In agreement with our nutrigenomic results, a significant decreased adhesion of monocytes pre-exposed to MOF could be observed at the endothelial cells compared to control. The potential of grape seed extract to decrease adhesion of monocytes to HUVECs has been reported recently, however at concentrations ranging from 50 to 100 mg/ml. These concentrations are higher than the concentrations used in our study. Our results emphasize the capacity of grape seed– derived MOF to decrease the adhesion of immune cells to the vascular endothelium and potentially lower infiltration of these immune cells into the vascular wall, which is an initial step in atherosclerosis development. It has been reported that supplementation of the diet with catechin, a flavanol monomer present in MOF, results in lower atherosclerosis development in apolipoprotein E-deficient mice. It could be postulated that the regular consumption of MOF could decrease blood cell infiltration into the vasculature and potentially protect against atherosclerotic lesions in humans. Our bioinformatic data also revealed that over 30 differentially expressed genes are involved in different processes related to inflammation. The role of chronic inflammation in the promotion, initiation and development of chronic diseases, such as cancer, cardiovascular disease or osteoporosis has been described. In our study, among the differentially expressed genes involved in inflammatory processes is the gene coding for the proinflammatory cytokine IL2, of which the expression has been down-regulated by the MOF supplementation. Together with IL2, we also observed a decrease in the expression of a subunit of its receptor, the IL2RB gene. These inflammation-related genes, as well as some of the cell adhesion molecules, are regulated by the transcription factor NF-kB. Bioinformatic analyses of the nutrigenomic data identified several transcription factors potentially involved in the regulation of the expression of differentially expressed genes, among which is NF-kB. This suggests that NF-kB is a potential target by which MOF exert their anti-inflammatory effects in circulating blood cells. Interestingly, our nutrigenomic data also revealed an increase in the expression of the gene coding for NFKBIA, the endogenous inhibitor of NF-kB. A previous in vivo study in an atherosclerotic ApoE mouse model identified NF-kB as a major upstream regulator in leukocyte adhesion and transendothelial migration through the vascular endothelium. Moreover, NF-kB activity in peripheral blood mononuclear cells from smokers has been found to be significantly higher than in PBMCs from non-smokers. In order to corroborate a direct effect of MOF on NF-kB we performed NF-kB reporter gene studies in an inflammatory human monocyte/macrophage cell model. The experiments revealed a dose- and time-dependent repression of NF-kB luciferase expression in the presence of MOF.

A key inhibitor of osteoclast activity, osteoprotegrin, is normally enriched in the cochlea relative to other sites in the body. In mice, OPG is produced at high levels by fibrocytes within the spiral ligament and secreted in the perilymph. Mice deficient in OPG show excessive remodeling throughout the middle and inner ear resulting in severe hearing loss. While there are cases of FD causing sensorineural hearing loss in humans, it has been hypothesized that this is due to auditory neural compression from the FD bone changes. The results in our mouse model with FD like lesions would support that mechanism, as well as possibly physical changes to the ossicular chain, as opposed to pathologic changes of sensory structures as seen in such lesions as cochlear otosclerosis. These results point to a role for peri-lacunar remodeling in the cochlea that may be disrupted in FD. In conclusion, our results show that the cochlea is a unique bony structure characterized by limited bone turnover that confers protection from proliferative and metabolically active FD bony lesions. The invasive fibro-osseous lesions seen in this mouse model cause conductive hearing loss through involvement of the ossicular chain, in a manner very similar to that seen in humans. These mechanisms could be new pharmacologic targets to treat the skeletal or hearing manifestations of FD or other skeletal diseases. The vitrification process plays a key role in cryopreservation for the long term conservation of plant genetic resources. Vitrification is defined as a physical process by which a concentrated aqueous solution solidifies into a stable amorphous glass without the formation of ice crystals when the temperature is decreased. Vitrification of plant specimens can be achieved in many ways, including air drying of embryos, and more recently through the use of highly concentrated plant vitrification solutions that readily form glasses on cooling and inhibit crystallization. However, exposure to PVS must be controlled to enable sufficient cellular dehydration whilst limiting injury from chemical toxicity and establishment of a simple and high-throughput cryopreservation method using cryoprotectant is highly desirable. Plant vitrification solutions combine cryoprotectants that vary in permeability, such that cellular water is replaced, cell viscosity is increased and the freezing behaviour of the remaining water is altered. PVS2 is probably the most commonly used cryoprotectant for plant cells, tissues and embryos; for example, the cryopreservation of embryonic axes of citrus and in vitro shoot-tips of Parkia speciosa, a tropical species with recalcitrant seeds. The conventional approach to vitrification generally involves a tissue pre-culture step on sucrose-enriched medium, before cooling, with highly concentrated vitrification solution for a period that varies with species, tissue and temperature.