• Title/Summary/Keyword: Signaling Effect

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Regulation of IL-6 signaling by miR-125a and let-7e in endothelial cells controls vasculogenic mimicry formation of breast cancer cells

  • Park, Youngsook;Kim, Jongmin
    • BMB Reports
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    • v.52 no.3
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    • pp.214-219
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    • 2019
  • The role of tumor-proximal factors in tumor plasticity during chemoresistance and metastasis following chemotherapy is well studied. However, the role of endothelial cell (EC) derived paracrine factors in tumor plasticity, their effect on chemotherapeutic outcome, and the mechanism by which these paracrine factors modulate the tumor microenvironment are not well understood. In this study, we report a novel mechanism by which endothelial miR-125a and let-7e-mediated regulation of interleukin-6 (IL-6) signaling can manipulate vasculogenic mimicry (VM) formation of MDA-MB-231 breast cancer cells. We found that endothelial IL-6 levels were significantly higher in response to cisplatin treatment, whereas levels of IL-6 upon cisplatin exposure remained unchanged in MDA-MB-231 breast cancer cells. We additionally found an inverse correlation between IL-6 and miR-125a/let-7e expression levels in cisplatin treated ECs. Interestingly, IL-6, IL-6 receptor (IL-6R), and signal transducer and activator of transcription 3 (STAT3) genes in the IL-6 pathway are closely regulated by miR-125a and let-7e, which directly target its 3' untranslated region. Functional analyses revealed that endothelial miR-125a and let-7e inhibit IL-6-induced adhesion of monocytes to ECs. Furthermore, conditioned medium from cisplatin treated ECs induced a significantly higher formation of VM in MDA-MB-231 breast cancer cells as compared to that from intact ECs; this effect of cisplatin treatment was abrogated by concurrent overexpression of miR-125a and let-7e. Overall, this study reveals a novel EC-tumor cell crosstalk mediated by the endothelial miR-125a/let-7e-IL-6 signaling axis, which might improve chemosensitivity and provide potential therapeutic targets for the treatment of cancer.

Effect of Synthetic CaM and NFAT Oligodeoxynucleotide on MPP+-Stimulated Mesencephalic Neurons

  • Jihyun Park;Kyung Mi Jang
    • Journal of Interdisciplinary Genomics
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    • v.5 no.2
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    • pp.35-41
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    • 2023
  • Background: Ca2+ signaling plays a vital role in neuronal signaling and altered Ca2+ homeostasis in Parkinson's disease (PD). Overexpression of αSYN significantly promote the Ca2+-Calmodulin (CaM) activity and subsequent nuclear translocation of nuclear factor of activated T cells (NFAT) transcription factor in dopaminergic neurons of midbrain. However, the exact role of Ca2+-CaM and NFAT in PD pathology is yet to be elucidated. Methods: We designed the CaM-NFAT-oligodeoxynucleotide (ODN), a synthetic short DNA containing complementary sequence for NFAT transcription factor and CaM mRNA. Then, the effect of CaM-NFAT-ODN on 1-methyl-4-phenylpyridinium (MPP+)-mediated neurotoxicity was investigated in mimic PD model in vitro. Results: First, the expression of αSYN and CaM was strongly increased in substantia nigra (SN) of PD and the expression of tyrosine hydroxylase (TH) was strongly increased in control SN. Additionally, the expression of apoptosis marker proteins was strongly increased in SN of PD. Transfection of CaM-NFAT-ODN repressed CaM and pNFAT, the target genes of this ODN in rat embryo primary mesencephalic neurons. It also reduced ERK phosphorylation, a downstream target of these genes. These results demonstrated that CaM-NFAT-ODN operated successfully in rat embryo primary mesencephalic neurons. Transfection of CaM-NFAT-ODN repressed TH reduction, αSYN accumulation, and apoptosis by MPP+-induced neurotoxicity response through Ca2+ signaling and mitogen-activated protein kinases (MAPK) signaling. Conclusion: Synthetic CaM-NFAT-ODN has substantial therapeutic feasibility for the treatment of neurodegenerative diseases.

Screening, Signalling and Wage Effect of English Scores in Korean Labor Market: Evidence from College Graduates (노동시장에서 영어점수의 선별·신호 및 임금효과: 대졸자를 중심으로)

  • Lee, Sangheon;Yang, Jun Seok
    • Journal of Labour Economics
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    • v.34 no.2
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    • pp.79-107
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    • 2011
  • This study investigates the status of English scores in the Korean labor market. We provide an empirical explanation of how English scores affect labor performances in Korea. Specifically, we focus on the effects of TOEIC scores on college graduates' job opportunity and wage premium. Our empirical tests for TOEIC scores are implemented in three dimensions: (1) Screening effects (2) Signaling effects (3) Wage effects. The results are as follows. First, we find the positive correlation between TOEIC scores and job opportunities, which implies that TOEIC scores play an important role in employee selection process. Second, our tests give the same results when it comes to job seeker's use of TOEIC scores as signaling instrument. That is, high TOEIC scores have positive signaling effects in the labor market. However, there also exists disadvantage effect of low TOEIC scores, in that job applicants with TOEIC scores below certain level are even more disadvantageous than those with no TOEIC scores. Finally, wage premium of TOEIC scores are found, even when other variables (e.g. GPA) are controlled or we use the instrumental variable estimate.

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Hepatoprotective effect of ultrasonicated ginseng berry extract on a rat mild bile duct ligation model

  • Nam, Yoonjin;Ko, Sung Kwon;Sohn, Uy Dong
    • Journal of Ginseng Research
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    • v.43 no.4
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    • pp.606-617
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    • 2019
  • Background: The Panax ginseng berry extract (GBE) is well known to have an antidiabetic effect. The aim of this study is to evaluate and investigate the protective effect of ultrasonication-processed P. ginseng berry extract (UGBE) compared with GBE on liver fibrosis induced by mild bile duct ligation (MBDL) model in rats. After ultrasonication process, the composition ratio of ginsenoside in GBE was changed. The component ratio of ginsenosides Rh1, Rh4, Rg2, Rg3, Rk1, Rk3, and F4 in the extract was elevated. Methods: In this study, the protective effect of the newly developed UGBE was evaluated on hepatotoxicity and neuronal damage in MBDL model. Silymarin (150 mg/kg) was used for positive control. UGBE (100 mg/kg, 250 mg/kg, 500 mg/kg), GBE (250 mg/kg), and silymarin (150 mg/kg) were orally administered for 6 weeks after MBDL surgery. Results: The MBDL surgery induced severe hepatotoxicity that leads to liver inflammation in rats. Also, the serum ammonia level was increased by MBDL surgery. However, the liver dysfunction of MBDL surgery-operated rats was attenuated by UGBE treatment via myeloid differentiation factor 88-dependent Toll-like receptor 4 signaling pathways. Conclusion: UGBE has a protective effect on liver fibrosis induced by MBDL in rats through inhibition of the TLR4 signaling pathway in liver.

20(S)-ginsenoside Rg3 exerts anti-fibrotic effect after myocardial infarction by alleviation of fibroblasts proliferation and collagen deposition through TGFBR1 signaling pathways

  • Honglin Xu;Haifeng Miao;Guanghong Chen;Guoyong Zhang;Yue Hua;Yuting Wu;Tong Xu;Xin Han;Changlei Hu;Mingjie Pang;Leyi Tan;Bin Liu;Yingchun Zhou
    • Journal of Ginseng Research
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    • v.47 no.6
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    • pp.743-754
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    • 2023
  • Background: Myocardial fibrosis post-myocardial infarction (MI) can induce maladaptive cardiac remodeling as well as heart failure. Although 20(S)-ginsenoside Rg3 (Rg3) has been applied to cardiovascular diseases, its efficacy and specific molecular mechanism in myocardial fibrosis are largely unknown. Herein, we aimed to explore whether TGFBR1 signaling was involved in Rg3's anti-fibrotic effect post-MI. Methods: Left anterior descending (LAD) coronary artery ligation-induced MI mice and TGF-β1-stimulated primary cardiac fibroblasts (CFs) were adopted. Echocardiography, hematoxlin-eosin and Masson staining, Western-blot and immunohistochemistry, CCK8 and Edu were used to study the effects of Rg3 on myocardial fibrosis and TGFBR1 signaling. The combination mechanism of Rg3 and TGFBR1 was explored by surface plasmon resonance imaging (SPRi). Moreover, myocardial Tgfbr1-deficient mice and TGFBR1 adenovirus were adopted to confirm the pharmacological mechanism of Rg3. Results: In vivo experiments, Rg3 ameliorated myocardial fibrosis and hypertrophy and enhanced cardiac function. Rg3-TGFBR1 had the 1.78×10-7 M equilibrium dissociation constant based on SPRi analysis, and Rg3 inhibited the activation of TGFBR1/Smads signaling dose-dependently. Cardiac-specific Tgfbr1 knockdown abolished Rg3's protection against myocardial fibrosis post-MI. In addition, Rg3 downregulated the TGF-β1-mediated CFs growth together with collagen production in vitro through TGFBR1 signaling. Moreover, TGFBR1 adenovirus partially blocked the inhibitory effect of Rg3. Conclusion: Rg3 improves myocardial fibrosis and cardiac function through suppressing CFs proliferation along with collagen deposition by inactivation of TGFBR1 pathway.

Effect of Submerged Culture of Ceriporia lacerata Mycelium on Insulin Signaling Pathway in 3T3-L1 Cell (Ceriporia lacerata 균사체 배양물이 3T3-L1 세포에서 인슐린 신호 전달에 미치는 영향)

  • Shin, Eun Ji;Kim, Ji-Eun;Kim, Ji-Hye;Park, Yong Man;Yoon, Sung Kyoon;Jang, Byeong-Churl;Lee, Sam-Pin;Kim, Byoung-Cheon
    • Journal of Life Science
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    • v.26 no.3
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    • pp.325-330
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    • 2016
  • In this study, we evaluated the antidiabetic effect of submerged culture of Ceriporia lacerata mycelium (CL01) on glucose uptake and the expression of mRNA and protein of major signal markers of insulin signaling pathway in 3T3-L1 adipocytes. After 3T3-L1 adipocytes were pre-treated by CL01 (0, 2, 10 mg/ml) for 8 hours, followed with treatment of insulin, the glucose uptake levels significantly increased by more 55.1%, 94.4% than negative control respectively (p<0.01, 0.001) in a dose-dependent manner. However, in case of CL01 pre-treatment without insulin, the glucose uptake did not increase compared with insulin-treated 3T3-L1. Also we demonstrated that the protein expression levels of pIR β, pAkt, pPI3K and pAMPK and the mRNA expression levels of GLUT4 in adipocytes inducing insulin resistance increased in CL01-treated group compared with negative control. These results demonstrated that CL01 affected glucose metabolism and the protein and gene expression through insulin signaling pathway, and increased glucose uptake levels effectively. More than 90% of those who have suffered for type 2 diabetes are more likely to have from hyperinsulinemia, hypertension, obesity and etc. because of altered insulin signaling pathway. So, it is probably considered that intake of CL01 may treat type 2 diabetes by normalization of insulin signaling pathway, and it will provide useful evidences regarding a mechanism for cure of type 2 diabetes.

Review of Effect of the Mechanical Stress on Muscle (근육에 대한 역학적 스트레스의 영향)

  • Kang, Jong-Ho;Kim, Jin-Sang
    • PNF and Movement
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    • v.6 no.2
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    • pp.51-57
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    • 2008
  • Purpose : Mechanical stress activates signaling cascades and leading to a specific response of a network of signaling pathways. The purpose of this study is to review the effect of mechanical stress-induced adaptation in skeletal muscle involves a biological mechanisms. Methods : This is literature study with Pubmed, Medline and books. Results : Skeletal muscle tissue demonstrates a malleability and may adjust its metabilic response, vascularization and neuromuscular characteristic makeup in response to alteration in functional demands. The adaptation in skeletal muscle involoves a multitude of signalling mechanisms related with insuline-like growth factor, vascular endothelial growth factor, neurotrophins. Conclusions : The identification of the basic relationships underlying the malleability of skeletal muscle tissue is likely to be of relevance for our understanding with PNF technique.

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Why Popular Employees Engage in Knowledge Sharing: The Motivational Approach (왜 인기 있는 직원이 지식공유를 하는가: 동기부여 관점에서)

  • Kim, Boyoung;Kim, Yonghyun
    • Knowledge Management Research
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    • v.21 no.1
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    • pp.151-173
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    • 2020
  • The purpose of this study is to identify the antecedents that impact on the individual knowledge sharing based on motivational perspectives. Specifically, the authors investigate the roles of general self-efficacy and popularity on knowledge sharing drawn on costly signaling theory and trait activation theory. Data from 227 pairs of employees and coworkers working in companies located in South Korea supported the model. General self-efficacy was positively related to knowledge sharing and popularity was positively associated to knowledge sharing. Also, by taking an interactional approach, our study demonstrated the moderating effect of popularity on the relationship between general self-efficacy and knowledge sharing. The positive relationship between general self-efficacy and knowledge sharing is significant when popularity is low, but not significant when popularity is high. Our findings suggest that the various motivation types including intrinsic and extrinsic motivations for knowledge sharing of individuals exist simultaneously and these motivations have an interactive effect on knowledge sharing.

A modelling on Shunt Reactors in Railway Power Transmission System (철도고배 전송선로 분로리액터 설치에 대한 모델링)

  • Lee, Jongsoo;Lee, Jongwoo
    • The Transactions of The Korean Institute of Electrical Engineers
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    • v.64 no.8
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    • pp.1262-1268
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    • 2015
  • I In power transmission systems, voltage changes continuously as reactive power is whether over supply or shortage. Reactive power produces in generators and consumes in transmission lines, and loads. Voltages at end points of transmission lines rise which is called Ferranti effect. Excessive voltage rising can reduce transmission equipment life, the voltage rising is usually permitted within the limit of 10%~30% excess. Shunt reactors are installed in transmission lines to put a curb on voltage rising. In this paper, we tried to do modelling for shunt reactor configuration types which are no grounding, grounded and grouded neutral reactor. Simulation are carried out for reactor magnitude for compensating transmission line capacitance.

Cytoprotective Effect of Taurine against Hydrogen Peroxide-Induced Oxidative Stress in UMR-106 Cells through the Wnt/β-Catenin Signaling Pathway

  • Lou, Jing;Han, Donghe;Yu, Huihui;Yu, Guang;Jin, Meihua;Kim, Sung-Jin
    • Biomolecules & Therapeutics
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    • v.26 no.6
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    • pp.584-590
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    • 2018
  • Osteoporosis development is closely associated with oxidative stress and reactive oxygen species (ROS). Taurine has potential antioxidant effects, but its role in osteoblasts is not clearly understood. The aim of this study was to determine the protective effects and mechanisms of actions of taurine on hydrogen peroxide ($H_2O_2$)-induced oxidative stress in osteoblast cells. UMR-106 cells were treated with taurine prior to $H_2O_2$ exposure. After treatment, cell viability, apoptosis, intracellular ROS production, malondialdehyde content, and alkaline phosphate (ALP) activity were measured. We also investigated the protein levels of ${\beta}-catenin$, ERK, CHOP and NF-E2-related factor 2 (Nrf2) along with the mRNA levels of Nrf2 downstream antioxidants. The results showed that pretreatment of taurine could reverse the inhibition of cell viability and suppress the induced apoptosis in a dose-dependent manner: taurine significantly reduced $H_2O_2$-induced oxidative damage and expression of CHOP, while it induced protein expression of Nrf2 and ${\beta}-catenin$ and activated ERK phosphorylation. DKK1, a Wnt/${\beta}-catenin$ signaling inhibitor, significantly suppressed the taurine-induced Nrf2 signaling pathway and increased CHOP. Activation of ERK signaling mediated by taurine in the presence of $H_2O_2$ was significantly inhibited by DKK1. These data demonstrated that taurine protects osteoblast cells against oxidative damage via Wnt/${\beta}-catenin$-mediated activation of the ERK signaling pathway.