Proteostasis networks in aging: novel insights from text-mining approaches

Aging is a topic of paramount importance in an increasingly elderly society and has been the focus of extensive research. Protein homeostasis (proteostasis) decline is a hallmark in aging and several age-related diseases, but which specific proteins and mechanisms are involved in proteostasis (de)regulation during the aging process remain largely unknown. Here, we used different text-mining tools complemented with protein–protein interaction data to address this complex topic. Analysis of the integrated protein interaction networks identified novel proteins and pathways associated to proteostasis mechanisms and aging or age-related disorders, indicating that this approach is useful to identify previously unknown links and for retrieving information of potential novel biomarkers or therapeutic targets.info:eu-repo/semantics/acceptedVersio

Design of double-walled carbon nanotubes for biomedical applications

Double-walled carbon nanotubes (DWNTs) prepared by catalytic chemical vapour deposition were functionalized in such a way that they were optimally designed as a nano-vector for the delivery of small interfering RNA (siRNA), which is of great interest for biomedical research and drug development. DWNTs were initially oxidized and coated with a polypeptide (Poly(Lys:Phe)), which was then conjugated to thiol-modified siRNA using a heterobifunctional cross-linker. The obtained oxDWNT–siRNA was characterized by Raman spectroscopy inside and outside a biological environment (mammalian cells). Uptake of the custom designed nanotubes was not associated with detectable biochemical perturbations in cultured cells, but transfection of cells with DWNTs loaded with siRNA targeting the green fluorescent protein (GFP) gene, serving as a model system, as well as with therapeutic siRNA targeting the survivin gene, led to a significant gene silencing effect, and in the latter case a resulting apoptotic effect in cancer cells

Antioxidant and anti-inflammatory activities of cytocompatible Salvia officinalis extracts: A comparison between traditional and soxhlet extraction

Chronic inflammation is characterized by an overproduction of several inflammatory mediators (e.g., reactive species and interleukins -IL) that play a central role in numerous diseases. The available therapies are often associated with serious side effects and, consequently, the need for safer drugs is of utmost importance. A plant traditionally used in the treatment of inflammatory conditions is Salvia officinalis. Therefore, conventional maceration and infusion of its leaves were performed to obtain hydroethanolic (HE-T) and aqueous extracts (AE-T), respectively. Their efficacy was compared to soxhlet extracts, namely aqueous (AE-S), hydroethanolic (HE-S), and ethanolic extracts (EE-S). Thin-layer chromatography demonstrated the presence of rosmarinic acid, carnosol, and/or carnosic acid in the different extracts. Generally, soxhlet provided extracts with higher antioxidant activities than traditional extraction. Moreover, under an inflammatory scenario, EE-S were the most effective, followed by HE-S, HE-T, AE-T, and AE-S, in the reduction of IL-6 and TNF-α production. Interestingly, the extracts presented higher or similar anti-inflammatory activity than diclofenac, salicylic acid, and celecoxib. In conclusion, the extraction method and the solvents of extraction influenced the antioxidant activity, but mainly the anti-inflammatory activity of the extracts. Therefore, this natural resource can enable the development of effective treatments for oxidative stress and inflammatory diseases.Fundação para a Ciência e a Tecnologia (FCT) to the PhD grant of SV (PD/BD/135246/2017) and the projects PATH (PD/00169/2013), Cells4_IDs (PTDC/BTM-SAL/28882/2017) and the NORTE 2020 Structured Project, cofunded by Norte2020 (NORTE-01-0145-FEDER-000021

Hyaluronic acid/poly-L-lysine bilayered silica nanoparticles enhance the osteogenic differentiation of human mesenchymal stem cells

First published online 15 Aug 2014Herein, we evaluate the influence of a PLL–HA bilayer on the surface of silica nanoparticles on their capacity to induce the osteogenic differentiation of human bone marrow stem cells (hBMSCs), as a function of their concentration (50 μg mL−1, 25 μg mL−1 and 12.5 μg mL−1). To this purpose, we synthesized silica nanoparticles (diameter of 250 nm; ζ-potential of −25 mV) that were coated with PLL–HA (diameter of 560 nm; ζ-potential of −35 mV). The cell viability, cell proliferation, protein quantification (i.e. MTS, DNA and ALP, respectively) and gene expression (of osteogenesis-related genes: ALP, osteocalcin, collagen type I, bone sialoprotein, Runx-2, osteopontin and osterix) were monitored, for 21 days. We observed the overexpression of most of the tested osteogenic transcripts in the hBMSCs cultured with SiO2–PLL–HA, at concentrations of 25 μg mL−1 and 12.5 μg mL−1. These results indicate that the proposed nanoparticles temporarily improve the osteogenic differentiation of hBMSCs at low nanoparticle concentrations.We acknowledge funding from the European Union Seventh Framework Programme (FP7/2007-2013) under grant agreement number REGPOT-CT2012-316331-POLARIS. AM acknowledges QREN (project "RL1-ABMR-NORTE-01-0124-FEDER-000016" co-financed by the North Portugal Regional Operational Programme (ON. 2, "O Novo Norte") under the NSRF through the ERDF) for financing this research work

Valinomycin Biosynthetic Gene Cluster in Streptomyces: Conservation, Ecology and Evolution

Many Streptomyces strains are known to produce valinomycin (VLM) antibiotic and the VLM biosynthetic gene cluster (vlm) has been characterized in two independent isolates. Here we report the phylogenetic relationships of these strains using both parsimony and likelihood methods, and discuss whether the vlm gene cluster shows evidence of horizontal transmission common in natural product biosynthetic genes. Eight Streptomyces strains from around the world were obtained and sequenced for three regions of the two large nonribosomal peptide synthetase genes (vlm1 and vlm2) involved in VLM biosynthesis. The DNA sequences representing the vlm gene cluster are highly conserved among all eight environmental strains. The geographic distribution pattern of these strains and the strict congruence between the trees of the two vlm genes and the housekeeping genes, 16S rDNA and trpB, suggest vertical transmission of the vlm gene cluster in Streptomyces with no evidence of horizontal gene transfer. We also explored the relationship of the sequence of vlm genes to that of the cereulide biosynthetic genes (ces) found in Bacillus cereus and found them highly divergent from each other at DNA level (genetic distance values≥95.6%). It is possible that the vlm gene cluster and the ces gene cluster may share a relatively distant common ancestor but these two gene clusters have since evolved independently

Preparação de sabão com propriedades fitoterápicas e emolientes a partir do óleo vegetal de cozinha.

Diariamente são descartados litros e litros de óleo doméstico usado, uma parte desse descarte se dá em latas de lixo, rede de esgoto, poucos são aqueles que reservam esse tipo de material para reciclagem, uma parte é por não saber como tratar os resíduos contidos em seu meio. Os projetos de preparação de sabão com propriedades fitoterápicas têm por objetivo dar um destino ao descarte desse óleo residual doméstico, promovendo a interação da comunidade local da região da Vila C a fazer desde a parte do tratamento de resíduo do óleo até a mistura de outros reagentes para a produção de um sabão para o banho de animais domésticos e que possa ser utilizável para limpeza de utensílios domésticos. Para a preparação deste material é considerado o fácil acesso aos reagentes envolvidos como a soda cáustica, a qual ainda é comercialmente vendida em mercearias locais e acesso às plantas medicinais que já tem suas propriedades conhecidas, como no caso a erva baleeira, calêndula, e citronela, também é realizado junto a comunidade, oficinas informando sobre os cuidados em manipular produtos químicos, como agir em caso de acidentes durante o manuseio, a quem é indicado a fazer esse tipo de tratamento e como preparar o produto. Existem análises laboratoriais que são acompanhadas e orientadas, as quais são necessárias para testes em pequena escala antes de cada oficina, essas análises são feitas para poder corrigir o pH do produto e mensurar a quantidade de aditivos na produção do sabão, após essas análises o modelo de produção é replicado em escala maior, já com a certeza dos resultados na qualidade do produto final. Desta forma se faz necessário uma investigação mais detalhada ao produto final, por meio de utilização de equipamentos cromatográficos e espectrofotômetros, como ferramenta na identificação dos compostos e/ou princípios ativos na composição, os quais dão a característica de fitoterápicos e comparar desta forma, com o que já temos em literatura conhecida

Characterization of non-volatile oxidation products formed from triolein in a model study at frying temperature

Frying allows cooking food while promoting their organoleptic properties, imparting crunchiness and flavor. The drawback is the oxidation of triacylglycerides (TAGs), leading to the formation of primary oxidized TAGs. Although they have been associated with chronic and degenerative diseases, they are precursors of pleasant flavors in fried foods. Nevertheless, there is a lack of knowledge about the oxidation species present in foods and their involvement in positive/negative health effects. In this work, high-resolution (HR) C30 reversed-phase (RP)−liquid chromatography (LC)−tandem HR mass spectrometry (MS/MS) was used to identify primary oxidation TAGs resulting from heating triolein (160 °C, 5 min). This allows simulating the initial heating process of frying oils usually used to prepare fried foods, such as chips, crisps, and snacks. Beyond hydroxy, dihydroxy, hydroperoxy, and hydroxy−hydroperoxy derivatives, already reported in phospholipids oxidized by Fenton reaction, new compounds were identified, such as dihydroxy−hydroperoxy−triolein derivatives and positional isomers (9/10- and 9/12-dihydroxy−triolein derivatives). These compounds should be considered when proposing flavor formation pathways and/or mitigating lipid-derived reactive oxygen species occurring during food frying.publishe

An insight on the role of photosensitizer nanocarriers for Photodynamic Therapy

Photodynamic therapy (PDT) is a modality of cancer treatment in which tumor cells are destroyed by reactive oxygen species (ROS) produced by photosensitizers following its activation with visible or near infrared light. The PDT success is dependent on different factors namely on the efficiency of the photosensitizer deliver and targeting ability. In this review a special attention will be given to the role of some drug delivery systems to improve the efficiency of tetrapyrrolic photosensitizers to this type of treatment.publishe

On the bioactivity of Echinacea purpurea extracts to modulate the production of inflammatory mediators

Inflammatory diseases are the focus of several clinical studies, due to limitations and serious side effects of available therapies. Plant-based drugs (e.g., salicylic acid, morphine) have become landmarks in the pharmaceutical field. Therefore, we investigated the immunomodulatory effects of flowers, leaves, and roots from Echinacea purpurea. Ethanolic (EE) and dichloromethanolic extracts (DE) were obtained using the Accelerated Solvent Extractor and aqueous extracts (AE) were prepared under stirring. Their chemical fingerprint was evaluated by liquid chromatography–high resolution mass spectrometry (LC-HRMS). The pro- and anti-inflammatory effects, as well as the reduction in intracellular reactive oxygen and nitrogen species (ROS/RNS), of the different extracts were evaluated using non-stimulated and lipopolysaccharide-stimulated macrophages. Interestingly, AE were able to stimulate macrophages to produce pro-inflammatory cytokines (tumor necrosis factor -TNF-α, interleukin -IL-1β, and IL-6), and to generate ROS/RNS. Conversely, under an inflammatory scenario, all extracts reduced the amount of pro-inflammatory mediators. DE, alkylamides-enriched extracts, showed the strongest anti-inflammatory activity. Moreover, E. purpurea extracts demonstrated generally a more robust anti-inflammatory activity than clinically used anti-inflammatory drugs (dexamethasone, diclofenac, salicylic acid, and celecoxib). Therefore, E. purpurea extracts may be used to develop new effective therapeutic formulations for disorders in which the immune system is either overactive or impaired.This research was funded by the Fundação para a Ciência e a Tecnologia (FCT) to the PhD grant of SFV (PD/BD/135246/2017 and COVID/BD/152012/2021) and the projects PATH (PD/00169/2013), FROnTHERA (NORTE-01-0145-FEDER-000023), Cells4_IDs (PTDC/BTM-SAL/28882/2017), and the NORTE 2020 Structured Project, co-funded by Norte2020 (NORTE-01-0145-FEDER-000021). This research was also partially supported by national funds by FCT through the projects UIDB/04423/2020 and UIDP/04423/2020 (Group of Natural Products and Medicinal Chemistry-CIIMAR) and ERDF, through the COMPETE—POFC program in the framework of the program PT2020