Performance assessment of a new serological diagnostic test for COVID-19 with candidate peptides from spike and nucleocapsid viral proteins.

Numerous commercial tests for the serological diagnosis of COVID-19 have been produced in recent years. However, it is important to note that these tests exhibit significant variability in their sensitivity, specificity, and accuracy of results. Therefore, the objective of this study was to utilize bioinformatics tools to map SARS-CoV-2 peptides, with the goal of developing a new serological diagnostic test for COVID-19. Two peptides from the S protein and one from the N protein were selected and characterized in silico, chemically synthesized, and used as a serological diagnostic tool to detect IgM, IgG, and IgA anti-SARS-CoV-2 antibodies through the ELISA technique, confirmed as positive and negative samples by RT-qPCR or serology by ELISA. The results showed a sensitivity, specificity, Positive Predictive Value and Negative Predictive Value of 100% (p < 00001, 95% CI) for the proposed test. Although preliminary, this study brings proof-of-concept results that are consistent with the high-performance rates of the ELISA test when compared to other well-established methods for diagnosing COVID-19.

Effects of Probiotics on Inflammatory Biomarkers and Its Associations With Cardiac Autonomic Function in Women With Arterial Hypertension: A Secondary Analysis of a Randomized Clinical Trial.

Preclinical evidence suggests that probiotic administration may exert an anti-inflammatory effect and reduce autonomic dysfunction and blood pressure. This study evaluated the effects of probiotic therapy on inflammatory biomarkers and characterized the correlations between inflammation and cardiac autonomic function in women with arterial hypertension. Women were randomized into probiotics (n = 20) or placebo (n = 20). The probiotic group received 109 CFU/day of Lactobacillus (L.) paracasei LPC-37, L. rhamnosus HN001, L. acidophilus NCFM, and Bifidobacterium lactis HN019, and the placebo group received polydextrose. Clinical, electrocardiogram, heart rate variability (HRV) analysis, and cytokine levels were assessed at baseline and after 8 weeks. Women who received probiotics for 8 weeks had increased serum levels of IL-17A (p = 0.02) and decreased INF-γ (p = 0.02) compared to baseline. Probiotic supplementation increased serum levels of IL-10 compared to the placebo group (p = 0.03). Probiotic or placebo administration did not change serum levels of TNFα and IL-6. Serum levels of IL-2 (p = 0.001, and p = 0.001) and IL-4 (p = 0.001, and p = 0.001) were reduced in women receiving placebo or probiotics, respectively. Correlations between HRV indices and inflammatory variables showed that INF-γ was positively correlated with heart rate (HR) and sympathetic HRV indices and negatively correlated with vagal HRV indices. IL-10 was negatively correlated with HR and sympathetic HRV indices. IL-6 was negatively correlated with parasympathetic HRV indices and positively correlated with SD2/SD1 ratio. Probiotic therapy has a discreet anti-inflammatory effect in hypertensive women, and pro-inflammatory cytokines were negatively correlated with vagal modulation and positively correlated with sympathetic modulation of HRV. The clinical trial was registered in the Brazilian Registry of Clinical Trials (ReBEC) with the identification RBR-9mj2dt.

Evaluation of cardiac autonomic function and low-grade inflammation in children with obesity living in the Northeast Brazilian region.

OBJECTIVE: Evaluate autonomic function and low-grade inflammation and characterize the correlation between these variables in schoolchildren with obesity living in the Brazilian northeast region. METHODS: 84 children with obesity and 41 with normal weight were included in this cross-sectional study. Anthropometry, body composition, blood pressure (BP), inflammatory biomarkers, and heart rate variability (HRV) indexes were analyzed in children aged 7 to 11 years. RESULTS: children with obesity had increased systolic (p = 0.0017) and diastolic (p = 0.0131) BP and heart rate (p = 0.0022). The children with obesity displayed significantly lower SDNN, RMSSD, NN50, HF (ms), HF (nu), SD1, SD2, and higher LF (ms), LF (nu), LF/HF, SD1/SD2, DFA-α1, and DFA-α2, compared to normal weight. A lower and higher capacity for producing IL-10 (p = 0.039) and IL-2 (p = 0.009), respectively, were found in children with obesity compared to children with normal weight. Although IL-2, IL-4 and IL17A did not correlate with HRV parameters, IL-6 was positively correlated with SDNN, LF (ms) and SD2, TNF-α was positively correlated with LF/HF and SD1/SD2 ratio, and IFN-γ was positively correlated with SDNN, RMMSSD, NN50, LF (ms), HF (ms), SD1, and SD2. CONCLUSIONS: The findings suggest that children with obesity have impaired autonomic function and systemic low-grade inflammation compared to children within the normal weight range, the inflammatory biomarkers were correlated with HRV parameters in schoolchildren living in the northeastern region of Brazil.

Emergence of SARS-CoV-2 serotype(s): Is it a matter of time?

Since its identification in late 2019, SARS-CoV-2 has undergone numerous mutations, resulting in the emergence of several viral variants, which may differ in transmissibility, virulence and/or evasion from host immunity. Particularly, immunity-related changes have been well documented in the Omicron variant, including reports of escaping neutralizing antibodies induced by infection/vaccination with heterologous SARS-CoV-2 or used in serological therapy. These findings may encourage some discussions about the possibility that Omicron is a distinct SARS-CoV-2 serotype. To contribute to this issue, we combined concepts from immunology, virology and evolution and performed an interesting brainstorm on the hypothesis that Omicron is a distinct SARS-CoV-2 serotype. Furthermore, we also discussed the likelihood of emergence of SARS-CoV-2 serotypes over time, which may not necessarily be related to Omicron. Finally, insights into this topic may have direct implications for vaccine formulations, immunodiagnostic platforms and serological therapies, contributing to better management of future outbreaks or waves.

Cytokine Regulation from Human Peripheral Blood Leukocytes Cultured In Vitro with Silver Doped Bioactive Glasses Microparticles.

Bioactive glasses (BG) applications include tissue engineering for bone regeneration, coating for implants, and scaffolds for wound healing. BG can be conjugated to ions like silver, which might add some antimicrobial properties to this biomaterial. The immunomodulatory activity of ion-doped bioactive glasses particles was not investigated before. The aim of this work was to evaluate the cytotoxic and immunomodulatory effect of BG and silver-doped bioactive glass (BGAg) in human peripheral blood cells. BG and BGAg samples belonging to the system 58SiO2 •(36-x)CaO·6P2O5 ·xAg2O, where x = 0 and 1 mol%, respectively, were synthesized via sol-gel method and characterized. Cytotoxicity, modulation of cytokine production (TNF-α, IL-1ß, IL-6, IL-4, and IL-10), and oxidative stress response were investigated in human polymorphonuclear cells (PMNs) and peripheral blood mononuclear cells (PBMCs) cultures. Cell viability in the presence of BG or BGAg was concentration-dependent. In addition, BGAg presented higher PBMCs toxicity (LC50 = 0.005%) when compared to BG (LC50 = 0.106%). Interestingly, interleukin4 was produced by PBMCs in response to BG and BGAg in absence of phytohemagglutinin (PHA) and did not modulate PHA-induced cytokine levels. Subtoxic concentrations (0.031% for BG and 0.0008% for BGAg) did not change other cytokines in PBMCs nor reactive oxygen species (ROS) production by PMN. However, BG and BGAg particles decreased zymosan-induced ROS levels in PMN. Although ion incorporation increased BG cytotoxicity, the bioactive glass particles demonstrated a in vitro anti-inflammatory potencial. Future studies are needed to clarify the scavenger potential of the BG/BGAg particles/scaffolds as well as elucidate the effect of the anti-inflammatory potential in modulating tissue growth in vivo.

Mediators Go Together: High Production of CXCL9, CXCL10, IFN-γ, and TNF-α in HTLV-1-Associated Myelopathy/Tropical Spastic Paraparesis.

HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a chronic demyelinating and disabling syndrome caused by human T lymphotropic virus 1 (HTLV-1). Although the pathogenic mechanisms that lead to HAM/TSP outcome have not been elucidated, genetic and immunological factors may be involved in the myelopathy occurrence. This study aimed to compare cytokines, chemokines, and nitric oxide (NO) levels in asymptomatic and HAM/TSP HTLV-1-infected patients. The study group consisted of 21 HAM/TSP and 48 asymptomatic HTLV-1 patients. Chemokines (CCL5, CCL2, CXCL8, CXCL9, and CXCL10) and cytokines [IL-2, interferon gamma (IFN-γ), tumor necrosis factor alpha (TNF-α), IL-4, IL-6, and IL-10] were measured using cytometric bead array, whereas NO production was measured after reaction of supernatants with nitrate reduction solution. CXCL9 and CXCL10 chemokines levels were found to be higher in the HAM/TSP group. CXCL9 was also strongly correlated with CXCL10 and both CXCL9 and CXCL10 were moderately correlated with CCL2 and CCL5 levels, in both HAM/TSP and asymptomatic groups. There was no significant difference related to NO, IL-4, IL-6, and IL-10 levels between the clinical groups but TNF-α and IFN-γ levels were increased in HAM/TSP patients. Thus, factors such as CXCL9, CXCL10, TNF-α, and IFN-γ could be good prognostic biomarker candidates, and further studies may help to clarify their association with HAM/TSP immunopathogenesis.

Evaluation of hemagglutination activity of chitosan nanoparticles using human erythrocytes.

Chitosan is a polysaccharide composed of randomly distributed chains of ß-(1-4) D-glucosamine and N-acetyl-D-glucosamine. This compound is obtained by partial or total deacetylation of chitin in acidic solution. The chitosan-based hemostatic agents have been gaining much attention in the management of bleeding. The aim of this study was to evaluate in vitro hemagglutination activity of chitosan nanoparticles using human erythrocytes. The preparation of nanoparticles was achieved by ionotropic gelification technique followed by neutralization with NaOH 1 mol/L(-1). The hemagglutination activity was performed on a solution of 2% erythrocytes (pH 7.4 on PBS) collected from five healthy volunteers. The hemolysis determination was made by spectrophotometric analysis. Chitosan nanoparticle solutions without NaOH addition changed the reddish colour of the wells into brown, suggesting an oxidative reaction of hemoglobin and possible cell lysis. All neutralized solutions of chitosan nanoparticles presented positive haemagglutination, without any change in reaction color. Chitosan nanoparticles presented hemolytic activity ranging from 186.20 to 223.12%, while neutralized solutions ranged from 2.56 to 72.54%, comparing to distilled water. Results highlight the need for development of new routes of synthesis of chitosan nanoparticles within human physiologic pH.

The effect of Zymomonas mobilis culture on experimental Schistosoma mansoni infection.

C57Bl/10 male mice infected with Schistosoma mansoni were distributed into mixed, prophylactic and curative groups. A culture of Zymomonas mobilis was orally administered to mice. A 61% protection from the infection was observed in the curative group (p <0.05). Histopathological study of the livers and intestines showed similar results.