👤 Gabriel Ribeiro Júnior

Understanding the immunopathogenesis of COVID-19 has yielded valuable insights into predicting adverse outcomes-particularly mortality. However, significant gaps persist in our comprehension of the complex interplay among the proposed pathophysiological mechanisms. Here, we aim to investigate the immunological factors associated with mortality in critically ill, unvaccinated COVID-19 patients admitted to the intensive care unit (ICU). We conducted a single-center, prospective study involving 56 unvaccinated COVID-19 patients admitted to the ICU. Plasma cytokine levels at admission were quantified using enzyme-linked immunosorbent assay (ELISA). Continuous variables were presented as median (IQR), and categorical variables as frequencies and percentages. Non-parametric tests assessed group differences. Logistic regression and receiver operating characteristic (ROC) curve analyses identified predictors of mortality, with bootstrapping (1000 re-samplings; 95 % BCa CI) applied for model validation. Deceased patients exhibited significantly higher levels of interleukin (IL)-1β, IL-2, IL-6, transforming growth factor (TGF)-β, and interferon (IFN)-γ compared to survivors. Conversely, IL-10 and IL-27 were associated with favorable outcomes. Logistic regression modeling identified elevated IL-2 and IFN-γ levels as significant predictors of mortality. Notably, individual ROC curve analyses demonstrated that IL-1β and TGF-β had excellent discriminatory ability for mortality, while IFN-γ, IL-2, and IL-27 showed very good to excellent discriminatory capacity. Our results indicate that distinct cytokine profiles differentiate survivors from non-survivors in critically ill, unvaccinated COVID-19 patients. These findings highlight the importance of cytokine dysregulation in severe COVID-19 cases and suggest potential targets for prognostic approaches. Further research is warranted to validate these results and translate them into effective clinical management strategies. Show less

This study explores the interaction between immune and cancer cells in the tumor microenvironment (TME) of cervical carcinoma (CC), with emphasis on tumor-associated macrophages (M2-TAMs) and the STAT3-NF-κB signaling pathway. It investigates how Treg cell polymorphisms and TAM infiltration through these pathways influence overall survival (OS) in CC patients. This prospective study follows 100 CC patients from 2018 to 2023 using qRT-PCR and immunohistochemistry on tumor samples, and flow cytometry on blood samples to evaluate immunosuppressive cytokines and Treg cell polymorphisms. High stromal CD163+204+ TAM density, mediated by STAT3/NF-κB, correlates with biomarkers such as Ki-67, VEGFα, and FOXP3 (p < 0.001). XPO5 expression is associated with increased STAT3, SNAIL, and HPV 16/18 levels. FOXP3 T allele deletion and HLA-G polymorphism in the blood of patients correlate with higher STAT3 tumor expression and elevated IL-4 and IL-17 blood cytokines. The CXCL12-CXCR4 axis shows a strong association with STAT3, SNAIL in TME and blood cytokines, including IL-6 and IL-12. Elevated CXCL12, CXCR4, and SNAIL expression in TME significantly increases mortality risk. These findings underscore the role of M2TAM infiltration and immune modulation in tumor progression and clinical outcomes in CC. Show less

Associations between the WNT5A rs566926 variant and non-syndromic orofacial cleft (NSOC) have been reported in different populations. This study aimed to investigate the role of the rs566926 single nucleotide polymorphism (SNP) in WNT5A and its interactions with SNPs in BMP4, FGFR1, GREM1, MMP2, and WNT3 in the occurrence of NSOC in a Brazilian population. A case-control genetic association study was carried out involving participants from four regions of Brazil, totaling 801 patients with non-syndromic cleft lip with or without cleft palate (NSCL±P), 273 patients with cleft palate only (NSCPO), and 881 health volunteers without any congenital condition (control). Applying TaqMan allelic discrimination assays, we evaluated WNT5A rs566926 in an ancestry-structured multiple logistic regression analysis, considering sex and genomic ancestry as covariates. Interactions between rs566926 and variants in genes involved in the WNT5A signaling pathway (BMP4, FGFR1, GREM1, MMP2, and WNT3) were also explored. WNT5A rs566926 was significantly associated with an increased risk of NSCL±P, particularly due to a strong association with non-syndromic cleft lip only (NSCLO), in which the C allele increased the risk by 32% (OR: 1.32, 95% CI: 1.04-1.67, p=0.01). According to the proportions of European and African genomic ancestry, the association of rs566926 reached significant levels only in patients with European ancestry. Multiple interactions were detected between WNT5A rs566926 and BMP4 rs2071047, GREM1 rs16969681 and rs16969862, and FGFR1 rs7829058. The WNT5A rs566926 polymorphism was associated with NSCL±P, particularly in individuals with NSCLO and high European ancestry. Epistatic interactions involving WNT5A rs566926 and variants in BMP4, GREM1, and FGFR1 may contribute to the risk of NSCL±P in the Brazilian population. Show less

The comprehension of dental pathogenesis and disorders derived from eruption failure requires a deep understanding of the molecular mechanisms underlying normal tooth eruption. As intense remodelling is needed during tooth eruption, we hypothesize that matrix metalloproteinase-1 (MMP-1) and acid phosphatase (ACP) play a role in the eruptive pathway degradation. We evaluated MMP-1-immunoexpression and the collagen content in the lamina propria at different eruptive phases. Immunohistochemistry and ultrastructural cytochemistry for detection of ACP were also performed. In the maxillary sections containing first molars of 9-, 11-, 13-, and 16-day-old rats, the birefringent collagen of eruptive pathway was quantified. MMP-1 and ACP-2 immunohistochemical reactions were performed and the number of MMP-1-immunolabelled cells was computed. Data were analyzed by one-way ANOVA and Tukey post-test ( Show less

Gestational exposure to air pollution is associated with negative outcomes in newborns and children. In a previous study, we demonstrated a synergistic negative effect of pre- and postnatal exposure to PM Show less