SARS-CoV-2 (COVID-19) infection is responsible for causing a disease with a wide spectrum of clinical presentations. Predisposition to thromboembolic disease due to excessive inflammation is also attributed to the disease. The objective of this study was to characterize the clinical and laboratory aspects of hospitalized patients, in addition to studying the pattern of serum cytokines, and associate them with the occurrence of thromboembolic events. Methodology: A retrospective cohort study with 97 COVID-19 patients hospitalized from April to August 2020 in the Triângulo Mineiro macro-region was carried out. A review of medical records was conducted to evaluate the clinical and laboratory aspects and the frequency of thrombosis, as well as the measurement of cytokines, in the groups that presented or did not present a thrombotic event. Results: There were seven confirmed cases of thrombotic occurrence in the cohort. A reduction in the time of prothrombin activity was observed in the group with thrombosis. Further, 27.8% of all patients had thrombocytopenia. In the group that had thrombotic events, the levels of IL1b, IL-10, and IL2 were higher (p < 0.05). Conclusions: In the studied sample, there was an increase in the inflammatory response in patients with thrombotic events, confirmed by the increase in cytokines. Furthermore, in this cohort, a link was observed between the IL-10 percentage and an increased chance of a thrombotic event.

Tegumentary leishmaniasis (TL) is caused by parasites of the genus Leishmania. Leishmania braziliensis (L.b) is one of the most clinically relevant pathogens that affects the skin and mucosa, causing single or multiple disfiguring and life-threatening injuries. Even so, the few treatment options for patients have significant toxicity, high dropout rates, high cost, and the emergence of resistant strains, which implies the need for studies to promote new and better treatments to combat the disease. Zinc oxide nanocrystals are microbicidal and immunomodulatory agents. Here, we develop new Ag-ZnO/xAgO nanocomposites (NCPs) with three different percentages of silver oxide (AgO) nanocrystals (x = 49%, 65%, and 68%) that could act as an option for tegumentary leishmaniasis treatment. Our findings showed that 65% and 68% of AgO inhibit the extra and intracellular replication of L.b. and present a high selectivity index. Ag-ZnO/65%AgO NCPs modulate activation, expression of surface receptors, and cytokine production by human peripheral blood mononuclear cells toward a proinflammatory phenotype. These results point to new Ag-ZnO/AgO nanocomposites as a promising option for L. braziliensis treatment.

Multiple sclerosis is mediated by self-reactive myelin T and B cells that lead to axonal and myelin damage. The immune response in multiple sclerosis involves the participation of CD4⁺ T cells that produce cytokines and chemokines. This participation is important to find markers for the diagnosis and progression of the disease. In our work, we evaluated the profile of cytokines and chemokines, as well as the production of double positive CD4⁺ T cells for the production of IFNγ IL-17 in patients with multiple sclerosis, at different stages of the disease and undergoing different treatments. We found that relapsing–remitting patients had a significant increase in IL-12 production. About IL-5, its production showed significantly higher levels in secondarily progressive patients when compared to relapsing–remitting patients. IFN-γ production by PBMCs from secondarily progressive patients showed significantly higher levels. This group also had a higher percentage of CD4⁺ IFNγ⁺ IL-17⁺ T cells. The combination of changes in certain cytokines and chemokines together with the presence of IFNγ⁺ IL-17⁺ double positive lymphocytes can be used to better understand the clinical forms of the disease and its progression.

Chagas disease is a neglected tropical disease caused by the parasite Trypanosoma cruzi. Despite the efforts and distinct methodologies, the search of antigens for diagnosis, vaccine, and drug targets for the disease is still needed. The present study is aimed at identifying possible antigens that could be used for diagnosis, vaccine, and drugs targets against T. cruzi using reverse vaccinology and molecular docking. The genomes of 28 T. cruzi strains available in GenBank (NCBI) were used to obtain the genomic core. Then, subtractive genomics was carried out to identify nonhomologous genes to the host in the core. A total of 2630 conserved proteins in 28 strains of T. cruzi were predicted using OrthoFinder and Diamond software, in which 515 showed no homology to the human host. These proteins were evaluated for their subcellular localization, from which 214 are cytoplasmic and 117 are secreted or present in the plasma membrane. To identify the antigens for diagnosis and vaccine targets, we used the VaxiJen software, and 14 nonhomologous proteins were selected showing high binding efficiency with MHC I and MHC II with potential for in vitro and in vivo tests. When these 14 nonhomologous molecules were compared against other trypanosomatids, it was found that the retrotransposon hot spot (RHS) protein is specific only for T. cruzi parasite suggesting that it could be used for Chagas diagnosis. Such 14 proteins were analyzed using the IEDB software to predict their epitopes in both B and T lymphocytes. Furthermore, molecular docking analysis was performed using the software MHOLline. As a result, we identified 6 possible T. cruzi drug targets that could interact with 4 compounds already known as antiparasitic activities. These 14 protein targets, along with 6 potential drug candidates, can be further validated in future studies, in vivo, regarding Chagas disease.

Dendritic cells (DCs) are a type of antigen-presenting cells that play an important role in the immune response againstTrypanosoma cruzi, the causative agent of Chagas disease.In vitroandin vivostudies have shown that the modulation of these cells by this parasite can directly affect the innate and acquired immune response of the host in order to facilitate its biological cycle and the spreading of the species. Many studies show the mechanisms by whichT. cruzimodulates DCs, but the interaction of these cells with the Mexican strains ofT. cruzisuch as Ninoa and INC5 has not yet been properly investigated. Here, we evaluated whether Ninoa and INC5 strains evaded the immunity of their hosts by modulating the biology and function of murine DCs. The CL-Brener strain was used as the reference strain. Herein, it was demonstrated that Ninoa was more infective toward bone marrow-derived dendritic cells (BMDCs) than INC5 and CL-Brener strains in both BMDCs of BALB/c and C57BL/6 mice. Mexican strains ofT. cruziinduced different cytokine patterns. In BMDCs obtained from BALB/c mice, Ninoa strain led to the reduction in IL-6 and increased IL-10 production, while in C57BL/6 mice Ninoa strain considerably increased the productions of TNF-αand IL-10. Also, Ninoa and INC5 differentially modulated BMDC expressions of MHC-II, TLR2, and TLR4 in both BALB/c and C57BL/6 mice compared to Brazilian strain CL-Brener. These results indicate thatT. cruziMexican strains differentially infect and modulate MHC-II, toll-like receptors, and cytokine production in DCs obtained from C57BL/6 and BALB/c mice, suggesting that these strains have developed particular modulatory strategies to disrupt DCs and, consequently, the host immune responses.

Leishmaniasis is a group of parasitic diseases with the potential to infect more than 1 billion people; however, its treatment is still old and inadequate. In order to contribute to changing this view, this work consisted of the development of complexes derived from M^I metal ions with thioureas, aiming to obtain potential leishmanicidal agents. The thiourea ligands (HL^R) were obtained by reactions of p-toluenesulfohydrazide with R-isothiocyanates and were used in complexation reactions with Ag^I and Au^I, leading to the formation of complexes of composition [M(HL^R)₂]X (M = Ag or Au; X = NO₃⁻ or Cl⁻). All compounds were characterized by FTIR, ¹H NMR, UV-vis, emission spectroscopy and elemental analysis. Some representatives were additionally studied by ESI-MS and single-crystal XRD. Their properties were further analyzed by DFT calculations. Their cytotoxicity on Vero cells and the extracellular leishmanicidal activity on Leishmania infantum and Leishmania braziliensis cells were evaluated. Additionally, the interaction of the complexes with the Old Yellow enzyme of the L. braziliensis (LbOYE) was examined. The biological tests showed that some compounds present remarkable leishmanicidal activity, even higher than that of the standard drug Glucantime, with different selectivity for the two species of Leishmania. Finally, the interaction studies with LbOYE revealed that this enzyme could be one of their biological targets.