Project description:The aim of this study was to examine the effects of dietary supplementation of St John’s wort extract on azoxymethane-induced colorectal carcinogenesis in mice. Microarray data showed atttenuation of NF-kB and ERK-mediated pathway in colon epithelium by St. Jone's wort suggesting that the anti-inflammatory effect is a possible cancer-preventing mechanism induced by St. Jone's wort. Gene expression will be compared between mice with the control vs. St. Jone's wort.
Project description:When confronted with non-psychotic mental disorders, pregnant women often refrain from using synthetic drugs. Instead, they resort to well-known herbal medicines (phytopharmaceuticals) such as St. John's wort, California poppy, valerian, lavender, and hops, which have proven sedative, anxiolytic, or antidepressant properties. Nevertheless, these herbal medicines are not officially approved in pregnancy due to lack of safety data. Using a variety of in vitro methods (determination of cytotoxicity, apoptosis induction, genotoxicity, effects on metabolic properties, inhibition/induction of differentiation) in a commonly used placental cell line (BeWo b30), we could previously show that extracts from these plants are likely to be safe at usual clinical doses. In the present work, we wanted to deepen our safety assessment of these herbal medicines by (i) looking for possible effects on gene expression and (ii) using the same in vitro methods to characterize effects of selected phytochemicals that might conceivably cause safety issues. Proteomics results were promising as none of the five extracts significantly affected the protein expression by up- or down-regulation. Protopine (contained in California poppy), valerenic acid (in valerian), and linalool (in lavender) were inconspicuous in all experiments and showed no adverse effects. Hyperforin and hypericin (two constituents from St. John's wort) and valtrate (typical for valerian) were the most discernible phytochemicals with respect to the selected safety parameters (cytotoxic and apoptotic effects). A decrease in BeWo b30 viability was evident with hypericin (≥ 1 µM) and valtrate (≥ 10 µM), whereas hyperforin (≥ 3 µM), hypericin (30 µM) and valtrate (≥ 10 µM) induced cell apoptosis. None of the tested phytochemicals resulted in genotoxic effects at concentrations of 0.1 and 1 µM and thus are not DNA damaging. No decrease in glucose consumption or lactate production was observed under the influence of the phytochemicals, except for valtrate (at all concentrations). No compound induced or inhibited BeWo b30 cell differentiation, except for hyperforin (≥ 1 µM) that had an inhibitory effect. This study confirms previous observations suggesting that the extracts from St. John's wort, California poppy, valerian, lavender, and hops are likely to be safe during pregnancy. Attainment of high plasma concentrations of a few relevant compounds – hyperforin and hypericin from St. John's wort and valtrate from valerian – deserves though special attention. Clinical studies during pregnancy are needed to substantiate these in vitro data.
Project description:Introgressed variants from other species can be an important source of genetic variation because they may arise rapidly, can include multiple mutations on a single haplotype, and have often been pretested by selection in the species of origin. Although introgressed alleles are generally deleterious, several studies have reported introgression as the source of adaptive alleles-including the rodenticide-resistant variant of Vkorc1 that introgressed from Mus spretus into European populations of Mus musculus domesticus. Here, we conducted bidirectional genome scans to characterize introgressed regions into one wild population of M. spretus from Spain and three wild populations of M. m. domesticus from France, Germany, and Iran. Despite the fact that these species show considerable intrinsic postzygotic reproductive isolation, introgression was observed in all individuals, including in the M. musculus reference genome (GRCm38). Mus spretus individuals had a greater proportion of introgression compared with M. m. domesticus, and within M. m. domesticus, the proportion of introgression decreased with geographic distance from the area of sympatry. Introgression was observed on all autosomes for both species, but not on the X-chromosome in M. m. domesticus, consistent with known X-linked hybrid sterility and inviability genes that have been mapped to the M. spretus X-chromosome. Tract lengths were generally short with a few outliers of up to 2.7 Mb. Interestingly, the longest introgressed tracts were in olfactory receptor regions, and introgressed tracts were significantly enriched for olfactory receptor genes in both species, suggesting that introgression may be a source of functional novelty even between species with high barriers to gene flow.