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      • The effects of oxytetracycline on Nitrogen Cycle in a model aquaculture system

        Carl Angelo Medriano,Kartik Chandran,Samir Khanal,Jae Woo Lee(이재우),Sungpyo Kim(김성표) 한국산학기술학회 2014 한국산학기술학회 학술대회 Vol.- No.-

        This study aims to investigate the effects of OTC in the response of a Nitrosomonas europaea, a model nitrifying bacterium. For this aim, the variations of nitrogen species in aquaculture water samples and Nitrosomonas europaea culture, as a function of OTC concentration, have been monitored. As a result, aquaculture samples show the nitrification level is lower by 23% from 5ppm, 43% from 50ppm, and 46% from 100ppm OTC as compared to a control (no added OTC). Also, the addition of 50ppm OTC to Nitrosomonas europaea culture showed 29% lower degradation level compared to a control. As compared to control, the 10ppm OTC showed increased nitrite level by 30% and nitrous oxide level by up to 29% after 80 hrs. RNA expression analysis was able correlate amoA expression to the reduced level of ammonia removal. The hao, nirK, and norB gene expressions did not show correlation to the oxytetracycline concentration, thus suggesting that the dose influenced in other ways perhaps somewhere during post-transcription to enzyme activity

      • Liquid Chromatography Mass Spectrometry-Based Metabolite Pathway Analyses of Myeloma and Non-Hodgkin’s Lymphoma Patients

        Medriano, Carl Angelo D.,Na, Jinhyuk,Lim, Kyung-min,Chung, Jin-ho,Park, Youngja H. Royan Institute 2017 Cell journal (Yakhteh) Vol.19 No.1

        <P><B>Objective</B></P><P> This study attempted to identify altered metabolism and pathways related to non-Hodgkin’s lymphoma (NHL) and myeloma patients. </P><P><B>Materials and Methods</B></P><P> In this retrospective study, we collected plasma samples from 11 patients-6 healthy controls with no evidence of any blood cancers and 5 patients with either multiple myeloma (n=3) or NHL (n=2) during the preliminary study period. Samples were analyzed using quadrupole time-of-flight liquid chromatography mass spectrometry (LC-MS). Significant features generated after statistical analyses were used for metabolomics and pathway analysis.</P><P><B>Results</B></P><P> Data after false discovery rate (FDR) adjustment at q=0.05 of features showed 136 for positive and 350 significant features for negative ionization mode in NHL patients as well as 262 for positive and 98 features for negative ionization mode in myeloma patients. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis determined that pathways such as steroid hormone biosynthesis, ABC transporters, and arginine and proline metabolism were affected in NHL patients. In myeloma patients, pyrimidine metabolism, carbon metabolism, and bile secretion pathways were potentially affected by the disease.</P><P><B>Conclusion</B></P><P>The results have shown tremendous differences in the metabolites of healthy individuals compared to myeloma and lymphoma patients. Validation through quantitative metabolomics is encouraged, especially for the metabolites with significantly expression in blood cancer patients.</P>

      • SCISCIESCOPUS

        Screening and identification of neuroprotective compounds from <i>Scrophularia buergeriana</i> using cell extraction coupled with LC–MS

        Shin, Hyeji,Medriano, Carl Angelo,Park, Byoungduck,Park, Youngja H,Lee, Ki Yong Pergamon Press 2018 Journal of pharmaceutical and biomedical analysis Vol.148 No.-

        <P><B>Abstract</B></P> <P>In the cell extraction_LC–MS method, when cells are incubated with natural product extracts, bioactive compounds selectively bind to extracellular or intracellular targets. The extracts and major compounds (phenylpropanoids and iridoid glycosides) of <I>Scrophularia buergeriana</I> Miquel have been reported to show neuroprotective effects both <I>in vitro</I> and <I>in vivo</I>. In this study, the cell extraction_LC–MS strategy was applied to screen and identify potential neuroprotective compounds from <I>S. buergeriana</I> by using immortalized mouse hippocampal HT22 cells. The results showed that two known compounds from <I>S. buergeriana</I> selectively bound HT22 cells. Additionally, metabolomics analyses were performed using the Mass Profiler Professional and Limma differential expression package of R to identify significant differences between HT22 cells treated with <I>S. buergeriana</I> and untreated cells. The cell extraction approach more accurately reflects <I>in vivo</I> conditions compared with other methods and can be readily used for screening bioactive components from natural products.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Cell extraction_LC–MS strategy was applied to screen and identify potential neuroprotective compounds from <I>S. buergeriana</I> by using HT22 cells. </LI> <LI> Two neuroprotective metabolites, buergeriside C<SUB>1</SUB> and buergeriside A<SUB>1</SUB>, were selectively bound HT22 cells. </LI> <LI> The significant metabolites, which are compounds that affect the statistical difference between the two groups, were identified. </LI> <LI> The cell extraction approach is a better representation of the <I>in vivo</I> situation than other methods. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

      • High-resolution metabolomics to identify urine biomarkers in corticosteroid-resistant asthmatic children

        Park, Youngja H.,Fitzpatrick, Anne M.,Medriano, Carl Angelo,Jones, Dean P. Elsevier 2017 The Journal of allergy and clinical immunology Vol.139 No.5

        <P><B>Background</B></P> <P>Corticosteroid (CS) treatment has been established as the first anti-inflammatory treatment for adults and children with asthma. However, a subset of patients fails to respond to combined systemic and inhaled CS treatment.</P> <P><B>Objective</B></P> <P>This study was aimed at further understanding CS resistance among children with severe asthma.</P> <P><B>Methods</B></P> <P>High-resolution metabolomics was performed on urine samples from CS-respondent (n = 15) and CS-nonrespondent (n = 15) children to determine possible urine biomarkers related to CS resistance. The metabolic phenotypes of CS responders and CS nonresponders were analyzed using bioinformatics including Manhattan plot with false- discovery rate, hierarchical cluster analysis, Kyoto Encyclopedia Genes and Genomes, and Mummichog pathway analysis.</P> <P><B>Results</B></P> <P>The 2-way hierarchical cluster analysis study determined 30 metabolites showing significantly different levels between CS responders and CS nonresponders. The important metabolites annotated were 3,6-dihydronicotinic acid (126.05 <I>m</I>/<I>z</I>, RT: 106, [M+H]<SUP>+</SUP>), 3-methoxy-4-hydroxyphenyl(ethylene)glycol (185.05 <I>m</I>/<I>z</I>, RT: 155, [M+H]<SUP>+</SUP>), 3,4-dihydroxy-phenylalanine (198.07 <I>m</I>/<I>z</I>, RT: 446, [M+H]<SUP>+</SUP>), γ-glutamylcysteine (236.06 <I>m</I>/<I>z</I>, RT: 528, [M+S(34)+H]<SUP>+</SUP>), Cys-Gly, (253.06 <I>m</I>/<I>z</I>, RT: 528, [M-NH<SUB>3</SUB>+H]<SUP>+</SUP>), and reduced Flavin mononucleotide (517.0794 <I>m/z</I>, RT: 533, [M+NaCl]<SUP>+</SUP>). Tyrosine metabolism, degradation of aromatic compounds, and glutathione metabolism are suggested to be significant pathways relating to CS resistance.</P> <P><B>Conclusions</B></P> <P>High-resolution metabolomics is a promising approach in asthma research. Five candidate markers were identified to be related to CS-resistant children with severe asthma. These compounds, upon validation, may contribute further in the understanding of CS resistance among children with severe asthma through the use of urine.</P>

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