Oligonucleotide probes for imaging and diagnosis of bacterial infections.

The rise of infectious diseases as a public health concern has necessitated the development of rapid and precise diagnostic methods. Imaging techniques like nuclear and optical imaging provide the ability to diagnose infectious diseases within the body, eliminating delays caused by sampling and pre-enrichments of clinical samples and offering spatial information that can aid in a more informed diagnosis. Traditional molecular probes are typically created to image infected tissue without accurately identifying the pathogen. In contrast, oligonucleotides can be tailored to target specific RNA sequences, allowing for the identification of pathogens, and even generating antibiotic susceptibility profiles by focusing on drug resistance genes. Despite the benefits that nucleic acid mimics (NAMs) have provided in terms of stabilizing oligonucleotides, the inadequate delivery of these relatively large molecules into the cytoplasm of bacteria remains a challenge for widespread use of this technology. This review summarizes the key advancements in the field of oligonucleotide probes for in vivo imaging, highlighting the most promising delivery systems described in the literature for developing optical imaging through in vivo hybridization.

Influence of in vitro neuronal membranes on the anti-amyloidogenic activity of gallic acid: Implication for the therapy of Alzheimer's disease.

Molecules inhibiting the amyloid beta (Aß) peptide aggregation and/or disaggregating mature fibrils are a promising approach for the Alzheimer's disease (AD) therapy, as the Aß fibrillation is one of the key triggers of the disease. Gallic acid (GA) is a phenolic acid with anti-amyloidogenic activity against Aß in buffered solutions. However, there is still no evidence of these properties in vivo. Given the rate of failures of AD drug development, there is a huge demand of replicating the in vivo environment in in vitro studies, thus allowing to stop earlier the study of molecules with no effect in vivo. Thus, this study aims to evaluate the effect of in vitro neuronal membranes on the GA's ability in preventing Aß1-42 aggregation and disrupting preformed fibrils. To this end, liposomes were employed to mimic the cell membrane environment. The results reveal that the lipid membranes did not affect the GA's ability in inhibiting Aß1-42 fibrillation. However, in vitro neuronal membranes modulate the GA-induced Aß fibrils disaggregation, which may be related with the moderate affinity of the compound for the lipid membrane. Even so, GA presented strong anti-amyloidogenic properties in the cell membrane-like environment. This work highlights the promising value of GA on preventing and treating AD, thus justifying its study in animal models.

Natural Compounds for Alzheimer's Disease Therapy: A Systematic Review of Preclinical and Clinical Studies.

Alzheimer's Disease (AD) is a neurodegenerative disorder related with the increase of age and it is the main cause of dementia in the world. AD affects cognitive functions, such as memory, with an intensity that leads to several functional losses. The continuous increase of AD incidence demands for an urgent development of effective therapeutic strategies. Despite the extensive research on this disease, only a few drugs able to delay the progression of the disease are currently available. In the last years, several compounds with pharmacological activities isolated from plants, animals and microorganisms, revealed to have beneficial effects for the treatment of AD, targeting different pathological mechanisms. Thus, a wide range of natural compounds may play a relevant role in the prevention of AD and have proven to be efficient in different preclinical and clinical studies. This work aims to review the natural compounds that until this date were described as having significant benefits for this neurological disease, focusing on studies that present clinical trials.

Indoor air quality in preschools (3- to 5-year-old children) in the Northeast of Portugal during spring-summer season: pollutants and comfort parameters.

Indoor air quality at schools (elementary, primary) has been the subject of many studies; however, there are still relative few data regarding preschool (3- to 5-year-old children) environments. This investigation determined the concentrations of particulate matter (PM)2.5, total volatile organic compounds (TVOC), formaldehyde, carbon monoxide (CO), and ozone (O3) as well as the levels of carbon dioxide (CO2), temperature, and relative humidity (RH) in the indoor and outdoor air of two preschools situated in different geographical regions of Portugal. The indoor concentrations of TVOC, CO, O3, and CO2 were predominantly higher at the end of school day compared to early morning periods. The TVOC and CO2 concentrations were higher indoors than outdoors suggesting predominantly an indoor origin. Outdoor air infiltrations were the major contributing source of CO and O3 to indoor air in both preschools. The concentrations of all pollutants were within the limits defined by national regulations and international organizations, except for TVOC that exceeded 8-12-fold higher than the recommendation of 0.2 mg/m3 proposed by European Commission. The levels of CO2 were below the protective guideline of 2250 mg/m3 (Portuguese legislation); however, the observed ranges exceeded the Portuguese margin of tolerance (2925 mg/m3) at the end of school days, indicating the impact of occupancy rates particularly at one of the preschools. Regarding comfort parameters, temperature exerted a significant influence on O3 concentrations, while RH values were significantly correlated with TVOC levels in indoor air of preschools, particularly during the late afternoon periods.

Polycyclic aromatic hydrocarbons (PAH) in Portuguese educational settings: a comparison between preschools and elementary schools.

The aim of this study was to determine levels and risks due to inhalation exposure to polycyclic aromatic hydrocarbons (PAH) in different educational settings, namely for 3- to 5- year-old and 6- to 10-year-old children. Eighteen PAH (16 priority designated by US Environmental Protection Agency (USEPA) and dibenzo[a,l]pyrene and benzo[j]fluoranthene) were simultaneously collected in indoor and outdoor air at two Portuguese preschools (PS1-PS2) and five elementary schools (ES1-ES5) from March to May 2014. Indoor concentrations at PS and ES were significantly different, with total levels (∑PAHs) 0.721-15.9 ng/m3 at PS1-PS2 and 5.03-23.6 ng/m3 at ES1-ES5. The corresponding outdoor concentrations were, respectively, 1.22-32.7 ng/m3 and 2.6-31.5 ng/m3. Polycyclic aromatic hydrocarbons with 2-3 aromatic rings were predominantly emitted by indoor sources, while compounds with 4-6 aromatic rings were mainly generated by infiltration of ambient PAH pollution to indoors. Excess lifetime risks of lung cancer exceeded the World Health Organization (WHO) designated guideline of 10-5 in both types of schools (15-42-fold at PS; 15-52-fold at ES). However, total (sum of indoor and outdoor exposure) incremental lifetime cancer risks (ILCR) were below the USEPA level of 10-6 at all studied institutions and thus considered negligible. Finally, ILCR due to indoor exposure represented 60-75% and 70-85% of the total ILCR at PS and ES, respectively, thus indicating the need for development and implementation of indoor air quality guidelines in educations settings.

Children's Indoor Exposures to (Ultra)Fine Particles in an Urban Area: Comparison Between School and Home Environments.

Due to their detrimental effects on human health, scientific interest in ultrafine particles (UFP), has been increasing but available information is far from comprehensive. Children, who represent one of the most susceptible subpopulation, spend the majority of time in schools and homes. Thus, the aim of this study is to (1) assess indoor levels of particle number concentrations (PNC) in ultrafine and fine (20-1000 nm) range at school and home environments and (2) compare indoor respective dose rates for 3- to 5-yr-old children. Indoor particle number concentrations in range of 20-1000 nm were consecutively measured during 56 d at two preschools (S1 and S2) and three homes (H1-H3) situated in Porto, Portugal. At both preschools different indoor microenvironments, such as classrooms and canteens, were evaluated. The results showed that total mean indoor PNC as determined for all indoor microenvironments were significantly higher at S1 than S2. At homes, indoor levels of PNC with means ranging between 1.09 × 10(4) and 1.24 × 10(4) particles/cm(3) were 10-70% lower than total indoor means of preschools (1.32 × 10(4) to 1.84 × 10(4) particles/cm(3)). Nevertheless, estimated dose rates of particles were 1.3- to 2.1-fold higher at homes than preschools, mainly due to longer period of time spent at home. Daily activity patterns of 3- to 5-yr-old children significantly influenced overall dose rates of particles. Therefore, future studies focusing on health effects of airborne pollutants always need to account for children's exposures in different microenvironments such as homes, schools, and transportation modes in order to obtain an accurate representation of children overall exposure.

Exposure of Children to Ultrafine Particles in Primary Schools in Portugal.

Children spend a large part of their time at schools, which might be reflected as chronic exposure. Ultrafine particles (UFP) are generally associated with a more severe toxicity compared to fine and coarse particles, due to their ability to penetrate cell membranes. In addition, children tend to be more susceptible to UFP-mediated toxicity compared to adults, due to various factors including undeveloped immune and respiratory systems and inhalation rates. Thus, the purpose of this study was to determine indoor UFP number concentrations in Portuguese primary schools. Ultrafine particles were sampled between January and March 2014 in 10 public primary schools (35 classrooms) located in Porto, Portugal. Overall, the average indoor UFP number concentrations were not significantly different from outdoor concentrations (8.69 × 10(3) vs. 9.25 × 10(3) pt/cm(3), respectively; considering 6.5 h of indoor occupancy). Classrooms with distinct characteristics showed different trends of indoor UFP concentrations. The levels of carbon dioxide were negatively correlated with indoor UFP concentrations. Occupational density was significantly and positively correlated with UFP concentrations. Although the obtained results need to be interpreted with caution since there are no guidelines for UFP levels, special attention needs to be given to source control strategies in order to reduce major particle emissions and ensure good indoor air quality.

Assessment of Portuguese fitness centers: Bridging the knowledge gap on harmful microbial contamination with focus on fungi.

The lack of knowledge regarding the extent of microbial contamination in Portuguese fitness centers (FC) puts attendees and athletes at risk for bioaerosol exposure. This study intends to characterize microbial contamination in Portuguese FC by passive sampling methods: electrostatic dust collectors (EDC) (N = 39), settled dust (N = 8), vacuum filters (N = 8), and used cleaning mops (N = 12). The obtained extracts were plated in selective culture media for fungi and bacteria. Filters, EDC, and mop samples' extracts were also screened for antifungal resistance and used for the molecular detection of the selected Aspergillus sections. The detection of mycotoxins was conducted using a high-performance liquid chromatograph (HPLC) system and to determine the cytotoxicity of microbial contaminants recovered by passive sampling, HepG2 (human liver carcinoma) and A549 (human alveolar epithelial) cells were employed. The results reinforce the use of passive sampling methods to identify the most critical areas and identify environmental factors that influence microbial contamination, namely having a swimming pool. The cardio fitness area presented the highest median value of total bacteria (TSA: 9.69 × 102 CFU m-2.day-1) and Gram-negative bacteria (VRBA: 1.23 CFU m-2.day-1), while for fungi it was the open space area, with 1.86 × 101 CFU m-2.day-1. Aspergillus sp. was present in EDC and in filters used to collect settled dust. Reduced azole susceptibility was observed in filters and EDC (on ICZ and VCZ), and in mops (on ICZ). Fumonisin B2 was the only mycotoxin detected and it was present in all sampling matrixes except settled dust. High and moderate cytotoxicity was obtained, suggesting that A549 cells were more sensitive to samples' contaminants. The observed widespread of critical toxigenic fungal species with clinical relevance, such as Aspergillus section Fumigati, as well as Fumonisin B2 emphasizes the importance of frequent and effective cleaning procedures while using shared mops appeared as a vehicle of cross-contamination.

Langmuir monolayers of monocationic lipid mixed with cholesterol or fluorocholesterol: DNA adsorption studies.

Monolayers of the cationic lipid DOTAP (1,2-dioleoyl-3-trimethylammonium-propane) and cholesterol or heptafluorocholesterol were prepared, and their interaction with DNA was characterized. The mixture of DOTAP with each of the sterols at 1:1 molar ratios leads to monolayers in a liquid expanded state, similarly to that of DOTAP alone. The area per molecule of the mixtures was smaller than that expected according to the additivity rule applicable if the two components are either completely miscible or immiscible within the monolayer. The observed negative deviation from the additivity indicates the existence of additional attractive interactions between the components. The surface potential of DOTAP monolayer is positive (+560 mV). It decreases only slightly after the addition of cholesterol (+540 mV) but drastically after the addition of heptafluorocholesterol (+20 mV) in the 1:1 mixtures at a surface pressure of 35 mN/m. This difference is attributed to the negative dipole moment of the fluorinated component. The adsorption of DNA is similar for both systems, which supports the possibility of using fluorinated cholesterol as helper lipid in DNA transfection vectors.

Charged surfactants induce a non-fibrillar aggregation pathway of amyloid-beta peptide.

The amyloid ß-peptide with a sequence of 42 amino acids is the major constituent of extracellular amyloid deposits in Alzheimer's disease plaques. The control of the peptide self-assembly is difficult to achieve because the process is fast and is affected by many variables. In this paper, we describe the effect of different charged and non-charged surfactants on Aß(1₋42) fibrillation to define common alternate aggregation pathways. The characterization of the peptide-surfactant interactions by ultra-structural analysis, thioflavin T assay and secondary structure analysis, suggested that charged surfactants interact with Aß(1₋42) through electrostatic interactions. Charged micelles slow down the aggregation process and stabilize the peptide in the oligomeric state, whereas non-charged surfactants promote the Aß(1₋42) fibril formation.

Chitosan conjugates for DNA delivery.

Graft copolymers of chitosan and maltodextrin were synthesized by reductive amination of a low molecular weight chitosan. The degree of substitution is 70% or above, as quantified by nuclear magnetic resonance spectroscopy, at molar ratios of chitosan glucosamine units and maltodextrin of 1 : 1 and 1 : 5. The high substitution degree generates a water-soluble compound at pH 7.4 by reducing the amino groups of chitosan. In addition, the copolymer self-assembles into spherical nanoparticles with diameters of about 300 nm. The mass polymer/DNA ratios at the isoelectric point are within the range of 3-3.5 for chitosan-maltodextrin nanoparticles as determined by electrophoretic mobility measurements. These results confirm that DNA interacts efficiently with the copolymer nanoparticles indicating a potential application of the system for DNA delivery.

Assessment of indoor air quality in health clubs: insights into (ultra)fine and coarse particles and gaseous pollutants.

Introduction: Exercising on regular basis provides countless health benefits. To ensure the health, well-being and performance of athletes, optimal indoor air quality, regular maintenance and ventilation in sport facilities are essential. Methods: This study assessed the levels of particulate, down to the ultrafine range (PM10, PM2.5, and particle number concentration in size range of 20-1,000 nm, i.e., - PNC20-1000 nm), gaseous pollutants (total volatile organic compounds - TVOCs, CO2, and O3) and comfort parameters (temperature - T, relative humidity - RH) in different functional spaces of health clubs (n = 8), under specific occupancy and ventilation restrictions. Results and Discussion: In all HCs human occupancy resulted in elevated particles (up to 2-3 times than those previously reported), considering mass concentrations (PM10: 1.9-988.5 µg/m3 PM2.5: 1.6-479.3 µg/m3) and number (PNC 1.23 × 103 - 9.14 × 104 #/cm3). Coarse and fine PM indicated a common origin (rs = 0.888-0.909), while PNC showed low-moderate associations with particle mass (rs = 0.264-0.629). In addition, up to twice-higher PM and PNC were detected in cardiofitness & bodybuilding (C&B) areas as these spaces were the most frequented, reinforcing the impacts of occupational activities. In all HCs, TVOCs (0.01-39.67 mg/m3) highly exceeded the existent protection thresholds (1.6-8.9 times) due to the frequent use of cleaning products and disinfectants (2-28 times higher than in previous works). On contrary to PM and PNC, TVOCs were higher (1.1-4.2 times) in studios than in C&B areas, due to the limited ventilations combined with the smaller room areas/volumes. The occupancy restrictions also led to reduced CO2 (122-6,914 mg/m3) than previously observed, with the lowest values in HCs with natural airing. Finally, the specific recommendations for RH and T in sport facilities were largely unmet thus emphasizing the need of proper ventilation procedures in these spaces.

Nanostructured label-free electrochemical immunosensor for detection of a Parkinson's disease biomarker.

Aggregation of α-synuclein has been recognized as a critical event in the pathogenesis of Parkinson's disease whose prevalence is increasing with great socio-economic challenges for future generations. Here, we developed a sensitive and specific electrochemical immunosensor for the detection and quantification of this biomarker, based on the voltammetric study of a redox indicator signal, which decreases upon the analyte recognition by the antibody due to the electronic resistance increase. The proposed immunosensor is based on a screen-printed carbon electrode modified in a layer-by-layer approach, which through extensive characterization led to the successful nanostructuration of the transducer, through the drop-cast of 3.0 µL of a 0.1 mg mL-1 single-walled carbon nanotubes suspension followed by electrodeposition of gold nanoparticles in a 3 mM HAuCl4 solution under a -0.2 V potential for 150 s. Monoclonal antibodies were immobilized on the gold nanoparticles surface through chemical modification at an optimal concentration of 200 µg mL-1. Using the proposed immunosensor, α-synuclein was detected in the range of 0.01-10 ng mL-1 with a 4.1 and 12.6 pg mL-1 limits of detection and quantification, respectively. Recovery values of 96.7, 106.2 and 102.9% were attained for the tested concentrations spiked in fetal bovine serum while also presenting excellent specificity and stability throughout one month. The nanostructured immunosensor provided a great interface for electronic transduction and biological recognition events, which enabled fast, sensitive and specific detection of α-synuclein while being based on a simple and inexpensive technology requiring small sample volumes, crucial characteristics for application in point-of-care testing.

Peptide-surfactant interactions: consequences for the amyloid-beta structure.

The conformation of amyloid-beta peptide (Aß) determines if toxic aggregates are formed. The peptide structure by its turn depends on the environment and molecule-molecule interactions. We characterized the secondary structure of Aß-(1-40) in surfactant solutions and interacting with monolayers. The peptide adopts ß-sheet structure in solutions of ionic surfactants at sub-micelle concentrations and α-helix in the presence of ionic micelles. Uncharged micelles induce ß-sheets. Aß-(1-40) alters the critical micelle concentration value of the non-ionic surfactant, underlining hydrophobic interactions. At ionic monolayers the peptide forms ß-sheets when its concentration at the surface is high enough. These results suggest that only electrostatic interactions of charged micelles that surround completely the peptide are able to induce non-aggregated α-helix structure.

Elemental characterization of indoor breathable particles at a Portuguese urban hospital.

Hospitals are a specific indoor environment with highly susceptible individuals for whom indoor air pollution represents additional health risks. Particulate matter (PM) is one of the most health-relevant indoor pollutants due to its association with respiratory and cardiovascular diseases. Particles can also act as a carrier for various harmful organisms present in the air of hospitals, thus leading to airborne transmission of infectious diseases. Thus, the objective of this study was to characterize indoor PM collected in a hospital in consideration of concentration, size distribution, and elemental composition. Emission sources of indoor PM were indentified and risks associated with indoor PM estimated. Sampling was performed at radiology ward of a Portuguese urban hospital where PM10, PM(2.5), and PM1 were collected during a period of 4 wk; PM elemental composition was determined by proton-induced x-ray emission (PIXE) analysis. Data showed that indoor PM10 concentrations ranged from 13 to 58.8 µg/m³ and from 10.5 to 41.9 µg/m³ for PM(2.5). Fine particles constituted 77% of PM10, indicating that PM(2.5) made a significant contribution to indoor air quality at the hospital. PM1 ranged from 9.9 to 35.6 µg/m³, accounting for 93% of PM(2.5). PIXE identified 21 elements in PM, including health-hazardous metals (manganese, iron, copper, and vanadium) and carcinogenic elements (nickel, chromium, arsenic, and lead). However, no significant indoor source of PM emissions was identified, while outdoor air was the major contributor of indoor particles. Further, no significant risks existed through PM10 inhalation for population at the respective hospital.

Nanocarriers Based on Gold Nanoparticles for Epigallocatechin Gallate Delivery in Cancer Cells.

Gold nanoparticles (AuNPs) are inorganic and biocompatible nanovehicles capable of conjugating biomolecules to enhance their efficacy in cancer treatment. The high and reactive surface area provides good advantages for conjugating active compounds. Two approaches were developed in this work to improve the Epigallocatechin-3-gallate (EGCG) antioxidant efficacy. AuNPs were synthesized by reducing gold salt with chitosan. One other nanosystem was developed by functionalizing AuNPs with cysteamine using the Turkevitch method. The physico-chemical characterization of EGCG conjugated in the two nanosystems-based gold nanoparticles was achieved. The in vitro toxic effect induced by the nanoconjugates was evaluated in pancreatic cancer cells, showing that encapsulated EGCG keeps its antioxidant activity and decreasing the BxPC3 cell growth. A significant cell growth inhibition was observed in 50% with EGCG concentrations in the range of 2.2 and 3.7 µM in EGCG-ChAuNPs and EGCG-Cyst-AuNPs nanoconjugates, respectively. The EGCG alone had to be present at 23 µM to induce the same cytotoxicity response. Caspase-3 activity assay demonstrated that the conjugation of EGCG induces an enhancement of BxPC3 apoptosis compared with EGCG alone. In conclusion, AuNPs complexes can be used as delivery carriers to increase EGCG antioxidant activity in cancer tissues.

Assessment of ultrafine particles in primary schools: Emphasis on different indoor microenvironments.

Due to the negative health impacts, significant efforts have been directed towards investigating ultrafine particle (UFP) exposure in various indoor environments. As children spend approximately one third of their time in schools, educatory environments deserve particular attention; however, majority of past research has focused on UFP assessment in classrooms. Thus, this work aims to expand the characterization of UFP in primary schools by considering different indoor and outdoor school microenvironments and estimating inhalation doses for the respective students (6-11yrs old). Real-time UFP measurements were daily conducted (9:00-17:30) in 20 primary schools in Oporto (January-April 2014; October-February 2015) in classrooms, canteens, gyms, libraries, and concurrently outdoors. Overall, UFP concentrations showed large temporal and spatial variations. For classrooms (n = 73), median UFP (1.56 × 103-16.8 × 103 # cm-3) were lower than the corresponding levels in ambient air of schools (1.79 × 103-24.1 × 103 # cm-3). Outdoor emissions contributed to indoor UFP (indoor-to-outdoor ratios I/O of 0.0.30-0.85), but ventilation, room characteristics and its occupancy were identified as important parameters contributing to overall indoor UFP levels. Considering specific indoor school microenvironments, canteens were the microenvironment with the highest UFP levels (5.47 × 103-36.4 × 103 # cm-3), cooking conducted directly on school grounds resulted in significantly elevated UFP in the respective classrooms (p < 0.05); the lowest UFP were found in libraries (4.45 × 103-8.50 × 103 # cm-3) mostly due to the limited occupancies. Although students spend majority of their school time in classrooms (66-71%), classroom exposure was not consistently the predominant contributor to school total UFP inhalation dose (29-75%). Outdoor exposure contributed 23-70% of school dose (depending on UFP levels in ambient levels and/or conducted activities) whereas short periods of lunch break accounted for 8-40%. Therefore, when evaluating UFP exposure in educatory settings other microenvironments beyond classrooms should be an integral part of the study.

Influence of fluorinated and hydrogenated nanoparticles on the structure and fibrillogenesis of amyloid beta-peptide.

Peptide aggregation in amyloid fibrils is implicated in the pathogenesis of several diseases such as Alzheimer's disease. There is a strong correlation between amyloid fibril formation and a decrease in conformational stability of the native state. Amyloid-beta peptide (Abeta), the aggregating peptide in Alzheimer's disease, is natively unfolded. The deposits found in Alzheimer's disease are composed of Abeta fibrillar aggregates rich in beta-sheet structure. The influence of fluorinated complexes on the secondary structure and fibrillogenesis of Abeta peptide was studied by circular dichroism (CD) spectroscopy and transmission electron microscopy (TEM). CD spectra show that complexes of polyampholyte and fluorinated dodecanoic acid induce alpha-helix structure in Abeta, but their hydrogenated analogous lead to beta-sheet formation and aggregation. The fluorinated nanoparticles with highly negative zeta potential and hydrophobic fluorinated core have the fundamental characteristics to prevent Abeta fibrillogenesis.

Indoor air quality in health clubs: Impact of occupancy and type of performed activities on exposure levels.

Associations between indoor air quality (IAQ) and health in sport practise environments are not well understood due to limited knowledge of magnitude of inhaled pollutants. Thus, this study assessed IAQ in four health clubs (HC1-HC4) and estimated inhaled doses during different types of activities. Gaseous (TVOCs, CO, O3, CO2) and particulate pollutants (PM1, PM4) were continuously collected during 40 days. IAQ was influenced both by human occupancy and the intensity of the performed exercises. Levels of all pollutants were higher when clubs were occupied (p < 0.05) than for vacant periods, with higher medians in main workout areas rather than in spaces/studios for group activities. In all spaces, TVOCs highly exceeded legislative limit (600 µg/m3), even when unoccupied, indicating possible risks for the respective occupants. CO2 levels were well correlated with relative humidity (rs 0.534-0.625) and occupancy due to human exhalation and perspiration during exercising. Clubs with natural ventilations exhibited twice higher PM, with PM1 accounting for 93-96% of PM4; both PM were highly correlated (rs 0.936-0.995) and originated from the same sources. Finally, cardio classes resulted in higher inhalation doses than other types of exercising (1.7-2.6).

Resveratrol Brain Delivery for Neurological Disorders Prevention and Treatment.

Resveratrol (RES) is a natural polyphenolic non-flavonoid compound present in grapes, mulberries, peanuts, rhubarb and in several other plants. Numerous health effects have been related with its intake, such as anti-carcinogenic, anti-inflammatory and brain protective effects. The neuroprotective effects of RES in neurological diseases, such as Alzheimer's (AD) and Parkinson's (PD) diseases, are related to the protection of neurons against oxidative damage and toxicity, and to the prevention of apoptotic neuronal death. In brain cancer, RES induces cell apoptotic death and inhibits angiogenesis and tumor invasion. Despite its great potential as therapeutic agent for the treatment of several diseases, RES exhibits some limitations. It has poor water solubility and it is chemically instable, being degraded by isomerization once exposed to high temperatures, pH changes, UV light, or certain types of enzymes. Thus, RES has low bioavailability, limiting its biological and pharmacological benefits. To overcome these limitations, RES can be delivered by nanocarriers. This field of nanomedicine studies how the drug administration, pharmacokinetics, and pharmacodynamics are affected by the use of nanosized materials. The role of nanotechnology, in the prevention and treatment of neurological diseases, arises from the necessity to mask the physicochemical properties of therapeutic drugs to prolong the half-life and to be able to cross the blood-brain barrier (BBB). This can be achieved by encapsulating the drug in a nanoparticle (NP), which can be made of different kinds of materials. An increasing trend to encapsulate and direct RES to the brain has been observed. RES has been encapsulated in many different types of nanosystems, as liposomes, lipid and polymeric NPs. Furthermore, some of these nanocarriers have been modified with targeting molecules able to recognize the brain areas. Then, this article aims to overview the RES benefits and limitations in the treatment of neurological diseases, as the different nanotechnology strategies to overcome these limitations.