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Bleomycin Inhibits Proliferation via Schlafen-Mediated Cell Cycle Arrest in Mouse Alveolar Epithelial Cells

  • Jang, Soojin;Ryu, Se Min;Lee, Jooyeon;Lee, Hanbyeol;Hong, Seok-Ho;Ha, Kwon-Soo;Park, Won Sun;Han, Eun-Taek;Yang, Se-Ran
    • Tuberculosis and Respiratory Diseases
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    • v.82 no.2
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    • pp.133-142
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    • 2019
  • Background: Idiopathic pulmonary fibrosis involves irreversible alveolar destruction. Although alveolar epithelial type II cells are key functional participants within the lung parenchyma, how epithelial cells are affected upon bleomycin (BLM) exposure remains unknown. In this study, we determined whether BLM could induce cell cycle arrest via regulation of Schlafen (SLFN) family genes, a group of cell cycle regulators known to mediate growth-inhibitory responses and apoptosis in alveolar epithelial type II cells. Methods: Mouse AE II cell line MLE-12 were exposed to $1-10{\mu}g/mL$ BLM and $0.01-100{\mu}M$ baicalein (Bai), a G1/G2 cell cycle inhibitor, for 24 hours. Cell viability and levels of pro-inflammatory cytokines were analyzed by MTT and enzyme-linked immunosorbent assay, respectively. Apoptosis-related gene expression was evaluated by quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR). Cellular morphology was determined after DAPI and Hoechst 33258 staining. To verify cell cycle arrest, propidium iodide (PI) staining was performed for MLE-12 after exposure to BLM. Results: BLM decreased the proliferation of MLE-12 cells. However, it significantly increased expression levels of interleukin 6, tumor necrosis factor ${\alpha}$, and transforming growth factor ${\beta}1$. Based on Hoechst 33258 staining, BLM induced condensation of nuclear and fragmentation. Based on DAPI and PI staining, BLM significantly increased the size of nuclei and induced G2/M phase cell cycle arrest. Results of qRT-PCR analysis revealed that BLM increased mRNA levels of BAX but decreased those of Bcl2. In addition, BLM/Bai increased mRNA levels of p53, p21, SLFN1, 2, 4 of Schlafen family. Conclusion: BLM exposure affects pulmonary epithelial type II cells, resulting in decreased proliferation possibly through apoptotic and cell cycle arrest associated signaling.

The polarization of labour market and social integration - social integrative law & institutions and labour market policy (노동시장양극화와 사회통합방안 - 사회통합적 법·제도와 노동시장정책을 중심으로)

  • Lee, Ho-Geun
    • 한국사회정책
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    • v.20 no.2
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    • pp.261-304
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    • 2013
  • This article is aiming intensively to analyze the polarizing tendency of labour market and social integration. The polarization of labour market is being regarded as one of the hottest issues not less important than those problems of economic growth, employment, income distribution and national security etc. in the national policy. In this article, we will first follow up the important phenomena of labour market polarization and the background as well as its consequence. Especially, it asks if the present labour policy in the new government which is now being concentrated on the improvement of employment rate(from the present 63% to the 70% in the future) could deserve to diminish the polarization of labour market in korea. At one side, this article makes the special attention on the diversifying tendency of labour market and the various phenomena of fragmentation and segmentation in the labour market according to the forms and types of employment and according to the employee's status as much as the company's size. At the other side, it emphasizes that to overcome the polarization of labour market should require the wide reform from the legal measure to the improvement of the wage system, and the qualification system and the social investment as well as the human resource development. Furthermore, this article stresses the importance of integrative approach between the active market policy and the social policy instead of choosing each policy option, seperatively.

The Effect of PET Scan Time on the Off-Line PET Image Quality in Proton Therapy (양성자 치료에서 영상 획득 시간에 따른 Off Line PET의 효율성 검증)

  • Hong, Gun-Chul;Jang, Joon-Yung;Park, Se-Joon;Cha, Eun-Sun;Lee, Hyuk
    • The Korean Journal of Nuclear Medicine Technology
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    • v.21 no.2
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    • pp.74-79
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    • 2017
  • Purpose Proton therapy can deliver an optimal dose to tumor while reducing unnecessary dose to normal tissue as compared the conventional photon therapy. As proton beams are irradiated into tissue, various positron emitters are produced via nuclear fragmentation reactions. These positron emitters could be used for the dose verification by using PET. However, the short half-life of the radioisotopes makes it hard to obtain the enough amounts of events. The aim of this study is to investigate the effect of off-line PET imaging scan time on the PET image quality. Materials and Methods The various diameters of spheres (D=37, 28, 22 mm) filled with distilled water were inserted in a 2001 IEC body phantom. Then proton beams (100 MU) were irradiated into the center of the each sphere using the wobbling technique with the gantry angle of $0^{\circ}$. The modulation widths of the spread out bragg peak were 16.4, 14.7 and 9.3 cm for the spheres of 37, 28 and 22 mm in diameters respectively. After 5 min of the proton irradiation, the PET images of the IEC body phantom were obtained for 50 min. The PET images with different time courses (0-10 min, 11-20 min, 21-30 min, 31-40 min and 41-50 min) were obtained by dividing the frame with a duration of 10 min. In order to evaluate the off-line PET image quality with the different time courses, the contrast-to-noise ratio (CNR) of the PET image calculated for each sphere. Results The CNRs of the sphere (D=37 mm) were 0.43, 0.42, 0.40, 0.31 and 0.21 for the time courses of 0-10 min, 11-20 min, 21-30 min, 31-40 min and 41-50 min respectively. The CNRs of the sphere (D=28 mm) were 0.36, 0.32, 0.27, 0.19 and 0.09 for the time courses of 0-10 min, 11-20 min, 21-30 min, 31-40 min and 41-50 min respectively. The CNR of 37 mm sphere was decreased rapidly after 30 min of the proton irradiation. In case of the spheres of 28 mm and 22 mm, the CNR was decreased drastically after 20 min of the irradiation. Conclusion The off-line PET imaging time is an important factor for the monitoring of the proton therapy. In case of the lesion diameter of 22 mm, the off-line PET image should be obtained within 25 min after the proton irradiation. When it comes to small size of tumor, the long PET imaging time will be beneficial for the proton therapy treatment monitoring.

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