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Arsenite Acutely Decreases Nitric Oxide Production via the ROS-Protein Phosphatase 1-Endothelial Nitric Oxide Synthase-Thr497 Signaling Cascade

  • Seo, Jungwon;Lee, Jee Young;Sung, Min-Sun;Byun, Catherine Jeonghae;Cho, Du-Hyong;Lee, Hyeon-Ju;Park, Jung-Hyun;Cho, Ho-Seong;Cho, Sung-Jin;Jo, Inho
    • Biomolecules & Therapeutics
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    • v.22 no.6
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    • pp.510-518
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    • 2014
  • Chronic (>24 h) exposure of arsenite, an environmental toxicant, has shown the decreased nitric oxide (NO) production in endothelial cells (EC) by decreasing endothelial NO synthase (eNOS) expression and/or its phosphorylation at serine 1179 ($eNOS-Ser^{1179}$ in bovine sequence), which is associated with increased risk of vascular diseases. Here, we investigated the acute (<24 h) effect of arsenite on NO production using bovine aortic EC (BAEC). Arsenite acutely increased the phosphorylation of $eNOS-Thr^{497}$, but not of $eNOS-Ser^{116}$ or $eNOS-Ser^{1179}$, which was accompanied by decreased NO production. The level of eNOS expression was unaltered under this condition. Treatment with arsenite also induced reactive oxygen species (ROS) production, and pretreatment with a ROS scavenger N-acetyl-L-cysteine (NAC) completely reversed the observed effect of arsenite on $eNOS-Thr^{497}$ phosphorylation. Although protein kinase C (PKC) and protein phosphatase 1 (PP1) were reported to be involved in $eNOS-Thr^{497}$ phosphorylation, treatment with PKC inhibitor, Ro318425, and overexpression of various PKC isoforms did not affect the arsenite-stimulated $eNOS-Thr^{497}$ phosphorylation. In contrast, treatment with PP1 inhibitor, calyculin A, mimicked the observed effect of arsenite on $eNOS-Thr^{497}$ phosphorylation. Lastly, we found decreased cellular PP1 activity in arsenite-treated cells, which was reversed by NAC. Overall, our study demonstrates firstly that arsenite acutely decreases NO production at least in part by increasing $eNOS-Thr^{497}$ phosphorylation via ROS-PP1 signaling pathway, which provide the molecular mechanism underlying arsenite-induced increase in vascular disease.

Correlation between Qi-Stagnation and Pressure Pain Threshold on $CV_{17}$ (Danzhong : 膻中) in Burning Mouth Syndrome Patients - In the Perspective of Quantification of Pressure Pain Threshold on $CV_{17}$ by using Algometer - (구강작열감증후군 환자에서 기울과 전중($CV_{17}$)압통의 상관성 - Algometer를 이용한 전중압통의 정량화 측면에서 -)

  • Kang, Kyung;Kim, Jin-Sung;Seon, Jong-Ki;Son, Ji-Hee;Kim, Ju-Yeon;Jang, Seung-Won;Son, Ji-Young;Lee, Hyun-Ju;Ryu, Bong-Ha
    • The Journal of Internal Korean Medicine
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    • v.33 no.4
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    • pp.498-510
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    • 2012
  • Objectives : This study was designed to find out whether there is a correlation between qi-stagnation score and pressure pain threshold (PPT) on acupuncture point $CV_{17}$ in burning mouth syndrome (BMS) patients. Methods : Thirty BMS patients who newly visited Oral Disease Clinic at the Kyung Hee University Korean Medicine Hospital were surveyed. The subjects were evaluated on age, illness duration, sex, self-assessed severity of BMS, qi-stagnation score, and PPT on 3 acupuncture points ($CV_{17}$, Rt. $SP_9$, Lt. $SP_9$). Results : There was significant correlation between age and PPT on $CV_{17}$ (p=0.005). Therefore, partial correlation analysis with age as control variable was done, and the result showed significant correlation between qi-stagnation score and PPT on $CV_{17}$ (p=0.001). Qi-stagnation diagnostic point by PPT on $CV_{17}$ was suggested as 3.8056 $kg/cm^2$ based on the fact that diagnostic score is 28.50 in the qi-stagnation questionnaire. Furthermore, considering that PPT is effected by age, we could attain qi-stagnation diagnostic equation of PPT on $CV_{17}$, that is suggested as $0.047{\times}(age)+0.848kg/cm^2$. PPT of 3 acupuncture points ($CV_{17}$, Rt. $SP_9$, Lt. $SP_9$) was compared, and the result showed that PPT was significantly lower on $CV_{17}$ (w/Rt $SP_9$: p=0.022, w/Lt. $SP_9$: p=0.012). Also, significance and correlation coefficient with qi-stagnation were higher on $CV_{17}$ (p<0.001, r=-0.620) than Rt. $SP_9$ (p=0.023, r=-0.413) or Lt. $SP_9$ (p=0.014, r=-0.444). Conclusions : The result of this study suggested that PPT on $CV_{17}$, measured quantitatively by algometer, had a strong correlation with qi-stagnation score in BMS patients. Therefore, the study showed that $CV_{17}$ can be a useful acupuncture point in diagnosing qi-stagnation by measuring PPT in BMS patients.

Comparison of Growth Characteristics and Quality of Korean Ginseng (Panax ginseng C.A. Meyer) by Different Shade Materials (해가림자재 종류별 고려인삼의 생육과 품질특성 비교)

  • Seong, Bong-Jae;Lee, Ka-Soon;Han, Seong-Ho;Kim, Sun-Ick;Kim, Gwan-Hou;Lee, Sox-Su;Won, Jun-Yeon;So, Jung D.;Cho, Jin-Woong
    • KOREAN JOURNAL OF CROP SCIENCE
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    • v.59 no.4
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    • pp.505-510
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    • 2014
  • This research investigated growth of ginseng regard to sunshade materials and micro metrological phenomena under the sunshade material to product high quality ginseng. Followings are results of investigation of active ingredient from raw ginseng producted under the sunshade materials. The highest temperature under the sunshade material from June to August was measured from a Three-layered blue and one-layered black polyethylene net (TBOBFN) followed by a aluminium-coated polyethylene sheet (ACPS) and blue polyethylene sheet (BPS). The highest light penetration of $381.7{\mu}mol/s/m^2$ was obtained from the BPS at August, also the temperature was highest at the ginseng field. Growth of above ground part of 2~3 year old ginseng under the ACPS was the highest, followed by the ACPS and the BPS. In case of 4 year old ginseng, the ACPS and the BPS was the same, followed by the TBOBPN. Root length and diameter of 2~3 year old ginseng showed difference among treatments, but 4 year old ginseng was not showed difference. Meanwhile, the highest amount of root of 4 year old ginseng of $896g/m^2$ was obtained from ACPS. The total amount of ginsenocide of 4 year old ginseng under the ACPS was highest, followed by the BPS and the TBOBPN. Chromaticity of ginseng root under the TBOBPN was highest, followed by the ACPS and the BPS.

Diabetes Mellitus and Risk of Colorectal Cancer Mortality in Japan: the Japan Collaborative Cohort Study

  • Tan, Ce;Mori, Mitsuru;Adachi, Yasushi;Wakai, Kenji;Suzuki, Sadao;Suzuki, Koji;Hashimoto, Shuji;Watanabe, Yoshiyuki;Tamakoshi, Akiko
    • Asian Pacific Journal of Cancer Prevention
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    • v.17 no.10
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    • pp.4681-4688
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    • 2016
  • Objective: Our aim was to estimate whether diabetes mellitus (DM) may be associated with an increased risk of colorectal cancer (CRC) mortality in Japan. Methods: The Japan Collaborative Cohort (JACC) Study is a nationwide prospective study, initiated in 1988, which involves 110,585 subjects (age range: from 40 to 79 years; 46,395 males and 64,190 females). Our present analysis population comprised 96,081 (40,510 men and 55,571 women) who provided details on DM history. The questionnaire also included age, sex, weight, height, family history of CRC, smoking, drinking and exercise habits, and education. Cox proportional-hazard regression was used to estimate the hazard ratio (HR). We used SPSS 21 software to analyze all data. Results: Among the participants with DM, we followed up for 71,174 person-years and 640. deaths from CRC were confirmed; and, among the non-diabetic participants, 785 CRC deaths were identified during 1,499,324 person-years. After adjusting for multivariate confounding factors, such as age, sex, body mass index (BMI), family history of colorectal cancer, smoking habit, drinking habit, physical activity (sports and walking) and education, DM was associated with an increased risk of CRC death (HR 1.4, 95% confidence interval [CI] 1.0-2.0). Diabetic women, but not diabetic men, experienced increased mortality from CRC (HR 1.7, 95% CI 1.0-3.0). Conclusion: The risk of CRC mortality is significantly increased in both sexes and women with diabetes, but no significant increase was seen for diabetic men among Japanese.

Proliferation and Functional Activity of Human Adipose Tissue-Derived CD146 Positive Endothelial Cells According to Culture Mediums (배지 성분에 따른 인간 지방조직기원 CD146 양성 혈관내피세포의 증식 및 기능의 평가)

  • Park, Bong-Wook;Hah, Young-Sool;Kim, Jin-Hyun;Cho, Hee-Young;Jung, Myeong-Hee;Kim, Deok-Ryong;Kim, Shin-Won;Kim, Uk-Kyu;Kim, Jong-Ryoul;Byun, June-Ho
    • Maxillofacial Plastic and Reconstructive Surgery
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    • v.32 no.6
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    • pp.504-510
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    • 2010
  • Purpose: This study was to examine the proliferation and function of the adipose tissue-derived endothelial cells according to different culture medium conditions. Materials and Methods: Adipose tissue-derived CD146 positive endothelial cells were cultured in according to different culture mediums (DMEM culture medium with or without osteogenic inductive agents and EBM-2 culture medium with or without osteogenic inductive agents). The proliferation and function of the adipose tissue-derived endothelial cells was examined in different culture medium conditions. Results: Adipose tissue-derived endothelial cells formed tube-like structures on Matrigel in EBM-2 culture medium with or without osteogenic inductive agents. However, the cells did not form tube-like structures on Matrigel in DMEM medium with or without osteogenic inductive agents. After 24 hours of culture, among the culture medium using EBM-2, the proliferation of the cells were promoted in EBM-2 medium without osteogenic inductive agents than in EBM-2 medium with osteogenic inductive agents. However, 72 hours of culture, the proliferation of the cells were promoted in EBM-2 medium with osteogenic inductive agents than in EBM-2 medium without osteogenic inductive agents. Conclusion: These results suggest that the proliferation and function of the adipose tissue-derived CD146 positive endothelial cells could be maintained in EBM-2 with osteogenic inductive agents.

Analysis and Survey for Contamination of Deoxynivalenol and Zearalenone in Feed by High Performance Liquid Chromatography (HPLC를 이용한 사료 중 Deoxynivalenol, Zearalenone의 분석과 오염도 조사)

  • Kim, Dong-Ho;Choi, Kyu-Il;Hong, Kyung-Suk;Kim, Hyun-Jung;Song, Yeong-Jin;Gang, Seung-Hun;Jang, Han-Sub;Cho, Hyun-Jung;Han, Gye-Su
    • Journal of Food Hygiene and Safety
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    • v.26 no.3
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    • pp.214-221
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    • 2011
  • Deoxynivalenol (DON) and zearalenone (ZEN) are mainly contaminated mycotoxins in feeds. The study was carried out to analyze and survey the contamination of DON and ZEN in one hundred thirteen samples of feeds. After cleaning all samples with immunoaffinity column, the mycotoxins were analysed by using high performance liquid chromatography/fluorescence with diode array detector (HPLC/FLD with DAD). The average recoveries of DON were 88.76 and 95.40% at the levels of 200 and 1,000 ${\mu}g/kg$ and 87.09 and 98.40% of ZEN were recovered at the levels of 100 and 500 ${\mu}g/kg$, respectively. The limit of detection (LOD) were 6.0 and 3.0 ${\mu}g/kg$ for DON and ZEN, respectively. The average concentrations of DON were 372.1, 324.0 and 990.9 ${\mu}g/kg$ in chicken, pig and cattle feed, respectively. Those of ZEN were 76.1, 43.7 and 196.2 ${\mu}g/kg$ for them, individually.

Comparison of Supply Costs, Contamination Rates and Convenience between Dopamine Premixed and Prefilled Systems (Dopamine Premixed System과 Prefilled System사용에 대한 경제성, 오염률, 사용편리성의 비교연구)

  • Oh, Yun Kyoung;Min, Myungh Sook;In, Yang Won;Choi, Kyung Eob;Sung, Young Hee;Cho, Young Ae;Oui, Mi Sook;Bok, Hae Sook;Suh, Gee Young
    • Korean Journal of Clinical Pharmacy
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    • v.13 no.2
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    • pp.82-90
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    • 2003
  • Dopamine is an effective pressor for the treatment of shock and hypotension when patients do not respond to plasma volume expansion. Two dopamine intravenous delivery systems are currently available in Korea. The objective of this study was to compare dopamine premixed with prefilled system in terms of supply costs (preparation costs + personnel time), contamination rates and convenience. Time-and-motion studies were conducted to determine the time and costs associated with preparation and administration of the two systems. They were analyzed and compared by Mann-Whitney test. To evaluate the contaminaton rates of the two systems, both systems were prepared in an open environment similar to that of practical situations. Premixed and compounded solutions were then filtered by $0.22{\mu}m$ membrane filters, which were cultured at $37^{\circ}C$ for 10 days and their contents were visually checked for bacterial contamination. The convenience of the two systems was compared by itemized user assessments on preparation, dose calculation, admixture, administration and disposal of waste matters. They were analyzed by Wilcoxon's signed rank test and 100 part percentage. It was found that the preparation costs $(mean{\pm}SD)$ for premixed and prefilled systems were $271.70\pm293.55\;Won$ (Korean currency) and $1521.04\pm510.63\;Won$, respectively. The preparation time $(mean{\pm}SD)$ for premixed system was $68.10\pm35.69\;sec.$ while at for prefilled system was $154.03\pm50.06\;sec.$ (n=59 each, p<0.001). No bacterium was observed in the samples of both systems (n=20, each). User assessments indicated that the premixed system was more convenient than the prefilled system except for the item of dose calculation (n=24, p<0.001). Subjective evaluations have proven that the use of the dopamine premixed system resulted in increased efficiency of intravenous preparation by allowing personnel to devote more time to other labor-intensive duties and lower total medical costs.

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Expression of Functional Pentameric Heat-Labile Enterotoxin B Subunit of Escherichia coli in Saccharomyces cerevisiae

  • Lim, Jung-Gu;Kim, Jung-Ae;Chung, Hea-Jong;Kim, Tae-Geum;Kim, Jung-Mi;Lee, Kyung-Ryul;Park, Seung-Moon;Yang, Moon-Sik;Kim, Dae-Hyuk
    • Journal of Microbiology and Biotechnology
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    • v.19 no.5
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    • pp.502-510
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    • 2009
  • Although the Escherichia coli heat-labile enterotoxin B subunit (LTB) has already been expressed in several different systems, including prokaryotic and eukaryotic organisms, studies regarding the synthesis of LTB into oligomeric structures of pentameric size in the budding yeast Saccharomyces cerevisiae have been limited. Therefore, this study used a functional signal peptide of the amylase 1A protein from rice to direct the yeast-expressed LTB towards the endoplasmci reticulum to oligomerize with the expected pentameric size. The expression and assembly of the recombinant LTB were confirmed in both the cell-free extract and culture media of the recombinant strain using a Western blot analysis. The binding of the LTB pentamers to intestinal epithelial cell membrane glycolipid receptors was further verified using a GM1-ganglioside enzyme-linked inmmunosorbent assay (GM1-ELISA). On the basis of the GM1-ELISA results, pentameric LTB proteins comprised approximately 0.5-2.0% of the total soluble proteins, and the maximum quantity of secreted LTB was estimated to be 3 mg/l after a 3-day cultivation period. Consequently, the synthesis of LTB monomers and their assembly into biologically active aligomers in a recombinant S. cerevisiae strain demonstrated the feasibility of using a GRAS microorganism-based adjuvant, as well as the development of carriers against mucosal disease.

Functional RsaI/PstI Polymorphism in Cytochrome P450 2E1 Contributes to Bladder Cancer Susceptibility: Evidence from a Meta-analysis

  • Deng, Xiao-Dong;Gao, Qin;Zhang, Bo;Zhang, Li-Xia;Zhang, Wei;Er, Zhe-Er Mu;Xie, Ying;Ma, Ying;Liu, Yun
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.12
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    • pp.4977-4982
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    • 2014
  • Background: Cytochrome P450 2E1 (CYP2E1) might be involved in the development of bladder cancer. However, previous studies of any association between CYP2E1 RsaI/PstI polymorphism and bladder cancer risk have yielded conflicting results. In this study, we performed a more precise estimation of the relationship by a meta-analysis based on the currently available evidence from the literature. Method: To assess the effect of CYP2E1 RsaI/PstI polymorphism on bladder cancer susceptibility, a meta-analysis of 6 available studies with 1,510 cases and 1,560 controls were performed through Feb 2014. Summary odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were used to estimate the strength of association for CYP2E1 RsaI/PstI polymorphism under different genetic models. Results: When available studies were pooled into the meta-analysis, we found that the C1C2 and C2C2 genotypes of CYP2E1 RsaI/PstI polymorphism significantly decreased bladder cancer risk under different genetic models (heterozygote: OR=0.766, 95%CI=0.613-0.957, $P_{OR}$=0.019; homozygote: OR=0.51, 95%CI=0.303-0.858, $P_{OR}$=0.011; dominant: OR=0.733, 95%CI=0.593-0.905, $P_{OR}$=0.004; recessive: OR=0.565, 95%CI=0.337-0.947, $P_{OR}$=0.030). Subgroup analysis indicated that C2C2 genotype was significantly associated with decreased bladder cancer risk under the homozygote genetic model in Caucasians. There was no evidence of heterogeneity or publication bias. Conclusions: The current meta-analysis suggested that the CYP2E1 RsaI/PstI polymorphism might be associated with bladder cancer susceptibility, especially in Caucasians. Further studies are needed to validate the above conclusion.

Application of coagulation pretreatment for enhancing the performance of ceramic membrane filtration (세라믹 막여과의 성능향상을 위한 응집 전처리의 적용)

  • Kang, Joon-Seok;Song, Jiyoung;Park, Seogyeong;Jeong, Ahyoung;Lee, Jeong-Jun;Seo, Inseok;Chae, Seonha;Kim, Seongsu;Kim, Han-Seung
    • Journal of Korean Society of Water and Wastewater
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    • v.31 no.6
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    • pp.501-510
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    • 2017
  • In this study, it is estimated that ceramic membrane process which can operate stably in harsh conditions replacing existing organic membrane connected with coagulation, sedimentation etc.. Jar-test was conducted by using artificial raw water containing kaolin and humic acid. It was observed that coagulant (A-PAC, 10.6%) 4mg/l is the optimal dose. As a results of evaluation of membrane single filtration process (A), coagulation-membrane filtration process (B) and coagulation-sedimentation-membrane filtration process (C), TMP variation is stable regardless of in Flux $2m^3/m^2{\cdot}day$. But in Flux $5m^3/m^2{\cdot}day$, it show change of 1-89.3 kpa by process. TMP of process (B) and (C) is increased 11.8, 0.6 kpa each. But, the (A) showed the greatest change of TMP. When evaluate (A) and (C) in Flux $10m^3/m^2{\cdot}day$, TMP of (A) stopped operation being exceeded 120 kpa in 20 minutes. On the other hand, TMP of (C) is increased only 3 kpa in 120 minutes. Through this, membrane filtration process can be operated stably by using the linkage between the pretreatment process and the ceramic membrane filtration process. Turbidity of treated water remained under 0.1 NTU regardless of flux condition and DOC and $UV_{254}$ showed a removal rate of 65-85%, 95% more each at process connected with pretreatment. Physical cleaning was carried out using water and air of 500kpa to show the recovery of pollutants formed on membrane surface by filtration. In (A) process, TMP has increased rapidly and decreased the recovery by physical cleaning as the flux rises. This means that contamination on membrane surface is irreversible fouling difficult to recover by using physical cleaning. Process (B) and (C) are observed high recovery rate of 60% more in high flux and especially recovery rate of process (B) is the highest at 95.8%. This can be judged that the coagulation flocs in the raw water formed cake layer with irreversible fouling and are favorable to physical cleaning. As a result of estimation, observe that ceramic membrane filtration connected with pretreatment improves efficiency of filtration and recovery rate of physical cleaning. And ceramic membrane which is possible to operate in the higher flux than organic membrane can be reduce the area of water purification facilities and secure a stable quantity of water by connecting the ceramic membrane with pretreatment process.