Healthcare workers exposed to COVID-19 patients present an inflammatory status and Th2/Th17/Th22 immune profile: findings from before vaccine application in Brazil.

Healthcare workers present an increased risk of contagion for the SARS-CoV-2 virus due to their labor exposure. Here, we describe the clinical, laboratory, and immunological characteristics of healthcare workers, before vaccine application, exposed to SARS-CoV-2-infected patients. We collected sociodemographic, clinical, and laboratory information from 50 professionals who worked during the COVID-19 pandemic at the Clinical Hospital of the Northwest in Brazil. The results showed that most workers are women, over 50 years old, and worked as nursing technicians. Approximately 56% of workers were positive for a previous infection by RT-PCR and/or anti-SARS-CoV-2-immunoglobulin tests. Increased levels of hematocrit, neutrophils, NK lymphocytes, and fibrinogen, were found in positive healthcare workers, suggesting a light inflammatory status. The immunological findings showed an increase in IL-17 production and a Th2/Th17/Th22 profile followed by high serology for anti-SARS-CoV-2 IgM and IgG. Those data reveal the importance of studies with healthcare workers to investigate if the continuous exposition to the virus may result in chronic activation of the immune system and/or pulmonary inflammation in this target group.

Memory elicitation, T-cell response and antibody production: an independent study of an inactivated entire virus vaccine (Coronavac).

Health professionals working to mitigate the COVID-19 pandemic are one of the main risk groups for the disease, being prioritized for vaccination. Considering this, the aim of this study was to analyze the immune response of these professionals immunized with CoronaVac in the first and second doses. Blood samples were collected after the first and second doses of the vaccine (CoronaVac) and used to investigate hematological and biochemical parameters, analysis of immunoglobulin production, cytokines, and gene expression profile, as well as the identification of subsets of immune cells. Post-first dose immunological phenotypic memory (CD27+) profiles (T CD4+, TCD8+ and CD19+) showed a significant increase, as did Monocyte APCs (CD80+HLA-DR+) in relation to the second dose. The cytokines IL-2, IL-6 and IFN-° showed increased values in relation to the other analyzed cytokines. The Th2/Th17 profile in the second dose was characterized by gene expression analysis. The production of IgM and IgG after vaccination showed statistically significant values in the comparison between doses. CoronaVac showed activation of APCs monocytes, memory response of T and B lymphocytes, with immunoglobulins production. This set of responses is characterized by the Th2/Th17 immunological profile.

Anti-inflammatory activity of novel thiosemicarbazone compounds indole-based as COX inhibitors.

BACKGROUND: In this article, a series of 20 new thiosemicarbazone derivatives containing indole were synthesized and evaluated for their anti-inflammatory potential. METHODS: The compounds were obtained through a synthetic route of only two steps, with yields that varied between 33.6 and 90.4%, and characterized by spectroscopic and spectrometric techniques. RESULTS: An initial screening through the lymphoproliferation assay revealed that compounds LT76, LT81, and LT87 were able to inhibit lymphocyte proliferation, with CC50 of 0.56 ± 0.036, 0.9 ± 0.01 and 0.5 ± 0.07 µM, respectively, better results than indomethacin (CC50 > 12 µM). In addition, these compounds were able to suppress the in-vitro production of TNF-α and NO, in addition to stimulating the production of IL-4. Reinforcing in-vitro assays, the compounds were able to inhibit COX-2 similar to Celecoxib showing greater selectivity for this isoform (LT81 SI: 23.06 versus Celecoxib SI: 11.88). Animal studies showed that compounds LT76 (64.8% inhibition after 6 h), LT81 (89% inhibition after 6 h) and LT87 (100% inhibition after 4 h) were able to suppress edema in mice after inoculation carrageenan with greater potency than indomethacin, and immunohistochemistry revealed that the groups treated with LT76, LT81 and LT87 reduced the expression of COX-2, similar or better results when compared to indomethacin. Complementarily, in-silico studies have shown that these compounds have a good pharmacokinetic profile, for respecting the parameters of Lipinski and Veber, showing their good bioavailability. CONCLUSIONS: These results demonstrate the potency of thiosemicarbazone derivatives containing indole and confirm their importance as scaffolds of molecules with notorious anti-inflammatory activity.

In Vitro and In Vivo Wound Healing and Anti-Inflammatory Activities of Babassu Oil (Attalea speciosa Mart. Ex Spreng., Arecaceae).

Babassu (Attalea speciosa Mart. ex Spreng., Arecaceae) is a palm tree endemic to Brazil and found mainly in the borders of Amazon forest, where the harvesting of its fruits is an important source of income for more than 300,000 people. Among the communities of coconut breakers women, babassu oil is used in culinary, as fuel, and mostly as medicinal oil for the treatment of skin wounds and inflammation. This study aimed to evaluate in vitro and in vivo the wound healing effects of babassu oil. In vitro, babassu oil increased the migration of L929 fibroblasts, inhibited the production of nitric oxide by LPS-stimulated peritoneal macrophages, and increased the levels of INF-γ and IL-6 cytokines production. In vivo, babassu oil accelerated the healing process in a full-thickness splinted wound model, by an increase in the fibroblasts number, blood vessels, and collagen deposition in the wounds. The babassu oil also increased the recruitment of inflammatory cells into the wound site and showed an anti-inflammatory effect in a chronic ear edema model, reducing ear thickness, epidermal hyperplasia, and myeloperoxidase activity. Thus, these data corroborate the use of babassu oil in folk medicine as a remedy to treat skin wounds.

COVID-19 pandemic outbreak: the Brazilian reality from the first case to the collapse of health services.

Coronavirus is associated with several infectious diseases that cause outbreaks in humans, such as SARS in 2002-2003 and MERS in 2012. In December 2019, COVID-19, promoted by the SARS-CoV-2 virus, was first reported in Wuhan (China) as a new coronavirus disease. This outbreak quickly reached a pandemic status, affecting at least 185 countries and territories to date on all continents. The first case of COVID-19 reported in São Paulo city (Brazil) occurred in February 26th. Days later, 182 suspected cases in 16 states were being monitored. In May 30th, 514,849 cases and 29,314 deaths were confirmed in Brazil comprising all 26 states and Federal District. The primary measure in order to contain the spread of SARS-CoV-2 involved social isolation. At that time there were not enough diagnostic tests to identify infected individuals and data were strongly associated with sub notifications. Nevertheless, the effectiveness of this measure largely depends on the individual's social responsibility. This measure has a severe economic and social impact, as in other countries. In this review, we present an overview and scientific perspectives of the evolution of COVID-19 from Brazilian databases in which climate and economic situations differ from China, European countries, and the USA.

Evaluation of the immunomodulatory effect against splenocytes of Balb/c mice of biflorin obtained from Capraria biflora by a new isolation method

Abstract Biflorin (6,9-dimethyl-3-(4-methylpent-3-en-1-yl) benzo[de]chromene-7,8-dione) is a promising substance that has been increasingly studied in the past decades due to its diverse pharmacological properties (i.e. antitumor, antioxidant, antiinflamatory, antimicrobial activity etc.). Aiming the comprehension of its antitumoral activity we investigated the cell proliferation and cytotoxicity habilities of biflorin against mice splenocytes Balb/c. Biflorin was able to stimulate mice splenocytes Balb/c in 48 h of incubation at a concentration of 20.2 µM. Its immunostimulation promoted the production of cytokines such as: TNF-α, IFN-γ, IL-2, IL-6 and IL-17, inducing the immune profile toward a Th1 response. Moreover, an original method which led to an excellent yield with less processing time compared to the methods described in the literature was developed to obtain biflorin, from sawdust of Capraria biflora L., Scrophulariaceae. This method shows a great potential of increasing the production of this pharmacological active compound.

Saline extract from Malpighia emarginata DC leaves showed higher polyphenol presence, antioxidant and antifungal activity and promoted cell proliferation in mice splenocytes.

Currently, the research of new natural compounds with biological potential demonstrates great ethnopharmacological importance. In this study, we evaluated the biological properties promoted by saline extract from Malpighia emarginata DC leaves, whose objective is to evaluate the antioxidant, antimicrobial and cytotoxicity potential. Phytochemical characterization was performed by UPLC-MS chromatography to identify the chemical compounds. For the antioxidant potential, DPPH, ATT and FRAP methods were used. The antibacterial and antifungal tests were performed evaluating the MIC50, MIC90, CMB and CMF parameters. Moreover, antibiofilm action was evaluated. Cytotoxicity and proliferation were performed using splenocytes from Balb/c mice and were evaluated by cytometry. We found a list of phenolic compounds among other bioactive compounds in the M. emarginata saline extract. In addition, higher antioxidant profile and antifungal activity against different strains of Candida spp. was promoted by the saline extract. Splenocytes showed greater cell viability (more than 90%) and showed higher proliferate index in 24 and 48 hours of incubation with the extract. Saline extract from Malpighia emarginata DC has potential action like antioxidant and antifungal agent without promote animal cell damage.

Immunomodulatory Effects of the Water-soluble Lectin from Moringa oleifera Seeds (WSMoL) on Human Peripheral Blood Mononuclear Cells (PBMC).

BACKGROUND: Moringa oleifera is used in traditional medicine as well as in food, cosmetic, and pharmaceutical industries. Water-soluble M. oleifera lectin (WSMoL) is an anionic protein isolated from the seeds of this tree. Until now, immune responses promoted by this lectin in human PBMC have not been investigated. OBJECTIVE: The main objective of this study was to investigate the immunomodulatory effects of WSMoL on human PBMC through measurement of lymphocytes subsets, cytokine and nitric oxide levels. METHODS: Human peripheral blood mononuclear cells (PBMC) were isolated through Ficoll technique, were incubated with WSMoL (10 µg/mL) for 24, 48 and 72 hours, and was performed immunophenotyping assay of lymphocytes and monocytes. Culture supernatants were used to determined cytokine and nitric oxide levels. Assays with cells subsets and cytokine production were performed through cytometry. Nitric oxide release assay was determinate by spectrophotometry. RESULTS: WSMoL induced the release of the cytokines TNF-α, IL-2, IL-6, IL-10 as well as nitric oxide. Incubation of PBMC with this lectin also led to activation of CD8+ T lymphocytes. CONCLUSION: WSMoL promotes immunomodulation in human PBMC inducing a potential wound healing profile and, in future in vivo assays, can be evaluated as adjuvant in immunosuppressive diseases and wound repair.

Investigation on the pharmacological profile of antimony(III) complexes with hydroxyquinoline derivatives: anti-trypanosomal activity and cytotoxicity against human leukemia cell lines.

Complexes [Sb(QN)(2)Cl] (1), [Sb(QC)(2)Cl] (2) and [Sb(QI)(2)Cl] (3) were obtained with 8-hydroxyquinoline (HQN), 5-chloro-8-hydroxyquinoline (HQC) and 5-chloro-7-iodo-8-hydroxyquinoline (clioquinol, HQI). The quinoline derivatives and their antimony(III) complexes were evaluated for their anti-trypanosomal activity as well as for their cytotoxicity against HL-60 and Jurkat human leukemia cell lines. Upon coordination to antimony(III) the anti-trypanosomal activity of HQC and HQI increases, the highest improvement being observed for complex (3), which was the most active among all studied compounds against both epimastigote and trypomastigote forms of Trypanosoma cruzi. All quinoline derivatives proved to be cytotoxic against both leukemia cell lineages. Upon coordination to antimony(III) the cytotoxicity of HQN improved against Jurkat leukemia cells. While SbCl(3) proved to be cytotoxic against HL-60 cells, it was not active against Jurkat cells. However, its coordination to the quinoline derivatives resulted in complexes with significant cytotoxicity against Jurkat cells.