Silica Materials for Medical Applications

The two main applications of silica-based materials in medicine and biotechnology, i.e. for bone-repairing devices and for drug delivery systems, are presented and discussed. The influence of the structure and chemical composition in the final characteristics and properties of every silica-based material is also shown as a function of the both applications presented. The adequate combination of the synthesis techniques, template systems and additives leads to the development of materials that merge the bioactive behavior with the drug carrier ability. These systems could be excellent candidates as materials for the development of devices for tissue engineering

Different methylation signatures at diagnosis in patients with high-risk myelodysplastic syndromes and secondary acute myeloid leukemia predict azacitidine response and longer survival

Background: Epigenetic therapy, using hypomethylating agents (HMA), is known to be effective in the treatment of high-risk myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) patients who are not suitable for intensive chemotherapy and/or allogeneic stem cell transplantation. However, response rates to HMA are low and there is an unmet need in finding prognostic and predictive biomarkers of treatment response and overall survival. We performed global methylation analysis of 75 patients with high-risk MDS and secondary AML who were included in CETLAM SMD-09 protocol, in which patients received HMA or intensive treatment according to age, comorbidities and cytogenetic. Results: Unsupervised analysis of global methylation pattern at diagnosis did not allow patients to be differentiated according to the cytological subtype, cytogenetic groups, treatment response or patient outcome. However, after a supervised analysis we found a methylation signature defined by 200 probes, which allowed differentiating between patients responding and non-responding to azacitidine (AZA) treatment and a different methylation pattern also defined by 200 probes that allowed to differentiate patients according to their survival. On studying follow-up samples, we confirmed that AZA decreases global DNA methylation, but in our cohort the degree of methylation decrease did not correlate with the type of response. The methylation signature detected at diagnosis was not useful in treated samples to distinguish patients who were going to relapse or progress. Conclusions: Our findings suggest that in a subset of specific CpGs, altered DNA methylation patterns at diagnosis may be useful as a biomarker for predicting AZA response and survival

Different methylation signatures at diagnosis in patients with high-risk myelodysplastic syndromes and secondary acute myeloid leukemia predict azacitidine response and longer survival

Altres ajuts: This work was supported in part by a grant from [...] and a grant from Celgene Spain. Research in the Buschbeck and Zamora labs is further supported by the following grants: [...] the Deutsche José Carreras Leukämie Stiftung DJCLS 14R/2018 (to MB);[...] and Fundació La Marató de TV3 254/C/2019 (to MB). Research at the IJC is supported by the "La Caixa" Foundation, the Fundació Internacional Josep Carreras, Celgene Spain and[...].Epigenetic therapy, using hypomethylating agents (HMA), is known to be effective in the treatment of high-risk myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) patients who are not suitable for intensive chemotherapy and/or allogeneic stem cell transplantation. However, response rates to HMA are low and there is an unmet need in finding prognostic and predictive biomarkers of treatment response and overall survival. We performed global methylation analysis of 75 patients with high-risk MDS and secondary AML who were included in CETLAM SMD-09 protocol, in which patients received HMA or intensive treatment according to age, comorbidities and cytogenetic. Unsupervised analysis of global methylation pattern at diagnosis did not allow patients to be differentiated according to the cytological subtype, cytogenetic groups, treatment response or patient outcome. However, after a supervised analysis we found a methylation signature defined by 200 probes, which allowed differentiating between patients responding and non-responding to azacitidine (AZA) treatment and a different methylation pattern also defined by 200 probes that allowed to differentiate patients according to their survival. On studying follow-up samples, we confirmed that AZA decreases global DNA methylation, but in our cohort the degree of methylation decrease did not correlate with the type of response. The methylation signature detected at diagnosis was not useful in treated samples to distinguish patients who were going to relapse or progress. Our findings suggest that in a subset of specific CpGs, altered DNA methylation patterns at diagnosis may be useful as a biomarker for predicting AZA response and survival

Low temperature synthesis of bioactive materials Síntese de materiais bioativos a baixas temperaturas

Bioactive materials possess properties that allow them to interact with natural tissues to induce reactions that favor the development and regeneration of those tissues. In this study, silica was prepared by the sol-gel method, using tetraethylorthosilicate as the precursor. The calcium and phosphor sources used here were calcium ethoxy and phosphoric acid, respectively, in ethanol solvent. The solid obtained was dried at 50 ºC. In vitro bioactivity assays were performed by soaking the materials in simulated body fluid (SBF). The samples were characterized by transmission electron microscopy (TEM), thermal analysis and photoluminescence. TEM images of the samples before contact with SBF revealed amorphous aggregates and after 12 days in SBF showed two phases, one amorphous with large quantities of Si and O, and the other a crystalline phase whose composition contained Ca and P. The electron diffraction pattern showed a planar distance of 2.86 Å, corresponding to 2&#952; = 32.2º. This was ascribed to hydroxyapatite. The Eu III was used as structural probe. The relative band intensity correspondent the transition 5D0 &#8594; 7F2 / 5D0 &#8594; 7F1 showed a high symmetry surrounding the Eu III ion. These materials, produced by the sol-gel route, open up new possibilities for obtaining bioactive biomaterials for medical applications.<br>Os materiais bioativos apresentam propriedades que permitem a sua interação com um tecido de origem natural podendo induzir a sua regeneração. Neste estudo, o método sol-gel foi utilizado para a preparação de sílica dopada com íons cálcio e fósforo, partindo dos precursores tetraetilortosilicato, etóxido de cálcio e ácido fosfórico em etanol como solvente. O sólido obtido foi seco a 50 ºC. Ensaios de bioatividade foram realizados in vitro em uma solução que simula o fluido corpóreo (SBF). As amostras foram caracterizadas por microscopia eletrônica de transmissão (MET), análise térmica e fotoluminescência. As imagens de MET das amostras antes do contato com SBF revelou a presença de aglomerados amorfos. Depois de 12 dias em SBF a amostra apresentou duas fases, uma amorfa com grande quantidade de silício e oxigênio, e outra cristalina contendo cálcio e fósforo. A difração de elétrons mostrou uma distância planar de 2,86 Å, correspondendo a 2&#952; = 32,2º. Esse ângulo foi atribuído ao principal pico da hidroxiapatita. O íon Eu III foi usado como sonda estrutural, apresentando em seu espectro de emissão uma intensidade relativa entre as transições 5D0 &#8594; 7F2 / 5D0 &#8594;7F1 que indica um ambiente de alta simetria para este íon. Estes materiais obtidos pelo método sol-gel a baixa temperatura apresentam possibilidade de se obter biomateriais bioativos para aplicação em medicina