• Title/Summary/Keyword: COX1 gene

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TI-I-174, a Synthetic Chalcone Derivative, Suppresses Nitric Oxide Production in Murine Macrophages via Heme Oxygenase-1 Induction and Inhibition of AP-1

  • Kim, Mi Jin;Kadayat, Taraman;Kim, Da Eun;Lee, Eung-Seok;Park, Pil-Hoon
    • Biomolecules & Therapeutics
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    • v.22 no.5
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    • pp.390-399
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    • 2014
  • Chalcones (1,3-diaryl-2-propen-1-ones), a flavonoid subfamily, are widely known for their anti-inflammatory properties. Propenone moiety in chalcones is known to play an important role in generating biological responses by chalcones. In the present study, we synthesized chalcone derivatives structurally modified in propenone moiety and examined inhibitory effect on nitric oxide (NO) production and its potential mechanisms. Among the chalcone derivatives used for this study, TI-I-174 (3-(2-Hydroxyphenyl)-1-(thiophen-3-yl)prop-2-en-1-one) most potently inhibited lipopolysaccharide (LPS)-stimulated nitrite production in RAW 264.7 macrophages. TI-I-174 treatment also markedly inhibited inducible nitric oxide synthase (iNOS) expression. However, TI-I-174 did not significantly affect production of IL-6, cyclooxygenase-2 (COX-2) and tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$), implying that TI-I-174 inhibits production of inflammatory mediators in a selective manner. Treatment of macrophages with TI-I-174 significantly inhibited transcriptional activity of activator protein-1 (AP-1) as determined by luciferase reporter gene assay, whereas nuclear factor-${\kappa}B$ (NF-${\kappa}B$) activity was not affected by TI-I-1744. In addition, TI-I-174 significantly inhibited activation of c-Jun-N-Terminal kinase (JNK) without affecting ERK1/2 and p38MAPK, indicating that down-regulation of iNOS gene expression by TI-I-174 is mainly attributed by blockade of JNK/AP-1 activation. We also demonstrated that TI-I-174 treatment led to an increase in heme oxygenase-1 (HO-1) expression both at mRNA and protein level. Transfection of siRNA targeting HO-1 reversed TI-I-174-mediated inhibition of nitrite production. Taken together, these results indicate that TI-I-174 suppresses NO production in LPS-stimulated RAW 264.7 macrophages via induction of HO-1 and blockade of AP-1 activation.

FoxM1 as a Novel Therapeutic Target for Cancer Drug Therapy

  • Xu, Xin-Sen;Miao, Run-Chen;Wan, Yong;Zhang, Ling-Qiang;Qu, Kai;Liu, Chang
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.1
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    • pp.23-29
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    • 2015
  • Background: Current cancer therapy mainly focuses on identifying novel targets crucial for tumorigenesis. The FoxM1 is of preference as an anticancer target, due to its significance in execution of mitosis, cell cycle progression, as well as other signal pathways leading to tumorigenesis. FoxM1 is partially regulated by oncoproteins or tumor suppressors, which are often mutated, lost, or overexpressed in human cancer. Since sustaining proliferating signaling is an important hallmark of cancer, FoxM1 is overexpressed in a series of human malignancies. Alarge-scale gene expression analysis also identified FoxM1 as a differentially-expressed gene in most solid tumors. Furthermore, overexpressed FoxM1 is correlated with the prognosis of cancer patients, as verified in a series of malignancies by Cox regression analysis. Thus, extensive studies have been conducted to explore the roles of FoxM1 in tumorigenesis, making it an attractive target for anticancer therapy. Several antitumor drugs have been reported to target or inhibit FoxM1 expression in different cancers, and down-regulation of FoxM1 also abrogates drug resistance in some cancer cell lines, highlighting a promising future for FoxM1 application in the clinic.

Comparative analysis of nitrite scavenging activity and anti-inflammation effects in the fruiting bodies of medicinal mushrooms (약용버섯류 자실체의 아질산염 소거능 및 항염증 효능 분석)

  • Cho, Jae-Han;Lee, Gang-Hyo;Han, Jae-Gu;Kim, Hyung-Don;Jhune, Chang-Sung
    • Journal of Mushroom
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    • v.13 no.4
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    • pp.330-333
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    • 2015
  • This study was carried out to compare the anti-inflammation effects of various fruiting body of Ganoderma species and Cordyceps militaris, Phelinus linteus extracts. We concentrated Ganoderma species and other medicinal mushrooms by extracting with ethanol. And We made it $100{\mu}g/ml$ concentration. As a result of nitrite scavenging activity, in the contrast to the positive control; Ascorbic acid was 25%, ASI 7080 of Ganoderma species was disappeared up to around 40%. And in the contrast to Ascorbic acid was 55%, ASI 7002 was 78.5% that was the highest anti-inflammation effect in the result of "No assay test". The Cordyceps militaris showed 75% and Hericium erinaceus showed 59.7% of anti-inflammation effect. As a result of the fungus yield control test of $TNF-{\alpha}$ through ELISA method to ASI 7002 of Ganoderma species that showed the highest anti-inflammation, it was reduced as same as LPS non-treatment. We extracted RNA from ASI 7002 Ganoderma species 10, 50, $100{\mu}g/ml$ concentration and LPS $10{\mu}g/ml$ of Raw 264.7 cell. And we tested the expression of iNOS, COX-2 and TNF-a that are kinds of inflammation gene after synthesizing RNA with cDNA. Finally we could find that iNOS, COX-2 and TNF-a were all controlled expression in the result of above experiment.

MicroRNA-101 Inhibits Cell Proliferation, Invasion, and Promotes Apoptosis by Regulating Cyclooxygenase-2 in Hela Cervical Carcinoma Cells

  • Huang, Fei;Lin, Chen;Shi, Yong-Hua;Kuerban, Gulinar
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.10
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    • pp.5915-5920
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    • 2013
  • Aim: Although aberrant miRNA expression has been documented, altered miR-101 expression in cervical cancer and its carcinogenic effects and mechanisms remain unexplored. The aim of our study was to investigate the role of miR-101 alteration in cervical carcinogenesis. Methods: Expression of miR-101 was examined by quantitative real-time reverse transcriptase PCR (qRT-PCR) in Hela cells. After modulating miR-101 expression using miR-101 mimics, cell growth, apoptosis and proliferation, and migration were tested separately by MTT or flow cytometry and cell wound healing assay and protein expression was detected by qRT-PCR. The expression of COX-2 in Hela cell was also examined by immunohistochemical staining and the correlation with miR-101 expression was analysed. Results: The miR-101 demonstrated significantly low expression in Hela cell. When we transfected miR-101 mimics into Hela cells, the modulation of miR-101 expression remarkably influenced cell proliferation, cycling and apoptosis: 1) The expression of microRNA-101 tended to increase after transfection; 2) Overexpression of miR-101 was able to promote cell apoptosis, the apoptosis rate being markedly higher (97.6%) than that seen pre-transfection (12.2%) (P<0.05); 3) The miR-101 negatively regulates cell migration and invasion, scratch results being lower ($42.7um{\pm}2um$) than that observed pre-transfection ($181.4um{\pm}2um$); 4) miRNA-101 inhibits the proliferation of Hela cells as well as the level of COX-2 protein, which was negatively correlated with miR-101 expression. Conclusions: Overexpression of miR-101 has obvious inhibitory effects on cell proliferation, migration and invasion. Thus reduced miR-101 expression could participate in the development of cervical cancer at least partly through loss of inhibition of target gene COX-2, which probably occurs in a relative late phase of carcinogenesis. Our data suggest an important role of miR-101 in the molecular etiology of cancer and indicate potential application of miR-101 in cancer therapy.

Effects of Carthami Tinctorius on Rat Calvarial Cell Activity and MG63 Cell mRNA Synthesis (랫드의 두개골세포 활성 및 mRNA 발현에 미치는 홍화자의 영향)

  • Kim, Tae-Woong;Hwang, Gwi-Seo
    • Journal of Society of Preventive Korean Medicine
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    • v.11 no.1
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    • pp.9-21
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    • 2007
  • This study was performed to evaluate the effect of Carthami tinctorius(HH) on osteoblast function and gene expression. The osteoblasts separated from the rat calvariae were cultivated to evaluate the cell function, and MG-63 cell was also cultivated for the test of mRNA synthesis. In this experiments, cell proliferation of rat calvarial cells was increased by HH. PKC activity, intracellular free calcium level and collgen synthesis from calvarial cells were increased by HH, but not PKA activity. And the mRNA of $PLA_2$, COX-2, and $PGE_2$ synthase from MG-63 were decreased by HH, but the mRNA of prostacyclin synthase was increased. It is concluded that HH might increase the proliferation of calvarial cell resulted from augumentation of osteoblast activity and its mRNA synthesis.

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Three Cases of Diphyllobothrium nihonkaiense Infection in Korea

  • Kim, Hong-Ja;Eom, Keeseon S.;Seo, Min
    • Parasites, Hosts and Diseases
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    • v.52 no.6
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    • pp.673-676
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    • 2014
  • Until 2012, a total of 48 cases of diphyllobothriasis had been reported in Korea, all of which were morphologically identified as Diphyllobothrium latum. However, some of these specimens were analyzed by nucleotide sequencing of the mitochondrial cox1 gene, which showed that all were D. nihonkaiense, not D. latum. After that, 3 further cases of diphyllobothriasis were confirmed as D. nihonkaiense. In the present study, 3 new cases of D. nihonkaiense were detected from 2011 through 2013. The hosts were infected through consumption of salmonid fishes, such as the trout or salmon, and 2 of them experienced severe diarrhea prior to proglottid passage. All of the tapeworms were confirmed to be D. nihonkaiense by genetic identification. This proved again that most diphyllobothriasis in Korea have been caused by D. nihonkaiense.

Effect of Phellinus igniarius Quel Extract on the Anti-inflammatory, Anti allergy, Anti-oxidant, Anti-wrinkle reaction (화피 추출물이 염증 및 알레르기 반응에 미치는 영향)

  • Jung, Ji-Young;Jung, Hyun-A
    • The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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    • v.23 no.3
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    • pp.42-65
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    • 2010
  • Objectives : Betula platyphylla var. japonica extract (BPE) was used to determine the modulation of cytokine secretion, the activation of inflammatory and allergic factor and the inhibition of gene expression. Inflammatory and allergic cytokines as IL-$1{\beta}$, IL-2, IL-4, IL-5, IL-6, IL-8, TNF-${\alpha}$, NO and COX-2 were measured to use effectively on improvement or treatment of atopic dermatitis. Methods : We used NC/Nga mouse induced by atopic dermatitis to observe the effects of BPE on the weight, water and feed, blood test, weight of organs, histological change, total IgE and histological change of main organs. Results : BPE is effective on anti-inflammatory and allergic reaction. However, further study is needed to prove which component of BPE indicates effective pharmacological action. Conclusions : The above results suggest that Phellinus igniarius Quel extract could be applicable for improvement of several skin functions.

Philodina wonkimi n. sp. and Five New Records of Bdelloids from Korea

  • Song, Min Ok;Lee, Chang-Ho
    • Animal Systematics, Evolution and Diversity
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    • v.36 no.4
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    • pp.363-371
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    • 2020
  • A taxonomic study on bdelloid rotifers collected from mosses and/or leaf litter at four different locations in Korea resulted in five new Korean records and a new species, Philodina wonkimi n. sp. Philodina wonkimi n. sp. is easily distinguished from its congeners by the very long antenna which is much longer than the height of the pseudosegment carrying a dorsal antenna in creeping. Among the five new Korean records, two species- and two subspecies-level taxa are new to Asia as well. Adineta rhomboidea Bērzinš, 1950 has been reported from only three European countries including the type locality, and is recorded outside Europe for the first time. Present study is the fourth record for Philodina eurystephana Schulte, 1954. In addition, a partial sequence of mitochondrial cytochrome c oxidase subunit I gene (mtCOX1) for P. wonkimi n. sp. is provided here.

Inhibition of Lipopolysaccharide-Inducible Nitric Oxide Synthase, $TNF-{\alpha}$, $IL-1{\beta}$ and COX-2 Expression by Flower and Whole Plant of Lonicera japonica (금은화(金銀花) 및 금은화전초(金銀花全草)가 Raw 264.7 cell에서 LPS로 유도된 NO의 생성, iNOS, COX-2 및 cytokine에 미치는 영향)

  • Lee, Dong-Eun;Lee, Jae-Ryung;Kim, Young-Woo;Kwon, Young-Kyu;Byun, Sung-Hui;Shin, Sang-Woo;Suh, Seong-Il;Kwon, Taeg-Kyu;Byun, Joon-Seok;Kim, Sang-Chan
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.19 no.2
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    • pp.481-489
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    • 2005
  • Lonicerae Flos has antibacterial effects against Staphylococcus aureus, streptococci, pneumococci, Bacillus dysenterii, Salmonella typhi, and paratyphoid. It is an antiviral agent. The herb has a cytoprotective effect against $CCl_{4}-induced$ hepatic injury. It has antilipemic action, interfering with lipid absorption from the gut. Nowadays this herb is used mainly in the treatment of upper respiratory infections, such as tonsillitis and acute laryngitis. It is also used in the treatment of skin suppurations, such as carbuncles, and to treat viral conjunctivitis, influenza, pneumonia, and mastitis. Lonicerae Flos is dried flower buds of Lonicera japonica, L. hypoglauca, L. confusa, or L. dasystyla. But, for the most part, we use whole plant of Lonicera japonica, as a flower bud of it. And, little is known of the original copy of effects of whole plant, except for the 'Bon-Cho-Gang-Mok', which is written the effects of flower of Lonicera japonica are equal to effects of leaves and branch of it. The present study was conducted to evaluate the effect of flower and whole plant of Lonicera japonica on the regulatory mechanism of cytokines, inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX-2) for the immunological activities in Raw 264.7 cells. In Raw 264.7 cells stimulated with lipopolysaccharide (LPS) to mimic inflammation, flower and whole plant of Lonicera japonica water extracts inhibited nitric oxide production in a dose-dependent manner and abrogated iNOS and COX-2. Flower and whole plant of Lonicera japonica water extract did not affect on cell viability. To investigate the mechanism by which flower and whole plant of Lonicera japonica water extract inhibits iNOS and COX-2 gene expression, we examined the on phosphorylation of inhibitor ${\kappa}B{\alpha}$ and assessed production of $TNF-{\alpha}$, $interleukin-1{\beta}$ $(IL-1{\beta})$ and interleukin-6 (IL-6). Results provided evidence that flower and whole plant of Lonicera japonica inhibited the production of $IL-1{\beta}$, IL-6 and activated the phosphorylation of inhibitor ${\kappa}B{\alpha}$ in Raw 264.7 cells activated with LPS. These findings suggest that flower and whole plant of Lonicera japonica can produce anti-inflammatory effect, which may play a role in adjunctive therapy in Gram-negative bacterial infections, respectively.

Effects of Pseudomonas fluorescens on Production of Several Inflammatory Mediators in the Human Alveolar Epithelial Cells. (재조합 단백질 생산에 이용되는 Pseudomonas fluorescens의 인체 폐포 상피세포의 염증성 인자들의 발현에 미치는 영향)

  • Yang, Hyun;Ryoo, Jung-Min;Park, Seung-Hwan;Choi, Hye-Jin;Kim, Na-Yeon;Cho, Hyung-Hoon;Ahn, Jung-Hoon;Moon, Yu-Seok
    • Journal of Life Science
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    • v.18 no.4
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    • pp.530-536
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    • 2008
  • To investigate the molecular mechanism of the airway inflammation by Pseudomonas fluorescens, effects on the inflammatory mediators such as interleukin-8 (IL-8), cyclooxygenase-2 (COX-2), macophage inhibitory cytokine 1 (MIC-1) were assessed in the human alveolar epithelial cells. Exposure to P. fluorescens and its recombinant bacteria suppressed cellular viability in the A549 epithelial cells and pro-inflammatory cytokine interleukin-8 production. However, pro-inflammatory prostaglandin-producing COX-2 protein was not altered by P. fluorescens though its mRNA was slightly elevated. As the inhibitory cytokine for the pro-inflammatory mediators, MIC-1 expression was monitored in A549 cells. MIC-1 gene induction was not significantly enhanced but the protein processing was changed by exposure to P. fluorescens. Pro-protein form of MIC-1 (${\sim}40\;kD$) was cleaved into active form mature MIC-1 (${\sim}15\;kD$) and propeptide (${\sim}28\;kD$) by the bacteria exposure. MIC-1 activation can contribute to the suppression of cellular viability by P. fluorescens and can retard IL-8-induced monocyte recruitment. However, sustained activation of MIC-1 can mediate the tissue injury by P. fluorescens exposure.