevier B.V. All rights reserved.</P>

Efficient proteolytic cleavage by insertion of oligopeptide linkers and its application to production of recombinant human interleukin-6 in Escherichia coli

Lee, E.G.,Baek, J.E.,Lee, S.H.,Kim, T.W.,Choi, J.H.,Rho, M.C.,Ahn, J.O.,Lee, H.W.,Jung, J.K. IPC Science and Technology Press ; Elsevier Scienc 2009 Enzyme and microbial technology Vol.44 No.5

Efficient expression and purification of bioactive recombinant human interleukin-6 (hIL6) was successfully achieved in Escherichia coli (E. coli) by fusion of the maltose-binding protein (MBP) with hIL6 and the insertion of oligopeptide linkers. MBP/hIL6 was over-expressed in the soluble form at a concentration of approximately 2.5g/L. For hIL6 recovery, enterokinase, factor Xa, and thrombin were employed to cleavage MBP from the fusion constructs. However, undesired and non-specific cleavage fragments as well as rhIL6 were obtained following the cleavage. The introduction of oligopeptide linkers at the C-terminal end of the fusion construct could improve the efficiency and the rate of the enzymatic cleavage reaction, and the rhIL6 purification was achieved by using MBP affinity chromatography, factor Xa cleavage, and reverse-phase chromatography, resulting in an overall yield as high as 33% (equivalent to 0.27ghIL6/L) at purity over 98%. The biological activity of the purified recombinant hIL6 was demonstrated by confirming the presence of the signal transducer and activator of transcription 3 (STAT3) signaling pathway. This study suggests that the optimized peptide linker specifically designed for both fusion partner and target molecule has a great potential for efficient recombinant protein production.

Removal of iopromide and degradation characteristics in electron beam irradiation process

Kwon, M.,Yoon, Y.,Cho, E.,Jung, Y.,Lee, B.C.,Paeng, K.J.,Kang, J.W. Elsevier Scientific Pub. Co 2012 Journal of hazardous materials Vol.227 No.-

The aim of this study is to evaluate the removal efficiency of iopromide using electron beam (E-beam) irradiation technology, and its degradation characteristics with hydroxyl radical (OH?) and hydrated electron (e<SUB>aq</SUB><SUP>-</SUP>). Studies are conducted with different initial concentrations of iopromide in pure water and in the presence of hydrogen peroxide, bicarbonate ion, or sulfite ion. E-beam absorbed dose of 19.6kGy was required to achieve 90% degradation of 100μM iopromide and the E-beam/H<SUB>2</SUB>O<SUB>2</SUB> system increased the removal efficiency by an amount of OH? generation. In the presence of OH? scavengers (10mM sulfite ion), the required dose for 90% removal of 100μM iopromide was only 0.9kGy. This greatly enhanced removal was achieved in the presence of OH? scavengers, which was rather unexpected and unlike the results obtained from most advanced oxidation process (AOP) experiments. The reasons for this enhancement can be explained by a kinetic study using the bimolecular rate constants of each reaction species. To explore the reaction scheme of iopromide with OH? or e<SUB>aq</SUB><SUP>-</SUP> and the percent of mineralization for the two reaction paths, the total organic carbon (TOC), released iodide, and intermediates were analyzed.