Icvs 3Bs Pt Government Assoct Laboratory

Braga, Portugal

Icvs 3Bs Pt Government Assoct Laboratory

Braga, Portugal
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Leite A.J.,University of Minho | Leite A.J.,Icvs 3Bs Pt Government Assoct Laboratory | Mano J.F.,University of Minho | Mano J.F.,Icvs 3Bs Pt Government Assoct Laboratory | Mano J.F.,University of Aveiro
Journal of Materials Chemistry B | Year: 2017

In recent years, the combination of natural polymers with nanoparticles has permitted the development of sophisticated and efficient bioinspired constructs. In this regard, the incorporation of bioactive glass nanoparticles (BGNPs) confers a bioactive nature to these constructs, which can then induce the formation of a bone-like apatite layer upon immersion in a physiological environment. Moreover, the incorporation of bioactive glass nanoparticles has been found to be beneficial; the constructs proved to be biocompatible, promote cell adhesion and spreading, and regulate osteogenic commitment. This review provides a summary and discussion of the composition, design, and applications of bioinspired nanocomposite constructs based on BGNPs. Examples of nanocomposite systems will be highlighted with relevance to biomedical applications. It is expected that understanding the principles and the state-of-the-art of natural nanocomposites may lead to breakthroughs in many research areas, including tissue engineering and orthopaedic devices. The challenges regarding the future translation of these nanostructured composites into clinical use are also summarized. © 2017 The Royal Society of Chemistry.

Morais P.,Catholic University of Leuven | Morais P.,Icvs 3Bs Pt Government Assoct Laboratory | Morais P.,University of Porto | Queiros S.,Catholic University of Leuven | And 7 more authors.
Physics in Medicine and Biology | Year: 2017

Cardiovascular diseases are among the leading causes of death and frequently result in local myocardial dysfunction. Among the numerous imaging modalities available to detect these dysfunctional regions, cardiac deformation imaging through tagged magnetic resonance imaging (t-MRI) has been an attractive approach. Nevertheless, fully automatic analysis of these data sets is still challenging. In this work, we present a fully automatic framework to estimate left ventricular myocardial deformation from t-MRI. This strategy performs automatic myocardial segmentation based on B-spline explicit active surfaces, which are initialized using an annular model. A non-rigid image-registration technique is then used to assess myocardial deformation. Three experiments were set up to validate the proposed framework using a clinical database of 75 patients. First, automatic segmentation accuracy was evaluated by comparing against manual delineations at one specific cardiac phase. The proposed solution showed an average perpendicular distance error of 2.35 ± 1.21 mm and 2.27 ± 1.02 mm for the endo- and epicardium, respectively. Second, starting from either manual or automatic segmentation, myocardial tracking was performed and the resulting strain curves were compared. It is shown that the automatic segmentation adds negligible differences during the strain-estimation stage, corroborating its accuracy. Finally, segmental strain was compared with scar tissue extent determined by delay-enhanced MRI. The results proved that both strain components were able to distinguish between normal and infarct regions. Overall, the proposed framework was shown to be accurate, robust, and attractive for clinical practice, as it overcomes several limitations of a manual analysis. © 2017 Institute of Physics and Engineering in Medicine.

Lopes S.,University of Minho | Lopes S.,Icvs 3Bs Pt Government Assoct Laboratory | Teplytska L.,Max Planck Institute of Psychiatry | Vaz-Silva J.,University of Minho | And 16 more authors.
Cerebral Cortex | Year: 2017

Tau protein in dendrites and synapses has been recently implicated in synaptic degeneration and neuronal malfunction. Chronic stress, a well-known inducer of neuronal/synaptic atrophy, triggers hyperphosphorylation of Tau protein and cognitive deficits. However, the cause-effect relationship between these events remainsto beestablished. To test the involvement of Tau in stress-induced impairments of cognition, we investigated the impact of stress oncognitive behavior, neuronal structure, and the synaptic proteome in the prefrontal cortex (PFC) of Tau knock-out (Tau-KO) and wild-type (WT) mice. Whereas exposure to chronic stress resulted in atrophy of apical dendrites and spine loss in PFC neurons as well as significant impairments in working memory in WT mice, such changes were absent in Tau-KO animals. Quantitative proteomic analysis of PFC synaptosomal fractions, combined with transmission electron microscopy analysis, suggested a prominent role for mitochondria in the regulation of the effects of stress. Specifically, chronically stressed animals exhibit Tau-dependent alterationsinthe levels ofproteins involvedin mitochondrial transport and oxidative phosphorylation as well as in the synaptic localization of mitochondria in PFC. These findings provide evidence for a causal role of Tau in mediating stress-elicited neuronal atrophy and cognitive impairment and indicate that Tau may exert its effects through synaptic mitochondria. © The Author 2016. Published by Oxford University Press. All rights reserved.

Cunha P.G.,Guimaraes Centro Hospitalar Do Alto Ave | Cunha P.G.,University of Minho | Cunha P.G.,Icvs 3Bs Pt Government Assoct Laboratory | Cotter J.,Guimaraes Centro Hospitalar Do Alto Ave | And 11 more authors.
Journal of Hypertension | Year: 2015

Background: By contrast with other southern European people, north Portuguese population registers an especially high prevalence of hypertension and stroke incidence. We designed a cohort study to identify individuals presenting accelerated and premature arterial aging in the Portuguese population. Method: Pulse wave velocity (PWV) was measured in randomly sampled population dwellers aged 18-96 years from northern Portugal, and used as a marker of early vascular aging (EVA). Of the 3038 individuals enrolled, 2542 completed the evaluation. Results: Mean PWV value for the entire population was 8.4 m/s (men: 8.6 m/s; women: 8.2 m/s; P<0.02). The individuals were classified with EVA if their PWV was at least 97.5th percentile of z-score for mean PWV values adjusted for age (using normal European reference values as comparators). The overall prevalence of EVA was 12.5%; 26.1% of individuals below 30 years presented this feature and 40.2% of individuals in that same age strata were placed above the 90th percentile of PWV; and 18.7% of the population exhibited PWV values above 10 m/s, with male predominance (17.2% of men aged 40-49 years had PWV>10 m/s). Logistic regression models indicated gender differences concerning the risk of developing large artery damage, with women having the same odds of PWV above 10 m/s 10 years later than men. Conclusion: The population PWV values were higher than expected in a low cardiovascular risk area (Portugal). High prevalence rates of EVA and noteworthy large artery damage in young ages were found. Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.

Silva S.S.,European Institute of Excellence on Tissue Engineering and Regenerative Medicine | Silva S.S.,Icvs 3Bs Pt Government Assoct Laboratory | Mano J.F.,European Institute of Excellence on Tissue Engineering and Regenerative Medicine | Mano J.F.,Icvs 3Bs Pt Government Assoct Laboratory | And 2 more authors.
Green Chemistry | Year: 2017

Ionic liquids (ILs) have huge potential to provide advances in many areas such as energy, pharmaceutical formulations, biomedical sciences, and technology. In the biomedical field, ILs have been intensively investigated for use as potential solvents for some polysaccharides to overcome their lack of solubility and processability. This review focuses on the application of ILs as solvents and reaction media to develop chitin- and chitosan-based materials. Dissolution of chitin and chitosan in ILs such as 1-butyl-imidazolium acetate (BMIMAc) and 1-ethyl-3-methylimidazolium chloride (BMIMCl) has been used to create materials including sponges, films, microspheres, and aerogels. Moreover, ILs have a key role in chemical reactions, hydrolysis, acetylation, deacetylation and graft copolymerization of chitin/chitosan, promoting homogeneous media and thus enhancing the efficiency of the reactions. The resulting materials can be applied in wound healing, tissue regeneration, gene delivery, and drug delivery systems. In particular, they have been designed to support tissue regeneration and to act as hemostatic and antibacterial agents and/or delivery vehicles for drugs. Although IL platforms offer new ways for the sustainable processing of chitin and chitosan to a variety of matrices, studies involving their in vivo biocompatibility are scarce, and this has prevented these advances being turned into clinical solutions. © 2017 The Royal Society of Chemistry.

Esteves S.,University of Minho | Esteves S.,Icvs 3Bs Pt Government Assoct Laboratory | Duarte-Silva S.,University of Minho | Duarte-Silva S.,Icvs 3Bs Pt Government Assoct Laboratory | And 10 more authors.
PLoS ONE | Year: 2015

Machado-Joseph disease (MJD) is an inherited neurodegenerative disease, caused by a CAG repeat expansion within the coding region of ATXN3 gene, and which currently lacks effective treatment. In this work we tested the therapeutic efficacy of chronic treatment with valproic acid (VPA) (200mg/kg), a compound with known neuroprotection activity, and previously shown to be effective in cell, fly and nematode models of MJD. We show that chronic VPA treatment in the CMVMJD135 mouse model had limited effects in the motor deficits of these mice, seen mostly at late stages in the motor swimming, beam walk, rotarod and spontaneous locomotor activity tests, and did not modify the ATXN3 inclusion load and astrogliosis in affected brain regions. However, VPA chronic treatment was able to increase GRP78 protein levels at 30 weeks of age, one of its known neuroprotective effects, confirming target engagement. In spite of limited results, the use of another dosage of VPA or of VPA in a combined therapy with molecules targeting other pathways, cannot be excluded as potential strategies for MJD therapeutics. © 2015 Esteves et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Oliveira T.G.,University of Minho | Oliveira T.G.,Icvs 3Bs Pt Government Assoct Laboratory | Chan R.B.,Columbia University | Chan R.B.,Columbia University Medical Center | And 18 more authors.
Molecular Psychiatry | Year: 2016

Chronic stress is a major risk factor for several human disorders that affect modern societies. The brain is a key target of chronic stress. In fact, there is growing evidence indicating that exposure to stress affects learning and memory, decision making and emotional responses, and may even predispose for pathological processes, such as Alzheimer's disease and depression. Lipids are a major constituent of the brain and specifically signaling lipids have been shown to regulate brain function. Here, we used a mass spectrometry-based lipidomic approach to evaluate the impact of a chronic unpredictable stress (CUS) paradigm on the rat brain in a region-specific manner. We found that the prefrontal cortex (PFC) was the area with the highest degree of changes induced by chronic stress. Although the hippocampus presented relevant lipidomic changes, the amygdala and, to a greater extent, the cerebellum presented few lipid changes upon chronic stress exposure. The sphingolipid and phospholipid metabolism were profoundly affected, showing an increase in ceramide (Cer) and a decrease in sphingomyelin (SM) and dihydrosphingomyelin (dhSM) levels, and a decrease in phosphatidylethanolamine (PE) and ether phosphatidylcholine (PCe) and increase in lysophosphatidylethanolamine (LPE) levels, respectively. Furthermore, the fatty-acyl profile of phospholipids and diacylglycerol revealed that chronic stressed rats had higher 38 carbon(38C)-lipid levels in the hippocampus and reduced 36C-lipid levels in the PFC. Finally, lysophosphatidylcholine (LPC) levels in the PFC were found to be correlated with blood corticosterone (CORT) levels. In summary, lipidomic profiling of the effect of chronic stress allowed the identification of dysregulated lipid pathways, revealing putative targets for pharmacological intervention that may potentially be used to modulate stress-induced deficits. © 2016 Macmillan Publishers Limited All rights reserved.

Reys L.L.,European Institute of Excellence on Tissue Engineering and Regenerative Medicine | Reys L.L.,Icvs 3Bs Pt Government Assoct Laboratory | Silva S.S.,European Institute of Excellence on Tissue Engineering and Regenerative Medicine | Silva S.S.,Icvs 3Bs Pt Government Assoct Laboratory | And 10 more authors.
ACS Biomaterials Science and Engineering | Year: 2016

Algae are abundant sources of bioactive components with extensive therapeutic properties, receiving much interest in recent years. The research on marine brown algae, namely one of its polysaccharide-fucoidan, has increased exponentially. Fucoidan is a sulfated cell-wall polysaccharide with several reported biological properties including anticancer, antivirus, anticoagulant, antioxidant and anti-inflammatory effects. In this study, fucoidan was functionalized by grafting methacrylic groups in the chain backbone, photo-cross-linkable under visible light to obtain biodegradable structures for tissue engineering. The functionalization reaction was carried out by concentrations (8 and 12%) of methacrylic anhydride (MA). The modified fucoidan (MFu) was characterized by FTIR and 1HNMR spectroscopy to confirm the functionalization. Further, modified fucoidan was photo-cross-linked under visible light and using superhydrophobic surfaces, to obtain spherical particles with controlled geometries benefiting from the high repellence of the surfaces. When using higher concentrations of MA, the particles were observed to exhibit a smaller average diameter. Moreover, the behavior of L929 mouse fibroblast-like cells was evaluated when cultured in contact with photo-cross-linked particles was investigated, being observed up to 14 days in culture. The photo-cross-linking of MFu under visible light enables thus the formation of particles here suggested as potentially relevant in a wide range of biomedical applications. © 2016 American Chemical Society.

Fernandes J.S.,European Institute of Excellence on Tissue Engineering and Regenerative Medicine | Fernandes J.S.,Icvs 3Bs Pt Government Assoct Laboratory | Martins M.,European Institute of Excellence on Tissue Engineering and Regenerative Medicine | Martins M.,Icvs 3Bs Pt Government Assoct Laboratory | And 7 more authors.
ACS Biomaterials Science and Engineering | Year: 2016

Three novel borosilicate bioactive glasses (BBGs) were prepared and used to investigate their bioactive and antibacterial properties. The BBGs were prepared by melt-quenching using different glass modifiers, i.e. Mg2+, Ca2+, and Sr2+, and their amorphous nature was confirmed by X-ray diffraction. Scanning electron microscopy with energy dispersive X-ray spectroscopy allowed the visualization of apatite-like structures upon 7 days of immersion in simulated body fluid. BBG-Ca generated surface structures with a Ca/P ratio ≈1.67, while the surface of the BBG-Sr was populated with structures with a Sr/P ratio ≈1.7. Moreover, bacterial tests showed that the BBG-Mg and BBG-Sr glasses (at concentrations of 9, 18, 36, and 72 mg/mL) present antibacterial characteristics. In particular, BBG-Sr, at concentrations of 9 mg/mL, exhibited bacteriostatic activity against Pseudomonas aeruginosa, and at concentrations ≥18 mg/mL it was able to eradicate this bacterium. These results evidence an antibacterial activity dependent on the BBGs composition, concentration, and bacterial species. Cellular studies showed that the developed BBGs do not present a statistically significant cytotoxic effect against Saos-2 cells after 3 days of culture, showing better performance (in the cases of BBG-Ca and BBG-Sr) than commercial 45S5 Bioglass up to 7 days of culture. Overall, this study demonstrates that BBGs can be effectively designed to combine bioactivity and intrinsic antibacterial activity targeting bone tissue engineering applications. © 2016 American Chemical Society.

Vaquero R.M.M.,Leibniz University of Hanover | Agibetov A.,CNR Institute for Applied Mathematics and Information Technologies | Rzepecki J.,Leibniz University of Hanover | Ondresik M.,European Institute of Excellence on Tissue Engineering and Regenerative Medicine | And 10 more authors.
Proceedings of the International Conference on Information Visualisation | Year: 2015

The exploration of biomedical data which involves heterogeneous sources coming from different spatial scales and medical domains is a challenging topic in current research. In this work, we combine efforts regarding multi-scale visualization, multimodal interaction and knowledge formalization for the exploration of multi-scale biomedical data. The knowledge formalization stores and organizes the information sources, the integrated visualization captures all relevant information for the domain expertise of the user and the multimodal interaction provides a natural exploration. We present a concrete example of use of the proposed exploratory system designed for a biologist investigating multi-scale pathologies. © 2015 IEEE.

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