Prostaglandin E2/Leukotriene B4 balance and viral load in distinct clinical stages of COVID-19: A cross-sectional study.

BACKGROUND: Prostaglandin E2 (PGE2) and leukotriene B4 (LTB4) are eicosanoids involved in modulation of the antiviral immune response. Recent studies have identified increased levels of several eicosanoids in the plasma and bronchoalveolar lavage of patients with coronavirus disease (COVID-19). This study investigated correlations between plasma levels of PGE2 and LTB4 and clinical severity of COVID-19. METHODS: This cross-sectional study involved non-infected (n = 10) individuals and COVID-19 patients classified as cured (n = 13), oligosymptomatic (n = 29), severe (n = 15) or deceased (n = 11). Levels of D-dimer a, known COVID-19 severity marker, PGE2 and LTB4 were measured by ELISAs and data were analysed with respect to viral load. RESULTS: PGE2 plasma levels were decreased in COVID-19 patients compared to the non-infected group. Changes in PGE2 and LTB4 levels did not correlate with any particular clinical presentations of COVID-19. However, LTB4 was related to decreased SARS-CoV-2 burden in patients, suggesting that only LTB4 is associated with control of viral load. CONCLUSIONS: Our data indicate that PGE2/LTB4 plasma levels are not associated with COVID-19 clinical severity. Hospitalized patients with COVID-19 are treated with corticosteroids, which may influence the observed eicosanoid imbalance. Additional analyses are required to fully understand the participation of PGE2 receptors in the pathophysiology of COVID-19.

Coagulopathy and the humoral response against viral proteins in patients at different stages of COVID-19.

BACKGROUND: Patients with severe coronavirus disease 2019 (COVID-19) often present with coagulopathies and have high titres of circulating antibodies against viral proteins. OBJECTIVES: Herein, we evaluated the association between D-dimer and circulating immunoglobulin levels against viral proteins in patients at different clinical stages of COVID-19. METHODS: For this, we performed a cross-sectional study involving patients of the first wave of COVID-19 clinically classified as oligosymptomatic (n = 22), severe (n = 30), cured (n = 27) and non-infected (n = 9). Next, we measured in the plasma samples the total and fraction of immunoglobulins against the nucleoprotein (NP) and the receptor-binding domain (RBD) of the spike proteins by enzyme-linked immunosorbent assay (ELISA) assays. FINDINGS: Patients with severe disease had a coagulation disorder with high levels of D-dimer as well as circulating IgG against the NP but not the RBD compared to other groups of patients. In addition, high levels of D-dimer and IgG against the NP and RBD were associated with disease severity among the patients in this study. MAIN CONCLUSIONS: Our data suggest that IgG against NP and RBD participates in the worsening of COVID-19. Although the humoral response against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is partially understood, and more efforts are needed to clarify gaps in the knowledge of this process.

Coagulopathy and the humoral response against viral proteins in patients at different stages of COVID-19

BACKGROUND Patients with severe coronavirus disease 2019 (COVID-19) often present with coagulopathies and have high titres of circulating antibodies against viral proteins. OBJECTIVES Herein, we evaluated the association between D-dimer and circulating immunoglobulin levels against viral proteins in patients at different clinical stages of COVID-19. METHODS For this, we performed a cross-sectional study involving patients of the first wave of COVID-19 clinically classified as oligosymptomatic (n = 22), severe (n = 30), cured (n = 27) and non-infected (n = 9). Next, we measured in the plasma samples the total and fraction of immunoglobulins against the nucleoprotein (NP) and the receptor-binding domain (RBD) of the spike proteins by enzyme-linked immunosorbent assay (ELISA) assays. FINDINGS Patients with severe disease had a coagulation disorder with high levels of D-dimer as well as circulating IgG against the NP but not the RBD compared to other groups of patients. In addition, high levels of D-dimer and IgG against the NP and RBD were associated with disease severity among the patients in this study. MAIN CONCLUSIONS Our data suggest that IgG against NP and RBD participates in the worsening of COVID-19. Although the humoral response against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is partially understood, and more efforts are needed to clarify gaps in the knowledge of this process.

Geometric morphometrics of Aedes aegypti populations and study of transmission of arboviral diseases in Barreiras, Brazil

Abstract Aedes (Stegomyia) aegypti (A. aegypti) transmits arboviral diseases of high public health importance, including those caused by Zika virus (ZIKV), Dengue virus (DENV), Chikungunya virus (CHIKV) and Yellow fever virus (YFV). Barreiras is a city with 157,638 inhabitants in the West of the State of Bahia, Northeast of Brazil. The climate is dry, with well-determined and concentrated seasons of rains. The city is crossed by a Federal Highway and by the Rio Grande river. In this study, we aimed to understand the dynamics of mosquito vectors and arboviral diseases in Barreiras. We used correlation statistics to investigate a possible relationship among rains, mosquito abundance and transmission of diseases. In addition, as a preliminary population genetics estimate, we used geometric morphometrics to compare mosquitoes from areas limited by a highway and a river. We found that i) infestation occurs in rain-dependent cycles and that ii) both, the river and the highway segregate populations of A. aegypti in different areas of the studied city. Our results indicate that it is necessary to treat anthropic containers with mosquito breading capacity during both, the dry and rain seasons in urban areas similar to Barreiras.

Geometric morphometrics of Aedes aegypti populations and study of transmission of arboviral diseases in Barreiras, Brazil

Aedes (Stegomyia) aegypti (A. aegypti) transmits arboviral diseases of high public health importance, including those caused by Zika virus (ZIKV), Dengue virus (DENV), Chikungunya virus (CHIKV) and Yellow fever virus (YFV). Barreiras is a city with 157,638 inhabitants in the West of the State of Bahia, Northeast of Brazil. The climate is dry, with well-determined and concentrated seasons of rains. The city is crossed by a Federal Highway and by the Rio Grande river. In this study, we aimed to understand the dynamics of mosquito vectors and arboviral diseases in Barreiras. We used correlation statistics to investigate a possible relationship among rains, mosquito abundance and transmission of diseases. In addition, as a preliminary population genetics estimate, we used geometric morphometrics to compare mosquitoes from areas limited by a highway and a river. We found that i) infestation occurs in rain-dependent cycles and that ii) both, the river and the highway segregate populations of A. aegypti in different areas of the studied city. Our results indicate that it is necessary to treat anthropic containers with mosquito breading capacity during both, the dry and rain seasons in urban areas similar to Barreiras.

Geometric morphometrics of Aedes aegypti populations and study of transmission of arboviral diseases in Barreiras, Brazil

Aedes (Stegomyia) aegypti (A. aegypti) transmits arboviral diseases of high public health importance, including those caused by Zika virus (ZIKV), Dengue virus (DENV), Chikungunya virus (CHIKV) and Yellow fever virus (YFV). Barreiras is a city with 157,638 inhabitants in the West of the State of Bahia, Northeast of Brazil. The climate is dry, with well-determined and concentrated seasons of rains. The city is crossed by a Federal Highway and by the Rio Grande river. In this study, we aimed to understand the dynamics of mosquito vectors and arboviral diseases in Barreiras. We used correlation statistics to investigate a possible relationship among rains, mosquito abundance and transmission of diseases. In addition, as a preliminary population genetics estimate, we used geometric morphometrics to compare mosquitoes from areas limited by a highway and a river. We found that i) infestation occurs in rain-dependent cycles and that ii) both, the river and the highway segregate populations of A. aegypti in different areas of the studied city. Our results indicate that it is necessary to treat anthropic containers with mosquito breading capacity during both, the dry and rain seasons in urban areas similar to Barreiras.

Screening of Transcription Factors Involved in Fetal Hemoglobin Regulation Using Phylogenetic Footprinting.

Fetal hemoglobin (Hb F) is an important genetic modulator of the beta-hemoglobinopathies. The regulation of Hb F levels is influenced by transcription factors. We used phylogenetic footprinting to screen transcription factors that have binding sites in HBG1 and HBG2 genes' noncoding regions in order to know the genetic determinants of the Hb F expression. Our analysis showed 354 conserved motifs in the noncoding regions of HBG1 gene and 231 motifs in the HBG2 gene between the analyzed species. Of these motifs, 13 showed relation to Hb F regulation: cell division cycle-5 (CDC5), myelo-blastosis viral oncogene homolog (c-MYB), transcription factor CP2 (TFCP2), GATA binding protein 1 (GATA-1), GATA binding protein 2 (GATA-2), nuclear factor erythroid 2 (NF-E2), nuclear transcription factor Y (NF-Y), runt-related transcription factor 1 (RUNX-1), T-cell acute lymphocytic leukemia 1 (TAL-1), YY1 transcription factor (YY1), beta protein 1 (BP1), chicken ovalbumin upstream promoter-transcription factor II (COUP-TFII), and paired box 1 (PAX-1). The last three motifs were conserved only in the noncoding regions of the HBG1 gene. The understanding of genetic elements involved in the maintenance of high Hb F levels may provide new efficient therapeutic strategies in the beta-hemoglobinopathies treatment, promoting reduction in clinical complications of these genetic disorders.

Influence of functional polymorphisms in TNF-α, IL-8, and IL-10 cytokine genes on mRNA expression levels and risk of gastric cancer.

Functional polymorphisms in promoter regions can produce changes in the affinity of transcription factors, thus altering the messenger ribonucleic acid (mRNA) expression levels of inflammatory cytokines associated with the risk of cancer development. The goal of this study was to evaluate the influence that polymorphisms in the cytokine genes known as TNF-α-308 G/A (rs1800629), TNF-α-857 C/T (rs1799724), IL-8-251 T/A (rs4073), IL-8-845 T/C (rs2227532), and IL-10-592 C/A (rs1800872) have on changes to mRNA expression levels and on the risks of chronic gastritis (CG) and gastric cancer (GC). A sample of 723 individuals was genotyped using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. Relative mRNA expression levels were measured using quantitative real-time PCR (qPCR). Polymorphisms TNF-α-308 G/A and IL-8-251 A/T were not associated with risks of these gastric lesions. However, TNF-α-857 C/T, IL-8-845 T/C, and IL-10-592 C/A were found to be associated with a higher risk of GC, and IL-10-592 C/A was found to be associated with a higher risk of CG. The relative mRNA expression levels (RQ) of TNF-α, IL-8, and IL-10 were markedly downregulated in the CG group (median RQs = 0.128, 0.247, and 0.614, respectively), while the RQ levels of TNF-α in the GC group were upregulated (RQ = 2.749), but were basal for IL-8 (RQ = 1.053) and downregulated for IL-10 (RQ = 0.179). When the groups were stratified according to wild-type and polymorphic alleles, only for IL-8-845 T/C the polymorphic allele was found to influence the expression levels of this cytokine. IL-8-845 C allele carriers were significantly upregulated in both groups (GC and CG; RQ = 3.138 and 2.181, respectively) when compared to TT homozygotes (RQ = -0.407 and 0.165, respectively). In silico analysis in the IL-8 promoter region revealed that the presence of the variant C allele in position -845 is responsible for the presence of the binding sites for two transcription factors (REL and CREB1), which are involved in increased gene expression. Polymorphic alleles were not shown to have any effect on the expression levels of TNF-α and IL-10. Taken together, our findings provide evidence for an association of TNF-α-857 C/T, IL-8-845 T/C, and IL-10-592 C/A with a higher risk of gastric cancer and also demonstrate the influence that the polymorphic C allele of IL-8-845 has on changes to the gene expression levels of this cytokine.

Pollution-induced metabolic responses in hypoxia-tolerant freshwater turtles.

The physiological control to support the absence of O2 for long periods of diving, and oxidative damage impact caused by the whole process of hypoxia/reperfusion in freshwater turtles is well known. However, effects of contaminants may act as co-varying stressors and cause biological damage, disrupting the hypoxia/reperfusion oxidative damage control. In order to investigate the action of environmental stressors present in domestic or industrial wastewater effluent, we performed a biochemical analysis of biotransformation enzymes, oxidative stress, as well as neuromuscular, physiological and morphological parameters in Phrynops geoffroanus, an hypoxic-tolerant freshwater turtle endemic of South America, using animals sampled in urban area, contaminated by sewage and industrial effluents and animals sampled in control area. Here we demonstrate the physiological and biochemical impact caused by pollution, and the effect that these changes cause in antioxidant activity. Animals from the urban area exhibited higher EROD (ethoxyresorufin-O-deethylase, CYP1A1), GST (glutathione S-transferase), G6PDH (glucose-6-phosphate deshydrogenase), AChE (acetilcholinesterase) activities and also TEAC (trolox-equivalent antioxidant capacity) and TBARS (thiobarbituric acid reactive substances) values. We examined whether two morphometric indices (K - condition factor and HIS - hepatosomatic index) which help in assessing the general condition and possible liver disease, respectively, were modified. The K of the urban animals was significantly decreased compared to the control animals, but the HIS value was increased in animals from the urban area, supporting the idea of an impact in physiology and life quality in the urban freshwater turtles. We propose that this freshwater turtle specie have the ability to enhance its antioxidants defenses in order to protect from tissue damage caused by hypoxia and reperfusion, but also that caused by environmental contamination and that the oxidative damage control in hypoxic conditions has resulted in an adaptive condition in hypoxic-tolerant freshwater turtle species, in order to better tolerate the release of contaminated effluents resulting from human activity.

Morphological, morphometrical and ultrastructural characterization of Phrynops geoffroanus' (Testudines: Chelidae) blood cells, in different environments.

The aim of this study was to evaluate the formed elements in the periferical blood of two amostral groups of Phrynops geoffroanus: one from an urban environment under domestic sewage dumping, and another from a non-contaminated environment. Blood samples of 36 animals (females and males) were collected through cardiocentesis. Sixteen specimens were from the urban environment, and 20 were from a control environment. Samples of blood tissue were used for light microscopy analysis, and also for morphometric analysis of red blood cells. For the ultrastructural analysis, blood samples of 2 animals were used. The formed elements found, using morphological and ultrastructural analysis were: nucleated red blood cells; thrombocytes; neutrophils, lymphocytes, monocytes, basophils; eosinophils; heterophils, and azurophils. The morphometric analysis of all red blood cells parameters examinated in females showed a statistically significant difference, but in males just the nuclear area showed difference between the specimens of the two environments. The elements identified by light microscopy were elucidated by electron transmission microscopy. This P. geoffroanus study is the first one that makes a correlation between these environments and the description of turtle's blood cells, thus contributing to the identification of the hematological characteristics of this group.