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Induction of Apoptosis in FRTL-5 Thyroid Cells by Okadaic Acid (Okadaic Acid에 의한 FRTL-5 갑상선 세포주의 Apoptosis 유도)

  • Cho Ji-Hyoung;Chung Ki-Yong;Park Jong-Wook
    • Korean Journal of Head & Neck Oncology
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    • v.18 no.2
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    • pp.142-149
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    • 2002
  • Objectve : Okadaic acid is a specific inhibitor of serine/threonine protein phosphatase 1 and 2A. In order to know the mechanism of apoptosis induced by okadaic acid, we treated FRTL-5 thyroid cells with okadaic acid and measured the changes of important proteins that are involved in apoptosis. Materials and Methods: We measured caspase 3 activity, $PLC-{\gamma}1$ degradation, the expression of XIAP, cIAP1, cIAP2, and cytochrome c release in okadaic acid-treated FRTL-5 thyroid cells. Results: Okadaic acid-induced caspase 3 activation and $PLC-{\gamma}1$ degradation and apoptosis were dose-dependent with a maximal effect at a concentration of 80 nmol and time-dependent with a maximal effect at 24 hours after treatment. The elevated caspase 3 activity in okadaic acid treated FRTL-5 thyroid cells are correlated with down-regulation of XIAP and cIAP1, but not cIAP2. General and potent inhibitor of caspases, z-VAD-fmk. abolished okadaic acid-induced caspase 3 activity and $PLC-{\gamma}1$ degradation. The release of cytochrome c in okadaic acid-induced FRTL-5 thyroid cells was dose-dependent with a maximal effect at a concentration of 80 nmol. Conclusions: These findings suggest that mechanism of okadaic acid-induced apoptosis is associated with cytochrome c release and increase of caspase 3 activation in FRTL-5 thyroid cells.

Effect of Bu-Zhong-Yi-Qi-Tang on Proliferation of T Cells (보중익기탕의 T세포 증식 유도 효과)

  • 채수연;신성해;하미혜;조성기;김성호;변명우;이성태
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.33 no.7
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    • pp.1085-1091
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    • 2004
  • Bu-Zhong-Yi-Qi- Tang extracts is a traditional oriental medicine in a mixture type exhibiting strong anti-bacterial, analgesic, and chemopreventive activities. In this study, we have evaluated effects of the total and polysaccharide fraction of Bu-Zhong-Yi-Qi- Tang extracts on the T cell proliferation, cytokine production, and induction of IL-2 receptor and MHC class n. For this experiment, we established CD4$^{+}$ CD8$^{[-10]}$ T cell line producing IL-2 and IFN-${\gamma}$ when stimulated with ovalbumin antigen in the presence of antigen presenting cells. The significant effect of Bu-Zhong-Yi-Qi-Tang on antigen-induced T cell proliferation in the presence of antigen presenting cells was observed. The proliferation and IFN-${\gamma}$ production of T cells was increased in a dose dependent manner, and expression of IL-2 receptor on T cells and MHC class n molecule on antigen presenting cells was also induced in the presence of Bu-Zhong-Yi-Qi-Tang polysaccharide fraction. It was demonstrated that polysaccharide fraction of Bu-Zhong-Yi-Qi-Tang stimulates the antigen-induced T cell proliferation and the production of IFN-${\gamma}$ possibly through the increase of IL-2 receptor and MHC class n expression. Therefore Bu-Zhong-Yi-Qi-Tang can be regarded as a natural and useful immunomodulator having a relatively nonotoxic property. Further studies are needed to better characterize the nature of Bu-Zhong- Yi-Qi-Tang extract.

Changes in Microbiological and General Quality Characteristics of Gamma Irradiated Kanjang and Shoyu (감마선을 조사한 간장의 미생물 및 일반품질 특성)

  • Song, Tae-Ho;Kim, Dong-Ho;Park, Byoung-Jun;Shin, Myung-Gon;Byun, Myung-Woo
    • Korean Journal of Food Science and Technology
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    • v.33 no.3
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    • pp.338-344
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    • 2001
  • The effect of gamma-irradiation on the microbiological and general qualities of Kanjang (fermented soy sauce, Korean type) and Shoyu (fermented soy sauce, Japanese type) was studied. Samples were prepared, irradiated at 5, 10 and 20 kGy, and then stored at $25^{\circ}C$ for 18 weeks. The results showed that the Bacillus spp. was inactivated by 3 log cycles with the irradiation dose of 10 kGy and the number of Bacillus cells that survived from 10 to 20 kGy of gamma irradiation was decreased gradually during storage. Yeasts and Lactobacillus were nearly eliminated at 5 to 10 kGy of irradiation. The $D_{10}$ values of Bacillus, yeast and Lactobacillus in Shoyu were 2.67 kGy, 0.81 kGy and 1.30 kGy, in Kanjang were 2.75 kGy, 0.99 kGy and 1.47 kGy, respectively. The general quality of gamma irradiated Shoyu and Kanjang, such as total nitrogen, amino nitrogen, protease activity and pH were more stable than that of control during storage periods. Decolorization was observed just after irradiation, but the color was recovered during storage. The sensory evaluations showed that irradiated samples were more acceptable. Therefore, it was considered that gamma irradiation was effective for maintaining better quality of Shoyu and Kanjang during storage.

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Microstructure and Tensile Deformation Behavior of Ni-Cr-Al Powder Porous Block Material (블록형 Ni-Cr-Al 분말 다공성 소재의 미세조직 및 인장 변형 거동)

  • Kim, Chul-O;Bae, Jung-Suk;Lee, Kee-Ahn
    • Journal of Powder Materials
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    • v.22 no.2
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    • pp.93-99
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    • 2015
  • This study investigated the microstructure and tensile properties of a recently made block-type Ni-Cr-Al powder porous material. The block-type powder porous material was made by stacking multiple layers of powder porous thin plates with post-processing such as additional compression and sintering. This study used block-type powder porous materials with two different cell sizes: one with an average cell size of $1,200{\mu}m$ (1200 foam) and the other with an average cell size of $3,000{\mu}m$ (3000 foam). The ${\gamma}$-Ni and ${\gamma}^{\prime}-Ni_3Al$ were identified as the main phases of both materials. However, in the case of the 1,200 foam, a ${\beta}$-NiAl phase was additionally observed. The relative density of each block-type powder porous material, with 1200 foam and 3000 foam, was measured to be 5.78% and 2.93%, respectively. Tensile tests were conducted with strain rates of $10^{-2}{\sim}10^{-4}sec^{-1}$. The test result showed that the tensile strength of the 1,200 foam was 6.0~7.1 MPa, and that of 3,000 foam was 3.0~3.3 MPa. The elongation of the 3,000 foam was higher (~9%) than that (~2%) of the 1,200 foam. This study also discussed the deformation behavior of block-type powder porous material through observations of the fracture surface, with the results above.

Separation Effect of Rainfall Data Based on Parameter Estimation Methods (매개변수 추정방법에 따른 강우자료의 분리효과)

  • 김경덕;배덕효
    • Water for future
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    • v.29 no.1
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    • pp.129-139
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    • 1996
  • It is very important to select appropriate distributions for hydrological data in planning and designing hydraulic structures. Also, it is necessary to check whether the selected distribution reproduces the statistical characteristics of the real data. In this study, the parameters of the two- and three-parameter gamma, two- and three-parameter lognormal, Gumbel, two- and three-parameter log-Gumbel, GEV, log-Pearsonn type III, two- and three-parameter Weibull, four- and five-parameter Wakeby distributions were estimated for the rainfall data of 22 sites in Korea with 7 different durations based on the methods of moments, probability weighted moments, and maximum likelihood. And the validity conditions were checked for the estimated parameters. The separation effect for each distribution was examined throught 10,000 simulations using the estimated parameters. As results, the separation effect was the smallest: log-Pearson type III for moment method, log-Pearson type III and GEV for probability weighted moment method, and GEV for maximum likelihood method. However, it is large for the two-parameter distributions.

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The Mechanism of Interferon-$\gamma$ Induced Cytotoxicity on the Lung Cancer Cell Line, A549 (인터페론감마에 의한 A549 폐암세포주 세포독성의 기전)

  • Oh, Yeon-Mok;Yoo, Chul-Gyu;Chung, Hee-Soon;Kim, Young-Whan;Han, Sung-Koo;Shim, Young-Soo
    • Tuberculosis and Respiratory Diseases
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    • v.43 no.1
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    • pp.63-68
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    • 1996
  • Background: Interferon-$\gamma$ has various biologic effects, including antiviral effect, antitumor proliferative effect, activation of macrophage and B lymphocyte, and increased expression of major histocompatibility complex. Especially, antitumor proliferative effect of interferon-$\gamma$ has already been proved to be important in vivo as well as in vitro. And, clinical studies of interferon-$\gamma$ have been tried in lung cancer patients. However, the mechanism of antitumor effect of interferon-$\gamma$ has not yet been established despite of many hypotheses. "Necrosis" is a type of cell death which is well known to occur in the circumstances of severe stresses. In contrast, "apoptosis" is another type of cell death which occurs in such biological circumstances as embryonic development, regression of organs, and self-tolerance of lymphocytes. And, apoptosis is an active process of cell death in which cells are dying with fragmentations of their cytoplasms and nuclei. And, in the process of apoptosis the DNAs of cells are cleaved between nucleosomes by unidentified endonuclease and therefore DNAs of apoptotic cells result in a typical electrophoresis pattern known as DNA ladder pattern. Recently it has been suggested that cytotoxic effect of interferon-$\gamma$ occurs via apoptosis. To elucidate the mechanism of antitumor cytotoxic effect of interferon-$\gamma$, we microscopically observed a lung cancer cell line, A549 which was treated with interferon-$\gamma$. We observed A545 treated with interferon-$\gamma$ was dying fragmented. And so, we performed this study to find out that the mechanism of antitumor cytotoxic effect of interferon-$\gamma$ be apoptosis. Method: We treated A549, human lung cancer cell line with various concentration of interferon-$\gamma$ and quantified its cytotoxic effect of various periods, 24 hours, 72 hours and, 120 hours by MTT(dimethylthiazolyl diphenyltetrazolium bromide) bioassay. Also, after we treated A549 with 100 units/mi of interferon-$\gamma$ for 120 hours, we observed the pattern of cell death with inverted microscope and we extracted DNAs from the dead A549 cells and observed the pattern of 1.5% agarose gel electrophoresis with ethidium bromide staining. Result: 1) Cytotoxic effect of interferon-$\gamma$ on A549: For the first 24 hours, threre was little cytotoxic effect and for between 24 hours and 72 hours, there was the beginning of cytotoxic effect and for 120 hours there was increased cytotoxic effect. 2) Pattern of A549 cell death by interferon-$\gamma$: We observed with inverted microscope that A549 cells were dying fragmented. 3) DNA ladder pattern of gel electrophoresis: We observed DNA ladder pattern of gel electrophoresis of extracted DNAs from dead A549 cells. Conclusion: We concluded that the mechanism of interferon-$\gamma$induced cytotoxicity on lung cancer cell line, A549 be via apoptosis.

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The Association of Central Obesity with Type 2 Diabetes among Koreans according to the Serum Gamma-Glutamyltransferase Level: Korean Genome and Epidemiology Study (혈청 Gamma-Glutamyltransferase에 따른 복부비만과 제2형 당뇨병간의 관련성: Korean Genome and Epidemiology Study)

  • Shin, Ji-Yeon;Hwang, Jun-Hyun;Jeong, Jin-Young;Kim, Sung-Hi;Moon, Jai-Dong;Roh, Sang-Chul;Kim, Young-Wook;Kim, Yang-Ho;Leem, Jong-Han;Ju, Young-Su;Hong, Young-Seoub;Ha, Eun-Hee;Lee, Yong-Hwan;Lee, Duk-Hee;Kim, Dong-Hyun
    • Journal of Preventive Medicine and Public Health
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    • v.42 no.6
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    • pp.386-391
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    • 2009
  • Objectives : This cross-sectional study was performed to examine if the serum gamma-glutamyltransferase (GGT) level that is within its normal range is associated with the risk of type 2 diabetes and if the association between the waist hip ratio (WHR) and type 2 diabetes is different depending on the serum GGT levels. Methods : The study subjects were 23,436 persons aged 40 years or older and who participated in regular health check-ups at 11 hospitals (males: 5,821, females: 17,615). The gender-specific quintiles of the serum GGT and WHR were used to examine the associations with type 2 diabetes. Results : The serum GGT levels within their normal range were positively associated with type 2 diabetes only in women. The adjusted odds ratios (ORs) were 1.0, 1.0, 1.4, 2.1, and 2.5 according to the quintiles of the serum GGT ($p_{trend}$<0.01). The WHR was more strongly associated with the prevalence of diabetes among the women with a high-normal serum GGT level as compared with those with a low-normal serum GGT level (p for interaction=0.02). For example, the adjusted ORs for women with a low normal serum GGT level were 1.0, 1.2, 1.5, 2.2, and 2.4 according to the quintiles of the WHR, while those figures were 1.0, 2.4, 3.6, 5.0, and 8.3 among the women with a high normal serum GGT level. However, in men, the serum GGT was very weakly associated with type 2 diabetes and the association between the WHR and type 2 diabetes was not different depending on the serum GGT level. Conclusions : Serum GGT within its normal range was positively associated with type 2 diabetes, and central obesity was more strongly associated with the prevalence of type 2 diabetes when the serum GGT level was highnormal. However, these associations were observed only in women, which is different from the previous findings. The stronger relation between central obesity and type 2 diabetes among women with a high-normal serum GGT level can be useful for selecting a group that is at high risk for type 2 diabetes irregardless of whatever the underlying mechanism is.

Increased Quality Characteristics and Physiological Effects of Chunggukjang Fermented with Bacillus subtilis-SKm (Bacillus subtilis-SKm를 스타터로 이용하여 제조한 청국장의 품질 및 기능성 증진 효과)

  • Zheng, Yanfei;Jeong, Ji-Kang;Choi, Hye-Sun;Park, Kun-Young
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.40 no.12
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    • pp.1694-1699
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    • 2011
  • The quality characteristics and physiological effects of chunggukjang fermented naturally (NF-c), with Bacillus subtilis-SKm (BS-c), with Bacillus subtilis HJ18-4 (BH-c), and with Bacillus subtilis KCCM 42923 (BK-c) were investigated. The characteristics of fermentation were determined by protease, ${\alpha}$-amylase and ${\gamma}$-GTP activities, and additionally the amounts of amino-type and ammonia-type nitrogens. BS-c showed the highest protease, ${\alpha}$-amylase, and ${\gamma}$-GTP activities, and also amino-type nitrogen content among the four types of chunggukjang. The ammonia-type nitrogen content in BS-c was similar to that of BK-c and NF-c. BH-c showed the lowest enzyme activities and amino-type and ammonia-type nitrogen content. BS-c, BH-c, BK-c, and NF-c showed a similar overall acceptability during sensory evaluation. BS-c also showed the strongest DPPH free radical scavenging and anti-proliferative activities in HT-29 human colon carcinoma cells. These results suggested that B. subtilis-SKm was suitable to be used as a starter to enhance the quality and effects of chunggukjang.

A Cannabinoid Receptor Agonist N-Arachidonoyl Dopamine Inhibits Adipocyte Differentiation in Human Mesenchymal Stem Cells

  • Ahn, Seyeon;Yi, Sodam;Seo, Won Jong;Lee, Myeong Jung;Song, Young Keun;Baek, Seung Yong;Yu, Jinha;Hong, Soo Hyun;Lee, Jinyoung;Shin, Dong Wook;Jeong, Lak Shin;Noh, Minsoo
    • Biomolecules & Therapeutics
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    • v.23 no.3
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    • pp.218-224
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    • 2015
  • Endocannabinoids can affect multiple cellular targets, such as cannabinoid (CB) receptors, transient receptor potential cation channel, subfamily V, member 1 (TRPV1) and peroxisome proliferator-activated receptor ${\gamma}$($PPAR{\gamma}$). The stimuli to induce adipocyte differentiation in hBM-MSCs increase the gene transcription of the $CB_1$ receptor, TRPV1 and $PPAR{\gamma}$. In this study, the effects of three endocannabinoids, N-arachidonoyl ethanolamine (AEA), N-arachidonoyl dopamine (NADA) and 2-arachidonoyl glycerol (2-AG), on adipogenesis in hBM-MSCs were evaluated. The adipocyte differentiation was promoted by AEA whereas inhibited by NADA. No change was observed by the treatment of non-cytotoxic concentrations of 2-AG. The difference between AEA and NADA in the regulation of adipogenesis is associated with their effects on $PPAR{\gamma}$ transactivation. AEA can directly activate $PPAR{\gamma}$. The effect of AEA on $PPAR{\gamma}$ in hBM-MSCs may prevail over that on the $CB_1$ receptor mediated signal transduction, giving rise to the AEA-induced promotion of adipogenesis. In contrast, NADA had no effect on the $PPAR{\gamma}$ activity in the $PPAR{\gamma}$ transactivation assay. The inhibitory effect of NADA on adipogenesis in hBM-MSCs was reversed not by capsazepine, a TRPV1 antagonist, but by rimonabant, a $CB_1$ antagonist/inverse agonist. Rimonabant by itself promoted adipogenesis in hBM-MSCs, which may be interpreted as the result of the inverse agonism of the $CB_1$ receptor. This result suggests that the constantly active $CB_1$ receptor may contribute to suppress the adipocyte differentiation of hBM-MSCs. Therefore, the selective $CB_1$ agonists that are unable to affect cellular $PPAR{\gamma}$ activity inhibit adipogenesis in hBM-MSCs.

Peroxisome Proliferator-Activated Receptor-Gamma Pro12Ala Polymorphism Could be a Risk Factor for Gastric Cancer

  • Zhao, Jing;Zhi, Zheng;Song, Guangyao;Wang, Juan;Wang, Chao;Ma, Huijuan;Yu, Xian;Sui, Aixia;Zhang, Hongtao
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.6
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    • pp.2333-2340
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    • 2015
  • Background: Due to the strong inhibitory effects of $PPAR{\gamma}$ gene on the growth of cancer cells, the role of Pro12Ala polymorphism in $PPAR{\gamma}$ gene has been extensively investigated in cancer recently. However, the results were inconsistent according to cancer type. The aim of this study was to comprehensively evaluate the $PPAR{\gamma}$ Pro12Ala polymorphism and gastric cancer susceptibility. Materials and Methods: Search strategies were conducted in Pubmed, Medline (Ovid), Chinese biomedical database (CBM), China national knowledge infrastructure (CNKI), VIP, and Wanfang database, covering all publications, with the last search up to November 01, 2014. The strength of association between $PPAR{\gamma}$ Pro12Ala polymorphism and gastric cancer risk was assessed by OR with 95%CI. Results: A total of 546 cases and 827 controls in 5 case-control studies were included in this meta-analysis. The results indicated that the variant G allele carriers (CG+GG) had a 2.31 times higher risk for gastric cancer when compared with the homozygote CC (odds ratio (OR)=2.31, 95% confidence interval (CI)=1.67-3.21 for CG+GG vs. CC). In the subgroup analysis by ethnicity, significantly elevated risks were both found in Asians (OR=2.56, 95% CI=1.42-4.64) and Caucasians (OR=2.20, 95% CI=1.48-3.25). Similarly, in the subgroup analysis by H. pylori status, a significantly increased risk was identified in H. pylori (+) populations (OR=3.68, 95%CI=2.07-6.52), but not in H. pylori(-) populations (OR=1.17, 95%CI=0.58-2.39). Conclusions: This pooled analysis suggested that the $PPAR{\gamma}$ Pro12Ala polymorphism could be an independent predictive risk factor for gastric cancer especially in H. pylori infected populations in Asians and Caucasians. Nevertheless, prospectively designed cohort studies are needed to further investigate gene-gene and gene-environment interactions to confirm the combined effects of $PPAR{\gamma}$ Pro12Ala polymorphisms and H. pylori infection on gastric cancer risk.