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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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    • v.15 no.5
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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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    • v.46 no.4
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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.

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

  • Park, Sang-Gil;Lee, Joong-Woo;Nam, Ki-Dae;Kim, Pill-Sung
    • Journal of Navigation and Port Research
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    • v.33 no.10
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    • pp.703-707
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    • 2009
  • In order to evaluate applicability of cylindrical slit type block breakwater to the field water, which was designed from the previous physical model study, it is analyzed the calmness of harbor area by the numerical model experiment. For a small fishery port in southern coast of Korea a SWAN model using the wave action balance equation was formulated. The reflection and transmission coefficients induced by the physical model test were introduced to the numerical model. The model response with cylindrical slit type breakwater was compared with the impermeable breakwater case and the possibility of water quality improvement through the water circulation by the new structure was investigated. For numerical simulation, parameters of deepwater design wave from the prediction report II for overall deepwater design wave by KORDI were used and wind parameters from the 50years return period observed for 37years(1970~2006) were adopted in the numerical model. The response of west breakwater in Mijo port applying the NE and NNE waves, which were dominant in this area, was analyzed. It was found that the transmission characteristic of designed cylindrical slit breakwater was well presented in the numerical model.

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

  • Na, Nan-Ju;Kwon, Kee-Choon;Bien, Zeungnam
    • Journal of the Korean Institute of Intelligent Systems
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    • v.3 no.2
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    • pp.18-35
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    • 1993
  • The water level control system of the steam generator in a pressurized water reactor and its control problems are analysed. In this work the stable control strategy during the low power operation and transient states is studied. To solve the problem, a fuzzy logic control method is applied as a basic algorithm of the controller. The control algorithm is based on the operator's knowledges and the experiences of manual operation for water level control at the compact nuclear simulator set up in Korea Atomic Energy Research Institute. From a viewpoint of the system realization, the control variables and rules are established considering simpler tuning and the input-output relation. The control strategy includes the dynamic tuning method and employs a substitutional information using the bypass valve opening instead of incorrectly measured signal at the low flow rate as the fuzzy variable of the flow rate during the pressure control mode of the steam generator. It also involves the switching algorithm between the control valves to suppress the perturbation of water level. The simulation results show that both of the fine control action at the small level error and the quick response at the large level error can be obtained and that the performance of the controller is improved.

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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 (산부인과용 펄스형 $CO_2$레이저의 펄스모듈 특성과 동작파형 변화에 따른 안정된 시스템의 설계 및 구현)

  • Kim, Whi-Young
    • Journal of the Korea Computer Industry Society
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    • v.8 no.2
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    • pp.97-102
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    • 2007
  • [ $CO_2$ ] laser sees that is most suitable to get this effect through minimum formation damage and advantage that is root enemy of effect that happen in minimum cellular tissue depth of 0.1mm is stable living body organization or internal organs institution. Formation damage by ten can be related in formation's kind or energy density, length of evaporation time. If shorten evaporation time, surroundings cellular thermal damage 200 - because happen within 400um laser beam in rain focus sacred ground surroundings cellular tissue without vitiation me by evaporation Poe of very small floor as is clean steam can . Application is possible to vulva cuticle cousins by a paternal aunt quantity, uterine cancer, cuticle tumor by laser system that $CO_2$ laser gets into standard in obstetrics and gynecology application. Because effect that super pulse output is ten enemies of laser if uniformity one pulse durations are short almost is decreased, most of all pulse module special quality of Pulse style $CO_2$ laser for obstetrics and gynecology mode stabilization by weight very, in this research to get into short pulse duration and higher frequency density, do switching by high frequency in DC-DC Converter output DC's ripple high frequency to be changed, high frequency done current ripple amount of condenser for output filter greatly reduce can . Ripple of output approximately to Zero realization applying possible inductor realization through a special quality experiment do.

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

  • Park, Soo-Yong;Hawang, Moon-Young;Chol, Eun-Soo
    • Journal of Distribution Science
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    • v.13 no.6
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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.

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

  • Kim, Jong-Won;Jj, Gyu-Yong;Kim, Kyung-Chul;Lee, In-Sun;Eun, Jong-Won;Kim, Kyu-Kon;Lee, Yong-Tae
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.22 no.5
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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.

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

  • Kim, Jong-Oh
    • Journal of Life Science
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    • v.30 no.4
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    • pp.402-409
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    • 2020
  • Nervous necrosis virus (NNV) contains a bi-segmented viral genome, RNA1 (3.4 kb, RdRp), and RNA2 (1.4 kb, capsid protein) in a small particle (25 nm). Despite its extremely compact size, NNV has caused serious damage by infecting approximately 120 fish species worldwide since it was first reported in the late 1980s. In order to minimize the damage caused by NNV infection and develop effective vaccines, it is necessary to understand the intra cellular signaling system according to NNV infection. NNV infection induces cell cycle arrest at the G1 phase via the p53-dependent pathway to use the cellular system for its replication. Otherwise, host cells recognize NNV infection through the RIG-1-like receptor (RLR) signaling pathway to control the virus and infected cells, and then ISGs required for antiviral action are activated via the IFN signaling pathway. Moreover, apoptosis of infected cells is triggered by the unfolded protein response (UPR) through ER stress and mitochondria-mediated cell death. Cell signaling studies on the NNV infection mechanisms are still at an early stage and many pathways have yet to be identified. Understanding the various disease-specific cellular signaling systems associated with NNV infection is essential for rapid and accurate diagnosis and vaccine development.

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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    • v.39 no.2
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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.

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

  • Kim, Mi-Sun;Lee, Sung-Ho;Kim, Il-Hyun;Hwang, Byong-Yong;Kim, Jung-Hwan
    • The Journal of Korean Physical Therapy
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    • v.20 no.1
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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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