The expression of TRAIL receptors in human VICs is associated inhibitor supplier with the sensitivity to TRAIL-mediated apoptosis involving caspase-3 activation [8]. VICs cultured in an osteogenic medium express higher mRNA levels of runx2 and OCN, together with the increase of DR4 levels compared to medium alone [8]; moreover, the addition of TRAIL to the osteogenic medium leads to a significant increase of mineralized matrix nodule deposition [8]. Taken together, all of these results suggest an active role of TRAIL-induced apoptosis in the pathogenesis of CAVD.5. ConclusionsAlthough, to date, no medical therapeutic options are able to prevent or reduce the progression of CAVD and the only treatment for severe AS is surgical aortic valve replacement (AVR), the understanding of the underlying pathogenic mechanisms of the disease is mandatory to identify promising therapeutic targets.

It is known that the recently available biologic drugs neutralizing RANKL and TNF-��, key cytokines in CAVD pathogenesis, are having a great success in the treatment of osteoporosis and arthritis, respectively [135, 136]. Thus, it could be that in the future these molecules could be useful in CAVD treatment/prevention, also because a strong association has been demonstrated between arterial and valvular calcification and osteoporotic bone remodelling [137].
In calcareous soils, phosphorus (P) retention and mobilization take place due to precipitation and adsorption; however, it is not always easy to distinguish between the two mechanisms. Water soluble P fertilizers applied to soil react with the soil constituents to form less soluble phosphates.

When added to soil containing large amounts of calcium, soluble P is usually precipitated as dicalcium phosphate or octacalcium phosphate [1]. At low P concentration up to 0.4mgL?1, active CaCO3 and/or Fe dithionite could result in P adsorption whereas, at high concentration, precipitation could be predominant over the adsorption process [2]. The reactivity of CaCO3 in soils depends upon the specific surface area of the carbonate and on its total surface area [3]. It has been demonstrated [4] that Ca2+ is dominant ion in Drug_discovery soil solution of calcareous soils and it is possible that formation of less soluble complexes with weak acid anions like orthophosphate is due to unavoidable dominance of this ion. The dynamics of P is managed by calcite, which strongly holds P and consequently maintains low P concentration in soil solution. It was noted [2] that low CaCO3 showed an upper limit of P adsorption varying from 1.4 to 3.5mg P kg?1 that was not modified by further increment of P in solution. Conversely, in soil with high CaCO3 content, P adsorption increased up to the maximum experimental concentration of P in solution (2gL?1).