• Title/Summary/Keyword: EMT-I

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Snail Switches 5-FU-induced Apoptosis to Necrosis through Akt/PKB Activation and p53 Down-regulation (Snail의 Akt/PKB의 활성화와 p53의 downregulation를 통한 5-FU-induced apoptosis의 necrosis로의 전환)

  • Lee, Su-Yeon;Jeon, Hyun-Min;Ju, Min-Kyung;Kim, Cho-Hee;Jeong, Eui-Kyong;Park, Hye-Gyeong;Kang, Ho-Sung
    • Journal of Life Science
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    • v.22 no.8
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    • pp.1018-1023
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    • 2012
  • Snail is a zinc finger transcription factor that induces epithelial-to-mesenchymal transition (EMT), which promotes tumor invasion and metastasis by repressing E-cadherin expression. In addition, Snail restricts the cellular apoptotic response to apoptotic stimuli or survival factor withdrawal; however, its molecular mechanism remains largely unknown. In this study, we have investigated the mechanism underlying Snail-mediated chemoresistance to 5-fluorouracil (5-FU), one of the most widely used anti-cancer drugs. When Snail was overexpressed by doxycycline (DOX) in MCF-7 #5 cells, it inhibited 5-FU-induced apoptotic cell death and switched the cell death mode to necrosis. Snail expression, either by DOX treatment in MCF-7 #5 cells or by the transfection of Snail expression vectors pCR3.1-Snail-Flg, phosphorylation-resistant pCR3.1-S104, and 107A Snail-Flg in MCF-7 cells specifically induced PTEN down-regulation/inactivation and Akt/PKB activation, without affecting ERK1/2 activity. In addition, Snail prominently suppressed 5-FU-induced increases in p53 levels. These findings demonstrate that Snail switches 5-FU-induced apoptosis to necrosis through the activation of Akt/PKB and the down-regulation of p53 levels.

Analysis of Distributed Computational Loads in Large-scale AC/DC Power System using Real-Time EMT Simulation (대규모 AC/DC 전력 시스템 실시간 EMP 시뮬레이션의 부하 분산 연구)

  • In Kwon, Park;Yi, Zhong Hu;Yi, Zhang;Hyun Keun, Ku;Yong Han, Kwon
    • KEPCO Journal on Electric Power and Energy
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    • v.8 no.2
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    • pp.159-179
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    • 2022
  • Often a network becomes complex, and multiple entities would get in charge of managing part of the whole network. An example is a utility grid. While the entire grid would go under a single utility company's responsibility, the network is often split into multiple subsections. Subsequently, each subsection would be given as the responsibility area to the corresponding sub-organization in the utility company. The issue of how to make subsystems of adequate size and minimum number of interconnections between subsystems becomes more critical, especially in real-time simulations. Because the computation capability limit of a single computation unit, regardless of whether it is a high-speed conventional CPU core or an FPGA computational engine, it comes with a maximum limit that can be completed within a given amount of execution time. The issue becomes worsened in real time simulation, in which the computation needs to be in precise synchronization with the real-world clock. When the subject of the computation allows for a longer execution time, i.e., a larger time step size, a larger portion of the network can be put on a computation unit. This translates into a larger margin of the difference between the worst and the best. In other words, even though the worst (or the largest) computational burden is orders of magnitude larger than the best (or the smallest) computational burden, all the necessary computation can still be completed within the given amount of time. However, the requirement of real-time makes the margin much smaller. In other words, the difference between the worst and the best should be as small as possible in order to ensure the even distribution of the computational load. Besides, data exchange/communication is essential in parallel computation, affecting the overall performance. However, the exchange of data takes time. Therefore, the corresponding consideration needs to be with the computational load distribution among multiple calculation units. If it turns out in a satisfactory way, such distribution will raise the possibility of completing the necessary computation in a given amount of time, which might come down in the level of microsecond order. This paper presents an effective way to split a given electrical network, according to multiple criteria, for the purpose of distributing the entire computational load into a set of even (or close to even) sized computational loads. Based on the proposed system splitting method, heavy computation burdens of large-scale electrical networks can be distributed to multiple calculation units, such as an RTDS real time simulator, achieving either more efficient usage of the calculation units, a reduction of the necessary size of the simulation time step, or both.

Phosphoinositides Signaling and Epithelial-to-Mesenchymal Transition: Putative Topic for Basic Toxicological Research

  • Lee, Chang-Ho
    • Toxicological Research
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    • v.24 no.1
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    • pp.1-9
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    • 2008
  • Ptdlns(4,5)$P_2$ is a key cellular phosphoinositide that localizes in separate and distinctive pools in subcellular membrane and vesicular compartments. In membranes, Ptdlns(4,5)$P_2$ acts as a precursor to second messengers and is itself a main signaling and targeting molecule. Specific subcellular localization of type I PIP kinases directed by interacting with specific targeting module differentiates Ptdlns(4,5)$P_2$ production in a spatial and temporal manner. Several lines of evidences support the idea that Ptdlns(4,5)$P_2$ is generated in very specific pools in a spatial and temporal manner or by feeding Ptdlns(4,5)$P_2$ directly to effectors. In this concept, the interaction of PIPKI isoforms with a specific targeting module to allow precise subcellular targeting modulates highly specific Ptdlns(4,5)$P_2$ synthesis and channeling overall effectors. For instance, localization of PIPKI${\gamma}$661 to focal adhesions by an interaction with talin results in spatial and temporal production of Ptdlns(4,5)$P_2$, which regulates EGF-stimulated directional cell migration. In addition, Type $I{\gamma}$ PIPK is targeted to E-cadherin in cell adherence junction and plays a role in controlling dynamics of cell adherence junction and endocytosis of E-cadherin. Characterizing how PIP kinase isoforms are regulated by interactions with their targeting modules, as well as the mechanisms by which their product, Ptdlns(4,5)$P_2$, exerts its effects on cellular signaling processes, is crucial to understand the harmonized control of numerous cellular signaling pathways. Thus, in this review the roles of the Ptdlns(4)P(5) kinases and Ptdlns(4,5)$P_2$ were described and critically reviewed in terms of regulation of the E-cadherin trafficking, cell migration, and formation of cell adherence junction which is indispensable and is tightly controlled in epithelial-to-mesenchymal transition process.

Tight junction protein 1 is regulated by transforming growth factor-β and contributes to cell motility in NSCLC cells

  • Lee, So Hee;Paek, A Rome;Yoon, Kyungsil;Kim, Seok Hyun;Lee, Soo Young;You, Hye Jin
    • BMB Reports
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    • v.48 no.2
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    • pp.115-120
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    • 2015
  • Tight junction protein 1 (TJP1), a component of tight junction, has been reported to play a role in protein networks as an adaptor protein, and TJP1 expression is altered during tumor development. Here, we found that TJP1 expression was increased at the RNA and protein levels in TGF-${\beta}$-stimulated lung cancer cells, A549. SB431542, a type-I TGF-${\beta}$ receptor inhibitor, as well as SB203580, a p38 kinase inhibitor, significantly abrogated the effect of TGF-${\beta}$ on TJP1 expression. Diphenyleneiodonium, an NADPH oxidase inhibitor, also attenuated TJP1 expression in response to TGF-${\beta}$ in lung cancer cells. When TJP1 expression was reduced by shRNA lentiviral particles in A549 cells (A549-sh TJP1), wound healing was much lower than in cells infected with control viral particles. Taken together, these data suggest that TGF-${\beta}$ enhances TJP1 expression, which may play a role beyond structural support in tight junctions during cancer development.

A Study on Perception types of Emergency Medical Technology major Student's concerning the Female 119 Paramedics: Focusing on a Q-Methodology Approach (응급구조(학)과 학생의 여성119구급대원에 대한 인식 유형 연구 : Q방법론적 접근)

  • Lee, Jaemin;Han, Seungtae;An, Juyeong
    • Journal of the Society of Disaster Information
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    • v.12 no.4
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    • pp.389-402
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    • 2016
  • This research is about Department of Emergency medical services students' cognition type of female 119 paramedics. The purpose of this research is to understand department of emergency medical servises students' cognition of female 119 paramedics and identify characteristics classified by types. To this end, applying Q-method, this research objectively analyzes 72 department of emergency medical services students' reaction who complete the field training about ambulance about female 119 paramedics. The result of the department of emergency medical services students recognized type of female 119 paramedics could be typed into four types. The type I is recognized as "Stamina limit type", the type II as "expert type", the type III as "guardian angel type", and the type IV as "feminine experience type". The type I has 28.3%, the type II has 12.7%, the type III has 6%, and the type IV has 3.8% explanation power, and these explain 51% of total variable. Generally department of emergency medical services students' cognition of female 119 paramedic is that they are expert in first aid but students' cognition is negative because of female 119 paramedic's limit of stamina, exposure to danger, and giving birth and infant care thus we should arrange solution of these cognition.

A study on the pedicatric accident (응급실 내원 아동에 대한 분석)

  • Son In-A
    • Journal of Korean Public Health Nursing
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    • v.14 no.2
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    • pp.332-341
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    • 2000
  • Children's accident is a largely preventable public health problem. Little is known. however, about population-based incident and outcome of pediatric accident. From 1997.9 through 1998,8. admission data from emergency center in I city were collected. 1418 patient from 0 through 13 years of age were selected. All children with unintensional accidental problems were identified through coded sheet which categorizes epidemiologic characteristics. The specific purposes of this study are analysis about the characteristics of pediatric accidents. And it aims to produce the basic data necessary for accident prevention policy development. The results of this study were as follows; 1. The number of male children$(62.6\%)$ were higher than female children$(37.4\%)$ 2. The age group from 1 to 3 years represents the highest proportion$(45.4\%)$ of every accidents except on traffic accident. 3. The highest proportion of accident were as follows occured during the June-August$(34\%)$, Sunday$(22.6\%)$, and 17-21 p.m. $(37.2\%)$ 4. The main causes of accident include general trauma$(70.9\%)$, environmental accident$(l6.8\%)$. and traffic accident$(l2.1\%)$, 5. Preschool age group represents more than half$(65.4\%)$ of traffic accident. 6. environmental injury includes burns $(46.6\%)$, foreign body$(43.6\%)$, exposure to poisonous materials$(6.3\%)$. and bite(3.3) This results could be used to develope prevention programs and assist in accident prevention system development. And also these data substantiate that accident prevention program decrease safety-related injury rate in preschool age group must be concentrated on enhancing access to a system to have a significant effect. Furthermore, it is necessary for accident prevention. So several suggestions are described here: 1. Development of parent's educational program for accident prevention and safety education should be done actively. 2. Home safety surveillance system should be initiated. 3. The initiation of children's accident report system could be contribute the analysis and the reduction of accident.

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Aspirin-Triggered Resolvin D1 Inhibits TGF-β1-Induced EndMT through Increasing the Expression of Smad7 and Is Closely Related to Oxidative Stress

  • Shu, Yusheng;Liu, Yu;Li, Xinxin;Cao, Ling;Yuan, Xiaolong;Li, Wenhui;Cao, Qianqian
    • Biomolecules & Therapeutics
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    • v.24 no.2
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    • pp.132-139
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    • 2016
  • The endothelial-mesenchymal transition (EndMT) is known to be involved in the transformation of vascular endothelial cells to mesenchymal cells. EndMT has been confirmed that occur in various pathologic conditions. Transforming growth factor ${\beta}1$ (TGF-${\beta}1$) is a potent stimulator of the vascular endothelial to mesenchymal transition (EMT). Aspirin-triggered resolvin D1 (AT-RvD1) has been known to be involved in the resolution of inflammation, but whether it has effects on TGF-${\beta}1$-induced EndMT is not yet clear. Therefore, we investigated the effects of AT-RvD1 on the EndMT of human umbilical vein vascular endothelial cells line (HUVECs). Treatment with TGF-${\beta}1$ reduced the expression of Nrf2 and enhanced the level of F-actin, which is associated with paracellular permeability. The expression of endothelial marker VE-cadherin in HUVEC cells was reduced, and the expression of mesenchymal marker vimentin was enhanced. AT-RvD1 restored the expression of Nrf2 and vimentin and enhanced the expression of VE-cadherin. AT-RvD1 did also affect the migration of HUVEC cells. Inhibitory ${\kappa}B$ kinase 16 (IKK 16), which is known to inhibit the NF-${\kappa}B$ pathway, had an ability to increase the expression of Nrf2 and was associated with the inhibition effect of AT-RvD1 on TGF-${\beta}1$-induced EndMT, but it had no effect on TGF-${\beta}1$-induced EndMT alone. Smad7, which is a key regulator of TGF-${\beta}$/Smads signaling by negative feedback loops, was significantly increased with the treatment of AT-RvD1. These results suggest the possibility that AT-RvD1 suppresses the TGF-${\beta}1$-induced EndMT through increasing the expression of Smad7 and is closely related to oxidative stress.

LncRNA H19/miR-29b-3p/PGRN Axis Promoted Epithelial-Mesenchymal Transition of Colorectal Cancer Cells by Acting on Wnt Signaling

  • Ding, Dayong;Li, Changfeng;Zhao, Tiancheng;Li, Dandan;Yang, Lei;Zhang, Bin
    • Molecules and Cells
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    • v.41 no.5
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    • pp.423-435
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    • 2018
  • This investigation was aimed at working out the combined role of lncRNA H19, miR-29b and Wnt signaling in the development of colorectal cancer (CRC). In the aggregate, 185 CRC tissues and corresponding para-carcinoma tissues were gathered. The human CRC cell lines (i.e. HT29, HCT116, SW480 and SW620) and normal colorectal mucosa cell line (NCM460) were also purchased. Si-H19, si-NC, miR-29b-3p mimics, miR-29b-3p inhibitor, si-PGRN and negative control (NC) were, respectively, transfected into the CRC cells. Luciferase reporter plasmids were prepared to evaluate the transduction activity of $Wnt/{\beta}-catenin$ signaling pathway, and dual-luciferase reporter gene assay was arranged to confirm the targeted relationship between H19 and miR-29b-3p, as well as between miR-29b-3p and PGRN. Finally, the proliferative and invasive capacities of CRC cells were appraised through transwell, MTT and scratch assays. As a result, overexpressed H19 and down-expressed miR-29b-3p displayed close associations with the CRC patients' poor prognosis (P < 0.05). Besides, transfection with si-H19, miR-29b-3p mimic or si-PGRN were correlated with elevated E-cadherin expression, decreased snail and vimentin expressions, as well as less-motivated cell proliferation and cell metastasis (P < 0.05). Moreover, H19 was verified to directly target miR-29b-3p based on the luciferase reporter gene assay (P < 0.05), and miR-29b-3p also bound to PGRN in a direct manner (P < 0.05). Finally, addition of LiCl ($Wnt/{\beta}-catenin$ pathway activator) or XAV93920 ($Wnt/{\beta}-catenin$ pathway inhibitor) would cause remarkably altered E-cadherin, c-Myc, vimentin and snail expressions, as well as significantly changed transcriptional activity of ${\beta}-catenin/Tcf$ reporter plasmid (P < 0.05). In conclusion, the lncRNA H19/miR-29b-3p/PGRN/Wnt axis counted a great deal for seeking appropriate diagnostic biomarkers and treatment targets for CRC.