Plasma Metabolic Signatures of Healthy Overweight Subjects Challenged With an Oral Glucose Tolerance Test.

Insulin secretion following ingestion of a carbohydrate load affects a multitude of metabolic pathways that simultaneously change direction and quantity of interorgan fluxes of sugars, lipids and amino acids. In the present study, we aimed at identifying markers associated with differential responses to an OGTT a population of healthy adults. By use of three metabolite profiling platforms, we assessed these postprandial responses of a total of 202 metabolites in plasma of 72 healthy volunteers undergoing comprehensive phenotyping and of which half enrolled into a weight-loss program over a three-month period.

Quantitative Metabolomics in Alzheimer's Disease: Technical Considerations for Improved Reproducibility.

Metabolomics is the comprehensive analysis of small molecules (metabolites) that are intermediates or endpoints of metabolism. Since metabolites change more rapidly to both external and internal stimuli than genes and proteins, metabolomics provides a more sensitive tool to study physiological changes to a wide range of factors such age, medication, or disease status. Therefore, metabolomics is being increasingly used for the study of several pathological states, including complex diseases like Alzheimer's disease (AD).

Plasma metabolome analysis identifies distinct human metabotypes in the postprandial state with different susceptibility to weight loss-mediated metabolic improvements.

Health has been defined as the capability of the organism to adapt to challenges. In this study, we tested to what extent comprehensively phenotyped individuals reveal differences in metabolic responses to a standardized mixed meal tolerance test (MMTT) and how these responses change when individuals experience moderate weight loss. Metabolome analysis was used in 70 healthy individuals.

Metabolic and Lipidomic Reprogramming in Renal Cell Carcinoma Subtypes Reflects Regions of Tumor Origin.

Background: Renal cell carcinoma (RCC) consists of prognostic distinct subtypes derived from different cells of origin (eg, clear cell RCC [ccRCC], papillary RCC [papRCC], and chromophobe RCC [chRCC]). ccRCC is characterized by lipid accumulation and metabolic alterations, whereas data on metabolic alterations in non-ccRCC are limited.

Objective: We assessed metabolic alterations and the lipid composition of RCC subtypes and ccRCC-derived metastases.

Comprehensive Metabolomic and Lipidomic Profiling of Human Kidney Tissue: A Platform Comparison.

Metabolite profiling of tissue samples is a promising approach for the characterization of cancer pathways and tumor classification based on metabolic features. Here, we present an analytical method for nontargeted metabolomics of kidney tissue. Capitalizing on different chemical properties of metabolites allowed us to extract a broad range of molecules covering small polar molecules and less polar lipid classes that were analyzed by LC-QTOF-MS after HILIC and RP chromatographic separation, respectively.

Blood metabolite markers of preclinical Alzheimer's disease in two longitudinally followed cohorts of older individuals.

Introduction: Recently, quantitative metabolomics identified a panel of 10 plasma lipids that were highly predictive of conversion to Alzheimer's disease (AD) in cognitively normal older individuals (n = 28, area under the curve [AUC] = 0.92, sensitivity/specificity of 90%/90%).

Methods: Quantitative targeted metabolomics in serum using an identical method as in the index study.

Systems-level organization of yeast methylotrophic lifestyle.

Background: Some yeasts have evolved a methylotrophic lifestyle enabling them to utilize the single carbon compound methanol as a carbon and energy source. Among them, Pichia pastoris (syn. Komagataella sp.

Reduced quenching and extraction time for mammalian cells using filtration and syringe extraction.

In order to preserve the in vivo metabolite levels of cells, a quenching protocol must be quickly executed to avoid degradation of labile metabolites either chemically or biologically. In the case of mammalian cell cultures cultivated in complex media, a wash step previous to quenching is necessary to avoid contamination of the cell pellet with extracellular metabolites, which could distort the real intracellular concentration of metabolites. This is typically achieved either by one or multiple centrifugation/wash steps which delay the time until quenching (even harsh centrifugation requires several minutes for processing until the cells are quenched) or filtration.

Oxidative stress in hypobaric hypoxia and influence on vessel-tone modifying mediators.

Increased pulmonary artery pressure is a well-known phenomenon of hypoxia and is seen in patients with chronic pulmonary diseases, and also in mountaineers on high altitude expedition. Different mediators are known to regulate pulmonary artery vessel tone. However, exact mechanisms are not fully understood and a multimodal process consisting of a whole panel of mediators is supposed to cause pulmonary artery vasoconstriction.

Interlaboratory comparison for quantitative primary metabolite profiling in Pichia pastoris.

For the first time, an interlaboratory comparison was performed in the field of quantitative metabolite profiling in Pichia pastoris. The study was designed for the evaluation of different measurement platforms integrating different quantification strategies using internal standardization. Nineteen primary metabolites including amino acids and organic acids were selected for the study.

Metabolomic analysis of resveratrol-induced effects in the human breast cancer cell lines MCF-7 and MDA-MB-231.

Resveratrol is a naturally occurring anticancer compound present in grapes and wine with antiproliferative properties against breast cancer cells and xenografts. Our objective was to investigate the metabolic alterations that characterize the effects of resveratrol in the human breast cancer cell lines MCF-7 and MDA-MB-231 using high-throughput liquid chromatography-based mass spectrometry. In both cell lines, growth inhibition was dose dependent and accompanied by substantial metabolic changes.

RP101 improves the efficacy of chemotherapy in pancreas carcinoma cell lines and pancreatic cancer patients.

RP101 [(E)-5-(2-bromovinyl)-2'-deoxyuridine (BVDU)], which supports apoptosis and prevents the acquisition of chemoresistance, was tested in cultured human pancreatic tumor cells. RP101 downregulated uridine phosphorylase, a marker of poor prognosis, and APEX1, which is involved in DNA repair, and repressed Stat3 and its target vascular endothelial growth factor. Furthermore, RP101 activated antitumor immunity as demonstrated by enhanced cytolytic activity of NK-92 natural killer cells.

Inhibition of induced chemoresistance by cotreatment with (E)-5-(2-bromovinyl)-2'-deoxyuridine (RP101).

Induced chemoresistance leads to the reduction of apoptotic responses. Although several drugs are in development that circumvent or decrease existing chemoresistance, none has the potential to prevent or reduce its induction. Here, we present data from a drug that could perhaps fill this gap.