Sepsis is a lethal syndrome characterized by systemic inflammation and abnormal coagulation. Despite therapeutic advances, sepsis mortality remains substantially high. Herein, we investigated the role of the plasminogen/plasmin (Plg/Pla) system during sepsis. Plasma levels of Plg were significantly lower in mice subjected to severe compared with nonsevere sepsis, whereas systemic levels of IL-6, a marker of sepsis severity, were higher in severe sepsis. Plg levels correlated negatively with IL-6 in both septic mice and patients, whereas plasminogen activator inhibitor-1 levels correlated positively with IL-6. Plg deficiency render mice susceptible to nonsevere sepsis induced by cecal ligation and puncture (CLP), resulting in greater numbers of neutrophils and M1 macrophages, liver fibrin(ogen) deposition, lower efferocytosis, and increased IL-6 and neutrophil extracellular trap (NET) release associated with organ damage. Conversely, inflammatory features, fibrin(ogen), and organ damage were substantially reduced, and efferocytosis was increased by exogenous Pla given during CLP- and LPS-induced endotoxemia. Plg or Pla protected mice from sepsis-induced lethality and enhanced the protective effect of antibiotics. Mechanistically, Plg/Pla–afforded protection was associated with regulation of NET release, requiring Pla-protease activity and lysine binding sites. Plg/Pla are important host-protective players during sepsis, controlling local and systemic inflammation and collateral organ damage.

Nucleotide oligomerization domain (NOD)‐like receptor‐12 (NLRP12) has emerged as a negative regulator of inflammation. It is well described that the Th17 cell population increases in patients with early Rheumatoid Arthritis (RA), which correlates with the disease activity. Here, we investigated the role of NLRP12 in the differentiation of Th17 cells and the development of experimental arthritis, using the antigen‐induced arthritis (AIA) murine model. We found that Nlrp12 ^{−/ −} mice develop severe arthritis characterized by an exacerbated Th17‐mediated inflammatory response with increases in the articular hyperalgesia, knee joint swelling, and neutrophil infiltration. Adoptive transfer of Nlrp12 ^{−/ −} cells into WT mice recapitulated the hyperinflammatory response seen in Nlrp12 ^{−/ −} mice and the treatment with anti‐IL‐17A neutralizing antibody abrogated arthritis development in Nlrp12 ^{−/ −} mice, suggesting that NLRP12 works as an inhibitor of Th17 cell differentiation. Indeed, Th17 cell differentiation markedly increases in Nlrp12 ^−/− T cells cultured under the Th17‐skewing condition. Mechanistically, we found that NLRP12 negatively regulates IL‐6‐induced phosphorylation of STAT3 in T cells. Finally, pharmacological inhibition of STAT3 reduced Th17 cell differentiation and abrogated hyperinflammatory arthritis observed in Nlrp12 ^{−/ −} mice. Thus, we described a novel role for NLRP12 as a checkpoint inhibitor of Th17 cell differentiation, which controls the severity of experimental arthritis.

We aimed to evaluate whether the administration of riboflavin to septic animals reduces inflammation, oxidative stress, organ dysfunction, and mortality. C57BL/6 mice, 6-8 weeks old, were allocated to the study group (polymicrobial sepsis induced by cecal ligation and puncture (CLP) + antibiotic + iv riboflavin), control (CLP + antibiotic + iv saline), or naïve (non-operated controls). Serum concentrations of alanine aminotransferase (ALT), creatine kinase-MB (CK-MB), urea, and creatinine, and markers of inflammation [interleukin (IL)-6, tumor necrosis factor (TNF)-α, keratinocyte-derived chemokine (KC), and macrophage inflammatory protein (MIP)-2)], and oxidative stress (malondialdehyde (MDA) were measured 12 h after the experiment. Animal survival rates were calculated after 7 days. Means between groups were compared using linear regression models adjusted under the Bayesian approach. No significant difference was observed between control and study groups in serum concentrations of IL-6 (95% credible interval) (-0.35 to 0.44), TNF-α (-15.7 to 99.1), KC (-0.13 to 0.05), MIP-2 (-0.84 to 0.06), MDA (-1.25 to 2.53), or ALT (-6.6 to 11.5). Serum concentrations of CK-MB (-145.1 to -30.1), urea (-114.7 to -15.1), and creatinine (-1.14 to -0.01) were higher in the study group. Survival was similar in both groups (P=0.8). Therefore, the use of riboflavin in mice undergoing sepsis induced by CLP did not reduce inflammation, oxidative stress, organ dysfunction, or mortality compared with placebo.

Objective: To determine the prevalence of and risk factors for congenital toxoplasmosis in neonates treated in the public health network of the eastern region of the Brazilian Amazon, northern Tocantins state. Methods: A retrospective cohort study was conducted with neonates born to mothers with gestational toxoplasmosis who received care between 2017 and 2024. The outcome under analysis was positivity for immunoglobulin M in the electrochemiluminescence assay (CLIA). We estimated the prevalence of transplacental infection and respective 95% confidence intervals (95% CI) and its association with risk factors using the odds ratio (or) with a p-value < 0.05 in infected neonates before and after 16 gestational weeks at maternal infection diagnosis. Results: A total of 1142 neonates were surveyed, in which 496 were diagnosed with congenital toxoplasmosis (IgM positive), thus obtaining a prevalence of vertical transmission of 45.4%. The main risk factors for vertical transmission were the mother’s education level equal to or less than eight years, (OR = 1.5; 95% CI 1.2; 2.0) and having less than six prenatal consultations (OR = 22.8; 95% CI 3.0; 172.6). Conclusions: A high prevalence of congenital toxoplasmosis was observed, with higher rates of infection in neonates born to mothers with lower levels of education.

Toxoplasmosis is a parasitic disease associated with significant morbidity and mortality. This cross-sectional study aimed to determine the prevalence, associated risk factors, and ocular health outcomes related to Toxoplasma gondii seropositivity in 161 residents from four Quilombolas communities in the northern region of Tocantins, Brazilian Legal Amazon. Peripheral blood samples were collected and tested by Enzyme-Linked Immunosorbent Assay (ELISA) for Immunoglobulin G (IgG) and/or Immunoglobulin M (IgM) and Polymerase Chain Reaction (PCR), while a standardized form was used to collect sociodemographic, health, and behavioral data. Statistical analysis, conducted using Epi-Info 3.3.2, considered T. gondii seropositivity as the primary outcome, with a significance level less than 5% (p ≤ 0.05). An overall seroprevalence of 62.11% (100/161) was observed. Key risk factors significantly, as measured by the Odds Ratio (OR), associated with T. gondii seropositivity included being elderly (OR: 4.07, CI: 2.05–8.06, p < 0.01), having cats (OR: 5.56, CI: 2.74–22.27, p < 0.01), a low parental education level (OR: 2.97, CI: 1.46–6.02, p < 0.01), children playing on the ground (OR: 2.50, CI: 1.30–4.82, p < 0.01), and having a home vegetable garden (OR: 3.80, CI: 1.94–7.47, p < 0.01). Regarding ocular health, no conclusive direct association was established between T. gondii seropositivity and specific ocular manifestations when analyzed for children and the elderly separately. Observed ocular problems in the grouped population were primarily linked to age-related comorbidities rather than parasitic infection. High rates of T. gondii seropositivity, driven by specific environmental and socioeconomic factors, highlight the vulnerability of these communities, emphasizing the need for targeted preventive strategies.