Rational design of polymer-based nanosystems for an efficient targeting of the immune system

The main goal of this thesis is the development of polymer-based nanosystems for antigen delivery to the immune system. To evaluate the influence of the physicochemical characteristics of the nanosystems in their biodistribution to the lymphatic system, we have developed two chitosan nanocapsule prototypes with different particle size and the corresponding nanoemulsions, apart from other nanocapsules with different polymeric coatings. Results have shown the importance of particle size, surface charge and specific characteristics of the polymers used as coating in the draining of the nanocarriers to the lymphatic system. Moreover, we have developed chitosan:carboxymethyl-β-glucan nanoparticles, with high ability to associate the model antigen ovalbumin and an adequate storage stability profile, both in suspension and in dry powder form. Finally, in vivo studies have shown a significant accumulation of the formulation in the lymph nodes, leading to an efficient antigen presentation to T cells. Overall, our results show the potential of polymer-based systems to be modulated in terms of their composition, aiming at a more effective immune response

Effectiveness of three-dimensional kinematic biofeedback on the performance of scapula-focused exercises

Artigo resultante do trabalho apresentado na International Conference on Physiological Computing Systems - PhyCS, 7-9 jan 2014, Lisboa, PortugalThree-dimensional (3D) kinematic biofeedback can help identify scapular movement disorders and assist the subjects' motor relearning process by facilitating changes in physiological and biomechanical function through real-time knowledge of performance and result during or immediately after a task execution. This study assessed the effectiveness of 3D kinematic biofeedback on the quality of the scapula-focused exercises execution, and motor learning transfer during shoulder flexion and a daily activity. Thirty healthy adults with no history of shoulder pain or dysfunction were randomly distributed into two groups. Skinmounted sensors allowed tracking of the thorax, scapula and humerus, and scapulothoracic and glenohumeral 3D angles were computed after reconstructing upper-extremity motions during daily activities and exercises for different phases of a motor relearning process. The results of this study demonstrate that the execution quality of scapula-focused exercises benefits of real-time 3D kinematic biofeedback and that transfer of learning occurs with a specific motor training intervention

Nanoengineering of vaccines using natural polysaccharides

Currently, there are over 70 licensed vaccines, which prevent the pathogenesis of around 30 viruses and bacteria. Nevertheless, there are still important challenges in this area, which include the development of more active, non-invasive, and thermo-resistant vaccines. Important biotechnological advances have led to safer subunit antigens, such as proteins, peptides, and nucleic acids. However, their limited immunogenicity has demanded potent adjuvants that can strengthen the immune response. Particulate nanocarriers hold a high potential as adjuvants in vaccination. Due to their pathogen-like size and structure, they can enhance immune responses by mimicking the natural infection process. Additionally, they can be tailored for non-invasive mucosal administration (needle-free vaccination), and control the delivery of the associated antigens to a specific location and for prolonged times, opening room for single-dose vaccination. Moreover, they allow co-association of immunostimulatory molecules to improve the overall adjuvant capacity. The natural and ubiquitous character of polysaccharides, together with their intrinsic immunomodulating properties, their biocompatibility, and biodegradability, justify their interest in the engineering of nanovaccines. In this review, we aim to provide a state-of-the-art overview regarding the application of nanotechnology in vaccine delivery, with a focus on the most recent advances in the development and application of polysaccharide-based antigen nanocarriers

Dermic diffusion and stratum corneum: a state of the art review of mathematical models

Transdermal biotechnologies are an ever increasing field of interest, due to the medical and pharmaceutical applications that they underlie. There are several mathematical models at use that permit a more inclusive vision of pure experimental data and even allow practical extrapolation for new dermal diffusion methodologies. However, they grasp a complex variety of theories and assumptions that allocate their use for specific situations. Models based on Fick's First Law found better use in contexts where scaled particle theory Models would be extensive in time-span but the reciprocal is also true, as context of transdermal diffusion of particular active compounds changes. This article reviews extensively the various theoretical methodologies for studying dermic diffusion in the rate limiting dermic barrier, the stratum corneum, and systematizes its characteristics, their proper context of application, advantages and limitations, as well as future perspectives

Projeto de Educação para a Saúde – Os desafios da alimentação

Introdução: As Necessidades Especiais na Alimentação (NEA) surgem, frequentemente, em pessoas com alterações neurológicas e perturbações do desenvolvimento, que poderão depender de cuidadores no processo de alimentação. O restrito acesso a (in)formação na área dos cuidados com a alimentação condiciona a implementação das melhores estratégias perante situações de risco e/ou rejeição alimentar, conduzindo à insegurança e ansiedade no cuidador. Objetivos: Apresentar e implementar uma proposta de programa de Educação para a Saúde (EpS) no âmbito das NEA; avaliá-lo em termos de outputs e outcomes; refletir quanto à pertinência deste tipo de programas. Métodos: Foram utilizados o Modelo Interativo de Planificação de Programas, a Abordagem dos Cinco Passos para a Monitorização e Avaliação e o Modelo de Avaliação Multinível. Resultados: Verificou-se que 90% dos cuidadores não tinha tido acesso a formação na área da alimentação e que as maiores dificuldades foram o seu posicionamento e o da pessoa cuidada. As dificuldades assinaladas com maior frequência nos indivíduos com NEA foram engasgamentos, queda anterior de alimento e o facto de a deglutição só ocorrer com quantidade excessiva de alimento na cavidade oral. A satisfação média dos participantes nas sessões formativas situou-se entre “Satisfeito(a)” e “Muito satisfeito(a)” e os mesmos adquiriram com sucesso os conhecimentos objetivados. Conclusões: O presente estudo permitiu a apresentação e implementação de uma proposta de programa de EpS no âmbito das NEA, fazendo-se uma avaliação positiva do mesmo. Compreendeuse a relevância deste tipo de programas, pois atuando numa problemática negligenciada e com externalidades pode gerar-se valor para a sociedade.info:eu-repo/semantics/publishedVersio

Nanovaccine Delivery Approaches and Advanced Delivery Systems for the Prevention of Viral Infections: From Development to Clinical Application

open access articleViral infections causing pandemics and chronic diseases are the main culprits implicated in devastating global clinical and socioeconomic impacts, as clearly manifested during the current COVID-19 pandemic. Immunoprophylaxis via mass immunisation with vaccines has been shown to be an efficient strategy to control such viral infections, with the successful and recently accelerated development of different types of vaccines, thanks to the advanced biotechnological techniques involved in the upstream and downstream processing of these products. However, there is still much work to be done for the improvement of efficacy and safety when it comes to the choice of delivery systems, formulations, dosage form and route of administration, which are not only crucial for immunisation effectiveness, but also for vaccine stability, dose frequency, patient convenience and logistics for mass immunisation. In this review, we discuss the main vaccine delivery systems and associated challenges, as well as the recent success in developing nanomaterials-based and advanced delivery systems to tackle these challenges. Manufacturing and regulatory requirements for the development of these systems for successful clinical and marketing authorisation were also considered. Here, we comprehensively review nanovaccines from development to clinical application, which will be relevant to vaccine developers, regulators, and clinicians

Nanotechnologies for the delivery of biologicals: Historical perspective and current landscape

Collaboration with Prof. María José Alonso's group at the University of Santiago de Compostela (Spain). open access articleBiological macromolecule-based therapeutics irrupted in the pharmaceutical scene generating a great hope due to their outstanding specificity and potency. However, given their susceptibility to degradation and limited capacity to overcome biological barriers new delivery technologies had to be developed for them to reach their targets. This review aims at analyzing the historical seminal advances that shaped the development of the protein/peptide delivery field, along with the emerging technologies on the lead of the current landscape. Particularly, focus is made on technologies with a potential for transmucosal systemic delivery of protein/peptide drugs, followed by approaches for the delivery of antigens as new vaccination strategies, and formulations of biological drugs in oncology, with special emphasis on mAbs. Finally, a discussion of the key challenges the field is facing, along with an overview of prospective advances are provided

Mutation of the surface layer protein SlpB has pleiotropic effects in the probiotic propionibacterium freudenreichii CIRM-BIA 129

Propionibacterium freudenreichii is a beneficial Gram-positive bacterium, traditionally used as a cheese-ripening starter, and currently considered as an emerging probiotic. As an example, the P. freudenreichii CIRM-BIA 129 strain recently revealed promising immunomodulatory properties. Its consumption accordingly exerts healing effects in different animal models of colitis, suggesting a potent role in the context of inflammatory bowel diseases. This anti-inflammatory effect depends on surface layer proteins (SLPs). SLPs may be involved in key functions in probiotics, such as persistence within the gut, adhesion to host cells and mucus, or immunomodulation. Several SLPs coexist in P. freudenreichii CIRM-BIA 129 and mediate immunomodulation and adhesion. A mutant P. freudenreichii CIRM-BIA 129ΔslpB (CB129ΔslpB) strain was shown to exhibit decreased adhesion to intestinal epithelial cells. In the present study, we thoroughly analyzed the impact of this mutation on cellular properties. Firstly, we investigated alterations of surface properties in CB129ΔslpB. Surface extractable proteins, surface charges (ζ-potential) and surface hydrophobicity were affected by the mutation. Whole-cell proteomics, using high definition mass spectrometry, identified 1,288 quantifiable proteins in the wild-type strain, i.e., 53% of the theoretical proteome predicted according to P. freudenreichii CIRM-BIA 129 genome sequence. In the mutant strain, we detected 1,252 proteins, including 1,227 proteins in common with the wild-type strain. Comparative quantitative analysis revealed 97 proteins with significant differences between wild-type and mutant strains. These proteins are involved in various cellular process like signaling, metabolism, and DNA repair and replication. Finally, in silico analysis predicted that slpB gene is not part of an operon, thus not affecting the downstream genes after gene knockout. This study, in accordance with the various roles attributed in the literature to SLPs, revealed a pleiotropic effect of a single slpB mutation, in the probiotic P. freudenreichii. This suggests that SlpB may be at a central node of cellular processes and confirms that both nature and amount of SLPs, which are highly variable within the P. freudenreichii species, determine the probiotic abilities of strains.Fil: do Carmo, Fillipe L. R.. Institut National de la Recherche Agronomique; Francia. Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas; BrasilFil: Marques Da Silva, Wanderson. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación en Ciencias Veterinarias y Agronómicas. Instituto de Biotecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Tavares, Guilherme C.. Universidade Federal de Minas Gerais; BrasilFil: Ibraim, Izabela C.. Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas; BrasilFil: Cordeiro, Barbara F.. Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas; BrasilFil: Oliveira, Emiliano R.. Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas; BrasilFil: Rabah, Houem. Institut National de la Recherche Agronomique; FranciaFil: Cauty, Chantal. Institut National de la Recherche Agronomique; FranciaFil: da Silva, Sara H.. Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas; BrasilFil: Canário Viana, Marcus V.. Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas; BrasilFil: Caetano, Ana C. B.. Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas; BrasilFil: dos Santos, Roselane G.. Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas; BrasilFil: de Oliveira Carvalho, Rodrigo D.. Instituto de Ciencias Da Saúde; BrasilFil: Jardin, Julien. Institut National de la Recherche Agronomique; FranciaFil: Pereira, Felipe L.. Universidade Federal de Minas Gerais; BrasilFil: Folador, Edson L.. Universidade Estadual da Paraiba; BrasilFil: Le Loir, Yves. Institut National de la Recherche Agronomique; FranciaFil: Figueiredo, Henrique C. P.. Universidade Federal de Minas Gerais; BrasilFil: Jan, Gwénaël. Institut National de la Recherche Agronomique; FranciaFil: Azevedo, Vasco. Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas; Brasi

Direct evidence for phosphorus limitation on Amazon forest productivity

The productivity of rainforests growing on highly weathered tropical soils is expected to be limited by phosphorus availability1. Yet, controlled fertilization experiments have been unable to demonstrate a dominant role for phosphorus in controlling tropical forest net primary productivity. Recent syntheses have demonstrated that responses to nitrogen addition are as large as to phosphorus2, and adaptations to low phosphorus availability appear to enable net primary productivity to be maintained across major soil phosphorus gradients3. Thus, the extent to which phosphorus availability limits tropical forest productivity is highly uncertain. The majority of the Amazonia, however, is characterized by soils that are more depleted in phosphorus than those in which most tropical fertilization experiments have taken place2. Thus, we established a phosphorus, nitrogen and base cation addition experiment in an old growth Amazon rainforest, with a low soil phosphorus content that is representative of approximately 60% of the Amazon basin. Here we show that net primary productivity increased exclusively with phosphorus addition. After 2 years, strong responses were observed in fine root (+29%) and canopy productivity (+19%), but not stem growth. The direct evidence of phosphorus limitation of net primary productivity suggests that phosphorus availability may restrict Amazon forest responses to CO2 fertilization4, with major implications for future carbon sequestration and forest resilience to climate change.The authors acknowledge funding from the UK Natural Environment Research Council (NERC), grant number NE/L007223/1. This is publication 850 in the technical series of the BDFFP. C.A.Q. acknowledges the grants from Brazilian National Council for Scientific and Technological Development (CNPq) CNPq/LBA 68/2013, CNPq/MCTI/FNDCT no. 18/2021 and his productivity grant. C.A.Q., H.F.V.C., F.D.S., I.A., L.F.L., E.O.M. and S.G. acknowledge the AmazonFACE programme for financial support in cooperation with Coordination for the Improvement of Higher Education Personnel (CAPES) and the National Institute of Amazonian Research as part of the grants CAPES-INPA/88887.154643/2017-00 and 88881.154644/2017-01. T.F.D. acknowledges funds from FundacAo de Amparo a Pesquisa do Estado de SAo Paulo (FAPESP), grant 2015/50488-5, and the Partnership for Enhanced Engagement in Research (PEER) programme grant AID-OAA-A-11-00012. L.E.O.C.A. thanks CNPq (314416/2020-0)

AVALIAÇÃO DO EQUILÍBRIO DE MULHERES COM CÂNCER DE MAMA

The objective of this study was to verify the balance of women with breast cancer. This cross-sectional study, tested balance of fifteen women, eight women with cancer and seven without cancer. The evaluation was performed through the Mini Balance Evaluation Systems (MiniBESTest), TUG with simple and dual- task. The mean of age was 59.2 ± 5 years for cancer group and 60.2 ± 5 years for the control group. Student's t-test for independent samples showed that there was no statistical difference (p> 0.05) between the groups for: MiniBESTest score, TUG with simple and dual-task. Women with cancer did not present balance impairments compared to control group according to MiniBESTest, and TUG with simple and dual-task.O objetivo desse estudo foi verificar o equilíbrio de mulheres com câncer de mama. Este estudo transversal avaliou o equilíbrio de quinze mulheres, sendo oito mulheres com câncer e sete sem câncer. Avaliação foi realizada através do Mini Balance Evaluation Systems (MiniBESTest), TUG simples e dupla tarefa. A média de idade foi de 59,2 ± 5 anos para o grupo de mulheres com câncer e 60,2 ± 5 anos para o grupo controle. Teste t Student para amostras independentes mostrou que não houve diferença estatística (p>0,05) entre os grupos para as variáveis: pontuação no MiniBESTest, tempo de realização do TUG simples e tempo de realização do TUG dupla tarefa. Mulheres com câncer não apresentaram alterações de equilíbrio comparadas ao grupo controle de acordo com o MiniBESTest, e TUG tarefa simples e dupla tarefa