• Title/Summary/Keyword: metabolomic approach

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Metabolic perturbation of an Hsp90 C-domain inhibitor in a lung cancer cell line, A549 studied by NMR-based chemometric analysis

  • Hur, Su-Jung;Lee, Hye-Won;Shin, Ai-Hyang;Park, Sung Jean
    • Journal of the Korean Magnetic Resonance Society
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    • v.18 no.1
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    • pp.10-14
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    • 2014
  • Hsp90 is a good drug target molecule that is involved in regulating various signaling pathway in normal cell and the role of Hsp90 is highly emphasized especially in cancer cells. Thus, much efforts for discovery and development of Hsp90 inhibitor have been continued and a few Hsp90 inhibitors targeting the N-terminal ATP binding site are being tested in the clinical trials. There are no metabolic signature molecules that can be used to evaluate the effect of Hsp90 inhibition. We previously found a potential C-domain binder named PPC1 that is a synthetic small molecule. Here we report the metabolomics study to find signature metabolites upon treatment of PPC1 compound in lung cancer cell line, A549 and discuss the potentiality of metabolomic approach for evaluation of hit compounds.

Untargeted metabolomics using liquid chromatography-high resolution mass spectrometry and chemometrics for analysis of non-halal meats adulteration in beef meat

  • Anjar Windarsih;Nor Kartini Abu Bakar;Abdul Rohman;Nancy Dewi Yuliana;Dachriyanus Dachriyanus
    • Animal Bioscience
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    • v.37 no.5
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    • pp.918-928
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    • 2024
  • Objective: The adulteration of raw beef (BMr) with dog meat (DMr) and pork (PMr) becomes a serious problem because it is associated with halal status, quality, and safety of meats. This research aimed to develop an effective authentication method to detect non-halal meats (dog meat and pork) in beef using metabolomics approach. Methods: Liquid chromatography-high resolution mass spectrometry (LC-HRMS) using untargeted approach combined with chemometrics was applied for analysis non-halal meats in BMr. Results: The untargeted metabolomics approach successfully identified various metabolites in BMr DMr, PMr, and their mixtures. The discrimination and classification between authentic BMr and those adulterated with DMr and PMr were successfully determined using partial least square-discriminant analysis (PLS-DA) with high accuracy. All BMr samples containing non-halal meats could be differentiated from authentic BMr. A number of discriminating metabolites with potential as biomarkers to discriminate BMr in the mixtures with DMr and PMr could be identified from the analysis of variable importance for projection value. Partial least square (PLS) and orthogonal PLS (OPLS) regression using discriminating metabolites showed high accuracy (R2 >0.990) and high precision (both RMSEC and RMSEE <5%) in predicting the concentration of DMr and PMr present in beef indicating that the discriminating metabolites were good predictors. The developed untargeted LC-HRMS metabolomics and chemometrics successfully identified non-halal meats adulteration (DMr and PMr) in beef with high sensitivity up to 0.1% (w/w). Conclusion: A combination of LC-HRMS untargeted metabolomic and chemometrics promises to be an effective analytical technique for halal authenticity testing of meats. This method could be further standardized and proposed as a method for halal authentication of meats.

Determination of Aspirin Tablet Manufacturers by an NMR-based Metabolomic Approach

  • Choi, Moon-Young;Kang, Sun-Mi;Park, Jeong-Hill;Kwon, Sung-Won
    • Journal of Pharmaceutical Investigation
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    • v.39 no.1
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    • pp.43-49
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    • 2009
  • Aspirin or acetylsalicylic acid, a member of the salicylate family, is frequently used as an analgesic, antipyretic, anti-inflammatory and antiplatelet drug. Because aspirin is chemically unstable in water and heat for tablet formulation, additives including lubricants are used in preparing aspirin tablets, using a dry-granulation process. Aspirin tablets are produced by a number of manufacturers which usually use their own unique combination of additives during the manufacturing process. In this study, we employed an NMR based metabolomics technique to identify the manufacturers of various aspirin tablets. Aspirin tablets from six different companies were analyzed by 1H 400 MHz NMR. The acquired data was then integrated and processed by principal component analysis (PCA). Based on the NMR data, we were able to identify peaks corresponding to acetylsalicylic acid in all of the six samples, whereas different NMR patterns were found in the aromatic and aliphatic regions depending on the unique additive used. These observations led to the conclusion that the differences in the NMR patterns among the different aspirin tablets were due to the presence of additives.

Determination of Differences in the Nonvolatile Metabolites of Pine-Mushrooms (Tricholoma matsutake Sing.) According to Different Parts and Heating Times Using $^1H$ NMR and Principal Component Analysis

  • Cho, In-Hee;Kim, Young-Suk;Lee, Ki-Won;Choi, Hyung-Kyoon
    • Journal of Microbiology and Biotechnology
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    • v.17 no.10
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    • pp.1682-1687
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    • 2007
  • The differences in the nonvolatile metabolites of pine-mushrooms (Tricholoma matsutake Sing.) according to different parts and heating times were analyzed by applying principal component analysis (PCA) to $^1H$ nuclear magnetic resonance (NMR) spectroscopy data. The $^1H$ NMR spectra and PCA enabled the differences of nonvolatile metabolites among mushroom samples to be clearly observed. The two parts of mushrooms could be easily discriminated based on PC 1, and could be separated according to different heattreated times based on PC 3. The major peaks in the $^1H$ NMR spectra that contributed to differences among mushroom samples were assigned to trehalose, succinic acid, choline, leucine/isoleucine, and alanine. The content of trehalose was higher in the pileus than in the stipe of all mushroom samples, whereas succinic acid, choline, and leucine/isoleucine were the main components in the stipe. Heating resulted in significant losses of alanine and leucine/isoleucine, whereas succinic acid, choline, and trehalose were the most abundant components in mushrooms heat-treated for 3 min and 5 min, respectively.

Proteomics in Insecticide Toxicology

  • Park, Byeoung-Soo;Lee, Sung-Eun
    • Molecular & Cellular Toxicology
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    • v.3 no.1
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    • pp.11-18
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    • 2007
  • Mechanisms of insecticide resistance found in insects may include three general categories. Modified behavioral mechanisms can let the insects avoid the exposure to toxic compounds. The second category is physiological mechanisms such as altered penetration, rapid excretion, lower rate transportation, or increased storage of insecticides by insects. The third category relies on biochemical mechanisms including the insensitivity of target sites to insecticides and enhanced detoxification rate by several detoxifying mechanisms. Insecticides metabolism usually results in the formation of more water-soluble and therefore more readily eliminated, and generally less toxic products to the host insects rather than the parent compounds. The representative detoxifying enzymes are general esterases and monooxygenases that catalyze the toxic compounds to be more water-soluble forms and then secondary metabolism is followed by conjugation reactions including those catalyzed by glutathione S-transferases (GSTs). However, a change in the resistant species is not easily determined and the levels of mRNAs do not necessarily predict the levels of the corresponding proteins in a cell. As genomics understands the expression of most of the genes in an organism after being stressed by toxic compounds, proteomics can determine the global protein changes in a cell. In this present review, it is suggested that the environmental proteomic application may be a good approach to understand the biochemical mechanisms of insecticide resistance in insects and to predict metabolomic changes leading to physiological changes of the resistant species.

Recreation of Korean Traditional Nuruk and the Analysis of Metabolomic Characteristics

  • Lee, Jang Eun;Kim, Jae Ho
    • 한국균학회소식:학술대회논문집
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    • 2015.11a
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    • pp.39-39
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    • 2015
  • Korean traditional Nuruk has been developed with various materials and shapes according to geographical environments and climates of their origins. Nuruk is also known as kokja in Korea, reflecting the understanding that microorganisms such as wild fungi, yeasts, and lactobacillus bacteria are naturally inoculated and reproduced. The objective of this study is to identify the characteristics of traditional Nuruk through recreating traditional production methods detailed in ancient Korean documents. In the present study, a total of 58 different kinds of Korean traditional Nuruk were prepared, including 46 kinds of recreated products. Each Nuruk sample was evaluated for its enzymatic activities, including glucoamylase, protease, and glucanase. Their suitability for alcoholic beverage production were compared to each other. To isolate valuable microorganisms from Nuruk samples, alcoholic beverages produced using each sample were subjected to sensory evaluation to determine their taste. In addition, metabolite changes in traditional alcoholic beverages fermented with different kinds of Nuruk were analyzed through mass-based metabolomics approach. This study presents, for the first time, the traditional production methods written in ancient Korean documents using workable production methods supported by modern technologies. In addition, this study analyzed the characteristics of reproduced Nuruk. It could be utilized as a basis for studying traditional Korean traditional alcoholic beverages and their valuable microorganisms.

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Effect of Exogenous Proline on Metabolic Response of Tetragenococcus halophilus under Salt Stress

  • He, Guiqiang;Wu, Chongde;Huang, Jun;Zhou, Rongqing
    • Journal of Microbiology and Biotechnology
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    • v.27 no.9
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    • pp.1681-1691
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    • 2017
  • This study investigated the effect of proline addition on the salt tolerance of Tetragenococcus halophilus. Salt stress led to the accumulation of intracellular proline in T. halophilus. When 0.5 g/l proline was added to hyperhaline medium, the biomass increased 34.6% (12% NaCl) and 27.7% (18% NaCl) compared with the control (without proline addition), respectively. A metabolomic approach was employed to reveal the cellular metabolic responses and protective mechanisms of proline upon salt stress. The results showed that both the cellular membrane fatty acid composition and metabolite profiling responded by increasing unsaturated and cyclopropane fatty acid proportions, as well as accumulating some specific intracellular metabolites (environmental stress protector). Higher contents of intermediates involved in glycolysis, the tricarboxylic acid cycle, and the pentose phosphate pathway were observed in the cells supplemented with proline. In addition, addition of proline resulted in increased concentrations of many organic osmolytes, including glutamate, alanine, citrulline, N-acetyl-tryptophan, and mannitol, which may be beneficial for osmotic homeostasis. Taken together, results in this study suggested that proline plays a protective role in improving the salt tolerance of T. halophilus by regulating the related metabolic pathways.

Integration of metabolomics and transcriptomics in nanotoxicity studies

  • Shin, Tae Hwan;Lee, Da Yeon;Lee, Hyeon-Seong;Park, Hyung Jin;Jin, Moon Suk;Paik, Man-Jeong;Manavalan, Balachandran;Mo, Jung-Soon;Lee, Gwang
    • BMB Reports
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    • v.51 no.1
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    • pp.14-20
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    • 2018
  • Biomedical research involving nanoparticles has produced useful products with medical applications. However, the potential toxicity of nanoparticles in biofluids, cells, tissues, and organisms is a major challenge. The '-omics' analyses provide molecular profiles of multifactorial biological systems instead of focusing on a single molecule. The 'omics' approaches are necessary to evaluate nanotoxicity because classical methods for the detection of nanotoxicity have limited ability in detecting miniscule variations within a cell and do not accurately reflect the actual levels of nanotoxicity. In addition, the 'omics' approaches allow analyses of in-depth changes and compensate for the differences associated with high-throughput technologies between actual nanotoxicity and results from traditional cytotoxic evaluations. However, compared with a single omics approach, integrated omics provides precise and sensitive information by integrating complex biological conditions. Thus, these technologies contribute to extended safety evaluations of nanotoxicity and allow the accurate diagnoses of diseases far earlier than was once possible in the nanotechnology era. Here, we review a novel approach for evaluating nanotoxicity by integrating metabolomics with metabolomic profiling and transcriptomics, which is termed "metabotranscriptomics."

$^1H$ NMR-Based Metabolomic Approach for Understanding the Fermentation Behaviors of Wine Yeast Strains

  • Son, Hong-Seok;Hwang, Geum-Sook;Kim, Ki-Myong;Kim, Eun-Young;Berg, Frans van den;Park, Won-Mok;Lee, Cherl-Ho;Hong, Young-Shick
    • Proceedings of the Microbiological Society of Korea Conference
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    • 2009.05a
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    • pp.78-78
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    • 2009
  • $^1H$ NMR spectroscopy coupled with multivariate statistical analysis was used for the first time to investigate metabolic changes in musts during alcoholic fermentation and wines during ageing. Three Saccharomyces cerevisiae yeast strains (RC-212, KIV-1116 and KUBY-501) were also evaluated for their impacts on the metabolic changes in must and wine. Pattern recognition (PR) methods, including PCA, PLS-DA and OPLS-DA scores plots, showed clear differences for metabolites among musts or wines for each fermentation stage up to 6 months. Metabolites responsible for the differentiation were identified to valine, 2,3-butanediol (2,3-BD), pyruvate, succinate, proline, citrate, glycerol, malate, tartarate, glucose, N-methylnicotinic acid (NMNA), and polyphenol compounds. PCA scores plots showed continuous movements away from days 1 to 8 in all musts for all yeast strains, indicating continuous and active fermentation. During alcoholic fermentation, highest levels of 2,3-BD, succinate and glycerol were found in musts with the KIV-1116 strain, which showed the fastest fermentation or highest fermentative activity of the 3 strains, whereas the KUBY-501 strain showed the slowest fermentative activity. This study highlights the applicability of NMR-based metabolomics for monitoring wine fermentation and evaluating the fermentative characteristics of yeast strains.

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Dietary Supplementation with Raspberry Extracts Modifies the Fecal Microbiota in Obese Diabetic db/db Mice

  • Garcia-Mazcorro, Jose F.;Pedreschi, Romina;Chew, Boon;Dowd, Scot E.;Kawas, Jorge R.;Noratto, Giuliana
    • Journal of Microbiology and Biotechnology
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    • v.28 no.8
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    • pp.1247-1259
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    • 2018
  • Raspberries are polyphenol-rich fruits with the potential to reduce the severity of the clinical signs associated with obesity, a phenomenon that may be related to changes in the gut microbiota. The aim of this study was to investigate the effect of raspberry supplementation on the fecal microbiota using an in vivo model of obesity. Obese diabetic db/db mice were used in this study and assigned to two experimental groups (with and without raspberry supplementation). Fecal samples were collected at the end of the supplementation period (8 weeks) and used for bacterial 16S rRNA gene profiling using a MiSeq instrument (Illumina). QIIME 1.8 was used to analyze the 16S data. Raspberry supplementation was associated with an increased abundance of Lachnospiraceae (p = 0.009), a very important group for gut health, and decreased abundances of Lactobacillus, Odoribacter, and the fiber degrader S24-7 family as well as unknown groups of Bacteroidales and Enterobacteriaceae (p < 0.05). These changes were enough to clearly differentiate bacterial communities accordingly to treatment, based on the analysis of UniFrac distance metrics. However, a predictive approach of functional profiles showed no difference between the treatment groups. Fecal metabolomic analysis provided critical information regarding the raspberry-supplemented group, whose relatively higher phytosterol concentrations may be relevant for the host health, considering the proven health benefits of these phytochemicals. Further studies are needed to investigate whether the observed differences in microbial communities (e.g., Lachnospiraceae) or metabolites relate to clinically significant differences that can prompt the use of raspberry extracts to help patients with obesity.