Cellular effects in an in vitro human 3D cellular airway model and A549/BEAS-2B in vitro cell cuultures following air exposure to cerium oxide particles at an air-liquid interface

There is a need for representative in vitro models to assess the effects of airborne particles on lung health. The ob-jective of this study was to assess the cellular effects of cerium oxide (Ce02) particles exposed via an air—liquid interface in three relevant cell models in parallel. BEAS-2B, A549, and MucilAirTM cells were exposed for 1 hour...

Prediction of the carcinogenic potential of human pharmaceuticals using repeated dose toxicity data and their pharmacological properties

In an exercise designed to reduce animal use, we analyzed the results of rat subchronic toxicity studies from 289 pharmaceutical compounds with the aim to predict the tumor outcome of carcinogenicity studies in this species. The results were obtained from the assessment reports available at the Medicines Evaluation Board of the Netherlands for...

Omics analysis of low dose acetaminophen intake demonstrates novel response pathways in humans

Acetaminophen is the primary cause of acute liver toxicity in Europe/USA, which led the FDA to reconsider recommendations concerning safe acetaminophen dosage/use. Unfortunately, the current tests for liver toxicity are no ideal predictive markers for liver injury, i.e. they only measure acetaminophen exposure after profound liver toxicity has...

Plasma metabolomics and proteomics profiling after a postprandial challenge reveal subtle diet effects on human metabolic status

We introduce the metabolomics and proteomics based Postprandial Challenge Test (PCT) to quantify the postprandial response of multiple metabolic processes in humans in a standardized manner. The PCT comprised consumption of a standardized 500 ml dairy shake containing respectively 59, 30 and 12 energy percent lipids, carbohydrates and protein....

Epigenetics: DNA demethylation promotes skeletal myotube maturation

Mesenchymal progenitor cells can be differentiated in vitro into myotubes that exhibit many characteristic features of primary mammalian skeletal muscle fibers. However, in general, they do not show the functional excitation-contraction coupling or the striated sarcomere arrangement typical of mature myofibers. Epigenetic modifications have been...

Delineation of amplification, hybridization and location effects in microarray data yields better-quality normalization

Background: Oligonucleotide arrays have become one of the most widely used high-throughput tools in biology. Due to their sensitivity to experimental conditions, normalization is a crucial step when comparing measurements from these arrays. Normalization is, however, far from a solved problem. Frequently, we encounter datasets with significant...

Developing computational model-based diagnostics to analyse clinical chemistry data

This article provides methodological and technical considerations to researchers starting to develop computational model-based diagnostics using clinical chemistry data.These models are of increasing importance, since novel metabolomics and proteomics measuring technologies are able to produce large amounts of data that are difficult to...