The inflammatory response in the regression of lumbar disc herniation

Lumbar disc herniation (LDH) is highly associated with inflammation in the context of low back pain. Currently, inflammation is associated with adverse symptoms related to the stimulation of nerve fibers that may lead to pain. However, inflammation has also been indicated as the main factor responsible for LDH regression. This apparent controversy places inflammation as a good prognostic indicator of spontaneous regression of LDH. This review addresses the molecular and cellular mechanisms involved in LDH regression, including matrix remodeling and neovascularization, in the scope of the clinical decision on conservative versus surgical intervention. Based on the evidence, a special focus on the inflammatory response in the LDH context is given, particularly in the monocyte/macrophage role. The phenomenon of spontaneous regression of LDH, extensively reported in the literature, is therefore analyzed here under the perspective of the modulatory role of inflammation.This work was financed by project “Bioengineered Therapies for infectious diseases and tissue regeneration” (NORTE-01-0145-FEDER-000012), supported by Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF), by FEDER/COMPETE 2020 (POCI), Portugal 2020, and by Portuguese funds through FCT/MCTES in the framework of the project "Institute for Research and Innovation in Health Sciences" (POCI-01- 0145-FEDER-007274). Cunha C and Gonçalves RM acknowledge FCT by their postdoc fellowship (SFRH/BDP/87071/2012) and FCT Investigator Grant (IF/ 00638/2014), respectively. Silva AJ acknowledges her fellowship under the framework of the project Norte-01-0145-FEDER-000012

Genetically engineered-MSC therapies for non-unions, delayed unions and critical-size bone defects

The normal bone regeneration process is a complex and coordinated series of events involving different cell types and molecules. However, this process is impaired in critical-size/large bone defects, with non-unions or delayed unions remaining a major clinical problem. Novel strategies are needed to aid the current therapeutic approaches. Mesenchymal stem/stromal cells (MSCs) are able to promote bone regeneration. Their beneficial effects can be improved by modulating the expression levels of specific genes with the purpose of stimulating MSC proliferation, osteogenic differentiation or their immunomodulatory capacity. In this context, the genetic engineering of MSCs is expected to further enhance their pro-regenerative properties and accelerate bone healing. Herein, we review the most promising molecular candidates (protein-coding and non-coding transcripts) and discuss the different methodologies to engineer and deliver MSCs, mainly focusing on in vivo animal studies. Considering the potential of the MSC secretome for bone repair, this topic has also been addressed. Furthermore, the promising results of clinical studies using MSC for bone regeneration are discussed. Finally, we debate the advantages and limitations of using MSCs, or genetically-engineered MSCs, and their potential as promoters of bone fracture regeneration/repair.This project is supported by Fundação para a Ciência e a Tecnologia (FCT)—in the framework of the project POCI-01-0145-FEDER-031402-R2Bone, under the PORTUGAL 2020 Partnership Agreement, through ERDF, co-funded by FEDER/FNR, and national funding (through FCT – Fundação para a Ciência e a Tecnologia, I.P., provided by the contract-program and according to numbers 4, 5 and 6 of art. 23 of Law No. 57/2016 of 29 August 2016, as amended by Law No. 57/2017 of 19 July 2017). RG, JHT, and MIA are supported by FCT, through the FCT Investigator Program (IF/00638/2014), SFRH/BD/112832/2015, and DL 57/2016/CP1360/CT0008, respectively

Localization of gravity on a de Sitter thick braneworld without scalar fields

In this work we present a simple thick braneworld model that is generated by an intriguing interplay between a 5D cosmological constant with a de Sitter metric induced in the 3-brane without the inclusion of scalar fields. We show that 4D gravity is localized on this brane, provide analytic expressions for the massive Kaluza-Klein (KK) fluctuation modes and also show that the spectrum of metric excitations displays a mass gap. We finally present the corrections to Newton's law due to these massive modes. This model has no naked singularities along the fifth dimension despite the existence of a mass gap in the graviton spectrum as it happens in thick branes with 4D Poincare symmetry, providing a simple model with very good features: the curvature is completely smooth along the fifth dimension, it localizes 4D gravity and the spectrum of gravity fluctuations presents a mass gap, a fact that rules out the existence of phenomenologically dangerous ultralight KK excitations in the model. We finally present our solution as a limit of scalar thick branes.Comment: 11 pages in latex, no figures, title and abstract changed, a new section and some references adde

Biomimetic Mineralizing Agents Recover the Micro Tensile Bond Strength of Demineralized Dentin

Biomimetic remineralization is an approach that mimics natural biomineralization, and improves adhesive procedures. The aim of this paper was to investigate the influence of Dentin Caries-like Lesions (DCLL)-Producing Model on microtensile bond strength (μTBS) of etch and rinse adhesive systems and investigate the effect of remineralizing agents such as Sodium Fluoride (NaF), MI Paste™ (MP) and Curodont™ Repair (CR) on caries-affected dentin (n = 6). Nine groups were established: (1) Sound dentin; (2) Demineralized dentin/Chemical DCLL: (3) Demineralized dentin/Biological DCLL; (4) Chemical/DCLL + NaF; (5) Chemical/DCLL + MP; (6) Chemical/DCLL + CR; (7) Biological/DCLL + NaF; (8) Biological/DCLL + MP; (9) Biological/DCLL + CR. Then all dentin blocks were subjected to a bonding procedure with Adper™ Single Bond 2 adhesive system/Filtek Z350XT 4 mm high block, following this they were immersed in deionized water/24 h and then sectioned with ≅1 mm2 beams. The μTBS test was conducted at 1 mm/min/500 N loading. Failure sites were evaluated by SEM (scanning electron microscopy (150×). μTBS data were submitted to factorial ANOVA and Tukey’s test (p < 0.05). The highest values were found when demineralized dentin was treated with MP and CR, regardless caries lesion depth (p < 0.05). There was a predominance of adhesive/mixed in the present study. It was concluded that the use of the artificial dentin caries production models produces differences in the μTBS. Additionally MP and CR remineralizing agents could enhance adhesive procedures even at different models of caries lesion

Teor de fenólicos e atividade antioxidante de própolis em áreas de floresta e savana de Roraima

Neste trabalho objetivou-se estudar própolis produzidas em Roraima por Apis mellifera com base na composição química e atividade antioxidante. Coletou-se amostras em áreas de floresta (MJ) e savana (BF) para posterior obtenção dos extratos etanólicos. Quantificou-se fenólicos e flavonoides, e determinou-se a atividade antioxidante por diferentes métodos. BF apresentou maior teor de fenólicos (40,89 mg ácido gálico/g própolis), flavonoides (3,41 mg quercetina/g; própolis 4,75 mg pinocembrina/g própolis) e se destacou com 85,89 µmol trolox/g própolis no ensaio com DPPH. No entanto, por β-caroteno/ácido linoleico o percentual praticamente não variou entre MJ (85,88%) e BF (84,98%)

Teor de fenólicos e atividade antioxidante de própolis em áreas de floresta e savana de Roraima

Neste trabalho objetivou-se estudar própolis produzidas em Roraima por Apis mellifera com base na composição química e atividade antioxidante. Coletou-se amostras em áreas de floresta (MJ) e savana (BF) para posterior obtenção dos extratos etanólicos. Quantificou-se fenólicos e flavonoides, e determinou-se a atividade antioxidante por diferentes métodos. BF apresentou maior teor de fenólicos (40,89 mg ácido gálico/g própolis), flavonoides (3,41 mg quercetina/g; própolis 4,75 mg pinocembrina/g própolis) e se destacou com 85,89 µmol trolox/g própolis no ensaio com DPPH. No entanto, por β-caroteno/ácido linoleico o percentual praticamente não variou entre MJ (85,88%) e BF (84,98%)