• ALGAE
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• 제32권2호
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• pp.155-160
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• 2017

Red rot disease has caused a major decline in Pyropia (Nori) crop production in Korea, Japan, and China. To date, only Pythium porphyrae (Pythiales, Oomycetes) has been reported as the pathogen causing red rot disease in Pyropia yezoensis (Rhodophyta, Bangiales). Recently, Pythium chondricola was isolated from the infected blades of Py. yezoensis during molecular analyses using the mitochondrial cox1 region. In this study, we evaluated the pathogenicity of P. chondricola as an algal pathogen of Py. yezoensis. Moreover, a new cox2 marker was developed with high specificity for Pythium species. Subsequent to re-inoculation, P. chondricola successfully infected Py. yezoensis blades, with the infected regions containing symptoms of red rot disease. A novel cox2 marker successfully isolated the cox2 region of Pythium species from the infected blades of Py. yezoensis collected from Pyropia aquaculture farms. cox2 sequences showed 100% identity with that of P. chondricola (KJ595354) and 98% similarity with that of P. porphyrae (KJ595377). The results of the pathogenicity test and molecular analysis confirm that P. chondricola is a new algal pathogen causing red rot disease in Pyropia species. Moreover, it could also suggest the presence of cryptic biodiversity among Korean Pythium species.

• Journal of Pharmaceutical Investigation
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• 제33권2호
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• pp.105-112
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• 2003

Selective COX (cyclooxygenase)-2 inhibitors including celecoxib have been shown to induce apoptosis and cell cycle changes in various tumor cells. New inhibitors are recently being developed as chemomodulating agents. We evaluated celecoxib and screened 150 synthetic compounds for anti-proliferative activities in vitro. Effects of celecoxib on COX activity, cell growth, cell cycle distribution, and apoptosis induction were determined in A549 COX-2 overexpressing human non-small cell lung cancer (NSCLC) cells. The COX inhibition of celecoxib increased with concentration up to 82% at $1\;{\mu}M$ after 24 hr exposure. Forty ${\mu}M$ and $50\;{\mu}M$ of ce1ecoxib induced $G_1$ arrest, and TUNEL-positive apoptotic cells, respectively. Among 150 compounds, several compounds were selected for having greater COX-2 inhibitory activity and higher selectivity than celecoxib with growth inhibitory activity. Celecoxib showed concentration-dependent COX inhibitory activity, and ability to induce cell cycle arrest and apoptosis in human NSCLC cells in vitro. Among synthetic analogues screened, several compounds showed promising in vitro activity as COX-2 inhibitory anticancer agents, which warrant further evaluation in vitro and in vivo.

• Biomolecules & Therapeutics
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• 제29권3호
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• pp.342-351
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• 2021

Liver colonization is initiated through the interplay between tumor cells and adhesion molecules present in liver sinusoidal endothelial cells (LSECs). This crosstalk stimulates tumor COX-2 upregulation and PGE2 secretion. To elucidate the role of the LSEC intercellular adhesion molecule-1 (ICAM-1) in the prometastatic response exerted by tumor and stromal COX-2, we utilized celecoxib (CLX) as a COX-2 inhibitory agent. We analyzed the in vitro proliferative and secretory responses of murine C26 colorectal cancer (CRC) cells to soluble ICAM-1 (sICAM-1), cultured alone or with LSECs, and their effect on LSEC and hepatic stellate cell (HSC) migration and in vivo liver metastasis. CLX reduced sICAM-1-stimulated COX-2 activation and PGE2 secretion in C26 cells cultured alone or cocultured with LSECs. Moreover, CLX abrogated sICAM-1-induced C26 cell proliferation and C26 secretion of promigratory factors for LSECs and HSCs. Interestingly, CLX reduced the protumoral response of HSC, reducing their migratory potential when stimulated with C26 secretomes and impairing their secretion of chemotactic factors for LSECs and C26 cells and proliferative factors for C26 cells. In vivo, CLX abrogated the prometastatic ability of sICAM-1-activated C26 cells while reducing liver metastasis. COX-2 inhibition blocked the creation of a favorable tumor microenvironment (TME) by hindering the intratumoral recruitment of activated HSCs and macrophages in addition to the accumulation of fibrillar collagen. These results point to COX-2 being a key modulator of processes initiated by host ICAM-1 during tumor cell/LSEC/HSC crosstalk, leading to the creation of a prometastatic TME in the liver.

• The Korean Journal of Physiology and Pharmacology
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• 제5권3호
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• pp.253-258
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• 2001

The present study was aimed to examine whether the expression of renin is associated with that of cyclooxygenase-2 (COX-2) in the kidney. Male Sprague-Dawley rats were made two-kidney, one clip (2K1C) or deoxycorticosterone acetate (DOCA)-salt hypertensive, to stimulate or to inhibit the endogenous renin-angiotensin system, respectively. The expression of renin and COX-2 mRNA was determined in the cortex of the kidney by reverse transcription-polymerase chain reaction. 2K1C hypertensive rats showed an increased expression of renin as well as of COX-2 in the clipped kidney. The expression of renin was decreased in parallel with that of COX-2 in the contralateral non-clipped kidney. Removal of the renal arterial clip reversed the expression of both genes, along with the blood pressure, to the control level. On the other hand, DOCA-salt hypertension was associated with parallel decreases of renin and COX-2 expression. These results indicate that renin and COX-2 genes are coordinately expressed in the kidney.

• 약학회지
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• 제42권6호
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• pp.558-566
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• 1998

Two isoforms of cyclooxygenase (COX) have been identified - COX-1, which is constitlitively expressed in most tissues, and the inducible form, COX-2, of which expression is induced by inflammatory signals and mitogens. It has been considered that the beneficial effects of NSAIDs are due to the inhibition of COX-2 activity and the side effects are from the inhibition of COX-1 activity. Therefore, it is essential to develop selective COX-2 inhibitor for developing new GI-tolerable NSAIDS. To discover new leads for developing selective COX-2 inhibitors, three-hundred extracts of natural products were primarily screened with the system of prostaglandin accumulation in LPS-stimulated mouse peritoneal macrophages. To identify whether these inhibitory activities of crude extracts on the accumulation of Prostaglandins were derived from direct action against COX-2, the effects of selected extracts on exogenous arachidonic acid-derived production of prostaglandins by LPS-stimulated macrophages were determined. Among them, 5 methanol extracts of natural products, such as Zingiberis Rhizoma, Alpinae Officinarum Rhizoma, Caryophilli Flos, Scutellariae Radix, Dalbergia ordorifera. inhibited more than 70% of the prostaglandin production in LPS-stimulated mouse peritoneal macrophages at a con-centration of 1${\mu}$g/ml.

• Biomolecules & Therapeutics
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• 제8권1호
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• pp.73-77
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• 2000

Rheum undulatum L. has been used as Rhei Radix in Korean Pharmacopea although their pharmacological effects were not studied much. In this studym, we tested anti-inflammatory effect as a representative activity of Rheum undulatum L. extracts using cyclooxygenase (COX)-2 inhibition. Murine macrophage, Raw 264.7 cells were incubated with lipopolysaccharide (1 $\mu\textrm{g}$/ml) to induce COX-2. The prostagladin $E_2$ ($PGE_2$) levels as an indicator of COX-2 activity were determined in the culture medium using ELISA. Inhibition of acetylsalicylic acid (ASA) as a standard, aloe-emodin, chrysophanol, rhein, 80% ethanol extract of Rheum undulatum L. (Ex) and ether fraction (Fr) after acid hydrolysis of Rheum undulatum L. were tested in induced COX-2 described above. $IC_{50}$ values were 0.082 $\mu\textrm{g}$/ml for ASA. 181 $\mu\textrm{g}$/ml for aloe-emodin, 3.65 $\mu\textrm{g}$/ml for emodin, 144 $\mu\textrm{g}$/ml for chrysophanol, 39.8 $\mu\textrm{g}$/ml for rhein, 141 $\mu\textrm{g}$ of herb/ml for Ex, and 95.7 $\mu\textrm{g}$ of herb/ml for Fr. We found that Ex and Fr of Rheum undulatum L. were more effective than other anthraquinones, since their $IC_{50}$ are lower than others.

• 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.

• 한국식품저장유통학회지
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• 제17권5호
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• pp.752-756
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• 2010

나비류 추출물은 전통적으로 다양한 활성을 보유하여 의약용으로 사용되어졌다. 5종의 나비(산제비나비[Papilio maackii], 호랑나비[Papilio xuthus], 배추흰나비[Pieris rapae], 남방호랑나비[Eurema hecabe], 왕오색나비[Sasakia charonda])를 이용하여 물, dimethly sulfoxide (DMSO), ehtanol 및 methanol로 추출한 추출물로 항산화 활성 및 Cox-2 promoter assay를 수행하였다. 그 결과 산제비나비의 추출물이 전반적으로 높은 항산화활성을 나타내었으며, Cox-2 promoter assay에서는 호랑나비의 DMSO 분획이 가장 저해활성이 높은 것으로 나타났다. 활성이 높은 추출물을 대상으로 분리 및 정제를 통하여 유용한 식의약 소재로의 기초연구가 더 필요하다.

• Genomics & Informatics
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• 제12권4호
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• pp.247-253
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• 2014

Osteosarcoma is the most common primary bone tumor, generally affecting young people. While the etiology of osteosarcoma has been largely unknown, recent studies have suggested that cyclooxygenase-2 (COX-2) plays a critical role in the proliferation, migration, and invasion of osteosarcoma cells. To understand the mechanism of action of COX-2 in the pathogenesis of osteosarcoma, we compared gene expression patterns between three stable COX-2-overexpressing cell lines and three control cell lines derived from U2OS human osteosarcoma cells. The data showed that 56 genes were upregulated, whereas 20 genes were downregulated, in COX-2-overexpressed cell lines, with an average fold-change > 1.5. Among the upregulated genes, COL1A1, COL5A2, FBN1, HOXD10, RUNX2, and TRAPPC2 are involved in bone and skeletal system development, while DDR2, RAC2, RUNX2, and TSPAN31 are involved in the positive regulation of cell proliferation. Among the downregulated genes, HIST1H1D, HIST1H2AI, HIST1H3H, and HIST1H4C are involved in nucleosome assembly and DNA packaging. These results may provide useful information to elucidate the molecular mechanism of the COX-2-mediated malignant phenotype in osteosarcoma.

• 대한약학회:학술대회논문집
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• 대한약학회 2002년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2
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• pp.355.3-356
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• 2002

Prostaglandins are synthesized by the enzyme cyclooxygenase (COX). Both constitutive (COX-1) and inducible (COX-2) isoforms have been identified. COX-2 expression is stimulated by inflammatory mediators such as growth factors and cytokines. Most non-steroidal anti-inflammatory drugs (NSAIDS) inhibit both isoforms of COX. Recent evidence suggests that selective inhibitors of COX-2 may possess diminished side effects reletive to common NSAIDS. Novel isothiazoles and isoxazoles were identified as selective inhibitiors of cycloxygenase-2(COX-2). (omitted)