The use of garlic and garlic-based extracts has been linked to decreased incidence of cancer in epidemiological studies. Here we examine the molecular and cellular activities of a simple homemade ethanol-based garlic extract (GE). We show that GE inhibits growth of several different cancer cells in vitro, as well as cancer growth in vivo in a syngeneic orthotopic breast cancer model. Multiple myeloma cells were found to be especially sensitive to GE. The GE was fractionated using solid-phase extractions, and we identified allicin in one GE fraction; however, growth inhibitory activities were found in several additional fractions. These activities were lost during freeze or vacuum drying, suggesting that the main anti-cancer compounds in GE are volatile. The anti-cancer activity was stable for more than six months in −20 °C. We found that GE enhanced the activities of chemotherapeutics, as well as MAPK and PI3K inhibitors. Furthermore, GE affected hundreds of proteins involved in cellular signalling, including changes in vital cell signalling cascades regulating proliferation, apoptosis, and the cellular redox balance. Our data indicate that the reduced proliferation of the cancer cells treated by GE is at least partly mediated by increased endoplasmic reticulum (ER) stress.

Absolute quantification of intracellular metabolite pools is a prerequisite for modeling and in-depth biological interpretation of metabolomics data. It is the final step of an elaborate metabolomics workflow, with challenges associated with all steps—from sampling to quantifying the physicochemically diverse metabolite pool. Chromatographic separation combined with mass spectrometric (MS) detection is the superior platform for high coverage, selective, and sensitive detection of metabolites. Herein, we apply our quantitative MS-metabolomics workflow to measure and present the central carbon metabolome of a panel of commonly applied biological model systems. The workflow includes three chromatographic methods combined with isotope dilution tandem mass spectrometry to allow for absolute quantification of 68 metabolites of glycolysis, the pentose phosphate pathway, the tricarboxylic acid cycle, and the amino acid and (deoxy) nucleoside pools. The biological model systems; Bacillus subtilis, Saccharomyces cerevisiae, two microalgal species, and four human cell lines were all cultured in commonly applied culture media and sampled in exponential growth phase. Both literature and databases are scarce with comprehensive metabolite datasets, and existing entries range over several orders of magnitude. The workflow and metabolite panel presented herein can be employed to expand the list of reference metabolomes, as encouraged by the metabolomics community, in a continued effort to develop and refine high-quality quantitative metabolomics workflows.

Studies in mice with ablation of Prnp , the gene that encodes the cellular prion protein (PrP ^C ), have led to the hypothesis that PrP ^C is important for peripheral nerve myelin maintenance. Here, we have used a nontransgenic animal model to put this idea to the test; namely, goats that, due to a naturally occurring nonsense mutation, lack PrP ^C . Teased nerve fiber preparation revealed a demyelinating pathology in goats without PrP ^C . Affected nerves were invaded by macrophages and T cells and displayed vacuolated fibers, shrunken axons, and onion bulbs. Peripheral nerve lipid composition was similar in young goats with or without PrP ^C , but markedly different between corresponding groups of adult goats, reflecting the progressive nature of the neuropathy. This is the first report of a subclinical demyelinating polyneuropathy caused by loss of PrP ^C function in a nontransgenic mammal.

Plastics constitute a vast array of substances, with over 16000 known plastic chemicals, including intentionally and non-intentionally added substances. Thousands of chemicals, including toxic ones, are extractable from plastics, however, the extent to which these compounds migrate from everyday products into food or water remains poorly understood. This study aims to characterize the endocrine and metabolism disrupting activity, as well as the chemical composition of migrates from plastic food contact articles (FCAs) from four countries as significant sources of human exposure. Fourteen plastic FCAs covering seven polymer types with high global market shares were migrated into water and a water-ethanol mixture as food simulants according to European regulations. The migrates were analyzed using reporter gene assays for nuclear receptors relevant to human health and non-target chemical analysis to characterize the chemical composition. Chemicals migrating from each FCA interfered with at least two nuclear receptors, predominantly targeting pregnane X receptor (24/28 migrates). Moreover, peroxisome proliferator receptor gamma was activated by 19 out of 28 migrates, though mostly with lower potencies. Estrogenic and antiandrogenic activity was detected in eight and seven migrates, respectively. Fewer chemicals and less toxicity migrated into water compared to the water-ethanol mixture. However, 73 % of the 15 430 extractable chemical features also transferred into food simulants, and the water-ethanol migrates exhibited a similar toxicity prevalence compared to methanol extracts. The chemical complexity differed largely between FCAs, with 8 to 10631 chemical features migrating into food simulants. Using stepwise partial least squares regressions, we successfully narrowed down the list of potential active chemicals, identified known endocrine disrupting chemicals, such as triphenyl phosphate, and prioritized chemical features for further identification. This study demonstrates the migration of endocrine and metabolism disrupting chemicals from plastic FCAs into food simulants, rendering a migration of these compounds into food and beverages probable.

Carotenoids are pigments that have a range of functions in human health. The carotenoid diatoxanthin is suggested to have antioxidant, anti-inflammatory and chemo-preventive properties. Diatoxanthin is only produced by a few groups of microalgae, where it functions in photoprotection. Its large-scale production in microalgae is currently not feasible. In fact, rapid conversion into the inactive pigment diadinoxanthin is triggered when cells are removed from a high-intensity light source, which is the case during large-scale harvesting of microalgae biomass. Zeaxanthin epoxidase (ZEP) 2 and/or ZEP3 have been suggested to be responsible for the back-conversion of high-light accumulated diatoxanthin to diadinoxanthin in low-light in diatoms. Using CRISPR/Cas9 gene editing technology, we knocked out the ZEP2 and ZEP3 genes in the marine diatom Phaeodactylum tricornutum to investigate their role in the diadinoxanthin–diatoxanthin cycle and determine if one of the mutant strains could function as a diatoxanthin production line. Light-shift experiments proved that ZEP3 encodes the enzyme converting diatoxanthin to diadinoxanthin in low light. Loss of ZEP3 caused the high-light-accumulated diatoxanthin to be stable for several hours after the cultures had been returned to low light, suggesting that zep3 mutant strains could be suitable as commercial production lines of diatoxanthin.