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        • Medicinal Chemistry : RESEARCH ARTICLE ; Anti-angiogenic activity of macrolactin A and its succinyl derivative is mediated through inhibition of class I PI3K activity and its signaling

          ( Youra Kang ), ( Sushil Chandra Regmi ), ( Mi Yeong Kim ), ( Suhrid Banskota ), ( Jaya Gautam ), ( Dong Hee Kim ), ( Jung Ae Kim ) 영남대학교 약품개발연구소 2015 영남대학교 약품개발연구소 연구업적집 Vol.25 No.-

          In the current study, macrolactin compounds, macrolactin A (MA) and 7-0-succinyl macrolactin A (SMA), were investigated for their anti-angiogenic activities and action mechanism. MA and SMA inhibited in vitro and in vivoangiogenesis induced by three differentclasses of pro-angiogenic factors, VEGF, IL-8, and TNF-α. SMA exhibited stronger anti-angiogenic activity than MA, and such anti-MDA-MB-231 human breast cancer cell-inoculated CAM assay showing dose-dependent suppression of tumor growth and tumor-induced angiogenesis. In an in vitro PI3K com-petitive activity assay, SMA induced concentration-depen-dent inhibition of class I PI3K isoforms, p110α, p110β, p110δ, and p110★. In addition, non-receptor tyrosine kinase c-Src, which is involved in the activation of PI3K heterodi-mer, was suppressed by MA and SMA. Correspondingly, MA and SMA significantly inhibited the stimulus-induced phos-phorylation of Akt, mTOR, p70S6K, and ribosomal S6 in human umbilical vein endothelial cells (HUVECs). At the same time, the stimulus-induced production of reactive oxygen species (ROS) and activation of NF-κB were signif-icantly suppressed by MA and SMA. Moreover, the macro-lactins suppressed NF-κB-regulated HSP90 protein expression, which stabilizes phosphorylated Akt and NADPH oxidase. Suppression of NF-κB in macrolactin-treated HUVECs with concurrent inhibition of rS6 indicates that Mas effectively block angiogenesis through down-reg-ulation of genes related to angiogenesis at both transcriptional and translational levels. Taken together, the results demon-strate that anti-angiogenic effect of MA and SMA is mediated through inhibition of PI3K/Akt and NADPH oxidase-derived ROS.NF-ΚB signaling pathways. These results further indi-cate that MA and SMA may be applicable for treatment of various diseases associated with angiogenesis.

        • KCI등재

          Post-transcriptional Regulation of Gcn5, a Putative Regulator of Hox in Mouse Embryonic Fibroblast Cells

          Youra,Lee,Ji,Hoon,Oh,Kyoung-Ah,Kong,Myoung,Hee,Kim 대한의생명과학회 2012 Biomedical Science Letters Vol.18 No.2

          Hox proteins containing DNA-binding homedomain act as transcription factors important for anteroposterior body patterning during vertebrate embryogenesis. However, the precise mechanisms by which signal pathways are transduced to regulate the Hox gene expression are not clear. In the course of an attempt to isolate an upstream regulatory factor(s) controlling Hox genes, protein kinase B alpha (Akt1) has been identified as a putative regulator of Hox genes through in silico analysis (GEO profile). In the Gene Expression Omnibus (GEO) dataset GDS1784 at the NCBI (National Center for Biotechnology Information) site, Hox genes were differentially expressed depending on the presence or absence of Akt1. Since it was not well known how Akt1 regulates the specific Hox genes, whose transcription was reported to be regulated by epigenetic modifications such as histone acetylation, methylation etc., the expression of Gcn5, a histone acetyltransferase (HAT), was analyzed in wild type (WT) as well as in Akt1-/- mouse embryonic fibroblast (MEF) cells. RT-PCR analysis revealed that the amount of Gcn5 mRNA was similar in both WT and Akt1-/- MEFs. However, the protein level of Gcn5 was significantly increased in Akt1-/- MEF cells. The half life of Gcn5 was 1 hour in wild type whereas 8 hours in Akt1-/- MEF. These data all together, indicate that Gcn5 is post-transcriptionally down-regulated and the protein stability is negatively regulated by Akt1 in MEF cells.

        • The radio-sensitizing effect of xanthohumol is mediated by STAT3 and EGFR suppression in doxorubicin-resistant MCF-7 human breast cancer cells

          ( Youra Kang ), ( Min A Park ), ( Se Woong Heo ), ( Su Young Park ), ( Keon Wook Kang ), ( Pil Hoon Park ), ( Jung Ae Kim ) 영남대학교 약품개발연구소 2013 영남대학교 약품개발연구소 연구업적집 Vol.23 No.0

          BACKGROUND: Chemotherapeutic drug resistance remains a clinical obstacle in cancer management. Drug-resistant cancer cells usually exhibit cross-resistance to ionizing radiation, which has devastating consequences for patients. With a better understanding of the molecular mechanisms, it will be possible to develop strategies to overcome this cross-resistance and to increase therapeutic sensitivity. METHODS: Natural and synthetic flavonoid compounds including xanthohumol, the principal flavonoid in hops, were investigated for its radio-sensitizing activity on human breast cancer MCF-7 and adriamycin-resistant MCF-7 (MCF-7/ADR) cells. Chemo-sensitizing or radio-sensitizing effect was analyzed by tetrazolium-based colorimetric assay and flow cytometry. Western blot analysis, confocal microscopy, gene silencing with siRNA transfection and luciferase reporter gene assay were performed to examine signaling molecule activation. RESULTS: Among the tested flavonoid compounds, pretreatment of the cells with xanthohumolsignificantly sensitized MCF-7/ADR cells to the radiation treatment by inducing apoptosis. In MCF-7/ADR cells, treatment with xanthohumol alone or with gamma-rays significantly decreased levels of anti-apoptotic proteins. Multi-drug resistance 1 (MDR1), epidermal growth factor receptor (EGFR) and signal transducer and activator of transcription 3 (STAT3) expression levels in MCF-7/ADR cells were suppressed by xanthohumol treatment. In addition, xanthohumol treatment increased death receptor (DR)-4 and DR5 expression. The xanthohumol-induced changes of these resistance-related molecules in MCF-7/ADR cells were synergistically increased by gamma-ray treatment. CONCLUSIONS: Xanthohumol restored sensitivity of MCF-7/ADR cells to doxorubicin and radiation therapies. GENERAL SIGNIFICANCE: Our results suggest that xanthohumol may be a potent chemo- and radio-sensitizer, and its actions are mediated through STAT3 and EGFR inhibition.ⓒ2012 Elsevier B. V. All rights reserved.

        • KCI등재

          Chalcone 유도체들의 사람 유방암세포주 및 사람 섬유육종 세포에 대한 세포독성효과

          강유라(Youra Kang), 박민아(Min-A Park), 조미연(Mi-Yeon Cho), 이경희(Kyung Hee Lee), 김정애(Jung-Ae Kim) 대한약학회 2010 약학회지 Vol.54 No.1

          '스콜라' 이용 시 소속기관이 구독 중이 아닌 경우, 오후 4시부터 익일 오전 7시까지 원문보기가 가능합니다.

          Xanthohumol, a prenylated chalcone of the Hop plant (Humulus lupulus L.), has been reported to suppress tumor growth. 4-hydroxychalcone and isobavachalcone are chalcone derivatives and they have similar structure with xanthohumol. In the present study, we investigated the cytotoxic activities of chalcone and its erivatives, 4-hydroxychalcone, xanthohumol, and isobavachalcone, in MCF-7 and adriamycin resistant MCF-7 (MCF-7/ADR) breast cancer cells and HT-1080 fibrosarcoma cells. In a cell viability assay using 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) reagent, chalcone and 4-hydroxychalcone decreased cell viability in HT-1080 cells, but not in MCF-7 and MCF-7/ADR cells. Isobavachalcone showed similar cytotoxicity in HT-1080 cells, and only limited cytotoxicity in MCF-7 and MCF-7/ADR cells at very high concentration (50 μM). In contrast, xanthohumol showed concentration-dependent cytotoxicity in MCF-7, MCF-7/ADR, and HT-1080 cancer cells. Taken together, the structure-activity relationship of chalcone and its derivatives indicate that chalcones may be valuable cytotoxic compounds against selective cancer types.


          Patient sample-oriented analysis of gene expression highlights extracellular signatures in breast cancer progression

          Hong,,Yourae,Kim,,Nayoung,Li,,Chao,Jeong,,Euna,Yoon,,Sukjoon Elsevier 2017 Biochemical and biophysical research communication Vol.487 No.2

          <P><B>Abstract</B></P> <P>Although a large collection of cancer cell lines are useful surrogates for patient samples, the physiological relevance of observed molecular phenotypes in cell lines remains controversial. Because transcriptome data are a representative set of molecular phenotypes in cancers, we systematically analyzed the discrepancy of global gene expression profiles between patient samples and cell lines in breast cancers. While the majority of genes exhibited general consistency between patient samples and cell lines, the expression of genes in the categories of extracellular matrix, collagen trimers, receptor activity, catalytic activity and transporter activity were significantly up-regulated only in tissue samples. Genes in the extracellular matrix, particularly collagen trimers, showed a wide variation of expression in tissue, but minimal expression and variation in cell lines. Further analysis of tissue samples exclusively revealed that collagen genes exhibited a cancer stage-dependent expressional variation based on their supramolecular structure. Prognostic collagen biomarkers associated with survival rate were also readily predicted from tissue-oriented transcriptome analysis. This study presents the limitations of cell lines and the exclusive features of tissue samples in terms of functional categories of the cancer transcriptome.</P>

        • KCI등재

          영어 -ly 유형 인식견지부사의 담화표지 기능 이해도 분석: 한국인 EFL 학습자와 원어민 화자를 대상으로

          이유라(Youra Lee), 유석훈(Seok-Hoon You) 서울대학교 언어교육원 2020 語學硏究 Vol.56 No.3

          English -ly adverbials (LY) with epistemic modality are frequently used as discourse markers (DM) in spoken language. In this paper, LY DM is defined as an epistemic stance marker. The experiment for this study aims to analyze Korean EFL learners" comprehension of LY used as a DM on the basis of the hypothesis that they would perceive LY differently from how English native speakers perceive them. In order to conduct the experiment, previous studies on DMs were thoroughly examined to establish the theoretical framework. Based on the framework, the Discourse Marker Interpretation Test (DMIT) was designed. The research data collected through the test were analyzed using quantitative methods. Additionally, interviews were conducted to supplement the interpretation of the research results. The experiment mainly determined that, unlike English native speakers, who properly interpreted LY with their DM function, Korean EFL learners are inclined to interpret LY used as DMs simply with their lexical meanings (the dictionary definition). Results suggest that there is a high possibility for Korean EFL learners to commit more errors when encountering LY DMs.


          Proteomic analysis of glutamate-induced toxicity in HT22 cells

          Lee,,Youra,Park,,Hye-won,Park,,Sung,Goo,Cho,,Sayeon,Myung,,Pyung,Keun,Park,,Byoung,Chul,Lee,,Do,Hee WILEY-VCH 2007 PROTEOMICS -WEINHEIM- Vol.7 No.2

          <P>In the present study, we have investigated the proteome changes associated with glutamate-induced HT22 cell death, a model system to study oxidative stress-mediated toxicity. Among a number of HT22 proteins exhibiting altered expression, several molecular chaperones demonstrated substantial changes. For example, the levels of Hsp90 and Hsp70 decreased as cell death progressed whereas that of Hsp60 increased dramatically. Interestingly, cytosolic Hsp60 increased more prominently than mitochondrial Hsp60. Concomitantly, the accumulation of poly-ubiquitylated proteins and differential regulation of the peptidase activities and the subunits of 26S proteasomes were observed in glutamate-treated HT22 cells. Our findings that the molecular chaperones and the ubiquitin-proteasome system undergo changes during glutamate-induced HT22 cell death may suggest the importance of a protein quality control system in oxidative damage-mediated toxicity.</P>

        • SCIESCOPUS

          BJ-1108, a 6-Amino-2,4,5-trimethylpyridin-3-ol analogue, regulates differentiation of Th1 and Th17 cells to ameliorate experimental autoimmune encephalomyelitis

          Kang,,Youra,Timilshina,,Maheshwor,Nam,,Tae-gyu,Jeong,,Byeong-Seon,Chang,,Jae-Hoon BioMed Central 2017 BIOLOGICAL RESEARCH Vol.50 No.-

          <P><B>Background</B></P><P>CD4<SUP>+</SUP> T cells play an important role in the initiation of an immune response by providing help to other cells. Among the helper T subsets, interferon-γ (IFN-γ)-secreting T helper 1 (Th1) and IL-17-secreting T helper 17 (Th17) cells are indispensable for clearance of intracellular as well as extracellular pathogens. However, Th1 and Th17 cells are also associated with pathogenesis and contribute to the progression of multiple inflammatory conditions and autoimmune diseases.</P><P><B>Results</B></P><P>In the current study, we found that BJ-1108, a 6-aminopyridin-3-ol analogue, significantly inhibited Th1 and Th17 differentiation in vitro in a concentration-dependent manner, with no effect on proliferation or apoptosis of activated T cells. Moreover, BJ-1108 inhibited differentiation of Th1 and Th17 cells in ovalbumin (OVA)-specific OT II mice. A complete Freund's adjuvant (CFA)/OVA-induced inflammatory model revealed that BJ-1108 can reduce generation of proinflammatory Th1 and Th17 cells. Furthermore, in vivo studies showed that BJ-1108 delayed onset of disease and suppressed experimental autoimmune encephalomyelitis (EAE) disease progression by inhibiting differentiation of Th1 and Th17 cells.</P><P><B>Conclusions</B></P><P>BJ-1108 treatment ameliorates inflammation and EAE by inhibiting Th1 and Th17 cells differentiation. Our findings suggest that BJ-1108 is a promising novel therapeutic agent for the treatment of inflammation and autoimmune disease.</P>

        • SCOPUSKCI등재

          Analysis of Field-Aligned Currents in the High-Altitude Nightside Auroral Region: Cluster Observation

          Shin,,Youra,Lee,,Ensang,Lee,,Jae-Jin The Korean Space Science Society 2019 Journal of Astronomy and Space Sciences Vol.36 No.1

          In this paper we present analysis of current density when the Cluster spacecraft pass the nightside auroral region at about $4-5R_E$ from the center of Earth. The analysis is made when the inter-spacecraft separation is within 200 km, which allows all four spacecraft to be situated inside the same current sheet. On 22 February 2002, two field-aligned current (FAC) events were observed in both the southern and the northern hemispheres. The FACs were calculated with magnetic field data obtained by the four spacecraft using the Curlometer method. The scales of the FACs along the spacecraft trajectory and the magnitudes were hundreds of kilometers and tens of $nA/m^2$, respectively, and both events were mapped to the auroral region in the ionosphere. We also examined reliability of the results with some parameters, and found that our results are adequately comparable with other studies. Nevertheless, some limitations that decrease the accuracy of current estimation exist.

        • GMR 프로틴칩의 성형 및 특성 분석에 관한 연구

          허유라(Youra Heo), 조익현(Eikhyun Cho), 강신일(Shinill Kang) 한국생산제조시스템학회 2011 한국생산제조시스템학회 학술발표대회 논문집 Vol.2011 No.4

          Guided mode resonance protein chips are capable of high sensitivity in the detection of molecular interactions, by measuring the movement of sharp transmittance peak. We designed a guided mode resonance protein chip by computer simulation based on rigorous coupled wave analysis, and created a prototype by UV nano imprinting. We also demonstrated the use of the guided mode resonance protein chip as a protein sensor by verifying the formation of peak wavelength value and the shift of the peak due to biotin and streptavidin interactions.

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