Assessment of coverage for endogenous metabolites and exogenous chemical compounds using an untargeted metabolomics platform

2019 ◽  
Author(s):  
Sek Won Kong ◽  
Carles Hernandez-Ferrer
Keyword(s):  
Chemical Compounds ◽  
Untargeted Metabolomics ◽  
Endogenous Metabolites

scholarly journals Effects of the Chiral Fungicides Metalaxyl and Metalaxyl-M on the Earthworm Eisenia fetida as Determined by 1H-NMR-Based Untargeted Metabolomics

Molecules ◽  
2019 ◽  
Vol 24 (7) ◽  
pp. 1293 ◽  
Author(s):  
Renke Zhang ◽  
Zhiqiang Zhou
Keyword(s):  
Nuclear Magnetic Resonance ◽  
Citric Acid ◽  
Magnetic Resonance ◽  
1H Nmr ◽  
Eisenia Fetida ◽  
Tricarboxylic Acid ◽  
Untargeted Metabolomics ◽  
1H Nuclear Magnetic Resonance ◽  
Endogenous Metabolites ◽  
Arginine Aspartate

Although metalaxyl and metalaxyl-M are widely used fungicides, very little is known about their subacute and enantiospecific effects on the earthworm metabolome. In this study, Eisenia fetida were exposed to metalaxyl and metalaxyl-M at three concentrations (0.5, 5 and 50 mg/kg) for seven days. 1H nuclear magnetic resonance (1H-NMR)-based untargeted metabolomics showed that metalaxyl and metalaxyl-M exposure disturbed earthworms’ metabolism at all three concentrations. Endogenous metabolites, such as succinate, arginine, aspartate, urea, asparagine, alanine, trimethylamine, taurine, cysteine, serine, threonine, histidine, lysine, glucose, choline, carnitine, citric acid, alpha-ketoisovaleric acid, fumaric acid and so on, were significantly changed. These results indicate that metalaxyl and metalaxyl-M produce different, enantiospecific disturbances in the earthworm metabolism, particularly in the tricarboxylic acid (TCA) and urea cycles. The application of untargeted metabolomics thus provides more information for evaluating the toxic risks of metalaxyl and metalaxyl-M.

scholarly journals Proteometabolomics of Melphalan Resistance in Multiple Myeloma

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 5619-5619
Author(s):  
David C. Koomen ◽  
Joy D. Guingab ◽  
Paula S. Oliveira ◽  
Bin Fang ◽  
Min Liu ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Cell Line ◽  
Cell Lines ◽  
Metabolic Pathways ◽  
Acute Treatment ◽  
Alkylating Agents ◽  
Resistant Cell ◽  
Untargeted Metabolomics ◽  
Drug Resistant ◽  
Endogenous Metabolites

Abstract Although advancements in therapeutic regimens for treating multiple myeloma (MM) have prolonged patient survival, the disease remains incurable. Several classes of drugs have contributed to these improvements, such as proteasome inhibitors, immunomodulators, deacetylase inhibitors, monoclonal antibodies, and alkylating agents including melphalan. An expanded arsenal of diverse chemotherapy targets has improved patient care significantly, yet we still lack sufficient knowledge of how cellular metabolism and drug processing can contribute to drug resistance. To address this issue, we utilize cell line models to simulate naïve and drug resistant states, which identify drug modifications, endogenous metabolites, proteins, and acute metabolic profile alterations associated with therapeutic escape. Here, we specifically focus on melphalan; an alkylating agent that forms DNA interstrand crosslinks, inhibits cell division, and leads to cell death through apoptosis (Povirk & Shuker. Mutat. Res. 1994, 318, 205). Melphalan remains a critical component of high dose therapy in the context of stem cell transplant and induction therapy in transplant ineligible patients outside the US. Ineffectiveness of alkylating agents remains a critical problem and serves as an excellent model for investigation of cellular metabolism and its contribution to drug resistance. Two parental MM cell lines (8226 & U266) were obtained from ATCC and resistant derivatives of each cell line (8226-LR5 & U266-LR6) were selected after chronic drug exposure. To assess mechanisms of melphalan resistance, we use liquid chromatography-mass spectrometry-based metabolomics and proteomics approaches, including studies of drug metabolism, untargeted metabolomics, and activity based protein profiling (ABPP). Drug metabolism monitors the intracellular and extracellular drug modifications over a 24-hour period after acute treatment. Untargeted metabolomics is used to compare the steady state endogenous intracellular metabolites of naïve and drug resistant cells. Differences in endogenous metabolites between naïve and drug resistant cell lines are also examined in the acute treatment dataset. ABPP utilizes desthiobiotinylating probes to enrich for ATP-utilizing enzymes, which are identified and quantified to enable comparison. We initially compared acute melphalan treatment in drug naive and resistant isogenic cell line pairs. Predictably, melphalan was converted into monohydroxylated and dihydroxylated metabolites more quickly in cells than in media controls. Differences in the formation of these metabolites between the naïve and resistant cell lines were not observed. The untargeted metabolomics data indicated in the 8226-LR5 model, glutathione and xanthine levels are elevated, while guanine is suppressed relative to naive cells. ABPP demonstrated changes in several enzymes related to purine and glutathione metabolism (Figure 1). Interestingly, the U266/U266-LR6 cell line models exhibit higher baseline levels of glutathione when compared with 8226/8226-LR5, indicating heterogeneous means of drug resistance. Alterations in arginine biosynthesis and nicotinate/nicotinamide metabolism are observed in the untargeted metabolomics and ABPP of U266/U266-LR6. Common pathways (e.g. purine biosynthesis) are altered in both models, although the changes involve different molecules. In examining two models of acquired melphalan resistance, we demonstrate frank differences in metabolic pathways associated with steady state and acute drug response. These data demonstrate the potential heterogeneity in drug resistance mechanisms and the need for more biomarkers to personalize treatment. Ongoing studies involve introduction of enzyme inhibitors in targeted pathways and supplementation of metabolites to validate their role in resistance. Furthermore, we will examine expression of these metabolic pathways associated with ex vivo melphalan resistance in a cohort of over 100 patient samples with paired RNA sequencing. The long term goals are to elucidate mechanisms of therapeutic response, identify biomarkers of metabolism in melphalan resistance, enhance drug efficacy, predict personalized patient treatment, and improve overall MM patient care. Disclosures No relevant conflicts of interest to declare.

Cytochemical analysis of mast cell granules after poly-dl-lysine action

1978 ◽  
Vol 36 (2) ◽  
pp. 278-279
Author(s):  
R. Courtoy ◽  
L.J. Simar ◽  
J. Christophe
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Chemical Compounds ◽  
Cellular Membrane ◽  
Thin Sections ◽  
Organic Bases ◽  
Ferric Thiocyanate ◽  
Cytochemical Analysis ◽  
Mast Cell Granule ◽  
Amine Liberation

Several chemical compounds induce amine liberation from mast cells but do not necessarily provoque the granule expulsion. For example, poly-dl-lysine induces modifications of the cellular membrane permeability which promotes ion exchange at the level of mast cell granules. Few of them are expulsed but the majority remains in the cytoplasm and appears less dense to the electrons. A cytochemical analysis has been performed to determine the composition of these granules after the polylysine action.We have previously reported that it was possible to demonstrate polyanions on epon thin sections using a cetylpyridinium ferric thiocyanate method. Organic bases are selectively stained with cobalt thiocyanate and the sulfhydryle groups are characterized with a silver methenamine reaction. These techniques permit to reveal the mast cell granule constituents, i.e. heparin, biogenic amines and basic proteins.

Growth of near noble metal Pd and Pt thin film silicides morphology and structure

1984 ◽  
Vol 42 ◽  
pp. 498-499
Author(s):  
E. I. Alessandrini ◽  
M. O. Aboelfotoh
Keyword(s):  
Noble Metals ◽  
Annealing Temperature ◽  
Chemical Compounds ◽  
Barrier Properties ◽  
Solid State Reactions ◽  
Transmission Electron ◽  
Stable Chemical ◽  
Metal Thickness ◽  
Amorphous Si ◽  
Si Films

Considerable interest has been generated in solid state reactions between thin films of near noble metals and silicon. These metals deposited on Si form numerous stable chemical compounds at low temperatures and have found applications as Schottky barrier contacts to silicon in VLSI devices. Since the very first phase that nucleates in contact with Si determines the barrier properties, the purpose of our study was to investigate the silicide formation of the near noble metals, Pd and Pt, at very thin thickness of the metal films on amorphous silicon.Films of Pd and Pt in the thickness range of 0.5nm to 20nm were made by room temperature evaporation on 40nm thick amorphous Si films, which were first deposited on 30nm thick amorphous Si3N4 membranes in a window configuration. The deposition rate was 0.1 to 0.5nm/sec and the pressure during deposition was 3 x 10 -7 Torr. The samples were annealed at temperatures in the range from 200° to 650°C in a furnace with helium purified by hot (950°C) Ti particles. Transmission electron microscopy and diffraction techniques were used to evaluate changes in structure and morphology of the phases formed as a function of metal thickness and annealing temperature.

Analysis of Bioactive Chemical Compounds of Trogoderma granarium (Insecta: Coleoptera: Dermestidae) Using Gas Chromatography – Mass Spectrometry

2017 ◽  
Vol 9 (03) ◽  
Author(s):  
Jenan Mohammed Ubaid ◽  
Abeer Fauzi Al-Rubaye ◽  
Imad Hadi Hameed
Keyword(s):  
Acetic Acid ◽  
Benzoyl Chloride ◽  
Methanolic Extract ◽  
Biological Activities ◽  
Chemical Compounds ◽  
Gas Chromatography Mass Spectrometry ◽  
Pentanoic Acid ◽  
Trogoderma Granarium ◽  
Trans Methyl ◽  
Phenacyl Thiocyanate

Methanolic extract of bioactive compounds of Trogoderma granarium was assayed. GC-MS analysis of Trogoderma granarium revealed the existence of the Pentanoic acid , 1,1-dimethylpropyl ester , (1H)-Pyrimidinone , 5-chloro-4,6- diphenyl, Cyclobutanemethanol , α-methyl- , Nitro-2-methyl-1,3-propanediol , Hydroxylamine ,O-(2-methylpropyl)- , Uridine , 2',3'-O-(phenylmethylene)- ,Acetic acid ,2-benzoylthio-,2-oxo-2-phenylethyl ester , methylpropyl)- , Uridine , 2',3'-O-(phenylmethylene)- , 5'-(4-methylbenzenesulfo , Indolinol , 1-benzoyl-, Benzeneethanol , β-methyl-,(s)- , Acetic acid ,2-benzoylthio-,2-oxo-2-phenylethyl ester , Phenacyl thiocyanate , Deoxy-L-ribose-2,5-dibenzoate , Methenamine , Alanine , N-methyl-n-propargyloxycarbonyl-, decyl ester , Benzoyl chloride , Thiophene-2-ol , benzoate , Ethanone , -(5- nitrotetrazol-2-yl)-1-phenyl- , 2,5-Dimethylhexane-2,5-dihydroperoxide , Benzamide , N-(3-benzylthio-1,2,4-thiadiazol- 5-yl)- , Methyl p-(2-phenyl-1-benzimidazolyl)benzoate , Methyl-2-phenoxyethylamine , Pentaborane(11) , cis-Methoxy- 5-trans-methyl-1R-cyclohexanol , Nitro-1-phenyl-3-(tetrahydropyran-2-yloxy)propan-1-one , cis-Methoxy-5-transmethyl-1R-cyclohexanol. Trogoderma granarium produce many important secondary metabolites with high biological activities.

Study effect of crude extracts of Hibiscus sabdarifa L. on some Enterobacteriaceae

2018 ◽  
Vol 9 (SPL1) ◽  
Author(s):  
Sabreen A Kamal ◽  
Ishraq A Salih ◽  
Hawraa Jawad Kadhim ◽  
Zainab A Tolaifeh
Keyword(s):  
Escherichia Coli ◽  
Ethyl Acetate ◽  
Bacterial Growth ◽  
Chemical Compounds ◽  
Inhibition Zone ◽  
Crude Extracts ◽  
And Control

Red rose or roselle (beauty rose ) is natively known as red tea belong to Malvaceae, it is flowers use traditionally for antihypertensive hepato protective, anticancer,antidiabetic,antibacterial, cytotoxicity and antidiarreal, By preparing red tea from it's flower. In this study, we extract chemical compounds by using two solvent which are Ethanol, Ethyl acetate. so we can extract Anthocyanin which is responsible for red colour of flower with many chemical compounds. then study the effect of these extracts on 5 genera from Enterobacteriacaea which can cause diarrheae (Shigella, Salmonella, Escherichia coli, Proteus and Klebsiella ) by preparing 3 concentrations for each solvent (250, 500, 750 ) mg/ml, and control then compare with two antibiotic (Azereonam 30 mg/ml and Bacitracin 10 mg/ml ) these extracts revealed obvious inhibition zone in bacterial growth.

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