• Molecules and Cells
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• v.40 no.4
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• pp.291-298
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• 2017

MicroRNAs (miRNAs) are short non-coding RNAs that regulate genes posttranscriptionally. Past studies have reported that miR-210 is up-regulated in many cancers including cervical cancer, and plays a pleiotropic role in carcinogenesis. However, its role in regulating response towards anti-cancer agents has not been fully elucidated. We have previously reported that the natural compound 1'S-1'-acetoxychavicol acetate (ACA) is able to induce cytotoxicity in various cancer cells including cervical cancer cells. Hence, this study aims to investigate the mechanistic role of miR-210 in regulating response towards ACA in cervical cancer cells. In the present study, we found that ACA down-regulated miR-210 expression in cervical cancer cells, and suppression of miR-210 expression enhanced sensitivity towards ACA by inhibiting cell proliferation and promoting apoptosis. Western blot analysis showed increased expression of mothers against decapentaplegic homolog 4 (SMAD4), which was predicted as a target of miR-210 by target prediction programs, following treatment with ACA. Luciferase reporter assay confirmed that miR-210 binds to sequences in 3'UTR of SMAD4. Furthermore, decreased in SMAD4 protein expression was observed when miR-210 was overexpressed. Conversely, SMAD4 protein expression increased when miR-210 expression was suppressed. Lastly, we demonstrated that overexpression of SMAD4 augmented the anti-proliferative and apoptosis-inducing effects of ACA. Taken together, our results demonstrated that down-regulation of miR-210 conferred sensitivity towards ACA in cervical cancer cells by targeting SMAD4. These findings suggest that combination of miRNAs and natural compounds could provide new strategies in treating cervical cancer.

• The Korean Journal of Physiology and Pharmacology
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• v.19 no.2
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• pp.141-149
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• 2015

"G protein-coupled receptor 40" (GPR40), a receptor for long-chain fatty acids, mediates the stimulation of glucose-induced insulin secretion. We examined the profiles of differential gene expression in GPR40-activated cells treated with linoleic acid, and finally predicted the integral pathways of the cellular mechanism of GPR40-mediated insulinotropic effects. After constructing a GPR40-overexpressing stable cell line (RIN-40) from the rat pancreatic ${\beta}$-cell line RIN-5f, we determined the gene expression profiles of RIN-5f and RIN-40. In total, 1004 genes, the expression of which was altered at least twofold, were selected in RIN-5f versus RIN-40. Moreover, the differential genetic profiles were investigated in RIN-40 cells treated with $30{\mu}M$ linoleic acid, which resulted in selection of 93 genes in RIN-40 versus RIN-40 treated with linoleic acid. Based on the Kyoto Encyclopedia of Genes and Genomes Pathway (KEGG, http://www.genome.jp/kegg/), sets of genes induced differentially by treatment with linoleic acid in RIN-40 cells were found to be related to mitogen-activated protein (MAP) kinase- and neuroactive ligand-receptor interaction pathways. A gene ontology (GO) study revealed that more than 30% of the genes were associated with signal transduction and cell proliferation. Thus, this study elucidated a gene expression pattern relevant to the signal pathways that are regulated by GPR40 activation during the acute period. Together, these findings increase our mechanistic understanding of endogenous molecules associated with GPR40 function, and provide information useful for identification of a target for the management of type 2 diabetes mellitus.

• Biomedical Science Letters
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• v.11 no.4
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• pp.487-492
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• 2005

The baculovirus/insect cell expression system is of great value in the study of structure-function relationships in mammalian glucose-transport proteins by site-directed mutagenesis and for the large-scale production of these proteins for mechanistic and biochemical studies. Spodoptera frugiperda Clone 21 (Sf2l) cells grow well on TC-100 medium that contains $0.1\%$ D-glucose as the major carbon source, strongly suggesting the presence of endogenous glucose transporters. However, very little is known about the properties of the endogenous sugar transporter(s) in Sf2l cells, although a saturable transport system for hexose uptake has been previously revealed in the Sf cells. In order to further examine the substrate and inhibitor recognition properties of the Sf2l cell transporter, the ability of hexoses to inhibit 2-deoxy-D-glucose (2dGlc) transport was investigated by measuring inhibition constants $(K_i)$. The $K_i's$ for reversible inhibitors were determined from plots of uptake versus inhibitor concentration. Transport was effectively inhibited by D-mannose and D-glucose. Of the hexoses tested, L-glucose had the least effect on 2dGlc transport in the Sf2l cells, indicating that the transport is stereoselective. Unlike the human HepG2 type glucose transport system, D-mannose had a somewhat greater affinity for the Sf2l cell transporter than D-glucose, implying that the hydroxyl group at the C-2 position is not necessary for strong binding. However, epimerization at the C-4 position of D-glucose (D-galactose) resulted in a dramatic decrease in affinity of the hexose for the Sf2l cell transporter. Such a lowering of affinity might be the result of the involvement of the C-4 hydroxyl in hydrogen bonding. It is therefore suggested that Sf2l cells were found to contain an endogenous sugar transport activity that in several aspects resembles the human HepG2 type glucose transporter, although the insect and human transporters do differ in their affinity for cytochalasin B.

• The Journal of Internal Korean Medicine
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• v.38 no.6
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• pp.877-890
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• 2017

Objectives: Lonicerae flos (LF), a dried flower part of Lonicera japonica Thunb., has been widely used in Korean medicine as anti-inflammatory and antioxidative agent. The purpose of this study was to determine the cardioprotective effects of LF, through potential antioxidant effects, on the pressure overload (PO)-induced heart failure (HF) in C57BL/6 mice after transverse aortic constriction (TAC) surgery. Methods: Resveratrol (10 mg/kg body weight) or LF (125, 250 or 500 mg/kg body weight) was orally administered, once daily for 14 days, starting 14 days after TAC surgery. Changes in the mortality, body weights, heart weights, histopathology of the heart, and antioxidant defense systems of the heart were analyzed. Results: Marked and noticeable increases of heart weights, mortalities, and hypertrophic, focal, and lytic fibrotic histological changes in the LVs were observed, with destruction of heart antioxidant defense systems after surgery. However, HF signs, induced by TAC surgery through PO, and destruction of heart antioxidant defense systems were significantly and dose-dependently inhibited by 14 days of maintained oral treatment with LF 500, 250 or 125 mg/kg. Treatment with 250 mg/kg LF was comparable to treatment with 10 mg/kg resveratrol. Conclusions: The results in this study suggest that oral administration of LF favorably relieves PO-induced HF following TAC, through increase of heart antioxidant defense systems. The overall effects of 250 mg/kg LF were similar to those of 10 mg/kg resveratrol. More detailed mechanistic studies should be conducted in the future, with screening of the biologically active compounds in LF.

• Journal of Soil and Groundwater Environment
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• v.20 no.5
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• pp.1-10
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• 2015

FeS, as a natural reduced iron mineral, has been recognized to be a viable reactive material for As(III) sequestration in natural and engineered systems. In this study, FeS-coated sand packed columns were tested to evaluate the As(III) removal capacities under anaerobic conditions at pH 5, 7 and 9. The column obtained As(III) removal capacity was then compared with the capacity result obtained from batch reactors. In the comparison, two different approaches were used. The first approach was used the total As(III) removal capacity which method was proved to be useful for interpreting pH 5 system. The second approach was used to consider sorption non-linearity and proved to be useful for interpreting the pH 9. The results demonstrated that a mechanistic understanding of the different removal processes at different pH conditions is important to interpret the column experimental results. At pH 5, where the precipitation of arsenic sulfide plays the major role in the removal of arsenic, the column shows a greater removal efficiency than the batch system due to the continuous dissolution of sulfide and precipitation of arsenic sulfide. At pH 9, where adsorption mainly governs the arsenic removal, the sorption nonlinearity should be considered in the estimation of the column capacity. This study highlighted the importance of understanding reaction mechanism to predict column performance using batch-obtained experimental results.

• Journal of Pharmaceutical Investigation
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• v.37 no.2
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• pp.73-78
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• 2007

The aim of this study was to investigate the absorption properties of ketoprofen. The in-situ perfusion model has advantages over in vitro models as it provides intact lymphatic and blood flow circulation. The absorption properties of six different concentrations of ketoprofen have been studied in single pass in-situ rat intestine model. $^{14}C-PEG$ 4000 was used as a permeability marker and the possibility of an energy dependent contribution to ketoprofen absorption was also Investigated using the metabolic inhibitor sodium azide. Three different concentrations of sodium azide were studied to examine its effect on absorption of ketoprofen from the rat intestine. The findings of this study suggest that mono-carboxylic type drugs like ketoprofen cause permeability changes in the intestine. This is shown by the increase in absorption of $^{14}C-PEG$ 4000 as the concentration of ketoprofen is increased. However, the trend for ketoprofen permeability is to decrease over the concentration ranges. It was observed that the Papp values for ketoprofen with sodium azide shows a trend towards reduction in the amount of ketoprofen absorbed from the rat intestine which was significantly different (p<0.05) from that of ketoprofen with sodium azide 3.0mM. This indicates that sodium azide has an affect on the absorption of ketoprofen. The pH of all the perfusion solutions was altered to ${\sim}pH\;6.7$ by the buffering capacity of the small intestine secretions. The results suggest that mechanisms other than passive diffusion may be involved in ketoprofen absorption. This would be consistent with the involvement of active transport or saturatable processes in the absorption of drugs containing monocarboxylic acid group, as has been previously suggested from in vitro data.

• Korean Institute of Interior Design Journal
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• v.23 no.5
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• pp.51-57
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• 2014

In the early 20st century, created distrust on the mechanistic and dualistic view based on the world of Descartes and Newton. As the features of this new science cannot be explained by the existing Western philosophy but can be explained by the thinking system immanent in the Oriental traditional thought, many scientists and philosophers are concentrating their interests on the Oriental philosophy. In addition, some have been making efforts to find solutions needed for a new paradigm from the thinking system of the Orient. A variety of discussions have also been raised in connection with architecture due to this philosophical change. It has now become possible to conduct free creative acts, staying away from physical limitations, including gravity by diversified simulations through a computer. This physical liberation in turn has caused new changes to the spatial concept of architecture, thereby granting the freedom of the expression that could not be even imagined before and opening a possibility of new architecture and space. At the same time, the digital space architecture actively accommodating this technology is generating a phenomenon that the existing physical and realistic things are rapidly being changed gradually to immaterial and unrealistic ones. This study has analyzed the properties of digital architectural space as the immateriality of our traditional architectural space. The results are as follows: It can be seen that the immaterial features exhibited in the digital architectural space and the traditional architectural one are not just interconnected with specific features, but they are correlated to all immaterial features. Thus, immateriality that are common in the traditional and digital architectural spaces is complementary organic, which is contained in the ambiguity of boundary between other spaces. It is regarded to the architecture as a living things in space diversity based on ideological similarities.

• Journal of Korean Neurosurgical Society
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• v.63 no.5
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• pp.640-648
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• 2020

Objective : This study aimed to assess the relationship between increased intracranial pressure (ICP) and mastoid effusions (ME). Methods : Between January 2015 and October 2018, patients who underwent intracranial surgery and had ICP monitoring catheters placed were enrolled. ICP was recorded hourly for at least 3 days. ME was determined by the emergence of opacification in mastoid air cells on follow-up brain imaging. C-reactive protein (CRP) levels, presence of endotracheal tube (ETT) and nasogastric tube (NGT), duration of intensive care unit (ICU) stay, duration of mechanical ventilator application, diagnosis, surgical modalities, and presence of sinusitis were recorded. Each factor's effect on the occurrence of ME was analyzed by binary logistic regression analyses. To analyze the independent effects of ICP as a predictor of ME a multivariable logistic regression analysis was performed. Results : Total of 61 (53%) out of 115 patients had ME. Among the patients who had unilateral brain lesions, 94% of subject (43/50) revealed the ipsilateral development of ME. ME developed at a mean of 11.1±6.2 days. The variables including mean ICP, peak ICP, age, trauma, CRP, ICU stays, application of mechanical ventilators and presence of ETT and NGT showed statistically significant difference between ME groups and non-ME groups in univariate analysis. Sex and the occurrence of sinusitis did not differ between two groups. Adding the ICP variables significantly improved the prediction of ME in multivariable logistic regression analysis. Conclusion : While multiple factors affect ME, this study demonstrates that ICP and ME are probably related. Further studies are needed to determine the mechanistic relationship between ICP and middle ear pressure.

• Nutrition Research and Practice
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• v.14 no.4
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• pp.412-422
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• 2020

BACKGROUND/OBJECTIVES: This study investigates correlations between circulating microRNAs (miRNAs) and obesity-related parameters among young women (aged 20-30 years old) in Korea. SUBJECTS/METHODS: We analyzed TaqMan low density arrays (TLDAs) of circulating miRNAs in 9 lean (body mass index [BMI] < 25 kg/㎡) and 15 obese (BMI > 25 kg/㎡) women. We also performed gene ontology (GO) analyses of the biological functions of predicted miRNA target genes, and clustered the results using the database for annotation, visualization and integrated discovery. RESULTS: The TLDA cards contain 754 human miRNAs; of these, the levels of 8 circulating miRNAs significantly declined (> 2-fold) in obese subjects compared with those in lean subjects, including miR-1227, miR-144-5p, miR-192, miR-320, miR-320b, miR-484, miR-324-3p, and miR-378. Among them, miR-484 and miR-378 displayed the most significant inverse correlations with BMI (miR-484, r = -0.5484, P = 0.0056; miR-378, r = -0.5538, P = 0.0050) and visceral fat content (miR-484, r = -0.6141, P = 0.0014; miR-378, r = -0.6090, P = 0.0017). GO analysis indicated that genes targeted by miR-484 and miR-378 had major roles in carbohydrate and lipid metabolism. CONCLUSION: Our result showed the differentially expressed circulating miRNAs in obese subjects compared to lean subjects. Although the mechanistic study to reveal the causal role of miRNAs remains, these miRNAs may be novel biomarkers for obesity.

• Journal of Korean Society of Steel Construction
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• v.27 no.1
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• pp.1-12
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• 2015

Well-designed bolted connections can exhibit excellent ductile behavior through bearing mechanism until the occurrence of bolt shear rupture. The ultimate strength analysis of eccentric bolted connections is an economical and mechanistic approach which uses such ductility. However, the bolt load-deformation relationship, which forms basis of the current practice, is based on very limited combinations of bolt and steel materials. The primary objective of this study was to establish the general bolt force-deformation relationship based on systematic single-bolt bearing connection tests. The test results showed that the projected area of the bolt hole and the strength and thickness of the plate to be connected are the main factors affecting the force-deformation relationship. The results of this study can be used for the instantaneous center of rotation method (ICRM) to achieve more accurate analysis and economical design of a variety of group-bolted connections subjected to eccentric shear.