• Biomolecules & Therapeutics
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• v.8 no.2
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• pp.140-146
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• 2000

Recently, we reported that immunostimulation of primary rat cortical astrocyte caused stimulation of glucose deprivation induced apoptotic cell death. To enhance the understanding of the mechanism of the potentiated cell death of clucose-deprived astrocyte by immunostimulation, we investigated the effect of immunostimulation on the glucose deprivation induced cell death of rat C6 glioma cells. Co-treatment of C6 glioma cells with lipopolysaccharide (LPS, $1\;{\mu}\textrm{g}/ml$) and interferon ${\gamma}(IFN{\gamma},\;100U/ml)$ is serum free condition caused marked elevationo f nitric oxide production ($>50\;{\mu}M$). In this condition, glucose deprivation caused significant release of lactate dehdrogenase (LDH) from C6 glioma cells while control cells did not show LDH release. To investigate whether elevated level of nitric oxide is responsible for the enhanced LDH release in glucose-deprived condition, C6 glioma cells were treated with 3-morphorinosydnonimine (SIN-1) and it was observed that SIN-1 caused increase in LDH release from glucose-deprived C6 glioma cells. Treatment of C6 glioma cells with $25\;{\mu}M$ of pyrrolidinedithiocarbamate (PDTC) which inhibit Nuclear factor kB (NF-kB) activation, caused complete inhibition of nitric oxide production. Treatment of C6 glioma cells with NO synthase inhibitors, $N^{G}$-nitro-L-arginine (NNA) or L-$N{\omega}$-nitro-L-arginine methyl ester (L-NAME), caused inhibition of nitric oxide production and also glucose deprivation induced cell death of cytokine-stimulated C6 glioma cells. In addition, diaminohydroxypyrimidine (DAHP, 5 mM) which inhibits the synthesis of tetrahydrobiopterine (BH4), one of essential cofactors for iNOS activity, caused complete inhibition of NO production from immunostimulated C6 glioma cells. The results from the present study suggest that immunostimulation causes potentiation of glucose deprivation induced death of C6 glioma cells which is mediated at least in part by the increased production of nitric oxide. The vulnerability of immunostimulated C6 glioma cells to hypoglycemic insults may implicate that the elevated level of cytokines in various ischemic and neurodegenerative diseases may play a role in their pathogenesis.

• Journal of Chest Surgery
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• v.25 no.1
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• pp.1-16
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• 1992

The quantitatively measured local myocardial perfusion rates with microspheres are used as an objective indicator of even distribution of cardioplegic solution, and the efficacy of the retrograde right atrial route of cardioplegia is evaluated in hearts with various levels of coronary arterial obstruction. After initial antegrade cardioplegia under the median sternotomy and aortic cannulation, 60 hearts from anesthetized New Zealand white rabbits are divided in random order as normal group [ligated left main coronary artery ; MA, MR] and diagonal group [ligated proximal diagonal artery ; LA, LR]. Half of each group [N=10] are perfused with antegrade cardioplegia[A] under the pressure of 100 cmH2O and the other half with retrograde right atrial route[R] under the pressure of 60 cmH2O[St. Thomas cardioplegic solution mixed with measured amount of microspheres]. The myocardium is subdivided into segments as A[atria], RV[right ventricle]. S[septum], LV[normally perfused left ventricular free wall], ROI[ischemic myocardium of left ventricular free wall]. LV and RQI are further divided into N[subendocardium] and P[subepicardium]. The resulting local myocardial perfusion rates and N /P of each group are compared with Wilcoxon rank sum test. The weight of the hearts is 5.94$\pm$0.66g, and there are no statistically significant dif-ferences[p>0.05, ANOVA] between six compared group. The mean flow rate[F: ml /g / min] of MR group is comparable with MA group[p>0.05], but in N and L group, there are significantly depressed F with right atrial route of cardioplegia, which means elevated perfusion resistance with this route. In spite of no significant differences in delivered doses of microsphere[DEL] between compared groups[p>0.05, ANOVA], there are significantly depressed REC and NF in hearts with right atrial cardioplegia which suggests increased requirement of cardioplegic solution with this route. The interventricular septum shows poor perfusion with right atrial route of cardioplegia without obstruction of supplying coronary arteries. But, with obstruction of coronary artery supplying septum as in M group, the flow rate is superior with right atrial route of infusion. The left ventricular free wall perfusion rates of every RQI with R route are superior to that of A route[p<0.05]. But, in LV segments, there are unfavorable effects of right atrial cardioplegia in L group, although the subendocardial perfusion is well maintained in N group. The LV free wall of left main group shows depressed perfusion rates with antegrade route as compared with RQI segments of diagonal group. But, by contraries, there are increased perfusion rates and superior N /P ratio with retrograde right atrial route. It implies more effective perfusion with right atrial route of cardioplegia in more proximal coronary arterial obstruction[i.e., M group as compared with L group]. As a conclusion, all region of ischemia have superior perfusion rates with right atrial car-dioplegia as compared with antegrade route, and especially excellent results can be obtained in hearts with more proximal obstruction of coronary arteries which would otherwise result in more severe ischemic damage. But, the depressed perfusion rates of the segments with normal coronary artery in hearts with coronary arterial obstruction may be a problem of concern with right atrial cardioplegia and needs solution.

• Proceedings of the Korea Water Resources Association Conference
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• 2007.05a
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• pp.2024-2028
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• 2007

우리나라의 물관련 이슈는 수자원뿐만 아니라 사회, 경제 환경 등의 범위까지 확대되어 복합적이며, 기존 방법론과 기술만으로는 해결에 어려움이 있다. 따라서 새로운 기술적/방법론적 도구 개발의 필요성에 따라 통합수자원관리가 하나의 방법으로 받아들여지고 있다. 통합수자원관리는 지속가능한 수자원관리를 목표로하며, 물과 이와 관련 다양한 요소를 고려하는 통합적인 방법론이다. 그러므로 의사결정에 있어 전체론적인 접근이 필요하며, 세부적인 요소와 요소간의 연관관계를 파악하는 것이 중요하다. 이를 위하여 본 연구에서는 통합수자원관리의 기반 도구 중의 하나인 통합수자원관리 모델링 환경인 WaterRing 시범시스템을 개발하였다. WaterRing은 모델연계에 있어 필수적인 표준성, 사용편의성 및 모델공유를 제공하며, 모델코드 자체보다 모델의 개발에 많은 노력을 기울일 수 있도록 설계되었다. 따라서 수자원분야 및 다양한 분야의 모델을 연계할 수 있다. 모델의 연계를 위하여 기본모델단위를 설정하고 각각의 기본모델단위의 결합을 통하여 보다 큰 시스템으로 구성할 수 있도록 하였다. 기본모델단위는 입력/상태/출력의 세 가지 기본요소와 내부수행 루틴으로 구성되어 있다. 기본모델단위 사이의 결합을 정의하기 위하여 BPM(Business Process Management)(Arkin, 2002)와 STELLA의 모델 결합방식을 활용하였다. 기본모델단위는 독립적인 수행단위로 표준적인 입력과 출력을 수행한다. 따라서 입력과 출력의 속성이 같은 기본모델단위는 결합할 수 있다. 본 연구에서 시범적으로 개발된 수자원통합모델링환경 WaterRing은 통합수자원관리의 실현에 있어 평가, 계획에 이용될 수 있다. 그러므로 향후 시스템의 개발이 완료되면 우리나라의 통합수자원관리의 실현을 위한 기반도구로서 많은 역할이 기대된다. 홍수기에 측정된 성과를 바탕으로 고수위대의 수위-유량관계 곡선식을 개발하여야 할 것으로 판단된다. 본 연구를 통해 일부 확인된 바와 같이, 일반적인 자연하천이 아닌 감조하천의 경우는, 각각의 수위대별 유량 값의 변화가 발생하는 바 기간별 혹은 간조와 만조부를 포함하여 유량측정을 하여야 할 것으로 판단된다. 청폐화담탕(淸肺化痰湯)은 LPS로 유도된 macrophage에서 NO와 염증Cytokine 생성량을 억제하였고 murine macrophage에서 NF-${\kappa}$B 활성을 억제함으로써 iNOS와 염증Cytokine 유전자 발현을 하향조절 하였다. 이러한 청폐화담탕(淸肺化痰湯)의 항염작용으로 천식, 기관지염, 폐렴, 결핵, 산후감모 등의 호흡기 질환에 응용할 수 있으리라 사료된다.im}$5개월), 9.44${\pm}$1.05 6${\sim}$ll개월)으로 개월에 관계없이 전반적으로 유사한 비율을 나타내었다. 분획물(첨가농도 15.6 ${\mu}$g/ml)은 60%의 저해효과를 나타내면서 농도 의존적으로 그 저해효과가 컸으며 250 ${\mu}$g/ml 농도에서는 80%의 저해효과를 관찰 할 수가 있었다. 에틸아세테이트분회물의 경우 디글로로메탄 분회물에 비해 다소 낮은 저해효과를 나타내었지만 250 ${\mu}$g/ml 농도에서 약 60%의 세포독성 효과를 나타내었다. 디클로로메탄 분획물과 에틸아세테이트 분획물에 의한 면역 활성 증진 효과를 검토한 결과, 디글로로메탄 분획물은 첨가농도 1 ${\mu}$g/ml에서 94%로 Yac-1표적세포를 사멸시켰으며 에틸아세테이트 분획물도 동일 농도에서 96%의 억제효과를 나타내었다. CTLL세포를 이용

• The Korea Journal of Herbology
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• v.30 no.6
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• pp.63-68
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• 2015

Objectives : Gastric lesions affect many people around the world and their development are results of the imbalance between destructive and protective factors in the gastric mucosa. Lycium chinense has been widely used as a traditional Korean medicine, it was recently reported that they have potent anti-inflammatory effects in chronic hepatitis models. Therefore, this study aimed to investigate the anti-inflammatory activity of Lycium chinense extract (LCE) on HCl-Ethanol induced gastric lesion mice.Methods : The ICR mice were divided randomly into five groups of six animals each. Group A was normal mice, and group B was treated orally with 0.5 ml 150 mM HCl-60% Ethanol. Mice in group C and D were pre-treatment of LCE (100 mg/kg and 200 mg/kg bodyweight, p.o before HCl/ethanol treatment) and group E was orally administered sucralfate (10 mg/kg).Results : 150mM HCl/60% ethanol-induced gastric mucosal injury mice were ameliorated mucosal damage upon histological evaluation by treatment of LCE. Pre-treatment of LCE attenuated reactive oxidative species (ROS) and produces peroxynitrite (ONOO^-) in stomach tissues. As results of stomach protein analyses, LCE effectively reduce inflammatory-related factors such as cyclooxygenase-2 (COX-2), tumor necrosis factor alpha (TNF-α), inducible nitric oxide synthase (iNOS) and interleukin-6 (IL-6) in gastric lesion mice. In addition, nuclear factor kappa B (NF-κB) and inhibitor of phosphorylation of nuclear factor kappa B (p-IκB) were down-regulated in LCE-administrated gastric lesion mice.Conclusions : Our discovery supports that the therapeutic activity of LCE ameliorate the development of gastric lesion via suppressing the oxidative stress and gastric partial inflammation induced by 150 mM HCl/60% ethanol.

• Nutrition Research and Practice
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• v.10 no.1
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• pp.33-41
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• 2016

BACKGROUND/OBJECTIVES: Diabetes mellitus (DM) is a major chronic disease which increases global health problems. Diabetes-induced renal damage is associated with inflammation and fibrosis. Alpha (AT) and gamma-tocopherols (GT) have shown antioxidant and anti-inflammatory effects in inflammation-mediated injuries. The primary aim of this study was to investigate effects of AT and GT supplementations on hyperglycemia induced acute kidney inflammation in alloxan induced diabetic mice with different levels of fasting blood glucose (FBG). MATERIALS/METHODS: Diabetes was induced by injection of alloxan monohydrate (150 mg/kg, i.p) in ICR mice (5.5-week-old, male) and mice were subdivided according to their FBG levels and treated with different diets for 2 weeks; CON: non-diabetic mice, m-DMC: diabetic control mice with mild FBG levels (250 mg/dl ${\leq}$ FBG ${\leq}$ 450 mg/dl), m-AT: m-DM mice fed AT supplementation (35 mg/kg diet), m-GT: m-DM mice with GT supplementation (35 mg/kg diet), s-DMC: diabetic control mice with severe FBG levels (450 mg/dl < FBG), s-AT: s-DM mice with AT supplementation, s-GT: s-DM mice with GT supplementation. RESULTS: Both AT and GT supplementations showed similar beneficial effects on $NF{\kappa}B$ associated inflammatory response (phosphorylated inhibitory kappa B-${\alpha}$, interleukin-$1{\beta}$, C-reactive protein, monocyte chemotactic protein-1) and pre-fibrosis (tumor growth factor ${\beta}$-1 and protein kinase C-II) as well as an antioxidant emzyme, heme oxygenase-1 (HO-1) in diabetic mice. On the other hands, AT and GT showed different beneficial effects on kidney weight, FBG, and oxidative stress associated makers (malondialdehyde, glutathione peroxidase, and catalase) except HO-1. In particular, GT significantly preserved kidney weight in m-DM and improved FBG levels in s-DM and malondialdehyde and catalase in m- and s-DM, while AT significantly attenuated FBG levels in m-DM and improved glutathione peroxidase in m- and s-DM. CONCLUSIONS: the results suggest that AT and GT with similarities and differences would be considered as beneficial nutrients to modulate hyperglycemia induced acute renal inflammation. Further research with careful approach is needed to confirm beneficial effects of tocopherols in diabetes with different FBG levels for clinical applications.

• Korean Journal of Pharmacognosy
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• v.50 no.1
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• pp.11-17
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• 2019

Cassia tora L. have been used as a folk medicine in Korea. This study investigated anti-inflammatory effect of aurantio-obtusin isolated from C. tora. We isolated aurantio-obtusin from 50% ethanol extracts of C. tora L. We investigated the anti-inflammatory effects of aurantio-obtusin on the lipopolysaccharide (LPS)-stimulated inflammatory response in murine macrophage cell line (Raw 264.7). To investigate the cytotoxicity of aurantio-obtusin on RAW 264.7 cells, MTS assay was performed. RAW 264.7 cells were treated with aurantio-obtusin at different concentrations (12.5, 25, 50, $100{\mu}M$) for 30 h. The result showed that aurantio-obtusin had no cytotoxic effect in a concentration range of $12.5-100{\mu}M$. To determine the effect of aurantio-obtusin on LPS-induced NO production, the NO concentration measurement was performed. RAW 264.7 cells were treated with aurantio-obtusin at 12.5, 25, 50 and $100{\mu}M$ for 24 h, and the results showed that the NO production of aurantio-obtusin-treated cells compared to LPS alone treated group was significantly decreased in a dose-dependent manner. Pretreatment of aurantio-obtusin inhibited LPS-induced NO production in a dose-dependent manner. To find out inhibitory mechanisms of aurantio-obtusin on inflammatory mediators, we examined the $PGE_2$ pathways. As a result, $PGE_2$ were decreased in a dose-dependent manner by aurantio-obtusin. The release of interleukin-$1{\beta}$ (IL-$1{\beta}$) and IL-6 were also reduced. Moreover, aurantio-obtusin suppressed LPL-induced $I{\kappa}B-{\alpha}$ degradation. These results suggest that the down regulation of NO, $PGE_2$, IL-$1{\beta}$ and IL-6 expression by aurantio-obtusin are achieved by the downregulation of NF-${\kappa}B$ activity.

• Korean Journal of Pharmacognosy
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• v.51 no.4
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• pp.244-254
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• 2020

Atractylodes macrocephala is a perennial herb and is a member of the Compositae family. This plant is known to contain various bioactive constituents indicating anti-inflammatory, neuroprotective, anti-oxidant, immunological enhancement, and gastroprotective effects. In this investigation, we isolated four compounds with similar chemical structures from A. macrocephala, and evaluated their anti-inflammatory effects. Among the four compounds, compound 2(atractylenolide II) showed the second-best inhibitory effect on the lipopolysaccharide(LPS)-induced production of nitric oxide in RAW264.7 macrophages and BV2 microglial cells. Compound 2 also inhibited the LPS-induced the production of prostaglandin E2(PGE2), and the expression of inducible nitric oxide synthase(iNOS) and cyclooxygenase(COX)-2 proteins in both cells. In addition, compound 2 suppressed the production of pro-inflammatory cytokines including interleukin(IL)-1β, IL-6, and tumor necrosis factor(TNF)-α. These inhibitory effects were contributed by inactivation of nuclear factor kappa B(NF-κB) and mitogen-activated protein kinases(MAPKs) pathways by treatment with compound 2. This compound did not induce the expression of heme oxygenase(HO)-1 protein indicating that the anti-inflammatory effect of compound 2 was independent with HO-1 protein. Taken together, these results suggested that atractylenolide II can be a candidate material to treat inflammatory diseases.

• Journal of Applied Biological Chemistry
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• v.65 no.2
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• pp.113-120
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• 2022

We examined the anti-inflammatory properties of Nostoc commune HCW0811 in lipopolysaccharide-stimulated RAW264.7 macrophage cells. The anti-inflammatory activity of HCW0811 on viability of treated cells was assessed by measuring the level of expression of NO, prostaglandin E₂ and pro-inflammatory cytokines, namely interleukin-1β, interleukin-6, and tumor necrosis factor-α in HCW0811 treated RAW 264.7 macrophages. HCW0811 was non-toxic to cells and inhibited the production of cytokines in a concentration-dependent manner. In addition its treatment suppressed the production of pro-inflammatory cytokines in a dose-dependent manner, and concomitantly decreased the protein expressions of inducible NO synthase and cyclooxygenase-2. Moreover, the levels of the phosphorylation of mitogen-activated protein kinase family proteins such as extracellular signal-regulated kinase, c-Jun N-terminal kinase, p38, and nuclear factor kappa B were reduced by HCW0811. These findings suggest that the HCW0811 collected from Daejeon National Cemetery have anti-inflammatory effects, and demonstrated its efficacy in cell-based in vitro assays.

• Animal Bioscience
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• v.35 no.7
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• pp.964-974
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• 2022

Objective: The highly pathogenic avian influenza virus (HPAIV) is a threat to the poultry industry and economy and remains a potential source of pandemic infection in humans. Antiviral genes are considered a potential factor for studies on HPAIV resistance. Therefore, in this study, we investigated gene expression related to the mitogen-activated protein kinase (MAPK) signaling pathway by comparing non-infected, HPAI-infected resistant, and susceptible Ri chicken lines. Methods: Resistant (Mx/A; BF2/B21) and susceptible Ri chickens (Mx/G; BF2/B13) were selected by genotyping the Mx and BF2 genes. Then, the tracheal tissues of non-infected and HPAIV H5N1 infected chickens were collected for RNA sequencing. Results: A gene set overlapping test between the analyzed differentially expressed genes (DEGs) and functionally categorized genes was performed, including biological processes of the gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) pathways. A total of 1,794 DEGs were observed between control and H5N1-infected resistant Ri chickens, 432 DEGs between control and infected susceptible Ri chickens, and 1,202 DEGs between infected susceptible and infected resistant Ri chickens. The expression levels of MAPK signaling pathway-related genes (including MyD88, NF-κB, AP-1, c-fos, Jun, JunD, MAX, c-Myc), cytokines (IL-1β, IL-6, IL-8), type I interferons (IFN-α, IFN-β), and IFN-stimulated genes (Mx1, CCL19, OASL, and PRK) were higher in H5N1-infected than in non-infected resistant Ri chickens. MyD88, Jun, JunD, MAX, cytokines, chemokines, IFNs, and IFN-stimulated expressed genes were higher in resistant-infected than in susceptible-infected Ri chickens. Conclusion: Resistant Ri chickens showed higher antiviral activity compared to susceptible Ri chickens, and H5N1-infected resistant Ri chickens had immune responses and antiviral activity (cytokines, chemokines, interferons, and IFN-stimulated genes), which may have been induced through the MAPK signaling pathway in response to H5N1 infection.

• The Korea Journal of Herbology
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• v.33 no.1
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• pp.47-55
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• 2018

Objectives : The current study is to evaluate the hepatoprotective effect of youngyanggak-san (YGS) on thioacetamide (TAA)-induced acute liver injury in rats. Methods : YGS is composed of Glycyrrhizae Radix, Asiasari Radix, Cimicifugae Rhizoma, Saigae Tataricae Cornu. While N-YGS (non-youngyanggak-san) doesn't include Saigae Tataricae Cornu. Two samples were administrated TAA together for 3 days. Thirty-six rats were divided into four groups. Rats except for the normal group were received TAA (200 mg/kg of body weight, I.P) were divided into three groups (n=9/group) : Group 1 (TAA only), Group 2 (TAA + 200 mg/kg YGS) and Group 3 (TAA + 200 mg/kg N-YGS). Acute liver damage confirmed using histological examination, The factors associated with oxidative stress and liver function activity measured in serum. Also, expressions of inflammation related proteins were investigated by western blot analysis. Results : Oxidative stress factors such as ROS and $ONOO^-$ in the Group 2 was manifested by a significant rise compared with Group 1. YGS markedly decreased the elevated ROS and $ONOO^-$. Furthermore, YGS significantly reduced the levels of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) The nuclear $factor-{\kappa}B$ ($NF-{\kappa}B$) activation induced by TAA led to increase both inflammatory mediators and cytokines. While YGS administration remarkably suppressed such the overexpression. In addition, the histopathological analysis showed that the liver tissue lesions were improved obviously in YGS treatment. Conclusion : YGS provided a hepatoprotective effect on acute liver damage through the suppression of oxidative stress. Especially, this effect enhanced markedly when Saigae Tataricae Cornu is included.