Detecting the effects of predator-induced stress on the global metabolism of an ungulate prey using fecal metabolomic fingerprinting.

Few field tests have assessed the effects of predator-induced stress on prey fitness, particularly in large carnivore-ungulate systems. Because traditional measures of stress present limitations when applied to free-ranging animals, new strategies and systemic methodologies are needed. Recent studies have shown that stress and anxiety related behaviors can influence the metabolic activity of the gut microbiome in mammal hosts, and these metabolic alterations may aid in identification of stress.

Fecal Metabolomics as a Novel Noninvasive Method for Short-Term Stress Monitoring in Beef Cattle.

Traditional measures of short-term stress response such as fecal glucocorticoid metabolites (FGM) are widely used in controlled settings to quantify the intensity of stimulation to which cattle are exposed. However, FGMs present several methodological and interpretation pitfalls when applied on animals in free-ranging conditions. In this study, we proposed an NMR-based fecal metabolomics strategy for noninvasive stress detection in beef cattle.

Dropwort-induced metabolic reprogramming restrains YAP/TAZ/TEAD oncogenic axis in mesothelioma.

Background: Over the past decade, newly designed cancer therapies have not significantly improved the survival of patients diagnosed with Malignant Pleural Mesothelioma (MPM). Among a limited number of genes that are frequently mutated in MPM several of them encode proteins that belong to the HIPPO tumor suppressor pathway.

Methods: The anticancer effects of the top flower standardized extract of Filipendula vulgaris (Dropwort) were characterized in "in vitro" and "in vivo" models of MPM.

Simulated microgravity promotes the formation of tridimensional cultures and stimulates pluripotency and a glycolytic metabolism in human hepatic and biliary tree stem/progenitor cells.

Many pivotal biological cell processes are affected by gravity. The aim of our study was to evaluate biological and functional effects, differentiation potential and exo-metabolome profile of simulated microgravity (SMG) on human hepatic cell line (HepG2) and human biliary tree stem/progenitor cells (hBTSCs). Both hBTSCs and HepG2 were cultured in a weightless and protected environment SGM produced by the Rotary Cell Culture System (Synthecon) and control condition in normal gravity (NG).

Gut microbiota signatures in cystic fibrosis: Loss of host CFTR function drives the microbiota enterophenotype.

Background: Cystic fibrosis (CF) is a disorder affecting the respiratory, digestive, reproductive systems and sweat glands. This lethal hereditary disease has known or suspected links to the dysbiosis gut microbiota. High-throughput meta-omics-based approaches may assist in unveiling this complex network of symbiosis modifications.

Metabolomics: Challenges and Opportunities in Systems Biology Studies.

Metabolomics has the capability of providing predisposition, diagnostic, prognostic, and therapeutic biomarker profiles of individual patients, since a large number of metabolites can be measured in an unbiased manner from biological samples. In this setting, H-Nuclear Magnetic Resonance (NMR) spectroscopy of biofluids such as plasma, urine, and fecal water offers the opportunity to identify patterns of biomarker changes that reflects the physiological or pathological status of an individual patient.In this chapter, we show as a metabolomics study can be used to diagnose a disease, classifying patients as healthy or as pathological taking into account individual variability.

Che-1 sustains hypoxic response of colorectal cancer cells by affecting Hif-1α stabilization.

Background: Solid tumours are less oxygenated than normal tissues. Consequently, cancer cells acquire to be adapted to a hypoxic environment. The poor oxygenation of solid tumours is also a major indicator of an adverse cancer prognosis and leads to resistance to conventional anticancer treatments.

3T multiparametric MRI of the prostate: Does intravoxel incoherent motion diffusion imaging have a role in the detection and stratification of prostate cancer in the peripheral zone?

Purpose: To evaluate the potential added value of the intravoxel incoherent motion model to conventional multiparametric magnetic resonance protocol in order to differentiate between healthy and neoplastic prostate tissue in the peripheral zone.

Material And Methods: Mono-exponential and bi-exponential fits were used to calculate ADC and IVIM parameters in 53 patients with peripheral zone biopsy proved tumor. Inferential statistics analysis was performed on T2, ADC and IVIM parameters (D, D*, f) comparing healthy and neoplastic tissues.

(1)H NMR Metabolomic Footprinting Analysis for the In Vitro Screening of Potential Chemopreventive Agents.

Metabolomics is the quantification and analysis of the concentration profiles of low-molecular-weight compounds present in biological samples. In particular metabolic footprinting analysis, based on the monitoring of metabolites consumed from and secreted into the growth medium, is a valuable tool for the study of pharmacological and toxicological effects of drugs. Mass spectrometry and nuclear magnetic resonance (NMR) are the two main complementary techniques used in this field.

¹H-NMR-Based Metabolomic Study for Identifying Serum Profiles Associated with the Response to Etanercept in Patients with Rheumatoid Arthritis.

Objective: A considerable proportion of patients with rheumatoid arthritis (RA) do not have a satisfactory response to biological therapies. We investigated the use of metabolomics approach to identify biomarkers able to anticipate the response to biologics in RA patients.

Methods: Due to gender differences in metabolomic profiling, the analysis was restricted to female patients starting etanercept as the first biological treatment and having a minimum of six months' follow-up.

Performance Assessment in Fingerprinting and Multi Component Quantitative NMR Analyses.

An interlaboratory comparison (ILC) was organized with the aim to set up quality control indicators suitable for multicomponent quantitative analysis by nuclear magnetic resonance (NMR) spectroscopy. A total of 36 NMR data sets (corresponding to 1260 NMR spectra) were produced by 30 participants using 34 NMR spectrometers. The calibration line method was chosen for the quantification of a five-component model mixture.

Metformin-induced metabolic reprogramming of chemoresistant ALDHbright breast cancer cells.

Metabolic remodeling is a hallmark of cancer progression and may affect tumor chemoresistance. Here we investigated by 1H-NMR/PCA analysis the metabolic profile of chemoresistant breast cancer cell subpopulations (ALDHbright cells) and their response to metformin, a promising anticancer metabolic modulator. The purified ALDHbright cells exhibited a different metabolic profile as compared to their chemosensitive ALDHlow counterparts.

Metabolomics approach in allergic and rheumatic diseases.

Metabolomics is the analysis of the concentration profiles of low molecular weight compounds present in biological fluids. Metabolites are nonpeptide molecules representing the end products of cellular activity. Therefore, changes in metabolite concentrations reveal the range of biochemical effects induced by a disease or its therapeutic intervention.

Metabolomics in rheumatic diseases: the potential of an emerging methodology for improved patient diagnosis, prognosis, and treatment efficacy.

Metabolomics belongs to the family of "-omics" sciences, also comprised of genomics, transcriptomics, and proteomics, all of which share the advantage of a non-targeted approach for identifying biomarkers and profiling the patient. This means that they do not require a preliminary knowledge of the substances to be studied. Moreover, even small quantities of biological fluids or tissues may be utilized for analysis.

Metformin elicits anticancer effects through the sequential modulation of DICER and c-MYC.

Diabetic patients treated with metformin have a reduced incidence of cancer and cancer-related mortality. Here we show that metformin affects engraftment and growth of breast cancer tumours in mice. This correlates with the induction of metabolic changes compatible with clear anticancer effects.

Metabolism and cell shape in cancer: a fractal analysis.

Fractal analysis in cancer cell investigation provided meaningful insights into the relationship between morphology and phenotype. Some reports demonstrated that changes in cell shape precede and trigger dramatic modifications in both gene expression and enzymatic function. Nonetheless, metabolomic pattern in cells undergoing shape changes have been not still reported.

Metabolic analysis of the removal of formic acid by unacclimated activated sludge.

This paper investigates the removal of formic acid by unacclimated biomass from a municipal activated sludge wastewater treatment plant. The biomass was initially able to remove formic acid, but its removal rate and Oxygen Uptake Rate (OUR) decreased with time, until formic acid removal stopped before the formic acid had been exhausted. Formaldehyde was removed in a similar way, whereas the same biomass was simultaneously able to grow and store PHAs when acetic acid was used as substrate.

Classification of prostatic diseases by means of multivariate analysis on in vivo proton MRSI and DCE-MRI data.

Multivariate analysis has been applied on proton magnetic resonance spectroscopic imaging ((1)H-MRSI) and dynamic contrast enhanced MRI (DCE-MRI) data of patients with different prostatic diseases such as chronic inflammation, fibrosis and adenocarcinoma. Multivariate analysis offers a global view of the entire range of information coming from both the imaging and spectroscopic side of NMR technology, leading to an integrated picture of the system relying upon the entire metabolic and dynamic profile of the studied samples. In this study, we show how this approach, applied to (1)H-MRSI/DCE-MRI results, allows us to differentiate among the various prostatic diseases in a non-invasive way with a 100% accuracy.

pH effects on the conformational preferences of amyloid beta-peptide (1-40) in HFIP aqueous solution by NMR spectroscopy.

The structure and aggregation state of amyloid beta-peptide (Abeta) in membrane-like environments are important determinants of pathological events in Alzheimer's disease. In fact, the neurotoxic nature of amyloid-forming peptides and proteins is associated with specific conformational transitions proximal to the membrane. Under certain conditions, the Abeta peptide undergoes a conformational change that brings the peptide in solution to a "competent state" for aggregation.

NMR-based metabolic profiling of human hepatoma cells in relation to cell growth by culture media analysis.

Metabolic profiling is a metabolomic approach that allows the characterization of metabolic phenotypes under specific set of conditions. In the present paper we investigated the metabolism of sparse and high density cultures in relation to different cell growth phases. Changes in the metabolome were evaluated by using 1H-NMR spectroscopy, correlation map and Multivariate Data Analysis on the net balances of metabolites in the medium.

Dissecting drug and vehicle metabolic effects in rats by a metabonomic approach.

A combined application of high resolution (1)H NMR spectroscopy and multivariate statistical techniques focused on establishing a consistent statistical approach to metabonomic studies was tested. The data reduction, which is preliminary to the application of multivariate analysis to NMR spectra, was carried out by means of two complementary methods: pure Pattern Recognition (PR) and Assigned Signal Analysis (ASA). The simultaneous use of both approaches allowed us to obtain additional information in the analysis of metabonomic data, compared to the use of PR alone.

Early events in protein aggregation: molecular flexibility and hydrophobicity/charge interaction in amyloid peptides as studied by molecular dynamics simulations.

In a previous article (Zbilut et al., Biophys J 2003;85:3544-3557), we demonstrated how an aggregation versus folding choice could be approached considering hydrophobicity distribution and charge. In this work, our aim is highlighting the mutual interaction of charge and hydrophobicity distribution in the aggregation process.

Protein aggregation/folding: the role of deterministic singularities of sequence hydrophobicity as determined by nonlinear signal analysis of acylphosphatase and Abeta(1-40).

The problem of protein folding vs. aggregation was investigated in acylphosphatase and the amyloid protein Abeta(1-40) by means of nonlinear signal analysis of their chain hydrophobicity. Numerical descriptors of recurrence patterns provided the basis for statistical evaluation of folding/aggregation distinctive features.