• Title/Summary/Keyword: Cox

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Associations between Single Nucleotide Polymorphisms of COX-2 and MMP-2 Genes and Colorectal Cancer Susceptibility in the Saudi Population

  • Shalaby, Manal Ali;Nounou, Howaida Attia;Alanazi, Mohammad Saud;Alharby, Othman;Azzam, Nahla;Saeed, Hesham Mahmoud
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.12
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    • pp.4989-4994
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    • 2014
  • Background: It has been reported that COX-2 expression is associated with MMP-2 expression in thyroid and breast cancers, suggesting that MMPs are linked to COX-2-mediated carcinogenesis. Several polymorphisms within the MMP2 promoter region have been reported in cases with oncogenesis and tumor progression, especially in colorectal carcinogenesis. Materials and Methods: This research evaluated risk of association of the SNPs, including genes for COX-2 (AIG transition at +202) and MMP-2 (Crr transition at-1306), with colorectal cancer in 125 patients and 125 healthy controls. Results and Conclusions: Our data confirmed that MMP2 C-1306 T mutations were significantly more common in colon cancer patients than in our control Saudi population; p=O.0121. On the other hand in our study, there was no significant association between genotype distribution ofthe COX2 polymorphism and colorectal cancer; p=0.847. An elevated frequency ofthe mutated genotype in the control group as compared to the patients subjects indeed suggested that this polymorphism could decrease risk in the Saudi population. Our study confirmed that the polymorphisms that could affect the expressions of MMP-2 and COX-2 the colon cancer patients were significantly higher than that in the COX-2 negative group. The frequency of individuals with MMP2 polymorphisms in colon cancer patients was higher than individuals with combination of COX2 and MMP2 polymorphisms. Our study confirmed that individuals who carried the polymorphisms that could affect the expressions ofCOX2 are more susceptible to colon cancer. MMP2 regulatory polymorphisms could be considered as protective; further studies need to confirm the results with more samples and healthy subjects.

Src Kinase Regulates Nitric Oxide-induced Dedifferentiation and Cyc1ooxygenase-2 Expression in Articular Chondrocytes via p38 Kinase-dependent Pathway

  • Yu, Seon-Mi;Lee, Won-Kil;Yoon, Eun-Kyung;Lee, Ji-Hye;Lee, Sun-Ryung;Kim, Song-Ja
    • IMMUNE NETWORK
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    • v.6 no.4
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    • pp.204-210
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    • 2006
  • Background: Nitric oxide (NO) in articular chondrocytes regulates dedifferentiation and inflammatory responses by modulating MAP kinases. In this study, we investigated whether the Src kinase in chondrocytes regulates NO-induced dedifferentiation and cyclooxygenase-2 (COX-2) expression. Methods: Primary chondrocytes were treated with various concentrations of SNP for 24 h. The COX-2 and type II collagen expression levels were determined by immunoblot analysis, and prostaglandin $E_2\;(PGE_2)$ was determined by using a $PGE_2$ assay kit. Expression and distribution of p-Caveolin and COX-2 in rabbit articular chondrocytes and cartilage explants were determined by immunohistochemical staining and immunocytochemical staining, respectively. Results: SNP treatment stimulated Src kinase activation in a dose-dependent manner in articular chondrocytes. The Src kinase inhibitors PP2 [4-amino-5-(4-chlorophenyl)-7-(t-butyl)pyrazolo(3,4-d)pyrimidine], a significantly blocked SNP-induced p38 kinase and caveolin-1 activation in a dose-dependent manner. Therefore, to determine whether Src kinase activation is associated with dedifferentiation and/or COX-2 expression and $PGE_2$ production. As expected, PP2 potentiated SNP-stimulated dedifferentiation, but completely blocked both COX-2 expression and $PGE_2$ production. And also, levels of p-Caveolin and COX-2 protein expression were increased in SNP-treated primary chondrocytes and osteoarthritic and rheumatoid arthritic cartilage, suggesting that p-Caveolin may playa role in the inflammatory responses of arthritic cartilage. Conclusion: Our previously studies indicated that NO caused dedifferentiation and COX-2 expression is regulated by p38 kinase through caveolin-1 (1). Therefore, our results collectively suggest that Src kinase regulates NO-induced dedifferentiation and COX-2 expression in chondrocytes via p38 kinase in association with caveolin-1.

Suppressive effects on the expression of cyclooxygenase-2 and inducible nitric oxide synthase by a natural sesquiterpenoid in lipopolysaccharide-stimulated mouse macrophage cells

  • Min, Hye-Young;Park, Hyen-Joo;Park, Eun-Jung;Lee, Sang-Kook
    • Proceedings of the Korean Society of Applied Pharmacology
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    • 2003.11a
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    • pp.101-101
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    • 2003
  • Prostaglandins (PGs) and nitric oxide (NO) produced by inducible cyclooygenase (COX-2) and nitric oxide synthase (iNOS), respectively, have been implicated as important mediators in the process of inflammation and carcinogenesis. On this line, the potential COX-2 or iNOS inhibitors have been considered as anti-inflammatory and cancer chemopreventive agents. In our continuing efforts of searching for novel cancer chemopreventive agents from natural products, we isolated natural sesquiterpenoids as potential COX-2 and iNOS inhibitors in cultured lipopolysaccharide (LPS)-activated mouse macrophage RAW 264.7 cells. Alantolactone, a natural eudesmane-type sesquiterpenoid, exhibited a potent inhibition of COX-2 (IC50 = 0.4 $\mu\textrm{g}$/$m\ell$) and iNOS activity (IC50 = 0.08 $\mu\textrm{g}$/$m\ell$) in the assay system determined by PGE2 and NO accumulation, respectively. The inhibitory potential of alantolactone on the PGE2 and NO production was well coincided with the suppression of COX-2 and iNOS protein and mRNA expression in LPS-induced macrophages. Furthermore, alantolactone inhibited NF-kB but not AP-l binding activity on nuclear extracts evoked by LPS-stimulated macrophage cells, suggesting the possible involvement of NF-kB in the regulation of COX-2 and iNOS expression. In further study with COX-2-expressing human colon HT-29 cells, alantolactone inhibited the cell proliferation, down-regulated COX-2, and inhibited the ERK phosphorylation in the early time. These results suggest that a natural sesquiterpenoid alantolactone might be a potential lead candidate for further developing COX-2 or iNOS inhibitor possessing cancer chemopreventive or anti-inflammatory activity

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The Characteriastics of Viscosity Behavior of EMC for Semi-conductor Encapsulant - Containing One Kind of Spherical Silica (반도체 봉지재용 EMC의 점도거동 특성 - 한 종류의 구형 실리카 포함)

  • Kim, In Beom;Lee, Myung Cheon;Lee, Euy Soo
    • Applied Chemistry for Engineering
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    • v.10 no.8
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    • pp.1175-1179
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    • 1999
  • The rheological properties of highly filled epoxy molding compound(EMC) for semi-conductor encapsulants are greatly affected by the content of filler loaded. In this study, the change of viscosity of EMC for semi-conductor encapsulants with the filler content was investigated. Also, both of Cox-Merz and modified Cox-Merz equations were applied to convert the viscosity change as a function of frequency to that of shear rate. It was ovserved that shear thinning and yield stress occured at high filler contents and that the Cox-Merz equation could not be applied at high filler contents because of the difference of viscosity according to the various strains. When the modified Cox-Merz equation was applied, the all the curves having different strain tend to be represented by one master curve, even though some deviation was obseved at high filler content and strain.

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Monitoring of Fasciola Species Contamination in Water Dropwort by COX1 Mitochondrial and ITS-2 rDNA Sequencing Analysis

  • Choi, In-Wook;Kim, Hwang-Yong;Quan, Juan-Hua;Ryu, Jae-Gee;Sun, Rubing;Lee, Young-Ha
    • Parasites, Hosts and Diseases
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    • v.53 no.5
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    • pp.641-645
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    • 2015
  • Fascioliasis, a food-borne trematode zoonosis, is a disease primarily in cattle and sheep and occasionally in humans. Water dropwort (Oenanthe javanica), an aquatic perennial herb, is a common second intermediate host of Fasciola, and the fresh stems and leaves are widely used as a seasoning in the Korean diet. However, no information regarding Fasciola species contamination in water dropwort is available. Here, we collected 500 samples of water dropwort in 3 areas in Korea during February and March 2015, and the water dropwort contamination of Fasciola species was monitored by DNA sequencing analysis of the Fasciola hepatica and Fasciola gigantica specific mitochondrial cytochrome c oxidase subunit 1 (cox1) and nuclear ribosomal internal transcribed spacer 2 (ITS-2). Among the 500 samples assessed, the presence of F. hepatica cox1 and 1TS-2 markers were detected in 2 samples, and F. hepatica contamination was confirmed by sequencing analysis. The nucleotide sequences of cox1 PCR products from the 2 F. hepatica-contaminated samples were 96.5% identical to the F. hepatica cox1 sequences in GenBank, whereas F. gigantica cox1 sequences were 46.8% similar with the sequence detected from the cox1 positive samples. However, F. gigantica cox1 and ITS-2 markers were not detected by PCR in the 500 samples of water dropwort. Collectively, in this survey of the water dropwort contamination with Fasciola species, very low prevalence of F. hepatica contamination was detected in the samples.

Development of New Molecular Markers for the Identification of Male Sterile Cytoplasm in Peppers (Capsicum annuum L.)

  • Min, Woong-Ki;Kim, Byung-Dong;Kim, Sung-Gil;Lee, Sang-Hyeob
    • Horticultural Science & Technology
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    • v.29 no.1
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    • pp.53-60
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    • 2011
  • Cytoplasmic male sterility (CMS) induced by mutant mitochondria genome, has been used for commercial seed production of $F_1$ hybrid cultivars in diverse crops. In pepper (Capsicum annuum L.), two sterile cytoplasm specific gene organization, atp6-2 and coxII were identified. An open reading frame, orf456 nearby coxII gene has been speculated to induce male sterility (MS) by mutagenic analysis. Moreover, molecular markers for atp6-2 and coxII of mitochondrial genotype (mitotype) were developed. However, the Cytoplasmic MS specific markers, atp6SCAR and coxIISCAR markers appeared in both N and S cytoplasms when polymerase chain reaction (PCR) cycles prolonged more than 40 cycles. Since the reported molecular markers were dominant markers, the presence of the faint sterile-specific band in normal cytoplasm may lead to the mis-classification of pepper breeding lines. To solve this problem, one common forward primer and two different reverse primers specific to normal coxII and sterile orf456 genes were designed after analyzing their gene organizations. By using these three primers, N and S coxII specific bands were co-amplified in male-sterile lines, but only normal coxII specific band was amplified in maintainer lines. Since the reverse primer for sterile coxII was specifically designed 275 bp downstream of orf456, relatively stable PCR amplification patterns were observed regardless of the number of PCR cycles. These primer sets easily identified different mitotypes among the divergent breeding lines, commercial cultivars and diverse germplasms.

NFATc Mediates Lipopolysaccharide and Nicotine-Induced Expression of iNOS and COX-2 in Human Periodontal Ligament Cells (사람 치주인대세포에서 Lipopolysaccharide와 니코틴으로 유도된 iNOS와 COX-2 발현에 NFATc의 관여)

  • Lee, Sang-Im;Yu, Ji-Su
    • Journal of dental hygiene science
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    • v.15 no.6
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    • pp.753-760
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    • 2015
  • Although nuclear factor of activated T cell (NFAT) plays a key role in inflammation, its anti-inflammatory effects and mechanism of action in periodontitis are still unknown. This study aimed to identify the effects of NFAT on the proinflammatory mediators activated by lipopolysaccharide (LPS) plus nicotine stimulation in human periodontal ligament cells (hPDLCs). The production of nitric oxide (NO) and prostaglandin $E_2(PGE_2)$ was evaluated using Griess reagent and an enzyme immunoassay, respectively. The expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2) and NFAT proteins was evaluated by Western blot analysis. LPS plus nicotine synergistically induced the production of NO and $PGE_2$ and increased the protein expression of iNOS, COX-2 and NFAT. Treatment with an NFAT inhibitor blocked the LPS plus nicotine-stimulated NO and $PGE_2$ release as well as the expression of iNOS and COX-2. Our data suggest that the LPS plus nicotine-induced inflammatory effects on hPDLCs may act through a novel mechanism involving the action of NFAT. Thus, NFAT may provide a potential therapeutic target for the treatment of periodontal disease associated with smoking and dental plaque.

Cyclooxygenase-2 Induction in Porphyromonas gingivalis-Infected THP-1 Monocytic Cells

  • Choi, Eun-Kyoung;Oh, Byung-Ho;Kang, In-Chol
    • International Journal of Oral Biology
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    • v.31 no.1
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    • pp.21-26
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    • 2006
  • Periodontopathogens including Porphyromonas gingivalis interact with host periodontal cells and the excessive subsequent host responses contribute a major part to the development of periodontal diseases. Cyclooxygenase(COX)-2-synthesized $PGE_2$ has detrimental activities in terms of periodontal pathogenesis. The present study investigated induction of COX-2 expression by P. gingivalis in human monocytic THP-1 cells. Live P. gingivalis increased expression of COX-2, but not that of COX-1, which was demonstrated at both mRNA and protein levels. Elevated levels of $PGE_2$ were released from P. gingivalis-infected THP-1 cells. Pharma-cological inhibition of p38 mitogen-activated protein kinase(MAPK) and extracellular signal-regulated kinase(ERK) substantially attenuated P. gingivalis-induced COX-2 mRNA expression. Indeed, activation of p38 MAPK and ERK was observed in P. gingivalis-infected THP-1 cells. Also, P. gingivalis induced activation of nuclear $factor-{\kappa}B\;(NF-{\kappa}B)$ which is an important transcription factor for COX-2. These results suggest that COX-2 expression is up regulated in P. gingivalis-infected monocytic cells, at least in part, via p38 MAPK, ERK, and $NF-{\kappa}B$.

Infection and cox2 sequence of Pythium chondricola (Oomycetes) causing red rot disease in Pyropia yezoensis (Rhodophyta) in Korea

  • Lee, Soon Jeong;Jee, Bo Young;Son, Maeng-Hyun;Lee, Sang-Rae
    • ALGAE
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    • v.32 no.2
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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.

Phylogenetic relationships and distribution of Gelidium crinale and G. pusillum (Gelidiales, Rhodophyta) using cox1 and rbcL sequences

  • Kim, Kyeong-Mi;Boo, Sung-Min
    • ALGAE
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    • v.27 no.2
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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.