• 제목/요약/키워드: Exogenous factor

검색결과 207건 처리시간 0.026초

Increased expression of interleukin-1β in triglyceride-induced macrophage cell death is mediated by p38 MAP kinase

  • Sung, Ho-Joong;Son, Sin-Jee;Yang, Seung-Ju;Rhee, Ki-Jong;Kim, Yoon-Suk
    • BMB Reports
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    • 제45권7호
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    • pp.414-418
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    • 2012
  • Triglycerides (TG) are implicated in the development of atherosclerosis through formation of foam cells and induction of macrophage cell death. In this study, we report that addition of exogenous TG induced cell death in phorbol 12-myristate 13-acetate-differentiated THP-1 human macrophages. TG treatment induced a dramatic decrease in interleukin-$1{\beta}$ (IL-$1{\beta}$) mRNA expression in a dose- and time-dependent manner. The expression of granulocyte macrophage colony-stimulating factor and platelet endothelial cell adhesion molecule remained unchanged. To identify signaling pathways involved in TG-induced downregulation of IL-$1{\beta}$, we added p38 MAPK, protein kinase C (PKC) or c-Raf1 specific inhibitors. We found that inhibition of p38 MAPK alleviated the TG-induced downregulation of IL-$1{\beta}$, whereas inhibition of PKC and c-Raf1 had no effect. This is the first report showing decreased IL-$1{\beta}$ expression during TG-induced cell death in a human macrophage line. Our results suggest that downregulation of IL-$1{\beta}$ expression by TG-treated macrophages may play a role during atherogenesis.

Neuregulin-1 promotes cardiomyocyte differentiation of genetically engineered embryonic stem cell clones

  • Wang, Zhi;Xu, Guotong;Wu, Yalan;Liu, Shaowen;Sun, Baogui;Dai, Qiuyan
    • BMB Reports
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    • 제41권10호
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    • pp.699-704
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    • 2008
  • Embryonic stem (ES) cell-derived cardiomyocytes (ESCMs) must be specifically purified in order to prevent teratoma formation, and this confusing issue has hampered their clinical application. We therefore investigated a technique to generate pure labeled ESCMs for possible use in cardiac repair. We generated transgenic ES cell lines expressing enhanced green fluorescent protein (EGFP) under the transcriptional control of the $\alpha$-cardiac myosin heavy chain ($\alpha$-MHC) promoter. Differentiated EGFP-positive ES cells displayed characteristics of CMs. Furthermore, neuregulin-1 (NRG-1) upregulated the expression of the cardiac-restricted transcription factors Nkx2.5 and GATA-4, as well as differentiated CM factors ($\alpha$-MHC, $\beta$-MHC). Immunohistochemistry demonstrated that NRG-1 increased expression of cardiac-specific troponin T in the beating foci of the embryoid bodies. This work revealed a potential method for specifically labeling and enriching ESCMs by combining genetically-engineered ES cell clones and exogenous growth factor treatment.

생쥐 대식세포의 감염균 치사활성과 종양 치사활성에 미치는 Polyamine 생합성 억제의 영향 (Effect of Polyamine Biosynthesis InhibItion on the Microbicidai and Jumoriddal Activities in Mouse Macrophage)

  • 이준백;정노팔
    • 한국동물학회지
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    • 제34권2호
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    • pp.173-180
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    • 1991
  • 생쥐 대식세포의 감염균 치사활성과 종양 치사활성에 미치는 Polyamine 생합성 억제의 영향을 알아보기 위하여 ornithine의 억제제인 $\alpha$ -Difluoromethylomithine (DFMO)과 S-adenosylmethionine decarboxylase의 억제제인 methylhlyoxal bis(guanylhydrazone)(MGBG)을 in vitro 또는 in vivo에서 처리하였다. 대시세포의 감염균 치사활성의 지표로서 화학발광(chemiluminescence)과 nitroblue tetrazolium(NBT)의 환원정도를 측정한 결과, 염증유발물질인 thioglycollate(TG)와 세균이 세포내 독소인 liopopolysac- charide(LPS)를 주사하였거나 BCG를 감염시킨 후 측정된 화학 발광의 수준은 TG, LPS, BCG의 순으로 증가하였다. 그러나 이런 화학발생의 수준은 DFMO를 경구투여 하였을 때 전체적으로 감소하였고, 이 세포에 의한 NBT 환원정도 또한 DFMO와 MGBG의 in vitro 처리에 의하여 감소되었다. 한편 BDG로 활성화시킨 대식세포의 종양 괴사인자분비에 의한 종양치사 및 종양세포와의 부착에 의한 직접적 치사정도를 측정한 결과, polyamine생합성억제제의 처리농도를 증가시킴에 따라 그 정도는 감소하였지만, 외부에서 polyamine인 putrescene을 처리 하였을 때 회복되었다. 위의 결과로부터 대식세포내의 polyamine 생합성은 이 세포의 최적 활성화와 과정에 필요한 것으로 생각된다.

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에너지 집약도, 에너지 가격 그리고 기술 수준 간의 동태적 관계 분석 (Analyzing the Relation between Energy Intensity, Energy Price and TFP in Korea)

  • 김기진;원두환;정수관
    • 자원ㆍ환경경제연구
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    • 제29권2호
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    • pp.195-217
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    • 2020
  • 지속가능한 발전을 달성하기 위한 방안으로 에너지 집약도 개선이 주목받고 있다. 에너지 가격과 기술 수준은 에너지 집약도에 영향을 미치는 주요한 요인으로 세 변수의 연관성에 관한 실증연구는 해외를 중심으로 진행되어왔다. 그러나 우리나라를 대상으로 한 연구는 드물다. 이에 본 연구에서는 우리나라를 대상으로 에너지 집약도, 에너지 가격, 총요소생산성 간 동태적 관계를 분석하였다. 분석 결과 세 변수는 장기균형관계를 형성하며, 총요소생산성의 증가는 장·단기에서 모두 에너지 집약도를 감소시키는 것으로 나타났다. 총요소생산성의 증가가 에너지 집약도 개선에 미치는 효과는 단기보다 장기에 더 큰 것으로 나타났다. 반면 에너지 가격은 에너지 집약도에 유의미한 영향을 미치지 못하였다. Granger 인과성 검정 결과, 에너지 집약도와 총요소생산성은 상호 Granger 인과하지만, 에너지 가격은 약외생적인 것으로 나타났다. 우리나라의 에너지 집약도 개선을 위해서는 전반적인 기술 수준의 개선이 필요하며, 단기적인 처방보다 장기적인 관점에서 정책적 방안을 마련하는 게 바람직하다는 것을 확인할 수 있었다.

Clomiphene Citrate와 성선자극호르몬을 병합한 배란유도주기에서 성교와 인공수정에 의한 임신율의 비교 (Pregnancy Rate by Intrauterine Insemination (IUI) or Timed-Intercourse In Stimulated Cycles with Clomiphene Citrate and Gonadotropins)

  • 홍정의;이지삼
    • Clinical and Experimental Reproductive Medicine
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    • 제26권1호
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    • pp.31-41
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    • 1999
  • To evaluate the effectiveness of intrauterine insemination (IUI) in the treatment of infertility, timed-intercourse and intrauterine insemination by husband in stimulated cycles with clomiphene citrate and gonadotropins were compared in a total of 105 cycles. Patients received 100mg of clomiphene citrate daily for 5 days starting on day 3 of the menstrual cycle followed by hMG or FSH. Doses of exogenous gonadotropins were adjusted by the follicular development and concentrations of serum estradiol $(E_2)$. More than 3 follicles reaching >16 mm were present in the ovary, 5,000 IU of hCG was administered intramusculary. Patients received a maximum of three intercourse or IUI cycles for the treatment. Severe male (<$10{\times}10^6$ motile sperm) or age factor (>39 y) patients were excluded in this study. Pregnancy was classified as clinical if a gestational sac or fetal cardiac activity was seen on ultrasound. The overall clinical pregnancy rates were 17.1% per cycle (18/105) and 21.2% per patient (18/85). The pregnancy rates (per cycle) were 17.5% (11/63) in intercourse and 16.7% (7/42) in IUI groups, respectively. IUI had no significant improvement in pregnancy rate compared with timed-intercourse. The multiple pregnancy rates were 11.1% (1 twin and 1 triplet). No patient developed ovarian hyperstimulation. Abortion rate was 28.6% (2/7) in IUI group only. The delivery and ongoing pregnancy rates were 15.2% per cycle (16/105) and 18.8% per patient (16/85). There were no differences in age, duration of infertility, follicle size and level of estradiol $(E_2)$ on the day of hCG injection in pregnant and non-pregnant groups. However, total doses of gonadotropins were higher in pregnant group than in non-pregnant group (p<0.01). Pregnancy rate was not affected by ovulatory status at the time of insemination. These results indicate that well timed-intercourse in stimulated cycles is as effective as IUI for infertile couples.

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Generation of Isthmic Organizer-Like Cells from Human Embryonic Stem Cells

  • Lee, Junwon;Choi, Sang-Hwi;Lee, Dongjin R;Kim, Dae-Sung;Kim, Dong-Wook
    • Molecules and Cells
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    • 제41권2호
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    • pp.110-118
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    • 2018
  • The objective of this study was to induce the production of isthmic organizer (IsO)-like cells capable of secreting fibroblast growth factor (FGF) 8 and WNT1 from human embryonic stem cells (ESCs). The precise modulation of canonical Wnt signaling was achieved in the presence of the small molecule CHIR99021 ($0.6{\mu}M$) during the neural induction of human ESCs, resulting in the differentiation of these cells into IsO-like cells having a midbrain-hindbrain border (MHB) fate in a manner that recapitulated their developmental course in vivo. Resultant cells showed upregulated expression levels of FGF8 and WNT1. The addition of exogenous FGF8 further increased WNT1 expression by 2.6 fold. Gene ontology following microarray analysis confirmed that IsO-like cells enriched the expression of MHB-related genes by 40 fold compared to control cells. Lysates and conditioned media of IsO-like cells contained functional FGF8 and WNT1 proteins that could induce MHB-related genes in differentiating ESCs. The method for generating functional IsO-like cells described in this study could be used to study human central nervous system development and congenital malformations of the midbrain and hindbrain.

PKC Downstream of PI3-Kinase Regulates Peroxynitrite Formation for Nrf2-Mediated GSTA2 Induction

  • Kim, Sang-Geon;Kim, Sun-Ok
    • Archives of Pharmacal Research
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    • 제27권7호
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    • pp.757-762
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    • 2004
  • The protective adaptive response to electrophiles and reactive oxygen species is mediated by the induction of phase II detoxifying genes including glutathione S-transferases (GSTs). NF-E2-related factor-2 (Nrf2) phosphorylation by protein kinase C (PKC) is a critical event for its nuclear translocation in response to oxidative stress. Previously, we have shown that peroxynitrite plays a role in activation of Nrf2 and Nrf2 binding to the antioxidant response element (ARE) via the pathway of phosphatidylinositol 3-kinase (PI3-kinase) and that nitric oxide synthase in hepatocytes is required for GSTA2 induction. In view of the importance of PKC and Pl3-kinase in Nrf2-mediated GST induction, we investigated the role of these kinases in peroxynitrite formation for GSTA2 induction by oxidative stress and determined the relationship between PKC and PI3-kinase. Although PKC activation by phorbol 12-myristate-13-acetate (PMA) did not increase the extents of constitutive and inducible GSTA2 expression, either PKC depletion by PMA or PKC inhibition by staurosporine significantly inhibited GSTA2 induction by tert-butylhydroquinone (t-SHa) a prooxidant chemical. Therefore, the basal PKC activity is req- uisite for GSTA2 induction. 3-Morpholinosydnonimine (SIN-1), which decomposes and yields peroxynitrite, induced GSTA2, which was not inhibited by PKC depletion, but slightly enhanced by PKC activation, suggesting that PKC promotes peroxynitrite formation for Nrf2-mediated GSTA2 induction. Treatment of cells with S-nitroso-N-acetyl-penicillamine (SNAP), an exogenous NO donor, in combination with t-BHQ may produce peroxynitrite. GSTA2 induction by SNAP + t-BHQ was not decreased by PKC depletion, but rather enhanced by PKC activation, showing that the activity of PKC might be required for peroxynitrite formation. LY294002 a P13-kinase inhibitor blocked GSTA2 induction by t-BHQ, which was reversed by PMA-induced PKC activation. These results provide evidence that PKC may playa role in formation of peroxynitrite that activates Nrf2 for GSTA2 induction and that PKC may serve an activator for GSTA2 induction downstream of PI3-kinase.

A Structural Relationship between Pleasure and Customer Satisfaction, Switching Costs, and Relationship Commitment in Fitness Center

  • Kim, Yang-Young;Byun, Kyung-Won
    • International journal of advanced smart convergence
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    • 제10권4호
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    • pp.158-164
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    • 2021
  • The purpose of this study is to analyze the structural relationship between customer's pleasure, customer satisfaction, switching cost, and relationship commitment using the fitness center and provide implications. Specifically, this study aims to investigate the effect of the degree of customer's awareness of pleasure on the relationship commitment through the medium of customer satisfaction and switching cost. For this purpose, the structural equation model was constructed based on the previous studies, and the exogenous variables were pleasure, and the endogenous variables were customer satisfaction, switching costs and relationship commitment. The subjects of this study were customers who used fitness centers in the metropolitan area. The sampling method for the sample survey was a total of 277 people using convenience sampling. 257 copies were used as final data except for 20 samples that were not appropriate for the study. The statistical program for data analysis was IBM SPSS Ver. 26.0 and Amos 21.0. The specific data processing method is as follows: First, frequency analysis was conducted to understand the general characteristics of the subjects. In order to verify the validity and reliability of the research tools, confirmatory factor analysis and reliability analysis were conducted. In order to understand the theoretical relationship between each variable, structural equation model was conducted. The results of data processing on the research model are as follows: First, the pleasure of the fitness center customers had a positive effect on customer satisfaction. Second, customer satisfaction had a positive effect on the switching costs. Third, customer satisfaction had a positive effect on the customer commitment. Fourth, switching costs had a positive effect on customer commitment.

구조방정식 모델을 이용한 사회경제적 수준과 치주질환과의 연관성 (Relationship between socioeconomic status and periodontal disease using Structural Equation Modeling)

  • 황수연;양진영;김기은
    • 한국치위생학회지
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    • 제18권6호
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    • pp.979-986
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    • 2018
  • Objectives: The purpose of this study was to investigate the relationship between socioeconomic status and periodontal disease. Methods: The data used for the analysis were obtained from the sixth Korean National Health and Nutrition Examination Survey (2015). A total of 5,632 adults, aged over 19 years, were included in the study. This study analyzed data relating to socioeconomic status and health behaviors. The socioeconomic status was defined as an exogenous factor. Periodontal disease was the endogenous variable. Health behavior was a mediating variable. The study hypotheses were tested using Structural Equation Modeling analysis with Mplus 7.0 software. Results: According to the model fit test, the associated root-mean-square error was 0.05 (90% CI: 0.046-0.059); comparative fit index was 0.93; Tucker-Lewis index was 0.88; and standardized root-mean-square residual was 0.03. We found that socioeconomic status had significant effects on health behaviors (${\beta}=0.304$, p<0.001) and periodontal disease (${\beta}=-0.289$, p=0.001). Moreover, health behaviors had significant effects on periodontal diseases (${\beta}=0.143$, p<0.001). The analysis of a possible relationship between socioeconomic status and periodontal disease using path analysis demonstrated health behaviors difficulties, along with direct and indirect effects, further increased the risk of periodontal disease. Conclusions: The findings suggest that future interventions for the prevention of periodontal disease should consider health behavior.

Celecoxib의 항산화 작용에 따른 성체 치주인대 줄기세포 사멸억제 (Inhibition of Human Periodontal Stem Cell Death Following the Antioxidant Action of Celecoxib)

  • 이경희
    • 대한통합의학회지
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    • 제11권2호
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    • pp.169-179
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    • 2023
  • Purpose : Although human periodontal ligament stem cells (hPDLSCs) are a supportive factor for tissue engineering, oxidative stress during cell culture and transplantation has been shown to affect stem cell viability and mortality, leading to failed regeneration. The aim of this study was to evaluate the antioxidant and protective effects against cell damage of celecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, and the antioxidant signal of hPDLSCs in H2O2-induced oxidative stress. Methods : To induce oxidative stress in cultured hPDLSCs, H2O2 was used as an exogenous reactive oxygen species (ROS). Dose-dependent celecoxib (.1, 1, 10, or 100 µM) was administered after H2O2 treatment. WST-1 assay was used to assess cell damage and western blot was used to observe antioxidant activity of hPDLSCs in oxidative stress. Immunohistochemistry was performed for inverting the localization of the SOD and Nrf2 antibody. Results : We found that progressive cell death was induced in hPDLSCs by H2O2 treatment. However, low-dose celecoxib reduced H2O2-induced cellular damage and eventually enhanced the SOD activity and Nrf2 signal of hPDLSCs. Oxidative stress-induced morphological change in hPDLSCs included lowered the survival and number of spindle-shaped cells, and shrinkage and shortening of cell fibers. Notably, celecoxib promoted cell survival function and activated antioxidants such as SOD and Nrf2 by positively regulating the cell survival signal pathway, and also reduced the number of morphological changes in hPDLS. Immunohistochemistry results showed a greater number of SOD- and Nrf2-stained cells in the celecoxib-treated group following oxidative stress. Conclusion : By increasing SOD and Nrf2 expression at the antioxidant system, the findings suggest that celecoxib enhanced the antioxidative ability of hPDLSCs and protected cell viability against H2O2-induced oxidative stress by increasing SOD and Nrf2 expression in the antioxidant system.