Rios R.,University of Granada |
Lupianez C.B.,University of Granada |
Campa D.,German Cancer Research Center |
Campa D.,University of Pisa |
And 31 more authors.
Endocrine-Related Cancer | Year: 2015
Type 2 diabetes (T2D) has been suggested to be a risk factor for multiple myeloma (MM), but the relationship between the two traits is still not well understood. The aims of this study were to evaluate whether 58 genome-wide-association-studies (GWAS)-identified common variants for T2D influence the risk of developing MM and to determine whether predictive models built with these variants might help to predict the disease risk. We conducted a case-control study including 1420MMpatients and 1858 controls ascertained through the International Multiple Myeloma (IMMEnSE) consortium. Subjects carrying the KCNQ1rs2237892T allele or the CDKN2A-2Brs2383208G/G, IGF1rs35767T/T and MADDrs7944584T/T genotypes had a significantly increased risk of MM(odds ratio (OR)=1.32-2.13) whereas those carrying the KCNJ11rs5215C, KCNJ11rs5219T and THADArs7578597C alleles or the FTOrs8050136A/A and LTArs1041981C/C genotypes showed a significantly decreased risk of developing the disease (OR=0.76-0.85). Interestingly, a prediction model including those T2D-related variants associated with the risk of MM showed a significantly improved discriminatory ability to predict the disease when compared to a model without genetic information (area under the curve (AUC)=0.645 vs AUC=0.629; P=4.05× 10-06). A gender-stratified analysis also revealed a significant gender effect modification for ADAM30rs2641348 and NOTCH2rs10923931 variants (Pinteraction=0.001 and 0.0004, respectively). Men carrying the ADAM30rs2641348C and NOTCH2rs10923931T alleles had a significantly decreased risk of MM whereas an opposite but not significant effect was observed in women (ORM=0.71 and ORM=0.66 vs ORW=1.22 and ORW=1.15, respectively). These results suggest that TD2-related variants may influence the risk of developing MM and their genotyping might help to improve MM risk prediction models. © 2015 Society for Endocrinology.
Martin C.J.,Harvard University |
Booty M.G.,Harvard University |
Rosebrock T.R.,Harvard University |
Nunes-Alves C.,Harvard University |
And 7 more authors.
Cell Host and Microbe | Year: 2012
Mycobacterium tuberculosis persists within macrophages in an arrested phagosome and depends upon necrosis to elude immunity and disseminate. Although apoptosis of M. tuberculosis-infected macrophages is associated with reduced bacterial growth, the bacteria are relatively resistant to other forms of death, leaving the mechanism underlying this observation unresolved. We find that after apoptosis, M. tuberculosis-infected macrophages are rapidly taken up by uninfected macrophages through efferocytosis, a dedicated apoptotic cell engulfment process. Efferocytosis of M. tuberculosis sequestered within an apoptotic macrophage further compartmentalizes the bacterium and delivers it along with the apoptotic cell debris to the lysosomal compartment. M. tuberculosis is killed only after efferocytosis, indicating that apoptosis itself is not intrinsically bactericidal but requires subsequent phagocytic uptake and lysosomal fusion of the apoptotic body harboring the bacterium. While efferocytosis is recognized as a constitutive housekeeping function of macrophages, these data indicate that it can also function as an antimicrobial effector mechanism. © 2012 Elsevier Inc.
Silva A.,University of Minho |
Oliveira T.,University of Minho |
Novais P.,University of Minho |
Neves J.,University of Minho |
Leao P.,Bs Pt Government Associate Laboratory
Advances in Intelligent Systems and Computing | Year: 2016
In this work a 5-year survival prediction model was developed for colon cancer using machine learning methods. The model was based on the SEER dataset which, after preprocessing, consisted of 38,592 records of colon cancer patients. Survival prediction models for colon cancer are not widely and easily available. Results showed that the performance of the model using fewer features is close to that of the model using a larger set of features recommended by an expert physician, which indicates that the first may be a good compromise between usability and performance. The purpose of such a model is to be used in Ambient Assisted Living applications, providing decision support to health care professionals. © Springer International Publishing Switzerland 2016.
Silva N.A.,University of Minho |
Silva N.A.,Bs PT Government Associate Laboratory |
Moreira J.,University of Minho |
Moreira J.,Bs PT Government Associate Laboratory |
And 14 more authors.
Biochimie | Year: 2013
It has been demonstrated that bone marrow mesenchymal stem cell (BM-MSCs) transplantation has beneficial effects on several central nervous system (CNS) debilitating conditions. Growing evidence indicate that trophic factors secreted by these cells are the key mechanism by which they are acting. These cells are frequently used in combination with 3D artificial matrices, for instance hydrogels, in tissue engineering-based approaches. However, so far, no study has been reported on the influence of such matrices, namely the presence or absence of extracellular matrix motifs, on BM-MSCs secretome and its effects in neuronal cell populations. In this sense, we herein studied the impact of a hydrogel, gellan gum, on the behavior and secretome of BM-MSCs, both in its commercial available form (commonly used in tissue engineering) and in a fibronectin peptide-modified form. The results showed that in the presence of a peptide in the gellan gum hydrogel, BM-MSCs presented higher proliferation and metabolic activity than in the regular hydrogel. Moreover, the typical spindle shape morphology of BM-MSCs was only observed in the modified hydrogel. The effects of the secretome of BM-MSCs were also affected by the chemical nature of the extracellular matrix. BM-MSCs cultured in the modified hydrogel were able to secrete factors that induced higher metabolic viabilities and neuronal cell densities, when compared to those of the unmodified hydrogel. Thus adding a peptide sequence to the gellan gum had a significant effect on the morphology, activity, proliferation and secretome of BM-MSCs. These results highlight the importance of mimicking the extracellular matrix when BM-MSCs are cultured in hydrogels for CNS applications. © 2013 Elsevier Masson SAS. All rights reserved.
Thorvaldsson A.,Swerea IVF |
Thorvaldsson A.,Chalmers University of Technology |
Silva-Correia J.,European Institute of Excellence on Tissue Engineering and Regenerative Medicine |
Silva-Correia J.,Bs PT Government Associate Laboratory |
And 6 more authors.
Journal of Applied Polymer Science | Year: 2013
In this work a new method is presented to efficiently produce hydrogel scaffolds reinforced with nanofibers to show enhanced mechanical properties and improved structural integrity. The method is based on a combination of air brush spraying of a hydrogel and electrospinning of nanofibers. With air brush spraying the controllability is enhanced and the potential for scale-up increased. The developed method was used to successfully reinforce gellan gum hydrogels with electrospun polycaprolactone nanofibers. Optical and rheological evaluations were performed and showed that parameters such as the amount of incorporated nanofibers, gellan gum concentration and calcium chloride (crosslinker) concentrations could be used to modulate material properties. Incorporation of a small amount of nanofibers had a reinforcing effect and resulted in a hydrogel with rheological properties similar to the human nucleus pulposus (NP). The method is flexible and carries potential for designing scaffolds for e.g. NP tissue regeneration. © 2012 Wiley Periodicals, Inc.
Caridade S.G.,European Institute of Excellence on Tissue Engineering and Regenerative Medicine |
Caridade S.G.,Bs PT Government Associate Laboratory |
Merino E.G.,European Institute of Excellence on Tissue Engineering and Regenerative Medicine |
Merino E.G.,Bs PT Government Associate Laboratory |
And 8 more authors.
Journal of Bioactive and Compatible Polymers | Year: 2012
In guided tissue/bone regeneration, membranes are used as barriers to prevent the faster growing soft tissue cells from entering the defect space and to regenerate periodontal ligament, cementum, and bone. The two sides of the membranes are in contact with distinct biological environments in which one faces a region in which osteointegration should be ideally promoted. Biocompatible and biodegradable composite membranes were produced by combining poly(d,l-lactic acid) and Bioglass® particles featuring an asymmetric bioactivity and a good integration between the polymeric and inorganic fractions. The asymmetric distribution of the osteoconductive particles was produced during the processing of the membrane using a solvent casting methodology. Only the inorganic-rich face promoted the deposition of bone-like apatite after immersing the composite membrane in simulated body fluid for 2 days. The mechanical properties of the membranes were evaluated using dynamic mechanical analysis by analyzing the viscoelastic properties and the glass transition of the samples in both dry and wet states. A clear plasticization effect of water was detected, but the composite membranes were found to be stiffer, at 37°C, compared with the pure polymer. SaOs-2 cells attached on both the surfaces and proliferated after 7 days in culture. © The Author(s) 2012.
Aroso I.M.,European Institute of Excellence on Tissue Engineering and Regenerative Medicine |
Aroso I.M.,Bs PT Government Associate Laboratory |
Duarte A.R.C.,European Institute of Excellence on Tissue Engineering and Regenerative Medicine |
Duarte A.R.C.,Bs PT Government Associate Laboratory |
And 6 more authors.
Journal of Supercritical Fluids | Year: 2015
Abstract The present study relates to the use of supercritical carbon dioxide (SCCO2) to modify the properties of cork by incorporation of new molecules. The impact of SCCO2processing on the morphology and on the mechanical properties was found to be negligible.The impregnation of disperse blue 14 (blue dye) on cubic shaped cork samples of 5 mm occurs progressively,is dependent of the processing conditions and of the presence of lenticels and growth rings. The impregnation of the samples bulk was achieved with processing at 10 MPa and 313 K for 16 h. The solubility and sorption of SCCO2 in the cork matrix was measured using circular discs and the diffusion coefficients calculated to be on the order of 10-8 cm2/s, the same order as for wood materials. This work demonstrates the feasibility of supercritical fluid technology to impart new features to cork, which may lead to innovative architectural, outdoor and industrial applications. © 2015 Elsevier B.V.
Costa A.M.S.,European Institute of Excellence on Tissue Engineering and Regenerative Medicine |
Costa A.M.S.,Bs PT Government Associate Laboratory |
Mano J.F.,European Institute of Excellence on Tissue Engineering and Regenerative Medicine |
Mano J.F.,Bs PT Government Associate Laboratory
European Polymer Journal | Year: 2015
Ideal candidates for the repair of robust biological tissues should exhibit diverse features such as biocompatibility, strength, toughness, self-healing ability and a well-defined structure. Among the available biomaterials, hydrogels, as highly hydrated 3D-crosslinked polymeric networks, are promising for Tissue Engineering purposes as result of their high resemblance with native extracellular matrix. However, these polymeric structures often exhibit a poor mechanical behavior, hampering their use in load-bearing applications. During the last years, several efforts have been made to create new strategies and concepts to fabricate strong and tough hydrogels. Although it is already possible to shape the mechanical properties of artificial hydrogels to mimic biotissues, critical issues regarding, for instance, their biocompatibility and hierarchical structure are often neglected. Therefore, this review covers the structural and mechanical characteristics of the developed methodologies to toughen hydrogels, highlighting some pioneering efforts employed to combine the aforementioned properties in natural-based hydrogels. © 2015 Elsevier Ltd.