Metabolomics Provides Novel Insights into the Potential Toxicity Associated with Heated Tobacco Products, Electronic Cigarettes, and Tobacco Cigarettes on Human Bronchial Epithelial BEAS-2B Cells.

Smoking is an established risk factor for various pathologies including lung cancer. Electronic cigarettes (e-cigs) and heated tobacco products (HTPs) have appeared on the market in recent years, but their safety or, conversely, their toxicity has not yet been demonstrated. This study aimed to compare the metabolome of human lung epithelial cells exposed to emissions of e-cigs, HTPs, or 3R4F cigarettes in order to highlight potential early markers of toxicity.

Prediction of a Large-Scale Database of Collision Cross-Section and Retention Time Using Machine Learning to Reduce False Positive Annotations in Untargeted Metabolomics.

Metabolite identification in untargeted metabolomics is complex, with the risk of false positive annotations. This work aims to use machine learning to successively predict the retention time (Rt) and the collision cross-section (CCS) of an open-access database to accelerate the interpretation of metabolomic results. Standards of metabolites were tested using liquid chromatography coupled with high-resolution mass spectrometry.

P-glycoprotein (ABCB1) and breast cancer resistance protein (ABCG2) localize in the microvessels forming the blood-tumor barrier in ependymomas.

Ependymomas are neuroepithelial tumors that arise from the ependymal layer bordering the cerebral ventricles and spinal canal. Intracranial ependymoma represents a major encephalic tumor in children, while spinal ependymoma develops more frequently in adults. To understand the pharmacoresistance that characterizes this tumoral entity, we analyzed the level of expression and localization of three major efflux transport proteins with a multidrug resistance function, P-glycoprotein, multidrug resistance-related protein 1 (MRP1) and breast cancer resistance protein (BCRP), in a series of 25 ependymomas from both children and adults.

Selective tonicity-induced expression of the neutral amino-acid transporter SNAT2 in oligodendrocytes in rat brain following systemic hypertonicity.

Sodium-coupled neutral amino-acid transporter member 2 (SNAT2) belongs to the family of neutral amino-acid transporters. SNAT2 is encoded by the gene Slc38a2, whose expression was reported to increase in vitro in fibroblasts, endothelial and renal cells exposed to a hypertonic medium. SNAT2 tonicity-induced expression brings about cellular accumulation of amino-acid, which contributes to osmoadaptation to hypertonicity.

Gene expression profiling in brain following acute systemic hypertonicity: novel genes possibly involved in osmoadaptation.

In brain osmoprotective genes known to be involved in cellular osmoadaptation to hypertonicity, as well as the related transcription factor tonicity-responsive enhancer binding protein (TonEBP) are only expressed in some cell subsets. In the search for other genes possibly involved in osmoadaptation of brain cells we have analyzed, through microarray, the transcriptional profile of forebrain from rats subjected to 45 min, 90 min, and 6 h systemic hypertonicity. Microarray data were validated by quantitative real-time PCR.

Antihyperglycemic activity of Arbutus unedo, Ammoides pusilla and Thymelaea hirsuta.

The effect of the water extract (WE) of three medicinal plants used as antidiabetic medication in Eastern Morocco (Arbutus unedo: Au, Ammoides pusilla: Ap and Thymelaea hirsuta: Th) was tested in rats with the Oral Glucose Tolerance Test (OGTT) and Intravenous Glucose Tolerance Test (IVGTT). In the OGTT the rats received water, glibenclamide (2 mg/kg) or WE (500 mg/kg for Au and 250 mg/kg for Th and Ap) 30 min before glucose loading (glucose: 1 g/kg). The WE of Au, Ap and Th produced a significant decrease in glycemia after glucose loading.

Large discrepancies in cellular distribution of the tonicity-induced expression of osmoprotective genes and their regulatory transcription factor TonEBP in rat brain.

Osmoprotective genes are tonicity-activated genes involved in cellular osmoadaptation to hypertonicity and considered to be regulated by a specific transcription factor called tonicity-responsive enhancer-binding protein (TonEBP). In the brain we had previously established that TonEBP was expressed and tonicity-induced in neurons only. Here we have compared in various brain regions of rats subjected to systemic hypertonicity, the cellular expression of TonEBP through immunocytochemistry and the cellular expression of osmoprotective genes, namely aldose reductase (AR), sodium-dependent myo-inositol transporter (SMIT), betaine/GABA transporter (BGT1) and taurine transporter (TauT), by in situ hybridization using non-radioactive digoxigenin-labeled riboprobes.

Differential cellular distribution of tonicity-induced expression of transcription factor TonEBP in the rat brain following prolonged systemic hypertonicity.

In a previous work performed on cerebral cortex and hippocampus we reported that tonicity-responsive enhancer binding protein (TonEBP), originally identified as a transactivator of osmoprotective genes involved in osmoadaptation of renal cells, was induced in neurons only, but to varying levels, following acute systemic hypertonicity. Whether or not this cellular specificity reflected a unique ability of neurons or a differential time course among brain cells for tonicity-induction of TonEBP was investigated throughout the brain in this study by subjecting the animals to prolonged systemic hypertonicity. In normal rats, TonEBP immunolabeling and TonEBP-mRNA in situ hybridization labeling showed a widespread, uneven and parallel distribution.