Among the familial forms of amyotrophic lateral sclerosis (fALS), 20% are associated with the Cu,Zn-superoxide dismutase (Sod1). fALS is characterized by the accumulation of aggregated proteins and ...the increase in oxidative stress markers. Here, we used the non-invasive bimolecular fluorescence complementation (BiFC) assay in human H4 cells to investigate the kinetics of aggregation and subcellular localization of Sod1 mutants. We also studied the effect of the different Sod1 mutants to respond against oxidative stress by following the levels of reactive oxygen species (ROS) after treatment with hydrogen peroxide. Our results showed that only 30% of cells transfected with A4VSod1 showed no inclusions while for the other Sod1 mutants tested (L38V, G93A and G93C), this percentage was at least 70%. In addition, we found that 10% of cells transfected with A4VSod1 displayed more than five inclusions per cell and that A4V and G93A Sod1 formed inclusions more rapidly than L38V and G93C Sod1. Expression of WTSod1 significantly decreased the intracellular oxidation levels in comparison with expression of fALS Sod1 mutants, suggesting the mutations induce a functional impairment. All fALS mutations impaired nuclear localization of Sod1, which is important for maintaining genomic stability. Consistently, expression of WTSod1, but not of fALS Sod1 mutants, reduced DNA damage, as measured by the comet assay. Altogether, our study sheds light into the effects of fALS Sod1 mutations on inclusion formation, dynamics, and localization as well as on antioxidant response, opening novel avenues for investigating the role of fALS Sod1 mutations in pathogenesis.
Currently, the world has been devastated by an unprecedented pandemic in this century. The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the agent of coronavirus disease 2019 ...(COVID-19), has been causing disorders, dysfunction and morphophysiological alterations in multiple organs as the disease evolves. There is a great scientific community effort to obtain a therapy capable of reaching the multiple affected organs in order to contribute for tissue repair and regeneration. In this regard, mesenchymal stem cells (MSCs) have emerged as potential candidates concerning the promotion of beneficial actions at different stages of COVID-19. MSCs are promising due to the observed therapeutic effects in respiratory preclinical models, as well as in cardiac, vascular, renal and nervous system models. Their immunomodulatory properties and secretion of paracrine mediators, such as cytokines, chemokines, growth factors and extracellular vesicles allow for long range tissue modulation and, particularly, blood-brain barrier crossing. This review focuses on SARS-CoV-2 impact to lungs, kidneys, heart, vasculature and central nervous system while discussing promising MSC's therapeutic mechanisms in each tissue. In addition, MSC's therapeutic effects in high-risk groups for COVID-19, such as obese, diabetic and hypertensive patients are also explored.
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•COVID-19 pathophysiology affects a miryad of organs and tissues. Even recovered patients have lingering tissue dysfunction•MSC have shown immunomodulatory, angiogenic, anti-inflammatory, and anti-apoptotic properties in related pre-clinical models•MSC generally improves inflamation resulotion, enhances cell survival and promotes tissue remodeling•MSC therapy may be benefetial even in high-risk patients with obesity, hypertension and diabetes
First and second generation of Grubbs catalysts (G1 and G2) were applied in the piperine olefin metathesis under different conditions. G1 was used in self-metathesis, G2 was implemented in both, self ...and cross-metathesis of piperine with eugenol. Results allowed to implicate about the main intermediate of the reaction and the position of olefin attachment to the catalyst, assuming that the reaction follows a pathway where 2A=B olefin leads to the formation of A=A and B=B. In addition, the results contributed to the studies of catalyst’s reactivity when the olefin metathesis product required the high electronic effect of the
N
-heterocyclic of G2. In this paper, the highest activity of G2 in the olefin metathesis of eugenol was observed when the first intermediate was Ru-eugenol-moiety in the cross-metathesis of the piperine with eugenol. This demonstrates that the acidity of the new carbene in the intermediate species causes inactivity only in the reaction with piperine.
This study evaluates the influence of information on the health benefits for acceptance of four exotic tropical fruit juices: açaí, camu-camu, cajá and umbu. One hundred and six evaluators ...participated in the tests and sensory acceptability of the four juices in relation to the overall impression was assessed using a hedonic scale of nine points. Testing was conducted in three stages: the first with no information, the second with the information on juice flavor and the last with the information on health benefits from consumption of such juice. Between the second and third session the evaluators were asked to fill out a questionnaire in order to obtain its socioeconomic and cultural profile. It was observed by internal preference mapping that the cajá and umbu juices showed higher sensory acceptance in all sessions. Camu-camu juice had the highest sensory rejection. It was found that the information on the taste of açaí and cajá juices positively influenced consumer acceptance. However the influence of information on health benefits can be observed for all evaluated juices, but despite this information the camu-camu juice continued in the area of sensory rejection (hedonic scores below 5). In the questionnaire it can be observed that the main factor of motivation for consumption of fruit juice is taste, and not the health benefits. It was concluded that the information of health benefits can positively influence sensory acceptance, provided there is sensory pleasure.
ArtinM, a D-mannose binding lectin from Artocarpus heterophyllus, has immunomodulatory activities through its interaction with N-glycans of immune cells, culminating with the establishment of T ...helper type 1 (Th1) immunity. This interaction protects mice against intracellular pathogens, including Leishmania major and Leishmania amazonensis. ArtinM induces neutrophils activation, which is known to account for both resistance to pathogens and host tissue injury. Although exacerbated inflammation was not observed in ArtinM-treated animals, assessment of neutrophil responses to ArtinM is required to envisage its possible application to design a novel immunomodulatory agent based on carbohydrate recognition. Herein, we focus on the mechanisms through which neutrophils contribute to ArtinM-induced protection against Leishmania, without exacerbating inflammation. For this purpose, human neutrophils treated with ArtinM and infected with Leishmania major were analyzed together with untreated and uninfected controls, based on their ability to eliminate the parasite, release cytokines, degranulate, produce reactive oxygen species (ROS), form neutrophil extracellular traps (NETs) and change life span. We demonstrate that ArtinM-stimulated neutrophils enhanced L. major clearance and at least duplicated tumor necrosis factor (TNF) and interleukin-1beta (IL-1β) release; otherwise, transforming growth factor-beta (TGF-β) production was reduced by half. Furthermore, ROS production and cell degranulation were augmented. The life span of ArtinM-stimulated neutrophils decreased and they did not form NETs when infected with L. major. We postulate that the enhanced leishmanicidal ability of ArtinM-stimulated neutrophils is due to augmented release of inflammatory cytokines, ROS production, and cell degranulation, whereas host tissue integrity is favored by their shortened life span and the absence of NET formation. Our results reinforce the idea that ArtinM may be considered an appropriate molecular template for the construction of an efficient anti-infective agent.
The present study proposes a maize sprouts hydroponic growth model to evaluate the As, Cd, Cr and Pb translocation from multinutrient fertilizer and to do speciation of As and Cr in this fertilizer ...and As in parts of plant in order to predict their phytoavailability. X-ray absorption near edge structure (XANES) was employed to speciate As and Cr directly on fertilizer solid sample. Arsenate (AsV) and a solid solution of FeCrO3 were the major species identified in the samples. The sprouts were hydroponically cultivated in water, fertilizer slurry and fertilizer extract media. Concentrations of As, Cd and Pb measured on leaves of maize sprouts ranged from 0.061 to 0.31 mg kg−1, whereas Cr was not translocated to the aerial parts of sprouts. High performance liquid chromatographic with inductively coupled plasma mass spectrometry (HPLC-ICP-MS) analysis was used to determine As speciation in maize sprouts, as well as in the fertilizer extracts and slurries. Arsenate was the only species identified in the initial fertilizer extract and this information is in agreement with the XANES results. However, the reduction of arsenate to arsenite was observed in extracts and slurries collected after sprout growth, probably due to the action of exudates secreted by plant roots. Arsenite was the predominant species identified in sprouts, the high phosphate concentration in the medium may have contributed to reduce arsenate phytoavailability.
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•Hydroponic maize showed phytoavailability of As, Cd and Pb from a mineral fertilizer.•As, Cd and Pb translocated to the aerial parts of the maize sprout, Cr no.•XANES analysis identified As(V) and Cr(III) directly on fertilizer solid sample.•As(III) was the predominant species identified in sprouts.
Mobility and phytoavailability of As, Cd, Cr and Pb from a mineral fertilizer were demonstrated in a simple experiment using hydroponic maize sprouts test.
Introduction
People with chronic obstructive pulmonary disease (COPD) present high prevalence of physical inactivity that leads to a negative effect on health-related quality of life (HRQoL). The ...present study investigated COPD phenotypes according to their levels of physical activity and sedentary behaviour, as well as body composition and skeletal muscle strength.
Methods
This is an observational and cross-sectional study. Anthropometric data and COPD clinical control were collected and all participants underwent assessments of lung function, HRQoL, dyspnoea, levels of physical activity and sedentary behaviour, body composition and skeletal muscle strength. Participants were classified using hierarchical cluster analysis. Age, dyspnoea and obstruction (ADO) index was used to determine prognosis and calculated for each cluster.
Results
One hundred and fifty-two participants were included. Three distinct phenotypes were identified. Participants in phenotype 1 were more physically active, less sedentary and had better body composition and lower ADO index (
p
< 0.0001 for all variables). Overall, participants in phenotypes 2 and 3 were less physically active, more sedentary having a higher ADO index. However, participants in phenotype 2 were older, whereas participants in phenotype 3 had worse HRQoL, clinical control and body composition. Lung function did not differ across the three phenotypes.
Conclusions
Our results show that physical activity, sedentary behaviour and body composition should be considered to determine phenotypes in people with COPD and are involved in the prognosis of the disease. Less sedentary patients have better prognosis while age, body composition and clinical control seems to differentiate physically inactive patients.
The goal of the study was to evaluate the ability of filamentous fungi to biotransform the pentacyclic triterpene lupeol. The microbial transformations were carried out in shake flasks in different ...media. Experiments were also run with control flasks. Samples of each culture were taken every 24 hours, extracted with ethyl acetate, and analyzed by GC-MS. The biotransformation of lupeol by Aspergillus ochraceus and Mucor rouxii afforded two compounds in each culture, which were detected in the cultures developed for more than seven days only in the Koch's K1 medium. The obtained data demonstrated that A. ochraceus is a good biocatalyst to introduce double bonds in the lupeol structure, whereas M. rouxii exhibits ability to biocatalyze oxygen insertions in that pentacyclic triterpene. Mass spectrometry was demonstrated to be an efficient analytical method to select promising biocatalysts for the compound investigated in this study. The biotransformation processes were influenced by the culture medium and incubation period. The obtained results open the perspective of using A. ochraceus and M. rouxii in pentacyclic triterpene biotransformations.
BACKGROUNDThere is emerging evidence that frail individuals present a decreased physiological reserve, decreased ability to maintain homeostasis, and increased vulnerability to stressors. The concept ...of frailty has become increasingly recognized as a valuable measure in oncological surgical patients, including those with head and neck cancer. Preoperative screening for frailty may provide an individualized risk assessment that can be used by an interdisciplinary team for preoperative counseling and to improve outcomes. The aim of this meta-analysis was to evaluate the relationship between frailty and the risk of major postoperative complications in frail individuals submitted to head and neck oncologic surgery. MATERIAL AND METHODSPubMed, SCOPUS, Web of Science, Google Scholar and OpenThesis were systematically searched to identify studies that evaluated the risk of major postoperative complications in frail individuals undergoing head and neck oncologic surgery. The search was performed on August 31, 2020, without language or date restrictions. Two independent investigators screened the searched studies based on each paper's title and abstract. Relevant studies were read in full and selected according to the eligibility criteria. Frailty was assessed by modified Frailty Index (mFI-11) and major postoperative complications were measured by the Clavien-Dindo classification. We performed a categorical and dose-response meta-analysis using a random-effects model to evaluate the association between frailty and the risk of major postoperative complications in patients submitted to head and neck oncologic surgery. The results of the meta-analysis were expressed as relative risk (RR) and 95% confidence interval (95% CI). The risk of bias was assessed using the Newcastle-Ottawa Scale (NOS). RESULTSFour studies (9,947 patients) were included in this systematic review and meta-analysis. Frail patients presented an increased risk of life-threatening complications requiring intensive care unit (ICU) admission (RR = 4.67; 95% CI 1.54-14.10) and 30-day mortality (RR = 8.10; 95% CI 2.30-28.57) compared to non-frail patients. We found evidence of dose-response trend between mFI-11 and major postoperative complications. CONCLUSIONSHigher frailty scores are associated with a significant increase in ICU-level complications and 30-day mortality after head and neck oncologic surgery.
Background: The correct understanding of the epidemiological dynamics of COVID-19, caused by the SARS-CoV-2, is essential for formulating public policies of disease containment. Methods: In this ...study, we constructed a picture of the epidemiological dynamics of COVID-19 in a Brazilian population of almost 17000 patients in 15 months. We specifically studied the fluctuations of COVID-19 cases and deaths due to COVID-19 over time according to host gender, age, viral load, and genetic variants. Results: As the main results, we observed that the numbers of COVID-19 cases and deaths due to COVID-19 fluctuated over time and that men were the most affected by deaths, as well as those of 60 or more years old. We also observed that individuals between 30- and 44-years old were the most affected by COVID-19 cases. In addition, the viral loads in the patients’ nasopharynx were higher in the early symptomatic period. We found that early pandemic SARS-CoV-2 lineages were replaced by the variant of concern (VOC) P.1 (Gamma) in the second half of the study period, which led to a significant increase in the number of deaths. Conclusions: The results presented in this study are helpful for future formulations of efficient public policies of COVID-19 containment.
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