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The regulatory mechanism of insulin like growth factor secretion by high glucose in mesangial cell: involvement of cAMP (Mesangial 세포에서 고포도당에 의한 insulin-like growth factor의 분비조절기전에 관한 연구: cAMP와의 관련성)

  • Heo, Jung-sun;Kang, Chang-won;Han, Ho-jae;Park, Soo-hyun
    • Korean Journal of Veterinary Research
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    • v.43 no.4
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    • pp.563-571
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    • 2003
  • Dysfunction of mesangial cells has been contributed to the onset of diabetic nephropathy. Insulin like growth factors (IGFs) are also implicated in the pathogenesis of diabetic nephropathy. However, it is not yet known about the effect of high glucose on IGF-I and IGF-II secretion in the mesangial cells. Furthermore, the relationship between cAMP and high glucose on the secretion of IGFs was not elucidated. Thus, we examined the mechanisms by which high glucose regulates secretion of IGFs in mesangial cells. Glucose increased IGF-I secretion in a time- (>8 hr) and dose- (>15 mM) dependent manner (p<0.05). Stimulatory effect of high glucose on IGF-I secretion is predominantly observed in 25 mM glucose (high glucose), while 25 mM glucose did not affect cell viability and lactate dehydrogenase release. High glucose also increased IGF-II secretion. The increase of IGF-I and IGF-II secretion is not mediated by osmotic effect, since mannitol and L-glucose did not affect IGF-I and IGF-II secretion. 8-Br-cAMP mimicked high glucose-induced secretion of IGF-I and IGF-II. High glucose-induced stimulation of IGF-I and IGF-II secretion was blocked not by pertussis toxin but by SQ 22536 (adenylate cyclase inhibitor). Rp-cAMP (cAMP antagonist), and myristoylated protein kinase A (PKA) inhibitor amide 14-22 (protein kinase A inhibitor). These results suggest that cAMP/PKA pathways independent of Gi protein may mediate high glucose-induced increase of IGF-I and IGF-II secretion in mesangial cells. Indeed, glucose (>15 mM glucose) increased cAMP formation. In conclusion, high glucose stimulates IGF-I and IGF-II secretion via cAMP/PKA pathway in mesangial cells.

Evaluation of Pressure Effects on Blast Valves for Facility Protection of Underground Computing Center (지하 전산센터의 시설보호를 위한 방폭밸브에 미치는 폭압 평가)

  • Pang, Seung-Ki;Shin, Jin-Won;Kim, Wae-deuk
    • Journal of the Korean Society for Geothermal and Hydrothermal Energy
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    • v.14 no.3
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    • pp.21-28
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    • 2018
  • This paper presents two-step simulations to calculate the influence of blast-induced pressures on explosion-protection valves installed at the boundary between a protection facility and a tunnel entering the facility. The first step is to calculate the respective overpressure on the entrance and exit of the tunnel when an explosion occurs near the tunnel entrance and exit to approach the protection facility. Secondly, the blast pressures on the explosion-protection valves mounted to walls located near the tunnel inside approaching the protection facility are analyzed with a 0.1 ms time variation using the results obtained from the first-step calculations. The following conclusions could be derived as a results: (1) The analysis of the entrance tunnel scenario, P1, leads to the maximum overpressure of 47 kPa, approximately a half of the ambient pressure, at the inner entrance due to the effect of blast barrier. For the scenario, P2, the case not blocked by the barrier, the maximum overpressure is 628 kPa, which is relatively high, namely, 5.2 times the ambient pressure. (2) It is observed that the pressure for the entrance tunnel is effectively mitigated because the initial blast pressures are partially offset from each other according to the geometry of the entrance and a portion of the pressures is discharged to the outside.

NFATc1 and NFATc3 is Involved in the Expression of Receptor Activator of NF-${\kappa}B$ Ligand in Activated T Lymphocytes

  • Heo, Sun-Jae;Park, Hyun-Jung;Baek, Jeong-Hwa
    • International Journal of Oral Biology
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    • v.38 no.1
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    • pp.37-42
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    • 2013
  • Receptor activator of NF-${\kappa}B$ ligand (RANKL) is an essential cytokine for osteoclast differentiation, activation and survival. T lymphocytes such as $T_{17}$ cells, a subset of T helper cells that produce IL-17, play an important role in rheumatoid arthritic bone resorption by producing inflammatory cytokines and RANKL. It has not yet been clearly elucidated how T cell activation induces RANKL expression. T cell receptor activation induces the activation of nuclear factor of activated T cell (NFAT) and expression of its target genes. In this study, we examined the role of NFAT in T cell activation-induced RANKL expression. EL-4, a murine T lymphocytic cell line, was used. When T cell activation was induced by phorbol 12-myristate 13-acetate (PMA) and ionomycin, RANKL expression increased in a time-dependent manner. In the presence of cyclosporin, an inhibitor of NFAT activation, this PMA/ionomycin-induced RANKL expression was blocked. Overexpression of either NFATc1 or NFATc3 induced RANKL expression. Chromatin immunoprecipitation results demonstrated that PMA/ionomycin treatment induced the binding of NFATc1 and NFATc3 to the mouse RANKL gene promoter. These results suggest that NFATc1 and NFATc3 mediates T cell receptor activation-induced RANKL expression in T lymphocytes.

A Study of the Residents' Use and Occupancy-Behavior in the Activity Areas of the Senior Nursing Facilities (노인요양시설 거주노인의 활동공간 이용행동 및 점유행태)

  • Lee, Min-Ah
    • Journal of Families and Better Life
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    • v.27 no.5
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    • pp.77-90
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    • 2009
  • The purpose of this study was to investigate the residents' use and occupancy-behavior in the activity areas of the senior nursing facilities, and to provide basic information to establish the appropriate physical elements for planning the activity areas. For the study, the observations in five facilities were conducted for one day, from 10 a.m. to 4 p.m by four researchers. The results of the study are summarized as follows: First, most of the using behaviors in the activity areas were the doing nothing or sleeping. The meals and program services were provided in only one activity area of the floor and it showed that the unit care system was perfunctorily conducted at those facilities. In the representative activity area, its openness was the main physical element influencing the spatial using frequency, while the accessibility and the openness in the sub-activity area were most important. The seating arrangements having comers were helpful for residents' interactions. Second, while facility programs and meals were provided in the specific activity area, there was no residents' occupancy in other activity areas at the same time. There were interactions including residents' conversations and watching/observations in non-designated activity areas such as the nursing stations and near corridors. But the residents' interactions and self-regulations were blocked by absence of territoriality, monotonous spatial compositions and furniture arrangements, insecurity of residents' privacy, wide or narrow areas, and isolated spatial type. Based on the results at the above, basic guidelines for planning the activity areas of senior nursing facilities can be proposed as follows: First, the isolated type and the sight interception should be avoided in representative activity areas. It should be partitioned with couple of areas through the appropriate furniture arrangements, and be prepared semi-private spaces in non-designated areas such as nursing station for the interactions among the residents and the staff. Second, in activity areas for small group, the isolated type is not also good for the residents' accessibility. The residents' privacy should be confirmed through the various spatial compositions, and enough areas need to be sure for the diverse furniture arrangements.

Effect of Herba Epimedii on hydrogen peroxide induced neurotoxicity in cultured rat dorsal root ganglion neurons

  • Park Seung-Taeck;Lee Young-Mi;Hong Gi-Youn;Choi Ki-Uk;Min Bu-Ki;Yoon Hyang-Suk;Chang Chul-Ho;Lee Kang-Chang;Juhng Seon-Kwan;Han Du-Seok;Lee Gap-Sang;Seong Kang-Kyung;Lee Geon-Mok
    • Advances in Traditional Medicine
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    • v.2 no.1
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    • pp.36-40
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    • 2002
  • Effects of hydrogen peroxide $(H_2O_2)-induced$ neurotoxicity were investigated in cultured newborn rat spinal dorsal root ganglion (DRG) neurons after DRG neurons were treated in the media containning various concentrations of $H_2O_2$. In addition, the protective effect of Herba Epimedii (HE) extract against $H_2O_2-induced$ neurotoxicity was examined. Cytotoxic values were determined by the cell viability of living cells using 3-(4,5-dimethylthiazol-2-yl) -2,5-diphenyltetrazolium bromide (MTT) assay. In the present study, exposure of neurons to $H_2O_2$ resulted in a significant cell death in a dose- and time-dependent manners in cultured DRG neurons. The decrement of cell viability by $H_2O_2$ was blocked by HE. These results suggest that the neuroprotective effect of HE against $H_2O_2-induced$ cytotoxicity may result from the prevention of injury induced by $H_2O_2$.

Silibinin Induces Apoptotic Cell Death Via ROS-dependent Mitochondrial Pathway in Human Glioma Cells

  • Shin, Won-Yong;Jeong, Ji-Cheon
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.23 no.4
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    • pp.888-894
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    • 2009
  • It has been reported that silibinin, a natural polyphenolic flavonoid, induces cell death in various cancer cell types. However, the underlying mechanisms by which silibinin induces apoptosis in human glioma cells are poorly understood. The present study was therefore undertaken to examine the effect of silibinin on glioma cell apoptosis and to determine its underlying mechanism in human glioma cells. Apoptosis was estimated by FACS analysis. Reactive oxygen species (ROS) generation and mitochondrial membrane potential (${\Psi}m$) were measured using fluorescence dyes DCFH-DA and $DiOC_6$(3), respectively. Cytochrome c release from mitochondria and caspase-3 activation were estimated by Western blot analysis using specific antibodies. Exposure of cells to 30 mM silibinin induced apoptosis starting at 6 h, with increasing effects after 12-48h in a time-dependent manner. Silibinin caused ROS generation and disruption of ym, which were associated with the silibinin-induced apoptosis. The silibinin-induced ROS generation and disruption in ym were prevented by inhibitors of mitochondrial electron transport chain. The hydrogen peroxide scavenger catalase blocked ROS generation and apoptosis induced by silibinin. Silibinin induced cytochrome c release into cytosolic fraction and its effect was prevented by catalase and cyclosporine A. Silibinin treatment caused caspase-3 activation, which was inhibited by DVED-CHO and cyclosporine A. Pretreatment of caspase inhibitors also protected against the silibinin-induced apoptosis. These findings indicate that ROS generation plays a critical role in the initiation of the silibinin-induced apoptotic cascade by mediation of the mitochondrial apoptotic pathway including the disruption of ${\Psi}m$, cytochrome c release, and caspase-3 activation.

Expression of Human Papillomavirus Type 16, Prototype and Natural Variant E7 Proteins using Baculovirus Expression System

  • Han, Hee-Sung;Kee, Sun-Ho;Hwang, Soon-Bong;Kim, Hyung-Jun;Cho, Kyung-A;Kim, Yoon-Won;Cho, Min-Kee;Chang, Woo-Hyun
    • The Journal of Korean Society of Virology
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    • v.28 no.1
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    • pp.53-62
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    • 1998
  • Human papillomavirus (HPV) 16, E7 proteins derived from the prototype (Bac73) and natural variant (Bac101) E7 open reading frame were produced in Sf9 insect cells. The variant E7 gene occurred naturally by substitution mutation at the position of 88 nucleotide, resulting serine instead of asparagine. Using E7 specific monoclonal antibody (VD6), both E7 proteins were identified in recombinant baculovirus infected SF9 cells. Radiolabelling and immunoprecipitation analysis revealed that both E7 proteins were phosphoproteins. Immunostaining result showed that E7 proteins were mainly localized in the cytoplasm. Nuclear form of E7 proteins was also detected after a sequential fractionation procedure for removing chromatin structure. Considering that the VD6 recognition site in E7 protein is located within 10 amino acid at the N-terminus, this region appears to be blocked by the nuclear component. Western blot analysis revealed that nuclear form was more abundant than cytoplasmic E7 proteins. Time course immunostaining showed that the primary location of E7 protein was the nucleus and exported to the cytoplasm as proteins were accumulated. These events occurred similarly in both Bac73 and Bac101 infected Sf9 cells, suggesting that these two proteins may have similar biological functions.

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Antiangiogenic Activity of the Lipophilic Antimicrobial Peptides from an Endophytic Bacterial Strain Isolated from Red Pepper Leaf

  • Jung, Hye Jin;Kim, Yonghyo;Lee, Hyang Burm;Kwon, Ho Jeong
    • Molecules and Cells
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    • v.38 no.3
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    • pp.273-278
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    • 2015
  • The induction of angiogenesis is a crucial step in tumor progression, and therefore, efficient inhibition of angiogenesis is considered a powerful strategy for the treatment of cancer. In the present study, we report that the lipophilic antimicrobial peptides from EML-CAP3, a new endophytic bacterial strain isolated from red pepper leaf (Capsicum annuum L.), exhibit potent antiangiogenic activity both in vitro and in vivo. The newly obtained antimicrobial peptides effectively inhibited the proliferation of human umbilical vein endothelial cells at subtoxic doses. Furthermore, the peptides suppressed the in vitro characteristics of angiogenesis such as endothelial cell invasion and tube formation stimulated by vascular endothelial growth factor, as well as neovascularization of the chorioallantoic membrane of growing chick embryos in vivo without showing cytotoxicity. Notably, the angiostatic peptides blocked tumor cell-induced angiogenesis by suppressing the expression levels of hypoxia-inducible $factor-1{\alpha}$ and its target gene, vascular endothelial growth factor (VEGF). To our knowledge, our findings demonstrate for the first time that the antimicrobial peptides from EML-CAP3 possess antiangiogenic potential and may thus be used for the treatment of hypervascularized tumors.

Bevacizumab Regulates Cancer Cell Migration by Activation of STAT3

  • Wu, Huan-Huan;Zhang, Shuai;Bian, Huan;Li, Xiao-Xu;Wang, Lin;Pu, Yin-Fei;Wang, Yi-Xiang;Guo, Chuan-Bin
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.15
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    • pp.6501-6506
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    • 2015
  • There are numerous clinical cases indicating that long-term use of bevacizumab may increase the invasiveness of tumors. However, to date, little is known about underlying molecular mechanisms. Therefore, the purpose of our study was to investigate effects of bevacizumab in four cancer cells lines (WSU-HN6, CAL27, Tca83, and HeLa). It was found to promote migration and invasion in the WSU-HN6 and Tca83 cases, while exerting inhibitory effects in CAL27 and HeLa cells. The signal transducer and activator of transcription (STAT) 3 inhibitors niclosamide and S3I-201 inhibited the STAT3 signal pathway, which is activated by bevacizumab. These inhibitors also substantially blocked bevacizumab-induced migration of WSU-HN6 and Tca83 cells. Bevacizumab upregulated interleukin (IL)-6 and phosphorylated (p)-STAT3 expression time-dependently. Therefore, we propose that bevacizumab has differential effects on the migration of different cancer cell lines and promotes migration via the IL-6/STAT3 signaling pathway.

A Study on Smart Monitoring and Automatic Control based Food Waste Disposer (스마트 모니터링과 자동 제어 기반의 음식물 처리장치 연구)

  • Ahn, Yoon-Ae;Byun, Sang-Hun
    • Journal of the Korea Convergence Society
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    • v.9 no.10
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    • pp.29-35
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    • 2018
  • A food waste disposer commonly used in restaurants or homes is a type of machine with an agitator attached. The food waste disposer of the crushing type has a problem that the agitator may be broken if the piping or decomposition filter is blocked. In addition, there is an inconvenience that the user must manually open the cover to check the level in the food waste disposer. To solve these problems, this paper proposes a device that combines basic IoT technology with food waste disposer. The proposed device additionally designs and implement a real-time monitor processor and an automatic control processor inside the existing food waste disposer. The proposed food waste disposer allows the user to monitor the inside of the device using the smartphone. In addition, when the food is filled up to a certain position in the food waste disposer, it automatically stops and alarms. Using the proposed system, the user can conveniently check the inside of the food waste disposer, which has the advantage of preventing malfunctions in advance and reducing the probability of malfunction.