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Lee, Won-Jae,Park, Ji-Sung,Lee, HyeonJeong,Lee, Seung-Chan,Lee, Jeong-Hyun,Ock, Sun-A,Rho, Gyu-Jin,Lee, Sung-Lim The Korean Society of Embryo Transfer 2017 한국동물생명공학회지 Vol.32 No.3
The estrogen-mediated effect of mesenchymal stem cells (MSCs) is a highly critical factor for the clinical application of MSCs. However, the present study is conducted on MSCs derived from adult donors, which have different physiological status with steroid hormonal changes. Therefore, we explores the important role of $17{\beta}$-estradiol (E2) in MSCs derived from female and male newborn piglets (NF- and NM-pBMSCs), which are non-sexually matured donors with steroid hormones. The results revealed that in vitro treatment of MSCs with E2 improved cell proliferation, but the rates varied according to the gender of the newborn donors. Following in vitro treatment of newborn MSCs with E2, mRNA levels of Oct3/4 and Sox2 increased in both genders of MSCs and they may be correlated with both estrogen receptor ${\alpha}$ ($ER{\alpha}$) and $ER{\beta}$ in NF-pBMSCs, but NM-pBMSCs were only correlated with $ER{\alpha}$. Moreover, E2-treated NF-pBMSCs decreased in ${\beta}$-galactosidase activity but no influence on NM-pBMSCs. In E2-mediated differentiation capacity, E2 induced an increase in the osteogenic and chondrogenic abilities of both pBMSCs, but adipogenic ability may increased only in NF-pBMSCs. These results demonstrate that E2 could affect both genders of newborn donor-derived MSCs, but the regulatory role of E2 varies depending on gender-dependent characteristics even though the original newborn donors had not been affected by functional steroid hormones.
Lee, Hyeonjeong,Oh, Yumin,Jeon, Young-Jun,Lee, Song-Yi,Kim, Hyunjoo,Lee, Ho-June,Jung, Yong-Keun American Association for Cancer Research 2019 Cancer Research Vol.79 No.11
<P>This study reports that a novel posttranslational modification by O-GlcNAcylation of TRAIL-R1 (DR4) plays a crucial role in enabling both apoptotic and necroptotic cell death induction by TRAIL.</P><P><B></B></P><P>TNF-related apoptosis-inducing ligand (TRAIL) resistance, including nongenetically acquired tolerance in cancer persister cells, is a major obstacle to translating TRAIL therapy into patients with cancer. However, the underlying mechanisms remain to be elucidated. Here, we show that DR4/TRAIL-R1 is <I>O</I>-GlcNAcylated at Ser424 in its death domain to mediate both apoptosis and necrosis upon TRAIL ligation. We found that DR4–Ser424 mutations, identified from our cell-based functional screen using a cancer patient–derived cDNA expression library and from The Cancer Genome Atlas, caused TRAIL resistance in various human cancer cell lines. Using <I>O</I>-GlcNAc transferase knockdown cells, DR4-preferred versus DR5-preferred cancer cells, and a DR5-neutralizing antibody, we evaluated the essential role of DR4-specific <I>O</I>-GlcNAc modification in TRAIL cytotoxicity. In contrast to DR4, DR5 was not <I>O</I>-GlcNAcylated by TRAIL treatment, discriminating DR4 from DR5-mediated signaling. Apart from genetic changes in DR4-Ser424, we further classified various cancer cell lines originated from stomach, colon, lung, and glioblastoma according to their sensitivity to and receptor preference upon TRAIL death signaling and generated TRAIL-tolerant persister-derived DLD-1<SUP>PER</SUP> cells. Among these, we discovered that DR4 was not modified by <I>O</I>-GlcNAc in most of the TRAIL-resistant cancer cells and DLD-1<SUP>PER</SUP> cells. Interestingly, promoting DR4 <I>O</I>-GlcNAcylation intentionally using 2-deoxy-<SMALL>D</SMALL>-glucose or a high concentration of glucose sensitized those resistant cancer cells to TRAIL. The <I>O</I>-GlcNAcylation–defective DR4 failed to form DISC/necrosome and could not translocate to aggregated platforms for receptor clustering. Our findings demonstrate that DR4 <I>O</I>-GlcNAcylation is crucial for TRAIL death signaling, providing new opportunities for TRAIL therapy overcoming TRAIL resistance in cancers.</P><P><B>Significance:</B></P><P>This study reports that a novel posttranslational modification by <I>O</I>-GlcNAcylation of one of the two human TRAIL receptors with a death domain, TRAIL-R1 (DR4), plays a crucial role in enabling both apoptotic and necroptotic cell death induction by TRAIL.</P>
Lee, Hyeon Ji,Latif, Muhammad,Choe, Hyeonjeong,Ali, Imran,Lee, Heung Kyoung,Yang, Eun Hye,Yun, Jeong In,Chae, Chong Hak,Jung, Jae-Kyung,Kim, Hyoung Rae,Lee, Chong Ock,Park, Chi Hoon,Lee, Kwangho 대한약학회 2014 Archives of Pharmacal Research Vol.37 No.9
Syntheses of various bis-ortho-alkoxy-parapiperazineanilino-pyrimidines and -triazines of KRCA-0008 analogs are described and their structure-activity-relationship to anaplastic lymphoma kinase (ALK) is discussed. 5-trifluoromethyl-2,4-pyrimidine analog (2) seems to be most potent in both biochemical and cellular assay in this study, however it shows inferior mice xenograft activity to Crizotinib presumably due to its sub-optimal PK parameters. 4,6-disubstituted pyrimidine and 2,4-disubstituted triazine derivatives of KRCA-0008 are less potent or inactive to ALK wt., and this observation is explained with their molecular modeling compared to KRCA-0008.
서술적 정체성 이론과 비극 이론을 통한 『광장』 서사 분석
이현정 ( Hyeonjeong Lee ) 사단법인 아시아문화학술원 2021 인문사회 21 Vol.12 No.2
본 연구는 그간 대립적이고 갈등적으로 공존해온 『광장』 해석과 관련, 이를 종합할 수 있는 해석을 마련함으로써 작가가 마지막 개작을 통해 궁극적으로 독자들에게 전달하고자 하는 의미를 파악하는 것을 목적으로 한다. 이를 위해 본 연구는 ‘서술적 정체성 이론’과 ‘비극 이론’을 통해 『광장』의 서사 분석을 세세히 수행, 주인공 이명준이 어떻게 ‘밀실’에서 벗어나 ‘푸른 광장’으로 나아가는지를 증명하고자 하였다. 연구결과, 작가는 주인공 이명준이 보여준 ‘나’ 중심의 지배 욕망을 ‘회상’과 같은 서사 장치(서술적 정체성)를 통해 이명준 스스로 반성의 대상으로 삼게끔 하고, 나아가 비극적 ‘과오’의 깨달음을 통해 이명준이 ‘나’를 벗어나 ‘사랑’의 힘을 깨닫고 이를 실천했음을 극적으로 전달하고 있었다. 위와 같은 연구결과는 기존의 양분화된 『광장』 해석이 증상적으로 보여주는 ‘밀실’과 ‘광장’ 사이의 갈등을 넘어설 수 있도록 하며, 나아가 독자로 하여금 멜로드라마적 이분법에서 벗어나 그들이 책임감 있는 성장서사로서 각자의 삶에 참여할 수 있도록 도와줄 수 있다. The purpose of this study is to establish an interpretation that can be combined with the Gwangjang interpretation, which has coexisted confrontationally and conflictingly, to understand the meaning that the writer ultimately intends to convey to the reader through 10 adaptations. To this end, this study tried to demonstrate how the main character Lee Myung-joon moved away from the “secret room” to the “blue square” by conducting detailed narrative analysis of Gwangjamg through ‘narrative identity’ theory and ‘tragedy’ theory. According to the study, the author made Lee Myung-joon reflect on himself through narrative devices such as “recipitation” (a descriptive identity), and the author was dramatically conveying that Lee Myung-joon realized the power of “love” beyond “me” and practiced his love. The above research results allow the reader to go beyond the conflict between “secret room” and “square” that the existing bifurcated Gwangjang interpretation shows symptomatically, and further help them escape from melodramatic dichotomy and participate in their own lives as responsible growth narration.
Won-Jae Lee,Ji-Sung Park,HyeonJeong Lee,Seung-Chan Lee,Jeong-Hyun Lee,Sun-A Ock,Gyu-Jin Rho,Sung-Lim Lee 한국수정란이식학회 2017 한국동물생명공학회지 Vol.32 No.3
The estrogen-mediated effect of mesenchymal stem cells (MSCs) is a highly critical factor for the clinical application of MSCs. However, the present study is conducted on MSCs derived from adult donors, which have different physiological status with steroid hormonal changes. Therefore, we explores the important role of 17β-estradiol (E2) in MSCs derived from female and male newborn piglets (NF- and NM-pBMSCs), which are non-sexually matured donors with steroid hormones. The results revealed that in vitro treatment of MSCs with E2 improved cell proliferation, but the rates varied according to the gender of the newborn donors. Following in vitro treatment of newborn MSCs with E2, mRNA levels of Oct3/4 and Sox2 increased in both genders of MSCs and they may be correlated with both estrogen receptor α (ERα) and ERβ in NF-pBMSCs, but NM-pBMSCs were only correlated with ERα. Moreover, E2-treated NF-pBMSCs decreased in β-galactosidase activity but no influence on NM-pBMSCs. In E2-mediated differentiation capacity, E2 induced an increase in the osteogenic and chondrogenic abilities of both pBMSCs, but adipogenic ability may increased only in NF-pBMSCs. These results demonstrate that E2 could affect both genders of newborn donor-derived MSCs, but the regulatory role of E2 varies depending on gender-dependent characteristics even though the original newborn donors had not been affected by functional steroid hormones.
Developing a semi-automatic data conversion tool for Korean ecological data standardization
Lee, Hyeonjeong,Jung, Hoseok,Shin, Miyoung,Kwon, Ohseok The Ecological Society of Korea 2017 Journal of Ecology and Environment Vol.41 No.3
Recently, great demands are rising around the globe for monitoring and studying of long-term ecological changes. To go with the stream, many researchers in South Korea have attempted to share and integrate ecological data for practical use. Although some achievements were made in the meantime, we still have to overcome a big obstacle that existing ecological data in South Korea are mostly spread all over the country in various formats of computer files. In this study, we aim to handle the situation by developing a semi-automatic data conversion tool for Korean ecological data standardization, based on some predefined protocols for ecological data collection and management. The current implementation of this tool works on only five species (libythea celtis, spittle bugs, mosquitoes, pinus, and quercus mongolica), helping data managers to quickly and efficiently obtain a standardized format of ecological data from raw collection data. With this tool, the procedure of data conversion is divided into four steps: data file and protocol selection step, species selection step, attribute mapping step, and data standardization step. To find the usability of this tool, we utilized it to conduct the standardization of raw five species data collected from six different observatory sites of Korean National Parks. As a result, we could obtain a common form of standardized data in a relatively short time. With the help of this tool, various ecological data could be easily integrated into the nationwide common platform, providing broad applicability towards solving many issues in ecological and environmental system.