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Besides its classical function of bone metabolism regulation, 1alpha, 25-dihydroxyvitamin D3 (1,25(OH) 2 D 3 ), acts on a variety of tissues including the nervous system, where the hormone plays an important role as neuroprotective, antiproliferating and differentiating agent. Sphingolipids are bioactive lipids that play critical and complex roles in regulating cell fate. In the present paper we have investigated whether sphingolipids are involved in the protective action of 1,25(OH) 2 D 3. We have found that 1,25(OH) 2 D 3 prevents amyloid-β peptide (Aβ(1−42)) cytotoxicity both in differentiated SH-SY5Y human neuroblastoma cells and in vivo . In differentiated SH-SY5Y cells, Aβ(1−42) strongly reduces the sphingosine-1-phosphate (S1P)/ceramide (Cer) ratio while 1,25(OH) 2 D 3 partially reverts this effect. 1,25(OH) 2 D 3 reverts also the Aβ(1−42)-induced reduction of sphingosine kinase activity. We have also studied the crosstalk between 1,25(OH) 2 D 3 and S1P signaling pathways downstream to the activation of S1P receptor subtype S1P1. Notably, we found that 1,25(OH) 2 D 3 prevents the reduction of S1P1 expression promoted by Aβ(1−42) and thereby it modulates the downstream signaling leading to ER stress damage (p38MAPK/ATF4). Similar effects were observed by using ZK191784. In addition, chronic treatment with 1,25(OH) 2 D 3 protects from aggregated Aβ(1−42)-induced damage in the CA1 region of the rat hippocampus and promotes cell proliferation in the hippocampal dentate gyrus of adult mice. In conclusion, these results represent the first evidence of the role of 1,25(OH) 2 D 3 and its structural analogue ZK191784 in counteracting the Aβ(1−42) peptide-induced toxicity through the modulation of S1P/S1P1/p38MAPK/ATF4 pathway in differentiated SH-SY5Y cells.

In the present work, X-rayphotoelectronspectroscopy (XPS) was used to study the surface chemical composition of three alloys for biomedical applications: Ti–7Nb–6Al, Ti–13Nb–13Zr and Ti–15Zr–4Nb. The surface of these alloys was modified by annealing in air at 750 °C for different times with the aim of developing an oxide thick layer on top. The evolution of surface composition with annealing time was studied by XPS, and compared with the composition of the native oxide layer present on the samples before annealing. Two different oxidation trends were observed depending on the alloying elements and their corresponding diffusion kinetics, which give rise to different chemical species at the topmost layers. These results were linked with an evaluation of the biological response of the alloys by bringing them in contact with human peripheral blood mononuclear cells (PBMC)., This work has been partially supported by the Spanish MEC under Projects MAT-2008-01497/NAN, MAT-2007-66719-C03-03, MAT-2006-13348 and CSD2007-00041, and by grants from Italian MIUR.