• The Korea Journal of Herbology
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• v.27 no.6
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• pp.131-137
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• 2012

Objectives : Cyclooxygenase (COX) plays a central role in the inflammatory cascade by converting arachidonic acid into prostaglandin. COX-2 is typically induced by inflammatory stimuli in the majority of tissues, it is responsible for propagating the inflammatory response and thus, considered as the best target for anti-inflammatory drugs. The present study investigated the modulatory effect of ginsenoside Rg3, a principle active ingredient in Panax ginseng, on COX-2 expression in the brain tissue induced by systemic lipopolysaccharide (LPS) treatment in C57BL/6 mice. Methods : Because systemic LPS treatment induces COX-2 expression immediately in the brain, ginsenoside Rg3 was treated orally with doses of 10, 20, and 30 mg/kg at 1 hour before the LPS (3 mg/kg, i.p.) injection. At 4 hours after the LPS injection, COX-2 mRNA was measured by real-time polymerase chain reaction method, COX-2 protein levels were measured by Western blotting. In addition, COX-2 expressions in brain tissue were observed with immunohistochemistry and double immunofluoresence labeling. Results : Ginsenoside Rg3 (20 and 30 mg/kg) significantly attenuates up-regulation of COX-2 mRNA and protein expression in brain tissue at 4 hours after the LPS injection. Moreover, ginsenoside Rg3 (20 mg/kg) significantly reduced the number of COX-2 positive neurons in the cerebral cortex and amygdala. Conclusion : These results indicate that ginsenoside Rg3 plays a modulatory role in neuroinflammation through the inhibition of COX-2 expression in the brain and suggest that ginsenoside Rg3 and ginseng may be effective on neurodegenerative diseases caused by neuroinflammation.

• The Korea Journal of Herbology
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• v.28 no.2
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• pp.93-101
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• 2013

Objects : Baicalein is a major bioactive flavonoid component of Scutellaria baicalensis Georgi that shows a wide range of biological activities, including neuroprotections and anti-inflammatory actions. Hence it is a potential therapeutic material for the treatment of neuroinflammation. In this study, we investigated the modulatory effect of baicalein on neuroinflammation. Method : Pro-inflammatory cytokines (TNF-${\alpha}$, IL-$1{\beta}$ and IL-6 mRNA), COX-2 mRNA expression and microglial activation in the brain tissue is induced by systemic lipopolysaccharide (LPS) treatment in C57BL/6 mice. Baicalein was treated orally with 10, 20, and 30 mg/kg 1 hour prior to the LPS (3 mg/kg, i.p.) injection. TNF-${\alpha}$, IL-$1{\beta}$, IL-6 and COX-2 mRNA expression in the brain tissue was measured by the quantitative real-time polymerase chain reaction(PCR) method. Iba1 expression in the brain was measured by western blotting method. Microglia was observed with immunohistochemistry. Results : Baicalein 30 mg/kg significantly attenuated the expression of TNF-${\alpha}$, IL-$1{\beta}$, IL-6 and COX-2 mRNA in the brain tissue. Baicalein 20 mg/kg significantly attenuated the expression of IL-6 mRNA in the brain tissue. Baicalein 30 mg/kg significantly attenuated the expression of Iba1 protein expression in the brain tissue. Baicalein 30 mg/kg significantly decreased the number and cell size of microglia in the cerebral cortex and hypothalamic region and the area percentage of Iba1-expressed microglia in the hippocampus. Conclusion : These results demonstrated that baicalein attenuates LPS induced neuroinflammation in the mice via reduction of pro-inflammatory cytokines (TNF-${\alpha}$, IL-$1{\beta}$, IL-6), COX-2 mRNA expression and microglial activation.

• The Korean Journal of Physiology and Pharmacology
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• v.14 no.3
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• pp.139-144
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• 2010

In this study, we evaluated the role of apurinic/apyrimidinic endonuclease1/redox factor-1 (Ref-1) on the tumor necrosis factor-$\alpha$ (TNF-$\alpha$) induced cyclooxygenase-2 (COX-2) expression using A549 lung adenocarcinoma cells. TNF-$\alpha$ induced the expression of COX-2 in A549 cells, but did not induce BEAS-2B expression. The expression of COX-2 in A549 cells was TNF-$\alpha$ dose-dependent (5~100 ng/ml). TNF-$\alpha$-stimulated A549 cells evidenced increased Ref-1 expression in a dose-dependent manner. The adenoviral transfection of cells with AdRef-1 inhibited TNF-$\alpha$-induced COX-2 expression relative to that seen in the control cells ($Ad{\beta}gal$). Pretreatment with $10\;{\mu}M$ of SB203580 suppressed TNF-$\alpha$-induced COX-2 expression, thereby suggesting that p38 MAPK might be involved in COX-2 expression in A549 cells. The phosphorylation of p38 MAPK was increased significantly after 5 minutes of treatment with TNF-$\alpha$, reaching a maximum level at 10 min which persisted for up to 60 min. However, p38MAPK phosphorylation was markedly suppressed in the Ref-1-overexpressed A549 cells. Taken together, our results appear to indicate that Ref-1 negatively regulates COX-2 expression in response to cytokine stimulation via the inhibition of p38 MAPK phosphorylation. In the lung cancer cell lines, Ref-1 may be involved as an important negative regulator of inflammatory gene expression.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.8
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• pp.4539-4543
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• 2013

Background: Transitional cell carcinoma (TCC) is the most predominant type of urinary bladder tumor. As cyclooxygenase (COX)-2 is recently introduced as an attractive target molecule in bladder TCC, we evaluated the immunohistochemical expression of this marker and its association with several clinicopathological characteristics. Materials and Methods: This cross-sectional study was performed in the Pathology department of Sina Hospital in Tehran, Iran during 2006-2011. Ninety-two paraffin embedded blocks were selected from patients with urinary bladder TCC who underwent cystectomy or transurethral resection (TUR). Then, we assessed COX-2 expression by immunohistochemical staining using antibody against COX-2. Staining in more than 5% of tumor cells was considered as positive expression. Results: COX-2 was expressed in 50 % of our patients. This marker was markedly expressed in high grade bladder TCC (62.1%) versus other grades and there was statistically a significant difference in COX-2 expression between various grades (p=0.008). In addition, patients' age, lymphatic and perineurial invasion were associated with the expression of COX-2 (p=0.001, 0.015 and 0.039, respectively). However, other parameters such as stage, tumor size, venous invasion and lymph node metastasis did not show any significant relationship with this marker (all, p>0.05). Conclusions: COX-2 was expressed in urinary bladder TCC especially in high grade forms, advocating its probable role in the differentiation of this tumor. Accordingly, COX-2 could be a valuable biological target molecule in the evaluation and treatment of patients with bladder TCC.

• Parasites, Hosts and Diseases
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• v.56 no.1
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• pp.87-91
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• 2018

Morphological and molecular characteristics of spirometrid tapeworms, Spirometra decipiens, were studied, which were recovered from a heavily infected stray cat road-killed in Eumseong-gun, Chungcheongbuk-do (Province), the Republic of Korea (=Korea). A total of 134 scolices and many broken immature and mature proglottids of Spirometra tapeworms were collected from the small intestine of the cat. Morphological observations were based on 116 specimens. The scolex was 22.8-32.6 mm (27.4 mm in average) in length and small spoon-shape with 2 distinct bothria. The uterus was coiled 3-4 times, the end of the uterus was ball-shaped, and the vaginal aperture shaped as a crescent moon was closer to the cirrus aperture than to the uterine aperture. PCR amplification and direct sequencing of the cox1 target fragment (377 bp in length and corresponding to positions 769-1,146 bp of the cox1 gene) were performed using total genomic DNA extracted from 134 specimens. The cox1 sequences (377 bp) of the specimens showed 99.0% similarity to the reference sequence of S. decipiens and 89.3% similarity to the reference sequence of S. erinaceieuropaei. In the present study, we report a stray cat heavily infected with S. decipiens identified by mitochondrial cox1 sequence analysis and morphological examinations of the adult worms.

• Intestinal research
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• v.15 no.1
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• pp.75-82
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• 2017

Background/Aims: Cyclooxygenase-2 (COX-2), 15-hydroxyprostaglandin dehydrogenase (15-PGDH), and microsomal prostaglandin E synthase-1 (mPGEs-1) regulate prostaglandin $E_2$ ($PGE_2$) expression and are involved in colon carcinogenesis. We investigated the expression of $PGE_2$ and its regulating genes in sporadic human colon tumors and matched normal tissues. Methods: Twenty colonic adenomas and 27 colonic adenocarcinomas were evaluated. COX-2 and 15-PGDH expression was quantified by real-time polymerase chain reaction. The expression of $PGE_2$ and mPGEs-1 was measured using enzyme-linked immunosorbent assay and Western blotting, respectively. Results: The expression of COX-2, mPGEs-1, and $PGE_2$ did not differ between the adenomas and matched distant normal tissues. 15-PGDH expression was lower in adenomas than in the matched normal colonic tissues (P<0.001). In adenocarcinomas, mPGEs-1 and $PGE_2$ expression was significantly higher (P<0.001 and P=0.020, respectively), and COX-2 expression did not differ from that in normal tissues (P=0.207). 15-PGDH expression was significantly lower in the normal colonic mucosa from adenocarcinoma patients than in the normal mucosa from adenoma patients (P=0.018). Conclusions: Early inactivation of 15-PGDH, followed by activation of COX-2 and mPGEs-1, contributes to $PGE_2$ production, leading to colon carcinogenesis. 15-PGDH might be a novel candidate marker for early detection of field defects in colon carcinogenesis.

• Journal of Chest Surgery
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• v.31 no.7
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• pp.668-673
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• 1998

During the past several years, the maze operation has become the most effective method of treatment for chronic atrial fibrillation. When the maze procedure is done concomittantly with other cardiac operations, surgeons, in their initial experiences, may be concerned about the additional operative risks and uncertainty of the results. We performed the Cox-maze III procedure in six cases of chronic atrial fibrillation associated with mitral, mitral & aortic, or coronary arterial disease. Maze III procedure was done with open mitral commissurotomy(3 cases), mitral valve replacement(1 case), aortic and mitral valve replacement(1 case), and two-vessel coronary bypass graft(1 case). In spite of rather prolonged aortic cross clamp time, cardiac recovery was uneventful in all cases. No cases required reexploration for postoperative bleeding. All patients showed regular sinus rhythms immediate or between 2 and 20 days postoperateratively. Transient postoperative supraventricular arrhythmarias were easily controlled by various antiarrhythmic agents. In follow up evaluations, all cases showed regular sinus rhythm on ECG and the right and left atrial transport function was confirmed by Doppler echocardiography in all except one. Though our experience was limited in case number, the Cox-maze III procedure was effective in controlling the chronic atrial fibrillation without serious additional operative risks.

• Parasites, Hosts and Diseases
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• v.42 no.3
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• pp.145-148
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• 2004

We compared the DNA sequence difference of isolates of Clonorchis sinensis from one Korean (Kimhae) and two Chinese areas (Guangxi and Shenyang), The sequences of nuclear rDNA (18S, internal transcribed spacer 1 and 2: ITS1 and ITS2) and mitochondrial DNA (cytochrome c oxidase subunit 1: cox1) were compared. A very few intraspecific nucleotide substitution of the 18S, ITS1, ITS2 and cox1 was found among three isolates of C. sinensis and a few nucleotide insertion and deletion of ITS1 were detected. The 18S, ITS1, ITS2 and cox1 sequences were highly conserved among three isolates. These findings indicated that the Korean and two Chinese isolates are similar at the DNA sequence level.

• Parasites, Hosts and Diseases
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• v.54 no.6
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• pp.743-750
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• 2016

Mus musculus (Rodentia: Muridae) has generally been infected with a rodent hookworm Nippostrongylus brasiliensis. In this report, we present morphological and molecular identification of N. brasiliensis by light and scanning electron microscopy and PCR amplification of mitochondrial cytochrome c oxidase subunit 1 (cox1) gene and the protein sequences encoded by cox1 gene, respectively. Despite the use of N. brasiliensis in many biochemistry studies from India, their taxonomic identification was not fully understood, especially at the species level, and no molecular data is available in GenBank from India. Sequence analysis of cox1 gene in this study revealed that the present specimen showed close identity with the same species available in GenBank, confirming that the species is N. brasiliensis. This study represents the first record of molecular identification of N. brasiliensis from India and the protein structure to better understand the comparative phylogenetic characteristics.

• The Journal of Korean Medicine
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• v.26 no.3 s.63
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• pp.215-227
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• 2005

Objectives : This study was carried out to investigate the effects of Pyungjintang on indomethacin-induced gastric mucosal lesions of mire. Methods : Experimental mice were classified into not-treated group (NOR group), gastro-inflammation elicitated group (CON group), misoprostol-administered group after gastro-inflammation elicitation (MA group), and Pyungjintang-administered group after gastro-inflammation elicitation (PA group). This study examined the morphological change, distribution of mast cells, mucus surface cells, neutral mucus secreting cells, acid mucus secreting cells, PNA reaction, angiogenesis (MIP-2), COX-1, Hsp70, NF-kB p50, COX-2IL-12B, ICAM-1, BrdU and apoptotic cells of gastric mucosa. Results : 1. The scars of diapedesis, dilatation of right gastric artery and the hemorrhagic erosions of gastric mucosa were reduced in the MA and PA groups. 2. Gastric perforation was observed in the gastro-inflammation elicitated group, but not in the MA and PA groups. 3. The COX-1 positive cellsl, cell proliferation of gastric mucosa, neutral mucus secreting ce31s, acid mucus secreting cells and PNA positive reaction of surface mucus cells were increased in the MA and PA groups. 4. The distribution of apoptotic cells, mast cells, MIP-2, Hsp70, NF-kB p50, COX-2, IL-l2B and ICAM-1 were decreased in the MA and PA groups. Conclusions : Pyungjintang had excellent effects on indomethacin-induced gastric mucosal lesions in mice.