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Cordycepin inhibits lipopolysaccharide-induced cell migration and invasion in human colorectal carcinoma HCT-116 cells through down-regulation of prostaglandin E2 receptor EP4

  • Jeong, Jin-Woo;Park, Cheol;Cha, Hee-Jae;Hong, Su Hyun;Park, Shin-Hyung;Kim, Gi-Young;Kim, Woo Jean;Kim, Cheol Hong;Song, Kyoung Seob;Choi, Yung Hyun
    • BMB Reports
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    • v.51 no.10
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    • pp.532-537
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    • 2018
  • Prostaglandin $E_2$ ($PGE_2$), a major product of cyclooxygenase-2 (COX-2), plays an important role in the carcinogenesis of many solid tumors, including colorectal cancer. Because $PGE_2$ functions by signaling through $PGE_2$ receptors (EPs), which regulate tumor cell growth, invasion, and migration, there has been a growing amount of interest in the therapeutic potential of targeting EPs. In the present study, we investigated the role of EP4 on the effectiveness of cordycepin in inhibiting the migration and invasion of HCT116 human colorectal carcinoma cells. Our data indicate that cordycepin suppressed lipopolysaccharide (LPS)-enhanced cell migration and invasion through the inactivation of matrix metalloproteinase (MMP)-9 as well as the down-regulation of COX-2 expression and $PGE_2$ production. These events were shown to be associated with the inactivation of EP4 and activation of AMP-activated protein kinase (AMPK). Moreover, the EP4 antagonist AH23848 prevented LPS-induced MMP-9 expression and cell invasion in HCT116 cells. However, the AMPK inhibitor, compound C, as well as AMPK knockdown via siRNA, attenuated the cordycepin-induced inhibition of EP4 expression. Cordycepin treatment also reduced the activation of CREB. These findings indicate that cordycepin suppresses the migration and invasion of HCT116 cells through modulating EP4 expression and the AMPK-CREB signaling pathway. Therefore, cordycepin has the potential to serve as a potent anti-cancer agent in therapeutic strategies against colorectal cancer metastasis.

A Caseinolytic Enzyme in Human Follicular Fluid (사람 난표액의 Caseinolytic Enzyme)

  • Shim Myung-Sun;Kim Haekwon
    • Development and Reproduction
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    • v.7 no.2
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    • pp.113-118
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    • 2003
  • Follicular fluid(FF) of mammalian Graafian follicles contains various kinds of proteins and proteinases that are believed to play important roles during follicular growth oocyte maturation and ovulation of mature oocytes. Previous studies of human FF(hFF) demonstrated the presence of many serine/threonine proteinases and matrix metalloproteinases such as gelatinases, however, little is known about the caseinases. Present study was aimed to examine the presence and the property of caseinolytic enzyme in hFF. Using casein zymographic method, it was found that hFF, human adult serum and cord serum exhibited one intense 80 kDa and another weak 78 kDa bands having caseinolytic activity. When inhibitors were added to the zymographic substrate buffer, caseinolytic activity of both 80 kDa and 78 kDa proteins were inhibited by othylenediarnine tetraacetic acid(EDTA) or soybean trypsin inhibitor(SBTI), but not by E-64, phenylmethylsulfonyl fluoride(PMSF) or 1,10-phenanthroline. Thus both enzymes appear to belong to a family of trypsin-like enzyme. Addition of EDTA to the zymographic substrate buffer almost abolished the caseinolytic activity of both enzymes. However, further addition of a divalent metal ion such as CaC $l_2$, MgC $l_2$, MnC $l_2$ or ZnC $l_2$ to the same buffer fully restored the enzyme activity at 5 mM concentration despite the presence of EDTA. Based upon these observations, 80 kDa and 78 kDa caseinolytic enzymes are present in human follicular fluid and they appear to be trypsin-like enzymes of which caseinolytic activity needs the presence of $Ca^{++}$, aM $g^{++}$, M $n^{++}$ or Z $n^{++}$././././.

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Effects of ID-CBT5101 in Preventing and Alleviating Osteoarthritis Symptoms in a Monosodium Iodoacetate-Induced Rat Model

  • Sim, Boo-Yong;Choi, Hak-Joo;Kim, Min-Goo;Jeong, Dong-Gu;Lee, Don-Gil;Yoon, Jong-Min;Kang, Dae-Jung;Park, Soobong;Ji, Joong-Gu;Joo, In-Hwan;Kim, Dong-Hee
    • Journal of Microbiology and Biotechnology
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    • v.28 no.7
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    • pp.1199-1208
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    • 2018
  • Osteoarthritis is a disease that affects the articular cartilage and osseous tissue, and can be worsened by aging, overweight status, and post-traumatic arthritis. The present study aimed to evaluate the effect of ID-CBT5101 (tyndallized Clostridium butyricum) on bone metabolism and the inflammatory response in a monosodium iodoacetate-induced rat model of osteoarthritis. ID-CBT5101 was administered orally at doses of $10^8$ or $10^{10}CFU/day$ for 2 weeks before direct injection of monosodium iodoacetate ($3mg/50{\mu}l$ of 0.9% saline) into the intra-articular space of the rats' right knees. The rats subsequently received the same doses of oral ID-CBT5101 for another 4 weeks. We evaluated the treatment effects based on serum biomarkers, mRNA expression, morphological and histopathological analyses of the knee joints, and weight-bearing distribution analysis. Compared with those in control rats, the ID-CBT5101 treatments significantly reduced the serum concentration of inflammation and bone metabolism markers (i.e., COX-2, IL-6, $LTB_4$, and COMP), and significantly increased the concentration of $IFN-{\gamma}$ and glycosaminoglycans. In addition, the ID-CBT5101 treatments inhibited the mRNA expression of matrix metalloproteinases and tissue inhibitors of metalloproteinases (i.e., MMP-2, MMP-3, MMP-9, MMP-13, TIMP-1, and TIMP-2). Furthermore, the ID-CBT5101 treatments effectively preserved the knee cartilage and synovial membrane, and significantly decreased the amount of fibrous tissue. Moreover, compared with that of the negative control group, the ID-CBT5101 treatments increased the weight-bearing distribution by ${\geq}20%$. The results indicate that ID-CBT5101 prevented and alleviated osteoarthritis symptoms. Thus, ID-CBT5101 may be a novel therapeutic option for the management of osteoarthritis.

Effects of Bujasasim-tang Ethanol Extract on Oxidative Stress, Inflammation and Osteoarthritic Rat Model (부자사심탕(附子瀉心湯)이 산화적 손상, 염증 및 골관절염 병태모델에 미치는 영향)

  • Woo, Chang-Hoon;Oh, Min-Seok
    • Journal of Korean Medicine Rehabilitation
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    • v.25 no.2
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    • pp.15-35
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    • 2015
  • Objectives This study was performed to investigate the effects of Bujasasim-tang ethanol extract (BST) on oxidative stress, inflammation and osteoarthritic rat model. Methods To ensure safety of BST, heavy metal levels were measured and cytotoxicity test was done. In vitro, To evaluate antioxidative effects of BST, total phenolic contents, 1,1-diphenyl-2-picryl-hydrazyl (DPPH), 2,2'-azino-bis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) scavenging activity, reactive oxygen species (ROS) levels were measured. Also, to evaluate anti-inflammatory effects of BST treated group, total nitric oxide (NO) and pro-inflammatory cytokines (IL-$1{\beta}$, IL-6, TNF-${\alpha}$) levels were measured in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. In vivo, We injected MIA $50{\mu}l$ (60 mg/ml) into knee joints of rats to induce osteoarthritis. Rats were divided into total 3 groups (normal, control, BST treated group, each n=7). Normal group was not treated at all without inducing osteoarthritis and taken normal diet. Control group was induced osteoarthritis by MIA and taken with 2 ml of distilled water once a day for 4 weeks. BST treated group was induced osteoarthritis by MIA and taken BST 2 ml (200 mg/kg/mouse) once a day for 4 weeks. We evaluated dynamic weight bearing with the Incapacitance Test Meter. At the end of experiment, the rats were sacrificed to observe the functions of liver and kidney, changes of WBC, neutrophil, lymphocyte, monocyte levels in blood, to evaluate the levels of pro-inflammatory cytokines, tissue inhibitor of metallopreteinases-1 (TIMP-1), matrix metalloproteinase-9 (MMP-9), prostaglandin $E_2$ ($PGE_2$), leukotriene $B_4$ ($LTB_4$) within serum. We observed change of articular structures by Hematoxylin & Eosin (H&E), safranin-O staining method and measured amount of cartilage by micro CT-arthrography. Statistical analysis was done by unpaired student's t-test with significance level at p<0.05 in SPSS 11.0 for windows. Results 1. Safety of the BST was identified. 2. AST, ALT, BUN, creatinine levels of BST treated group were within normal limit. In vitro, 1. DPPH and ABTS free radical scavenging activities of BST showed dose-dependent increase. 2. ROS production were significantly decreased. 3. Total nitric oxide (NO) and IL-$1{\beta}$ production were decreased. 4. IL-6 and TNF-${\alpha}$ production were significantly decreased. In vivo, 1. Weight bearing ability was significantly increased. 2. WBC, neutrophil, lymphocyte, monocyte levels in blood were decreased. 3. IL-$1{\beta}$ and TNF-${\alpha}$ levels in serum were significantly decreased. and the IL-6 level was decreased. 4. TIMP-1, MMP-9, $LTB_4$, $PGE_2$ levels in serum were significantly decreased. 5. Cartilage volume of BST treated group was significantly increased. Also changes of cartilage, synovial membrane, fibrous tissue were suppressed. Conclusions The results obtained in this study Bujasasim-tang have effects of antioxidative, anti-inflammatory, relieve pain and protection of cartilage. Therefore we expect that Bujasasim-tang is effective treatment for osteoarthritis.

Thermal, Frictional and Wear Behavior of Carbon Nanofiber/Poly(methyl methacrylate) Composites (탄소나노섬유/폴리(메틸 메타크릴레이트) 복합재료의 열적 및 마찰 마모 거동 연구)

  • Park Soo-Jin;Im Se-Hyuk;Lee Jae-Rock;Rhee John-M.
    • Polymer(Korea)
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    • v.30 no.5
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    • pp.385-390
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    • 2006
  • In this work, the effect of carbon nanofiber (CNF) on thermal properties, and friction and wear behavior of CNF/PMMA composites were examined. While thermal properties of the composites were investigated with differential scanning calorimetry, thermograyimetric analyzer, and dynamic mechanical analyzer friction and wear behaviors were examined using a friction and wear tester. The glass transition temperature (Tg), integral procedural decomposition temperature (IPDT), storage modulus (E'), and tan ${\delta}$ appeared at higher temperatures with increasing CNF content, which were probably attributed to the presence of strong interactions between the carbonaceous fillers and the PMMA resins matrix. The wear loss in the composites decreased at 0.1 wt% CNF and then increased with 5-10 wt% CNF content. This was due to the existence of large aspect ratio CNF in PMMA which led to an alignment of PMMA chains and an increase of mechanical interlocking, resulting in the formation of crosslinked structures between CNF and PMMA in the composite.

A Study on the Fiber-Optic Voltage Sensor Using EMO-BSO (EOM-BSO 소자를 이용한 광전압센서에 관한 연구)

  • Kim, Yo-Hee;Lee, Dai-Young
    • Journal of the Korean Institute of Telematics and Electronics
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    • v.27 no.11
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    • pp.119-125
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    • 1990
  • This paper describes fiber optic voltage sensor using EOM-BSO (Electro-Optic Modulator-Bismuth Silicon Oxcide). Transceiver has an electical/optical converter and an optical/electrical converter which consist of light emitting diode, PIN-PD, and electronic circuits. Multimode fiber cable of $100/140{\mu}m$ core/clad diameter is used for connecting the transceiver to fiber cable and fiber optic voltage sensor. Before our experiments, by applying the Maxwell equations and wave equations, We derive matrix equation on wave propagation in the BSO single crystal. And also we derive optimal equation on intensity modulation arising through an analyzer. According to experi-mental results, fiber optic voltage sensor has maximum $2.5{\%}$ error within the applied AC voltage of 800V. As the applied voltage increases, saturation values of voltage sensor also increase. This phenomenon is caused by optical rotatory power of BSO single crystal. And temperature dependence of sensitivity for fiber optical rotatory power of BSO single crystal. And temperature dependence of sensitivity for fiber optic voltage sensor in the temperature range from$-20^{\circ}C\to\60^{\circ}C$ are measured within ${\pm}0.6{\%}$. And frequency characteristics of the voltage sensor has good frequency characteristics from DC to 100kHz.

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The effect of rhBMP-2 on ${\Delta}^{12}-PGJ_2$ induced osteoblastic differentiation and mineralization (골형성유도단백질의 첨가가 ${\Delta}^{12}-PGJ_2$가 유도하는 석회화에 미치는 영향)

  • Kim, Won-Kyung;Kim, Kyoung-Hwa;Kim, Jong-Jin;Lee, Young-Kyu;Ku, Young
    • Journal of Periodontal and Implant Science
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    • v.35 no.2
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    • pp.345-357
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    • 2005
  • Prostaglandin plays a significant role in the local control of bone metabolism associated with periodontal disease. ${\Delta}^{12}-PGJ_2$ is a natural $PGD_2$ metabolite that is formed in vivo in the presence of plasma. It is known for ${\Delta}^{12}-PGJ_2$ to stimulate calcification in osteoblastic cells. Bone morphogenetic protein(BMP) stimulated osteoblastic differentiation in various types of cells and greatly enhanced healing of bony defects. The purpose of this study was to evaluate the effect of rhEMP-2 on ${\Delta}^{12}-PGJ_2$ induced osteoblastic differentiation and mineralization in vitro. A human osteosarcoma cells line Saos-2 were cultured. In the test groups, 10-7M of ${\Delta}^{12}-PGJ_2$ or mixture of 10-8M of ${\Delta}^{12}-PGJ_2$ and 100ng/ml of rhBMP-2 or 100ng/ml of rhEMP-2 were added to culture media. After 1 day, 2 days and 4 days of culture period, the cell number was measured. Alkaline phosphatase activity was measure at 3 days. Reverse transcription polymerase chain reaction(RT-PCR) was performed to determine the expression of mRNA of bone matrix protein at 8 hours, 1 day and 7 days. The ability to produce mineralized nodules in rat osteoblasts(MC3T3-E1) was evaluated at 21 days. The results were as follows : 1. rhEMP-2 or mixture of rhBMP-2 and ${\Delta}^{12}-PGJ_2$ inhibited cell proliferation of human osteosarcoma cells. 2. rhEMP-2 or mixture of rhBMP-2 and ${\Delta}^{12}-PGJ_2$ stimulated alkaline phosphatase activity significantly higher than ${\Delta}^{12}-PGJ_2$ alone. 3. rhBMP-2 or mixture of rhEMP-2 and ${\Delta}^{12}-PGJ_2$ stimulated mineralization compared to ${\Delta}^{12}-PGJ_2$ alone. 4. mRNA of alkaline phosphatase, BMP-2, cbfa 1, Type I collagen were detected in the group treated with ${\Delta}^{12}-PGJ_2$/rhBMP-2, rhBMP-2 alone, ${\Delta}^{12}-PGJ_2$ alone. These results show that mixture of ${\Delta}^{12}-PGJ_2$ and rhBMP-2 causes more bone formation than ${\Delta}^{12}-PGJ_2$ alone while the bone formation effects of mixture of ${\Delta}^{12}-PGJ_2$ and rhBMP-2 are less than those of rhBMP-2 alone. Further researches would be necessary to clarify the interactions of these agents.

A Study on the Solubility of Nb in Zr-0.8Sn Alloy by Thermoelectric Power Measurement (TEP 측정방법을 이용한 Zr-0.8Sn 합금의 Nb 고용도에 관한 연구)

  • Oh, Yeong-Min;Jeong, Heung-Sik;Jeong, Yong-Hwan;Kim, Seon-Jin
    • Korean Journal of Materials Research
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    • v.11 no.6
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    • pp.453-459
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    • 2001
  • It is important for the fabrication of nuclear cladding to optimize the microstructure, because the properties of Zr-based nuclear claddings such as mechanical properties, oxidation-resistance and corrosion- resistance vary widely with its microstructure. The microstructure in Zr-based alloy is strongly dependent on the solubility of alloying element. However, it is very difficult to measure the solubility due to the low solution limit of alloying elements in Zr-based alloy. In this study, Thermoelectric Power(TEP) measurements are used to determine the solubility of Nb in Zr-0.8Sn alloy, which is confirmed by optical microscopy and transmission electron microscopy. The solutioning of Nb obtained by a homogenization treatment and water-quench leads to a decrease of TEP The saturation of TEP appears with the increase of homogenization temperature, which means the saturation of the Nb content in the matrix. From these results, the solubility ($C_{Nb}$) of Nb in Zr-0.8Sn with temperature could be expressed as fellow equation : $4.69097{\times}10^{16}{\times}e^{-25300\times\;I/T}$(ppm.at.%)

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Selection of Biofilter Support for Removing MEK (MEK 제거를 위한 바이오필터용 담체의 선택)

  • Jeong Gwi-Taek;Lee Gwang-Yeon;Lee Kyoung-Min;Sunwoo Chang-Shin;Lee Woo-Tae;Jung Seong-Ho;Cha Jin-Myoung;Jang Young-Seon;Park Don-Hee
    • KSBB Journal
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    • v.21 no.1 s.96
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    • pp.34-41
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    • 2006
  • The aim of this study is the development of biological removal process of methyl ethyl ketone (MEK) in odor gas, which is generated from the waste food recycling process. To develop the removal process of odor gas, MEK, the selection of proper biofilter support was carried out. When the biofilter equipment was passed by synthetic odor gas composed of 250 ppm of MEK, the maximum removal was achieved to $586.6g-MEK/m^3\;hr$ for polypropylene fibril as support. Under the same experimental conditions, the maximum removal in polyurethane support was obtained to $359.7 g-MEK/m^3\;hr$. Finally, the maximum removal in volcanic stone support was $56.2g-MEK/m^3\;hr$.

Tailoring Low-field Strain Properties of [0.97Bi1/2(Na0.78K0.22)1/2TiO3-0.03LaFeO3]-Bi1/2(Na0.82K0.18)1/2TiO3 Lead-Free Relaxor/Ferroelectric Composites (무연 완화형/정규 강유전체 복합소재 [0.97Bi1/2(Na0.78K0.22)1/2TiO3-0.03LaFeO3]-Bi1/2(Na0.82K0.18)1/2TiO3의 저전계 전계유기 변형 특성 연구)

  • Hong, Chang-Hyo;Kang, Jin-Kyu;Jo, Wook;Lee, Jae-Shin
    • Journal of the Korean Institute of Electrical and Electronic Material Engineers
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    • v.29 no.6
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    • pp.342-347
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    • 2016
  • We investigated the effect of $Bi_{1/2}(Na_{0.82}K_{0.18})_{1/2}TiO_3$ (BNKT) modification on the ferroelectric and electric-field-induced strain (EFIS) properties of lead-free $0.97Bi_{1/2}(Na_{0.82}K_{0.18})_{1/2}TiO_3-0.03LaFeO_3$ (BNKTLF) ceramics as a function of BNKT content (x= 0, 0.1, 0.2, 0.3, 0.5, and 1). BNKT-modified BNKTLF powders were synthesized using a conventional solid-state reaction method. As the BNKT content x increased from 0 to 1 the normalized electric-field-induced strain ($S_{max}/E_{max}$) was observed to increase at relatively low fields, i.e., below the poling field. Moreover, BNKTLF-30BNKT showed about 460 pm/V as low as at 3 kV/mm, which is a considerably high value among the lead-free systems reported so far. Consequently, it was confirmed that ceramic-ceramic composite, a mixture of an ergodic relaxor matrix and embedded ferroelectric seeds, is a salient way to make lead-free piezoelectrics practical with enhanced EFIS at low field as well as less hysterical.