Activated T Cells Secrete an Alternatively Spliced Form of Common γ-Chain that Inhibits Cytokine Signaling and Exacerbates Inflammation

Hong, C.,Luckey, Megan A.,Ligons, Davinna L.,Waickman, Adam T.,Park, J.Y.,Kim, Grace Y.,Keller, Hilary R.,Etzensperger, R.,Tai, X.,Lazarevic, V.,Feigenbaum, L.,Catalfamo, M.,Walsh, Scott T.R.,Park, J. Cell Press 2014 Immunity Vol.40 No.6

The common γ-chain (γc) plays a central role in signaling by IL-2 and other γc-dependent cytokines. Here we report that activated T cells produce an alternatively spliced form of γc mRNA that results in protein expression and secretion of the γc extracellular domain. The soluble form of γc (sγc) is present in serum and directly binds to IL-2Rβ and IL-7Rα proteins on T cells to inhibit cytokine signaling and promote inflammation. sγc suppressed IL-7 signaling to impair naive T cell survival during homeostasis and exacerbated Th17-cell-mediated inflammation by inhibiting IL-2 signaling upon T cell activation. Reciprocally, the severity of Th17-cell-mediated inflammatory diseases was markedly diminished in mice lacking sγc. Thus, sγc expression is a naturally occurring immunomodulator that regulates γc cytokine signaling and controls T cell activation and differentiation.

Korean Byungkyul - Citrus platymamma Hort.et Tanaka flavonoids induces cell cycle arrest and apoptosis, regulating MMP protein expression in Hep3B hepatocellular carcinoma cells

Hong, G. E.,Lee, H. J.,Kim, J. A.,Yumnam, S.,Raha, S.,Saralamma, V. Venkatarame Gowda,Heo, J. D.,Lee, S. J.,Kim, E. H.,Won, C. K. Lychnia 2017 International journal of oncology Vol.50 No.2

<P>Citrus platymamma Hort.et Tanaka is an indigenous fruit of Jeju island in Korea. In this study the bioactivity of C. platymamma flavonoids were evaluated on human hepatoma Hep3B cell lines. Eleven flavonoids were identified from the peels of C. platymamma Hort.et Tanaka through high-performance liquid chromatography-Tandem mass spectrometry and the anticancer effect of these C. platymamma flavonoids on human hepatoma Hep3B were studied. Chromatin condensation was observed in Hep3B cells treated with C. platymamma flavonoids. DNA fragmentation was confirmed through agarose gel electrophoresis and TUNEL assay. An increase in the total apoptotic cells and G2/M cell cycle arrest with decreased protein expression of CDC25C, CDK1, cycl in B1 and p21 were observed in Hep3B cells treated with flavonoids of C. platymamma. Further, protein expression of Bcl-XL, Bax, caspase-3 and -9 were also modulated by C. platymamma flavonoids treatment indicating that cell death is through intrinsic apoptotic pathway. Moreover, C. platymamma flavonoids also regulated the phosphorylation of MAPKs, PI3K, and Akt in Hep3B cells. Relevant to inhibiting metastasis, C. platymamma treatment reduced wound closure of Hep3B cells and the protein expression of matrix metalloproteinase-2 and -9 were reduced in C. platymamma treated cells. The results show that C. platymamma flavonoids induce cell cycle arrest and apoptosis following activation of MAPKs and suppression of PI3K/Akt pathway which eventually inhibits cell migration in Hep3B cells. The finding provides evidence on biochemical activities of C. platymamma Hort.et Tanaka, which would be an essential agent for hepatocellular carcinoma (HCC) treatment.</P>

Holocene environmental change at the southern coast of Korea based on organic carbon isotope (δ¹³C) and C/S ratios

Lim, J.,Lee, J.Y.,Kim, J.C.,Hong, S.S.,Yang, D.Y. Pergamon Press 2015 QUATERNARY INTERNATIONAL Vol.384 No.-

<P>To trace the environmental change that occurred at a coastal area during the Holocene, we performed radiocarbon dating and geochemical analyses using sedimentary cores recovered from the Beolgyo tidal flats on the south coast of Korea. The delta C-13 values of total organic carbon (TOC), which represent relative inputs of terrestrial (or freshwater) and marine organic sources, revealed a long-term increasing trend from -27.5 to -21.7 parts per thousand during the period between 10,000 and 3000 cal BP, suggesting an evolutionary series of fluvial-dominant to marine-dominant environments, coupled with weakened summer monsoon intensity. From 3000 cal BP to the present, the delta C-13(TOC) decreased gradually from -21.7 to -24 parts per thousand, indicating enhancement of freshwater input during this time. The observed long-term environmental change was divided into six stages based on the averages of the total sulfur content (TS%) and the organic carbon to sulfur ratio (C/S), proxies for paleosalinity. On multi-centennial to millennial timescales, higher C/S ratios and lower TS% were linked to higher delta C-13(TOC) values, indicating strong freshwater input at Stage 2 (similar to 8300-7400 cal BP), Stage 4 (similar to 4500-3300 cal BP), and Stage 6 (similar to 1100 cal BP to present). Strong freshwater discharge events synchronously occurred at 4300 cal BP and 3600 cal BP along the south coast of Korea. Further testing should be carried out in other East Asian coastal areas. This study suggests that sedimentary delta C-13(TOC) values and C/S ratios can be used in Asian coastal regions to trace past freshwater input events and summer monsoon intensity during relatively stable sea level periods (e.g., the middle to late Holocene). (C) 2015 Elsevier Ltd and INQUA. All rights reserved.</P>

산란계 사료내 CLA 함유 Oil (CLAzen 80) 첨가가 난황내 지방산 조성에 미치는 영향

황보종,장종수,정일병,이병석,김동운,조성백,김희도,배해득,손진혁,홍의철,최낙진,Hwangbo J.,Chang J. S.,Chung I. B.,Lee B. S.,Kim D. U.,Cho S. B.,Kim H. D.,Bae H. D.,Son J. H.,Hong U. C.,Choi N. J. 한국가금학회 2005 韓國家禽學會誌 Vol.32 No.1

본 연구는 oil 형태의 conjugated linoleic acid(CLAzen 80)를 산란계 사료에 수준별로 첨가 급여하였을 때 산란율과 난황내 지방산 조성의 변화를 조사하기 위하여 수행하였다. 59주령의 산란계 72수를 완전임의배치법으로 4개 처리구에 6주간 공시하였다. 처리구는 CLAzen 80를 첨가하지 않은 대조구와 각각 1, 2 및 $3\%$를 첨가구를 두었다. 연구 결과를 살펴보면 산란율은 처리구별 통계적 유의차가 없었지만, 난황내 지방산 조성은 CLAzen 80 첨가에 의하게 크게 영향을 받았다. 난황내 C16:0과 C18:0과 같은 포화 지방산 함량은 CLAzen 80 첨가에 의하여 증가하였으나, 일가불포화지방산인 C18:1 함량은 오히려 감소하였다. 한편, 난황내 C18:2와 C18:3와 같은 다가불포화지방산은 CLAzen 80 급여 2$\~$4주사이에는 모든처리구들에 있어서 그 함량이 일정하게 유지되었다. 그러나, 대조구와 비교하여 CLAzen 80 급여 6주 째에는 난황내 C18:2 함량이 감소하였다. 불포화지방산:포화지방산 비율과 n-6:n-3 불포화지방산 비율은 2$\~$4주 사이에는 처리구별간에 통계적 유의차가 없었고, 6주째 불포화지방산:포화지방산 비율이 CLAzen 80 첨가에 의하여 감소하였다. 한편, 난황내 CLA 함량은 CLAzen 80 첨가수준에 비례하여 증가하였다. 따라서, 산란계 사료 내 CLAzen 80 첨가는 난황내 CLA 함량을 증진시키는 것으로 요약할 수 있다. The objectives of the present study were to investigate the effects of varying levels of dietary oil containing conjugated linoleic acid (CLA) on the egg production and fatty acid composition of egg yolk. Seventy-two 59-wk-old ISA Brown laying hens were randomly allotted to four dietary treatments, each consisting of three replicates with six birds per replicate. There were four treatments that consist of diets containing 0, 1, 2, or $3\%$ commercial CLA-containing oil. Egg production was not significantly different among the dietary treatments at 0, 2, 4, and 6 week. The proportion of saturated fatty acids such as C16:0 and C18:0 in egg yolk were increased, but that of monounsaturated fatty acid C18:1 was decreased by feeding CLA-containing oil supplementation. However, the proportion of polyunsaturated fatty acids such as C18:2 and C18:3 in egg yolk were not different among dietary treatments at 2 and 4 wk of the experiment. At 6 week, the proportion of C18:2 in egg yolk was decreased by feeding CLA-containing oil compared with the control. Polyunsaturated fatty acid:saturated fatty acid (P:S) ratio and n-6:n-3 polyunsaturated fatty acid ratio were similar across the treatments between 2 and 4 week. The P:S ratio was decreased by dietary CLA-containing oil supplementation at 6 week. The proportion of CLA in egg yolk was linearly increased with increasing levels of CLA-containing oil supplementation. In conclusion, dietary supplementation of CLA-containing oil to laying hens increased beneficially increased CLA content in their egg yolk.

The C₃H-type zinc finger protein GDS1/C3H42 is a nuclear-speckle-localized protein that is essential for normal growth and development in Arabidopsis

Kim, D.W.,Jeon, S.J.,Hwang, S.M.,Hong, J.C.,Bahk, J.D. Elsevier Scientific Publishers Ireland Ltd 2016 Plant science Vol.250 No.-

<P>Eukaryotic C3H-type zinc finger proteins (Znfs) comprise a large family of regulatory proteins involved in many aspects of plant stress response, growth and development. However, compared to mammalian, only a few plant Znfs have been functionally characterized. Here, T-DNA inserted gdsl (growth, development and splicing 1) mutant, displayed abnormal growth throughout the lifecycle owing to the reduction of cell size and number. Inverse PCR analysis revealed that the abnormal growth was caused by the disruption of At3g47120, which encodes a C3H42 protein belonging to the C-X-7-C-X-5-C-X-3-H class of the Znf family. GDS1 was ubiquitously transcribed, but shows high levels of expression in young seedling and unexpanded new leaves. In gdsl, the transcripts of many growth- and development-related genes were down-regulated, and the auxin response was dramatically reduced. A fluorescence-based assay revealed that the GDS1 protein was localized to the nucleus, prominently in the speckle compartments. Its arginine/serine dipeptide-rich-like (RS-like) domain was essential for nuclear localization. In addition, the SRI, SRm102 and U1-70K components of the U1 spliceosome interacted with GDS1 in the nuclear speckle compartments. Taken together, these suggest that GDS1, a nuclear-speckle-associated Znf, might play a significant role in splicing during plant growth and development. (C) 2016 Elsevier Ireland Ltd. All rights reserved.</P>

Relationship between environmental change on Geoje Island, southern coast of Korea, and regional monsoon and temperature changes during the late Holocene

Lim, J.,Lee, J.Y.,Kim, J.C.,Hong, S.S.,Yang, D.Y. Pergamon Press 2014 QUATERNARY INTERNATIONAL Vol.344 No.-

To reconstruct environmental change during the late Holocene, we investigated sedimentary δ<SUP>13</SUP>C values from an exposed section on Geoje Island, on the southern coast of Korea. The δ<SUP>13</SUP>C values ranged from -24.3%% to -21.2%% and were divided into five stages based on the average value (-22.5%%). A comparison with the regional climate index revealed that wet periods linked to intensified summer monsoon conditions occurred at Stage 1 (4500-3600 cal BP), Stage 3 (1350-900 cal BP), and Stage 5 (300 cal BP to present). Dry intervals were found at Stage 2 (3600-1350 cal BP) and Stage 4 (900-300 cal BP). We found two different vegetational responses to changes in regional temperature and summer monsoons. Stage 3, corresponding to the MWP, was characterized by an association between the δ<SUP>13</SUP>C values on the island and the regional temperature, but Stage 4, including the LIA interval, did not show such a relationship. Furthermore, based on comparison with the summer monsoon index, this study suggested that, on the southern coast of Korea, vegetational change was controlled by an MWP-like mode during the warm and wet periods following regional climate change, whereas a LIA-like mode showing independent climate change was dominant during the cold and dry periods. This difference in vegetational changes along the southern coast of Korea and regional (mainly terrestrial-signal based) climate change may be attributed to the influence of sea surface temperature changes in the tropical ocean through the transport of warming seawater by the Kuroshio and Tsushima currents on the East Asian coastal area, including this study area, than on the inner part of the East Asian continent.

The essential oils of Chamaecyparis obtusa promote hair growth through the induction of vascular endothelial growth factor gene

Lee, G.S.,Hong, E.J.,Gwak, K.S.,Park, M.J.,Choi, K.C.,Choi, I.G.,Jang, J.W.,Jeung, E.B. Inverni Della Beffa S.p.A ; Elsevier Science 2010 Fitoterapia Vol.81 No.1

Chamaecyparis obtusa (C. obtusa) is a conifer in the cypress family Cupressaceae, native to northeast Asia. The essential oils of C. obtusa have antibacterial and antifungal effects and several products such as hygienic bands, aromatics, and shampoos contain these oils as a natural source of antimicrobial/antifungal agents. Interestingly, some consumers suffering from baldness and/or other forms of hair loss have reported a hair growth promoting effect of shampoos containing these oils. In the present study, the hair growth promoting effect of C. obtusa oils was elucidated in an animal model. C. obtusa oils promoted the early phase of hair growth in shaved mice. In addition, we examined the molecular effect of C. obtusa oils on the regulation of hair morphogenesis and hair growth using the human keratinocyte cell line HaCaT. In the current study of hair growth regulating genes, the expressions of vascular endothelial growth factor (VEGF), transforming growth factor (TGFβ1), and keratinocyte growth factor(KGF) have been analyzed by real-time PCR in HaCaT cells. The essential oils of C. obtusa were divided into seven fractions for treatment of HaCaT cells. VEGF transcripts were induced by fractions 6 and 7; however, TGFβ1 and KGF mRNA levels were unchanged by C. obtusa oils or fractions. Fraction 7 was separated into seven sub-fractions and studied further. Sub-fractions E and D significantly increased VEGF and KGF gene expression without up-regulating the hair growth inhibition factor, TGFβ1. The components of the two sub-fractions were further analyzed by gas chromatography and mass spectrometry. Cuminol, eucarvone, and calamenene were common to these two sub-fractions, although the effects of these individual components were not determined. Taken together, these results suggest that C. obtusa oils promote hair growth in an animal model and a positive regulator of hair growth, VEGF, was induced by particular components of these oils.

BAX inhibitor-1 enhances cancer metastasis by altering glucose metabolism and activating the sodium-hydrogen exchanger: the alteration of mitochondrial function

Lee, G-H,Yan, C,Shin, S-J,Hong, S-C,Ahn, T,Moon, A,Park, S J,Lee, Y C,Yoo, W H,Kim, H-T,Kim, D-S,Chae, S-W,Kim, H-R,Chae, H-J Macmillan Publishers Limited 2010 Oncogene Vol.29 No.14

The anti-apoptotic protein, BAX inhibitor-1 (BI-1), has a role in cancer/tumor progression. BI-1-overexpressing HT1080 and B16F10 cells produced higher lung weights and tumor volumes after injection into the tail veins of mice. Transfection of BI-1 siRNA into cells before injection blocked lung metastasis. in vitro, the overexpression of BI-1 increased cell mobility and invasiveness, with highly increased glucose consumption and cytosolic accumulation of lactate and pyruvate, but decreased mitochondrial O<SUB>2</SUB> consumption and ATP production. Glucose metabolism-associated extracellular pH also decreased as cells excreted more H<SUP>+</SUP>, and sodium hydrogen exchanger (NHE) activity increased, probably as a homeostatic mechanism for intracellular pH. These alterations activated MMP 2/9 and cell mobility and invasiveness, which were reversed by the NHE inhibitor, 5-(N-ethyl-N-isopropyl) amiloride (EIPA), suggesting a role for NHE in cancer metastasis. In both in vitro and in vivo experiments, C-terminal deleted (CΔBI-1) cells showed similar results to control cells, suggesting that the C-terminal motif is required for BI-1-associated alterations of glucose metabolism, NHE activation and cancer metastasis. These findings strongly suggest that BI-1 reduces extracellular pH and regulates metastasis by altering glucose metabolism and activating NHE, with the C-terminal tail having a pivotal role in these processes.

마우스에 대한 Surfactin C의 급성경구독성시험

박병권(Byung-Kwon Park),임종환(Jong-Hwan Lim),황윤환(Youn-Hwan Hwang),김명석(Myung-Seok Kim),송인배(In-Bae Song),이홍기(Hong-Gee Lee),한성진(Sung-Jin Han),황미현(Mi-Hyun Hwang),김종우(Jong-Woo Kim),이만휘(Man-Hee Rhee),박승춘(Seong-C 한국독성학회 2006 Toxicological Research Vol.22 No.4

This study was carried out to investigate the acute toxicity of surfactin C in mice. Surfactin C was administered orally at does of 0, 381, 610, 977, 1562 and 2500 ㎎/㎏. Number of deaths, clinical signs, body weights, feed and water consumptions, and biochemical examinations were investigated for 14 days after single oral administration of surfactin C. LD?? value was over 2500 ㎎/㎏ in mice. In addition, no differences were found between control and treated groups in clinical signs, body weight gains, hematology, serum chemistry, feed and water consumptions. The results indicate that surfactin C did not show any toxic effects at 2500 ㎎/㎏ in mice.

Ba-Ferrite 단결정의 자기적 특성에 관한 뫼스바우어 분광학적 연구

서정철,지성훈,홍양기,Sur, J.C.,Gee, S.H.,Hong, Y.K. 한국자기학회 2007 韓國磁氣學會誌 Vol.17 No.2

Ba-Ferrite single crystals were prepared and characterized by X-ray, SEM and Mossbauer spectroscopy. The single crystal layers was cut in the c-axis and radiated to the surface by ${\gamma}-rays$ for Mossbauer spectroscopy. We found out that the spin states in Fe atoms were parallel to the ${\gamma}-rays$ direction. The temperature dependence of the hyperfine field is almost similar to that of powder samples. The crystal structure is a Magnetoplumbite without any other phases and the lattice parameters are found out with $a_0=5.892{\AA},\;b_0=5.892{\AA},\;c_0=23.198{\AA}$. $M\"{o}ssbauer$ spectrum in single crystal have 5 sets off absorption lines in each Fe site when the ${\gamma}-rays$ have the same radiation direction with the c-axis in the crystal, which mean that the whole crystal bulk formed only one crystal and same spin direction. The hysteresis curve shows the saturation moment and coercive force of 70.71 emu/g and 320 Oe respectively. Ba-ferrite 단결정을 제조하여 자기적 성질을 Mossbauer 분광법으로 연구하였다. 단결정 시료를 c-축 방향으로 얇게 절단하고 그 면에 감마선을 조사한 결과 결정 전체에 걸쳐 Fe 이온의 스핀 방향이 c-축과 일치함을 확인하였다. 온도에 따른 초미세자기장의 감소 추세는 입자상태와 거의 비슷하였으며 결정 내 Fe원자의 이온 상태 역시 일치하였다. 결정구조는 Magnetoplumbite로서 결정상수는 $a_0=5.892{\AA},\;b_0=5.892{\AA},\;c_0=23.198{\AA}$로 정되었으며 그 외의 다른 상은 존재하지 않는 것으로 나타났다. $M\"{o}ssbauer$ spectrum은 결정 내에 존재하는 Fe의 자리에 따라 5의 각각의 다른 subspectrum이 존재하였는데 감마선의 방향이 c-축과 일치하여 모든 자리에서 4개의 공명흡수선 만이 존재하였다. 따라서 결정의 형태는 전체적으로 단일상으로 형성되었음을 확인하였고 여분의 ${\alpha}-Fe_2O_3$ 등은 존재하지 않음을 명확히 하였다. 자기이력곡선을 통하여 실온상태에서 포화자기모멘트는 70.71 emu/g, 보자력이 320 Oe의 값으로 측정되었다.