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검색결과 595건 처리시간 0.026초

Matrine Reduces Proliferation of Human Lung Cancer Cells by Inducing Apoptosis and Changing miRNA Expression Profiles

  • Liu, Yong-Qi;Li, Yi;Qin, Jie;Wang, Qian;She, Ya-Li;Luo, Ya-Li;He, Jian-Xin;Li, Jing-Ya;Xie, Xiao-Dong
    • Asian Pacific Journal of Cancer Prevention
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    • 제15권5호
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    • pp.2169-2177
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    • 2014
  • Matrine, a main active component extracted from dry roots of Sophora flavecens, has been reported to exert antitumor effects on A549 human non-small lung cancer cells, but its mechanisms of action remain unclear. To determine effects of matrine on proliferation of A549 cells and assess possible mechanisms, MTT assays were employed to detect cytotoxicity, along with o flow cytometric analysis of DNA content of nuclei of cells following staining with propidium iodide to analyze cell cycle distribution. Western blotting was performed to determined expression levels of Bax, Bcl-2, VEGF and HDAC1, while a microarray was used to assessed changes of miRNA profiles. In the MTT assay, matrine suppressed growth of human lung cancer cell A549 in a dose- and timedependent manner at doses of 0.25-2.5 mg/ml for 24h, 48h or 72h. Matrine induced cell cycle arrest in G0/G1 phase and decreased the G2/M phase, while down-regulating the expression of Bcl2 protein, leading to a reduction in the Bcl-2/Bax ratio. In addition, matrine down regulated the expression level of VEGF and HDAC1 of A549 cells. Microarray analysis demonstrated that matrine altered the expression level of miRNAs compared with untreated control A549 cells. In conclusion, matrine could inhibit proliferation of A549 cells, providing useful information for understanding anticancer mechanisms.

Triptolide Inhibits the Proliferation of Immortalized HT22 Hippocampal Cells Via Persistent Activation of Extracellular Signal-Regulated Kinase-1/2 by Down-Regulating Mitogen-Activated Protein Kinase Phosphatase-1 Expression

  • Koo, Hee-Sang;Kang, Sung-Don;Lee, Ju-Hwan;Kim, Nam-Ho;Chung, Hun-Taeg;Pae, Hyun-Ock
    • Journal of Korean Neurosurgical Society
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    • 제46권4호
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    • pp.389-396
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    • 2009
  • Objective : Triptolide (TP) has been reported to suppress the expression of mitogen-activated protein kinase (MAPK) phosphatase-1 (MKP-1), of which main function is to inactivate the extracellular signal-regulated kinase-1/2 (ERK-1/2), the p38 MAPK and the c-Jun N-terminal kinase-1/2 (JNK-1/2), and to exert antiproliferative and pro-apoptotic activities. However, the mechanisms underlying antiproliferative and pro-apoptotic activities of TP are not fully understood. The purpose of this study was to examine whether the down-regulation of MKP-1 expression by TP would account for antiproliferative activity of TP in immortalized HT22 hippocampal cells. Methods : MKP-1 expression and MAPK phosphorylation were analyzed by Western blot. Cell proliferation was assessed by $^3H$-thymidine incorporation. Small interfering RNA (siRNA) against MKP-1, vanadate (a phosphatase inhibitor), U0126 (a specific inhibitor for ERK-1/2), SB203580 (a specific inhibitor for p38 MAPK), and SP600125 (a specific inhibitor for JNK-1/2) were employed to evaluate a possible mechanism of antiproliferative action of TP. Results : At its non-cytotoxic dose, TP suppressed MKP-1 expression, reduced cell growth, and induced persistent ERK-1/2 activation. Similar growth inhibition and ERK-1/2 activation were observed when MKP-1 expression was blocked by MKP-1 siRNA and its activity was inhibited by vanadate. The antiproliferative effects of TP, MKP-1 siRNA, and vanadate were significantly abolished by U0126, but not by SB203580 or SP600125. Conclusion : Our findings suggest that TP inhibits the growth of immortalized HT22 hippocampal cells via persistent ERK-1/2 activation by suppressing MKP-1 expression. Additionally, this study provides evidence supporting that MKP-1 may play an important role in regulation of neuronal cell growth.

실린더 슬릿형 소파블록 방파제의 실해역 적용을 위한 수치실험분석 (Analysis of Numerical Experiment for Field Application of Cylindrical Slit Type Block Breakwater)

  • 박상길;이중우;남기대;김필성
    • 한국항해항만학회지
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    • 제33권10호
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    • pp.703-707
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    • 2009
  • 선행되었던 연구인 실린더 슬릿형 소파블록 방파제에 대하여 실해역에서의 적용성을 평가하기 위하여 수치모델 해석을 통해 항내정온도를 분석하였다. 남해의 소규모 어항에 대해 파랑작용 평형방정식을 이용하는 SWAN 모델을 구성하고 수리모형실험에서 분석된 실린더 슬릿형 방파제의 반사와 투과계수를 도입하였다. 항내의 정온도의 변화를 불투과성 방파제와 비교하여 다루고 새로운 구조물로 해수교환을 통한 해역수질환경의 개선 가능성을 검토해보았다. 수치실험은 한국해양연구원의 전해역 심해설계파 추정 보고서 II(2005)중의 심해설계파 제원을 사용하였으며, 대상해역의 1970년~2006년(37년간) 관측된 연최대 풍속자료를 이용하여 산정된 50년빈도 설계풍을 모델에 반영하였다. 미조항에서 서방파제에 주로 영향을 미치는 NE, NNE계열의 파랑의 내습에 대한 분석을 수행하였으며, 그 결과 투과성구조물의 특성이 수치모형에서도 잘 재현하고 있음을 파악하였다.

저출력 및 과도상태시 원전 증기발생기 수위제어에 관한 연구 (A Study on Water Level Control of PWR Steam Generator at Low Power Operation and Transient States)

  • 나난주;권기춘;변증남
    • 한국지능시스템학회논문지
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    • 제3권2호
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    • pp.18-35
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    • 1993
  • 가압경수로형 원자력발전소 수위제어시스템과 특히 저출력시 수위제어상의 문제점들이 분석 및 고찰되었으며 저출력으로 운전시의 여러 과도특성에서도 안정된 제어를 하고 급수펌프고장과 같은 큰 수위변동 발생시에는 신속한 수위응답을 얻기 위한 방법이 주로 연구되었다. 제어기의 기본 알고리즘으로 퍼지제어기법을 적용하였으며 여기에 필요한 제어규칙 및 알고리즘은 운전원의 지식과 한국원자력연구소에 설치된 교육훈련용 모의제어반에서의 수동운전경험을 바탕으로 설정되었다. 실제 시스템 구현관점에서 제어변수 및 적용규칙은 보다 간편한 튜닝과 입출력변수간의 영향을 고려하여 세워졌다. 저유량일 때 측정이 불량한 유량신호에 대해, 중기발생기를 압력제어모드로 운전할 때에는 유량차의 퍼지변수로서 우회급수밸브의 개도를 이용한 대체정보를 채용하였으며 수위오차의 크기에 따라 유량차의 소속함수를 달리하는 동적인 튜닝방법을 사용하였다. 또한 우회급수와 주급수밸브간 간단한 전환알고리즘의 적용으로 밸브절환시의 수위요동을 억제하고자 하였다. 시뮬레이션 결과 저출력구간에서 원자로출력변동에 대해 기존에 설치된 방법보다 안정된 제어를 하고 동적 튜닝의 적용으로 미세제어동작과 수위오차가 큰 영역의 제어에 대해 신속한 응답과 함께 제어성능이 개선되었음을 보였다.

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산부인과용 펄스형 $CO_2$레이저의 펄스모듈 특성과 동작파형 변화에 따른 안정된 시스템의 설계 및 구현 (Design and embodiment of stable system by change of action waveform by pulsemodule special quality of pulse style$CO_2$ laser for obstetrics and gynecology)

  • 김휘영
    • 한국컴퓨터산업학회논문지
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    • 제8권2호
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    • pp.97-102
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    • 2007
  • [ $CO_2$ ] 레이저는 최소한 조직손상으로 이러한 효과를 얻는데 최적이라고 보며 0.1mm의 최소한의 세포조직 깊이에서 일어나는 효과의 근본적인 장점은 생체조직이나 내장기관에 안정적이다. 열에 의한 조직손상은 조직의 종류나 에너지밀도, 증발시간의 장단에 관계될 수가 있다 증발시간을 짧게 하면 주위세포의 열적손상은 $200\sim400um$이내에 일어나므로 레이저 빔은 비초점 영역에서 주위세포조직을 손상함이 없이 증발에 의한 제거나, 아주 얇은 층의 포를 깨끗하게 증발시킬 수 가 있다. $CO_2$레이저는 산부인과 응용에 표준이 되는 레이저시스템으로 외음부 상피내종양, 자궁암, 상피 종양에도 적용이 가능하다. 슈퍼펄스 출력은 거의 동일하나 펄스지속시간이 짧으면 레이저의 열적인 효과가 감소가 되므로 무엇보다도 산부인과용 펄스형 $CO_2$ 레이저의 펄스모듈 특성은 모드안정화가 매우 중요함으로, 본 연구에서는 짧은 펄스지속시간과 고출력밀도 되도록, DC-DC Converter에서 고주파로 스위칭 할수록 출력 DC의 ripple은 고주파화 되는데, 고주파화된 전류 리플은 출력 필터용 콘덴서의 량을 크게 줄일 수 있다. 출력의 ripple을 근사적으로 Zero까지 실현이 가능한 인덕터를 적용하여 특성실험을 통하여 실현하였다.

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중소기업에서 경영자의 배려와 용서가 학습조직 활동과 조직성과에 미치는 영향 (Effects of Executive Compassion and Forgiving Behavior on Organizational Activities and Performance)

  • 박수용;황문영;최은수
    • 유통과학연구
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    • 제13권6호
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    • pp.105-118
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    • 2015
  • Purpose - Currently, strengthening small and medium-sized enterprises (SME) in terms of competitiveness is a key economic issue. However, the problem is that many SMEs lack the internal competence required to cope with a rapidly changing market structure. Such problems can act as an obstacle to economic development, yet most SMEs in Korea are dealing with this problem today. A company's source of competitive advantage is changing from quantity to quality, facility to knowledge, and hardwork to creativity. Under such circumstances, a company should place learning and sharing of knowledge and continuously creating new knowledge as its priority. This study aims to identify the effect of a chief executive officer's (CEO) compassion and forgiveness - positive factors in organizational emotion - on learning organization activities and organizational performance, through a theoretical comparison. Research design, data, and methodology - For this study, SMEs based in Daejeon and Chungcheong area were selected. To secure credibility of the data, the subjects were selected among those who have been working at the business for six months or longer. The survey was conducted for 30 days from March 5, 2015 to April 5, 2015. Both offline and online surveys were conducted. Fifty companies were chosen and 700 questionnaires were distributed, with 506 used for analysis. Fifty subject companies (25 from Daejeon, 10 from Chungnam, 10 from Chungbuk, and five from Sejong) were selected and the objective, target, and survey content were explained to a manager at each company either face-to-face or on the phone. Of the total of 700 questionnaires distributed via mail or e-mail, 78.6% or 550 copies were returned. Excluding 44 insufficient questionnaires, the remainder, 506 questionnaires, were used for analysis. Results - This study analyzed how the CEO's compassion and forgiveness affects learning organization activities and organizational performance. First, compassion of the CEO at the SMEs directly affected the learning organization activities and indirectly affected the organizational performance. Second, forgiveness of the CEO at the SMEs did not affect the learning organization activities and organizational performance directly or indirectly. Conclusions - The study conclusions are as follows. First, CEO compassionate behavior at the SMEs was a significant variable that directly and indirectly affected learning organization activities and organizational performance. Therefore, the CEO of an SME can create a positive organizational atmosphere through compassionate behaviors in the organization. Second, the forgiving behavior of the CEO did not have direct or indirect effects on learning organization activities and organizational performance. However, the reason for a CEO to continue his or her forgiving behavior is because it strengthens employee resilience, commitment, and self-efficacy to protect the organization from negative influences such as layoffs, risks, and wrongdoings. The action of forgiveness does not have direct or indirect effects. However, the CEO shall continue such behavior to strengthen members' physiological resilience, commitment, and self - effectiveness, and to protect the organization from risks including layoff and external negative factors.

우울증(憂鬱症)에 대한 형상의학적 고찰 (Inquiry on Post Surgery Induced Consumption in HyungSang Medicine View)

  • 김종원;지규용;김경철;이인선;은종원;김규곤;이용태
    • 동의생리병리학회지
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    • 제22권5호
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    • pp.1035-1046
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    • 2008
  • I looked into hypochondria, an increasing social problem, in psychological and Korean medical aspects and these conclusions were made through 16 clinical cases based on HyungSang medicine. Hypochondria is a disorder that is caused when feeble minded person could not fight the reality. It is caused by deficiency and stagnation of Ki which connects body and mind. In Korean medical view point mind and body is the same. Particularly, in HyungSang medicine believes that everyone's way of life and how to deal with situation differs according to the characteristics and traits. HyungSang medical treatment in hypochondria Mind and body is in line with each other, so manifestation of mental activity is caused by deficiency of combining action of vital Ki. Medication that helps combining force of vital Ki is needed. As the way people handle situation is different, according to characteristics and trait it is valid to differ counselling and treatment according to the criteria. Looking at 16 case studies of hypochondria patients, in gender wise, woman with astriction quality and engaging in much mental activities are more vulnerable. In view of vital substances, more cases were found in Jung type and Ki type. In animal type, bird and reptile type were, and in six meridian type, Tae yang, Yang Myong, Tae Eum and Kwolum type were more susceptible. Especially, cases of Indang being stagnant was noticeable. Moreover, the pulse activated parallel with the Heart which is a leading organ that manifests mental activity and controls seven emotions, so many cases were found that was far from Heart-Small intestine and Heart-Gall Bladder relationship.

어류신경괴사증바이러스(nervous necrosis virus, NNV) 감염에 따른 숙주의 방어기전관련 세포신호전달 (Intracellular Signaling Pathway for Host Defense Mechanisms against Piscine Nervous Necrosis Virus (NNV))

  • 김종오
    • 생명과학회지
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    • 제30권4호
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    • pp.402-409
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    • 2020
  • 신경괴사증바이러스(NNV)는 25 nm의 작은 입자 크기에 RNA1 (3.4 kb, RdRp), RNA2 (1.4 kb, capsid protein) 두 가닥의 RNA를 유전정보를 가진다. NNV는 1980년대 말 처음 보고된 이후 전 세계적으로 120여종의 어류에 감염을 일으키며 심각한 피해를 일으키고 있는 바이러스이다. NNV 감염에 의한 피해를 최소화하고 효율적인 백신들을 개발하기 위해서는 무엇보다 NNV 감염에 따른 세포내 신호전달체계를 이해할 필요가 있다. NNV는 세포내 감염 이후 숙주가 가진 바이러스 복제에 필요한 요소들을 이용할 수 있도록 숙주세포의 cell cycle arrest 등의 기작을 이용하는 것으로 알려졌다. 반면에 숙주 세포는 NNV와 감염된 세포를 제어하기 위해 RIG-1-like receptor signaling pathway 등을 통해 NNV 감염을 인지한 다음 IFN signaling pathway를 통해 항바이러스 작용에 필요한 ISG들을 발현시킨다. 또한 감염된 세포들을 사멸시키기 위해 ER stress를 통한 unfolded protein response (UPR), mitochondria-mediated cell death 작용을 통해 감염된 세포의 apoptosis를 유발한다. NNV 감염 기작에 대한 세포신호전달연구는 아직 초기단계이며 검증해야 할 pathway들이 아직도 많이 남아있는 상황이다. 따라서 NNV 감염과 연관된 다양한 세포신호전달체계를 탐색하고 질병 특이적인 세포신호전달체계를 이해함으로써 신속하고 정확한 진단법 및 백신 개발에 많은 도움이 될 것으로 생각된다.

MiR-29a and MiR-140 Protect Chondrocytes against the Anti-Proliferation and Cell Matrix Signaling Changes by IL-1β

  • Li, Xianghui;Zhen, Zhilei;Tang, Guodong;Zheng, Chong;Yang, Guofu
    • Molecules and Cells
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    • 제39권2호
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    • pp.103-110
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    • 2016
  • As a degenerative joint disease, osteoarthritis (OA) constitutes a major cause of disability that seriously affects the quality of life of a large population of people worldwide. However, effective treatment that can successfully reverse OA progression is lacking until now. The present study aimed to determine whether two small non-coding RNAs miR-29a and miR-140, which are significantly down-regulated in OA, can be applied together as potential therapeutic targets for OA treatment. MiRNA synergy score was used to screen the miRNA pairs that potentially synergistically regulate OA. An in vitro model of OA was established by treating murine chondrocytes with IL-$1{\beta}$. Transfection of miR-29a and miR-140 via plasmids was investigated on chondrocyte proliferation and expression of nine genes such as ADAMTS4, ADAMTS5, ACAN, COL2A1, COL10A1, MMP1, MMP3, MMP13 and TIMP metallopeptidase inhibitor 1 (TIMP1). Western blotting was used to determine the protein expression level of MMP13 and TIMP1, and ELISA was used to detect the content of type II collagen. Combined use of miR-29a and miR-140 successfully reversed the destructive effect of IL-$1{\beta}$ on chondrocyte proliferation, and notably affected the MMP13 and TIMP1 gene expression that regulates extracellular matrix. Although co-transfection of miR-29a and miR-140 did not show a synergistic effect on MMP13 protein expression and type II collagen release, but both of them can significantly suppress the protein abundance of MMP13 and restore the type II collagen release in IL-$1{\beta}$ treated chondrocytes. Compared with single miRNA transfection, cotransfection of both miRNAs exceedingly abrogated the suppressed the protein production of TIMP1 caused by IL-$1{\beta}$, thereby suggesting potent synergistic action. These results provided1novel insights into the important function of miRNAs' collaboration in OA pathological development. The reduced MMP13, and enhanced TIMP1 protein production and type II collagen release also implies that miR-29a and miR-140 combination treatment may be a possible treatment for OA.

스트레스-유도 열충격단백질 27(Heat Shock Protein 27)의 활성과 물리치료의 상관성 (The Activation of Stress-induced Heat Shock Protein 27 and the Relationship of Physical Therapy)

  • 김미선;이성호;김일현;황병용;김중환
    • The Journal of Korean Physical Therapy
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    • 제20권1호
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    • pp.57-65
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    • 2008
  • Purpose: Heat shock proteins (HSPs) are a group of proteins that are activated when cells are exposed to a variety of environmental stresses, such as infection, inflammation, exposure to toxins, starvation, hypoxia, brain injury, or water deprivation. The activation of HSPs by environmental stress plays a key role in signal transduction, including cytoprotection, molecular chaperone, anti-apoptotic effect, and anti-aging effects. However, the precise mechanism for the action of small HSPs, such as HSP27 and mitogen-activated protein kinases (MAPKs: extracellular-regulated protein kinase 1/2 (ERK1/2), p38MAPK, stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK), is not completely understood, particularly in application of cell stimulators including platelet-derived growth factor (PDGF), angiotensin II (AngII), tumor necrosis factor $\alpha$ (TNF$\alpha$), and $H_2O_2$. This study examined the relationship between stimulators-induced enzymatic activity of HSP27 and MAPKs from rat smooth and skeletal muscles. Methods: 2-dimensional electrophoresis (2DE) and matrix assisted laser desorption ionizationtime-of-flight/time-of-flight (MALDI-TOF/TOF) analysis were used to identify HSP27 from the intact vascular smooth and skeletal muscles. Three isoforms of HSP27 were detected on silver-stained gels of the whole protein extracts from the rat aortic smooth and skeletal muscle strips. Results: The expression of PDGF, AngII, TNF$\alpha$, and $H_2O_2$-induced activation of HSP27, p38MAPK, ERK1/2, and SAPK/JNK was higher in the smooth muscle cells than the control. SB203580 (30${\mu}$M), a p38MAPK inhibitor, increased the level of HSP27 phosphorylation induced by stimulators in smooth muscle cells. Furthermore, the age-related and starvation-induced activation of HSP27 was higher in skeletal muscle cells (L6 myoblast cell lines) and muscle strips than the control. Conclusion: These results suggest, in part, that the activity of HSP27 and MAPKs affect stressors, such as PDGF, AngII, TNF$\alpha$, $H_2O_2$, and starvation in rat smooth and skeletal muscles. However, more systemic research will be needed into physical therapy, including thermotherapy, electrotherapy, radiotherapy and others.

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