Programmed cell death ligand 1 alleviates psoriatic inflammation by suppressing IL-17A production from programmed cell death 1-high T cells

Kim, J.H.,Choi, Y.J.,Lee, B.H.,Song, M.Y.,Ban, C.Y.,Kim, J.,Park, J.,Kim, S.E.,Kim, T.G.,Park, S.H.,Kim, H.P.,Sung, Y.C.,Kim, S.C.,Shin, E.C. Mosby 2016 The journal of allergy and clinical immunology Vol.137 No.5

<P>Background: Psoriasis is one of the most common chronic inflammatory diseases of the skin. Recently, IL-17-producing T cells have been shown to play a critical role in psoriatic inflammation. Programmed cell death 1 (PD-1) is a coinhibitory receptor expressed on T cells in various chronic inflammatory diseases; however, the expression and function of PD-1 during psoriatic inflammation have not previously been characterized. Objective: We examined PD-1 expression on IL-17A-producing T cells from imiquimod-treated mice and patients with psoriasis. Additionally, we investigated the therapeutic effect of recombinant programmed cell death ligand 1 (PD-L1) protein on imiquimod-induced psoriatic inflammation. Methods: PD-1 expression on IL-17A-producing gamma delta T cells from imiquimod-treated mice was examined by means of multicolor flow cytometric analysis. In the psoriatic skin of patients, PD-1 and IL-17A expression was analyzed by using immunofluorescence. The therapeutic effect of PD-L1-Fc fusion protein (PD-L1-Fc) was assessed in imiquimod-treated mice ex vivo and in vivo. Results: During imiquimod-induced psoriatic inflammation, PD-1 is overexpressed on CD27(-)V gamma 1(-) gamma delta T cells. Furthermore, PD-1 expression on IL-17A(+) T cells was confirmed in psoriatic skin tissues from patients and imiquimod-treated mice. In the CD27(-)V gamma 1(-) gamma delta T-cell population, V gamma 4(-) gamma delta T cells with V gamma 6 mRNA expression showed a high level of PD-1 expression. Furthermore, these PD-1(hi)V gamma 4(-)(V gamma 6(+)) gamma delta Tcells were specialized for anti-CD3-induced IL-17A production, which was inhibited by PD-L1-Fc treatment. In imiquimod-treated mice PD-L1-Fc reduced psoriatic inflammation when given alone and enhanced the therapeutic effect of anti-p40 when given in combination. Conclusion: PD-1 is overexpressed in IL-17A-producing T cells in both imiquimod-treated mice and patients with psoriasis. Moreover, recombinant PD-L1-Fc alleviates psoriatic inflammation in imiquimod-treated mice.</P>

A Single-Flux-Quantum Shift Register based on High-$T_c$ Superconducting Step-edge Josephson Junctions

Sung G.Y.,Choi, C.H.,Suh J.D.,Han, S. K.,Kang, K.Y.,Hwang, J.S.,Yoon, S.G.,Jung, K.R.,Lee, Y.H.,Kang, J.H.,Kim, Y.H.,Hahn, T.S. The Korean Superconductivity Society 1999 Progress in superconductivity Vol.1 No.1

We have fabricated and tested a simple circuit of the rapid single-flux-quantum(RSFQ) four-stage shift register using a single layer high-$T_c$ superconducting (HTS) $YBa_2Cu_3O_{7-x}$ (YBCO) thin film structure with 9 step-edge Josephson junctions. The circuit includes two read superconducting quantum interference devices(SQUID) and four stages. To establish a robust HTS RSFQ device fabrication process, we have focussed on the reproducible process of sharp and straight step-edge formation as well as the ratio of film thickness to step height, t/h. The spread of step-edge junction parameters was measured from each 13 junctions with t/h=1/3, 1/2, and 2/3 at various temperatures. We have demonstrated the simplified operation of the shift register at 65 K.

Adenovirus-mediated gene transfer of interleukin-23 shows prophylactic but not therapeutic antitumor effects

Jin, H-T,Youn, J-I,Choi, S-Y,Seo, S-H,Park, S-H,Song, M-Y,Yang, S-H,Sung, Y-C Nature Publishing Group 2008 Cancer gene therapy Vol.15 No.11

A novel cytokine interleukin (IL)-23 bears a structural and functional resemblance to IL-12. A recombinant adenovirus expressing IL-23N220L (recombinant replication-defective adenovirus (rAd)/IL-23N220L) that selectively secrets IL-23 was constructed and compared with rAd/IL-12N220L in terms of immunological and antitumor effects. In a prophylactic setting, vaccination with rAd/ovalbumin (OVA) and rAd/IL-23N220L enhanced OVA-specific CD8<SUP>+</SUP> T-cell responses that were closely associated with complete protection against the subsequent challenge of OVA-expressing E.G7 thymoma. However, in a therapeutic setting, the intratumoral injection of rAd/IL-23N220L showed only marginal antitumor activity against several established tumors such as E.G7, CT26 and B16F10. Interestingly, whereas IL-23 still induced tumor-specific CD8<SUP>+</SUP> T-cell responses, it could not activate natural killer (NK) cells in vitro and in vivo. In addition, the adoptive transfer of activated NK cells partially restored the therapeutic antitumor effect of IL-23, indicating that NK cells are one of the crucial factors responsible for the regression of established tumors. Taken together, we demonstrated that adenovirus-mediated gene transfer of IL-23 induces a potent prophylactic, but not a therapeutic, antitumor effect.Cancer Gene Therapy (2008) 15, 693–702; doi:10.1038/cgt.2008.41; published online 4 July 2008

PHF2 histone demethylase acts as a tumor suppressor in association with p53 in cancer

Lee, K-H,Park, J-W,Sung, H-S,Choi, Y-J,Kim, W H,Lee, H S,Chung, H-J,Shin, H-W,Cho, C-H,Kim, T-Y,Li, S-H,Youn, H-D,Kim, S J,Chun, Y-S Macmillan Publishers Limited 2015 Oncogene Vol.34 No.22

Plant homeodomain finger 2 (PHF2) has a role in epigenetic regulation of gene expression by demethylating H3K9-Me2. Several genome-wide studies have demonstrated that the chromosomal region including the PHF2 gene is often deleted in some cancers including colorectal cancer, and this finding encouraged us to investigate the tumor suppressive role of PHF2. As p53 is a critical tumor suppressor in colon cancer, we tested the possibility that PHF2 is an epigenetic regulator of p53. PHF2 was associated with p53, and thereby, promoted p53-driven gene expression in cancer cells under genotoxic stress. PHF2 converted the chromatin that is favorable for transcription by demethylating the repressive H3K9-Me2 mark. In an HCT116 xenograft model, PHF2 was found to be required for the anticancer effects of oxaliplatin and doxorubicin. In PHF2-deficient xenografts, p53 expression was profoundly induced by both drugs, but its downstream product p21 was not, suggesting that p53 cannot be activated in the absence of PHF2. To find clinical evidence about the role of PHF2, we analyzed the expressions of PHF2, p53 and p21 in human colon cancer tissues and adjacent normal tissues from patients. PHF2 was downregulated in cancer tissues and PHF2 correlated with p21 in cancers expressing functional p53. Colon and stomach cancer tissue arrays showed a positive correlation between PHF2 and p21 expressions. Informatics analyses using the Oncomine database also supported our notion that PHF2 is downregulated in colon and stomach cancers. On the basis of these findings, we propose that PHF2 acts as a tumor suppressor in association with p53 in cancer development and ensures p53-mediated cell death in response to chemotherapy.

목초액 함유 활성탄의 첨가가 육계 생산성 및 계란 내 항생제 잔류에 미치는 영향

성은일,유선종,안병기,조태수,안병준,최돈하,강창원,Sung, E.I.,You, S.J.,Ahn, B.K.,Jo, T.S.,Ahn, B.J.,Choi, D.H.,Kang, C.W. 한국가금학회 2006 韓國家禽學會誌 Vol.33 No.4

본 연구의 목적은 목초액 함유 활성탄(activated charcoal mixed with wood vinegar, AC)의 급여가 육계의 생산성 및 산란계에서 혈중 및 계란내 항생제 수준에 미치는 영향을 규명하기 위하여 본 연구를 실시하였다. 실험 1은 450수의 1일령 육용종 Ross 수평아리를 공시하여 처리당 3반복 반복당 25수씩 완전임의 배치하고, 항생제 0%(T1), 항생제 0.1%(T2), AC 1%(T3), AC 1% + 항생제 0.1%(T4), AC 2% (T5), AC 2% + 항생제 0.1%(T6)를 함유하는 실험 사료를 각각 5주간 급여하였다. 사료 섭취량과 증체량은 주 단위로 조사하여 성장 성적에 미치는 영향을 평가하였다. 실험 5주차 종료시에 각 처리구별로 10수씩 선발하여 도살하였고, 간, 복강지방, 가슴육, 기타 기관의 상대적 중량을 측정함으로서 도체 특성을 조사하였다. 가식성 근육의 물리적 특성은 가열 감량, 전단력가, 보수력, 육색을 측정하였고, 육질의 관능적 특성은 연도, 맛, 풍미, 다즙성 등을 측정하였다. 장 내 균 총 변화에 미치는 영향에서 총 균수, 대장균 및 유산균수를 조사하였다. 실험 2는 40주령의 Hy-Line Brown 산란계 90수를 공시하여 항생제 0.5%에 AC 0%(C), AC 1.0%(T1), AC 2.0%(T2)를 함유하는 실험 사료를 각각 2주간 급여하였다. 종료 후 혈액 채취 및 계란을 수거하여 혈액 및 계란 내 항생제 잔류 수준을 측정하였다. 실험 1에서 사료 섭취량, 증체량 및 사료 요구율은 처리구간에 통계적으로 유의한 차이는 없었다. 대사 에너지, 조 단백질 및 기타 필수 영양소 수준을 고려하면 AC의 급여가 성장에 부정적인 영향은 없는 것으로 판단되었다. 간, 복강 지방, 가슴육, 기타 기관의 상대적 중량에서는 처리간에 통계적으로 유의한 차이는 인정되지 않았다. 보수력과 가열감량 항목에서는 처리간에 큰 차이가 없었으나, 전단력가는 대조구에 비해 AC 첨가구에서 유의하게 높아지는(P<0.05) 경향을 나타내었다. 대조구에 비해 실험구에서 적색도는 낮아지는 경향을, 황색도는 증가하는 경향을 나타내었다. 풍미, 연도, 다즙성 및 총체적 선호도 항목 모두 처리간에 유의한 차이는 인정되지 않았다. 장 내 총균수, coli form 및 lactic acid bacteria 수는 항생제를 첨가한 (+) 대조구와 AC를 첨가한 처리구가 항생제를 첨가하지 않은 (-) 대조구에 비해 유의하게 낮은 수준이거나(P<0.05), 낮은 경향을 보였다. 실험 2에서는 AC 급여에 의해 혈청 및 계란 내 항생제 잔류량이 유의하게 감소하는 결과가 관찰되었다(P<0.05). 특히 AC급여 수준이 증가함에 따라 계란 내 항생제 잔류량은 유의하게 감소하였다. 본 연구에서는 육계 사료 내 AC의 첨가 급여가 생산된 계육의 외관적 특성을 개선시키는 효과가 시사되었고, 장내 총균수, 대장균 및 유산균수를 감소시키는 시키는 결과를 보였다. 산란계 사료 내 AC의 첨가 급여가 혈청 및 계란 내 항생제 잔류를 감소시키는 결과를 나타내었다. Two experiments were conducted to investigate the effects of dietary activated charcoal mixed with wood vinegar (AC) on broiler performance and antibiotics residue in eggs. In experiment 1, a total of low hundred fifty, 1-day-old male broile. chicks (Ross) were divided into 6 groups, consisting 3 replicates of 25 birds each, and 134 one of the six experimental diets: devoid of AC and antibiotics (negative control), devoid of AC with 0.1% antibiotics (positive control), devoid of antibiotics with 1% AC, with 0.1% antibiotics and 1% AC, devoid of antibiotics with 2% AC, with 0.1% antibiotics and 2% AC, for 5 wks. Feed consumption and body weights were measured weekly. At the end of the experiment, eight birds from each group were selected and sacrificed. The relative weight of organs and characteristics of breast muscle were investigated. There were no significant differences in feed intake, body weight gain and feed conversion rate among the treatments. There were also no significant differences in the relative weight of breast meat, leg and liver. The abdominal fat tended to be decreased by the dietary AC. Significant differences were shown (P<0.05) in meat redness (a) and yellowness (b) among the treatments. However, the sensual characteristics of breast muscle was not affected by the dietary treatments. There were significant differences in total microbes, Coli forms and lactic acid bacteria (P<0.05) among the treatments. In experiment 2, a total of ninety, 40-wk-old Hy-line Brown laying hens were divided into 3 groups, consisting 3 replicates of 10 birds each and fed medicated control diet devoid of AC or diets containing 1% AC and 2% AC for 2 wks. The residue of antibiotics in Plasma and egg Yolk were significantly decreased (P<0.05) in 2% AC group compared to that of control. This study suggest that dietary AC may improve the external quality of edible meat and reduced antibiotics residue in chicken eggs without affecting laying performance.

Temperature and magnetic field dependent optical properties of superconducting $MgB_2$ thin film

정종훈,이해자,김경완,김명훈,노태원,강원남,정창욱,이성익,Jung, J. H.,Lee, H. J.,Kim, K. W.,Kim, M. W.,Noh, T. W.,Wang, Y. J.,Kang, W. N.,Jung, C. U.,Lee, Sung-Ik 한국초전도학회 2001 Progress in superconductivity Vol.3 No.1

We investigated the temperature and magnetic field dependent optical properties of a$ MgB_2$ thin film in the far-infrared region. In the superconducting state, i.e. 5 K, we obtained the values of superconducting gap $2\Delta$ ~ 5.2 meV and $2\Delta$ $_{k}$ $B/T_{c}$ ~1.8. Although the value of$ 2\Delta$</TEX$B/T_{c}$ was nearly half of the BCS value, the $2\Delta$ seemed to follow the temperature dependence of the BCS formula. Under the magnetic field (H), the superconducting state became suppressed. Interestingly, we found that the normal state area fraction abruptly increased at low field but slowly increased at high field. It did not follow the H-dependences predicted for a s-wave superconductor (i.e. a linear dependence) nor for a s-wave one (i.e. $H^{1}$2/ dependence). We discussed the complex gap nature of $MgB_2$ in comparison with two gap and anisotropic s-wave scenarios.ios.

Mucosally administered Lactobacillus surface-displayed influenza antigens (sM2 and HA2) with cholera toxin subunit A1 (CTA1) Induce broadly protective immune responses against divergent influenza subtypes

Li, R.,Chowdhury, M.Y.E.,Kim, J.H.,Kim, T.H.,Pathinayake, P.,Koo, W.S.,Park, M.E.,Yoon, J.E.,Roh, J.B.,Hong, S.P.,Sung, M.H.,Lee, J.S.,Kim, C.J. Elsevier Scientific Pub. Co 2015 Veterinary microbiology Vol.179 No.3

The development of a universal influenza vaccine that provides broad cross protection against existing and unforeseen influenza viruses is a critical challenge. In this study, we constructed and expressed conserved sM2 and HA2 influenza antigens with cholera toxin subunit A1 (CTA1) on the surface of Lactobacillus casei (pgsA-CTA1sM2HA2/L. casei). Oral and nasal administrations of recombinant L. casei into mice resulted in high levels of serum immunoglobulin G (IgG) and their isotypes (IgG1 & IgG2a) as well as mucosal IgA. The mucosal administration of pgsA-CTA1sM2HA2/L. casei may also significantly increase the levels of sM2- or HA2-specific cell-mediated immunity because increased release of both IFN-γ and IL-4 was observed. The recombinant pgsA-CTA1sM2HA2/L. casei provided better protection of BALB/c mice against 10 times the 50% mouse lethal doses (MLD<SUB>50</SUB>) of homologous A/EM/Korea/W149/06(H5N1) or A/Aquatic bird/Korea/W8½005 (H5N2) and heterologous A/Puerto Rico/8/34(H1N1), or A/Chicken/Korea/116/2004(H9N2) or A/Philippines/2/08(H3N2) viruses, compared with L. casei harboring sM2HA2 and also the protection was maintained up to seven months after administration. These results indicate that recombinant L. casei expressing the highly conserved sM2, HA2 of influenza and CTA1 as a mucosal adjuvant could be a potential mucosal vaccine candidate or tool to protect against divergent influenza viruses for human and animal.

Roles of AKT1 and AKT2 in non-small cell lung cancer cell survival, growth, and migration.

Lee, Myoung W,Kim, Dae S,Lee, Joo H,Lee, Bum S,Lee, Soo H,Jung, Hye L,Sung, Ki W,Kim, Heung T,Yoo, Keon H,Koo, Hong H Japanese Cancer Association 2011 Cancer Science Vol.102 No.10

<P>Although AKT ? protein kinase B is constitutively active in nonsmall cell lung cancer (NSCLC) cells and is an attractive target for enhancing the cytotoxicity of therapeutic agents, the distinct roles of the AKT isoforms in NSCLC are largely unknown. In the present study, we investigated the roles of AKT1 and AKT2 in NSCLC cells using RNAi. The siRNA targeting of AKT1 or AKT2 effectively decreased protein levels of AKT1 and AKT2, respectively, in A549 and H460 cells. Cisplatin treatment of these cells increased apoptotic cell death compared with control. The siRNA-induced knockdown of AKT1 in H460 cells significantly decreased basal MEK? ERK1 ? 2 activity, resulting in nuclear factor-κB activation, whereas knockdown of AKT2 resulted in anti-apoptotic Bcl-2 family protein MCL-1 (MCL-1) cleavage, the collapse of mitochondrial membrane potential, cytochrome c release, and activation of the caspase cascade. Consequently, both siRNA treatments enhanced the chemosensitivity of H460 cells to cisplatin. However, neither AKT1 nor AKT2 siRNA treatment had any effect of p27 expression, and although both treatments tended to induced G2 ?M phase arrest, the effect was not statistically significant. Treatment with AKT1 siRNA markedly decreased colony formation growth and migration, but AKT2 siRNA had no significant effects on these parameters. These data suggest that AKT1 and AKT2 both contribute to cell survival, albeit via different mechanisms, and that the effects on cell growth and migration are predominantly regulated by AKT1. These findings may aid in refining targeted strategies for the inhibition of AKT isoforms towards the sensitization of NSCLC cells to therapeutic agents.</P>

톱밥 발효사료 및 분말어유의 첨가사료가 돈육의 선도에 미치는 영향

이정일,정명섭,박구부,박범영,박태선,황보종,김진형,성필남 한국축산학회 1998 한국축산학회지 Vol.40 No.1

This study was conducted to investigate the influence feeding fermented sawdust and powdered sardin oil on meat quality of pork. The pigs were randomly assigned to one of four treatments: a), control (normal feed); b), T1 (normal feed and fermented sawdust 30%); c), T2 (normal feed and sardin powder oil 10%); d), T3 (normal feed, fermented sawdust 30%, sardin powder oil 10% and limited amino acid 30%) from live weight 30 ㎏ to 110 ㎏ and slaughtered. The samples were stored at 0 ± 1℃. The shelf life was determined for on the days of 2, 4, 6, 8 and 15. The results obtained were summarized as follows: The thiobarbituric acid reaction substance(TBARS) values of all the treatments were increased with the storage periods (P$lt;0.05). T1 had lower TBARS value than the other treatments until the 8th day, there were no significant differences among treatments at the 15th day. There were no significant differences among volatile basic nitrogen (VBN) of the treatments with the storage periods. The peroxide value of all the treatments was decreased with days of the storage (P$lt;0.05), but was increased again after 8th day. That of T1 was significantly lower than that of others at the 15th day. The TBARS of all the treatments increased with days of the storage(P$lt;0.05), and they were not significantly different each others. There were no significant differences among VBN of treatments with the storage periods. The peroxide values of all the treatments were decreased with the storage periods(P$lt;0.05), but was increased again after 8th day. That of T1 was significantly lower than those of the others at the 15th day.

熱分解된 Polyacrylonitrile의 電氣的 性質

成墉吉,李延煥,李載珍,李丁桂,洪致裕,姜泰遠 동국대학교 자연과학연구소 1984 자연과학연구 논문집 Vol.4 No.-

질소 분위기 하에서 200ㄹ7로 열처리한 PAN 膜을 10³V/cm~10⁴V/cm의 電氣場을 걸어 分極시킨 후 溫度變化에 따른 TSD 電流를 測定하였다. 이 같이 分極된 PAN의 TSD spectrum은 nitrile side group의 방향의 弛緩에 관계되는 한개 또는 두개의 peak를 나타냈으며, 이것으로부터 5×10³V/cm의 電氣場에서 分極시킨 PAN膜의 trap energy level은 0.545 eV이었다. The electric behavior of the polyacrylonitrile(PAN) pyrolyzed at 200℃ in the N₂gas is investigated through the formation fo electrically polarized films. The formation fo the films is achieved by applying electric fields of the order 10³-10⁴V/cm to the prepared PAN specimens at the tmeperature ranging from 100℃ to 200℃. The TSD spectrum of PAN reveals one or twonpeaks, which might to related to the relaxation of oriented nitrile side group. This suggests that nitrile orientation with an applied electric field results in the formation of a highly developed level of intermolecular bonding. The polarized PAN film by the field of 5×10³V/cm at 200℃ also shows the trap level of 0.545 eV above the valence band.