Search

BackgroundCytokines induced by SARS-CoV-2 infection play a crucial role in the pathophysiology of COVID-19 and hyperinflammatory responses have been associated with poor clinical outcomes, with progression to severe conditions or long-term subacute complications named as long-COVID-19.MethodsIn this cross-sectional study, we aimed to evaluate a set of antigen-specific inflammatory cytokines in blood from recovered COVID-19 individuals or who suffered a post-acute phase of SARS-CoV-2 infection compared to healthy individuals with no history of COVID-19 exposition or infection. Interferon-gamma (IFN-γ), IFN-γ-induced protein 10 (IP-10), tumor necrosis factor (TNF), IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12, and IL-17A were quantified by multiplex cytometric bead assay and enzyme-linked immunosorbent assay after stimulation of whole blood with recombinant Spike protein from SARS-CoV-2. Additionally, all participants have evaluated for anti-(S) protein-specific IgG antibodies. Clinical specimens were collected within two months of COVID-19 diagnosis.ResultsA total of 47 individuals were enrolled in the study, a median age of 43 years (IQR = 14.5), grouped into healthy individuals with no history of infection or exposure to SARS-CoV-2 (unexposed group; N = 21); and patients from the Health Complex of the Rio de Janeiro State University (UERJ), Brazil, who were SARS-CoV-2 positive by RT-PCR (COVID-19 group)-categorized as recovered COVID-19 (N = 11) or long-COVID-19 (N = 15). All COVID-19 patients presented at least one signal or symptom during the first two weeks of infection. Six patients were hospitalized and required invasive mechanical ventilation. Our results showed that COVID-19 patients had significantly higher levels of IFN-γ, TNF, IL-1β, IL-2, IL-6, IL-8, and IP-10 than the unexposed group. The long-COVID-19 group has presented significantly high levels of IL-1β and IL-6 compared to unexposed individuals, but not from recovered COVID-19. A principal-component analysis demonstrated 84.3% of the total variance of inflammatory-SARS-CoV-2 response in the first two components, and it was possible to stratify IL-6, TNF, IL-1β, IL-10, and IL-2 as the top-five cytokines which are candidates to discriminate COVID-19 group (including long-COVID-19 subgroup) and healthy unexposed individuals.ConclusionWe revealed important S protein-specific differential biomarkers in individuals affected by COVID-19, bringing new insights into the inflammatory status or SARS-CoV-2 exposition determination.

Leishmaniasis is a parasitic disease caused by several species of intracellular protozoa of the genus Leishmania that present manifestations ranging from cutaneous ulcers to the fatal visceral form. Leishmania Viannia braziliensis is an important species associated with American tegumentary leishmaniasis and the main agent in Brazil, with variable sensitivity to available drugs. The search for new therapeutic alternatives to treat leishmaniasis is an urgent need, especially for endemic countries. Not only is quercetin well known for its antioxidant activity in radical scavenging but also several other biological effects are described, including anti-inflammatory, antimicrobial, and pro-oxidant activities. This study aimed to investigate the flavonoid quercetin’s therapeutic potential in L. (V.) braziliensis infection. Quercetin showed antiamastigote (IC50 of 21 ± 2.5 µM) and antipromastigote (25 ± 0.7 µM) activities and a selectivity index of 22. The treatment of uninfected or L. (V.) braziliensis–infected macrophages with quercetin increased reactive oxygen species (ROS)/H202 generation without altering Nitric Oxide (NO) production. Oral treatment with quercetin of infected hamsters, starting at 1 week of infection for 8 weeks, reduced the lesion thickness (p > 0.01) and parasite load (p > 0.001). The results of this study suggest that the antiamastigote activity of the flavonoid quercetin in vitro is associated, at least in part, with the modulation of ROS production by macrophages. The efficacy of oral quercetin treatment in hamsters infected with L. (V.) braziliensis was presented for the first time and shows its promising therapeutic potential.

Although physical inactivity figures as one of the main causes attributed to mortality, the damage caused by excessive exercise is also a reality. Professional athletes, amateur or uncompetitive modalities beneficiaries are often affected by deleterious conditions resulting from excessive exercise, such as neurological, endocrine and immune origin. The thin line between losses and benefits of successive fatiguing sessions effort depends on the understanding of concepts and methodological training principles. Exercise may have a paradoxical relationship and its consistent prescription in terms of public health depends on a better understanding of their cellular mechanisms. In this sense, the purpose of this review was to explore a promising topic in sports science, able to contribute to elucidate such mechanisms: Th1 and Th2 profile of the immune response related with chronic exhausting exercise and overtraining.

Leishmaniasis is a neglected tropical disease with no effective vaccines. Actin, microtubules and the actin-based molecular motor myosin Va were investigated for their involvement in Leishmania braziliensis macrophage interactions. Results showed a decrease in the association index when macrophages were without F-actin or microtubules regardless of the activation state of the macrophage. In the absence of F-actin, the production of NO in non-activated cells increased, while in activated cells, the production of NO was reduced independent of parasites. The opposite effect of an increased NO production was observed in the absence of microtubules. In activated cells, the loss of cytoskeletal components inhibited the release of IL-10 during parasite interactions. The production of IL-10 also decreased in the absence of actin or microtubules in non-activated macrophages. Only the disruption of actin altered the production of TNF-α in activated macrophages. The expression of myosin Va tail resulted in an acute decrease in the association index between transfected macrophages and L. braziliensis promastigotes. These data reveal the importance of F-actin, microtubules, and myosin-Va suggesting that modulation of the cytoskeleton may be a mechanism used by L. braziliensis to overcome the natural responses of macrophages to establish infections.

Current therapeutic ways adopted for the treatment of leishmaniasis are toxic and expensive including parasite resistance is a growing problem. Given this scenario, it is urgent to explore treatment alternatives for leishmaniasis. The aim of this study was to evaluate the effect of 3-phenyl-lawsone (3-PL) naphthoquinone on Leishmania (Viannia) braziliensis infection, both in vitro and in vivo, using two local routes of administration: subcutaneous (higher dose) and tattoo (lower dose). In vitro 3-PL showed low toxicity for macrophages (CC50 >3200 µM/48h) and activity against intracellular amastigotes (IC50 = 193 ± 19 µM/48h) and promastigotes (IC50 = 116 ± 26 µM/72h), in which induced increased ROS generation. Additionally, 3-PL up-regulated the production of cytokines such as tumor necrosis factor alpha (TNF-α), monocyte chemotactic protein 1 (MCP-1), interleukin-6 (IL-6) and IL-10 in infected macrophages. However, the anti-amastigote action was independent of nitric oxide production. Treatment of hamsters infected with L. (V.) braziliensis from one week after infection with 3-PL by subcutaneous (25 µg/Kg) or tattooing (2.5 µg/Kg) route, during 3 weeks (3 times/week) or 2 weeks (2 times/week) significantly decreased the parasite load (p