• The Korean Journal of Physiology and Pharmacology
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• v.19 no.6
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• pp.549-555
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• 2015

We attempted to investigate molecular mechanisms underlying phenotypic change of vascular smooth muscle cells (VSMCs) by determining signaling molecules involved in chemokine production. Treatment of human aortic smooth muscle cells (HAoSMCs) with thrombin resulted not only in elevated transcription of the (C-C motif) ligand 11 (CCL11) gene but also in enhanced secretion of CCL11 protein. Co-treatment of HAoSMCs with GF109230X, an inhibitor of protein kinase C, or GW5074, an inhibitor of Raf-1 kinase, caused inhibition of ERK1/2 phosphorylation and significantly attenuated expression of CCL11 at transcriptional and protein levels induced by thrombin. Both Akt phosphorylation and CCL11 expression induced by thrombin were attenuated in the presence of pertussis toxin (PTX), an inhibitor of Gi protein-coupled receptor, or LY294002, a PI3K inhibitor. In addition, thrombin-induced production of CCL11 was significantly attenuated by pharmacological inhibition of Akt or MEK which phosphorylates ERK1/2. These results indicate that thrombin is likely to promote expression of CCL11 via PKC/Raf-1/ERK1/2 and PTX-sensitive protease-activated receptors /PI3K/Akt pathways in HAoSMCs. We propose that multiple signaling pathways are involved in change of VSMCs to a secretory phenotype.

• The Korean Journal of Physiology and Pharmacology
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• v.15 no.1
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• pp.31-36
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• 2011

To understand the roles of purinergic receptors and cellular molecules below the receptors in the vascular inflammatory response, we determined if extracellular nucleotides up-regulated chemokine expression in vascular smooth muscle cells (VSMCs). Human aortic smooth muscle cells (AoSMCs) abundantly express $PSY_1$, $PSY_6$, and $PSY_{11}$ receptors, which all respond to extracellular nucleotides. Exposure of human AoSMCs to $NAD^+$, an agonist of the human $PSY_{11}$ receptor, and $NADP^+$ as well as ATP, an agonist for $PSY_1$ and $PSY_{11}$ receptors, caused increase in chemokine (C-C motif) ligand 2 gene (CCL2) transcript and CCL2 release; however, UPT did not affect CCL2 expression. CCL2 release by $NAD^+$ and $NADP^+$ was inhibited by a concentration dependent manner by suramin, an antagonist of P2-purinergic receptors. $NAD^+$ and $NADP^+$ activated protein kinase C and enhanced phosphorylation of mitogen-activated protein kinases and Akt. $NAD^+$- and $NADP^+$-mediated CCL2 release was significantly attenuated by SP6001250, U0126, LY294002, Akt inhibitor IV, RO318220, GF109203X, and diphenyleneiodium chloride. These results indicate that extracellular nucleotides can promote the proinflammatory VSMC phenotype by up-regulating CCL2 expression, and that multiple cellular elements, including phosphatidylinositol 3-kinase, Akt, protein kinase C, and mitogen-activated protein kinases, are involved in that process.

• Toxicological Research
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• v.11 no.2
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• pp.247-252
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• 1995

To evaluate the effect of xanthine oxidase on liver injury by $CCl_4$, liver damage was induced both in allopurinol pretreated rats (500 mg/kg. ip) and control group by twice intraperitoneal injection of $CCl_4$ (0.1 ml/100 g body wt. 50% in olive oil) at interval of one day. Increases in the levels of serum alanine aminotransferase and liver weight/body weight (%) by $CCl_4$ were significantly smaller inallopurinol pretreated rats than in control whereas the hepatic microsomal glucose-6-pholphatase activities were significantly higher in allopurinol pretreated rats than control group by $CCl_4$ treatment. These results indicates that allopurinol pretreatment may reduce the liver damage in $CCl_4$ intoxicated rats. In rats either with $CCl_4$or not, hepatic type O xanthine oxidase activities were significantly reduced by allopurinol pretreatment and the increasing rate of these enzymes to each control was remarkably lower in allopurinol pretreated rats than control. Liver cytosolic protein contents and aniline hydroxylase, aminopyrine demethylase activities were higher in allopurinol pretreated rats than coirol rats when animals were treated with $CCl_4$. On the other hand, neither allopurinol pretreated nor $CCl_4$ treatment caused any significant changes in hepatic superoxide dismutase and catalase activities. Hepatic glutathione contents were higher in $CCl_4$-treated rats than control, but no significant changes were found in both between the allopurinol treated rats and $CCl_4$-treated rats pretreated with allopurinol, and glutathione and glutathione S-transferase activities were significantly reduced in $CCl_4$-treated rats than control whereas these enzyme activities showed on significant change in both between allopurinel treated and $CCl_4$-treated rats pretreated with allopurinol. It is concluded that xanthine oxidase reaction system augment $CCl_4$ induced liver injury via even oxygen free radical system.

• Applied Chemistry for Engineering
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• v.4 no.2
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• pp.318-323
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• 1993

Pentachloroethane($CHCl_2CCl_3$) was synthesized and reacted with hydrogen fluoride using antimony pentahalide catalyst($SbCl_xF_y$) in order to manufacture HCFC-123$(CF_3CHCl_2)$, a potential CFC-11$(CFCl_3$) substitute candidate. Products analyses showed the fluorination proceeds through fluorine-chlorine exchanges between $HF/SbCl_xF_y$ and $SbCl_xF_y/CCl_3CHCl_2$ respectively. The degree of fluorination of $CCl_3$ group in pentachloroethane was greatly affected on the reaction temperature, but the effect of catalyst concentration was relatively small. Mechanistic study was also performed to elucidate the pathway to the formation of side-products such as $CCl_3CFCl_2$, $CFCl_2CFCl_2$ and $CF_2ClCFCl_2$.

• IMMUNE NETWORK
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• v.16 no.3
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• pp.189-194
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• 2016

Obesity is characterized as an accumulation of adipose tissue mass represented by chronic, low-grade inflammation. Obesity-derived inflammation involves chemokines as important regulators contributing to the pathophysiology of obesity-related diseases such as cardiovascular disease, diabetes and some cancers. The obesity-driven chemokine network is poorly understood. Here, we identified the profiles of chemokine signature between human preadipocytes and adipocytes, using PCR arrays and qRT-PCR. Both preadipocytes and adipocytes showed absent or low levels in chemokine receptors in spite of some changes. On the other hand, the chemokine levels of CCL2, CCL7-8, CCL11, CXCL1-3, CXCL6 and CXCL10-11 were dominantly expressed in preadipocytes compared to adipocytes. Interestingly, CXCL14 was the most dominant chemokine expressed in adipocytes compared to preadipocytes. Moreover, there is significantly higher protein level of CXCL14 in conditioned media from adipocytes. In addition, we analyzed the data of the chemokine signatures in adipocytes obtained from healthy lean and obese postmenopausal women based on Gene Expression Omnibus (GEO) dataset. Adipocytes from obese individuals had significantly higher levels in chemokine signature as follows: CCL2, CCL13, CCL18-19, CCL23, CCL26, CXCL1, CXCL3 and CXCL14, as compared to those from lean ones. Also, among the chemokine networks, CXCL14 appeared to be the highest levels in adipocytes from both lean and obese women. Taken together, these results identify CXCL14 as an important chemokine induced during adipogenesis, requiring further research elucidating its potential therapeutic benefits in obesity.

• Toxicological Research
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• v.23 no.1
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• pp.11-17
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• 2007

This study was carried out to investigate the effect of LAB (Lactic acid bacteria: Lactobacillus acidophilus, Bifidobacterium bifidum and Streptococcus thermophilus) on detoxication of damaged liver in carbon tetrachloride ($CCl_4$) and ethanol (25%)-treated rats. Rats had been daily (twice a day) pre-treated with saline (0.5 ml/kg: untreated group), $CCl_4$ (0.5 ml/kg: other groups) for 6 days. At seventh day, after treating rat with $CCl_4$ and then, mixture of LAB ($10^{11}$/0.5 ml: LAB group), saline (0.5 ml/kg: untreated group, $CCl_4$ group), and biphenyl dimethyl dicarboxylate (DDB) (50 mg/kg: DDB group) were treated orally with $CCl_4$ for 8 days. Ethanol is treated as the same manner instead of $CCl_4$. To investigate the hepatoprotective effect, rats treated with $CCl_4$ and ethanol were analyzed with serum GOT and GPT level. The GOT and GPT levels of LAB group was lower than the level of $CCl_4$ and DDB group. Especially, compared with data of $CCl_4$ group, GPT activity showed statistically significant result in the significance level of p < 0.05. The LAB group treated with ethanol also showed lower level of GOT and GPT than the other control groups treated with ethanol. The triglyceride level of serum decreased more in a group treated special materials (DDB and LAB group) than ethanol group. As well, the effect of LAB on the antifatigue has been investigated. The animals (10/group) were divided into 4 groups (untreated group, Carrier group, Red-ginseng group, LAB group). Each group was given carrier (0.9 mg/0.2 ml), red ginseng extract (200 mg/kg), and mixture of LAB ($10^{11}$/0.2 ml). Special materials were given for three weeks. After finishing treating through oral, horizontal wire test, rotarod test, and forced swimming test were performed. The time of resistance to fatigue of the group, fed with mixture of LAB, was longer than the time when mice treated with red-ginseng that the effect was already revealed. The result of this study revealed that LAB could decrease hepatocelluar injury compared with rats treated orally with $CCl_4$ and ethanol, and could also decrease fatigue.

• Annual Conference of KIPS
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• 2010.11a
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• pp.917-920
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• 2010

Web 2.0 시대를 대표하는 핵심적인 컨텐츠는 단연 UCC이다. 사용자가 직접 만드는 컨텐츠를 의미하는 UCC는 유투브, 아프리카TV 등을 통하여 많은 수익을 거두며 관련 업계의 주목을 받고 있으나 복제와 수정, 전송이 쉬운 인터넷 환경에서 많은 저작권 문제를 내포하고 있다. 최근에는 웹을 중심으로 CCL을 통해 자신의 저작물에 대한 허용조건을 명시하여 다른 사용자에게 명시된 조건하에서 자유롭게 저작물을 이용할 수 있게 하는 방법이 널리 이용되고 있다. 그러나 CCL로 허용된 컨텐츠를 이용함에 있어서 CCL의 누락 및 위변조를 통해 저작물을 불법으로 이용하는 행위가 증가하고 있어 CCL 활성화의 장애물이 되고 있다. 또한 다양한 응용프로그램에 CCL을 적용하고 검증하기 위한 SW 플랫폼이 부재한 상태이다. 이에 본 논문에서는 효과적으로 컨텐츠에 CCL을 적용하고 CCL로 사용허가된 컨텐츠를 검증 할 수 있는 SW 플랫폼을 제안한다.

• Environmental Analysis Health and Toxicology
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• v.11 no.3_4
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• pp.59-63
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• 1996

In present study, we fractionated polysaccharides from Croton tiglium and investigated their hepatoprotective effects on CCl$_4$ intoxication. Polysaccharide fraction of which molecular weight is over 300,000 (HP) showed the most potent hepatoprotective effects on CCl$_4$ intoxication. Lipid peroxidation, sAST and sALT were used as parameters to evaluate the liver damage. Glucose, xylose and arabinose were found to be monosaccharides composing sugar moiety of HP.

• IMMUNE NETWORK
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• v.11 no.4
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• pp.203-209
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• 2011

Background: T cell immunoglobulin mucin containing molecule (TIM)-3 is expressed in differentiated Th1 cells and is involved in the suppression of the cytokine production by these cells. However, the regulation of the expression of other T cell genes by TIM-3 is unclear. Herein, we attempted to identify differentially expressed genes in cells abundantly expressing TIM-3 compared to cells with low expression of TIM-3. Methods: TIM-3 overexpressing cell clones were established by transfection of Jurkat T cells with TIM-3 expression vector. For screening of differentially expressed genes, gene fishing technology based on reverse transcription-polymerase chain reaction (RT-PCR) using an annealing control primer system was used. The selected candidate genes were validated by semi quantitative and real-time RT-PCR. Results: The transcription of TIMP-1, IFITM1, PAR3 and CCL1 was different between TIM-3 overexpressing cells and control cells. However, only CCL1 transcription was significantly different in cells transiently transfected with TIM3 expression vector compared with control cells. CCL1 transcription was increased in primary human $CD4^+$ T cells abundantly expressing TIM-3 but not in cells with low expression of TIM-3. Conclusion: CCL1 was identified as a differentially transcribed gene in TIM-3-expressing $CD4^+$ T cells.

• Journal of Pharmaceutical Investigation
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• v.11 no.4
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• pp.1-11
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• 1981

In order to elucidate the effects of Panax Ginseng on the pharmacokinetics of sulfobromophthalein (BSP) in a pathological condition, patho-physiological changes, the kinetics of the disappearance of BSP from the blood and appearance in the bile were studied in rats. Group I , the control group, was produced by repeated injection of olive oil 0.1ml/100g under the skin of the back twice a week for 9 weeks. Group II , the Ginseng pretreated group, was produced by administration of Ginseng total saponin 200mg/kg/day P.O. for 10 days and subsequent injection of $CCl_4$ 0.1ml/100g under the skin of the back twice a week for 9 weeks. Group III , the chronically intoxicated group, was produced by repeated injection of $CCl_4$ 0.1ml/100g under the skin of the back twice a week for 9 weeks. The results obtained were summarized as follows; 1. The activities of GOT GPT of rat blood serum, body weight, and liver weight were affected by the pretreatment with Ginseng saponin. 2. The kinetics of the disappearance of BSP from the blood were affected by the pretreatment with Ginseng saponin. 3. The appearance of BSP in the bile was significantly affected by the pretreatment with Ginseng saponin.