Plasma and Serum Metabolite Association Networks: Comparability within and between Studies Using NMR and MS Profiling

Blood is one of the most used biofluids in metabolomics studies, and the serum and plasma fractions are routinely used as a proxy for blood itself. Here we investigated the association networks of an array of 29 metabolites identified and quantified via NMR in the plasma and serum samples of two cohorts of ∼1000 healthy blood donors each. A second study of 377 individuals was used to extract plasma and serum samples from the same individual on which a set of 122 metabolites were detected and quantified using FIA–MS/MS. Four different inference algorithms (ARANCE, CLR, CORR, and PCLRC) were used to obtain consensus networks. The plasma and serum networks obtained from different studies showed different topological properties with the serum network being more connected than the plasma network. On a global level, metabolite association networks from plasma and serum fractions obtained from the same blood sample of healthy people show similar topologies, and at a local level, some differences arise like in the case of amino acids

Untargeted 1H-NMR Urine Metabolomic Analysis of Preterm Infants with Neonatal Sepsis

One of the most critical medical conditions occurring after preterm birth is neonatal sepsis, a systemic infection with high rates of morbidity and mortality, chiefly amongst neonates hospitalized in Neonatal Intensive Care Units (NICU). Neonatal sepsis is categorized as early-onset sepsis (EOS) and late-onset sepsis (LOS) regarding the time of the disease onset. The accurate early diagnosis or prognosis have hurdles to overcome, since there are not specific clinical signs or laboratory tests. Herein, a need for biomarkers presents, with the goals of aiding accurate medical treatment, reducing the clinical severity of symptoms and the hospitalization time. Through nuclear magnetic resonance (NMR) based metabolomics, we aim to investigate the urine metabolomic profile of septic neonates and reveal those metabolites which could be indicative for an initial discrimination between the diseased and the healthy ones. Multivariate and univariate statistical analysis between NMR spectroscopic data of urine samples from neonates that developed EOS, LOS, and a healthy control group revealed a discriminate metabolic profile of septic newborns. Gluconate, myo-inositol, betaine, taurine, lactose, glucose, creatinine and hippurate were the metabolites highlighted as significant in most comparisons

Metabolite and Bioactive Compounds Profiling of Meteora Sea Buckthorn Berries through High-Resolution NMR Analysis

Sea buckthorn berries (Hippophaë rhamnoides L.) (SB) are considered as a fruit with a high nutritional value with a plethora of bioactive ingredients. The present work focusses on the analysis of the whole NMR metabolic profile of SB berries grown in an organic orchard of Meteora/Greece. In parallel, this study validates/highlights qualitative characteristics of the osmotic processed berries according to the fresh fruit. The composition in bioactive metabolites of SB berries was elucidated through sophisticated high-resolution NMR spectroscopy. The lipophilic profile maintains the vitamins, flavonoid glycosides, phenolic esters and the essential lipid components of SB, while the polar profile reveals a variety of flavonoids, saccharides, organic acids, amino acids and esterified glycosides. This approach towards identification of SB bioactive ingredients may serve as basis for simultaneous profiling and quality assessment and may be applied to monitor fresh food quality regarding other food preservation methods

Three-dimensional cell metabolomics deciphers the anti-angiogenic properties of the radioprotectant amifostine

Aberrant angiogenesis is a hallmark for cancer and inflammation, a key notion in drug repurposing efforts. To delineate the anti-angiogenic properties of amifostine in a human adult angiogenesis model via 3D cell metabolomics and upon a stimulant-specific manner, a 3D cellular angiogenesis assay that recapitulates cell physiology and drug action was coupled to untargeted metabolomics by liquid chromatography-mass spectrometry and nuclear magnetic resonance spectroscopy. The early events of angiogenesis upon its most prominent stimulants (vascular endothelial growth factor-A or deferoxamine) were addressed by cell sprouting measurements. Data analyses consisted of a series of supervised and unsupervised methods as well as univariate and multivariate approaches to shed light on mechanism-specific inhibitory profiles. The 3D untargeted cell metabolomes were found to grasp the early events of angiogenesis. Evident of an initial and sharp response, the metabolites identified primarily span amino acids, sphingolipids, and nucleotides. Profiles were pathway or stimulant specific. The amifostine inhibition profile was rather similar to that of sunitinib, yet distinct, considering that the latter is a kinase inhibitor. Amifostine inhibited both. The 3D cell metabolomics shed light on the anti-angiogenic effects of amifostine against VEGF-A- and deferoxamine-induced angiogenesis. Amifostine may serve as a dual radioprotective and anti-angiogenic agent in radiotherapy patients