• International Journal of Oral Biology
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• v.35 no.2
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• pp.61-67
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• 2010

Selenoprotein S (SelS) is widely expressed in diverse tissues where it localizes in the plasma membrane and endoplasmic reticulum. We studied the potential function of SelS in erythrocyte differentiation using K562 cells stably over-expressing SelS wild-type (WT) or one of two SelS point mutants, $U_{188}S$ or $U_{188}C$. We found that in the K562 cells treated with $1\;{\mu}M$ Ara-C, SelS gradually declined over five days of treatment. On day 4, intracellular ROS levels were higher in cells expressing SelS-WT than in those expressing a SelS mutant. Moreover, the cell cycle patterns in cells expressing SelS-WT or $U_{188}C$ were similar to the controls. The expression and activation of SIRT1 were also reduced during K562 differentiation. Cells expressing SelS-WT showed elevated SIRT1 expression and activation (phosphorylation), as well as higher levels of FoxO3a expression. SIRT1 activation was diminished slightly in cells expressing SelS-WT after treatment with the ROS scavenger NAC (12 mM), but not in those expressing a SelS mutant. After four days of Ara-C treatment, SelS-WT-expressing cells showed elevated transcription of $\beta$-globin, $\gamma$-globin, $\varepsilon$-globin, GATA-1 and zfpm-1, whereas cells expressing a SelS mutant did not. These results suggest that the suppression of SelS acts as a trigger for proerythrocyte differentiation via the ROS-mediated downregulation of SIRT1.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.13
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• pp.5181-5186
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• 2014

Tumors have evolved numerous mechanisms by which they can escape from immune surveillance. One of these is to produce immunosuppressive cytokines. Transforming growth factor-${\beta}$(TGF-${\beta}$) is a pleiotropic cytokine with a crucial function in mediating immune suppression, especially in the tumor microenvironment. TGF-${\beta}$ produced by T cells has been demonstrated as an important factor for suppressing antitumor immune responses, but the role of tumor-derived TGF-${\beta}$ in this process is poorly understood. In this study, we demonstrated that knockdown of tumor-derived TGF-${\beta}$ using shRNA resulted in dramatically reduced tumor size, slowing tumor formation, prolonging survival rate of tumor-bearing mice and inhibiting metastasis. We revealed possible underlying mechanisms as reducing the number of myeloid-derived suppressor cells (MDSC) and $CD4^+Foxp3^+$ Treg cells, and consequently enhanced IFN-${\gamma}$ production by CTLs. Knockdown of tumor-derived TGF-${\beta}$ also significantly reduced the conversion of na$\ddot{i}$ve $CD4^+$ T cells into Treg cells in vitro. Finally, we found that knockdown of TGF-${\beta}$ suppressed cell migration, but did not change the proliferation and apoptosis of tumor cells in vitro. In summary, our study provided evidence that tumor-derived TGF-${\beta}$ is a critical factor for tumor progression and evasion of immune surveillance, and blocking tumor-derived TGF-${\beta}$ may serve as a potential therapeutic approach for cancer.

• Korean Journal of Fisheries and Aquatic Sciences
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• v.47 no.6
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• pp.776-784
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• 2014

Tuna cooking juice concentrate (TCJC) is by-produced during the canning processing of skipjack tuna Katsuwonus pelamis and it is well known that TCJC contains various nutritional components. Therefore, the immuno-stimulating activity of TCJC was investigated using macrophage RAW 264.7 cell line and the spleen cell isolated from BALB/c mice. The TCJC increased the production of IL-6, TNF-${\alpha}$, and IL-$1{\beta}$ in a dose-dependent manner compared to the control in RAW 264.7 cells without any toxicity. In particular, the production of TNF-${\alpha}$ was increased over 300-fold. The production of both Th1 cytokine (such as IFN-${\gamma}$, TNF-${\alpha}$, IL-2, and IL-12) and Th2 cytokine (IL-4, IL-6, IL-10) was also increased by TCJC treatment in splenocytes. Moreover, the TCJC increased the splenocyte proliferation in a concentration-dependent manner compared to control. These results indicate that TCJC may enhance immune function by promoting various cytokine production.

• Progress in Medical Physics
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• v.8 no.2
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• pp.67-76
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• 1997

We studied optical behavior of scintillation light generated in NaI(TI) crystal using Monte Carlo simulation method. The simulation was performed for the model of NaI(TI) scintillator (size: 60 mm ${\times}$ 60 mm ${\times}$ 6 mm) using an optical tracking code. The sensitivity as a function of surface treatment (Ground, Polished, Metal-0.95RC, Polished-0.98RC, Painted- 0.98RC) of the incident surface of the scintillator was compared. The effects of NaI(TI) scintillator thickness and the refractive index of light guide optically coupling between the NaI(TI) scintillator and photomultiplier tube (PMT) were simulated. We also evaluated intrinsic position resolution of the system by calculating the spread of scintillation light generated. The sensitivities of the system having the surface treatment of Ground, Polished, Metal-0.95RC, Polished-0.98RC and Painted-0.98RC were 70.9％, 73.9％, 78.6％, 80.1％ and 85.2％, respectively, and the surface treatment of Painted-0.98RC allowed the highest sensitivity. As increasing the thickness of scintillation crystal and light guide, the sensitivity of the system was decreased. As the refractive index of light guide increases, the sensitivity was increased. The intrinsic position resolution of the system was estimated to be 1.2 mm in horizontal and vertical directions. In this study, the performance of NaI(TI)-PMT detector system was evaluated using Monte Carlo simulation. Based on the results, we concluded that the NaI(TI)-PMT detector array is a favorable configuration for small gamma camera imaging breast tumor using Tc-99m labeled radiopharmaceuticals.

• Journal of Korean Neurosurgical Society
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• v.61 no.6
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• pp.753-760
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• 2018

Objective : We investigated the effect of optimization in dose-limiting shell method on the dosimetric quality of CyberKnife (CK) plans in treating brain metastases (BMs). Methods : We selected 19 BMs previously treated using CK between 2014 and 2015. The original CK plans ($CK_{original}$) had been produced using 1 to 3 dose-limiting shells : one at the prescription isodose level (PIDL) for dose conformity and the others at low-isodose levels (10-30% of prescription dose) for dose spillage. In each case, a modified CK plan ($CK_{modified}$) was generated using 5 dose-limiting shells : one at the PIDL, another at intermediate isodose level (50% of prescription dose) for steeper dose fall-off, and the others at low-isodose levels, with an optimized shell-dilation size based on our experience. A Gamma Knife (GK) plan was also produced using the original contour set. Thus, three data sets of dosimetric parameters were generated and compared. Results : There were no differences in the conformity indices among the $CK_{original}$, $CK_{modified}$, and GK plans (mean 1.22, 1.18, and 1.24, respectively; p=0.079) and tumor coverage (mean 99.5%, 99.5%, and 99.4%, respectively; p=0.177), whereas the $CK_{modified}$ plans produced significantly smaller normal tissue volumes receiving 50% of prescription dose than those produced by the $CK_{original}$ plans (p<0.001), with no statistical differences in those volumes compared with GK plans (p=0.345). Conclusion : These results indicate that significantly steeper dose fall-off is able to be achieved in the CK system by optimizing the shell function while maintaining high conformity of dose to tumor.

• Korean Journal of Veterinary Research
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• v.43 no.2
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• pp.181-188
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• 2003

Cordyceps has a reputation for its broad biological activities and as a tonic which replenishs vital function in Chinese traditional medicines. As an attempt to obtain fundamental data for the development of new type Cordyceps, the effects of the fruiting bodies of cultivated fungus of Paecilomyces japonica grown on silkworm larvae on radiationinduced damages were investigated. We performed this study to determine the effect of Dongchongxiacao (Paecilomyces japonica) on jejunal crypt survival, endogenous spleen colony formation, and apoptosis in jejunal crypt cells and hair follicles of mice irradiated with high and low dose of gamma-radiation. Treatment with Dongchongxiacao showed no significant modifying effects on the jejunal crypt survival and endogenous spleen colony formation. The frequency of radiationinduced apoptosis was reduced by pretreatment of Dongchongxiacao (i.p.: 50 mg/kg of body weight, at 12 and 36 hours before irradiation, p<0.01). The spontaneous levels of apoptotic cells are $0.082{\pm}0.041$ in intestinal crypts and $0.231{\pm}0.084$ per hair follicle section of skin. Pretreatment of Dongchongxiacao was associated with decreases of 26.86% in intestinal crypt and 66.36% in hair follicle decrease in the number of cells with nuclei positively stained for apoptosis compared with the irradiation control group. We demonstrated for the first time that Dongchongxiacao administration could reduce the extent of apoptosis produced by radiation in the hair follicle. The results presented herein that Dongchongxiacao given before irradiation is capable of reducing the severity of cell loss as a result of apoptosis.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.27 no.1
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• pp.1-8
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• 2005

This study was aimed to characterize osteogenic potential of rat bone marrow stromal cells (BMSC) isolated with standard flushing method and investigate the plasticity of transdifferentiation between osteoblastic and adipocytic lineage of cultured BMSC. Unlike aspiration method in human, rat bone marrow was extracted by means of irrigation with culture media that elevates the possibility of co-extraction of committed osteoprogenitor, or preosteoblast or other progenitor cells of several types present inside bone marrow. The cultured stromal cells showed high ALP activity which is representative marker of osteoblast without any treatment. Osteogenic inducers such as Dex and BMP-2 were examined for the evaluation of their effect on osteogenic and adipocytic differentiation of stromal cells, because they function as osteoinductive agent in stromal cells, but simultaneously induce adipogenic differentiation. Osteogenic differentiation was evaluated by measuring alkaline phosphatase activity or mRNA expression of osteoblast markers such as osteopontin, bone sialoprotein, collagen type I and CbfaI, and in vitro matrix mineralization by von Kossa staining. Oil red staining method was used to detect adipocyte and adipocytic marker, aP2 and $PPAR{\gamma}2$ expression was examined using RT-PCR. It can be supposed that irrigation procedure resulted in high portion of already differentiation-committed osteoprogenitor cell showing elevated ALP activity and strong mineralization only under the supplement of $100{\mu}M$ ascorbic 2-phosphate and 10mM ${\beta}$-glycerophosphate without any treatment of osteogenic inducers such as Dex and BMP-2. Dex and BMP-2 seemed to transdifferentiate osteoprogenitor cells having high ALP activity into adipocytes temporarily, but continuous treatment redifferentiated into osteoblast and developed in vitro matrix mineralization. This property must be considered either in tissue engineering for bone regeneration, or in research of characterization of osteogenic differentiation, with rat BMSC isolated by the standard irrigation method.

• Journal of Pharmacopuncture
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• v.20 no.2
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• pp.107-111
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• 2017

Objectives: Radiation is one of the most important sources of free radical (such as reactive oxygen species) production, which plays an essential role in the etiology of over hundred diseases. The aim of the study was to investigate some immune parameters and hematological indices in healthy workers of the Radiology Department, University Hospital of Mashhad, Iran. Methods: The study was performed on 50 healthy workers: 30 radiology staff as the case group and 20 laboratory workers as the control group. The radiation dose received by the radiology staff participating in the study was less than the annual maximum permissible level, 50 millisievert. Hematological parameters, lymphocyte proliferation and cytokine production were studied in both groups. Results: Among healthy radiology workers, the hematological indices did not differ statistically; however, their proliferation indices and $IFN-{\gamma}$ levels showed significant increases in parallel with decreases in the IL-4 levels as compared to controls. The immune system of workers exposed to low-dose ionizing radiation was found to be shifted from a Type 2 to a Type 1 response to promote cellular immunity. Conclusion: Based on our data, exposure to low-dose ionizing radiation may decrease the prevalence, frequency, and recurrence of various cancers and infectious diseases because of an increase in Th1-cell-based response, thus leading to more protection of the human body against tumor cells and foreign agents and possibly increased longevity. However, due to high rate of fluoroscopy use for interventional radiology, we suggest continuing research projects on radiation protection and hazards to prevent irreversible damage. As a recommendation, in future studies, radiology staff with a weakened immunity due to high radiation exposure should be considered as good choices to be treated using acupuncture techniques because acupuncture has been demonstrated to enhance the function and the number of immune cells.

• Biomolecules & Therapeutics
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• v.9 no.3
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• pp.167-175
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• 2001

Recent studies have shown that cytokines are capable of modulating cardiovascular function and that some drugs used in the treatment of heart failure variably modulate the production of cytokines. Hige- namine, a positive inotropic isoquinoline alkaloid, has been used traditionally as cardiac stimulant, and reported to reduce nitric oxide (NO) and inducible nitric oxide synthase (iNOS) expression in LPS- and/or cytokine-activated cells in vitro and in vivo. Therefore, we investigated whether higenamine modulates the production of proinflammatory cytokines in myocardial infarction. In addition, effects of higenamine on antioxidant action and antioxidant enzyme expression (MnSOD) were studied. Myocardial infarction (MI) was confirmed by measuring left ventricular (LV) pressure after occlusion of the left anterior descending coronary artery (LAD) for 5 weeks in rats. Treatment of higenamine (10 mg/kg/day) reduced infarct size about 35 %, which accompanied by reduction of production TNF-$\alpha$, IL-6, but not IFN-${\gamma}$ and IL-1$\beta$ in the myocardium. The expression of TNF-$\alpha$ mRNA in infracted myocardium was significantly reduced by higenamine. Although iNOS mRNA was not detected, nitrotyrosine staining was significantly increased in myocardium of Ml compared to higenamine-treated one, Indicating that peroxynitrite-induced damage is evident in MI. Cytochrome c oxidation by peroxynitrite was concentration-dependently reduced by higenamine, an effect which was almost compatible to glutathion. Higenamine treatment did not affect the expression of MnSOD mRNA in myocardial tissues in MI. Taken together, higenamine may be beneficial in oxidative stress conditions such as ischemic-reperfusion injury and MI due to antioxidant action as well as modulation of cytokines.

• Journal of Periodontal and Implant Science
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• v.36 no.3
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• pp.613-625
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• 2006

Periodontal ligament(PDL) cells and human gingival fibroblasts(HGFs) play important roles in development, regeneration, normal function, and pathologic alteration. PDL cells and HGFs have the similarity related with general characteristics of fibroblast such as spindle shaped morphology, the presence of vimentin intermediate filament and the synthesis of interstitial collagens and fibronectin. There were many studies about the differences between PDL cells and HGFs, but they were not about whole gene level. In this study, we tried to explain the differences of gene expression profiles between PDL cells and HGFs, and the differences among three individuals by screening gene expression patterns of PDL cells and HGFs, using cDNA microarray. Although there were some variants among three experiments, a set of genes were consistentely and differentially expressed in one cell type. Among 3,063 genes, 49 genes were more highly expressed in PDL cells and 12 genes were more highly expressed in HGFs. The genes related with cell structure and motility were expressed more highly in PDL cells. These are cofilin 1, proteoglycan 1 secretory granule, collagen type I(${\alpha}$ 1), adducin gamma subunit, collagen type III(${\alpha}$ 1), fibronectin, lumican(keratan sulfate proteoglycan), and ${\alpha}$ -smooth muscle actin. Tissue inhibitor of metalloproteinase known as the enzyme controlling extracellular matrix with matrix metalloproteinase is more highly expressed in PDL cells, osteoprotegerin known as osteoclastogenesis inhibitory factor is more highly expressed in HGFs. We performed northern blot to verify cDNA microarray results on selected genes such as tissue inhibitor of metalloproteinase, fibronectin, osteoprogeterin. The result of northern blot analysis showed that each cell expressed the genes in similar pattern with cDNA microarray result. This result indicates that cDNA microarray is a reliable method in screening of gene expression profiles.