• 한국식품과학회지
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• 제41권4호
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• pp.405-412
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• 2009

본 연구는 꾸지뽕 나무 열매로부터 75 kDa의 당단백질(꾸지뽕 당단백질)을 추출한 후 꾸지뽕 당단백질의 첨가에 따른 알레르기성 염증 인자인 histamine 유리 억제능력 및 COX-2의 활성 억제 효과를 평가하였다. RBL-2H3세포를 22시간 동안 IgE로 감작시킨 후, HSA를 처리하여 histamine의 유리양을 측정한 결과 꾸지뽕 당단백질을 처리한 농도가 증가함에 따라 histamine의 유리와 COX-2의 활성 억제율은 증가하였다. 또한 꾸지뽕 당단백질의 처리는 HSA에 의해 유도된 세포내 ROS 생성량을 농도에 의존적으로 억제하였다. 한편 꾸지뽕 당단백질을 농도별로 처리하여 세포내 단백질을 추출하여 western blot을 실시한 결과 100 ${\mu}g$/mL 농도의 꾸지뽕 당단백질을 처리한 그룹에서 ERK1/2, AP-1과 COX-2의 활성 수준은 현저히 억제 되었다(p<0.05). 따라서 이러 한 결과에 미루어볼 때, 꾸지뽕 당단백질은 세포내 해독효소의 활성을 증가시킴으로써 ROS 수준을 감소시켰으므로 꾸지뽕 당단백질의 역할이 다른 천연물 유래의 당단백질과 마찬가지로 특이적인 항산화 능력을 지니고 있음을 나타내며 histamine의 유리 억제와 COX-2의 활성이 억제되었을 것으로 생각된다. 이는 꾸지뽕 당단백질이 항 알레르기 효능을 갖는 물질로써 알레르기성 비염, 아토피 등과 같은 알레르기 관련 질환의 예방 및 치료제로 사용될 수 있을 것 사료된다.

• International Journal of Oral Biology
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• 제42권4호
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• pp.149-153
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• 2017

Cyclooxygenase-2 (COX-2)-mediated prostaglandin $E_2$ ($PGE_2$) plays a key role in development and progression of inflammatory responses and Porphyromonas gingivalis is a common endodontic pathogen. In this study, we investigated induction of COX-2 and $PGE_2$ by P. gingivalis in human dental pulp cells (HDPCs). P. gingivalis increased expression of COX-2, but not that of COX-1. Increased levels of $PGE_2$ were released from P. gingivalis-infected HDPCs and this $PGE_2$ increase was blocked by celecoxib, a selective COX-2 inhibitor. P. gingivalis activated all three types of mitogen-activated protein kinases (MAPKs). P. gingivalis-induced activation of nuclear $factor-{\kappa}B$ ($NF-{\kappa}B$) was demonstrated by the results of phosphorylation of $NF-{\kappa}B$ p65 and degradation of inhibitor of ${\kappa}B-{\alpha}$ ($I{\kappa}B-{\alpha}$). Pharmacological inhibition of each of the three types of MAPKs and $NF-{\kappa}B$ substantially attenuated P. gingivalis-induced $PGE_2$ production. These results suggest that P. gingivalis should promote endodontic inflammation by stimulating dental pulp cells to produce $PGE_2$.

• 대한한의학회지
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• 제26권1호
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• pp.37-45
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• 2005

In the present study, we examined the effect of crude methanolic extract (CME) from Euonymus alatus (Thunb.) Sieb on arachidonic acid (AA) cascade in SKBR3 human breast cancer cell line. CME had a potent inhibitory activity of prostaglandin E2 (PGE2) release induced by A23187, a $Ca^{2+}$ ionophore. The inhibition was concentration-dependent, with the 50 value of about 5 M. CME had no inhibitory effect on A23187-induced phosphorylation of p42/p44 extracellular signal regulated kinase/mitogen-activated protein kinase or on the liberation of [14C]-AA from the cells labeled with [14C]-AA. However, CME concentration-dependently inhibited the conversion of AA to $PGE_2$ in microsomal preparations, showing its possible inhibition of cyclooxygenase (COX). In enzyme assay in vitro, CME inhibited the activities of both constitutive COX (COX­I) and inducible COX (COX-2) in a concentration-dependent manner, with the 50 values of about 0.8 and 2M, respectively. Lineweaver-Burk plot analysis indicated that CME competitively inhibited the activities of both COX-l and -2. This study is a first demonstration that CME directly inhibits COX activity.

• The Korean Journal of Physiology and Pharmacology
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• 제21권4호
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• pp.407-413
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• 2017

Vascular reactivity can be influenced by the vascular region, animal age, and pathologies present. Prostaglandins (produced by COX-1 and COX-2) play an important role in the contractile response to phenylephrine in the abdominal aorta of young rats. Although these COXs are found in many tissues, their distribution and role in vascular reactivity are not clear. At a vascular level, they take part in the homeostasis functions involved in many physiological and pathologic processes (e.g., arterial pressure and inflammatory processes). The aim of this study was to analyze changes in the contractile response to phenylephrine of thoracic/abdominal aorta and the coronary artery during aging in rats. Three groups of rats were formed and sacrificed at three distinct ages: prepubescent, young and old adult. The results suggest that there is a higher participation of prostanoids in the contractile effect of phenylephrine in pre-pubescent rats, and a lower participation of the same in old rats. Contrarily, there seems to be a higher participation of prostanoids in the contractile response of the coronary artery of older than pre-pubescent rats. Considering that the changes in the expression of COX-2 were similar for the three age groups and the two tissues tested, and that expression of COX-1 is apparently greater in older rats, COX-1 and COX-2 may lose functionality in relation to their corresponding receptors during aging in rats.

• ALGAE
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• 제27권2호
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• pp.83-94
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• 2012

The taxonomic distinctiveness and cosmopolitan distributions of the red algae $Gelidium$ $crinale$ and $G.$ $pusillum$ remain unclear. Both species were first described in Devon in southwestern England; namely in Ilfracome for $G.$ $crinale$ and Sidmouth for $G.$ $pusillum$. We analyzed mitochondrial $cox$1 and plastid $rbc$L sequences from specimens collected in East Asia, Australia, Europe and North America. In all phylogenetic analyses of $cox$1 and $rbc$L sequences, $G.$ $crinale$ was distinct from congeners of the genus. The analyses also revealed a sister relationship with the $G.$ $coulteri$ and $G.$ $capense$ clade. Nineteen $cox$1 haplotypes were identified for $G.$ $crinale$, and they were likely geographically structured. Despite the distinctiveness in both $cox$1 and $rbc$L datasets, the sister relationship of $G.$ $pusillum$ in the genus was not resolved. Our $cox$1 and $rbc$L datasets indicate that $G.$ $crinale$ is a cosmopolitan species, found in East Asia, Australia, Europe and North America, while the distribution of $G.$ $pusillum$ is restricted to Europe and Atlantic North America. Our results suggest that infraspecific classification of $G.$ $pusillum$ may be abandoned.

• Journal of Acupuncture Research
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• 제17권2호
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• pp.187-208
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• 2000

By the activation of ovary hormone, many morphological changes occur in the epithelial cell lines and muscle cells in rat uterus. These two cells in uterus are important to the implantation of embryo, maintaining pregnancy and starting parturition. One important change associated with the morphological change of these two cells in uterus is the change on prostaglandin(PG) metabolism. Its presence and synthesis in endometriurn and myometrium in uterus affects estrous cycle and the start of embryo implantation in uterus. It also performs as an important modulator in parturition. So the abnormally weak expression of PG causes difficulty during labor and over-expression causes pre-term labor. PG biosynthesis starts from either free or liberated arachidonic acids from membrane phospholipid by phospholipase. Such arachidonic acids are converted into PG catalyzed by Cyclooxygenase. Under normal physiological condition, Cyclooxygenase-1(COX-1) having 602 units of amino acids controls the synthesis of PG. It acts as a local hormone regulating vasomodulation of blood flow, flexible muscle movement, increasing the blood permeability and contributing the protective role in preserving integrity of the stomach lining and Cyclooxygenase-2 (COX-2) is induced by the inflammation, pregnancy and increased its expression until parturition. Lipid metabolite like PG is located in uterine and expression of COX-2 increased with pregnancy. Increased expression of COX proteins in epithelial cells and myometrial cells are told to increase the muscle contractility in uterus but decreased right after the labor in rat. It is a good sign indicating that COX proteins are deeply related to the start of labor. Currently, Several studies report the use of PG and COX-2 inhibitor as medication for controlled abortion or to prevent pre-term labor but they entail various side-effects. Our study proposed to suggest use of acupuncture as an another mediator to control abortion or pre-term labor without causing unnecessary side-effects by those medicines. Two acupuncture sites, LI-4 & SP-6 were selected due to their known efficacy. From the immunohistochemical staining of COX-2, normal expression of COX-2 protein in nonpregnant SD rat's uterus revealed that COX-2 protein was primarily detected in the lumina epithelial lining and in the epithelial cell lining contacting the stromal cells. High resolution optical microscopic scanning revealed distinguishable staining in the myometrial mucosa. LI-4 acupuncture administered nonpregnant rat's uterus showed strong expression for COX-2 in endometrium contacted with lumina epithelial lining of rat uterus and in myometrial mucosa. Stromal cells showed more staining than untreated nonpregnant rat's uterus and stronger staining in stromal cells contacting myometrial layer compared to untreated nonpregnant rat's uterus. SP-6 acupuncture administered nonpregnant rat's uterus showed weak expression for COX-2 in myometrial layers and stromal cells but no staining was visible in lumina epitheliai and glandular epithelial cells. Few stromal cells and myometrial mucosa were positively stained for COX-2. Pregnant SD rat's uterus was also immunostained for COX-2 expression after 18 days of pregnancy. Unlike to untreated nonpregnant rat's uterus, luminal epithelial cells were not positively stained for COX-2 but stronger staining for COX-2 was revealed in stromal cells. LI-4 acupunctured SD rat's uterus had very strong expression of COX-2 in luminal epithelial lining. Few stromal cells showed stronger positive COX-2 staining and myometrial layers also showed more expression than untreated pregnant rat. SP-6 acupuncture administered pregnant SD rat's uterus showed positive expression of COX-2 in epithelial cells of luminal mucosa layer but weaker than that of LI-4 acupuncture treatment's case. However, strong positive staining was revealed in stromal mucosa and myometrial layers. Virgin SD rat's uterus motility index during LI-4 acupuncture was 66.52 % (Prob〉T = 0.0197) compared to its motility before the acupuncture treatment but the motility index was slighdy elevated up to 79.58 % (Prob〉T = 0.1175) after the acupuncture. During the SP-6 acupuncture treatment for 30 minutes, uterus motility index was 90.52 % (Prob〉T = 0.1832) showing lesser decrement but consequently reached similar motility index decreasal to 79.95 % (Prob〉T = 0.0215) after the acupuncture treatment as LI-4 showed. LI-4 acupuncture tend to be a quick treatment to reducing the uterus motility in a virgin rat but eventually both two acupuncture administration created very similar reduction of uterus motility seeing the index after the both acupunctures. The uterus movement monitored during the LI-4 acupuncture administered for 30 minutes, Pregnant SD rat showed decreased motility down to 77.90 % (Prob〉 T = 0.0076) compared to uterus motility before the acupuncture and it continuously decreased down to 71.81 %(Prob〉T = 0.0214) after the removal of needle. The statistical analysis using paired t-test showed significance difference for both two motility indexs at =0.05. SP-6 acupuncture administered to pregnant SD rat also had similar pattern of decreasing uterus motility index down to 74.70 % (Prob〉T = 0.1730) during the initial 30 minutes acupuncture administration and it was continuously lowered to 71.52 % (Prob〉T = 0.0155) after the acupuncture. The paired t-test resuit for SP-6 suggest prompt response of uterus motility index to the SP-6 acupuncture treatment but consequently reached same level of inducing the motility reduction as LI-4 at =0.05 level.

• Radiation Oncology Journal
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• 제25권1호
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• pp.43-53
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• 2007

목 적: 비인강암종 환자들의 종양조직으로부터 EGFR, p53, Cox-2, Bcl-2 단백발현정도를 측정하고 임상양상, 치료성적과의 관련성을 조사하여 이들 단백이 치료에 대한 반응 및 예후를 예측할 수 있는 생물학적 표지자(biomarker)로 이용할 수 있는지 알아보고자 하였다. 대상 및 방법: 1988년 3월 1일부터 2002년 8월 15일까지 성모병원과 강남성모병원에서 비인강암으로 진단받고 근치적 방사선치료와 항암치료를 받았던 환자 104명 중 파라핀 블록이 보존되어 있는 75명을 대상으로 하여 후향적 분석을 시행하였다. 병기는 2002년에 개정된 AJCC로 재분류하였으며, 대상환자의 Hematoxylin-Eosin 염색 슬라이드를 두경부 병리 전문의사가 재검토하여 WHO 분류에 맞게 환자군을 분류하였으며 역형성(anaplasia) 유무, 유사분열(mitosis) 빈도 측정 등 병리조직학적 소견을 확인하였다. EGFR, p53, Cox-2, Bcl-2 단백발현 정도를 면역조직 화학염색을 통해 측정하였으며 이들 단백의 발현정도와 임상병기, 치료성적과의 관련성을 조사하였다. 결 과: 전체 104명 환자의 추적기간은 $5.5{\sim}201$개월이었고 3년 생존율은 68.7%, 5년 생존율은 53.5%, 중앙생존기간은 85.5개월이었으며 3년 무병생존율은 68.2%, 5년 무병생존율은 51.5%, 중앙무병생존기간은 61.1개월이었다. WHO 분류 2와 3 종양은 완전관해율이 높아 항암방사선치료(chemoradiotherapy)에 대한 반응성이 높은 경향을 보였으며(p=0.075), 상대적으로 진단당시 림프절전이율이 높았고, 원격전이할 확률이 높았다. p53은 발현 정도가 증가함에 따라 생존율이 떨어지고 유사분열은 증가하였다. Bcl-2 발현이 증가함에 따라 재발률이 떨어지는 경향을 보였으며, WHO 분류와 연관성을 보였다. Cox-2의 발현이 증가함에 따라 생존율이 떨어지고, 림프절치료율도 낮은 것으로 나타났다. 그러나 EGFR은 어떤 인자와도 상관관계를 보이지 않았다. 결 론: 비인강암에서 치료 후 예후를 예측할 수 있는 생물학적 표지자의 가능성을 가진 것으로 보고되고 있는 Cox-2, p53, Bcl-2, EGFR에 대한 연구결과 Cox-2, p53, Bcl-2의 발현정도는 항암방사선치료후 반응률, 생존율, 재발률과 연관을 보여 향후 치료결과를 예측할 수 있는 예후인자로서의 이용가능성이 있음을 알 수 있었으며 보다 실용적인 생물학적 표지자의 규명을 위해서 향후 보다 많은 환자를 대상으로 한 전향적 연구가 필요할 것으로 생각된다.

• 대한의생명과학회지
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• 제15권4호
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• pp.343-347
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• 2009

Cytochalasin D (CD) is known as a disruptor of actin cytoskeleton architecture in chondrocytes. We have studied the role of CD in retinoic acid (RA) caused dedifferentiation and inflammation responses in rabbit articular chondrocytes. We have examined the effect of CD on RA induced dedifferentiation of chondrocytes. CD inhibited RA induced dedifferentiation determined by Western blot analysis and Alcian blue staining in rabbit articular chondrocytes. Also, CD additionally reduced inflammation response molecules such as cyclooxygenase-2 (COX-2) and prostaglandin $E_2$ ($PGE_2$) in RA treated cells. Treatment of CD reduced phosphorylation of p38 by treatment of RA. Inhibiton of p38kinase with SB203580 reduced expression of COX-2 and production of $PGE_2$ by treatment of CD in RA treated cells. But, Inhibiton of p38kinase with SB203580 did not any relationship with effect of CD on RA caused dedifferentiation. In summary, our results indicate that CD regulates RA reduced expression of COX-2 and production of PGE2 via p38kinase pathway.

• Biomolecules & Therapeutics
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• 제20권6호
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• pp.520-525
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• 2012

Prostaglandin (PG) $E_2$, the most abundant prostaglandin in the human body, is synthesized from arachidonic acid via the actions of cyclooxygenase (COX) enzymes. $PGE_2$ exerts homeostatic, cytoprotective, inflammatory, and in some cases anti-inflammatory effects. Also, it has been reported that $PGE_2$ is involved in hair growth. Diphlorethohydroxycarmalol (DPHC) is a phlorotannin compound isolated from the brown algae Ishige okamurae, with various biological activities in vitro and in vivo. In this study, the biological effect and mechanism of action of DPHC on prostaglandin synthesis in HaCaT human keratinocytes was examined. The results showed that, in these cells, DPHC significantly and dose-dependently induced $PGE_2$ synthesis by increasing the protein and mRNA levels of COX-1 and COX-2. Interestingly, DPHC-induced COX-1 expression preceded that of COX-2. Also, while both rofecoxib and indomethacin inhibited $PGE_2$ production, the latter was seems to be the more potent. From above results, we can expect that DPHC has some beneficial effects via increasing of $PGE_2$ production.

• The Korean Journal of Physiology and Pharmacology
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• 제9권4호
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• pp.215-221
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• 2005

We investigated the effects of testosterone and dihydrotestosterone on inflammatory response of iNOS and COX-2 expression in rat vascular smooth muscle cells. Rat vascular smooth muscle cells (VSMC) stimulated with bacterial lipopolysaccharide $(LPS;\;10{\mu}g/ml)$ for 24 hours were incubated with increasing amounts of testosterone and dihydrotestosterone (1 and 100 nM). LPS was found to induce inflammatory response of iNOS and COX-2 mRNA and protein in VSMC. These processes were affected by male sex steroid hormones. For 3 hours, however, pretreatment of the cells with 100 nM each of testosterone and dihydrotestosterone suppressed LPS induced iNOS and COX-2 protein expression. RT-PCR analysis revealed that testosterone and dihydrotestosterone did not inhibit mRNA expression of iNOS and COX-2 stimulated by 24 hours of LPS incubation. Proliferation rate was slower in VSMC treated with testosterone and dihydrotestosterone. Testosterone enhanced androgen receptor expression, and LPS significantly reduced androgen receptor protein expression in VSMC. These results indicate that the expression of both iNOS and COX-2 proteins was suppressed by testosterone and dihydrotestosterone in LPS stimulated VSMC and leading to reduction of vascular inflammation.