• Journal of Korean Neurosurgical Society
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• v.63 no.4
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• pp.444-454
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• 2020

Objective : Glioblastoma multiforme (GBM) is the most aggressive for of brain tumor and treatment often fails due to the invasion of tumor cells into neighboring healthy brain tissues. Activation of the Janus kinase-signal transducer and activator of transcription (JAK/STAT) signaling pathway is essential for normal cellular function including angiogenesis, and has been proposed to have a pivotal role in glioma invasion. This study aimed to determine the dose-dependent effects of ruxolitinib, an inhibitor of JAK, on the interferon (IFN)-I/IFN-α/IFN-β receptor/STAT and IFN-γ/IFN-γ receptor/STAT1 axes of the IFN-receptor-dependent JAK/STAT signaling pathway in glioblastoma invasion and tumorigenesis in U87 glioblastoma tumor spheroids. Methods : We administered three different doses of ruxolitinib (50, 100, and 200 nM) to human U87 glioblastoma spheroids and analyzed the gene expression profiles of IFNs receptors from the JAK/STAT pathway. To evaluate activation of this pathway, we quantified the phosphorylation of JAK and STAT proteins using Western blotting. Results : Quantitative real-time polymerase chain reaction analysis demonstrated that ruxolitinib led to upregulated of the IFN-α and IFN-γ while no change on the hypoxia-inducible factor-1α and vascular endothelial growth factor expression levels. Additionally, we showed that ruxolitinib inhibited phosphorylation of JAK/STAT proteins. The inhibition of IFNs dependent JAK/STAT signaling by ruxolitinib leads to decreases of the U87 cells invasiveness and tumorigenesis. We demonstrate that ruxolitinib may inhibit glioma invasion and tumorigenesis through inhibition of the IFN-induced JAK/STAT signaling pathway. Conclusion : Collectively, our results revealed that ruxolitinib may have therapeutic potential in glioblastomas, possibly by JAK/STAT signaling triggered by IFN-α and IFN-γ.

• BMB Reports
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• v.44 no.11
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• pp.753-757
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• 2011

Heme oxygenase-1 (HO-1), an inducible enzyme with broad tissue expression, is wel1-regulated in response to hematopoietic stress and preserves vascular homeostasis. We investigated the involvement of HO-1 in HL-60 cell differentiation. Dimethyl sulfoxide (DMSO) completely decreased HO-1 expression in a time-dependent manner, but clearly induced HL-60 cell differentiation, as evidenced by a marked increase in CD11b expression. Interestingly, zinc protoporphyrin (ZnPP), a strong inhibitor of HO-1, induced HL-60 cell differentiation. In contrast, treatment with cobalt protoporphyrin (CoPP), an activator of HO-1, decreased CD11b expression. Additionally, ZnPP down-regulated HO-1 protein expression in HL-60 cells, whereas CoPP induced upregulation. These results suggest that HO-1 might have a negative function in DMSO-induced HL-60 cell differentiation. This study provides the first evidence that HO-1 plays an important role in DMSO-induced HL-60 cell differentiation.

• Journal of the Korean Society of Environmental Restoration Technology
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• v.12 no.6
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• pp.153-163
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• 2009

This study was carried out to offer ecological restoration plan of local streams by analyzing the vegetation and flora around four local streams (Pungchoncheon, Namchangcheon, Ganggicheon, Woncheoncheon) in Namwon. Flora and vegetation investigation was done at April 2007 to August 2007, and June 2009. The 194 of vascular plants were identified which contain 53 families, 143 genera, 194 species. The Family frequencies arranged by the order of Family Compositae (14.4%), Family Gramineae (13.4%) Family Leguminosae (6.7%) and Family Polygonaceae (5.2%). The naturalized plants were listed as 33 species, and their naturalization ratio and urban index were found to be 17.0%, and 12.2%, respectively. In this study a total of 21 relev$\acute{e}$s collected and analyzed. 6 plant communities are differentiated : Riverine softwood forests (Phragmites japonica-Salix gracilistyla community), Perennial herb vegetations on lotic water zone (Phragmites japonica community, Phalaris arundinacea community), Perennial herb vegetations on lentic water zone (Persicaria thunbergii-Typha orientalis community, Phragmites communis community), Annual or biennial vegetations on waterside (Persicaria thunbergii community). Species showing the higer value in the plant communities were Persicaria thunbergii, Phragmites japonica, Artemisia princeps, Humulus scandens, Bidens frondosa, Oenanthe javanica, Agropyron tsukusinense var. transiens, Stellaria aquatica, and Lactuca indica var. laciniata.

• Molecules and Cells
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• v.40 no.10
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• pp.761-772
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• 2017

Glioblastoma is the most frequent and most aggressive brain tumor in adults. Solute carrier family 8 member 2 (SLC8A2) is only expressed in normal brain, but not present in other human normal tissues or in gliomas. Therefore, we hypothesized that SLC8A2 might be a glioma tumor suppressor gene and detected the role of SLC8A2 in glioblastoma and explored the underlying molecular mechanism. The glioblastoma U87MG cells stably transfected with the lentivirus plasmid containg SLC8A2 (U87MG-SLC8A2) and negative control (U87MG-NC) were constructed. In the present study, we found that the tumorigenicity of U87MG in nude mice was totally inhibited by SLC8A2. Overexpression of SLC8A2 had no effect on cell proliferation or cell cycle, but impaired the invasion and migration of U87MG cells, most likely through inactivating the extracellular signal-related kinases (ERK)1/2 signaling pathway, inhibiting the nuclear translocation and DNA binding activity of nuclear factor kappa B ($NF-{\kappa}B$), reducing the level of matrix metalloproteinases (MMPs) and urokinase-type plasminogen activator (uPA)-its receptor (uPAR) system (ERK1/2-$NF-{\kappa}B$-MMPs/uPA-uPAR), and altering the protein levels of epithelial to mesenchymal transitions (EMT)-associated proteins E-cardherin, vimentin and Snail. In addition, SLC8A2 inhibited the angiogenesis of U87MG cells, probably through combined inhibition of endothelium-dependent and endothelium-nondependent angiogenesis (vascular mimicry pattern). Totally, SLC8A2 serves as a tumor suppressor gene and inhibits invasion, angiogenesis and growth of glioblastoma.

• Journal of Community Nutrition
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• v.2 no.1
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• pp.5-11
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• 2000

Populations both in the US and worldwide are aging. It is projected that by the year 2030 the population of Americans over 65 will increase to 70 million, more than twice their number in 1998. About one-third of elderly over the age of 65 have debilitating chronic health conditions that greatly impede their activities. Age-associated chronic diseases are believed to be associated with free radicals and the imbalance in antioxidant and oxidative stress contributes to development of several chronic health conditions. Diet and nutrients can have great impact in the health status of elderly. Several factors may contributor to the inadequate consumption of nutrients in elderly, including an inability to chew food adequately, polypharmacy, living along and limited income. Low intake of energy and several micronutrients are common among the elderly. Although overt deficiency of nutrients among the elderly is not common. a recent study showed that while elderly consume more fat, the total energy intake is low among the elderly. Inadequate intake of antioxidant nutrients such as vitamin E in elderly may contribute to the development of chronic health problems. Intake of higher than normal RDA levels of vitamin E for long periods of time has been shown to reduce the risk of many degenerative diseases, such as cardiovascular diseases(CVD) and cancer, and improve immune response in elderly. High intake of other antioxidants is also associated with reduced risk chronic diseases. Dietary antioxidants are abundant in fruits and vegetables. However, due to variety of factors, the elderly may not be able to receive these and other micronutrients through diet. Therefore, supplemental intake of micronutrients in the form of multi vitamins/minerals and/or specific micronutrients is a more practical approach to the maintenance of health status in the elderly.

• Development and Reproduction
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• v.19 no.4
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• pp.227-234
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• 2015

The objective of this study was to investigate the expression of bovine luteum expressed sequence tags (ESTs), vascular endothelial growth factor (VEGF), and tumor necrosis factor receptor 1 (TNFR1) and the presence of functional ESTs in the bovine corpus luteum (CL) during different stages of the estrus cycle. Reverse transcription-polymerase chain reaction (RT-PCR) analysis showed a difference in the expression of ESTs during the CL stage. Concentration of ESTs in the CL tissue increased significantly from the mid-luteal stage and decreased thereafter. RT-PCR analysis showed higher levels of the EST genes in the CL of the mid-luteal stage than in other stages, and the same level of expression of VEGF. Immunohistochemistry analysis of the tissue from CL formation to regression showed low cytosol and aggregation of the nucleus. And activity caspase 3 (apoptosis detector) was most strongly detected in the CL1 stage of bovine. During the estrous cycle, the cytosol was magnified and differentiation of the nucleus was clearly manifested. The ESTs affected the CL, and the relationship between VEGF and TNFR1 played a pivotal role for CL development and activation, dependent on the stage of CL. These results suggest local production of ESTs, the presence of functional ESTs in the bovine CL, and that ESTs play a role in regulating the function of cell death in bovine CL.

• Journal of Marine Bioscience and Biotechnology
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• v.1 no.3
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• pp.156-162
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• 2006

The halophilic enterobacteria, Enterobacteria cancerogenus, was isolated from the intestines of the fusiform fish (Trachurus japonicus) to yield a protein-like material termed PLM-f74. PLM-f74 was characterized by strong inhibition ratios to angiogenesis (82.8% at the concentration of $18.5{\mu}g/mL$) and elevated antioxidative capacities with low toxicity. The PLM-f74 is a glycoprotein comprised of saccharides and amino acids. PLM-f74 inhibited non-activated U937 monocytic cell adhesion to HUVECs activated with IL-$1{\beta}$ by 78.0%, and the adherence of U937 cells treated with the PLM-f74 and stimulated with IL-$1{\beta}$ to unstimulated HUVECs decreased by 102%. When both cell types were pretreated with PLM-f74, the adhesion of U937 cells to IL-$1{\beta}$ stimulated HUVECs was completely suppressed by 121% at a concentration of 18.5 ug/mL. PLM-f74 blocked signal pathways from VEGFR2, PI3K, ${\beta}$-catenin and VE-cadherin to NF-kB based on western bolt analysis. And also inhibited IL-1-stimulated HUVEC expression of the adhesion molecules, ICAM-1 by 40%, VCAM-1 by 60%, and E-selectin by 70% at the same concentration noted above. New anti-angiogenic and anti-cell adhesion materials showing elevated antioxidative capacities and non-toxicity may be expected from these results.

• Journal of Ginseng Research
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• v.42 no.4
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• pp.524-531
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• 2018

Background: Fermented black ginseng (FBG) is produced through several cycles of steam treatment of raw ginseng, at which point its color turns black. During this process, the original ginsenoside components of raw ginseng (e.g., Re, Rg1, Rb1, Rc, and Rb2) are altered, and less-polar ginsenosides are generated (e.g., Rg3, Rg5, Rk1, and Rh4). The aim of this study was to determine the effect of FBG on wound healing. Methods: The effects of FBG on tube formation and on scratch wound healing were measured using human umbilical vein endothelial cells (HUVECs) and HaCaT cells, respectively. Protein phosphorylation of mitogen-activated protein kinase was evaluated via Western blotting. Finally, the wound-healing effects of FBG were assessed using an experimental cutaneous wounds model in mice. Results and Conclusion: The results showed that FBG enhanced the tube formation in HUVECs and migration in HaCaT cells. Western blot analysis revealed that FBG stimulated the phosphorylation of p38 and extracellular signal-regulated kinase in HaCaT cells. Moreover, mice treated with $25{\mu}g/mL$ of FBG exhibited faster wound closure than the control mice did in the experimental cutaneous wounds model in mice.

• The Korean Journal of Ecology
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• v.21 no.5_1
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• pp.465-473
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• 1998

This study was carried out to investigate the developmental process of plant community during the secondary succession and changes of soil properties in the burned areas lapsed 28 years after the forest fire in Mt.Palgong. The forest fire occurred on March, 1969 and the red pine (pinus densiflora) forest and its floor vegetation were burned down. The results are summarized as follows: the floristic composition of burned and unburned areas were composed of 49 and 48 species of vascular plants, respectively. The dominant species based on SDR4 of the burned sites were Lespedeza maximowicxii(87.75), Carex humilis (62.94), Rhododendron schippenbachii(55.78) and Miscanthus sinensis var.purpurascens (51.94). In contrast, Pinus densiflora (81.17), Quercus serrata (53.58)m Carex humilis (53.11) and Miscanthus sinenis var. purpuracens (52.42) were dominant in the unburned area. The biological spectra showed the $H-D_1-R_5-e$ type in both areas. The indices of similarity (CCs) between the two areas were 0.80. Degree of succession (DS) was 734 in the burned area and 809 in the unburned area. The species diversity (H) and evenness indices (e) in the burned and unburned areas were 2.05, 2.13 and 0.53, 0.55, respectively. Dominance index (C) in the burned and unburned areas were 0.30 and 0.32, respectively. Soil properties such as soil pH, content of organic matter, total nitrogen, total carbon, exchangeable potassium, sodium, calcium, and magnesium in burned area were comparatively higher than those of unburned area. Monthly changes of soil properties were of little significance except for some cases. These results suggest that there was relationship between trend of vegetation recovery and the changes of soil properties after the forest fire. Mixed forestation of fire-resistant species and nitrogen fixation species will be effective for reforestation after the forest fire.

• BMB Reports
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• v.35 no.2
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• pp.186-193
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• 2002

The acid-bible subunit (ALS) associates with the insulinlike growth factor (IGF)-I or II, and the IGF binding protein-3 (IGFBP-3) in order to form a 150-kD complex in the circulation. This complex may regulate the serum IGFs by restricting them in the vascular system and promoting their endocrine actions. Little is known about how ALS binds to IGFBP3, which connects the IGFs to ALS. Xenopus oocyte was utilized to study the function of ALS in assembling IGFs into the ternary complexes. Xenopus oocyte was shown to correctly translate in vitro transcribed mRNAs of ALS and IGFBP3. IGFBP3 and ALS mRNAs were injected in a mixture, and their products were immunoprecipitated by antisera against ALS and IGFBP3. Contrary to traditional reports that ALS interacts only with IGF-bound IGFBP3, this study shows that ALS is capable of forming a binary complex with IGFBP3 in the absence of IGF When cross-linked by disuccinimidyl suberate, the band that represents the ALS-IGFBP3 complex was evident on the PAGE. IGFBP3 movement was monitored according to the distribution between the hemispheres. Following a localized translation in the vegetal hemisphere, IGFBP3 remained in the vegetal half in the presence of ALS. However, the mutant IGFBP3 freely diffused into the animal half, despite the presence of ALS, which is different from the wild type IGFBP3. This study, therefore, suggests that ALS may play an important role in sequestering IGFBP3 polypeptides via the intermolecular aggregation. Studies using this heterologous model will lead to a better understanding of the IGFBP3 and ALS that assemble into the ternary structure and circulate the IGF system.