Coronavirus disease 19 (COVID-19) is caused by SARS-Cov-2 and the manifestations of this infection range from an absence of symptoms all the way up to severe disease leading to death. To estimate the ...prevalence of past infection in a population, the most readily available method is the detection of antibodies against the virus. This study has investigated the prevalence of anti-SARS-CoV-2 antibodies in outpatients of the Hospital das Clinicas, in Sao Paulo city (Brazil), which is a large university hospital belonging to the public health system that cares for patients with complex diseases who need tertiary or quaternary medical care. Our serological inquiry was carried out for 6 weeks, with once-a-week blood sampling and included 439 patients from several outpatient services. Overall, 61 patients tested positive for anti-SARS-CoV-2 IgG (13.9%); 56.1 % of the patients live in Sao Paulo city, with the remaining living in other towns of the metropolitan area; 32.8% of the patients testing positive for IgG antibodies to SARS-CoV-2 were asymptomatic, 55.7% developed mild or moderate disease and 11.5% had to be hospitalized. The prevalence of SARS-CoV-2 positive serology was lower among patients who had received the seasonal influenza vaccine compared to the ones who did not. These findings may indicate that those individuals care more about health issues, and/or that they have a better access to health care and/or a better quality of health care service. The large proportion of patients who were unaware of having had contact with SARS-CoV-2 deserves attention, reflecting the scarcity of tests performed in the population.
We investigated the anti-SARS-CoV-2 post-vaccine response through serum and salivary antibodies, serum antibody neutralizing activity and cellular immune response in samples from health care workers ...who were immunized with two doses of an inactivated virus-based vaccine (CoronaVac) who had or did not have COVID-19 previously. IgA and IgG antibodies directed at the spike protein were analysed in samples of saliva and/or serum by ELISA and/or chemiluminescence assays; the neutralizing activity of serum antibodies against reference strain B, Gamma and Delta SARS-CoV-2 variants were evaluated using a virus neutralization test and SARS-CoV-2 reactive interferon-gamma T-cell were analysed by flow cytometry. CoronaVac was able to induce serum and salivary IgG anti-spike antibodies and IFN-γ producing T cells in most individuals who had recovered from COVID-19 and/or were vaccinated. Virus neutralizing activity was observed against the ancestral strain, with a reduced response against the variants. Vaccinated individuals who had previous COVID-19 presented higher responses than vaccinated individuals for all variables analysed. Our study provides evidence that the CoronaVac vaccine was able to induce the production of specific serum and saliva antibodies, serum virus neutralizing activity and cellular immune response, which were increased in previously COVID-19-infected individuals compared to uninfected individuals.
Staphylococcus aureus colonizes the skin of atopic dermatitis (AD) individuals, but the impact of its enterotoxins on the chronic activation of CD4
T cells demands further analysis. We aimed to ...analyze the CD4
T cell anergy profile and their phenotypic and functional features through differential expression of cellular activation markers, cytokine production and response to staphylococcal enterotoxin A (SEA). A panel of 84 genes relevant to T cell anergy was assessed by PCR array in FACS-sorted CD4
T cells, and the most prominent genes were validated by RT-qPCR. We evaluated frequencies of circulating CD4
T cells secreting single or multiple (polyfunctional) cytokines (IL-17A, IL-22, TNF, IFN-γ, and MIP-1β) and expression of activation marker CD38 in response to SEA stimulation by flow cytometry. Our main findings indicated upregulation of anergy-related genes (EGR2 and IL13) promoted by SEA in AD patients, associated to a compromised polyfunctional response particularly in CD4
CD38
T cells in response to antigen stimulation. The pathogenic role of staphylococcal enterotoxins in adult AD can be explained by their ability to downmodulate the activated effector T cell response, altering gene expression profile such as EGR2 induction, and may contribute to negative regulation of polyfunctional CD4
T cells in these patients.
Atopic dermatitis, commonly referred to as atopic eczema, is a persistent inflammatory skin disorder that predominantly manifests in children but may endure into adulthood. Its clinical management ...poses challenges due to the absence of a definitive cure, and its prevalence varies across ethnicities, genders, and geographic locations. The epigenetic landscape of AD includes changes in DNA methylation, changes in histone acetylation and methylation, and regulation by non-coding RNAs. These changes affect inflammatory and immune mechanisms, and research has identified AD-specific variations in DNA methylation, particularly in the affected epidermis. Histone modifications, including acetylation, have been associated with the disruption of skin barrier function in AD, suggesting the potential therapeutic benefit of histone deacetylase inhibitors such as belinostat. Furthermore, non-coding RNAs, particularly microRNAs and long non-coding RNAs (lncRNAs), have been implicated in modulating various cellular processes central to AD pathogenesis. Therapeutic implications in AD include the potential use of DNA methylation inhibitors and histone deacetylase inhibitors to correct aberrant methylation patterns and modulate gene expression related to immune responses and skin barrier functions. Additionally, the emerging role of lncRNAs suggests the possibility of using small interfering RNAs or antisense oligonucleotides to inhibit lncRNAs and adjust their regulatory impact on gene expression. In conclusion, the importance of epigenetic elements in AD is becoming increasingly clear as studies highlight the contribution of DNA methylation, histone modifications and, control by non-coding RNAs to the onset and progression of the disease. Understanding these epigenetic changes provides valuable insights for developing targeted therapeutic strategies.
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Abstract
Zika virus (ZIKV) is a clinically important flavivirus that can cause neurological disturbances in newborns. Here, we investigated comparatively the outcome of in vitro infection of newborn ...monocytes by ZIKV. We observed that neonatal cells show defective production of interleukin 1β, interleukin 10, and monocyte chemoattractant protein 1 in response to ZIKV, although they were as efficient as adult cells in supporting viral infection. Although CLEC5A is a classical flavivirus immune receptor, it is not essential to the cytokine response, but it regulates the viral load only in adult cells. Greater expression of viral entry receptors may create a favorable environment for viral invasion in neonatal monocytes. We are the first to suggest a role for CLEC5A in human monocyte infectivity and to show that newborn monocytes are interesting targets in ZIKV pathogenesis, owing to their ability to carry the virus with only a partial triggering of the immune response, creating a potentially favorable environment for virus-related pathologies in young individuals.
Zika virus infects newborn monocytes without triggering a significant cytokine response, suggesting that these cells are a silent replication site in viral pathogenesis. CLEC5A seems to be redundant in newborns, although it plays a role in the infection of adult monocytes.
DNA methylation is one of the epigenetic modifications that configures gene transcription programs. This study describes the DNA methylation profile of HIV-infected individuals with distinct ...characteristics related to natural and artificial viremia control. Sheared DNA from circulating mononuclear cells was subjected to target enrichment bisulfite sequencing designed to cover CpG-rich genomic regions. Gene expression was assessed through RNA-seq. Hypermethylation in virologic responders was highly distributed closer to Transcription Start Sites (p-value = 0.03). Hyper and hypomethylation levels within TSS adjacencies varied according to disease progression status (Kruskal-Wallis, p < 0.001), and specific differentially methylated regions associated genes were identified for each group. The lower the promoter methylation, the higher the gene expression in subjects undergoing virologic failure (R = - 0.82, p = 0.00068). Among the inversely correlated genes, those supporting glycolysis and its related pathways were hypomethylated and up-regulated in virologic failures. Disease progression heterogeneity was associated with distinct DNA methylation patterns in terms of rates and distribution. Methylation was associated with the expression of genes sustaining intracellular glucose metabolism in subjects undergoing antiretroviral virologic failure. Our findings highlight that DNA methylation is associated with latency, disease progression, and fundamental cellular processes.
Therapeutic vaccines based on monocyte-derived dendritic cells have been shown to be promising strategies and may act as complementary treatments for viral infections, cancers, and, more recently, ...autoimmune diseases. Alpha-type-1-polarized dendritic cells (aDC1s) have been shown to induce type-1 immunity with a high capacity to produce interleukin-12p70 (IL-12p70). In the clinical use of cell-based therapeutics, injectable solutions can affect the morphology, immunophenotypic profile, and viability of cells before delivery and their survival after injection. In this sense, preparing a cell suspension that maintains the quality of aDC1s is essential to ensure effective immunotherapy. In the present study, monocytes were differentiated into aDC1s in the presence of IL-4 and GM-CSF. On day 5, the cells were matured by the addition of a cytokine cocktail consisting of IFN-α , IFN-γ , IL-1β , TNF-α , and Poly I:C. After 48hr, mature aDC1s were harvested and suspended in two different solutions: normal saline and Ringer's lactate. The maintenance of cells in suspension was evaluated after 4, 6, and 8hr of storage. Cell viability, immunophenotyping, and apoptosis analyses were performed by flow cytometry. Cellular morphology was observed by electron microscopy, and the production of IL-12p70 by aDC1s was evaluated by ELISA. Compared with normal saline, Ringer's lactate solution was more effective at maintaining DC viability for up to 8hr of incubation at 4 or 22°C.
In this study, high-throughput sequencing of 16S rRNA amplicons and predictive PICRUSt functional profiles were used to perform a comprehensive analysis of the temporal bacterial distribution and ...metabolic functions of 19 bimonthly samples collected from July 2019 to January 2020 in the surface water of Billings Reservoir, São Paulo. The results revealed that most of the bacterial 16S rRNA gene sequences belonged to Cyanobacteria and Proteobacteria, which accounted for more than 58% of the total bacterial abundance. Species richness and evenness indices were highest in surface water from summer samples (January 2020), followed by winter (July 2019) and spring samples (September and November 2019). Results also showed that the highest concentrations of sulfate (SO
), phosphate (P), ammonia (NH
), and nitrate (NO
) were detected in November 2019 and January 2020 compared with samples collected in July and September 2019 (P < 0.05). Principal component analysis suggests that physicochemical factors such as pH, DO, temperature, and NH
are the most important environmental factors influencing spatial and temporal variations in the community structure of bacterioplankton. At the genus level, 18.3% and 9.9% of OTUs in the July and September 2019 samples, respectively, were assigned to Planktothrix, while 14.4% and 20% of OTUs in the November 2019 and January 2020 samples, respectively, were assigned to Microcystis. In addition, PICRUSt metabolic analysis revealed increasing enrichment of genes in surface water associated with multiple metabolic processes rather than a single regulatory mechanism. This is the first study to examine the temporal dynamics of bacterioplankton and its function in Billings Reservoir during the winter, spring, and summer seasons. The study provides comprehensive reference information on the effects of an artificial habitat on the bacterioplankton community that can be used to interpret the results of studies to evaluate and set appropriate treatment targets.
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