Background
The precise mechanism involved in the acquisition of the IL‐17+ profile of γδT cells, the ligands responsible for this change, and whether this default is acquired during intrathymic ...maturation need to be elucidated.
Objective
This study aimed to evaluate whether IL‐17‐producing γδT cells are present in the airways of tolerant offspring from allergen‐sensitized mothers and the possible implication of maternal IgG in the generation of these cells.
Methods
Female mice were immunized or not, and the allergic response, frequency of γδT cell subsets and cytokine production of the offspring were analysed by flow cytometry. The effects of passive in vivo transfer of purified IgG were investigated in offspring. A translational approach was employed to analyse γδT cells in the thymus and PBMCs from humans.
Results
Maternal immunization reduced the frequency of spontaneous IL‐17‐producing γδT cells in the thymus, spleen and lung of offspring. This effect was mimicked by the in vivo treatment of females with purified IgG. IgG directly interacted with γδT cell membranes. The modulatory effect of human IgG on human infant intrathymic and adult peripheral γδT cells showed similarities to murine γδT cells, which is rarely reported in the literature.
Conclusions & Clinical Relevance
Together, our results reveal that IgG from potentially tolerant atopic mothers can influence offspring thymic IL‐17‐producing γδT cell maturation. Furthermore, we suggest that IgG is an unprecedented modulatory factor of murine and human γδT cells. These observations may support the future development of IgG‐based immunoregulatory therapeutic strategies.
Although aging correlates with a worse prognosis for Covid-19, super elderly still unvaccinated individuals presenting mild or no symptoms have been reported worldwide. Most of the reported genetic ...variants responsible for increased disease susceptibility are associated with immune response, involving type I IFN immunity and modulation;
cluster genes; inflammasome activation; genes of interleukins; and chemokines receptors. On the other hand, little is known about the resistance mechanisms against SARS-CoV-2 infection. Here, we addressed polymorphisms in the MHC region associated with Covid-19 outcome in super elderly resilient patients as compared to younger patients with a severe outcome.
SARS-CoV-2 infection was confirmed by RT-PCR test. Aiming to identify candidate genes associated with host resistance, we investigated 87 individuals older than 90 years who recovered from Covid-19 with mild symptoms or who remained asymptomatic following positive test for SARS-CoV-2 as compared to 55 individuals younger than 60 years who had a severe disease or died due to Covid-19, as well as to the general elderly population from the same city. Whole-exome sequencing and an in-depth analysis of the MHC region was performed. All samples were collected in early 2020 and before the local vaccination programs started.
We found that the resilient super elderly group displayed a higher frequency of some missense variants in the
gene (a member of the mucins' family) as one of the strongest signals in the MHC region as compared to the severe Covid-19 group and the general elderly control population. For example, the missense variant rs62399430 at
is two times more frequent among the resilient super elderly (p = 0.00002, OR = 2.24).
Since the pro-inflammatory basal state in the elderly may enhance the susceptibility to severe Covid-19, we hypothesized that
might play an important protective role against severe Covid-19, by reducing overactive immune responses in the senior population.
Various beneficial biological activities have been reported for passion fruit (Passiflora edulis), grown in tropical and subtropical regions. However, no study has yet demonstrated its action against ...the Zika virus (ZIKV) infection. The present study aimed to investigate the anti-ZIKV of the ethanolic passion fruit seed extract (PFSE), from which, liquid chromatography tandem mass spectrometry (LC-MS/MS) analysis allowed to putatively annotate the occurrence of piceatannol, astringin, scirpusin A, scirpusin B, isookanin-7-O-glucoside and naringenin-7-O-glucoside, two quadranguloside derivatives, tyrosine, and phenylalanine. PFSE is well tolerated by cell lines (Vero E6 and HTR-8/SVneo) and tissue explants from the human placenta. With 1- and 24-h treatments, PFSE consistently reduced the viral load and NS1 protein expression of the two strains of ZIKV (MR766 and PE243) in placental explants and cell lines. Thus, PFSE has a promising potential for developing anti-ZIKV treatments, protecting the placenta against infection caused by ZIKV, along with relevant antioxidant potential, represented by ferric reducing antioxidant power (FRAP) of 390.5 Trolox eq per g dry extract and half maximal inhibitory concentration (IC50) for 2,2-diphenyl-1-picrylhydrazyl radical (DPPH•) of 12.1 μg mL–1, and more than 90% protection from lipid peroxidation. Although further studies need to be conducted, PFSE treatment was safe and effective in trophoblast cells and placental explants, thus representing a promising class of all-accessible products based on the reuse of industrial by-products.
Thimet oligopeptidase (EC 3.4.24.15; EP24.15; THOP1) is a potential therapeutic target, as it plays key biological functions in processing biologically functional peptides. The structural ...conformation of THOP1 provides a unique restriction regarding substrate size, in that it only hydrolyzes peptides (optimally, those ranging from eight to 12 amino acids) and not proteins. The proteasome activity of hydrolyzing proteins releases a large number of intracellular peptides, providing THOP1 substrates within cells. The present study aimed to investigate the possible function of THOP1 in the development of diet-induced obesity (DIO) and insulin resistance by utilizing a murine model of hyperlipidic DIO with both C57BL6 wild-type (WT) and THOP1 null (THOP1
) mice. After 24 weeks of being fed a hyperlipidic diet (HD), THOP1
and WT mice ingested similar chow and calories; however, the THOP1
mice gained 75% less body weight and showed neither insulin resistance nor non-alcoholic fatty liver steatosis when compared to WT mice. THOP1
mice had increased adrenergic-stimulated adipose tissue lipolysis as well as a balanced level of expression of genes and microRNAs associated with energy metabolism, adipogenesis, or inflammation. Altogether, these differences converge to a healthy phenotype of THOP1
fed a HD. The molecular mechanism that links THOP1 to energy metabolism is suggested herein to involve intracellular peptides, of which the relative levels were identified to change in the adipose tissue of WT and THOP1
mice. Intracellular peptides were observed by molecular modeling to interact with both pre-miR-143 and pre-miR-222, suggesting a possible novel regulatory mechanism for gene expression. Therefore, we successfully demonstrated the previously unanticipated relevance of THOP1 in energy metabolism regulation. It was suggested that intracellular peptides were responsible for mediating the phenotypic differences that are described herein by a yet unknown mechanism of action.
Bats are the second most diverse mammal order and they provide vital ecosystem functions (e.g., pollination, seed dispersal, and nutrient flux in caves) and services (e.g., crop pest suppression). ...Bats are also important vectors of infectious diseases, harboring more than 100 different virus types. In the present study, we compiled information on bat communities from the Atlantic Forests of South America, a species‐rich biome that is highly threatened by habitat loss and fragmentation. The ATLANTIC BATS data set comprises 135 quantitative studies carried out in 205 sites, which cover most vegetation types of the tropical and subtropical Atlantic Forest: dense ombrophilous forest, mixed ombrophilous forest, semideciduous forest, deciduous forest, savanna, steppe, and open ombrophilous forest. The data set includes information on more than 90,000 captures of 98 bat species of eight families. Species richness averaged 12.1 per site, with a median value of 10 species (ranging from 1 to 53 species). Six species occurred in more than 50% of the communities: Artibeus lituratus, Carollia perspicillata, Sturnira lilium, Artibeus fimbriatus, Glossophaga soricina, and Platyrrhinus lineatus. The number of captures divided by sampling effort, a proxy for abundance, varied from 0.000001 to 0.77 individuals·h−1·m−2 (0.04 ± 0.007 individuals·h−1·m−2). Our data set reveals a hyper‐dominance of eight species that together that comprise 80% of all captures: Platyrrhinus lineatus (2.3%), Molossus molossus (2.8%), Artibeus obscurus (3.4%), Artibeus planirostris (5.2%), Artibeus fimbriatus (7%), Sturnira lilium (14.5%), Carollia perspicillata (15.6%), and Artibeus lituratus (29.2%).
Appropriate dietary recommendations represent a key part of secondary prevention in cardiovascular disease (CVD). We evaluated the effectiveness of the implementation of a nutritional program on ...quality of diet, cardiovascular events, and death in patients with established CVD.
In this open-label, multicenter trial conducted in 35 sites in Brazil, we randomly assigned (1:1) patients aged 45 years or older to receive either the BALANCE Program (experimental group) or conventional nutrition advice (control group). The BALANCE Program included a unique nutritional education strategy to implement recommendations from guidelines, adapted to the use of affordable and regional foods. Adherence to diet was evaluated by the modified Alternative Healthy Eating Index. The primary end point was a composite of all-cause mortality, cardiovascular death, cardiac arrest, myocardial infarction, stroke, myocardial revascularization, amputation, or hospitalization for unstable angina. Secondary end points included biochemical and anthropometric data, and blood pressure levels.
From March 5, 2013, to Abril 7, 2015, a total of 2534 eligible patients were randomly assigned to either the BALANCE Program group (n = 1,266) or the control group (n = 1,268) and were followed up for a median of 3.5 years. In total, 235 (9.3%) participants had been lost to follow-up. After 3 years of follow-up, mean modified Alternative Healthy Eating Index (scale 0-70) was only slightly higher in the BALANCE group versus the control group (26.2 ± 8.4 vs 24.7 ± 8.6, P < .01), mainly due to a 0.5-serving/d greater intake of fruits and of vegetables in the BALANCE group. Primary end point events occurred in 236 participants (18.8%) in the BALANCE group and in 207 participants (16.4%) in the control group (hazard ratio, 1.15; 95% CI 0.95-1.38; P = .15). Secondary end points did not differ between groups after follow-up.
The BALANCE Program only slightly improved adherence to a healthy diet in patients with established CVD and had no significant effect on the incidence of cardiovascular events or death.
PURPOSE:To compare functional and cardiovascular variables of men and women with peripheral artery disease (PAD).
METHODS:This observational, cross-sectional study included 67 women and 144 men (age ...66 ± 9 and 67 ± 10 yr, respectively) with PAD. Patients were submitted to a clinical evaluation, 6-min walk test (6MWT) and cardiovascular evaluation, including blood pressure, arterial stiffness variables, and heart rate variability.
RESULTS:Women had lower claudication onset distance (P = .033) and 6MWT distance (P < .001), and similar percentage of the predicted 6MWT distance (P > .05). Women had higher pulse pressure (P = .002), augmentation index (P < .001), augmentation index corrected by 75 bpm (P < .001), and brachial and central systolic blood pressure (P = .041 and P = .029). Diastolic blood pressure, pulse wave velocity, and heart rate variability were similar between sexes (P > .05).
CONCLUSION:Although predicted 6MWT performance was similar between sexes, women had higher blood pressure and wave reflection variables compared with men. Interventions to reduce blood pressure and wave reflection should be emphasized in women with PAD.
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Genetic and omics analyses frequently require independent observations, which is not guaranteed in real datasets. When relatedness cannot be accounted for, solutions involve removing ...related individuals (or observations) and, consequently, a reduction of available data. We developed a network-based relatedness-pruning method that minimizes dataset reduction while removing unwanted relationships in a dataset. It uses node degree centrality metric to identify highly connected nodes (or individuals) and implements heuristics that approximate the minimal reduction of a dataset to allow its application to complex datasets. When compared with two other popular population genetics methodologies (PLINK and KING), NAToRA shows the best combination of removing all relatives while keeping the largest possible number of individuals in all datasets tested and also, with similar effects on the allele frequency spectrum and Principal Component Analysis than PLINK and KING. NAToRA is freely available, both as a standalone tool that can be easily incorporated as part of a pipeline, and as a graphical web tool that allows visualization of the relatedness networks. NAToRA also accepts a variety of relationship metrics as input, which facilitates its use. We also release a genealogies simulator software used for different tests performed in this study.
It is possible that physical education professionals, especially those who participate in aerobic activities, have predisposing factors, signs and symptoms of overreaching (OVR) and overtraining ...(OVT) due to a high load and volume of exercise followed by suboptimal recovery time. The present study aimed to identify the predisposing factors, signs and symptoms of OVR and OVT in physical education professionals.
A questionnaire consisting of 42 questions (10 questions group) about predisposing factors and signs/symptoms was answered by 132 physical education professionals from both sexes (83 men and 49 women) who were allocated into a resistance training group (RG,
= 74), aerobic training group (AG,
= 20) and resistance and aerobic training group (RAG,
= 38). A mean score was calculated ranging from 1 (completely absent) to 5 (severe) for each question group. A low occurrence of predisposing factors and signs and symptoms of OVR and OVT was considered to be a question group score 4 or lower. Profile of Mood State Questionnaire (POMS) was also applied.
A mean score of 2.5 ± 0.7, 2.7 ± 0.7 and 2.7 ± 0.8 was found for all question groups for RG, AG and RAG, respectively. Of the total sample, 40.6% trained at least five times/week. The POMS revealed that 67.5% of the RG (
= 50), 80% of the AG (
= 16) and 60.5% of the RAG (
= 23) were classified as having no mood disorders and a standard graphic iceberg was presented. There were no statistical differences (
> 0.05) in the total mood disorders among RG (13.9 ± 24.5), AG (10.3 ± 25.1) and RAG (14.6 ± 27.9) groups.
Despite the volume of training/body working performed by the physical education professionals surveyed being greater than the recommended to achieve improvements on physical fitness, they did not show predisposing factors, signs or symptoms of OVR and OVT.
5-Nitro-furan nitrones (1) and 5-nitro-thiophene nitrones (2) were synthesized in one step. Compounds 1a–c had the most potent leishmanicidal activity against intracellular amastigote forms of ...Leishmania amazonensis and L. infantum (from 0.019 to 2.76 μM), with excellent selectivity (from 39 to 5673). The comparison of the leishmanicidal activity in promastigotes of wild type L. donovani with those overexpressing nitroreductases NRT1 or NRT2 shows that 1a,b are activated by both, which could slow the development of resistance. Their redox potential (E redox) obtained by cyclic voltammetry (−0.67 and −0.62 V) shows that the reduction of the nitro group is modulated by the nitrone group. Oral administration of 1b to mice infected by L. infantum reduced the parasite load on the spleen by 76.6 and 95.0% with doses of 50 and 100 mg/kg, respectively, administered twice a day, for 5 days. In the liver, the parasite load suppression was above 75% with either treatment.
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