Nanotechnology solutions for controlled cytokine delivery: an applied perspective

Around 200 cytokines with roles in cell signaling have been identified and studied, with the vast majority belonging to the four-α-helix bundle family. These proteins exert their function by binding to specific receptors and are implicated in many diseases. The use of several cytokines as therapeutic targets has been approved by the FDA, however their rapid clearance in vivo still greatly limits their efficacy. Nano-based drug delivery systems have been widely applied in nanomedicine to develop safe, specific and controlled delivery techniques. Nevertheless, each nanomaterial has its own specifications and their suitability towards the biochemical and biophysical properties of the selected drug needs to be determined, weighing in the final choice of the ideal nano drug delivery system. Nanoparticles remain the most used vehicle for cytokine delivery, where polymeric carriers represent the vast majority of the studied systems. Liposomes and gold or silica nanoparticles are also explored and discussed in this review. Additionally, surface functionalization is of great importance to facilitate the attachment of a wide variety of molecules and modify features such as bioavailability. Since the monitoring of cytokine levels has an important role in early clinical diagnosis and for assessing therapeutic efficacy, nanotechnological advances are also valuable for nanosensor development.This work was supported by the “Contrato-Programa” UIDB/04050/2020 funded by national funds through the FCT I.P. and project FUN2CYT: Harnessing the potential for biomedical applications of pleiotropic cytokines LIF and oncostatin M (POCI-01-0145-FEDER-030568) supported by Programa Operacional Competitividade e Internacionalização (FEDER) and FCT, IP. Anabela Gonçalves acknowledges her PhD scholarship from FCT (SFRH/BD/146807/2019)

History-indicated transvaginal cerclage: results from a single-centre

Background: Cervical incompetence occasionally results in mid-trimester pregnancy loss, preterm labour and increased foetal morbimortality. History-indicated cerclage is proposed when obstetric history suggests cervical incompetence. The aim of this study was to evaluate the maternal-foetal outcomes following prophylactic cervical cerclage.Methods: Retrospective study reviewing data of all women undergoing transvaginal history-indicated cerclage from January 1st, 2008 to December 31th, 2017 at Centro Hospitalar Universitário do Algarve - Faro. Primary outcome: gestational age <37weeks at birth. Secondary outcomes: neonatal morbimortality and intensive care unit (NICU) admission and maternal morbidity. Data were analyzed with IBM SPSS Statistics 23.Results: A total of 12 history-indicated cerclages were performed (9 women). At first cerclage, mean maternal age, gestity, parity and live children were 27.6, 2.44, 1.11 and 0.78 (87.7% preterm), respectively. At cerclage placement, mean gestational age and cervical length were 16.1 weeks and 27.5mm. Average hospital admission was 10.7 days. In all cases McDonald technique was performed. Four hospital readmissions occurred for threatened labour. Mean gestational age at cerclage removal was 36.9 weeks (83.3% in ambulatory) and 38.9 at delivery. Average time between cerclage removal and labour was 14.5 days. Spontaneous onset of labour occurred in 75% and vaginal delivery in 83.4%. There were no reports of preterm birth, foetal admission to NICU or maternal complications. Mean number of live children after procedure was 1.58.Conclusions: Prophylactic cervical cerclage seems to improve pregnancy outcome with minimal maternal risks. However, our data suggest over inclusion of women, with unnecessary procedures, emphasizing the importance of re-evaluating inclusion criteria

Tendências Seculares na Mortalidade por Doenças Cerebrovasculares em Portugal: 1902-2012

Introduction: Cerebrovascular diseases (CVD) are one of the main causes of death in Portugal. Research on the epidemiologic history might help to understand the phenomenon and guide intervention strategies. Objectives: (1) Describe historic trends in mortality. (2) Estimate the impact of demographic variations on the registered number of cases. Methods: (1) We calculated rates, specific and standardized, for deaths registered as CVD (ICD-10: I60-I69, G45; ICD8/9: 430-438; ICD-6/7: 330-334) by sex (1902-2012) and by sex and age groups (1913-2012). We used Join point analysis to identify statistically significant changes in standardized death rates, and multivariate regression models, Poisson and negative binomial, controlling for demographic dynamics and time trend, from 1913 to 2012. (2) We calculated the contribution of demographic variations using the application RiskDiff. (3) We evaluated if changes in coding rules might have been a source of bias. Data source: National Institute of Statistics. Results: (1) We gathered the longest and most discriminated mortality series from CVD in Portugal with data since the beginning of nationwide collection. Mortality increases exponentially with age and is higher in men. (2) We observed significant variations in age-standardized time trends (1913-1933: APC 2.0%; 1933-1955: APC -0.9%; 1955-1974: 2.9%; 1974- 1996: -2.4%; 1996-2012: -6.5%). (3) Population ageing exerted a significant pressure to increase the number of deaths, particularly in the second half of the twentieth century. However, this effect was counterweighted by protective factors. Conclusion: CVD mortality in Portugal is particularly expressive when compared to other European countries, although significant gains have been observed in the last decades. Population ageing combined with a transition between the morbid and mortality dimensions changed the public health paradigm.Introdução: As doenças cerebrovasculares (DCV) são uma das principais causas de morte em Portugal. O estudo da história epidemiológica deste fenómeno contribui para a sua compreensão e ajuda a orientar estratégias de intervenção. Objetivos: (1) Descrever tendências históricas na mortalidade. (2) Estimar o impacto das variações demográficas no número de casos registado. Métodos: (1) Calculámos taxas, específicas e padronizadas, para as mortes registadas como resultantes de DCV (CID-10: I60-I69, G45; ICD-8/9: 430-438; ICD-6/7: 330-334) por sexo (1902-2012) e por sexo e grupos etários (1913- 2012). Utilizámos Joinpoint-analysis para identificar variações estatisticamente significativas na tendência temporal e modelos multivariados de regressão, Poisson e binomial negativo, controlando dinâmicas demográficas e tendências temporais, constrangidos à população exposta, de 1913 a 2012. (2) Aferimos o peso relativo de variações demográficas recorrendo à aplicação RiskDiff. (3) Avaliámos se as interrupções na continuidade das séries definidas por alterações nos critérios de codificação da causa de morte podem ter constituído factores confundentes. Fontes dos dados: Instituto Nacional de Estatística. Resultados: (1) Elencámos a mais longa e discriminada série de mortalidade por DCV em Portugal com dados desde que há registo com abrangência nacional. A mortalidade aumenta exponencialmente com a idade e é superior nos homens. (2) Observámos variações significativas na direcção e amplitude da tendência temporal das taxas padronizadas (1913-1933: APC 2,0%; 1933-1955: APC -0,9%; 1955-1974: 2,9%; 1974-1996: -2,4%; 1996-2012: -6,5%). (3) O envelhecimento demográfico exerceu uma pressão significativa para o aumento no número de casos particularmente na segunda metade do século XX. No entanto este efeito foi neutralizado por factores protectores. Conclusão: Em Portugal a DCV é particularmente expressiva quando comparada com outros países da Europa embora se tenham observado ganhos significativos nas últimas décadas. O envelhecimento demográfico combinado com uma eventual transição relativa entre as dimensões morbil e de mortalidade proporcionaram uma mudança no paradigma de saúde pública.info:eu-repo/semantics/publishedVersio

APOBEC3 host factors modulate viral production and infectivity of HIV-2

Poster presented at the 15th European AIDS Conference/EACS. Barcelona, 21-24 October 2015.This work was funded by FCT – SFRH/BD/81921/2011 and Egas Moniz, Cooperativa de Ensino Superior, CRL, Portugal

Release of fragrances from cotton functionalized with carbohydrate-binding module proteins

Perspiration as a response to daily activity and physical exercise results in unpleasant odors that cause social unrest and embarrassment. To tackle it, functional textiles incorporating fragrances could be an effective clothing deodorizing product. This work presents two strategies for the release of -citronellol from functionalized cotton with carbohydrate-binding module (CBM)-based complexes (OBP::GQ20::CBM/-citronellolapproach 1 and CBM::GQ20::SP-DS3-liposome/-citronellolapproach 2). CBM from Cellulomonas fimi was fused with the odorant-binding protein (OBP::GQ20::CBM) and with an anchor peptide with affinity to the liposome membrane (CBM::GQ20::SP-DS3). In approach 1, OBP fusion protein served as a fragrance container, whereas in approach 2, the fragrance was loaded into liposomes with a higher cargo capacity. The two strategies showed a differentiated -citronellol release profile triggered by an acidic sweat solution. OBP::GQ20::CBM complex revealed a fast release (31.9% and 25.8% of the initial amount, after 1.5 and 24 h of exposure with acidic sweat solution, respectively), while the CBM::GQ20::SP-DS3-liposome complex demonstrated a slower and controlled release (5.9% and 10.5% of the initial amount, after 1.5 and 24 h of exposure with acidic sweat solution, respectively). Both strategies revealed high potential for textile functionalization aimed at controlled release of fragrances. The OBP::GQ20::CBM/-citronellol complex is ideal for applications requiring fast release of a high amount of fragrance, whereas the CBM::GQ20::SP-DS3-liposome/-citronellol complex is more suitable for prolonged and controlled release of a lower amount of -citronellol.This study was supported by the Portuguese Foundation for Science and Technology (FCT) under the scope of the strategic funding of UID/BIO/04469/2019 unit and BioTecNorte operation (NORTE-01-0145-FEDER-000004) funded by European Regional Development Fund under the scope of Norte2020 - Programa Operacional Regional do Norte. F.G. and C.S. thanks FCT for their funding (SFRH/BD/114684/2016; SFRH/IF/00186/2015).info:eu-repo/semantics/publishedVersio

Surface Grafted MSI-78A Antimicrobial Peptide has High Potential for Gastric Infection Management

As we approach the end of the antibiotic era, newer therapeutic options, such as antimicrobial peptides (AMPs), are in urgent demand. AMP surface grafting onto biomaterials has been described as a good strategy to overcome problems associated with their in vivo stability. Helicobacter pylori is among the bacteria that pose greatest threat to human health, being MSI-78A one of the few bactericidal AMPs against this bacterium. Here, we report that MSI-78A grafted onto model surfaces (Self-Assembled Monolayers –SAMs), in a concentration of 30.3 ± 1.2 ng/cm2 determined by quartz crystal microbalance with dissipation (QCM-D), was able to kill, by contact, 98% of planktonic H. pylori in only 2 h. This fact was not verified against the control bacteria (Staphylococcus epidermidis), although the minimal inhibitory concentration (MIC) of MSI-78A in solution is much lower for S. epidermidis (2 µg/mL) than for H. pylori (64 µg/mL). Our results also demonstrated that, in opposite to other bacteria, H. pylori cells were attracted to ethylene glycol terminated (antiadhesive) surfaces, which can explain the high bactericidal potential of grafted MSI-78A. This proof of concept study establishes the foundations for development of MSI-78A grafted nanoparticles for gastric infection management within a targeted nanomedicine concept.This article is a result of the project NORTE-01-0145-FEDER-00012, (NORTE 2020) and FCT/MCTES-through the UID/BIM/04293/2019, PTDC/CTM-BIO/4043/2014, UID/QUI/50006/2013 (LAQV-REQUIMTE) projects. Claudia Monteiro acknowledges FCT for the SFRH/BPD/79439/2011 grant