Targeted urine metabolomics in preterm neonates with intraventricular hemorrhage.

Intraventricular hemorrhage (IVH) is a major cause of morbidity and mortality in preterm neonates. Elucidation of the mechanisms underlying IVH and/or development of disease biomarkers is essential. The aim of the study was to investigate the urine metabolic profile of preterm neonates (gestational age < 32 weeks) IVH and explore the role of metabolomics in understanding pathophysiological mechanisms of the disease from which novel biomarkers could be derived. In this single-center, prospective, case-control study, urine samples were collected from seven preterm infants with early IVH (IVH group) and from 11 preterm ones without IVH (control group) on days 1, 3 and 9 of life. Urine metabolites were evaluated using targeted liquid chromatography-tandem mass spectrometry. Demographic and perinatal-clinical characteristics were recorded. Univariate and multivariate statistical analyses were performed. Orthogonal Partial Least Squares-Discriminant Analysis showed that the study groups differed significantly due to alternation in 20 out of the 40 metabolites detected in the urine. Elevated differentiated metabolites included energy intermediates and other important compounds, whereas reduced ones various amino acids, hypoxanthine and nicotinamide. A set of metabolites showed high performance as indicators of IVH, especially during day 1. As evidenced by metabolomics, preterm neonates with IVH demonstrate significant metabolism perturbations. Potentially, a selected panel of metabolites could be used as urine biomarkers of IVH development and/or progression in high-risk preterm infants.

Metabolic profiling study of shikonin's cytotoxic activity in the Huh7 human hepatoma cell line.

Shikonin and its enantiomer alkannin, which are natural products, have been extensively studied in vitro and in vivo for, among others, their antitumor activity. The investigation of the molecular pathways involved in their action is of interest, since they are not yet clearly defined. Metabolic profiling in cells can provide a picture of a cell's phenotype upon intervention, assisting in the elucidation of the mechanism of action. In this study, the cytotoxic effect of shikonin on a human hepatocarcinoma cell line was studied. Huh7 cells were treated with shikonin at 5 µM, and it was found that shikonin markedly inhibited cell growth. Metabolic profiling indicated alterations in the metabolic content of the cells and the culture media upon treatment, detecting the metabolic response of the cells. This study demonstrates the potential of metabolomics to improve knowledge on the mechanisms involved in shikonin's antitumor action.