Soft cationic nanoparticles for drug delivery: production and cytotoxicity of solid lipid nanoparticles (SLNs)

The surface properties of nanoparticles have decisive influence on their interaction with biological barriers (i.e., living cells), being the concentration and type of surfactant factors to have into account. As a result of different molecular structure, charge, and degree of lipophilicity, different surfactants may interact differently with the cell membrane exhibiting different degrees of cytotoxicity. In this work, the cytotoxicity of two cationic solid lipid nanoparticles (SLNs), differing in the cationic lipids used as surfactants CTAB (cetyltrimethylammonium bromide) or DDAB (dimethyldioctadecylammonium bromide), referred as CTAB-SLNs and DDAB-SLNs, respectively, was assessed against five different human cell lines (Caco-2, HepG2, MCF-7, SV-80, and Y-79). Results showed that the cationic lipids used in SLN production highly influenced the cytotoxic profile of the particles, with CTAB-SLNs being highly cytotoxic even at low concentrations (IC50 < 10 µg/mL, expressed as CTAB amount). DDAB-SLNs produced much lower cytotoxicity, even at longer exposure time (IC50 from 284.06 ± 17.01 µg/mL (SV-80) to 869.88 ± 62.45 µg/mL (MCF-7), at 48 h). To the best of our knowledge, this is the first report that compares the cytotoxic profile of CTAB-SLNs and DDAB-SLNs based on the concentration and time of exposure, using different cell lines. In conclusion, the choice of the right surfactant for biological applications influences the biocompatibility of the nanoparticles. Regardless the type of drug delivery system, not only the cytotoxicity of the drug-loaded nanoparticles should be assessed, but also the blank (non-loaded) nanoparticles as their surface properties play a decisive role both in vitro and in vivo.This research was funded by the Portuguese Science and Technology Foundation, Ministry of Science and Education (FCT/MEC) through national funds, and co-financed by FEDER, under the project references M-ERA-NET/0004/2015 (PAIRED) and UID/AGR/04033/2019 (CITAB), co-financed by FEDER, under the Partnership Agreement PT2020.info:eu-repo/semantics/publishedVersio

ANÁLISE DO POTENCIAL ENERGÉTICO RENOVÁVEL BASEADO EM SISTEMAS DE INFORMAÇÃO GEOGRÁFICA: CASO DO LITORAL NORTE, RS

The present study aims to present a methodology based on GIS to identify and locate the renewable energy potential as a contribution to sustainable energy exploration in coastal zones. The developed methodology was applied to North Littoral of Rio Grande do Sul, including 17 municipalities. A database was developed containing thematic layers of coverage and land use, hydrography, geology/geomorphology, digital terrain model (DTM), insolation, solar radiation, wind energy potential, and statistical information about population, agricultural production and electrical energy consumption. Processes of spatial selection, attributes selection, reclassification, overlays, and qualitative and quantitative analyses were applied in order to creating a general table of the predominant energy sources, the diversification of the energy matrix and the possible harnessing potential. The results show that all of the coastal municipalities offer at least two renewable energy sources that can be exploited, fourteen of which possess very high or high renewable energy potential.Este artigo apresenta uma metodologia baseada em SIG para identificação e localização do potencial energético renovável a fim de contribuir com a exploração energética sustentável nas zonas costeiras. A metodologia desenvolvida é aplicada no Litoral Norte do Rio Grande do Sul, com área total de 4.469 km2 e abrange 17 municípios. Foi elaborado um banco de dados contendo layers temáticos de cobertura e uso da terra, hidrografia, geologia/geomorfologia, modelo digital de elevação (MDE), insolação, radiação solar, potencial eólico e informações estatísticas de população, produção agrícola e consumo de energia elétrica. Procedimentos de análise espacial, seleção de atributos, reclassificação, overlays e análises qualitativas e quantitativas foram aplicados, com vistas à criação de um quadro geral das fontes renováveis predominantes, da diversificação da matriz energética e do possível potencial de aproveitamento. Os resultados indicam que todos os municípios litorâneos apresentam pelo menos duas fontes de energia renovável passíveis de aproveitamento (resíduos de biomassa, pequenas hidrelétricas, solar e eólica) e 14 deles possuem alto ou ouito alto potencial energético renovável

Perfil de desempenho de técnicas coproscópicas Coproplus® e Hoffman, Pons e Janner no diagnóstico de giardíase

Justificativa e Objetivos: Os parasitas intestinais representam um problema de saúde pública no Brasil, e sua identificação é feita rotineiramente, por meio de várias técnicas diagnósticas. Muitas dessas técnicas são criticadas por suas limitações, como a de Hoffman, Pons e Janner. Considerou-se avaliar o grau de sensibilidade diagnóstica dessa técnica em comparação ao método coproscópico de coleta e filtragem Coproplus®, uma vez que esta metodologia também é baseada na concentração de estruturas parasíticas e é uma adaptação prática aos métodos usuais, pois não há documentos diagnósticos de protozoários. Métodos: A análise gráfica pelo método de Bland-Altman mostrou que há concordância entre os dois métodos de identificação dos cistos avaliados, ao traçar as diferenças entre o número de cistos contra as médias de ambos os valores. Resultados: Verificou-se que, para os protozoários, o uso de apenas um método parasitológico de Hoffman, Pons e Janner não é suficiente para identificar todas as amostras. Conclusão: Os métodos têm se mostrado eficazes na identificação de parasitas intestinais, mas nem todos os agentes foram identificados simultaneamente em ambas as técnicas e números de cistos, o que leva à conclusão de que uma técnica pode complementar a outra

The Yeast PNC1 Longevity Gene Is Up-Regulated by mRNA Mistranslation

Translation fidelity is critical for protein synthesis and to ensure correct cell functioning. Mutations in the protein synthesis machinery or environmental factors that increase synthesis of mistranslated proteins result in cell death and degeneration and are associated with neurodegenerative diseases, cancer and with an increasing number of mitochondrial disorders. Remarkably, mRNA mistranslation plays critical roles in the evolution of the genetic code, can be beneficial under stress conditions in yeast and in Escherichia coli and is an important source of peptides for MHC class I complex in dendritic cells. Despite this, its biology has been overlooked over the years due to technical difficulties in its detection and quantification. In order to shed new light on the biological relevance of mistranslation we have generated codon misreading in Saccharomyces cerevisiae using drugs and tRNA engineering methodologies. Surprisingly, such mistranslation up-regulated the longevity gene PNC1. Similar results were also obtained in cells grown in the presence of amino acid analogues that promote protein misfolding. The overall data showed that PNC1 is a biomarker of mRNA mistranslation and protein misfolding and that PNC1-GFP fusions can be used to monitor these two important biological phenomena in vivo in an easy manner, thus opening new avenues to understand their biological relevance

Nanoparticle delivery systems in the treatment of diabetes complications

Diabetes mellitus, an incurable metabolic disease, is characterized by changes in the homeostasis of blood sugar levels, being the subcutaneous injection of insulin the first line treatment. This administration route is however associated with limited patients compliance, due to the risk of pain, discomfort and local infection. Nanoparticles have been proposed as insulin carriers to make possible the administration of the peptide via friendlier pathways without the need of injection, i.e., via oral or nasal routes. Nanoparticles stand for particles in the nanometer range that can be obtained from different materials (e.g., polysaccharides, synthetic polymers, lipid) and are commonly used with the aim to improve the physicochemical stability of the loaded drug and thereby its bioavailability. This review discusses the use of different types of nanoparticles (e.g., polymeric and lipid nanoparticles, liposomes, dendrimers, niosomes, micelles, nanoemulsions and also drug nanosuspensions) for improved delivery of different oral hypoglycemic agents in comparison to conventional therapies.The authors acknowledge the financial support received from Portuguese Science and Technology Foundation (FCT/MCT) and from European Funds (PRODER/COMPETE) under the project reference M-ERA-NET/0004/2015-PAIRED, co-financed by FEDER, under the Partnership Agreement PT2020. The authors also acknowledge the support of the research project: “Nutraceutica come supporto nutrizionale nel paziente oncologico”, CUP: B83D18000140007.info:eu-repo/semantics/publishedVersio

A combined linkage and exome sequencing analysis for electrocardiogram parameters in the Erasmus Rucphen family study

Electrocardiogram (ECG) measurements play a key role in the diagnosis and prediction of cardiac arrhythmias and sudden cardiac death. ECG parameters, such as the PR, QRS, and QT intervals, are known to be heritable and genome-wide association studies of these phenotypes have been successful in identifying common variants; however, a large proportion of the genetic variability of these traits remains to be elucidated. The aim of this study was to discover loci potentially harboring rare variants utilizing variance component linkage analysis in 1547 individuals from a large family-based study, the Erasmus Rucphen Family Study (ERF). Linked regions were further explored using exome sequencing. Five suggestive linkage peaks were identified: two for QT interval (1q24, LOD = 2.63; 2q34, LOD = 2.05), one for QRS interval (1p35, LOD = 2.52) and two for PR interval (9p22, LOD = 2.20; 14q11, LOD = 2.29). Fine-mapping using exome sequence data identified a C > G missense variant (c.713C > G, p.Ser238Cys) in the FCRL2 gene associated with QT (rs74608430; P = 2.8 × 10-4, minor allele frequency = 0.019). Heritability analysis demonstrated that the SNP explained 2.42% of the trait's genetic variability in ERF (P = 0.02). Pathway analysis suggested that the gene is involved in cytosolic Ca2+ levels (P = 3.3 × 10-3) and AMPK stimulated fatty acid oxidat

A combined linkage, microarray and exome analysis suggests MAP3K11 as a candidate gene for left ventricular hypertrophy

Background: Electrocardiographic measures of left ventricular hypertrophy (LVH) are used as predictors of cardiovascular risk. We combined linkage and association analyses to discover novel rare genetic variants involved in three such measures and two principal components derived from them. Methods: The study was conducted among participants from the Erasmus Rucphen Family Study (ERF), a Dutch family-based sample from the southwestern Netherlands. Variance components linkage analyses were performed using Merlin. Regions of interest (LOD &gt; 1.9) were fine-mapped using microarray and exome sequence data. Results: We observed one significant LOD score for the second principal component on chromosome 15 (LOD score = 3.01) and 12 suggestive LOD scores. Several loci contained variants identified in GWAS for these traits; however, these did not explain the linkage peaks, nor did other common variants. Exome sequence data identified two associated variants after multiple testing corrections were applied. Conclusions: We did not find common SNPs explaining these linkage signals. Exome sequencing uncovered a relatively rare variant in MAPK3K11 on chromosome 11 (MAF = 0.01) that helped account for the suggestive linkage peak observed for the first principal component. Conditional analysis revealed a drop in LOD from 2.01 to 0.88 for MAP3K11, suggesting that this variant may partially explain the linkage signal at this chromosomal location. MAP3K11 is related to the JNK pathway and is a pro-apoptotic kinase that plays an important role in the induction of cardiomyocyte apoptosis in various pathologies, including LVH. © 2018 The Author(s)

A combined linkage, microarray and exome analysis suggests MAP3K11 as a candidate gene for left ventricular hypertrophy

Background: Electrocardiographic measures of left ventricular hypertrophy (LVH) are used as predictors of cardiovascular risk. We combined linkage and association analyses to discover novel rare genetic variants involved in three such measures and two principal components derived from them. Methods: The study was conducted among participants from the Erasmus Rucphen Family Study (ERF), a Dutch family-based sample from the southwestern Netherlands. Variance components linkage analyses were performed using Merlin. Regions of interest (LOD > 1.9) were fine-mapped using microarray and exome sequence data. Results: We observed one significant LOD score for the second principal component on chromosome 15 (LOD score = 3.01) and 12 suggestive LOD scores. Several loci contained variants identified in GWAS for these traits; however, these did not explain the linkage peaks, nor did other common variants. Exome sequence data identified two associated variants after multiple testing corrections were applied. Conclusions: We did not find common SNPs explaining these linkage signals. Exome sequencing uncovered a relatively rare variant in MAPK3K11 on chromosome 11 (MAF = 0.01) that helped account for the suggestive linkage peak observed for the first principal component. Conditional analysis revealed a drop in LOD from 2.01 to 0.88 for MAP3K11, suggesting that this variant may partially explain the linkage signal at this chromosomal location. MAP3K11 is related to the JNK pathway and is a pro-apoptotic kinase that plays an important role in the induction of cardiomyocyte apoptosis in various pathologies, including LVH