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Ginsenosides Rk1 and Rg5 inhibit transforming growth factor-β1-induced epithelial-mesenchymal transition and suppress migration, invasion, anoikis resistance, and development of stem-like features in lung cancer

  • Kim, Hyunhee;Choi, Pilju;Kim, Taejung;Kim, Youngseok;Song, Bong Geun;Park, Young-Tae;Choi, Seon-Jun;Yoon, Cheol Hee;Lim, Won-Chul;Ko, Hyeonseok;Ham, Jungyeob
    • Journal of Ginseng Research
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    • v.45 no.1
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    • pp.134-148
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    • 2021
  • Background: Lung cancer has a high incidence worldwide, and most lung cancer-associated deaths are attributable to cancer metastasis. Although several medicinal properties of Panax ginseng Meyer have been reported, the effect of ginsenosides Rk1 and Rg5 on epithelial-mesenchymal transition (EMT) stimulated by transforming growth factor beta 1 (TGF-β1) and self-renewal in A549 cells is relatively unknown. Methods: We treated TGF-β1 or alternatively Rk1 and Rg5 in A549 cells. We used western blot analysis, real-time polymerase chain reaction (qPCR), wound healing assay, Matrigel invasion assay, and anoikis assays to determine the effect of Rk1 and Rg5 on TGF-mediated EMT in lung cancer cell. In addition, we performed tumorsphere formation assays and real-time PCR to evaluate the stem-like properties. Results: EMT is induced by TGF-β1 in A549 cells causing the development of cancer stem-like features. Expression of E-cadherin, an epithelial marker, decreased and an increase in vimentin expression was noted. Cell mobility, invasiveness, and anoikis resistance were enhanced with TGF-β1 treatment. In addition, the expression of stem cell markers, CD44, and CD133, was also increased. Treatment with Rk1 and Rg5 suppressed EMT by TGF-β1 and the development of stemness in a dose-dependent manner. Additionally, Rk1 and Rg5 markedly suppressed TGF-β1-induced metalloproteinase-2/9 (MMP2/9) activity, and activation of Smad2/3 and nuclear factor kappa B/extra-cellular signal regulated kinases (NF-kB/ERK) pathways in lung cancer cells. Conclusions: Rk1 and Rg5 regulate the EMT inducing TGF-β1 by suppressing the Smad and NF-κB/ERK pathways (non-Smad pathway).

Effect Analysis of WBS-Based Technology Research and Analysis Methodology for Defense Technology Planning : With 'A' Missile System (국방기술기획을 위한 WBS 기반 기술 조사·분석 방법론의 효과분석 : 'A' 미사일 무기체계 중심으로)

  • Kim, Mi Seon
    • Journal of the Korea Academia-Industrial cooperation Society
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    • v.21 no.12
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    • pp.211-217
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    • 2020
  • Technology planning in the defense field aims to develop core technologies in order to develop weapon systems to satisfy the force integration period by researching and analyzing necessary technologies for weapon systems. In the past, core technology development projects were conducted by deriving core technology based on the main required operational capability. But in this case, there is the limitation that technologies which are necessary to develop weapon systems but do not directly affect required operational capability, such as system integration technologies, are not considered. In this paper, we propose a work breakdown structure-based technology research and analysis methodology that prevents vacant technologies by identifying core technologies that must be secured for the development of weapon systems at the component level. With the proposed methodology, it is possible to identify technologies that must be acquired to realize the required operational capability of systems or which must be secured even they do not affect the required operational capability.

Comparison of the spatial-temporal distributions of the heterotrophic dinoflagellates Gyrodinium dominans, G. jinhaense, and G. moestrupii in Korean coastal waters

  • Lee, Sung Yeon;Jeong, Hae Jin;Kang, Hee Chang;Ok, Jin Hee;You, Ji Hyun;Park, Sang Ah;Eom, Se Hee
    • ALGAE
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    • v.36 no.1
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    • pp.37-50
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    • 2021
  • Heterotrophic dinoflagellates Gyrodinium spp. are one of the major grazers of phytoplankton in many coastal waters. Gyrodinium dominans, G. jinhaense, and G. moestrupii have similar morphologies but different edible prey species. To explore the variations in the ecological niches of these three species, we investigated their spatial-temporal distributions in Korean waters. Because of the high similarity in morphology among these three Gyrodinium species, we used real-time polymerase chain reactions to quantify their abundance in water samples that were seasonally collected from 28 stations along the Korean Peninsula from April 2015 to October 2018. Cells of G. dominans were found at all sampling stations, G. jinhaense at 26 stations, and G. moestrupii at 22 stations, indicating that all three species were widely distributed in Korea. Furthermore, all three species displayed strong seasonal distributions. The largest numbers of the stations where G. dominans and G. jinhaense cells were present were found during the summer (26 and 23 stations, respectively), but that for G. moestrupii was found in the autumn (15 stations). The abundance of G. dominans was positively correlated with that of G. jinhaense, but not with that of G. moestrupii. The highest abundances of G. dominans (202.5 cells mL-1) and G. jinhaense (20.2 cells mL-1) were much greater than that of G. moestrupii (1.2 cells mL-1). The highest abundances of G. dominans and G. jinhaense were found in July, whereas that of G. moestrupii was found in March. The abundances of G. dominans and G. jinhaense, but not G. moestrupii, were positively correlated with water temperature. Therefore, the spatial-temporal distributions of G. dominans and G. jinhaense were closer than those of G. moestrupii and G. dominans or G. jinhaense. This differs from results based on the relative differences in ribosomal DNA sequences and the types of edible prey reported in the literature. Thus, the variations in spatial-temporal distributions and prey species of these three Gyrodinium species suggest that they may have different ecological niches in Korean coastal waters.

Interface Establishment between Reinforcement Learning Algorithm and External Analysis Program for AI-based Automation of Bridge Design Process (AI기반 교량설계 프로세스 자동화를 위한 강화학습 알고리즘과 외부 해석프로그램 간 인터페이스 구축)

  • Kim, Minsu;Choi, Sanghyun
    • Journal of the Computational Structural Engineering Institute of Korea
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    • v.34 no.6
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    • pp.403-408
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    • 2021
  • Currently, in the design process of civil structures such as bridges, it is common to make final products by repeating the process of redesigning, if the initial design is found to not meet the standards after a structural review. This iterative process extends the design time, and causes inefficient consumption of engineering manpower, which should be put into higher-level design, on simple repetitive mechanical work. This problem can be resolved by automating the design process, but the external analysis program used in the design process has been the biggest obstacle to such automation. In this study, we constructed an AI-based automation system for the bridge design process, including an interface that could control both a reinforcement learning algorithm, and an external analysis program, to replace the repetitive tasks in the current design process. The prototype of the system built in this study was developed for a 2-span RC Rahmen bridge, which is one of the simplest bridge systems. In the future, it is expected that the developed interface system can be utilized as a basic technology for linking the latest AI with other types of bridge designs.

Sensory characteristics and preferences of rice-based distilled soju aged in different types of containers using Check-All-That-Apply (CATA) (숙성 기간과 저장용기를 달리한 쌀 증류식 소주의 Check-All-That-Apply (CATA)를 활용한 감각특성 및 기호도 분석)

  • Kim, Wan-Keun;Lee, Seung-Joo
    • Korean Journal of Food Science and Technology
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    • v.54 no.3
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    • pp.362-368
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    • 2022
  • The sensory characteristics of nine rice-based distilled soju were determined using check-all-that-apply (CATA) profiling. A total of 53 consumers evaluated the soju for two appearance attributes, nine aroma attributes, nine flavor/taste attributes, four mouth-feel related sensory attributes, and overall desirability. The total sum of CATA terms indicated that 14 characteristics showed frequency differences of over 10 and that there were significant differences among nine samples for eleven sensory attributes as determined using Cochran's q test (p<0.05). Based on correspondence analysis of CATA data, the samples were primarily separated by the first dimension, which accounted for 89% of the total variance among samples. The "brown color," "fruit taste," and "grain aroma" characteristics had higher frequencies than those for the "white color," "acetone aroma," and 'alcohol taste" characteristics. Overall, there was a higher preference for oak-aged samples than for samples aged in other containers. "sweet aroma', 'fruit aroma," and "sweet taste" seemed to positively affect consumer preferences, while "bitter taste," "alcohol taste," and "acetone aroma" appeared to negatively affect consumer preferences as determined by principal coordinate analysis.

Relationship between DNA mismatch repair and CRISPR/Cas9-mediated knock-in in the bovine β-casein gene locus

  • Kim, Seung-Yeon;Kim, Ga-Yeon;You, Hyeong-Ju;Kang, Man-Jong
    • Animal Bioscience
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    • v.35 no.1
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    • pp.126-137
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    • 2022
  • Objective: Efficient gene editing technology is critical for successful knock-in in domestic animals. RAD51 recombinase (RAD51) gene plays an important role in strand invasion during homologous recombination (HR) in mammals, and is regulated by checkpoint kinase 1 (CHK1) and CHK2 genes, which are upstream elements of RAD51 recombinase (RAD51). In addition, mismatch repair (MMR) system is inextricably linked to HR-related pathways and regulates HR via heteroduplex rejection. Thus, the aim of this study was to investigate whether clustered regularly interspaced short palindromic repeats/CRISPR-associated 9 (CRISPR/Cas9)-mediated knock-in efficiency of human lactoferrin (hLF) knock-in vector in the bovine β-casein gene locus can be increased by suppressing DNA MMR-related genes (MSH2, MSH3, MSH6, MLH1, and PMS2) and overexpressing DNA double-strand break (DSB) repair-related genes (RAD51, CHK1, CHK2). Methods: Bovine mammary epithelial (MAC-T) cells were transfected with a knock-in vector, RAD51, CHK1, or CHK2 overexpression vector and CRISPR/sgRNA expression vector to target the bovine β-casein gene locus, followed by treatment of the cells with CdCl2 for 24 hours. After 3 days of CdCl2 treatment, the knock-in efficiency was confirmed by polymerase chain reaction (PCR). The mRNA expression levels of DNA MMR-related and DNA DSB repair-related genes were assessed by quantitative real-time PCR (RT-qPCR). Results: Treatment with CdCl2 decreased the mRNA expression of RAD51 and MMRrelated genes but did not increase the knock-in efficiency in MAC-T cells. Also, the overexpression of DNA DSB repair-related genes in MAC-T cells did not significantly affect the mRNA expression of MMR-related genes and failed to increase the knock-in efficiency. Conclusion: Treatment with CdCl2 inhibited the mRNA levels of RAD51 and DNA MMR-related genes in MAC-T cells. However, the function of MMR pathway in relation to HR may differ in various cell types or species.

Cardioprotective effect of ginsenoside Rb1 via regulating metabolomics profiling and AMP-activated protein kinase-dependent mitophagy

  • Hu, Jingui;Zhang, Ling;Fu, Fei;Lai, Qiong;Zhang, Lu;Liu, Tao;Yu, Boyang;Kou, Junping;Li, Fang
    • Journal of Ginseng Research
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    • v.46 no.2
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    • pp.255-265
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    • 2022
  • Background: Ginsenoside Rb1, a bioactive component isolated from the Panax ginseng, acts as a remedy to prevent myocardial injury. However, it is obscure whether the cardioprotective functions of Rb1 are related to the regulation of endogenous metabolites, and its potential molecular mechanism still needs further clarification, especially from a comprehensive metabolomics profiling perspective. Methods: The mice model of acute myocardial ischemia (AMI) and oxygen glucose deprivation (OGD)-induced cardiomyocytes injury were applied to explore the protective effect and mechanism of Rb1. Meanwhile, the comprehensive metabolomics profiling was conducted by high-performance liquid chromatography and quadrupole time-of-flight mass spectrometry (HPLC-Q/TOF-MS) and a tandem liquid chromatography and mass spectrometry (LC-MS). Results: Rb1 treatment profoundly reduced the infarct size and attenuated myocardial injury. The metabolic network map of 65 differential endogenous metabolites was constructed and provided a new inspiration for the treatment of AMI by Rb1, which was mainly associated with mitophagy. In vivo and in vitro experiments, Rb1 was found to improve mitochondrial morphology, mitochondrial function and promote mitophagy. Interestingly, the mitophagy inhibitor partly attenuated the cardioprotective effect of Rb1. Additionally, Rb1 markedly facilitated the phosphorylation of AMP-activated protein kinase α (AMPKα), and AMPK inhibition partially weakened the role of Rb1 in promoting mitophagy. Conclusions: Ginsenoside Rb1 protects acute myocardial ischemia injury through promoting mitophagy via AMPKα phosphorylation, which might lay the foundation for the further application of Rb1 in cardiovascular diseases.

Heat Shock Protein 90 Gene Expression in Juvenile Sea Cucumber Apostichopus japonicus (Echinodermata; Holothuroidea) according to Releasing Methods (어린 돌기해삼 Apostichopus japonicus (Echinodermata; Holothuroidea) 방류 방법에 따른 열충격단백질90 유전자의 발현 분석)

  • Lee, Dong-Han;Lee, Seungheon;Jeong, Dong-Bin;Sohn, Young Chang
    • Journal of Marine Life Science
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    • v.7 no.1
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    • pp.29-36
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    • 2022
  • Sea cucumber, Aposticopus japonicus, is a major invertebrate species in the coastal regions of Korea. To evaluate the short-term stress levels according to the releasing methods, this study investigated the gene expression profiles of heat shock protein 90 (HSP90) by real-time quantitative polymerase chain reaction. When the juvenile sea cucumbers were packed in the vinyl bag with oxygen followed by transportation for 30 min or air-exposed for 1 h, the HSP90 gene expression levels in the experimental groups were significantly increased compared to those of the control groups (transported group, p=0.001; air-exposed group, p=0.032). The experimental group at 6 h post-release by seed-spreading method and at 2~6 h post-release by underwater hose-releasing method on board a fishing boat showed that the levels of HSP90 gene expression were not statistically significant but decreased slightly compared to the control group (seed-spreading group, p=0.069; hose-releasing group, p=0.093). On the other hand, the HSP90 gene expression showed an increasing pattern as the time passed (~6 h) after underwater release of juvenile sea cucumbers by divers (p=0.061). These results suggest that HSP90 gene expression can be used to investigate short-term stress response and effective releasing methods of juvenile sea cucumbers.

Effect of Halophyte (Spartina anglica and Calystegia soldanella) Extracts on Skin Moisturizing and Barrier Function in HaCaT Cells (염생식물인 갯끈풀과 갯메꽃 추출물의 HaCaT 세포에서 피부 보습 및 피부 장벽 기능에 미치는 영향)

  • Ha, Yuna;Jeong, JaeWoo;Lee, Won Hwi;Oh, Jun Hyuk;Kim, Youn-Jung
    • Journal of Marine Life Science
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    • v.6 no.2
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    • pp.58-65
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    • 2021
  • As aging progresses, reactive oxygen species (ROS) reduces skin moisturization and collapses skin barrier function. In this study, we evaluated the efficacy of skin moisturizing and skin barrier function enhancement by extracts from halophytes using HaCaT cells. Spartina anglica (S. anglica; SAE) and Calystegia soldanella (C. soldanella; CSE), a kind of halophytes, were collected from Dongmak beach in Incheon, and extracted with 70% ethanol. At the first, we evaluated the cytotoxicity of extracts in HaCaT cell using WST-8 Kit. As a result, the other experiment was conducted by setting the concentration at which the cell viability was 90% or more. SAE and CSE showed high radical scavenging activity through ABTS assay. Expression levels of genes related to skin moisturizing and skin barrier functions, were analyzed by real-time qPCR. As a result, it showed that the expression of aquaporin 3, hyaluronan synthase 2, and transglutaminase 1 was increased by SAE treatment but not changed by CSE. Activation of extracellular signal regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38 mitogen activated protein kinase was induced by SAE. These results suggest that SAE can be used as functional materials for cosmetics for skin moisturizing and barrier function enhancement.

OGLE-2019-BLG-0362Lb: A SUPER-JOVIAN-MASS PLANET AROUND A LOW-MASS STAR

  • Chung, Sun-Ju;Yee, Jennifer C.;Udalski, Andrej;Gould, Andrew;Albrow, Michael D.;Jung, Youn Kil;Hwang, Kyu-Ha;Han, Cheongho;Ryu, Yoon-Hyun;Shin, In-Gu;Shvartzvald, Yossi;Zang, Weicheng;Cha, Sang-Mok;Kim, Dong-Jin;Kim, Seung-Lee;Lee, Chung-Uk;Lee, Dong-Joo;Lee, Yongseok;Park, Byeong-Gon;Pogge, Richard W.;Poleski, Radek;Mroz, Przemek;Pietrukowicz, Pawel;Skowron, Jan;Szymanski, Michal K.;Soszynski, Igor;Kozlowski, Szymon;Rybicki, Krzysztof A.;Iwanek, Patryk;Wrona, Marcin;Gromadzki, Mariusz;Ulaczyk, Krzysztof
    • Journal of The Korean Astronomical Society
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    • v.55 no.4
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    • pp.123-130
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    • 2022
  • We present the analysis of a planetary microlensing event OGLE-2019-BLG-0362 with a shortduration anomaly (~0.4 days) near the peak of the light curve, which is caused by the resonant caustic. The event has a severe degeneracy with ∆𝜒2 = 0.9 between the close and the wide binary lens models both with planet-host mass ratio q ≃ 0.007. We measure the angular Einstein radius but not the microlens parallax, and thus we perform a Bayesian analysis to estimate the physical parameters of the lens. We find that the OGLE-2019-BLG-0362L system is a super-Jovian-mass planet $M_p=3.26^{+0.83}_{-0.58}M_J $ orbiting an M dwarf $M_h=0.42^{+0.34}_{-0.23}M_{\odot}$ at a distance $D_L=5.83^{+1.04}_{-1.55}kpc$. The projected star-planet separation is ${\alpha}_{\bot}= 2.18^{+0.58}_{-0.72}AU$, which indicates that the planet lies beyond the snow line of the host star.