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Induction of Apoptosis in Human Leukemic Cell Lines by Diallyl Disulfide via Modulation of EGFR/ERK/PKM2 Signaling Pathways

  • Luo, Nian;Zhao, Lv-Cui;Shi, Qing-Qiang;Feng, Zi-Qiang;Chen, Di-Long;Li, Jing
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.8
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    • pp.3509-3515
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    • 2015
  • Background: Diallyl disulfide (DADS) may exert potent anticancer action both in vitro and in vivo. Although its effects on cancer are significant, the underlying mechanisms remain unknown. In this study, we sought to elucidate possible links between DADS and pyruvate kinase (PKM2). Materials and Methods: $KG1{\alpha}$, a leukemia cell line highly expressing PKM2 was used with a cell counting kit (CCK)-8 and flow cytometry (FCM) to investigate the effects of DADS. Relationships between PKM2 and DADS associated with phosphorylation of EGFR, ERK1/2 and MEK, were assessed by western blot analysis. Results: In $KG1{\alpha}$ cells highly expressing PKM2, we found that DADS could affect proliferation, apoptosis and EGFR/ERK/PKM2 signaling pathways, abrogating EGF-induced nuclear accumulation of PKM2. Conclusions: These results suggested that DADS suppressed the proliferation of $KG1{\alpha}$ cells, providing evidence that its proapoptotic effects are mediated through the inhibition of EGFR/ERK/PKM2 signaling pathways.

TUTUM Easy-seismic: Development of a Seismic Design Automation Software for Building Fire Protection Systems (TUTUM Easy-seismic: 소방시설 내진설계 자동화 소프트웨어 개발)

  • Oh, Chang-Soo;Choi, Jun-Ho
    • Fire Science and Engineering
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    • v.33 no.5
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    • pp.140-148
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    • 2019
  • In line with the "mandatory seismic design of fire protection facilities," development of design automation software is indispensable for improving the reliability and efficiency of seismic design. The seismic design automation software developed in this study is an automated S/W for seismic design of fire-fighting facilities, and functions such as automatic arrangement of anti-shake braces according to Korea National Fire Agency's Seismic Design Standards for fire-fighting facilities, output of seismic bracing calculation bills and automatic quantities counting. In addition, the seismic design automation software not only reduces the work speed by three times compared to the manual design of the designer, but also improves the reliability of the design by reducing the human error related to the design quantity such as the brace. In addition, in the seismic design method of fire protection facilities that have been approached conservatively, it was possible to perform the optimal seismic design by using computer algorithms for at least in the use of braces.

Knockdown of microtubule actin crosslinking factor 1 inhibits cell proliferation in MC3T3-E1 osteoblastic cells

  • Hu, Lifang;Su, Peihong;Li, Runzhi;Yan, Kun;Chen, Zhihao;Shang, Peng;Qian, Airong
    • BMB Reports
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    • v.48 no.10
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    • pp.583-588
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    • 2015
  • Microtubule actin crosslinking factor 1 (MACF1), a widely expressed cytoskeletal linker, plays important roles in various cells by regulating cytoskeleton dynamics. However, its role in osteoblastic cells is not well understood. Based on our previous findings that the association of MACF1 with F-actin and microtubules in osteoblast-like cells was altered under magnetic force conditions, here, by adopting a stable MACF1-knockdown MC3T3-E1 osteoblastic cell line, we found that MACF1 knockdown induced large cells with a binuclear/multinuclear structure. Further, immunofluorescence staining showed disorganization of F-actin and microtubules in MACF1-knockdown cells. Cell counting revealed significant decrease of cell proliferation and cell cycle analysis showed an S phase cell cycle arrest in MACF1-knockdown cells. Moreover and interestingly, MACF1 knockdown showed a potential effect on cellular MTT reduction activity and mitochondrial content, suggesting an impact on cellular metabolic activity. These results together indicate an important role of MACF1 in regulating osteoblastic cell morphology and function.

Experimental Research of ZrO2/BCP/PCL Scaffold with Complex Pore Pattern for Bone Tissue Regeneration (골 조직 재생을 위한 복합 공극 패턴을 가진 ZrO2/BCP/PCL 인공지지체의 실험적 평가)

  • Sa, Min-Woo;Shim, Hae-Ri;Kim, Jong Young
    • Transactions of the Korean Society of Mechanical Engineers A
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    • v.39 no.11
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    • pp.1153-1159
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    • 2015
  • Recently, synthetic biopolymers and bioceramics such as poly (${\varepsilon}$-caprolactone)(PCL), hydroxyapatite, tricalcium phosphate, biphasic calcium phosphate(BCP), and zirconia have been used as substrates to generate various tissues or organs in tissue engineering. Thus, the purpose of this study was the characterization of $ZrO_2$/BCP/PCL(ZBP) scaffold for bone tissue regeneration. Based on the result of single-line test, blended 3D ZBP scaffolds with fully interconnected pores and new complex pore pattern of $45^{\circ}+135^{\circ}$-type and staggered-type were successfully fabricated using a polymer deposition system. Furthermore, the effect of ZBP scaffold on mechanical property was analyzed. In addition, in vitro cell interaction of ZBP scaffold on MG63 cells was evaluated using a cell counting kit-8(CCK-8) assay.

Lactobacillus acidophilus Contributes to a Healthy Environment for Vaginal Epithelial Cells

  • Pi, Woo-Jin;Ryu, Jae-Sook;Roh, Jae-Sook
    • Parasites, Hosts and Diseases
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    • v.49 no.3
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    • pp.295-298
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    • 2011
  • Lactobacillus species in the female genital tract are thought to act as a barrier to infection. Several studies have demonstrated that lactobacilli can adhere to vaginal epithelial cells. However, little is known about how the adherence of lactobacilli to vaginal epithelial cells affects the acidity, cell viability, or proliferation of the lactobacilli themselves or those of vaginal epithelial cells. Lactobacillus acidophilus was co-cultured with immortalized human vaginal epithelial cells (MS74 cell line), and the growth of L. acidophilus and the acidity of the culture medium were measured. MS74 cell density and viability were also assessed by counting cell numbers and observing the cell attachment state. L. acidophilus showed exponential growth for the first 6 hr until 9 hr, and the pH was maintained close to 4.0-5.0 at 24 hr after culture, consistent with previous studies. The growth curve of L. acidophilus or the pH values were relatively unaffected by co-culture with MS74 cells, confirming that L. acidophilus maintains a low pH in the presence of MS74 cells. This co-culture model could therefore potentially be used to mimic vaginal conditions for future in vitro studies. On the other hand, MS74 cells co-cultured with L. acidophilus more firmly attached to the culture plate, and a higher number of cells were present compared to cells cultured in the absence of L. acidophilus. These results indicate that L. acidophilus increases MS74 cell proliferation and viability, suggesting that lactobacilli may contribute to the healthy environment for vaginal epithelial cells.

A Study on a Home Teaching Method to Prevent Slow Learner in Elementary School Mathematics (수학 학습부진아 예방을 위한 가정학습 효율화 방안 연구)

  • 이영하;박희연
    • The Mathematical Education
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    • v.40 no.2
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    • pp.195-215
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    • 2001
  • The purpose of this paper is to present a specific set of home teaching methods in hopes to prevent slow learner of the elementary mathematics. This paper deals with the number and operations, one of five topics in the elementary mathematics A survey of two hundred elementary school teachers was made to see the teacher's opinions of the role of home studying and to concretize the contents of the research topics. There were asked which is the most essential contents for the concrete loaming and which is the most difficult monad that might cause slow leaner. And those were found to be; counting, and arithmetic operations(addition and subtraction) of one or two-digit numbers and multiplication and their concepts representations and operations(addition and subtraction) of fractions. The home teaching methods are based on the situated learning about problem solving in real life situations and on the active teaming which induces children's participation in the process of teaching and learning. Those activities in teaching each contents are designed to deal with real objects and situations. Most teaching methods are presented in the order of school curriculum. To teach the concepts of numbers and the place value, useful activities using manipulative materials (Base ten blocks, Unifix, etc.) or real objects are also proposed. Natural number's operations such as addition, subtraction and multiplication are subdivided into small steps depending upon current curriculum, then for understanding of operational meaning and generalization, games and activities related to the calculation of changes are suggested. For fractions, this paper suggest 10 learning steps, say equivalent partition, fractional pattern, fractional size, relationship between the mixed fractions and the improper fraction, identifying fractions on the number line, 1 as a unit, discrete view point of fractions, comparison of fractional sizes, addition and subtraction, quantitative concepts. This research basically centers on the informal activities of kids under the real-life situation because such experiences are believed to be useful to prevent slow learner. All activities and learnings in this paper assume children's active participation and we believe that such active and informal learning would be more effective for learning transfer and generalization.

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Assessment of neovascularization during bone healing using contrast-enhanced ultrasonography in a canine tibial osteotomy model: a preliminary study

  • Jeon, Sunghoon;Jang, Jaeyoung;Lee, Gahyun;Park, Seungjo;Lee, Sang-kwon;Kim, Hyunwook;Choi, Jihye
    • Journal of Veterinary Science
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    • v.21 no.1
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    • pp.10.1-10.12
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    • 2020
  • Blood perfusion of skeletal muscle and callus was evaluated using contrast-enhanced ultrasonography (CEUS) in a canine osteotomy model to determine the applicability of CEUS in the assessment of neovascularization during fracture healing and to compare the vascular signals on CEUS between external skeletal fixation and cast-applied dogs. In 6 Beagle dogs, a simple transverse osteotomy was performed at the left tibial shaft and external skeletal fixation (n = 3) or a cast (n = 3) was applied. Radiography, power Doppler ultrasonography (power Doppler), and CEUS were performed until complete union was achieved. On CEUS, vascular changes were quantitatively evaluated by measuring peak intensity (PI) and time to PI in the soft tissue and callus and by counting the vascular signals. Vascular signals from the soft tissue were detected on power Doppler and CEUS on day 2. Significantly more vascular signals were detected by CEUS than by power Doppler. On CEUS, PI in the surrounding soft tissue was markedly increased after the fracture line appeared indistinctively changed on radiography in all dogs. In the cast-applied dogs, vascular signals from the periosteal and endosteal callus were detected on CEUS before mineralized callus was observed on radiography. CEUS was useful in assessing the vascularity of soft tissue and callus, particularly in indirect fracture healing, and provided indications of a normally healing fracture.

Effects of Leptin on Osteoclast Generation and Activity

  • Ko, Seon-Yle;Cho, Sang-Rae;Kim, Se-Won;Kim, Jung-Keun
    • International Journal of Oral Biology
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    • v.30 no.2
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    • pp.47-57
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    • 2005
  • Leptin, the product of the obese gene, is a circulating hormone secreted primarily from adipocytes. Several results suggest that leptin is important mediators of bone metabolism. The present study was undertaken to determine the effects of leptin on anti-osteoclastogenesis using murine precursors cultured on Ca-P coated plates and on the production of osteoprotegerin (OPG) in osteoblastic cells. Additionally, this study examined the possible involvement of prostaglandin $E_2\;(PGE_2)$/protein kinase C (PKC)-mediated signals on the effect of leptin on anti-osteoclastogenesis to various culture systems of osteoclast precursors. Osteoclast generation was determined by counting tartrate-resistant acid phosphatase positive [TRAP (+)] multinucleated cells (MNCs). Osteoclastic activity was determined by measuring area of resorption pits formed by osteoclasts on Ca-P coated plate. The number of 1,25-dihydroxycholecalciferol $(1,25[OH]_2D_3)$- or $PGE_2$-induced TRAP (+) MNCs in the mouse bone marrow cell culture decreased significantly after treatment with leptin. The number of receptor activator of NF-kB ligand (RANKL)-induced TRAP (+) MNCs in M-CSF dependent bone marrow macrophage (MDBM) cell or RAW264.7 cell culture decreased significantly with leptin treatment. Indomethacin inhibited osteoclast generation induced by $1,25[OH]_2D_3$ and dexamethasone, however, no significant differences were found in the leptin treated group when compared to the corresponding indomethacin group. Phorbol 12-myristate 13-acetate (PMA), a PKC activator, inhibited osteoclast generation induced by $1,25[OH]_2D_3$. The number of TRAP (+) MNCs decreased significantly with treatment by PMA at concentrations of 0.01 and $0.1{\mu}M$ in culture. Leptin inhibited PMA-mediated osteoclast generation. Isoquinoline-5-sulfonic 2-methyl-1-piperazide dihydrochloride (H7) had no effect on osteoclast generation induced by $1,25[OH]_2D_3$. Cell culture treatment with leptin resulted in no significant differences in osteoclast generation compared to the corresponding H7 group. Indomethacin showed no significant effect on TRAP (+) MNCs formation from the RAW264.7 cell line. PMA inhibited TRAP (+) MNCs formation induced by RANKL in the RAW264.7 cell culture. H7 had no effect on osteoclast generation from the RAW264.7 cell line. There was no difference compared with the corresponding control group after treatment with leptin. $1,25[OH]_2D_3$- or $PGE_2$-induced osteoclastic activity decreased significantly with leptin treatment at a concentration of 100 ng/ml in mouse bone marrow cell culture. Indomethacin, PMA, and H7 significantly inhibited osteoclastic activity induced by $1,25[OH]_2D_3$ in mouse bone marrow cell culture. No significant differences were found between the leptin treated group and the corresponding control group. The secretion of OPG, a substance known to inhibit osteoclast formation, was detected from the osteoblasts. Treatment by leptin resulted in significant increases in OPG secretion by osteoblastic cells. Taken these results, leptin may be an important regulatory cytokines within the bone marrow microenvironment.

Reduction of Patient Dose in Radiation Therapy for the Brain Tumors by Using 2-Dimensional Vertex or Oblique Vertex Beam Technique

  • Kim, Il-Han;Chie, Eui-Kyu;Park, Charn-Il
    • Journal of Radiation Protection and Research
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    • v.28 no.3
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    • pp.225-231
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    • 2003
  • Up-front irradiation technique as 3-dimensional conformation, or intensity modulation has kept large proportion of brain tumors from being complicated with acute radiation reactions in the normal tissue during or shortly after radiotherapy. For years, we've cannot help but counting on 2-D vertex beam technique to reduce acute reactions in the brain tumor patients because we're not equipped with 3-dimensional planning system. We analyzed its advantages and limitations in the clinical application. From 1998 to 2001, vertex or oblique vertex beams were applied to 35 patients with primary brain tumor and 25 among them were eligible for this analysis. Vertex(V) plans were optimized on the reconstructed coronal planes. As the control, we took the bilateral opposed techniques(BL) otherwise being applied. We compared the volumes included in 105% to 50% isodose lines of each plan. We also measured the radiation dose at various extracranial sites with TLD. With vertex techniques, we reduced the irradiated volumes of contralateral hemisphere and prevented middle ear effusion at contralateral side. But the low dose volume increased outside 100%; the ratio of V to BL in irradiated volume included in 100%, 80%, 50% was 0.55+/-0.10, 0.61+/-0.10, and 1.22+/-0.21, respectively. The hot area within 100% isodose line almost disappeared with vertex plan; the ratio of V to BL in irradiated volume included in 103%, 105%, 108% was 0.14+/-0.14, 0.05./-0.17, 0.00, respectively. The dose distribution within 100% isodose line became more homogeneous; the ratio of volume included in 103% and 105% to 100% was 0.62+/-0.14 and 0.26+/-0.16 in BL whereas was 0.16+/-0.16 and 0.02+/-0.04 in V. With the vertex techniques, extracranial dose increased up to $1{\sim}3%$ of maximum dose in the head and neck region except submandibular area where dose ranged 1 to 21%. From this data, vertex beam technique was quite effective in reduction of unnecessary irradiation to the contralateral hemispheres, integral dose, obtaining dose homogeneity in the clinical target. But it was associated with volume increment of low dose area in the brain and irradiation toward the head and neck region otherwise being not irradiated at all. Thus, this 2-D vertex technique can be a useful quasi-conformal method before getting 3-D apparatus.

Comparison of Parallel and Fan-Beam Monochromatic X-Ray CT Using Synchrotron Radiation

  • Toyofuku, Fukai;Tokumori, Kenji;Kanda, Shigenobu;Ohki, Masafumi;Higashida, Yoshiharu;Hyodo, Kazuyuki;Ando, Masami;Uyama, Chikao
    • Proceedings of the Korean Society of Medical Physics Conference
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    • 2002.09a
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    • pp.407-410
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    • 2002
  • Monochromatic x-ray CT has several advantages over conventional CT, which utilizes bremsstrahlung white x-rays from an x-ray tube. There are several methods to produce such monochromatic x-rays. The most popular one is crystal diffraction monochromatization, which has been commonly used because of the fact that the energy spread is very narrow and the energy can be changed continuously. The alternative method is the use of fluorescent x-ray, which has several advantages such as large beam size and fast energy change. We have developed a parallel-beam and a fan-beam monochromatic x-ray CT, and compared some characteristics such as accuracy of CT numbers between those systems. The fan beam monochromatic x-rays were generated by irradiating target materials by incident white x-rays from a bending magnet beam line NE5 in 6.5 GeV Accumulation Ring at Tukuba. The parallel beam monochromatic x-rays were generated by using a silicon double crystal monochromator at the bending magnet beam line BL-20BM in Spring-8. A Cadmium telluride (CdTe) 256 channel array detector with 512mm sensitive width capable of operating at room temperature was used in the photon counting mode. A cylindrical phantom containing eight concentrations of gadolinium was used for the fan beam monochromatic x-ray CT system, while a phantom containing acetone, ethanol, acrylic and water was used for the parallel monochromatic x-ray CT system. The linear attenuation coefficients obtained from CT numbers of those monochromatic x-ray CT images were compared with theoretical values. They showed a good agreement within 3%. It was found that the quantitative measurement can be possible by using the fan beam monochromatic x-ray CT system as well as a parallel beam monochromatic X-ray CT system.

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