A Synthetic Naringenin Derivative, 5-Hydroxy-7,4′-diacetyloxyflavanone-<i>N</i>-phenyl Hydrazone (N101-43), Induces Apoptosis through Up-regulation of Fas/FasL Expression and Inhibition of PI3K/Akt Signaling Pathways in Non-Small-Cell Lung Cancer Cells

Bak, Yesol,Kim, Heejong,Kang, Jeong-Woo,Lee, Dong Hun,Kim, Man Sub,Park, Yun Sun,Kim, Jung-Hee,Jung, Kang-Yeoun,Lim, Yoongho,Hong, Jintae,Yoon, Do-Young American Chemical Society 2011 Journal of agricultural and food chemistry Vol.59 No.18

<P>Naringenin, a well-known naturally occurring flavonone, demonstrates cytotoxicity in a variety of human cancer cell lines; its inhibitory effects on tumor growth have spurred interest in its therapeutic application. In this study, naringenin was derivatized to produce more effective small-molecule inhibitors of cancer cell proliferation, and the anticancer effects of its derivative, 5-hydroxy-7,4′-diacetyloxyflavanone-<I>N</I>-phenyl hydrazone (N101-43), in non-small-cell lung cancer (NSCLC) cell lines NCI-H460, A549, and NCI-H1299 were investigated. Naringenin itself possesses no cytotoxicity against lung cancer cells. In contrast, N101-43 inhibits proliferation of both NCI-H460 and A549 cell lines; this capacity is lost in p53-lacking NCI-H1299 cells. N101-43 induces apoptosis via sub-G<SUB>1</SUB> cell-cycle arrest in NCI-H460 and via G<SUB>0</SUB>/G<SUB>1</SUB> arrest in A549 cells. Expression of apoptosis and cell-cycle regulatory factors is altered: Cyclins A and D1 and phospho-pRb are down-regulated, but expression of CDK inhibitors such as p21, p27, and p53 is enhanced by N101-43 treatment; N101-43 also increases expression levels of the extrinsic death receptor Fas and its binding partner FasL. Furthermore, N101-43 treatment diminishes levels of cell survival factors such as PI3K and p-Akt dose-dependently, and N101-43 additionally induces cleavage of the pro-apoptotic factors caspase-3, caspase-8, and poly ADP-ribose polymerase (PARP). Cumulatively, these investigations show that the naringenin derivative N101-43 induces apoptosis via up-regulation of Fas/FasL expression, activation of caspase cascades, and inhibition of PI3K/Akt survival signaling pathways in NCI-H460 and A549 cells. In conclusion, these data indicate that N101-43 may have potential as an anticancer agent in NSCLC.</P>

2,4-bis (p-hydroxyphenyl)-2-butenal (HPB242) induces apoptosis via modulating E7 expression and inhibition of PI3K/Akt pathway in SiHa human cervical cancer cells.

Kim, Man Sub,Kim, Jung Hee,Bak, Yesol,Park, Yun Sun,Lee, Dong Hun,Kang, Jeong Woo,Shim, Jung-Hyun,Jeong, Heon Sang,Hong, Jin Tae,Yoon, Do Young Lawrence Erlbaum Associates, Publishers [etc.] 2012 Nutrition and cancer Vol.64 No.8

<P>The Maillard reaction is a chemical reaction occurring between an amino acid and a reducing sugar, usually requiring thermal processing. Maillard reaction products (MRPs) have antioxidant, antimutagenic, and antibacterial effects, and although 2,4-bis (p-hydroxyphenyl)-2-butenal (HPB242), a fructose-tyrosine MRP, appears to inhibit proliferation of cancer cells, its mechanism of action has not been studied in detail. We found that HPB242 treatment modulated expression of cyclins and tumor suppressor genes in SiHa human cervical cancer cell lines: cyclins and phospho-pRB were downregulated, whereas the expression of CDK inhibitors and p53 was enhanced. HPB242 induced apoptosis dose-dependently by suppressing E7 expression and leading to sub-G1 cell-cycle arrest in SiHa cell lines; treatment also led to the proteolytic cleavage of caspase-3, -9, and poly (ADP-ribose) polymerase. Moreover, HPB242 upregulated Fas expression, altered expressions of pro- and antiapoptotic factors, and also inhibited nuclear translocation of nuclear factor κB and phosphorylation of IκB. HPB242 treatment decreased phosphatidyl inositol-3 kinase and p-Akt expression levels, demonstrating that this survival pathway may also be inhibited by HPB242. Cumulatively, HPB242 promotes apoptosis by influencing E7 expression, inducing cell-cycle arrest at sub-G1 phase, and promoting both intrinsic (mitochondrial) and extrinsic (Fas-dependent) apoptosis in SiHa human cervical cancer cells.</P>

연쇄중합효소반응을 이용한 태아성별진단

이희섭,김용신,김화선,김정중,김원신 원광대학교 생명공학연구소 1996 생명공학연구소보 Vol.4 No.1

For sex determination by the PCR method, oligoprimers to Y-chromosome gene, DYZ1, SRY, and AMGL were synthesized and genomic DNA was extracted from male and female placenta for the control use. DYZ1 represented 154 bp single band to 0.001pg/ml male genomic DNA but did not represent 154 bp band in female genomic DNA, SRY represented 341 bp band to 1 pg/ml male genomic DNA but did not represent 341 bp band in female genomic DNA, and AMGL represented 977 and 788 bp double band to 1 pg/ml male genomic DNA and 977 bp single band to 1 pg/ml female genomic DNA in 2% agarose gel electrophoresis stained with ethidium bromide. DYZ1 was 1,000-fold sensitive than SRY and AMGL. DYZ1 and SRY could not identify the PCR failure from female but AMGL identified. To increase the sensitivity, the dual amplification of AMGL was performed and the sensitivity increased to 1,000-fold. During the dual amplification of female genomic DNA mixed with male genomic DNA, 0.00125pg/l, 1:400 part male genomic DNA contamination represented double bands as male. In 2 cases of 46, XY female, DYZ1 and AMGL amplification represented male band but SRY amplification did not represent male band. It was suggested that SRY gene was deleted in two 46, XY female cases. for fetal sex determination, PCR with DYZ1, SRY, and AMGL was performed in 10 cases of chorionic villi and 15 cases of amnionic cells. By the comparison with karyotyping result, fetal sex determination was achieved successfully in all 23 samples using PCR of SRY and AMGL but false result was detected in 3 cases(13%) using DYZ1. According to our results, it was concluded that DYZ1 was 1,000-fold sensitive than SRY and AMGL but could not be used because of its false results, and AMGL and SRY must be used concomitantly for precise sex determination.

The Establishment of the International Financial Center (IFC) in Jeju Free International City

Heonkyu JEONG,Hyo KIM,Yong-Bok CHOI,Mun-Sub CHUNG 제주대학교 관광과경영경제연구소 2020 産經論集 Vol.40 No.3

Purpose: Jeju Free International City is growing around the tourism industry. However, for Jeju Free International City to grow in line with the concept of free international city, it is necessary to move away from the current industrial structure that is focused on the tourism industry. It is necessary to reorganize the industrial structure centered on the financial industry in the long term, and for this, it is necessary to develop interest and fostering the financial industry within Jeju Special Self-Governing Province. This study intends to reconsider the necessity through the academic approach to fostering the financial industry in Jeju Free International City, which has been planned from the policy perspective. To this end, this study empirically analyzed the factors necessary to build the foundation for fostering the financial industry in Jeju Free International City. The purpose of this study is to examine the necessity for the establishment of an international financial center in Jeju and to derive the necessity for each factor through analysis of sub-factors necessary for the establishment of an international financial center in Jeju. Research design, data and methodology: This study carried out IPMA for analysis of components for fostering the financial industry. Through IPMA, this study identified priorities for the need for configuration factors and sub-factors. In addition, the thesis further performed a cross-group comparison. Result: The analysis confirmed that the factors in the living environment are the highest priority. It also confirmed that the priority of institutional policy factors and infra-facility factors is high. This study found that financial and non-financial employees differed in the priorities of factors in the comparison analysis between groups. This study also confirmed that Jeju residents and non-Jeju residents have distinct differences in the priorities of factors. Conclusion: Through this study, factors necessary for Jeju Free International City were identified. In addition, it was confirmed that there was a clear difference between the factors necessary for Jeju residents and non-Jeju residents. In the future, it is necessary to seriously consider these differences in the decision on whether to introduce, how to introduce, and priorities in the introduction of international financial center.

논문 : 연극 공연의 감성학적 연구 -괴르노트 뵈메(Gernont Bohme)의 감성학을 중심으로

김정섭 ( Jeong Sub Kim ) 한국연극교육학회 2015 연극교육연구 Vol.27 No.-

This article focuses on two aspects. First, it introduces and examines Bohme``s Aisthetik theory. Second, it defines an application plan for its integration into the aesthetics of the performing arts. The first point is examinedin relation to four sub-topics. First, the study considers the appearance of Aisthetik as a new form of aesthetics in the 20th century. The driving forces behind the appearance of Aisthetik were environmental problems, the aestheticization of daily life, and a new definition of the arts. Second, the study explains the perception of Aisthetik asa sense of bodily existence. Third, it evokes a general perception method that is not based on individual senses but on special perceptual functions. Fourth, it presents atmospheric perception as one of the basic ideas of the Aisthetik theory. The atmosphereis experienced through two kinds of affective senses. One is the presence of objects, and the other the unique presence of oneself. The second part of the study focuses on the co-presence, materiality, and generation of meanings within the Aisthetik framework. Those areimportant terms in performative aesthetics studies and in Aisthetik. In particular, the study states that the perceptional process of spectators does not receive delivered meanings but generates its own. The study of the Theatre Aisthetik in this article is based on the vision of performative aesthetics as animportant aesthetic discourse in the contemporary performing arts. This study shows that Theatre Aisthetik should be part of the development of the contemporary performing arts aesthetics. The paper hopes to encourage active discussions and a keen interest in the Theatre Aisthetik.

A sub-1-volt nanoelectromechanical switching device.

Lee, Jeong Oen,Song, Yong-Ha,Kim, Min-Wu,Kang, Min-Ho,Oh, Jae-Sub,Yang, Hyun-Ho,Yoon, Jun-Bo Nature Pub. Group 2013 Nature nanotechnology Vol.8 No.1

<P>Nanoelectromechanical (NEM) switches have received widespread attention as promising candidates in the drive to surmount the physical limitations currently faced by complementary metal oxide semiconductor technology. The NEM switch has demonstrated superior characteristics including quasi-zero leakage behaviour, excellent density capability and operation in harsh environments. However, an unacceptably high operating voltage (4-20 V) has posed a major obstacle in the practical use of the NEM switch in low-power integrated circuits. To utilize the NEM switch widely as a core device component in ultralow power applications, the operation voltage needs to be reduced to 1 V or below. However, sub-1 V actuation has not yet been demonstrated because of fabrication difficulties and irreversible switching failure caused by surface adhesion. Here, we report the sub-1 V operation of a NEM switch through the introduction of a novel pipe clip device structure and an effective air gap fabrication technique. This achievement is primarily attributed to the incorporation of a 4-nm-thick air gap, which is the smallest reported so far for a NEM switch generated using a 'top-down' approach. Our structure and process can potentially be utilized in various nanogap-related applications, including NEM switch-based ultralow-power integrated circuits, NEM resonators, nanogap electrodes for scientific research and sensors.</P>

기니픽에서 Magnesium의 혈관 이완과 혈압 하강 효과

김정곤,강형섭,김진상 한국수의공중보건학회 2003 예방수의학회지 Vol.27 No.2

The present study evaluated the effects of various agents on magnesium sulfate (Mg^(2+))-induced relaxation in aorta and blood pressure lowering in anesthetized guinea pigs. Mg^(2+) inhibited phenylephrine (PE)- or 40 mM KC1-induced sustained contraction of endothelium-intact (+E) guinea pig aortic rings in concentration-dependent manner. In preparations preconstricted with PE or KC1, Mg^(2+)-induced concentration-dependent relaxations. In preparations preconstricted with PE or KCl, Mg^(2+)-induced relaxations were not affected by the removal of endothelium (-E) and by the pretreatment of aortic rings with NO synthase (NOS) inhibitors (L-NAME and LNNA), guanylate cyclase inhibitors (methylene blue and ODQ, adenylate cyclase inhibitor (MDL), K^(+) channel blockers (glibenclamide and tetrabutylammonium), nifedipine or ryanodine. However, Mg^(2+)-induced relaxations were inhibited by Na^(+)-Mg^(2+) exchange inhibitor (imipramine) or removal (or attenuation) of extracellular Ca^(2+) in +E aortic rings. PE-induced contraction was not inhibited by nifedipine. In addition, Mg^(2+)-induced relaxations were inhibited by phospholipase C inhibitor (NCDC) or inositol monophosphatase inhibitor (lithium), but not by protein kinase C inhibitor (staurosporine). In vi패 infusion of Mg^(2+), directly into the femoral veins of guinea pigs, elicited sustained decrease in arterial blood pressure. The Mg^(2+)-lowered blood pressure was attenuated by intravenous administration of imipramine or lithium, but not by methylene blue, indomethacin, tetrabutylammonium nifedipine, LNNA, L-NAME or saponin (as an endothelium removal agent). These results suggest that endothelium independent vasorelaxant effect of Mg^(2+) on aortic ring appear to play important roles on the antihypertensive action in guinea pig, most likely via the inhibitory action of Mg^(2+) on the intracellular C^(2+) involve in PLC-IP pathway and influx (through the Na^(+)-Mg^(2+) exchanger) into the cell in guinea pig aorta.

산모 말초 혈액으로부터 태아 세포의 분리

이희섭,김정중,김원신 원광대학교 생명공학연구소 1997 생명공학연구소보 Vol.5 No.1

We synthesized rabbit antisera to the enzyme, human type Ⅰ 3-HSD(3-hydroxy-5-ene steroid dehydrogenase, EC 1.1.1.145) that is the key enzyme in the stroidogenesis and membrane-bounding enzyme of trophoblasts, by oligopeptide coupling method. This anti-3-HSD antisera reacts with 43kDa protein in human placental lysate by SDS-PAGE and Western blot, and the syncytiotrophoblasts and cytotrophoblasts from placental villi are stained positively with this antisera by immunohistochemistry (published in Bulletin of Life Science and Biotechnology 1995;3:68). Fetal trophoblast cells were isolated from peripheral blood of pregnant women by the immune-bead method using anti-3-HSD antibody and Dynabeads M-280(Dynal A.S. Oslo Norway). Isolated cells were observed directly by inverted microscope and observed with Pap stain by light microscope. Isolated trophoblast cells were adherent to Dynabeads M-280 and exhibited the typical morphology of syncytiotrophoblast cells. We mentioned previously polymerase chain reaction to the Y-chromosome containing gene, DYZ1, SRY, and AMGL is the easy method in sex-determination(published in Kor J Obstet Gynecol 1997;40:1412). For the purpose of fetal cell identification, fetal cells were isolated from peripheral blood of five women who were pregnant with male fetus ascertained by karyotyping of amnionic cells and ultrasonography. Sex-determination of the isolated fetal cells was performed by PCR method. In all cases(5/5, 100%), maleness was confirmed. According to our results, it was concluded that isolation of these fetall cells by immune beads method could allow noninvasive diagnosis of wide range of inherited disorders.

합성펩타이드를 이용한 영양배엽세포-특이 가토 다클론 항혈청의 제작

이희섭,오재민,김정중,문형배,김원신,이황희 원광대학교 생명공학연구소 1995 생명공학연구소보 Vol.3 No.1

Within the last few years, a different approach to generating protein-reactive antibodies has been developed that has several advantages over conventional immunization. This involves synthesizing short peptide sequences, coupling them to immunogenic carrier molecules, and immunizing animals with the conjugates. 3βHSD(3β-hydroxy-5-ene steroid dehydrogenase; EC 1.1.1.145) is the enzyme of the plasma membrane of human trophoblast and it's cDNA sequence was identified by Nickon et al(Molecular cloning and expression of human trophoblast antigen FDO161G and its identification as 3β-hydroxy-5-ene steroid dehydrogenase. J Reprod Fert 1991;149;156). For the production of trophoblast-specific antibody, we synthesized three oligopeptides that are epitope sites chosen from cDNA sequence of 3βHSD. Oligopetides were coupled with KLH(keyhole limpet hemocyanin) under 25% glutaraldehyde. The trophoblast-specific rabbit polyclonal antisera was produced by conventional methods. This antisera reacts with a 43kDa protein in human placental lysate by Western blotting analysis and The syncytiotrophoblasts and cytotrophoblasts from villi are stained positively with this antisera by immunohistochemistry. Villous trophoblasts were cultured in methionine-free media for 1 hour and [^(35)S]-Methionine for 24 hours. Media and cell lysate were immunoprecipitated with this antisera and 12% SDS-PAGE was performed. In fluorography, bend was not noted in media and 43kDa band was noted in medis and 43kDa band was noted in lysate. It was concluded that anti-3βHSD antibody produced by synthetic peptide was specific to trophoblasts and 3βHSD was membrane-bound protein of trophoblasts.

양막상피세포와 영양배엽세포에서 α1-antitrypsin 의 발현에 시토카인이 미치는 영향

이희섭,전병훈,김정중,김원신 원광대학교 생명공학연구소 1995 생명공학연구소보 Vol.3 No.1

We have examined indirectly the expression of α1-antitrypsin by determined the TIC(trypsin inhibitory capacity) in the cultured medium of the amnionic ephithelial cell and trophoblasts. The TIC of the cells was cultured in the presence of supernatent by treatment of neutrophils with(CNMP) or without(CNM) phorbol myristate acetate(PMA) is identical in both coultured cells. By the western blotting analysis, the substance possess the TIC in the cultured medium is identified to the α1-antitrypsin. From these results, the cytokines secreted by the neutrophils did not affected the secretion of α1-antitrypsin in the both cultured cells. But, some unidentified proteinases cleaved the α1-antitrypsin. Thus the neutrophil proteinases might be involved in premature rupture of the membranes(PROM) by any means.