Airway macrophage glycolysis controls lung homeostasis and responses to aeroallergen.

The lungs represent a dynamic microenvironment where airway macrophages (AMs) are the major lung-resident macrophages. AMs dictate the balance between tissue homeostasis and immune activation and thus have contradictory functions by maintaining tolerance and tissue homeostasis, as well as initiating strong inflammatory responses. Emerging evidence has highlighted the connection between macrophage function and cellular metabolism.

The surfactant co-formulant POEA in the glyphosate-based herbicide RangerPro but not glyphosate alone causes necrosis in Caco-2 and HepG2 human cell lines and ER stress in the ToxTracker assay.

The toxicity of co-formulants present in glyphosate-based herbicides (GBHs) has been widely discussed leading to the European Union banning the polyoxyethylene tallow amine (POEA). We identified the most commonly used POEA, known as POE-15 tallow amine (POE-15), in the widely used US GBH RangerPro. Cytotoxicity assays using human intestinal epithelial Caco-2 and hepatocyte HepG2 cell lines showed that RangerPro and POE-15 are far more cytotoxic than glyphosate alone.

Urinary excretion of herbicide co-formulants after oral exposure to roundup MON 52276 in rats.

The toxicity of surfactants, which are an integral component of glyphosate-formulated products is an underexplored and highly debated subject. Since biomonitoring human exposure to glyphosate co-formulants is considered as a public health priority, we developed and validated a high-resolution mass spectrometry method to measure the urinary excretion of surfactants present in Roundup MON 52276, the European Union (EU) representative formulation of glyphosate-based herbicides. Quantification was performed measuring the 5 most abundant compounds in the mixture.

Use of Shotgun Metagenomics and Metabolomics to Evaluate the Impact of Glyphosate or Roundup MON 52276 on the Gut Microbiota and Serum Metabolome of Sprague-Dawley Rats.

Background: There is intense debate on whether glyphosate can inhibit the shikimate pathway of gastrointestinal microorganisms, with potential health implications.

Objectives: We tested whether glyphosate or its representative EU herbicide formulation Roundup MON 52276 affects the rat gut microbiome.

Methods: We combined cecal microbiome shotgun metagenomics with serum and cecum metabolomics to assess the effects of glyphosate [0.

NADPH oxidase 4 regulates homocysteine metabolism and protects against acetaminophen-induced liver damage in mice.

Glutathione is the major intracellular redox buffer in the liver and is critical for hepatic detoxification of xenobiotics and other environmental toxins. Hepatic glutathione is also a major systemic store for other organs and thus impacts on pathologies such as Alzheimer's disease, Sickle Cell Anaemia and chronic diseases associated with aging. Glutathione levels are determined in part by the availability of cysteine, generated from homocysteine through the transsulfuration pathway.

Creation of libraries of recurring mass spectra from large data sets assisted by a dual-column workflow.

An analytical methodology has been developed for extracting recurrent unidentified spectra (RUS) from large GC/MS data sets. Spectra were first extracted from original data files by the Automated Mass Spectral Deconvolution and Identification System (AMDIS; Stein, S. E.

Rapid screening of low-molecular-weight phenols from persimmon (Diospyros kaki) pulp using liquid chromatography/UV-visible/electrospray mass spectrometry analysis.

Background: Persimmon fruits have been widely used in traditional medicine owing to their phenolic composition. This research aims to perform a rapid, detailed and affordable study of the profile of low-molecular-weight phenols from persimmon pulp.

Results: Two different HPLC-DAD/ESI-MS(n) analyses were performed using a routine three-dimensional ion trap mass spectrometer to analyze the ethanolic extract of persimmon pulp: (1) an untargeted data-dependent analysis to identify the majority of small phenols that included full MS and MS(2) scan events; (2) a targeted data-dependent analysis to identify polymerized phenols (dimers and formic acid adducts) through a source-induced dissociation analysis that included full MS and MS(2) scan events.

Signal enhancement of glucuronide conjugates in LC-MS/MS by derivatization with the phosphonium propylamine cation tris(trimethoxyphenyl) phosphonium propylamine, for forensic purposes.

Although chemical derivatization for signal enhancement in drug testing is most often associated with gas chromatography, it also has the potential to improve the detection of analytes poorly ionized by atmospheric pressure ionization techniques, such as electrospray ionization used in liquid chromatography-mass spectrometry. A number of acidic compounds, namely drug glucuronides (e.g.

Proteome changes in tomato lines transformed with phytoene synthase-1 in the sense and antisense orientations.

The commercial cultivation of genetically engineered (GE) crops in Europe has met with considerable consumer resistance, which has led to vigorous safety assessments including the measurement of substantial equivalence between the GE and parent lines. This necessitates the identification and quantification of significant changes to the metabolome and proteome in the GE crop. In this study, the quantitative proteomic analysis of tomato fruit from lines that have been transformed with the carotenogenic gene phytoene synthase-1 (Psy-1), in the sense and antisense orientations, in comparison with a non-transformed, parental line is described.

Quantitation of hepcidin in serum using ultra-high-pressure liquid chromatography and a linear ion trap mass spectrometer.

Hepcidin is a peptide hormone that functions as a key regulator of mammalian iron metabolism. Biological levels are increased in end-stage renal disease and during inflammation but suppressed in hemochromatosis. Thus hepcidin levels have diagnostic importance.

Tumor targeting of functionalized quantum dot-liposome hybrids by intravenous administration.

A strategy to target functionalized quantum dot-liposome (f-QD-L) hybrid vesicles in the solid tumor tissue of tumor-bearing mice is explored. Functionalized polyethylene glycol (PEG)-lipid coated QD (f-QD) were encapsulated into the aqueous core of 100 nm cationic (DOPC:Chol: DOTAP); sterically stabilized, fluid-phase (DOPC:Chol:DSPE-PEG2000); and sterically stabilized, gel-phase (DSPC:Chol:DSPE-PEG2000) liposome vesicles. Double tracking of f-QD-L in blood was performed at different time points after intravenous administration in B16F10 melanoma tumor-bearing C57BL6 mice.

Blood circulation and tissue biodistribution of lipid--quantum dot (L-QD) hybrid vesicles intravenously administered in mice.

The present work describes the pharmacokinetics of recently developed liposome-quantum dot (L-QD) hybrid vesicles in nude mice following systemic administration. Hydrophobic QD were incorporated into different bilayer compositions, and the serum stability of such hybrid vesicles was evaluated using turbidity and carboxyfluorescein release measurements. L-QD hybrid blood profile and organ biodistribution were also determined by elemental (cadmium) analysis.

Use of human microsomes and deuterated substrates: an alternative approach for the identification of novel metabolites of ketamine by mass spectrometry.

In vitro biosynthesis using pooled human liver microsomes was applied to help identify in vivo metabolites of ketamine by liquid chromatography (LC)-tandem mass spectrometry. Microsomal synthesis produced dehydronorketamine, seven structural isomers of hydroxynorketamine, and at least five structural isomers of hydroxyketamine. To aid identification, stable isotopes of the metabolites were also produced from tetra-deuterated isotopes of ketamine or norketamine as substrates.

Quantification of hepcidin using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry.

Hepcidin is known to be a key systemic iron-regulatory hormone which has been demonstrated to be associated with a number of iron disorders. Hepcidin concentrations are increased in inflammation and suppressed in hemochromatosis. In view of the role of hepcidin in disease, its potential as a diagnostic tool in a clinical setting is evident.

Evaluation of stable isotope labelling strategies for the quantitation of CP4 EPSPS in genetically modified soya.

The introduction of genetically modified (GM) crops into the market has raised a general alertness relating to the control and safety of foods. The applicability of protein separation hyphenated to mass spectrometry to identify the bacterial enolpyruvylshikimate-3-phosphate synthase (CP4 EPSPS) protein expressed in GM crops has been previously reported [M.F.

Salicylic acid sans aspirin in animals and man: persistence in fasting and biosynthesis from benzoic acid.

Salicylic acid (SA), which is central to defense mechanisms in plants and the principal metabolite of aspirin, occurs naturally in man with higher levels of SA and its urinary metabolite salicyluric acid (SU) in vegetarians overlapping with levels in patients on low-dose aspirin regimens. SA is widely distributed in animal blood. Fasting for major colorectal surgery did not cause disappearance of SA from plasma, even in patients following total proctocolectomy.

Detection of ketamine and its metabolites in urine by ultra high pressure liquid chromatography-tandem mass spectrometry.

Current analytical methods used for screening drugs and their metabolites in biological samples from victims of drug-facilitated sexual assault (DFSA) or other vulnerable groups can lack sufficient sensitivity. The application of liquid chromatography, employing small particle sizes, with tandem mass spectrometry (MS/MS) is likely to offer the sensitivity required for detecting candidate drugs and/or their metabolites in urine, as demonstrated here for ketamine. Ultra-performance liquid chromatography-mass spectrometry (UPLC-MS/MS) was performed following extraction of urine (4 mL) using mixed-mode (cation and C8) solid-phase cartridges.

Quantitation of hepcidin in human urine by liquid chromatography-mass spectrometry.

Hepcidin is a peptide hormone that functions as a key regulator of mammalian iron metabolism. Serum and urine levels are increased in inflammation and suppressed in hemochromatosis, and they may have diagnostic importance. This study describes the development and validation of an analytical method for the quantitative determination of the concentration of hepcidin in clinical samples.

The effect of Khat (Catha edulis) as an appetite suppressant is independent of ghrelin and PYY secretion.

Background: The leaves of the khat plant (Catha edulis) are chewed for their pleasurable effects. Chewing releases cathinone which may decrease appetite through an unknown mechanism. Levels of the peptide ghrelin increase with hunger and decrease immediately post-prandially, while peptide YY is released following a meal.

Liquid chromatographic-mass spectrometric analysis of glucuronide-conjugated anabolic steroid metabolites: method validation and interlaboratory comparison.

Liquid chromatography electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) method for simultaneous and direct detection of 12 glucuronide-conjugated anabolic androgenic steroid (AAS) metabolites in human urine is described. The compounds selected were the main metabolites detected in human urine after dosing of the most widely abused AAS in sports, e.g.

Manipulation of phytoene levels in tomato fruit: effects on isoprenoids, plastids, and intermediary metabolism.

In tomato (Solanum lycopersicum), phytoene synthase-1 (PSY-1) is the key biosynthetic enzyme responsible for the synthesis of fruit carotenoids. To further our understanding of carotenoid formation in tomato fruit, we characterized the effect of constitutive expression of an additional tomato Psy-1 gene product. A quantitative data set defining levels of carotenoid/isoprenoid gene expression, enzyme activities, and metabolites was generated from fruit that showed the greatest perturbation in carotenoid content.

Mass spectrometric detection of CP4 EPSPS in genetically modified soya and maize.

The potential of protein fractionation hyphenated to mass spectrometry (MS) to detect and characterize the transgenic protein present in Roundup Ready soya and maize has been investigated. Genetically modified (GM) soya and maize contain the 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS) gene from Agrobacterium tumefaciens CP4, which confers resistance to the herbicide glyphosate. The GM soya and maize proteomes were fractionated by gel filtration, anion-exchange chromatography and sodium dodecyl sulfate/polyacrylamide gel electrophoresis (SDS-PAGE) prior to MS.

Derivatization in mass spectrometry--8. Soft ionization mass spectrometry of small molecules.

This is the first of two reviews devoted to derivatization approaches for "soft" ionization mass spectrometry (FAB, MALDI, ESI, APCI) and deals, in particular, with small molecules. The principles of the main "soft" ionization mass spectrometric methods as well as the reasons for derivatizing small molecules are briefly described. Derivatization methods for modification of amines, carboxylic acids, amino acids, alcohols, carbonyl compounds, monosaccharides, thiols, unsaturated and aromatic compounds etc.