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Reduced graphene oxide (rGO) is a promising graphene-based material, with transversal applicability to a wide range of technological fields. Nevertheless, the common use of efficient—but hazardous to environment and toxic—reducing agents prevents its application in biological and other fields. Consequently, the development of green reducing strategies is a requirement to overcome this issue. Herein, a green, simple, and cost-effective one-step reduction methodology is presented. Graphene oxide (GO) was hydrothermally reduced in the presence of caffeic acid (CA), a natural occurring phenolic compound. The improvement of the hydrothermal reduction through the presence of CA is confirmed by XRD, Raman, XPS and TGA analysis. Moreover, CA polymerizes under hydrothermal conditions with the formation of spherical and non-spherical carbon particles, which can be useful for further rGO functionalization. FTIR and XPS confirm the oxygen removal in the reduced samples. The high-resolution scanning transmission electron microscopy (HRSTEM) images also support the reduction, showing rGO samples with an ordered graphitic layered structure. The promising rGO synthesized by this eco-friendly methodology can be explored for many applications.

Cardiovascular (CV) toxicity is nowadays recognized as a class effect of non-aspirin nonsteroidal anti-inflammatory drugs (NSAIDs). However, their mechanisms of cardiotoxicity are not yet well understood, since different compounds with similar action mechanisms exhibit distinct cardiotoxicity. For instance, diclofenac (DIC) is among the most cardiotoxic compounds, while naproxen (NAP) is associated with low CV risk. In this sense, this study aimed to unravel the role of drug-lipid interactions in NSAIDs-induced cardiotoxicity. For that, DIC and NAP interactions with lipid bilayers as model systems of cell and mitochondrial membranes were characterized by derivative spectrophotometry, fluorometric leakage assays, and synchrotron X-ray scattering. Both DIC and NAP were found to have the ability to permeabilize the membrane models, as well as to alter the bilayers’ structure. The NSAIDs-induced modifications were dependent on the lipid composition of the membrane model, the three-dimensional structure of the drug, as well as the drug:lipid molar ratio tested. Altogether, this work supports the hypothesis that NSAIDs-lipid interactions, in particular at the mitochondrial level, may be another key step among the mechanisms underlying NSAIDs-induced cardiotoxicity.

Chronic neuroinflammation associated with neurodegenerative disorders has been reported to be prevented by dietary components. Particularly, dietary (poly)phenols have been identified as having anti-inflammatory and neuroprotective actions, and their ingestion is considered a major preventive factor for such disorders. To assess the relation between (poly)phenol classes and their bioactivity, we used five different raspberry genotypes, which were markedly different in their (poly)phenol profiles within a similar matrix. In addition, gastro-intestinal bio-accessible fractions were produced, which simulate the (poly)phenol metabolites that may be absorbed after digestion, and evaluated for anti-inflammatory potential using LPS-stimulated microglia. Interestingly, the fraction from genotype 2J19 enriched in ellagitannins, their degradation products and ellagic acid, attenuated pro-inflammatory markers and mediators CD40, NO, TNF-α, and intracellular superoxide via NF-κB, MAPK and NFAT pathways. Importantly, it also increased the release of the anti-inflammatory cytokine IL-10. These effects contrasted with fractions richer in anthocyanins, suggesting that ellagitannins and its derivatives are major anti-inflammatory (poly)phenols and promising compounds to alleviate neuroinflammation

Polar lipids from microalgae have aroused greater interest as a natural source of omega-3 (n-3) polyunsaturated fatty acids (PUFA), an alternative to fish, but also as bioactive compounds with multiple applications. The present study aims to characterize the polar lipid profile of cultured microalga Emiliania huxleyi using hydrophilic interaction liquid chromatography coupled with high-resolution mass spectrometry (HILIC–MS) and fatty acids (FA) analysis by gas chromatography (GC–MS). The lipidome of E. huxleyi revealed the presence of distinct n-3 PUFA (40% of total FA), namely docosahexaenoic acid (22:6n-3) and stearidonic acid (18:4n-3), which give this microalga an increased commercial value as a source of n-3 PUFA present in the form of polar lipids. A total of 134 species of polar lipids were identified and some of these species, particularly glycolipids, have already been reported for their bioactive properties. Among betaine lipids, the diacylglyceryl carboxyhydroxymethylcholine (DGCC) class is the least reported in microalgae. For the first time, monomethylphosphatidylethanolamine (MMPE) has been found in the lipidome of E. huxleyi. Overall, this study highlights the potential of E. huxleyi as a sustainable source of high-value polar lipids that can be exploited for different applications, namely human and animal nutrition, cosmetics, and pharmaceuticals.

This review aims to showcase the current use of graphene derivatives, graphene-based nanomaterials in particular, in biopolymer-based composites for food packaging applications. A brief introduction regarding the valuable attributes of available and emergent bioplastic materials is made so that their contributions to the packaging field can be understood. Furthermore, their drawbacks are also disclosed to highlight the benefits that graphene derivatives can bring to bio-based formulations, from physicochemical to mechanical, barrier, and functional properties as antioxidant activity or electrical conductivity. The reported improvements in biopolymer-based composites carried out by graphene derivatives in the last three years are discussed, pointing to their potential for innovative food packaging applications such as electrically conductive food packaging.

A presente investigação teve com objectivo principal estudar as relações entre exercício físico, autoconceito e o aproveitamento escolar em estudantes do segundo e terceiro ciclos de escolaridade com idades compreendidas entre os 12 e os 19 anos. Visa, ainda, constatar se os hábitos de exercício refletem as recomendações para a manutenção da saúde. A amostra foi constituída por 624 indivíduos (268 do sexo masculino, 354 do sexo feminino). Avaliou-se o autoconceito através do Self-Description Questionnaire II (SDQ-II) (Marsh, 1990; versão portuguesa de Gonçalves & Vasconcelos-Raposo, 2001) e o aproveitamento escolar foi quantificado a partir do número de reprovações na escola. De uma forma geral conclui-se que existe uma relação positiva entre autoconceito e exercício físico e uma correlação também positiva entre o autoconceito e aproveitamento escolar.

Commercial production of microalgal biomass for food and feed is a recent worldwide trend. Although it is common to publish nutritional data for microalgae grown at the lab-scale, data about industrial strains cultivated in an industrial setting are scarce in the literature. Thus, here we present the nutritional composition and a microbiological and toxicological evaluation of Tetraselmis sp. CTP4 biomass, cultivated in 100-m3 photobioreactors at an industrial production facility (AlgaFarm). This microalga contained high amounts of protein (31.2 g/100 g), dietary fibres (24.6 g/100 g), digestible carbohydrates (18.1 g/100 g) and ashes (15.2 g/100 g), but low lipid content (7.04 g/100 g). The biomass displayed a balanced amount of essential amino acids, n-3 polyunsaturated fatty acids, and starch-like polysaccharides. Significant levels of chlorophyll (3.5 g/100 g), carotenoids (0.61 g/100 g), and vitamins (e.g., 79.2 mg ascorbic acid /100 g) were also found in the biomass. Conversely, pathogenic bacteria, heavy metals, cyanotoxins, mycotoxins, polycyclic aromatic hydrocarbons, and pesticides were absent. The biomass showed moderate antioxidant activity in several in vitro assays. Taken together, as the biomass produced has a balanced biochemical composition of macronutrients and (pro-)vitamins, lacking any toxic contaminants, these results suggest that this strain can be used for nutritional applications.

Cyclosporine A (CsA) is an immunosuppressant frequently used in the therapy of autoimmune disorders, including skin-related diseases. Aiming towards topical delivery, CsA was successfully incorporated into lipid nanoparticles of Lipocire DM and Pluronic F-127 using the hot homogenization method. Two different nanocarriers were optimized: solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) where oleic acid was the liquid lipid. The developed nanoparticles showed mean sizes around 200 nm, a negative surface charge, and drug entrapment efficiencies around 85% and 70% for SLNs and NLCs, respectively. The spherical CsA-loaded lipid nanoparticles were stable for 9 weeks when stored at room temperature, and exhibited in vitro pH-dependent release under skin mimetic conditions, following the Peppas−Korsmeyer model. CsA, when loaded in SLNs, was safe to be used up to 140 μg mL−1 in fibroblasts and keratinocytes, while CsA-loaded NLCs and free drug exhibited IC50 values of 55 and 95 μg mL−1 (fibroblasts) and 28 and 30 μg mL−1 (keratinocytes), respectively. The developed SLNs were able to retain the drug in pork skin with a reduced permeation rate in relation to NLCs. These findings suggest that SLNs are a potential alternative to produce stable and safe CsA nanocarriers for topical administration.

PURPOSE: To evaluate if the ileum resection changes the functioning liver cell mass, the hepatic metabolism and the biodistribution of radiopharmaceutical in rats. METHODS: Twelve Wistar rats weighing 285g±34g were randomly divided into the ileum resection group (n = 6) and sham group rats (n = 6). After 30 days, they were anesthetized and 0.1mL of 99m-Tc-phytate (0.66MBq) was injected via femoral vein. After 30 minutes, blood samples were collected for red blood cells radioactive labeling and serum ALT, AST and gammaGT. Liver samples were used for 99m-Tc-phytate percentage of radioactivity/gram of tissue and histopathology. Student 's t test was used with significance 0.05. RESULTS: There was a higher uptake of 99m-Tc-phytate in the liver of sham rats, compared to the ileum resection group (p

(1) Background: Membrane lipids have been disregarded in drug development throughout the years. Recently, they gained attention in drug design as targets, but they are still disregarded in the latter stages. Thus, this study aims to highlight the relevance of considering membrane lipids in the preclinical phase of drug development. (2) Methods: The interactions of a drug candidate for clinical use (licofelone) with a membrane model system made of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) were evaluated by combining Langmuir isotherms, Brewster angle microscopy (BAM), polarization-modulation infrared reflection-absorption spectroscopy (PM-IRRAS), and grazing-incidence X-ray diffraction (GIXD) measurements. (3) Results: Licofelone caused the expansion of the DPPC isotherm without changing the lipid phase transition profile. Moreover, licofelone induced the reduction of DPPC packing density, while increasing the local order of the DPPC acyl chains. (4) Conclusions: The licofelone-induced alterations in the structural organization of phosphatidylcholine monolayers may be related to its pharmacological actions. Thus, the combination of studying drug-membrane interactions with the pharmacological characterization that occurs in the preclinical stage may gather additional information about the mechanisms of action and toxicity of drug candidates. Ultimately, the addition of this innovative step shall improve the success rate of drug development.

The use of many traditional medicinal plants is often hampered by the absence of a proper biochemical characterization, essential to identify the bioactive compounds present. The leaves from five species endemic to the Macaronesian islands with recognized ethnobotanical applications were analysed: Apollonias barbujana (Cav.) Bornm., Ocotea foetens (Ainton) Baill, Prunus azorica (Mouill.) Rivas-Mart., Lousã, Fern. Prieto, E. Días, J.C. Costa & C. Aguiar, Rumex maderensis Lowe and Plantago arborescens Poir. subsp. maderensis (Dcne.) A. Hans. et Kunk.. Since oxidative stress is a common feature of most diseases traditionally treated by these plants, it is important to assess their antioxidant capacity and determine the molecules responsible for this capacity. In this study, the antioxidant capacity of these plants against two of the most important reactive species in human body (hydroxyl and peroxyl radicals) was determined. To trace the antioxidant origin total phenol and flavonoid contents as well as the polyphenolic profile and the amount of trace elements were determined. There was a wide variation among the species analysed in what concerns their total leaf phenol and flavonoid contents. From the High Performance Liquid Chromatography (HPLC) electrochemically detected peaks it was possible to attribute to flavonoids the antioxidant capacity detected in A. barbujana, O. foetens, R. maderensis and P. azorica extracts. These potential reactive flavonoids were identified for A. barbujana, R. maderensis and P. azorica. For R. maderensis a high content (7 mg g-1 dry weight) of L-ascorbic acid, an already described antioxidant phytomolecule, was found. A high content in selenomethionine (414.35 μg g-1 dry weight) was obtained for P. arborescens subsp. maderensis extract. This selenocompound is already described as a hydroxyl radical scavenger is reported in this work as also possessing peroxyl radical scavenging capacity. This work is a good illustration of different phytomolecules (flavonoids, organic acids and selenocompounds), presents in leaves of the five traditional medicinal plants endemic to Macaronesia, all exhibiting antioxidant properties.

Previous cytochrome B (CytB) mtDNA studies have suggested four species for the opossum genus Philander (four-eyed opossums), three (P. mcilhennyi, P. andersoni and P. opossum) from the Amazon and one (P. frenata) from the Brazilian Atlantic forest. During a faunal survey nine specimens of Philander sp. and four of Didelphis marsupialis were collected in the Mamirauá Sustainable Reserve, Amazonas State, Brazil. Preliminary analyses based on morphology and geographical distributions were not conclusive, suggesting that Philander specimens could belong to either P. andersoni or P. opossum. In order to elucidate the relationship of this taxon to the remaining Amazonian taxa, seven Philander and two Didelphis specimens animals were sequenced for the cytB mtDNA gene and compared to other previously studied taxa. The maximum likelihood (ML), neighbor-Joining (NJ) and maximum parsimony (MP) consensus bootstrap trees depicted six groups: Didelphis., P. frenata, P andersoni, P. mcilhennyi, P.o. opossum and Philander sp. and Philander canus in a common assemblage supported by significant bootstrap values, suggesting that the Philander sp. from Mamiraua in fact belongs to the species Philander canus.

The aggregation of amyloid-β peptide (Aβ) has been linked to the formation of neuritic plaques, which are pathological hallmarks of Alzheimer’s disease (AD). Various natural compounds have been suggested as therapeutics for AD. Among these compounds, resveratrol has aroused great interest due to its neuroprotective characteristics. Here, we provide evidence that grape skin and grape seed extracts increase the inhibition effect on Aβ aggregation. However, after intravenous injection, resveratrol is rapidly metabolized into both glucuronic acid and sulfate conjugations of the phenolic groups in the liver and intestinal epithelial cells (within less than 2 h), which are then eliminated. In the present study, we show that solid lipid nanoparticles (SLNs) functionalized with an antibody, the anti-transferrin receptor monoclonal antibody (OX26 mAb), can work as a possible carrier to transport the extract to target the brain. Experiments on human brain-like endothelial cells show that the cellular uptake of the OX26 SLNs is substantially more efficient than that of normal SLNs and SLNs functionalized with an unspecific antibody. As a consequence, the transcytosis ability of these different SLNs is higher when functionalized with OX-26.

ScopeDiets rich in (poly)phenols have been associated with positive effects on neurodegenerative disorders, such as Parkinson's disease (PD). Several low-molecular weight (poly)phenol metabolites (LMWPM) are found in the plasma after consumption of (poly)phenol-rich food. It is expected that LMWPM, upon reaching the brain, may have beneficial effects against both oxidative stress and neuroinflammation, and possibly attenuate cell death mechanisms relate to the loss of dopaminergic neurons in PD.Methods and resultsThis study investigates the neuroprotective potential of two blood-brain barrier permeant LMWPM, catechol-O-sulfate (cat-sulf), and pyrogallol-O-sulfate (pyr-sulf), in a human 3D cell model of PD. Neurospheroids were generated from LUHMES neuronal precursor cells and challenged by 1-methyl-4-phenylpyridinium (MPP+ ) to induce neuronal stress. LMWPM pretreatments were differently neuroprotective towards MPP+ insult, presenting distinct effects on the neuronal transcriptome. Particularly, cat-sulf pretreatment appeared to boost counter-regulatory defense mechanisms (preconditioning). When MPP+ is applied, both LMWPM positively modulated glutathione metabolism and heat-shock response, as also favorably shifting the balance of pro/anti-apoptotic proteins.ConclusionsOur findings point to the potential of LMWPM to trigger molecular mechanisms that help dopaminergic neurons to cope with a subsequent toxic insult. They are promising molecules to be further explored in the context of preventing and attenuating parkinsonian neurodegeneration.

Este artigo tem como objectivo avaliar as dimensões da vinculação na população dependente de substâncias (DS), bem como as variáveis associadas a este construto, particularmente as memórias de infância associadas à relação com os pais e os mecanismos de defesa. Numa primeira fase é feita a comparação entre um grupo de DS (n=65) e um grupo de sujeitos da população geral (n=65) emparelhados ao nível do género, idade e escolaridade. As diferenças entre grupos mostraram-se significativas ao nível da vinculação, memórias de infância e mecanismos de defesa específicos, como a clivagem e a supressão. Numa segunda fase, estuda-se a relação entre estas variáveis no grupo DS, tendo os resultados mostrado que a memória da rejeição da mãe e a clivagem têm um efeito preditor ao nível das dimensões da vinculação estudadas, sendo a clivagem o estimador mais consistente destas dimensões.

ABSTRACT Objective: to evaluate whether colectomy, associated with 70% hepatectomy, influences liver regeneration in rats. Methods: we distributed 18 Wistar rats in three groups of six animals each. In group I (sham), we performed laparotomy; In group II, colectomy + 70% hepatectomy; In group III, only 70% hepatectomy. On the 6th postoperative day, we collected blood by cardiac puncture under anesthesia, followed by euthanasia. We performed serum dosages of aspartate aminotransferase (AST), alanine aminotransferase (ALT), albumin and alkaline phosphatase (AF), hepatocyte growth factor (HGF) and transforming growth factor-α (TGF-α). We calculated liver regeneration by the formula: liver weight ratio per 100g body weight at the time of euthanasia / liver weight preoperatively projected for 100g body weight × 100. Results: ALT and AST levels were significantly lower in group II when compared with group III (p

Lipopolysaccharide (LPS) challenge in mice has been used to identify the mechanisms and therapeutics for neuroinflammation. In this study, we aimed to comprehensively evaluate the behavioral changes including locomotion, exploration, and memory, correlating them with a panel of thirteen inflammatory cytokines in both blood and brain. We found that acute LPS administration (0.83 mg/Kg i.p.) reduced body weight, food intake, and glucose levels compared to the saline-injected mice, concomitant with decreased activity in home cage monitoring. Locomotion was significantly reduced in Open Field, Introduced Object, and Y-Maze tests. Decreased exploratory behavior in the Y-Maze and Introduced Object tests was noticed, by measuring the number of arms explored and object interaction time, respectively. Additionally, in rotarod, LPS administration led to a significant decrease in the distance achieved, while in the MouseWalker, LPS led to a reduction in average velocity. LPS induced a decrease in microglia ramification index in the motor cortex and the striatum, while surprisingly a reduction in microglia number was observed in the motor cortex. The concentrations of thirteen cytokines in the blood were significantly altered, while only CXCL1, CCL22, CCL17, G-CSF, and IL-12p40 were changed in the brain. Correlations between cytokine levels in blood and brain were found, most notably for CCL17 and CCL22. TGFβ was the only one with negative correlations to other cytokines. Correlations between cytokines and behavior changes were also disclosed, especially for CCL17, CCL22, G-CSF, and IL-6 and negatively for TGFβ and IL-10. In summary, our study employing acute LPS challenge in mice has revealed a comprehensive profile of behavioral alterations alongside significant changes in inflammatory cytokine levels, both in peripheral blood and brain tissue. These findings contribute to a deeper understanding of the interplay between inflammation and behavior, with possible implications for identifying prognostics and therapeutic targets for neuroinflammatory conditions. [ABSTRACT FROM AUTHOR]