Zika virus (ZIKV) infection has been associated with severe complications both in the developing and adult nervous system. To investigate the deleterious effects of ZIKV infection, we used human ...neural progenitor cells (NPC), derived from induced pluripotent stem cells (iPSC). We found that NPC are highly susceptible to ZIKV and the infection results in cell death. ZIKV infection led to a marked reduction in cell proliferation, ultrastructural alterations and induction of autophagy. Induction of apoptosis of Sox2
cells was demonstrated by activation of caspases 3/7, 8 and 9, and by ultrastructural and flow cytometry analyses. ZIKV-induced death of Sox2
cells was prevented by incubation with the pan-caspase inhibitor, Z-VAD-FMK. By confocal microscopy analysis we found an increased number of cells with supernumerary centrosomes. Live imaging showed a significant increase in mitosis abnormalities, including multipolar spindle, chromosome laggards, micronuclei and death of progeny after cell division. FISH analysis for chromosomes 12 and 17 showed increased frequency of aneuploidy, such as monosomy, trisomy and polyploidy. Our study reinforces the link between ZIKV and abnormalities in the developing human brain, including microcephaly.
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•Different methods were applied to recover bioactive compounds from umbu seeds.•Polar extracts showed higher phenolic contents and antioxidant activities.•High correlation found ...between antioxidant activity and polyphenolic content.•Antioxidant activities found were compared with those of butylated hydroxytoluene.•Integrated approach was an interesting procedure for biomass valorization.
The fruit of Spondias tuberosa (umbu) is widely consumed in the northeast region of Brazil. In this work, the potential of umbu seeds as source of bioactive compounds was evaluated. Different extraction techniques were compared in terms of yield, free-fatty acids composition, total phenolic content (TPC) and antioxidant activity (AA). The extraction techniques used were supercritical fluid extraction (SFE) with CO2, performed at 40 °C and pressures from 15 to 30 MPa, and Soxhlet and ultrasound-assisted extraction (UAE) with different solvents. The highest yields were obtained by UAE with ethanol/water mixtures and by Soxhlet with ethanol. The higher values for TPC and AA were observed for the extracts obtained with polar solvents. Furthermore, a biorefinery approach considering integrated processes (SFE + UAE) in order to recover polyphenols from the SFE residues has also been investigated and the results showed that combining processes may lead to a most effective valorization of agro-industrial residues.
This work reports the construction of an HIV-specific genosensor through the modification of carbon screen-printed electrodes (CSPE) with graphene quantum dots decorated with L-cysteine and gold ...nanoparticles (cys-GQDs/AuNps). Cys-GQDs were characterized by FT-IR and UV–vis spectra and electronic properties of the modified electrodes were evaluated by cyclic voltammetry and electrochemical impedance spectroscopy. The modification of the electrode surface with cys-GQDs and AuNps increased the electrochemical performance of the electrode, improving the electron transfer of the anionic redox probe Fe(CN)63−/4- on the electrochemical platform. When compared to the bare surface, the modified electrode showed a 1.7 times increase in effective electrode area and a 29 times decrease in charge transfer resistance. The genosensor response was performed by differential pulse voltammetry, monitoring the current response of the anionic redox probe, confirmed with real genomic RNA samples, making it possible to detect 1 fg/mL. In addition, the genosensor maintained its response for 60 days at room temperature. This new genosensor platform for early detection of HIV, based on the modification of the electrode surface with cys-GQDs and AuNps, discriminates between HIV-negative and positive samples, showing a low detection limit, as well as good specificity and stability, which are relevant properties for commercial application of biosensors.
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•Ultrasensitive electrochemical genosensor for HIV RNA detection was manufactured.•Figures of merit were used to characterize the electrochemical device performance.•Detection limit was 1 fg/mL and stability of 60 days.•Genosensor evaluated with plasma of HIV positive and HIV negative individuals.
Currently, there is a lack of efficient recurrence prediction methods for papillary thyroid carcinoma (PTC). In this study, we enrolled 202 PTC patients submitted to total thyroidectomy and ...radioiodine therapy with long-term follow-up (median = 10.7 years). The patients were classified as having favorable clinical outcome (PTC-FCO, no disease in the follow-up) or recurrence (PTC-RE). Alterations in
, and
were investigated (
= 202) and the transcriptome of 48 PTC (>10 years of follow-up) samples was profiled. Although no mutation was associated with the recurrence risk, 68 genes were found as differentially expressed in PTC-RE compared to PTC-FCO. Pathway analysis highlighted a potential role of cancer-related pathways, including signal transduction and FoxO signaling. Among the eight selected genes evaluated by RT-qPCR,
and
showed down-expression exclusively in the PTC-FCO group compared to non-neoplastic tissues (NT). Increased expression of
was an independent marker of shorter disease-free survival hazard ratio (HR) 2.9; 95% confidence interval (CI95) 1.2-7.0 in our cohort and with overall survival in the TCGA dataset (HR = 4.38, CI95 1.2-15.5). In conclusion,
transcript was identified as a novel prognostic marker candidate in PTC patients treated with total thyroidectomy and radioiodine therapy.
BACKGROUND The impact of OSA on new cardiovascular events in patients undergoing coronary artery bypass graft (CABG) surgery is poorly explored. METHODS Consecutive patients referred for CABG ...underwent clinical evaluation and standard polysomnography in the preoperative period. CABG surgery data, including percentage of off-pump and on-pump CABG, number of grafts, and intraoperative complications, were collected. The primary end point was major adverse cardiac or cerebrovascular events (MACCEs) (combined events of all-cause death, myocardial infarction, repeated revascularization, and cerebrovascular events). Secondary end points included individual MACCEs, typical angina, and arrhythmias. Patients were evaluated at 30 days (short-term) and up to 6.1 years (long term) after CABG. RESULTS We studied 67 patients (50 men; mean age, 58 ± 8 years; mean BMI, 28.5 ± 4.1 kg/m2 ). OSA (apnea-hypopnea index ≥ 15 events/h) was present in 56% of the population. The patients were followed for a mean of 4.5 years (range, 3.2-6.1 years). No differences were observed in the short-term follow-up. In contrast, MACCE (35% vs 16%, P = .02), new revascularization (19% vs 0%, P = .01), episodes of typical angina (30% vs 7%, P = .02), and atrial fibrillation (22% vs 0%, P = .0068) were more common in patients with than without OSA in the long-term follow-up. OSA was an independent factor associated with the occurrence of MACCE, repeated revascularization, typical angina, and atrial fibrillation in the multivariate analysis. CONCLUSIONS OSA is independently associated with a higher rate of long-term cardiovascular events after CABG and may have prognostic and economic significance in CABG surgery.
Pickering emulsions, emulsified systems stabilized by particles, have been comprehensively reported in the literature, mainly due to the advantages they have to conventional ones, such as the ...possibility of using natural particles, in addition to greater long-term stability, being a plausible choice for obtaining products. Zein is a protein derived from corn, being one of the few non-hydrophilic proteins approved by the Food and Drug Administration for oral use. Since 2012, this polymer, in its particulate form, has been reported as a possible stabilizing agent for Pickering emulsions, since some of its characteristics can be adjusted, making these particles present ideal properties for adsorption in droplets, leading to a stabilization steric of the formulations. These adjustments can be made from the processing and manufacturing stages, varying the preparation methodology, pH, protein concentration, and solvent type. However, the hybridization of these particles with other compounds (polysaccharides, proteins, surfactants, and polyphenols) proved to be effective in modulating the physicochemical characteristics, leading to more appropriate wettability, zeta potential, size, among others. In addition to providing the formation of emulsions in gels with improved stability. Therefore, it was demonstrated that zein particles and their complexes are configured as potential stabilizers of Pickering systems, especially when it comes to use in the pharmaceutical and food industries, as it was found that these particles stabilize formulations, contributing to the inhibition of processes of physicochemical instability, such as chemical degradation of the system, coalescence, Ostwald maturation, and lipid oxidation, leading to a possible increase in shelf life.
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•Zein particles are being studied for use as stabilizers in dispersed systems.•Manufacturing and other factors influence particle characteristics and performance as an emulsion stabilizer.•Complexation of zein with other compounds results in more stable particles.•Formulations with zein have applicability in the food and pharmaceutical industry.•Formulations with zein particles present physicochemical stability and delay the degradation of bioactive compounds.
Candida albicans is the leading cause of life-threatening bloodstream candidiasis, especially among immunocompromised patients. The reversible morphological transition from yeast to hyphal filaments ...in response to host environmental cues facilitates C. albicans tissue invasion, immune evasion, and dissemination. Hence, it is widely considered that filamentation represents one of the major virulence properties in C. albicans. We have previously characterized Ppg1, a PP2A-type protein phosphatase that controls filament extension and virulence in C. albicans. This study conducted RNA sequencing analysis of samples obtained from C. albicans wild type and ppg1Δ/Δ strains grown under filament-inducing conditions. Overall, ppg1Δ/Δ strain showed 1448 upregulated and 710 downregulated genes, representing approximately one-third of the entire annotated C. albicans genome. Transcriptomic analysis identified significant downregulation of well-characterized genes linked to filamentation and virulence, such as ALS3, HWP1, ECE1, and RBT1. Expression analysis showed that essential genes involved in C. albicans central carbon metabolisms, including GDH3, GPD1, GPD2, RHR2, INO1, AAH1, and MET14 were among the top upregulated genes. Subsequent metabolomics analysis of C. albicans ppg1Δ/Δ strain revealed a negative enrichment of metabolites with carboxylic acid substituents and a positive enrichment of metabolites with pyranose substituents. Altogether, Ppg1 in vitro analysis revealed a link between metabolites substituents and filament formation controlled by a phosphatase to regulate morphogenesis and virulence.
In this study was evaluated the influence of the extraction factors on the extract’s properties to improve the recovery of high concentrations of the phytochemicals important for the biological ...activities from pods of Libidibia ferrea (Mart. ex Tul.) L. P. Queiroz. The extracts were obtained by turbo-extraction and a factorial design 32 was used to study the importance of the drug amount (5, 10 or 15 g) and the solvent (Ethanol 40, 60 or 80%, v/v) on the variables of response, and the optimization was performed by Response Surface Methodology (RSM) and Desirability profile. Mathematical models were fitted according to experimental data and the validated equations were used to generate RSM for each dependent variable (dry residue; total polyphenol content; content of gallic acid and ellagic acid; and, efficiency of extraction). The factors studied within the applied experimental field presented different influence profiles for the responses, and significant interactions between linear and quadratic terms. The statistical analysis showed high R2 > 0.99. The RSM and Desirability (> 0.95) allowed to show that the optimum conditions to produce extractive solutions of Libidibia ferrea with high efficiency for ellagic acid and gallic acid were 15 g and ethanol 40%.
Due to global warming, in the northeastern semiarid coastal regions of Brazil, regional and global drivers are responsible for decreasing continental runoff and increasing estuarine water residence ...time, which promotes a greater mobilization of bioavailable mercury (Hg) and allows increasing fluxes and/or bioavailability of this toxic trace element and an acceleration of biogeochemical transformation of Hg. In this work, an application of dendrochemistry analysis (annular tree rings analysis) was developed for the reconstruction of the historical pattern of mercury contamination in a contaminated area, quantifying chronological Hg contamination trends in a tropical semiarid ecosystem (Ceará River Estuary, northeastern coast of Brazil) through registration of mercury concentration on growth rings in specimens of Rhizophora mangle L. and using the assessment in sediments as a support for the comparison of profiles of contamination. The comparison with sediments from the same place lends credibility to this type of analysis, as well as the relationship to the historical profile of contamination in the region, when compared with local data about industries and ecological situation of sampling sites. In order to evaluate the consequences of the described increase in Hg bioavailability and bioaccumulation in aquatic biota, and to assess the biological significance of Hg concentrations in sediments to fish and wildlife, muscle and liver from a bioindicator fish species, S. testudineus, were also analyzed. The results of this work reinforce the indicators previously described in the semiarid NE region of Brazil, which showed that global climate change and some anthropogenic factors are key drivers of Hg exposure and biomagnification for wildlife and humans. Considering the Hg concentration present in the top layers of sediment (~20 cm around 15 to 20 years) with the outer layers in the tree ring cores and in the sediment’s cores from Pacoti estuary and the Ceará estuary, overall the data indicate an increase in mercury in recent years in the Hg surface sediments, especially associated with the fine sediment fraction, mainly due to the increased capacity of small particles to adsorb Hg. There was revealed a positive and significant correlation (p < 0.05) between Hg trends in sediments and Hg trends in annular tree rings. This shared Hg pattern reflects local environmental conditions. The Hg concentration values in S. testudineus from both study areas are not restrictive to human consumption, being below the legislated European limit for Hg in foodstuffs. The results from S. testudineus muscles analysis suggest a significant and linear increase in Hg burden with increasing fish length, indicating that the specimens are accumulating Hg as they grow. The results from both rivers show an increase in BSAF with fish growth. The Hg liver/Hg muscles ratio >1, which indicates that the S. testudineus from both study areas are experiencing an increase in Hg bioavailability. Possible climate-induced shifts in these aquatic systems processes are inducing a greater mobilization of bioavailable Hg, which could allow an acceleration of the biogeochemical transformation of Hg.
Background and
This study considered the use of a generalized additive multilevel model to describe the joint-angle-specific functional hamstring to quadriceps ratio (H:Q ratio) in the knee, using ...all of the available truly isokinetic data within the range.
Thirty healthy male basketball players aged 15.0 (1.4) years (average stature = 180.0 cm,
= 11.1 cm; average body mass = 71.2,
= 14.9 kg) years were considered. All players considered had no history of lower extremity musculoskeletal injury at the time of testing or during the 6 months before testing, and had been engaged in formal basketball training and competition for 5.9 (2.4) years. Moments of force of the reciprocal concentric and eccentric muscular actions for the knee extensors and flexors assessed by isokinetic dynamometry at 60°∙s
were used.
Maximum moments of force were attained at different angle positions for knee extension. For knee flexion, it was apparent that there was an ability to maintain high levels of moment of force between 30° and 60° in the concentric muscular action, corresponding to the concentric action of the hamstrings. However, for the eccentric knee flexion, corresponding to the quadriceps action, there was a marked peak of moment of force at about 55°. The functional H:Q ratio for the knee extension was non-linear, remaining higher than 1.0 (i.e., point of equality) from the beginning of the extension until approximately 40° of the knee extension, leveling off below the point of equality thereafter. On average, the functional H:Q ratio for the knee flexion did not attain 1.0 across the range of motion. The functional H:Q ratio for the knee in the present sample peaked at 20° and 80°, declining between these angle positions to below 0.50 at about 0.54.
Estimating the form of the non-linear relationship on-the-fly using a generalized additive multilevel model provides joint-angle-specific curves and joint-angle-specific functional H:Q ratio patterns, allowing the identification and monitoring of strength development, with potential implications for injury and performance.
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