21st Century Tools for Nanotoxicology: Transcriptomic Biomarker Panel and Precision-Cut Lung Slice Organ Mimic System for the Assessment of Nanomaterial-Induced Lung Fibrosis.

There is an urgent need for reliable toxicity assays to support the human health risk assessment of an ever increasing number of engineered nanomaterials (ENMs). Animal testing is not a suitable option for ENMs. Sensitive in vitro models and mechanism-based targeted in vitro assays that enable accurate prediction of in vivo responses are not yet available. In this proof-of-principle study, publicly available mouse lung transcriptomics data from studies investigating xenobiotic-induced lung diseases are used and a 17-gene biomarker panel (PFS17) applicable to the assessment of lung fibrosis is developed. The PFS17 is validated using a limited number of in vivo mouse lung transcriptomics datasets from studies investigating ENM-induced responses. In addition, an ex vivo precision-cut lung slice (PCLS) model is optimized for screening of potentially inflammogenic and pro-fibrotic ENMs. Using bleomycin and a multiwalled carbon nanotube, the practical application of the PCLS method as a sensitive alternative to whole animal tests to screen ENMs that may potentially induce inhalation toxicity is shown. Conditional to further optimization and validation, it is established that a combination of PFS17 and the ex vivo PCLS method will serve as a robust and sensitive approach to assess lung inflammation and fibrosis induced by ENMs.

Examination of the Culturable Microbiota from Low-Moisture Foods Imported into Canada for Antibacterial Activity against Listeria monocytogenes.

ABSTRACT: Listeria monocytogenes, a resilient and ubiquitous foodborne pathogen, is associated with a high case-fatality rate in humans. This study investigated the culturable microbiota of low-moisture foods (LMFs) imported into Canada to see how well bacteria isolated from these foods could inhibit or inactivate the growth of L. monocytogenes. Imported LMFs were acquired from various supermarkets in the Greater Toronto Area (Ontario, Canada). The foods included dried apples, bee pollen, cumin seeds, date fruits, fennel seeds, pistachios, raisins, and seaweed. Bacterial strains were isolated from the foods using blood agar and then screened using an in-house-designed growth inhibition plate assay against L. monocytogenes. The inhibitory strains detected were then identified using 16S rRNA sequencing. Diverse bacteria were recovered from the foods; 236 isolates belonging to 122 observed phenotypes were obtained. From the inhibition plate assays, 10 of the 11 imported LMFs harbored inhibitory strains against L. monocytogenes, whereby 48 of the collected isolates (20%) were found to produce a zone of inhibition against this pathogen. The inhibitory strains belonged to six genera (Acinetobacter, Aerococcus, Bacillus, Lysinibacillus, Paenibacillus, and Sporosarcina) and 15 unique species. Among all foods tested, the date fruit microbiota displayed the greatest number and diversity of anti-L. monocytogenes inhibitory strains. Overall, it was found that the culturable microbiota of LMFs, imported into Canada, possess bacterial members that can inhibit the growth of L. monocytogenes. These results could lead to the discovery of either novel antimicrobial metabolites or beneficial anti-L. monocytogenes bacteria that could be added to foods to inactivate and/or control L. monocytogenes.