• Journal of Microbiology and Biotechnology
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• v.23 no.8
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• pp.1154-1158
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• 2013

Ganciclovir resistance of human cytomegalovirus is associated with mutations in the viral UL97 gene and poses severe problems for immunocompromised patients. In this study, PCR-based restriction fragment length polymorphism and sequencing analyses detected the UL97 D605E mutation in all five clinical isolates from patients with ganciclovir-resistant human cytomegalovirus infection during prolonged ganciclovir therapy, whereas the M460V mutation was only present in 1 of 5 isolates. On the other hand, the detection rates of the D605E mutation in the stored available DNA samples from the donor and allogeneic stem cell transplantation recipients were 66.7% and 93.7%, respectively, suggesting that the presence of D605E mutation was not associated with the ganciclovir exposure. Although the D605E mutation may not be related to ganciclovir resistance, we suggest that this mutation could be an important molecular marker of human cytomegalovirus evolution in East Asian countries. Moreover, the restriction fragment length polymorphism method using the restriction enzyme HaeIII, which is generally used to detect the UL97 A591V mutation, could also detect the D605E mutation and may therefore be a useful tool for future research on the investigation of UL97 gene mutations.

• Journal of Korean Neurosurgical Society
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• v.55 no.5
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• pp.237-243
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• 2014

Objective : Symptomatic disc degeneration develops from inflammatory reactions in the annulus fibrosus (AF). Although inflammatory mediators during annular inflammation have been studied, the roles of matrix metalloproteinases (MMPs) and their inhibitors have not been fully elucidated. In this study, we evaluated the production of MMPs and tissue inhibitors of metalloproteinase (TIMPs) during annular inflammation using an in vitro co-culture system. We also examined the effect of notochordal cells on annular inflammation. Methods : Human AF (hAF) pellet was co-cultured for 48 hours with phorbol myristate acetate-stimulated macrophage-like THP-1 cells. hAF pellet and conditioned media (CM) from co-cultured cells were assayed for MMPs, TIMPs, and insulin-like growth factor (IGF)-1 levels using real-time reverse-transcriptase polymerase chain reaction and enzyem-linked immunosorbent assay. To evaluate whether notochordal cells affected MMPs or TIMPs production on annular inflammation, hAF co-cultured with notochordal cells from adult New Zealand White rabbits, were assayed. Results : MMP-1, -3, -9; and TIMP-1 levels were significantly increased in CM of hAF co-cultured with macrophage-like cells compared with hAF alone, whereas TIMP-2 and IGF-1 levels were significantly decreased (p<0.05). After macrophage exposure, hAF produced significantly more MMP-1 and -3 and less TIMP-1 and -2. Interleukin-$1{\beta}$ stimulation enhanced MMP-1 and -3 levels, and significantly diminished TIMP-2 levels. Co-culturing with rabbit notochordal cells did not significantly influence MMPs and TIMPs production or COL1A2 gene expression. Conclusion : Our results indicate that macrophage-like cells evoke annular degeneration through the regulation of major degradative enzymes and their inhibitors, produced by hAF, suggesting that the selective regulation of these enzymes provides future targets for symptomatic disc degeneration therapy.

• The Korean Journal of Physiology and Pharmacology
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• v.18 no.1
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• pp.61-66
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• 2014

Lung cancer is still the number one cause of death from cancer worldwide. The clinical effect of platinum-based chemotherapy for non-small cell lung cancer is constrained by the resistance to drug. To overcome chemo-resistance, various modified treatment including combination therapy has been used, but overall survival has not been improved yet. In this study, chemo-resistant lung cancer cells, A549/Cis and H460/Cis, were developed by long-term exposure of cells to cisplatin and the proliferative capability of these resistant cells was verified to be reduced. We found cytotoxic effect of epigallocatechin gallate (EGCG), a major catechin derived from green tea, on both the parental lung cancer cells, A549 and H460, and their cisplatin resistant cells, A549/Cis and H460/Cis. ELISA and Western blot analysis revealed that EGCG was able to increase interlukine-6 (IL-6) production per cell, whereas its downstream effector Signal transducers and activators of transcription 3 (STAT3) phosphorylation was not changed by EGCG, indicating that IL-6/STAT3 axis is not the critical signaling to be inhibited by EGCG. We next found that EGCG suppresses the expression of both Axl and Tyro 3 receptor tyrosine kinases at mRNA and protein level, explaining the cytotoxic effect of EGCG on lung cancer cells, especially, regardless of cisplatin resistance. Taken together, these data suggest that EGCG impedes proliferation of lung cancer cells including their chemo-resistant variants through downregulation of Axl and Tyro 3 expression.

• Korean Journal of Veterinary Research
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• v.49 no.4
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• pp.345-349
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• 2009

Polychlorinated biphenyls (PCBs) are synthetic organic compounds with two benzene rings and well known environmental pollutants. This study examined the effect of persistent exposure to 2,$3^{\prime}$,4,$4^{\prime}$,5-pentachlorobiphenyl (PCB118) on the proinflammatory and proapoptotic factors in male rats. Male Sprague Dawley rats were administered weekly intraperitoneal injections of either PCB118 (20 mg/kg) dissolved in corn oil or corn oil alone. One week after 2 and 5 administrations, the rats were sacrificed by a pentobarbital injection. The effect of PCB118 on the expression of cyclooxygenase 2 (COX-2), cytosolic phospholipase A2 (cPLA2), peroxisome proliferator-activated receptor gamma, Bcl and Bcl-2-associated X protein (BAX) was investigated. The level of COX-2 and cPLA2 expression was higher in the PCB118-treated rats than the control. These results suggest that PCB118 has a proinflammatory effect in rats.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.7
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• pp.2701-2705
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• 2015

Chondrosarcoma, the second most common type of bone malignancy, is characterized by distant metastasis and local invasion. Previous studies have shown that treatment by pulsed electromagnetic field (PEMF) has beneficial effects on various cancer cells. In this study, we investigated the effects of PEMF applied for 3 and 7 days on the matrix metalloproteinase (MMP) levels in chondrosarcoma SW1353 cells stimulated with two different doses of $IL-1{\beta}$. SW1353 cells were treated with (0.5 and 5 ng/ml) $IL-1{\beta}$ and PEMF exposure was applied either 3 or 7 days. MMP-9 and TIMP-1 levels were measured in conditioned media by enzyme-linked immunosorbent assay. The results were relative to protein levels. Statistical analyses were performed using one-way analysis of variance (ANOVA). P<0.05 was considered significant. PEMF treatment significantly decreased MMP-9 protein levels in human chondrosarcoma cells stimulated with 0.5 ng/ml $IL-1{\beta}$ at day 7, whereas it did not show any effect on cells stimulated with 5 ng/ml $IL-1{\beta}$. There was no significant change in TIMP-1 protein levels either by $IL-1{\beta}$ stimulation or by PEMF treatment. The results of this study showed that PEMF treatment suppressed $IL-1{\beta}$-mediated upregulation of MMP-9 protein levels in a dual effect manner. This finding may offer new perspectives in the therapy of bone cancer.

• Journal of dental hygiene science
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• v.7 no.1
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• pp.31-35
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• 2007

Caesalpinia sappan L. (Leguminosae) is an oriental medicinal herb distributed in China and Taiwan, and its heartwood has been traditionally used as an analgesic, a therapy for thrombosis or tumor. This study was to investigate the proliferation and inhibition effects of Caesalpinia sappan extracts against human epithelial cell and cancer cell lines. The methanol extract of dried C. sappan heartwood was evaporated (KS-6), and then sequentially extracted by hexane (KS-01), chloroform (KS-02), ethyl acetate (KS-03), n-butanol (KS-04), and water (KS-05). After 48 hr of exposure, these fractions at a concentration of $50{\mu}g/ml$ significantly increased, and reduced cell proliferation in both human normal epithelial and cancer cell lines. The ethyl acetate fraction (KS-03) among organic solvent fractions was 120.2% of the most proliferation activity ($50{\mu}g/ml$) against HaCaT human epithelial cell. However, fractions from chloroform, butanolic and methanolic extract had 7.2, 28.7 and 20.8% of antiproliferative effect on HaCaT cell, respectively. In cell proliferation effects of C. sappan extract on HeLa, SiHa and C33A human cervical cancer cells, chloroform fraction (KS-2) was the most antiproliferative activity, its antiproliferative rate (dosage, $50{\mu}g/ml$) relative to control was 25.8, 12.2 and 17.4% for SiHa, HeLa and C33A, respectively. The results indicated that the six extract fractions could induce cell cycle stimulate or arrest in some way. Finally, further investigation is needed to assess the molecular mechanisms mediated anticancer activities of this plant.

• Journal of Environmental Health Sciences
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• v.37 no.5
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• pp.387-395
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• 2011

Purpose: This study measured the burden of disease in Korea related to outdoor air pollution using disability-adjusted life year (DALY). Materials and Methods: As a risk factor of outdoor air pollution, particulate matter with a diameter less than 10 ${\mu}m$($PM_{10}$) was used. First, $PM_{10}$-related diseases and their relative risk (RR) were selected by means of a literature review. Second, population attributable fractions were computed by using formulae including RR and population exposure to $PM_{10}$. Third, DALYs of $PM_{10}$-related diseases in Korea were estimated. Finally, the attributable burden of disease due to $PM_{10}$ was measured as the sum of the products that multiplied the DALYs of $PM_{10}$-related diseases by their population attributable fractions. Results: The disease burden of PM10 was 6.9 DALY per 1,000 persons in 2007. The attributable burden of $PM_{10}$ was 2.68 for lung cancer, 2.41 for COPD, 0.62 for ischemic heart disease, 0.61 for pneumonia, 0.55 for asthma, and 0.03 for preterm. Conclusions: This study showed the environmental burden of disease of $PM_{10}$ and burden of $PM_{10}$-related disease through objective data. It also suggested that active efforts are needed to continuously measure and reduce the burden of environmental diseases in Korea.

• Journal of Periodontal and Implant Science
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• v.48 no.3
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• pp.164-173
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• 2018

Purpose: The aim of this study was to evaluate the antimicrobial effect of a newly devised toothbrush with light-emitting diodes (LEDs) on Porphyromonas gingivalis attached to sandblasted and acid-etched titanium surfaces. Methods: The study included a control group, a commercial photodynamic therapy (PDT) group, and 3 test groups (B, BL, and BLE). The disks in the PDT group were placed in methylene blue and then irradiated with a diode laser. The B disks were only brushed, the BL disks were brushed with an LED toothbrush, and the BLE disks were placed into erythrosine and then brushed with an LED toothbrush. After the different treatments, bacteria were detached from the disks and spread on selective agar. The number of viable bacteria and percentage of bacterial reduction were determined from colony counts. Scanning electron microscopy was performed to visualize bacterial alterations. Results: The number of viable bacteria in the BLE group was significantly lower than that in the other groups (P<0.05). Scanning electron microscopy showed that bacterial cell walls were intact in the control and B groups, but changed after commercial PDT and LED exposure. Conclusions: The findings suggest that an LED toothbrush with erythrosine treatment was more effective than a commercial PDT kit in reducing the number of P. gingivalis cells attached to surface-modified titanium in vitro.

• Journal of Radiation Protection and Research
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• v.44 no.4
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• pp.149-155
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• 2019

Background: Magnetic resonance (MR) image guided radiation therapy system, enables real time MR guided radiotherapy (RT) without additional radiation exposure to patients during treatment. However, MR image lacks electron density information required for dose calculation. Image fusion algorithm with deformable registration between MR and computed tomography (CT) was developed to solve this issue. However, delivered dose may be different due to volumetric changes during image registration process. In this respect, synthetic CT generated from the MR image would provide more accurate information required for the real time RT. Materials and Methods: We analyzed 1,209 MR images from 16 patients who underwent MR guided RT. Structures were divided into five tissue types, air, lung, fat, soft tissue and bone, according to the Hounsfield unit of deformed CT. Using the deep learning model (U-NET model), synthetic CT images were generated from the MR images acquired during RT. This synthetic CT images were compared to deformed CT generated using the deformable registration. Pixel-to-pixel match was conducted to compare the synthetic and deformed CT images. Results and Discussion: In two test image sets, average pixel match rate per section was more than 70% (67.9 to 80.3% and 60.1 to 79%; synthetic CT pixel/deformed planning CT pixel) and the average pixel match rate in the entire patient image set was 69.8%. Conclusion: The synthetic CT generated from the MR images were comparable to deformed CT, suggesting possible use for real time RT. Deep learning model may further improve match rate of synthetic CT with larger MR imaging data.

• International Journal of Oral Biology
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• v.35 no.2
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• pp.43-49
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• 2010

Enterococcus faecalis, a gram-positive bacterium, has been implicated in endodontic infections, particularly in chronic apical periodontitis. Proinflammatory cytokines, including tumor necrosis factor-$\alpha$ (TNF-$\alpha$), are involved in the pathogenesis of these apical lesions. E. faecalis has been reported to stimulate macrophages to produce TNF-$\alpha$. The present study investigated the mechanisms involved in TNF-$\alpha$ production by a murine macrophage cell line, RAW 264.7 in response to exposure to E. faecalis. Both live and heat-killed E. faecalis induced high levels of gene expression and protein release of TNF-$\alpha$. Treatment of RAW 264.7 cells with cytochalasin D, an inhibitor of endocytosis, prevented the mRNA up-regulation of TNF-$\alpha$ by E. faecalis. In addition, antioxidant treatment reduced TNF-$\alpha$ production to baseline levels. Inhibition of extracellular signal-regulated kinase (ERK) and p38 mitogen-activated protein (MAP) kinase also significantly attenuated E. faecalis-induced TNF-$\alpha$ expression by RAW 264.7 cells. Furthermore, activation of NF-${\kappa}B$ and AP-1 in RAW 264.7 cells was also stimulated by E. faecalis. These results suggest that the phagocytic uptake of bacteria is necessary for the induction of TNF-$\alpha$ in E. faecalis-stimulated macrophages, and that the underlying intracellular signaling pathways involve reactive oxygen species, ERK, p38 MAP kinase, NF-${\kappa}B$, and AP-1.