Supporting data for the MS identification of distinct transferrin glycopeptide glycoforms and citrullinated peptides associated with inflammation or autoimmunity

This data article presents the results of all the statistical analyses applied to the relative intensities of the detected 2D-DiGE protein spots for each of the 3 performed DiGE experiments. The data reveals specific subsets of protein spots with significant differences between WT and CD38-deficient mice with either Collagen-induced arthritis (CIA), or with chronic inflammation induced by CFA, or under steady-state conditions. This article also shows the MS data analyses that allowed the identification of the protein species which serve to discriminate the different experimental groups used in this study. Moreover, the article presents MS data on the citrullinated peptides linked to specific protein species that were generated in CIA(+) or CFA-treated mice. Lastly, this data article provides MS data on the efficiency of the analyses of the transferrin (Tf) glycopeptide glycosylation pattern in spleen and serum from CIA(+) mice and normal controls. The data supplied in this work is related to the research article entitled "identification of multiple transferrin species in spleen and serum from mice with collagen-induced arthritis which may reflect changes in transferrin glycosylation associated with disease activity: the role of CD38" [1]. All mass spectrometry data have been deposited to the ProteomeXchange Consortium via the PRIDE partner repository with identifiers PRIDE: PXD002644, PRIDE: PXD002643, PRIDE: PXD003183 and PRIDE: PXD003163

Role of FGFs in the control of programmed cell death during limb development

10 páginas, 8 figuras.We have investigated the role of FGFs in the control of programmed cell death during limb development by analyzing the effects of increasing and blocking FGF signaling in the avian limb bud. BMPs are currently considered as the signals responsible for cell death. Here we show that FGF signaling is also necessary for apoptosis and that the establishment of the areas of cell death is regulated by the convergence of FGF- and BMP-mediated signaling pathways. As previously demonstrated, cell death is inhibited for short intervals (12 hours) after administration of FGFs. However, this initial inhibition is followed (24 hours) by a dramatic increase in cell death, which can be abolished by treatments with a BMP antagonist (Noggin or Gremlin). Conversely, blockage of FGF signaling by applying a specific FGF-inhibitor (SU5402) into the interdigital regions inhibits both physiological cell death and that mediated by exogenous BMPs. Furthermore, FGF receptors 1, 2 and 3 are expressed in the autopodial mesoderm during the regression of the interdigital tissue, and the expression of FGFR3 in the interdigital regions is regulated by FGFs and BMPs in the same fashion as apopotosis. Together our findings indicate that, in the absence of FGF signaling BMPs are not sufficient to trigger apoptosis in the developing limb. Although we provide evidence for a positive influence of FGFs on BMP gene expression, the physiological implication of FGFs in apoptosis appears to result from their requirement for the expression of genes of the apoptotic cascade. We have identified MSX2 and Snail as candidate genes associated with apoptosis the expression of which requires the combined action of FGFs and BMPs.This work was supported by grants to J. M. H. (DGESIC/PM98-0061 and Fundación Valdecilla) to M. A. N. (DGESIC/PM98-0125) and to D. Macias (Junta de Extremadura; IPR99C035). J. J. S.-E. was supported by an MRC programme grant to Cheryll Tickle; J. C.-M. was supported by DGAPA (UNAM) and J. A. M. by a grant from the Junta de Extremadura (Consejeria de Educación y Juventud/Fondo Social Europeo).Peer reviewe

Profibrotic role of inducible heat shock protein 90α isoform in systemic sclerosis

Systemic sclerosis (SSc) is an autoimmune disease that affects skin and multiple internal organs. TGF-β, a central trigger of cutaneous fibrosis, activates fibroblasts with the involvement of the stress-inducible chaperone heat shock protein 90 isoform α (Hsp90α). Available evidence supports overexpression and secretion of Hsp90α as a feature in profibrotic pathological conditions. The aim of this work is to investigate the expression and function of Hsp90α in experimental models of skin fibrosis such as human fibroblasts, C57BL/6 mice, and in human SSc. For this purpose, we generated a new experimental model based on doxorubicin administration with improved characteristics with respect to the bleomycin model. We visualized disease progression in vivo by fluorescence imaging. In this work, we obtained Hsp90α mRNA overexpression in human skin fibroblasts, in bleomycin- and doxorubicin-induced mouse fibrotic skin, and in lungs of bleomycin- and doxorubicin-treated mice. Hsp90α-deficient mice showed significantly decreased skin thickness compared with wild-type mice in both animal models. In SSc patients, serum Hsp90α levels were increased in patients with lung involvement and in patients with the diffuse form of SSc (dSSc) compared with patients with the limited form of SSc. The serum Hsp90α levels of patients dSSc were correlated with the Rodnan score and the forced vital capacity variable. These results provide new supportive evidence of the contribution of the Hsp90α isoform in the development of skin fibrosis. In SSc, these results indicated that higher serum levels were associated with dSSc and lung fibrosis.This work was supported by Spanish Ministerio de Economía, Industria y Competitividad, Gobierno de España Grant RTI2018-095214-B-I00, as well as by the Instituto de Formación e Investigación Marqués de Valdecilla IDIVAL (InnVal 17/22; InnVal 20/34), 2020UCI22-PUB-0003 Gobierno de Cantabria (to A.V.V.), SAF2016-75195-R (to J.M.), SAF2017-82905-R (to R.M.), and (NextVal 18/14) to A.P

Mesoporous silica microparticles gated with a bulky azo derivative for the controlled release of dyes/ drugs in colon

[EN] Mesoporous silica microparticles were prepared, loaded with the dye safranin O (M-Saf) or with the drug budesonide (M-Bud) and capped by the grafting of a bulky azo derivative. Cargo release from M-Saf at different pH values (mimicking those found in the gastrointestinal tract) in the absence or presence of sodium dithionite (a reducing agent mimicking azoreductase enzyme present in the colon) was tested. Negligible safranin O release was observed at pH 6.8 and 4.5, whereas a moderate delivery at pH 1.2 was noted and attributed to the hydrolysis of the urea bond that linked the azo derivative onto the external surface of the inorganic scaffold. Moreover, a marked release was observed when sodium dithionite was present and was ascribed to the rupture of the azo bond in the molecular gate. Budesonide release from M-Bud in the presence of sodium dithionite was also assessed by ultraviolet-visible spectroscopy and high performance liquid chromatography measurements. In addition, preliminary in vivo experiments with M-Saf carried out in mice indicated that the chemical integrity of the microparticles remained unaltered in the stomach and the small intestine, and safranin O seemed to be released in the colon.We thank the Spanish Government (projects MAT2015-64139-C4-4-R, MAT2015-64139-C4-2-R and MAT2015-64139-C4-1-R) and Generalitat Valenciana (project PROMETEOII/2014/047 and project AICO/2017/093) for financial support.Ferri, D.; Gaviña, P.; Parra Álvarez, M.; Costero, AM.; El Haskouri, J.; Amorós Del Toro, P.; Merino Sanjuán, V.... (2018). Mesoporous silica microparticles gated with a bulky azo derivative for the controlled release of dyes/ drugs in colon. Royal Society Open Science. 5(8). https://doi.org/10.1098/rsos.180873S58Xu, X.-M., & Zhang, H.-J. (2016). miRNAs as new molecular insights into inflammatory bowel disease: Crucial regulators in autoimmunity and inflammation. World Journal of Gastroenterology, 22(7), 2206-2218. doi:10.3748/wjg.v22.i7.2206DeFilippis, E. M., Longman, R., Harbus, M., Dannenberg, K., & Scherl, E. J. (2016). Crohn’s Disease: Evolution, Epigenetics, and the Emerging Role of Microbiome-Targeted Therapies. Current Gastroenterology Reports, 18(3). doi:10.1007/s11894-016-0487-zFakhoury, M., Al-Salami, H., Negrulj, R., & Mooranian, A. (2014). Inflammatory bowel disease: clinical aspects and treatments. Journal of Inflammation Research, 113. doi:10.2147/jir.s65979Mowat, C., Cole, A., Windsor, A., Ahmad, T., Arnott, I., … Driscoll, R. (2011). Guidelines for the management of inflammatory bowel disease in adults. Gut, 60(5), 571-607. doi:10.1136/gut.2010.224154Zeng, J., Lv, L., & Mei, Z.-C. (2017). Budesonide foam for mild to moderate distal ulcerative colitis: A systematic review and meta-analysis. Journal of Gastroenterology and Hepatology, 32(3), 558-566. doi:10.1111/jgh.13604Gareb, B., Eissens, A. C., Kosterink, J. G. W., & Frijlink, H. W. (2016). Development of a zero-order sustained-release tablet containing mesalazine and budesonide intended to treat the distal gastrointestinal tract in inflammatory bowel disease. European Journal of Pharmaceutics and Biopharmaceutics, 103, 32-42. doi:10.1016/j.ejpb.2016.03.018Marín-Jiménez, I., & Peña, A. S. (2006). Budesonide for ulcerative colitis. Revista Española de Enfermedades Digestivas, 98(5). doi:10.4321/s1130-01082006000500007Abdalla, M. I., & Herfarth, H. (2016). Budesonide for the treatment of ulcerative colitis. Expert Opinion on Pharmacotherapy, 17(11), 1549-1559. doi:10.1080/14656566.2016.1183648Horcajada, P., Chalati, T., Serre, C., Gillet, B., Sebrie, C., Baati, T., … Gref, R. (2009). Porous metal–organic-framework nanoscale carriers as a potential platform for drug delivery and imaging. Nature Materials, 9(2), 172-178. doi:10.1038/nmat2608Florek, J., Caillard, R., & Kleitz, F. (2017). Evaluation of mesoporous silica nanoparticles for oral drug delivery – current status and perspective of MSNs drug carriers. Nanoscale, 9(40), 15252-15277. doi:10.1039/c7nr05762hDu, X., Li, X., Xiong, L., Zhang, X., Kleitz, F., & Qiao, S. Z. (2016). Mesoporous silica nanoparticles with organo-bridged silsesquioxane framework as innovative platforms for bioimaging and therapeutic agent delivery. Biomaterials, 91, 90-127. doi:10.1016/j.biomaterials.2016.03.019Argyo, C., Weiss, V., Bräuchle, C., & Bein, T. (2013). Multifunctional Mesoporous Silica Nanoparticles as a Universal Platform for Drug Delivery. Chemistry of Materials, 26(1), 435-451. doi:10.1021/cm402592tNoureddine, A., & Brinker, C. J. (2018). Pendant/bridged/mesoporous silsesquioxane nanoparticles: Versatile and biocompatible platforms for smart delivery of therapeutics. Chemical Engineering Journal, 340, 125-147. doi:10.1016/j.cej.2018.01.086Wight, A. P., & Davis, M. E. (2002). Design and Preparation of Organic−Inorganic Hybrid Catalysts. Chemical Reviews, 102(10), 3589-3614. doi:10.1021/cr010334mStein, A. (2003). Advances in Microporous and Mesoporous Solids—Highlights of Recent Progress. Advanced Materials, 15(10), 763-775. doi:10.1002/adma.200300007Alberti, S., Soler-Illia, G. J. A. A., & Azzaroni, O. (2015). Gated supramolecular chemistry in hybrid mesoporous silica nanoarchitectures: controlled delivery and molecular transport in response to chemical, physical and biological stimuli. Chemical Communications, 51(28), 6050-6075. doi:10.1039/c4cc10414eColl, C., Bernardos, A., Martínez-Máñez, R., & Sancenón, F. (2012). Gated Silica Mesoporous Supports for Controlled Release and Signaling Applications. Accounts of Chemical Research, 46(2), 339-349. doi:10.1021/ar3001469Croissant, J., Maynadier, M., Gallud, A., Peindy N’Dongo, H., Nyalosaso, J. L., Derrien, G., … Zink, J. I. (2013). Two-Photon-Triggered Drug Delivery in Cancer Cells Using Nanoimpellers. Angewandte Chemie, 125(51), 14058-14062. doi:10.1002/ange.201308647Croissant, J., Chaix, A., Mongin, O., Wang, M., Clément, S., Raehm, L., … Zink, J. I. (2014). Two-Photon-Triggered Drug Delivery via Fluorescent Nanovalves. Small, 10(9), 1752-1755. doi:10.1002/smll.201400042Ambrogio, M. W., Thomas, C. R., Zhao, Y.-L., Zink, J. I., & Stoddart, J. F. (2011). Mechanized Silica Nanoparticles: A New Frontier in Theranostic Nanomedicine. Accounts of Chemical Research, 44(10), 903-913. doi:10.1021/ar200018xBansal, A., & Zhang, Y. (2014). Photocontrolled Nanoparticle Delivery Systems for Biomedical Applications. Accounts of Chemical Research, 47(10), 3052-3060. doi:10.1021/ar500217wDoane, T. L., & Burda, C. (2012). The unique role of nanoparticles in nanomedicine: imaging, drug delivery and therapy. Chemical Society Reviews, 41(7), 2885. doi:10.1039/c2cs15260fAmidon, S., Brown, J. E., & Dave, V. S. (2015). Colon-Targeted Oral Drug Delivery Systems: Design Trends and Approaches. AAPS PharmSciTech, 16(4), 731-741. doi:10.1208/s12249-015-0350-9Hua, S., Marks, E., Schneider, J. J., & Keely, S. (2015). Advances in oral nano-delivery systems for colon targeted drug delivery in inflammatory bowel disease: Selective targeting to diseased versus healthy tissue. Nanomedicine: Nanotechnology, Biology and Medicine, 11(5), 1117-1132. doi:10.1016/j.nano.2015.02.018Aznar, E., Oroval, M., Pascual, L., Murguía, J. R., Martínez-Máñez, R., & Sancenón, F. (2016). Gated Materials for On-Command Release of Guest Molecules. Chemical Reviews, 116(2), 561-718. doi:10.1021/acs.chemrev.5b00456Llopis-Lorente, A., Lozano-Torres, B., Bernardos, A., Martínez-Máñez, R., & Sancenón, F. (2017). Mesoporous silica materials for controlled delivery based on enzymes. Journal of Materials Chemistry B, 5(17), 3069-3083. doi:10.1039/c7tb00348jPopat, A., Jambhrunkar, S., Zhang, J., Yang, J., Zhang, H., Meka, A., & Yu, C. (2014). Programmable drug release using bioresponsive mesoporous silica nanoparticles for site-specific oral drug delivery. Chem. Commun., 50(42), 5547-5550. doi:10.1039/c4cc00620hLi, X., Tang, T., Zhou, Y., Zhang, Y., & Sun, Y. (2014). Applicability of enzyme-responsive mesoporous silica supports capped with bridged silsesquioxane for colon-specific drug delivery. Microporous and Mesoporous Materials, 184, 83-89. doi:10.1016/j.micromeso.2013.09.024Teruel, A., Coll, C., Costero, A., Ferri, D., Parra, M., Gaviña, P., … Sancenón, F. (2018). Functional Magnetic Mesoporous Silica Microparticles Capped with an Azo-Derivative: A Promising Colon Drug Delivery Device. Molecules, 23(2), 375. doi:10.3390/molecules23020375Bernardos, A., Aznar, E., Marcos, M. D., Martínez-Máñez, R., Sancenón, F., Soto, J., … Amorós, P. (2009). Enzyme-Responsive Controlled Release Using Mesoporous Silica Supports Capped with Lactose. Angewandte Chemie International Edition, 48(32), 5884-5887. doi:10.1002/anie.200900880Llopis-Lorente, A., Díez, P., Sánchez, A., Marcos, M. D., Sancenón, F., Martínez-Ruiz, P., … Martínez-Máñez, R. (2017). Interactive models of communication at the nanoscale using nanoparticles that talk to one another. Nature Communications, 8(1). doi:10.1038/ncomms15511Viscido, A., Capannolo, A., Latella, G., Caprilli, R., & Frieri, G. (2014). Nanotechnology in the treatment of inflammatory bowel diseases. Journal of Crohn’s and Colitis, 8(9), 903-918. doi:10.1016/j.crohns.2014.02.024Kickelbick, G. (2004). Hybrid Inorganic–Organic Mesoporous Materials. Angewandte Chemie International Edition, 43(24), 3102-3104. doi:10.1002/anie.200301751Perry, M. J., Mendes, E., Simplício, A. L., Coelho, A., Soares, R. V., Iley, J., … Francisco, A. P. (2009). Dopamine- and tyramine-based derivatives of triazenes: Activation by tyrosinase and implications for prodrug design. European Journal of Medicinal Chemistry, 44(8), 3228-3234. doi:10.1016/j.ejmech.2009.03.025Cabrera, S., El Haskouri, J., Guillem, C., Latorre, J., Beltrán-Porter, A., Beltrán-Porter, D., … Amorós *, P. (2000). Generalised syntheses of ordered mesoporous oxides: the atrane route. Solid State Sciences, 2(4), 405-420. doi:10.1016/s1293-2558(00)00152-

Gated Mesoporous Silica Nanocarriers for a "two-Step" Targeted System to Colonic Tissue

[EN] Colon targeted drug delivery is highly relevant not only to treat colonic local diseases but also for systemic therapies. Mesoporous silica nanoparticles (MSNs) have been demonstrated as useful systems for controlled drug release given their biocompatibility and the possibility of designing gated systems able to release cargo only upon the presence of certain stimuli. We report herein the preparation of three gated MSNs able to deliver their cargo triggered by different stimuli (redox ambient (S1), enzymatic hydrolysis (S2), and a surfactant or being in contact with cell membrane (S3)) and their performance in solution and in vitro with Caco-2 cells. Safranin O dye was used as a model drug to track cargo fate. Studies of cargo permeability in Caco-2 monolayers demonstrated that intracellular safranin O levels were significantly higher in Caco-2 monolayers when using MSNs compared to those of free dye. Internalization assays indicated that S2 nanoparticles were taken up by cells via endocytosis. S2 nanoparticles were selected for in vivo tests in rats. For in vivo assays, capsules were filled with S2 nanoparticles and coated with Eudragit FS 30 D to target colon. The enteric coated capsule containing the MSNs was able to deliver S2 nanoparticles in colon tissue (first step), and then nanoparticles were able to deliver safranin O inside the colonic cells after the enzymatic stimuli (second step). This resulted in high levels of safranin O in colonic tissue combined with low dye levels in plasma and body tissues. The results suggested that this combination of enzyme-responsive gated MSNs and enteric coated capsules may improve the absorption of drugs in colon to treat local diseases with a reduction of systemic effects.The authors acknowledge the financial support from the Spanish Government (Projects MAT2015-64139-C4-1-R, SAF2016-78756 and AGL2015-70235-C2-2-R) and the Generalitat Valenciana (Project GVA/2014/13).Gonzalez-Alvarez, M.; Coll Merino, MC.; Gonzalez-Alvarez, I.; Giménez Morales, C.; Aznar, E.; Martínez-Bisbal, M.; Lozoya Agulló, I.... (2017). Gated Mesoporous Silica Nanocarriers for a "two-Step" Targeted System to Colonic Tissue. Molecular Pharmaceutics. 14(12):4442-4453. https://doi.org/10.1021/acs.molpharmaceut.7b00565S44424453141

Cd38 deficiency ameliorates chronic graft versus Host disease murine lupus via a b-cell dependent mechanism

Trabajo presentado en el II Congreso investigación PTS, celebrado en Granada (España) del 09 al 11 de febrero de 2022.Absence of mouse cell surface receptor CD38 in Cd38-/- mice suggests that this receptor acts as positive regulator of inflammatory and autoimmune responses. Here we report that in the setting of a chronic graft versus host disease (cGVHD) lupus model induced by the transfer of B6.C-H2bm12/KhEg (bm12) spleen cells into co-isogenic Cd38-/- B6 mice causes milder lupus-like autoimmunity with lower levels of anti-ssDNA autoantibodies than the transfer of bm12 spleen cells into WT B6 mice. I In addition, significantly lower percentages of Tfh cells, as well as GC B cells, plasma cells and T-bet+CD11chi B cells are observed in Cd38-/- mice than in WT mice, while the expansion of Treg cells, and Tfr cells is normal, suggesting that the ability of Cd38-/- B cells to respond to allogeneic help from bm12 CD4+ T cells is greatly diminished. The frequencies of T-bet+CD11chi B cells, which are considered the precursors of the autoantibody secreting cells, correlate with anti-ssDNA autoantibody serum levels, with IL-27, and sCD40L. Proteomics profiling of spleens from WT cGVHD mice reflects a STAT1-driven type I IFN-signature, which is absent in Cd38-/- cGVHD mice. Kidney, spleen and liver inflammation was mild and resolved faster in Cd38-/- cGVHD mice than in WT cGVHD mice. We conclude that in B cells CD38 functions as a modulator receptor that controls autoimmune responses

Equality, Equity, and Diversity: Educational Solutions in the Basque Country

Public education is one of the greatest achievements of European countries during the twentieth century. While schooling systems neither exclusively form citizens, nor are they sufficient to alleviate all inequalities, education plays an increasingly important strategic role in relieving social problems and promoting the civic and ethical upbringing of our children. Researchers and professors at the UPV/EHU have had the privilege to design and implement important educational projects in conjunction with government of Autonomous Community of the Basque Country, which has the authority over education in its territory. This book presents the timely (in most cases since 2000) observations, research, and programs that have resulted from this cooperation. Our stress—in both our theoretical and analytical dimensions—has been on the importance of diversity, the promotion of social and human values, and respect for basic human rights. In addition, we describe the cooperation that must be fostered—and the various needs met—between all educational "agents": academic researchers, administrators, teachers, parents, and the community at large to promote equality and fairness in our society.This book was published with generous financial support from the Basque Government.Introduction: Alfonso Unceta and Concepción Medrano ? Part 1 Education in the Basque Country ? 1. Education Provision in the Basque Country by Alfonso Unceta and Andrés Davila ? 2. Addressing Basque Diversity in the Classroom: Measures to Avoid Excluding At-Risk Youth by Begoña Martínez Domínguez ? 3. Improving Social Interaction: Experimentally Validated Proposals for Psycho-educational Intervention by Maite Garaigodobil and Jone Aliri ? 4. Socialization to Prevent Gender Violence in the Basque Country by Maria José Alonso Olea, Aitor Gómez González, and Nekane Beloki Arizti ? 5. Resolution and Transformation of At-School Conflicts by Ramón Alzate Sáez de Heredia, Lucía Gorbeña, and Cristina Merino ? Part 2 Socioeducational Context in the Basque Country ? 6. Learning Communities: A Basque Egalitarian Educational Project by Maite Arandia Loroño, Isabel Martínez Domínguez, and Iñaki Santa Cruz Ayo ? 7. Migrants en Route: Community Socioeducational Action by Miguel Arriaga Landeta and Begoña Abad Miguélez ? 8. Educating from the Family: A Proposal to Connect Homes and Institutions by Enrique Arranz Freijo, Fernando Olabarrieta Artetxe, Juan Luis Martín Ayala ? 9. The Development of Values and the Media by Concepción Medrano, Ana Aierbe, and Juan Ignacio Martínez de Morentin ? Index ? List of Contributor

CD38 Deficiency Ameliorates Chronic Graft-Versus-Host Disease Murine Lupus via a B-Cell-Dependent Mechanism

© 2021 Martínez-Blanco, Domínguez-Pantoja, Botía-Sánchez, Pérez-Cabrera, Bello-Iglesias, Carrillo-Rodríguez, Martin-Morales, Lario-Simón, Pérez-Sánchez-Cañete, Montosa-Hidalgo, Guerrero-Fernández, Longobardo-Polanco, Redondo-Sánchez, Cornet-Gomez, Torres-Sáez, Fernández-Ibáñez, Terrón-Camero, Andrés-León, O’Valle, Merino, Zubiaur and Sancho.The absence of the mouse cell surface receptor CD38 in Cd38−/− mice suggests that this receptor acts as a positive regulator of inflammatory and autoimmune responses. Here, we report that, in the context of the chronic graft-versus-host disease (cGVHD) lupus inducible model, the transfer of B6.C-H2bm12/KhEg(bm12) spleen cells into co-isogenic Cd38−/− B6 mice causes milder lupus-like autoimmunity with lower levels of anti-ssDNA autoantibodies than the transfer of bm12 spleen cells into WT B6 mice. In addition, significantly lower percentages of Tfh cells, as well as GC B cells, plasma cells, and T-bet+CD11chi B cells, were observed in Cd38−/− mice than in WT mice, while the expansion of Treg cells and Tfr cells was normal, suggesting that the ability of Cd38−/− B cells to respond to allogeneic help from bm12 CD4+ T cells is greatly diminished. The frequencies of T-bet+CD11chi B cells, which are considered the precursors of the autoantibody-secreting cells, correlate with anti-ssDNA autoantibody serum levels, IL-27, and sCD40L. Proteomics profiling of the spleens from WT cGVHD mice reflects a STAT1-driven type I IFN signature, which is absent in Cd38−/− cGVHD mice. Kidney, spleen, and liver inflammation was mild and resolved faster in Cd38−/− cGVHD mice than in WT cGVHD mice. We conclude that CD38 in B cells functions as a modulator receptor that controls autoimmune responses.S and MZ received financial support through “Proyecto del Plan Estatal”: SAF2017–89801-R. The IPBLN-CSIC Proteomics Unit belonged to ProteoRed-ISCIII (PRB2; PRB3) and was supported by grants PT13/0001/0011 (IPBLN-CSIC) and PT17/0019/0010 (CIB-CSIC; IPBLN-CSIC). RM: Project: SAF2017-82905-R. FO'V: Cátedra MIS IMPLANT-UGR. The stay of AC-G in Sancho’s lab was supported by a fellowship-contract JAE-Intro (CSIC). The stay of MD-P in Sancho’s lab was supported by a 1-year post-doctoral fellowship (Reference No. 502492) from the Consejo Nacional de Ciencia y Tecnología (CONACYT) of México. EA-L was recipient of a postdoctoral fellowship from the regional Andalusian Government

AKT activation seems to be associated with apoptotic signals and not with pro-survival signals in a pristane-induced lupus model.

Several studies have shown that in addition to its role as a survival factor and tumor promoting agent, AKT is also able to exhibit pro-apoptotic effects under diverse conditions, including oxidative stress, cytokine stimulation and exposure to cytotoxic chemicals like staurosporine, methotrexate, docetaxel and etoposide. Moreover, phosphorylation of second mitochondria-derived activator of caspases (SMAC) by AKT promotes caspase-3 activation during etoposide-induced apoptosis in HeLa cells. Our data show that injection of pristane into the peritoneum induces apoptosis-mediated cell death of peritoneal exudate cells (PECs), as evidenced by the increased number of annexin V+ peritoneal cells and their increased levels of cleaved/active caspase-3. Indeed, the higher levels of activated caspase-3 protein in WT PECs, particularly at 2-weeks post pristane treatment, are indicative of a higher rate of apoptosis compared to Cd38¿/¿ cells. In contrast, no differences were observed in the levels of MCL-1, an anti-apoptotic protein and member of the BCL2 family. Furthermore, kinases ERK1/2 and AKT showed distinct activation kinetics in pristane-elicited PECs. Interestingly, caspase-3 activation followed similar kinetics to AKT activation in both WT and Cd38¿/¿ PECs, while ERK activation correlated with increased levels of MCL-1. In summary our data strongly suggest that in the pristane-induced lupus model AKT activation is associated with apoptotic signals and not with survival signals. Further studies, however, are required to identify specific pro- and anti-apoptotic target proteins that are phosphorylated by ERK or AKT following pristane treatment, and that regulate the apoptotic process

Functional magnetic mesoporous silica microparticles capped with an azo-derivative: A promising colon drug delivery device

[EN] Magnetic micro-sized mesoporous silica particles were used for the preparation of a gated material able to release an entrapped cargo in the presence of an azo-reducing agent and, to some extent, at acidic pH. The magnetic mesoporous microparticles were loaded with safranin O and the external surface was functionalized with an azo derivative 1 (bearing a carbamate linkage) yielding solid S1. Aqueous suspensions of S1 at pH 7.4 showed negligible safranin O release due to the presence of the bulky azo derivative attached onto the external surface of the inorganic scaffold. However, in the presence of sodium dithionite (azoreductive agent), a remarkable safranin O delivery was observed. At acidic pH, a certain safranin O release from S1 was also found. The pH-triggered safranin O delivery was ascribed to the acid-induced hydrolysis of the carbamate moiety that linked the bulky azo derivatives onto the mesoporous inorganic magnetic support. The controlled release behavior of S1 was also tested using a model that simulated the gastro intestinal tract.We thank the Spanish Government (projects MAT2015-64139-C4-1-R and AGL2015-70235C2-2-R (MINECO/FEDER)) and the Generalitat Valenciana (project PROMETEOII/2014/047) for support. AHT thanks to the Spanish MEC for his FPU grant. The authors also thank the Electron Microscopy Service at the Universitat Politecnica de Valencia for support. SCSIE (Universitat de Valencia) is also gratefully acknowledged for all the equipment employed. NMR was registered at the U26 facility of ICTS "NANBIOSIS" at the Universitat de Valencia. The authors thanks L.A. Villaescusa for his helpful discussion about the 1H-NMR analysis of the composition of loaded and functionalized supports.Teruel, AH.; Coll Merino, MC.; Costero, AM.; Ferri, D.; Parra Álvarez, M.; Gaviña, P.; Gonzalez -Alvarez, M.... (2018). Functional magnetic mesoporous silica microparticles capped with an azo-derivative: A promising colon drug delivery device. Molecules. 23(2). https://doi.org/10.3390/molecules23020375S23