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Analysis of Global Gene Expression Profile of Human Adipose Tissue Derived Mesenchymal Stem Cell Cultured with Cancer Cells (암세포주와 공동 배양된 인간 지방 조직 유래 중간엽 줄기 세포의 유전자 발현 분석)

  • Kim, Jong-Myung;Yu, Ji-Min;Bae, Yong-Chan;Jung, Jin-Sup
    • Journal of Life Science
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    • v.21 no.5
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    • pp.631-646
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    • 2011
  • Mesenchymal stem cells (MSC) are multipotent and can be isolated from diverse human tissues including bone marrow, fat, placenta, dental pulp, synovium, tonsil, and the thymus. They function as regulators of tissue homeostasis. Because of their various advantages such as plasticity, easy isolation and manipulation, chemotaxis to cancer, and immune regulatory function, MSCs have been considered to be a potent cell source for regenerative medicine, cancer treatment and other cell based therapy such as GVHD. However, relating to its supportive feature for surrounding cell and tissue, it has been frequently reported that MSCs accelerate tumor growth by modulating cancer microenvironment through promoting angiogenesis, secreting growth factors, and suppressing anti-tumorigenic immune reaction. Thus, clinical application of MSCs has been limited. To understand the underlying mechanism which modulates MSCs to function as tumor supportive cells, we co-cultured human adipose tissue derived mesenchymal stem cells (ASC) with cancer cell lines H460 and U87MG. Then, expression data of ASCs co-cultured with cancer cells and cultured alone were obtained via microarray. Comparative expression analysis was carried out using DAVID (Database for Annotation, Visualization and Integrated Discovery) and PANTHER (Protein ANalysis THrough Evolutionary Relationships) in divers aspects including biological process, molecular function, cellular component, protein class, disease, tissue expression, and signal pathway. We found that cancer cells alter the expression profile of MSCs to cancer associated fibroblast like cells by modulating its energy metabolism, stemness, cell structure components, and paracrine effect in a variety of levels. These findings will improve the clinical efficacy and safety of MSCs based cell therapy.

The Properties of Beam Intensity Scanner (BInS) for Dose Verification in Intensity Modulated Radiation Therapy (방사선 세기 조절 치료에서 선량을 규명하는 데 사용된 BlnS System의 특성)

  • 박영우;박광열;박경란;권오현;이명희;이병용;지영훈;김근묵
    • Progress in Medical Physics
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    • v.15 no.1
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    • pp.1-8
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    • 2004
  • Patient dose verification is one of the most Important responsibilities of the physician in the treatment delivery of radiation therapy. For the task, it is necessary to use an accurate dosimeter that can verify the patient dose profile, and it is also necessary to determine the physical characteristics of beams used in intensity modulated radiation therapy (IMRT) The Beam Intensity Scanner (BInS) System is presented for the dosimetric verification of the two dimensional photon beam. The BInS has a scintillator, made of phosphor Terbium-doped Gadolinium Oxysulphide (Gd$_2$O$_2$S:Tb), to produce fluorescence from the irradiation of photon and electron beams. These fluoroscopic signals are collected and digitized by a digital video camera (DVC) and then processed by custom made software to express the relative dose profile in a 3 dimensional (3D) plot. As an application of the BInS, measurements related to IWRT are made and presented in this work. Using a static multileaf collimator (SMLC) technique, the intensity modulated beam (IMB) is delivered via a sequence of static portals made by controlled leaves. Thus, when static subfields are generated by a sequence of abutting portals, the penumbras and scattered photons of the delivered beams overlap in abutting field regions and this results in the creation of “hot spots”. Using the BInS, inter-step “hot spots” inherent in SMLC are measured and an empirical method to remove them is proposed. Another major MLC technique in IMRT, the dynamic multileaf collimator (DMLC) technique, has different characteristics from SMLC due to a different leaf operation mechanism during the irradiation of photon and electron beams. By using the BInS, the actual delivered doses by SMLC and DMLC techniques are measured and compared. Even if the planned dose to a target volume is equal in our experimental setting, the actual delivered dose by DMLC technique is measured to be larger by 14.8% than that by SMLC, and this is due to scattered photons and contaminant electrons at d$_{max}$.

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Effect of Moutan Cortex Radicis on gene expression profile of differentiated PC12 rat cells oxidative-stressed with hydrogen peroxide (모단피의 PC12 cell 산화억제 효과 및 neuronal 유전자 발현 profile 분석에 대한 연구)

  • Kim Hyun Hee;Rho Sam Woong;Na Youn Gin;Bae Hyun Su;Shin Min Kyu;Kim Chung Suk;Hong Moo Chang
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.17 no.2
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    • pp.529-541
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    • 2003
  • Yukmijihwang-tang has been widely used as an and-aging herbal medicine for hundred years in Asian countries. Numerous studies show that Yukmijihwangtang has anti-oxidative effect both in vivo and in vitro. It has been reported that Moutan Cortex Radicis extract (MCR) was the most effective herb in Yukmijihwang-tang on undifferentiated PC12 cells upon oxidative-stressed with hydrogen peroxide. The purpose of this study is to; 1) evaluate the recovery of neuronal damage by assessing the anti-oxidant effect of MCR on PC12 cells differentiated with nerve growth factor (NGF), 2) identify candidate genes responsible for anti-oxidative effect on differentiated PC12 cells by oligonucleotide chip microarray. PC12 cells, which were differentiated by treating with NGF, were treated without or with hydrogen peroxide in the presence or absence of various concentration of MCR. Cell survival was determined by using MTS assay. Measurement of intracellular reactive oxygen species (ROS) generation was determined using the H2DCFDA assay The viability of cells treated with MCR was significantly recovered from stressed PC12 cell. In addition, wide rage of concentrations of MCR shows dose-dependent inhibitory effect on ROS production in oxidative-stressed cells. Total RNAs of cells without treatment(Control group), only treated with H₂O₂ (stressed group) and treated with both H₂O₂ and of MCR (MCR group) were isolated, and cDNAs was synthesized using oligoT7(dT) primer. The fragmented cRNAs, synthesized from cDNAs, were applied to Affymetrix GeneChip Rat Neurobiology U34 Array. mRNA of Calcium/calmodulin-dependent protein kinase II delta subunit(CaMKII), neuron glucose transporter (GLUT3) and myelin/oligodendrocyte glycoprotein(MOG) were downregulated in Stressed group comparing to Control group. P2X2-5 receptor (P2X2R-5), P2X2-4 receptor (P2X2R-4), c-fos, 25 kDa synaptosomal attachment protein(SNAP-25a) and GLUT3 were downregulated, whereas A2 adenosine receptor (A2AR), cathechol-O-methyltransferase(COMT), glucose transporter 1 (GLUT1), EST223333, heme oxygenase (HO), VGF, UI-R-CO-ja-a-07-0-Ul.s1 and macrophage migration inhibitory factor (MIF) were upregulated in MCA group comparing to Control group. Expression of Putative potassium channel subunit protein (ACK4), P2X2A-5, P2X2A-4, Interferon-gamma inducing factor isoform alpha precursor (IL-18α), EST199031, P2XR, P2X2 purinoceptor isoform e (P2X2R-e), Precursor interleukin 18 (IL-18) were downregulated, whereas MOO, EST223333, GLUT-1, MIF, Neuronatin alpha, UI-R-C0-ja-a-07-0-Ul.s1, A2. adenosine receptor, COMT, neuron-specific enolase (NSE), HO, VGF, A rat novel protein which is expressed with nerve injury (E12625) were upregulated in MCR group comparing to Stressed group. The results suggest that decreased viability and AOS production of PC12 cell by H₂O₂ may be, at lease, mediated by impaired glucose transporter expression. It is implicated that the MCR treatment protect PC12 cell from oxidative stress via following mechanisms; improving glucose transport into the cell, enhancing expression of anti-oxidative genes and protecting from dopamine cytotoxicity by increment of COMT and MIF expression. The list of differentially expressed genes may implicate further insight on the action and mechanism behind the anti-oxidative effects of herbal extract Moutan Cortex Radicis.

Replicative Senescence of Periodontal Fibroblasts Induces the Changes in Gene Expression Pattern

  • Yi, Tac-Ghee;Jun, Ji-Hae;Min, Byung-Moo;Kim, Moon-Kyu;Kim, Gwan-Shik;Baek, Jeong-Hwa
    • International Journal of Oral Biology
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    • v.32 no.1
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    • pp.35-43
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    • 2007
  • Tooth loss in elderly is mainly caused by alveolar bone loss via severe periodontitis. Although the severity of periodontitis is known to be affected by age, the aging process or the genetic changes during the aging of periodontal tissue cells are not well characterized. In this study, we investigated the effect of in vitro aging on the change of gene expression pattern in periodontal fibroblasts. Gingival fibroblasts (GF) and periodontal ligament fibroblasts (PDL) were obtained from two young patients and replicative senescence was induced by sequential subcultivation. When more than 90% cells were positively stained with senescence-associated ${\beta},-galactosidase$, those cells were regarded as aged cells. In aged GF and PDL, the level of phosphorylated retinoblastoma (RB) and $p16^{INK4A}$ protein was significantly decreased and increased, respectively. However, the protein level of p53 and p21, well known senescence-inducing genes, did not increase in aged GF and PDL. Although $p27^{Kip1}$ and $p15^{INK4B}$, another cyclin-dependent kinase inhibitors, were reported to be involved in replicative senescence of human cells, they were decreased in aged GF and PDL. Because senescent cells showed flattened and enlarged cell shape and are known to have increased focal adhesion, we examined the protein level of several integrins. Aged GF and PDL showed increased protein level of integrin ${\alpha}2$, ${\alpha}v$, and ${\beta}1$. When the gene expression profiles of actively proliferating young cells and aged cells were compared by cDNA microarray of 3,063 genes and were confirmed by reverse transcription-polymerase chain reaction, 7 genes and 15 genes were significantly and commonly increased and decreased, respectively, in aged GF and PDL. Among them, included are the genes that were known to be involved in the regulation of cell cycle, gene transcription, or integrin signaling. The change of gene expression pattern in GF and PDL was minimally similar to that of oral keratinocyte. These results suggest that $p16^{INK4A}/RB$ might be involved in replicative senescence of periodontal fibroblasts and the change of gene expression profile during aging process is cell type specific.

Sol-Gel Synthesis, Crystal Structure, Magnetic and Optical Properties in ZnCo2O3 Oxide

  • Das, Bidhu Bhusan;Barman, Bittesh
    • Journal of the Korean Chemical Society
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    • v.63 no.6
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    • pp.453-458
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    • 2019
  • Synthesis of ZnCo2O3 oxide is performed by sol-gel method via nitrate-citrate route. Powder X-ray diffraction (XRD) study shows monoclinic unit cell having lattice parameters: a = 5.721(1) Å, b = 8.073(2) Å, c = 5.670(1) Å, β = 93.221(8)°, space group P2/m and Z = 4. Average crystallite sizes determined by Scherrer equation are the range ~14-32 nm, whereas SEM micrographs show nano-micro meter size particles formed in ZnCo2O3. Endothermic peak at ~798 K in the Differential scanning calorimetric (DSC) trace without weight loss could be due to structural transformation and the endothermic peak ~1143 K with weight loss is due to reversible loss of O2 in air atmosphere. Energy Dispersive X-ray (EDX) analysis profile shows the presence of elements Zn, Co and O which indicates the purity of the sample. Magnetic measurements in the range of +12 kOe to -12 kOe at 10 K, 77 K, 120 K and at 300 K by PPMS-II Physical Property Measurement System (PPMS) shows hysteresis loops having very low values of the coercivity and retentivity which indicates the weakly ferromagnetic nature of the oxide. Observed X-band EPR isotropic lineshapes at 300 K and 77 K show positive g-shift at giso ~2.230 and giso ~2.217, respectively which is in agreement with the presence of paramagnetic site Co2+(3d7) in the oxide. DC conductivity value of 2.875 ×10-8 S/cm indicates very weakly semiconducting nature of ZnCo2O3 at 300 K. DRS absorption bands ~357 nm, ~572 nm, ~619 nm and ~654 nm are due to the d-d transitions 4T1g(4F)→2Eg(2G), 4T1g(4F)→4T1g(4P), 4T1g(4F)→4A2g(4F), 4T1g(4F)→4T2g(4F), respectively in octahedral ligand field around Co2+ ions. Direct band gap energy, Eg~ 1.5 eV in the oxide is obtained by extrapolating the linear part of the Tauc plot to the energy axis indicates fairly strong semiconducting nature of ZnCo2O3.

DOX-MTX-NPs Augment p53 mRNA Expression in OSCC Model in Rat: Effects of IV and Oral Routes

  • Abbasi, Mehran Mesgari;Khiavi, Monir Moradzadeh;Monfaredan, Amir;Hamishehkar, Hamed;Seidi, Khaled;Jahanban-Esfahlan, Rana
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.19
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    • pp.8377-8382
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    • 2014
  • Background: Oral squamous cell carcinoma (OSCC) is the sixth most common malignancy worldwide. Cancer development and progression require inactivation of tumor suppressor genes and activation of proto-oncogenes. The well recognized mechanism of action demonstrated for chemotherapeutic agents is induction of apoptosis via reactivation of p53. In this context, we evaluate the efficacy of IV and oral routes of our novel PH and temperature sensitive doxorubicin-methotrexate-loaded nanoparticles (DOX-MTX NP) in affecting p53 profile in an OSCC rat model. Methods: In this study, 120 male rats were divided into 8 groups of 15 animals each. The new formulated DOX-MTX NP and free doxorubicin were IV and orally given to rats with 4-nitroquinoline-1-oxide induced OSCC. Results: Results showed that both DOX and DOX-MTX-NP caused significant increase in mRNA levels of P53 compared to the untreated group (p<0.000). With both DOX and DOX-MTX NP, the IV mode was more effective than the oral (gavage) route (p<0.000). Surprisingly, in oral mode, p53 mRNA was not affected in DOX treated groups (p>0.05), Nonetheless, both IV and oral administration of MTX-DOX NP showed superior activity (~3 fold) over free DOX in reactivation of p53 in OSCC (p<0.000). The effectiveness of oral route in group treated with nanodrug accounts for the enhanced bioavailability of nanoparticulated DOX-MTX compared to free DOX. Moreover, in treated groups, tumor stage was markedly related to the amount of p53 mRNA (p<0.05). Conclusion: Both oral and IV application of our novel nanodrug possesses superior activity over free DOX-in up-regulation of p53 in a OSCC model and this increase in p53 level associated with less aggressive tumors in our study. Although, impressive results obtained with IV form of nanodrug (-21 fold increase in p53 mRNA level) but both forms of nanodrug are effective in OSCC, with less toxicity normal cells.

Antioxidant action of soy isoflavones on oxidative stress and antioxidant enzyme activities in exercised rats

  • Yoon, Gun-Ae;Park, Sunmin
    • Nutrition Research and Practice
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    • v.8 no.6
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    • pp.618-624
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    • 2014
  • BACKGROUND/OBJECTIVES: Isoflavones are widely believed to be beneficial to human health, in relation to their antioxidant potentials. Exercise can cause an imbalance between reactive oxygen species (ROS) and antioxidants. This study was conducted in order to investigate the ability of isoflavones in amelioration of oxidative stress induced by exercise. MATERIALS/METHODS: Male Sprague-Dawley rats were assigned to one of four groups: isoflavone-free with no exercise (CON-sd), isoflavone-free with exercise (CON-ex), isoflavone-supplemented with no exercise (ISF-sd), and isoflavone-supplemented with exercise (ISF-ex). Animals exercised on the treadmill for 30 minutes per day, five days per week. TBARS as a marker of oxidative stress and antioxidant enzyme activity, including SOD, GSH-px, and catalase were determined in liver tissue. Serum lipid profile was also examined. RESULTS: A significant effect of isoflavone alone was observed on abdominal fat pad mass. ISF-ex had significantly less abdominal fat pad than CON-ex. Both exercise and isoflavone treatment had significant effects on lowering plasma triglyceride (TG), thus, the ISF-ex group had a significantly lower TG level than the CON-sd group, by 30.9%. However, no differences were observed in plasma cholesterol, HDL-C, and cholesterol/HDL-C ratio. Exercise, isoflavone, and exercise-isoflavone interaction effects were significant on thiobarbituric acid reactive substances (TBARS) (P = 0.001, 0.002, and 0.005, respectively). The CON-ex group showed a higher TBARS level than the other three groups. By contrast, in the ISF-ex group, TBARS was restored to the level of the ISF-sd or CON-sd group. Isoflavone had a significant effect on superoxide dismutase (SOD) (P = 0.022) and catalase activities (P = 0.049). Significantly higher SOD and catalase activities were observed in ISF-ex than CON-ex. SOD and catalase activities showed an inverse pattern of TBARS. Taken together, isoflavones increased the activities of SOD and catalase with concomitant decreases in TBARS, indicative of decreased oxidative stress. CONCLUSIONS: Isoflavone supplementation enhances antioxidant action with attenuation of exercise-induced oxidative stress, as measured by decreases in TBARS, and inhibits body fat accumulation and plasma TG increase. Antioxidative effects ascribed to isoflavones may be partially exerted via enhancement of antioxidant enzyme activities.

A Study on Vulnerability Prevention Mechanism Due to Logout Problem Using OAuth (OAuth를 이용한 로그아웃 문제로 인한 취약점 방지 기법에 대한 연구)

  • Kim, Jinouk;Park, Jungsoo;Nguyen-Vu, Long;Jung, Souhwan
    • Journal of the Korea Institute of Information Security & Cryptology
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    • v.27 no.1
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    • pp.5-14
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    • 2017
  • Many web services which use OAuth Protocol offer users to log in using their personal profile information given by resource servers. This method reduces the inconvenience of the users to register for new membership. However, at the time a user finishes using OAuth client web service, even if he logs out of the client web service, the resource server remained in the login state may cause the problem of leaking personal information. In this paper, we propose a solution to mitigate the threat by providing an additional security behavior check: when a user requests to log out of the Web Client service, he or she can make decision whether or not to log out of the resource server via confirmation notification regarding the state of the resource server. By utilizing the proposed method, users who log in through the OAuth Protocol in the public PC environment like department stores, libraries, printing companies, etc. can prevent the leakage of personal information issues that may arise from forgetting to check the other OAuth related services. To verify our study, we implement a Client Web Service that uses OAuth 2.0 protocol and integrate it with our security behavior check. The result shows that with this additional function, users will have a better security when dealing with resource authorization in OAuth 2.0 implementation.

Comparative Analysis of Effective RCS Prediction Methods for Chaff Clouds (효과적인 채프 구름의 RCS 예측 방법 비교 분석 연구)

  • Kim, Min;Lee, Myung-Jun;Lee, Seong-Hyeon;Park, Sung-ho;Kong, Young-Joo;Woo, Seon-Keol;Kim, Hong-Rak;Kim, Kyung-Tae
    • The Journal of Korean Institute of Electromagnetic Engineering and Science
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    • v.29 no.3
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    • pp.233-240
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    • 2018
  • Radar cross section (RCS) analysis of chaff clouds is essential for the accurate detection and tracking of missile targets using radar. For this purpose, we compare the performance of two existing methods of predicting RCS of chaff clouds. One method involves summing up the RCS values of individual chaffs in a cloud, while the other method predicts the RCS values using aerodynamic models based on the probability density function. In order to compare and analyze the two techniques more precisely, the RCS of a single chaff computer-aided design model consisting of a half wavelength dipole was calculated using the commercial electromagnetic numerical analysis software, FEKO 7.0, to estimate the RCS values of chaff clouds via simulation. Thus, we verified that our method using the probability density distribution model is capable of analyzing the RCS of chaff clouds more efficiently.

Comparison of Optimum Drilling Conditions of Aircraft CFRP Composites using CVD Diamond and PCD Drills (CVD 다이아몬드 및 PCD이 드릴을 이용한 항공용 CFRP 복합재료의 홀 가공성 비교)

  • Kwon, Dong-Jun;Wang, Zuo-Jia;Gu, Ga-Young;Park, Joung-Man
    • Composites Research
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    • v.24 no.4
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    • pp.23-28
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    • 2011
  • Recently CFRP laminate joints process by bolts and nets are developed rapidly in aircraft industries. However, there are serious drawback during jointing process. Many hole processes are needed for the manufacturing and structural applications using composite materials. Generally, very durable polycrystalline crystalline diamond (PCD) drill has been used for the CFRP hole process. However, due to the expensive price and slow process speed, chemical vapor deposition (CVD) diamond drill has been used increasingly which are relatively-low durability but easily-adjustable process speed via drill shape change and price is much lower. In this study, the comparison of hole process between PCD and CVD diamond coated drills was done. First of all, CFRP hole processbility was evaluated using the equations of hole processing conditions (feed amount per blade, feed speed). The comparison on thermal damage occurring from the CFRP specimen was also studied during drilling process. Empirical equation was made from the temperature photo profile being taken during hole process by infrared thermal camera. In addition, hole processability was compared by checking hole inside condition upon chip exhausting state for two drills. Generally, although the PCD can exhibit better hole processability, hole processing speed of CVD diamond drill exhibited faster than PCD case.