Sickle cell disease (SCD) is an inherited hemolytic anemia whose pathophysiology is driven by polymerization of the hemoglobin S (Hb S), leading to hemolysis and vaso-occlusive events. Inflammation ...is a fundamental component in these processes and a continuous inflammatory stimulus can lead to tissue damages. Thus, pro-resolving pathways emerge in order to restore the homeostasis. For example there is the annexin A1 (ANXA1), an endogenous anti-inflammatory protein involved in reducing neutrophil-endothelial interactions, accelerating neutrophil apoptosis and stimulating macrophage efferocytosis. We investigated the expression of ANXA1 in plasma of SCD patients and its relation with anemic, hemolytic and inflammatory parameters of the disease. Three SCD genotypes were considered: the homozygous inheritance for Hb S (Hb SS) and the association between Hb S and the hemoglobin variants D-Punjab (Hb SD) and C (Hb SC). ANXA1 and proinflammatory cytokines were quantified by ELISA in plasma of SCD patients and control individuals without hemoglobinopathies. Hematological and biochemical parameters were analyzed by flow cytometry and spectrophotometer. The plasma levels of ANXA1 were about three-fold lesser in SCD patients compared to the control group, and within the SCD genotypes the most elevated levels were found in Hb SS individuals (approximately three-fold higher). Proinflammatory cytokines were higher in SCD groups than in the control individuals. Anemic and hemolytic markers were higher in Hb SS and Hb SD genotypes compared to Hb SC patients. White blood cells and platelets count were higher in Hb SS genotype and were positively correlated to ANXA1 levels. We found that ANXA1 is down-regulated and differentially expressed within the SCD genotypes. Its expression seems to depend on the inflammatory, hemolytic and vaso-occlusive characteristics of the diseased. These data may lead to new biological targets for therapeutic intervention in SCD.
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•An interorgan mercapturic acid pathway (MAP) was detected in oysters using CDNB.•CDNB uptake was followed by fast buildup of MAP-related metabolites in the tissues.•CDNB uptake and ...glutathione-dependent metabolism was effective in the gills.•Hemolymph acted in metabolite transport along the organism.•The final MAP metabolite was detected in the seawater and in the tissues.
The mercapturic acid pathway (MAP) is a major phase II detoxification route, comprising the conjugation of electrophilic substances to glutathione (GSH) in a reaction catalyzed by glutathione S-transferase (GST) enzymes. In mammals, GSH-conjugates are exported from cells, and the GSH-constituent amino acids (Glu/Gly) are subsequently removed by ectopeptidases. The resulting Cys-conjugates are reabsorbed and, finally, a mercapturic acid is generated through N-acetylation. This pathway, though very well characterized in mammals, is poorly studied in non-mammalian biological models, such as bivalve mollusks, which are key organisms in aquatic ecosystems, aquaculture activities and environmental studies. In the present work, the compound 1-chloro-2,4-dinitrobenzene (CDNB) was used as a model electrophile to study the MAP in Pacific oysters Crassostrea gigas. Animals were exposed to 10μM CDNB and MAP metabolites were followed over 24h in the seawater and in oyster tissues (gills, digestive gland and hemolymph). A rapid decay was detected for CDNB in the seawater (half-life 1.7h), and MAP metabolites peaked in oyster tissues as soon as 15min for the GSH-conjugate, 1h for the Cys-conjugate, and 4h for the final metabolite (mercapturic acid). Biokinetic modeling of the MAP supports the fast CDNB uptake and metabolism, and indicated that while gills are a key organ for absorption, initial biotransformation, and likely metabolite excretion, hemolymph is a possible milieu for metabolite transport along different tissues. CDNB-induced GSH depletion (4h) was followed by increased GST activity (24h) in the gills, but not in the digestive gland. Furthermore, the transcript levels of glutamate-cysteine ligase, coding for the rate limiting enzyme in GSH synthesis, and two phase II biotransformation genes (GSTpi and GSTo), presented a fast (4h) and robust (∼6–70 fold) increase in the gills. Waterborne exposure to electrophilic compounds affected gills, but not digestive gland, while intramuscular exposure was able to modulate biochemical parameters in both tissues. This study is the first evidence of a fully functional and interorgan MAP pathway in bivalves. Hemolymph was shown to be responsible for the metabolic interplay among tissues, and gills, acting as a powerful GSH-dependent metabolic barrier against waterborne electrophilic substances, possibly also participating in metabolite excretion into the sea water. Altogether, experimental and modeled data fully agree with the existence of a classical mechanism for phase II xenobiotic metabolism and excretion in bivalves.
Feedlot cattle are usually adapted to high-concentrate diets containing sodium monensin (MON) in more than 14 days. However, considering that the dry matter intake DMI is usually lower during ...adaptation when compared to the finishing period, the use of MON during adaptation may decrease even further the DMI, and virginiamycin (VM) may be an alternative. This study was designed to investigate the effects of shortening the adaptation length from 14 to 9 or 6 days on ruminal metabolism, feeding behavior, and nutrient digestibility of Nellore cattle fed high-concentrate diets containing only VM as the sole feed additive. The experimental design was a 5 × 5 Latin square, where each period lasted 21 days. Five 17 mo-old Nellore yearling bulls were used (415 ± 22 kg of body weight), which were assigned to five treatments: (1) MON (30 mg/kg) and adaptation for 14 days; (2) MON (30 mg/kg) + VM (25 mg/kg) and adaptation for 14 days; (3) VM (25 mg/kg) and adaptation for 14 days; (4) VM (25 mg/kg) and adaptation for 9 days, and (5) VM (25 mg/kg) and adaptation for 6 days. A quadratic effect for adaptation length when only VM was fed was observed for mean pH (
= 0.03), duration of pH below 5.2 (
= 0.01) and 6.2 (
= 0.01), where cattle consuming VM adapted for 9 days had higher mean pH and shorter period of pH below 5.2 and 6.2. Cattle that consumed only MON had a lower concentration of butyrate (
= 0.02) and a higher concentration of propionate (
= 0.04) when compared to those consuming VM and adapted for 14 days. As the adaptation length decreased for animals consuming only VM, the rumen degradability of dry matter (
< 0.01), neutral detergent fiber (
< 0.01), and starch (
< 0.01) decreased; however, protozoa numbers of
and total protozoa increased. It is not recommended to shorten the adaptation length of these animals to either 6 or 9 days without negatively impacting nutrient disappearance and ruminal fermentation patterns.
Studies have shown that the loss of the FOXO3 transcriptional function is involved in the pathophysiology of some chronic erythroid disorders, including beta-thalassemia (β-thal). Therefore, the ...single nucleotide polymorphism (SNP) rs3800231 (35-2764A > G) could contribute to alterations in its transcriptional activity, acting as a modifier of β-thal phenotypic manifestations.
In order to better understand the genotypic and/or allelic distributions among β-thal patients, we evaluated 83 β-thal heterozygous and 20 homozygous, compared to 117 individuals without hemoglobinopathies (control group). Additionally, we verified any influence of the FOXO3 polymorphism on clinical manifestations among β-thal homozygotes.
We obtained higher frequencies of the wild-type homozygous (AA) and the wild-type allele (A) in the β-thal group (p < 0.0001 and p = 0.00014, respectively). The most common clinical manifestations found among β-thal homozygotes were iron overload (90%), splenomegaly (65%) and bone complications (35%), e.g., osteopenia/osteoporosis. We observed that close to 80% of the patients presenting such manifestations had the genotype AA. However, we did not find any significant involvement of the FOXO3 polymorphism in clinical manifestation occurrences.
Thus, we concluded that the SNP rs3800231 did not play a significant role as a modifier of the clinical manifestations observed in the β-thal homozygotes studied.
Progenesis QI (PQI) is a multiplatform bioinformatics tool that facilitates the identification workflow for metabolomics experiments. PQI uses fragmentation data provided by MassBank of North America ...(MoNA) libraries, among others, for metabolite annotation. However, PQI does not officially support MoNA libraries and other libraries based on structure-data files (.sdf). This paper describes the development and application of a software named MoNA to Progenesis QI Library Converter, allowing PQI and MoNA by correcting the fragmentation data of the library for Progenesis readability. We evaluated several public experimental datasets, including human plasma, plant extracts, cultured cells, bacteria, rat serum, and rat hippocampus. The results showed that it is mandatory to proceed with file conversion of each library to allow PQI to access fragmentation information from .msp (main spectra profile) files. This step is highly recommended to improve the identification level of the metabolites.
Beta S-globin gene cluster haplotypes (β(S)-haplotypes) can modulate the response to hydroxycarbamide (HC) treatment in sickle cell anemia (SCA) patients. In Brazil, the most common haplotypes are ...Bantu and Benin, and both confer a poor prognosis for patients when untreated with HC. We evaluated oxidative and hemolytic biomarkers in 48 SCA patients undergoing HC treatment separated in three subgroups: Bantu/Bantu, Bantu/Benin and Benin/Benin haplotype. On the basis of reduced haptoglobin (HP) levels, patients with Bantu/Bantu haplotypes had 3.0% higher hemolysis degree when compared with those with Bantu/Benin haplotypes (P=0.01). The Benin/Benin patients had 53.6% greater lipid peroxidation index than the Bantu/Bantu patients (P=0.01) because of evaluated thiobarbituric acid reactive species levels. The Bantu/Benin subgroup had intermediate levels of hemolytic and oxidative stress markers compared with the homozygous subgroups. Through strict inclusion criteria adopted, as well as consolidated and well-described hemolytic and the oxidative parameters evaluated, we suggest a haplotype-interaction response to HC treatment mediated by a 'balance' between the genetic factors of each haplotype studied.
Phenotypic heterogeneity for sickle cell disease is associated to several genetic factors such as genotype for sickle cell disease, β-globin gene cluster haplotypes and Hb F levels. The coinheritance ...of Hb S (HBB: c.20A > T) and Hb D-Punjab (HBB: c.364G > C) results in a double heterozygosity, which constitutes one of the genotypic causes of sickle cell disease. This study aimed to assess the phenotypic diversity of sickle cell disease presented by carriers of the Hb S/Hb D-Punjab genotype and the Bantu - + - - - - haplotype. We evaluated medical records from 12 patients with sickle cell disease whose Hb S/Hb D-Punjab genotype and Bantu haplotype were confirmed by molecular analysis. Hb S and Hb D-Punjab levels were quantified by chromatographic analysis. Mean concentrations of Hb S and Hb D-Punjab were 44.8 ± 2.3% and 43.3 ± 1.8%, respectively. Painful crises were present in eight (66.7%) patients evaluated, representing the most common clinical event. Acute chest syndrome (ACS) was the second most prevalent manifestation, occurring in two individuals (16.7%). Three patients were asymptomatic, while another two exhibited greater diversity of severe clinical manifestations. Medical records here analyzed reported a significant clinical diversity in sickle cell disease ranging from the absence of symptoms to wide phenotypic variety. The sickle cell disease genotype, Bantu haplotype and hemoglobin (Hb) levels did not influence the clinical diversity. Thus, we concluded that the phenotypic variation in sickle cell disease was present within a specific genotype for disease regardless of the β-globin gene cluster haplotypes.
The current study aimed to explore the association of individual characteristics, social and environmental factors - school and region - in the intention to be physically active in Brazilian ...adolescents.
This is a cross sectional study based on the third edition of the National School Health Survey. The study included a total of 53,937 adolescents. To assess the intention to be physically active, only who engaged in less than 300 min of physical activity per week were included. Participants were asked: "If you had the opportunity to practice physical activity most days of the week, what would your attitude be?" Individual characteristics, physical activity domains, social factors, school, and regional environments were used as exposures. Network analysis was utilized to evaluate the associations.
We observed that boys had higher intentions to be physically active compared to their peers, as did adolescents who perceived themselves as fat. In addition, students from private schools show a higher intention to regularly engage in physical activities, and in general, private schools offer more extracurricular physical activities.
In conclusion, individual factors such as sex and body image perception, and environmental factors such as school administrative dependency and availability of extracurricular activities had a significant contribution to the intention to be physically active among Brazilian adolescents.
Parent material is the main source for soil textural, mineralogical, and other physical attributes. The knowledge over this factor is explored generally in low scale geology maps, insufficient for ...most users. Remote sensing can offer assistance in this regard, since it allows the evaluation of soil properties, as largely indicated in literature, being a potential tool to delineate parent material. Thus, we explored a multi temporal Landsat image composition with bare soil reflectance to extract soil properties and distinguish discrepant lithological classes at the western plateau, São Paulo State, Brazil. The area is 247,737 ha large, where 981 soil samples were collected at 0–20 cm depth. We acquired the synthetic soil image and linked the pixel's spectra with soil attributes. We performed a digital soil mapping procedure to generate maps of attributes related to parent material. The soil maps offered a great input on identifying the transitions between sandstone and basalt as soils from these formations have significant differences in clay, sand, Fe2O3 and TiO2 contents. Therefore, the use of remote sensing coupled with digital soil mapping is a strong alternative to conventional methods to improve low scale PM maps to enhance detail on regional and local scales.
•The sand and clay content at 0–20 cm are significantly different (p < 0.001) in soils developed from sandstone and basalt.•Bare soil reflectance is significantly different (p < 0.001) over soils developed from sandstone and basalt.•DSM products can be used to identify PM through statistical analysis•PM prediction through environmental variables reached accuracy of 0.75 and kappa coefficient of 0.4
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