Development of an injectable PHBV microparticles-GG hydrogel hybrid system for regenerative medicine

Uncontrollable displacements that greatly affect the concentration of active agents at the target tissues are among a major limitation of the use of microparticulate drug delivery systems (DDS). Under this context a biphasic injectable DDS combining poly(hydroxybutyrate-co-hydroxyvalerate) (PHBV) microparticles (MPs) and a gellan gum (GG) injectable hydrogel is herein proposed for the localized delivery and long-term retention of MPs carrying hydrophilic and hydrophobic model active agents. A double emulsion-solvent evaporation method was adopted to develop the PHBV MPs, carrying bovine serum albumin (BSA) or dexamethasone (Dex) as hydrophilic and hydrophobic active agents’ models, respectively. Moreover, this method was modified, together with the properties of the hydrogel to tailor the delivery profile of the active agents. Variations of the composition of the organic phase during the process allowed tuning surface topography, particle size distribution and core porosity of the PHBV MPs and, thus, the in vitro release profile of Dex but not of BSA. Besides, after embedding hydrogels of higher GG concentration led to a slower and more sustained release of both active agents, independently of the processing conditions of the microparticulate system.The authors would like to acknowledge the Project RL1 - ABMR - NORTE-01-0124-FEDER-000016 co-financed by North Portugal Regional Operational Programme (ON.2 - O Novo Norte), under the National Strategic Reference Framework (NSRF), through the European Regional Development Fund (ERDF). This work was partially supported by European Research Council grant agreement ERC-2012-ADG 20120216-321266 for project ComplexiTE

Nitric oxide production, inhibitory, antioxidant and antimycobacterial activities of the fruits extract and flavonoid content of Schinus terebinthifolius

AbstractThe extract of the fruits from Schinus terebinthifolius Raddi, Anacardiaceae, was obtained by exhaustive extraction with methanol. Its fractions and isolated compounds were collected by fractionation with RP-2 column chromatography. The crude extract, the flavonoid fraction and the isolated compound identified as apigenin (1), were investigated regarding its inhibitory action of nitric oxide production by LPS-stimulated macrophages, antioxidant activity by DPPH and the antimycobacterial activity against Mycobacterium bovis BCG. The samples exhibited a significant inhibitory effect on the nitric oxide production (e.g., 1, IC50 19.23 ± 1.64μg/ml) and also showed antioxidant activity. In addition, S. terebinthifolius samples inhibited the mycobacterial growth (e.g., 1, IC50 14.53 ± 1.25μg/ml). The necessary concentration to produce 50% of the maximum response (IC50) of these activities did not elicit a significant cytotoxic effect when compared with the positive control (100% of lysis). The antioxidant and nitric oxide inhibition activity displayed by S. terebinthifolius corroborates its ethnopharmacological use of this specie as an anti-inflammatory. In addition, our results suggest that the flavonoids of S. terebinthifolius are responsible for the activities found. We, describe for the first time the activity against Mycobacterium bovis BCG and the inhibition of nitric oxide production for S. terebinthifolius

Influéncia da aplicacao de cálcio e alagamento do solo sobre características anatómicas das folhas de milho (Zea mays L.) ¨Saracura¨ BRS-4154

A cultivar de milho “Saracura” BRS-4154 apresenta-se tolerante às condições de hipoxia decorrentes do encharcamento do solo. Alterações fisiológicas e anatômicas estão envolvidas no processo de adaptação de plantas a ambientes com baixa pressão de oxigênio. Ao mesmo tempo, o cálcio, além de ser um elemento estrutural que participa dos constituintes da parede celular, mostrou-se eficiente no aumento da tolerância de plantas do milho “Saracura” submetidas a estresse gasoso. O objetivo deste trabalho foi avaliar as alterações morfo-anatômicas das folhas da cultivar de milho “Saracura” sob influência da aplicação de cloreto de cálcio e alagamento do solo em plantas em estádio de floração. O experimento foi conduzido em casa de vegetação, cujos tratamentos consistiram na aplicação ou não de cálcio ao solo com irrigação normal ou alagamento. Cortes transversais e paradérmicos foram preparados de acordo com as técnicas usuais de microtécnica vegetal. Foram observadas alterações significativas para o tamanho dos estômatos, ângulo de curvatura de lâmina foliar, diâmetro polar de células buliformes e espessura de nervura mediana, feixe vascular, metaxilema, mesofilo, epiderme das superfícies adaxial e abaxial.Cacao-Theobroma caca

Segurança e integridade de dados em sistemas operacionais móveis–Um estudo de caso sobre a plataforma Android

Este estudo sobre o sistema Android tem como objetivo demonstrar métodos para incrementos de níveis de segurança dentro do sistema. Foram apresentados pontos tais como: vulnerabilidades do sistema, recuperação de dados, backup de dados e foram apresentadas opções para o usuário manter a integridade e usabilidade do sistema operacional

Magnetoliposomes containing calcium ferrite nanoparticles for applications in breast cancer therapy

Magnetoliposomes containing calcium ferrite (CaFe2O4) nanoparticles were developed and characterized for the first time. CaFe2O4 nanoparticles were covered by a lipid bilayer or entrapped in liposomes forming, respectively, solid or aqueous magnetoliposomes as nanocarriers for new antitumor drugs. The magnetic nanoparticles were characterized by UV/Visible absorption, XRD, HR-TEM, and SQUID, exhibiting sizes of 5.2 ± 1.2 nm (from TEM) and a superparamagnetic behavior. The magnetoliposomes were characterized by DLS and TEM. The incorporation of two new potential antitumor drugs (thienopyridine derivatives) specifically active against breast cancer in these nanosystems was investigated by fluorescence emission and anisotropy. Aqueous magnetoliposomes, with hydrodynamic diameters around 130 nm, and solid magnetoliposomes with sizes of ca. 170 nm, interact with biomembranes by fusion and are able to transport the antitumor drugs with generally high encapsulation efficiencies (70%). These fully biocompatible drug-loaded magnetoliposomes can be promising as therapeutic agents in future applications of combined breast cancer therapy.This research was funded by the Portuguese Foundation for Science and Technology (FCT) in the framework of the Strategic Funding of CF-UM-UP (UID/FIS/04650/2013; UID/FIS/04650/2019), CQUM (UID/QUI/00686/2016; UID/QUI/00686/2019) and LA-26 (PEst-C/SAU/LA0026/2013), and through the research project PTDC/QUI-QFI/28020/2017 (POCI-01-0145-FEDER-028020), financed by FCT, European Fund of Regional Development (FEDER), COMPETE2020 and Portugal2020. The magnetic measurements were supported by projects UTAP-EXPL/NTec/0046/2017, NORTE-01-0145-FEDER-028538 e PTDC/FIS-MAC/29454/2017. The APC was also funded by FCT. B.D.C. acknowledges FCT for a PhD grant (SFRH/BD/141936/2018)

Discovery of 74 new bright ZZ Ceti stars in the first three years of TESS

We report the discovery of 74 new pulsating DA white dwarf stars, or ZZ Cetis, from the data obtained by the Transiting Exoplanet Survey Satellite mission, from Sectors 1 to 39, corresponding to the first 3 cycles. This includes objects from the Southern hemisphere (Sectors 1–13 and 27–39) and the Northern hemisphere (Sectors 14–26), observed with 120 s- and 20 s-cadence. Our sample likely includes 13 low-mass and one extremely low-mass white dwarf candidate, considering the mass determinations from fitting Gaia magnitudes and parallax. In addition, we present follow-up time series photometry from ground-based telescopes for 11 objects, which allowed us to detect a larger number of periods. For each object, we analysed the period spectra and performed an asteroseismological analysis, and we estimate the structure parameters of the sample, i.e. stellar mass, effective temperature, and hydrogen envelope mass. We estimate a mean asteroseismological mass of 〈Msis〉 = 0.635 ± 0.015 M⊙, excluding the candidate low or extremely low-mass objects. This value is in agreement with the mean mass using estimates from Gaia data, which is 〈Mphot〉 = 0.631 ± 0.040 M⊙, and with the mean mass of previously known ZZ Cetis of 〈M*〉 = 0.644 ± 0.034 M⊙. Our sample of 74 new bright ZZ Cetis increases the number of known ZZ Cetis by ∼20 per cent

Insulin resistance in adolescents with Down syndrome: a cross-sectional study

BACKGROUND: The prevalence of diabetes mellitus is higher in individuals with Down syndrome (DS) than in the general population; it may be due to the high prevalence of obesity presented by many of them. The aim of this study was to evaluate the insulin resistance (IR) using the HOMA (Homeostasis Model Assessment) method, in DS adolescents, describing it according to the sex, body mass index (BMI) and pubertal development. METHODS: 15 adolescents with DS (8 males and 7 females) were studied, aged 10 to 18 years, without history of disease or use of medication that could change the suggested laboratory evaluation. On physical examination, the pubertal signs, acanthosis nigricans (AN), weight and height were evaluated. Fasting plasma glucose and insulin were analysed by the colorimetric method and RIA-kit LINCO, respectively. IR was calculated using the HOMA method. The patients were grouped into obese, overweight and normal, according to their BMI percentiles. The EPIINFO 2004 software was used to calculate the BMI, its percentile and Z score. RESULTS: Five patients were adults (Tanner V or presence of menarche), 9 pubertal (Tanner II – IV) and 1 prepubertal (Tanner I). No one had AN. Two were obese, 4 overweight and 9 normal. Considering the total number of patients, HOMA was 1.7 ± 1.0, insulin 9.3 ± 4.8 μU/ml and glucose 74.4 ± 14.8 mg/dl. The HOMA values were 2.0 ± 1.0 in females and 1.5 ± 1.0 in males. Considering the nutritional classification, the values of HOMA and insulin were: HOMA: 3.3 ± 0.6, 2.0 ± 1.1 and 1.3 ± 0.6, and insulin: 18.15 ± 1.6 μU/ml, 10.3 ± 3.5 μU/ml and 6.8 ± 2.8 μU/ml, in the obese, overweight and normal groups respectively. Considering puberty, the values of HOMA and insulin were: HOMA: 2.5 ± 1.3, 1.4 ± 0.6 and 0.8 ± 0.0, and insulin: 13.0 ± 5.8 μU/ml, 7.8 ± 2.9 μU/ml and 4.0 ± 0.0 μU/ml, in the adult, pubertal and prepubertal groups respectively. CONCLUSION: The obese and overweight, female and adult patients showed the highest values of HOMA and insulin

Direct tissue-sensing reprograms TLR4+ Tfh-like cells inflammatory profile in the joints of rheumatoid arthritis patients

Funding Information: We thank Cláudia Andrade for technical support and Juliana Gonçalves for testing samples for SARS-CoV-2 exposure. We are extremely grateful to all the participants of the study and to the whole rheumatology department at Hospital Egas Moniz that made this study possible. This work was supported by Fundação para a Ciência e Tecnologia (FCT) PTDC/MEC-REU/29520/2017, by iNOVA4Health UID/Multi/04462 and by Portuguese Society for Rheumatology (SPR) grants to H.S. H.S. is supported by FCT through IF/01722/2013 and CEECIND/01049/2020, DAS and RCT were supported by FCT through PD/BD/137409/2018 and UID/Multi/04462, respectively. Publisher Copyright: © 2021, The Author(s).CD4+ T cells mediate rheumatoid arthritis (RA) pathogenesis through both antibody-dependent and independent mechanisms. It remains unclear how synovial microenvironment impinges on CD4+ T cells pathogenic functions. Here, we identified a TLR4+ follicular helper T (Tfh) cell-like population present in the blood and expanded in synovial fluid. TLR4+ T cells possess a two-pronged pathogenic activity whereby direct TLR4+ engagement by endogenous ligands in the arthritic joint reprograms them from an IL-21 response, known to sponsor antibody production towards an IL-17 inflammatory program recognized to fuel tissue damage. Ex vivo, synovial fluid TLR4+ T cells produced IL-17, but not IL-21. Blocking TLR4 signaling with a specific inhibitor impaired IL-17 production in response to synovial fluid recognition. Mechanistically, we unveiled that T-cell HLA-DR regulates their TLR4 expression. TLR4+ T cells appear to uniquely reconcile an ability to promote systemic antibody production with a local synovial driven tissue damage program.publishersversionpublishe