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Background and Purpose: Leishmaniasis is a globally prevalent vector-borne disease caused by parasites of the genus Leishmania. The available chemotherapeutic drugs present problems related to efficacy, emergence of parasite resistance, toxicity and high cost, justifying the search for new drugs. Several classes of compounds have demonstrated activity against Leishmania, including icetexane-type diterpenes, previously isolated from Salvia and other Lamiaceae genera. Thus, in this study, compounds of Salvia procurrens were investigated for their leishmanicidal and immunomodulatory activities., Methods: The exudate of S. procurrens was obtained by rapidly dipping the aerial parts in dichloromethane. The compounds were isolated by column and centrifugal planar chromatography over silica gel. The effects on L. amazonensis growth, survival, membrane integrity, reactive oxygen species (ROS) generation, mitochondrial membrane potential and cytotoxicity of the compounds towards human erythrocytes, peripheral blood mononuclear cells and macrophages were evaluated. The effects on intracellular amastigote forms, nitric oxide (NO) and TNF-α production were also investigated., Results: The exudate from the leaves afforded the novel icetexane 7-hydroxyfruticulin A (1) as well as the known demethylisofruticulin A (2), fruticulin A (3) and demethylfruticulin A (4). The compounds (1-4) were tested against promastigotes of L. amazonensis and showed an effective inhibition of the parasite survival (IC 50 = 4.08-16.26 μM). In addition, they also induced mitochondrial ROS production, plasma membrane permeability and mitochondrial dysfunction in treated parasites, and presented low cytotoxicity against macrophages. Furthermore, all diterpenes tested reduced the number of parasites inside macrophages, by mechanisms involving TNF-α, NO and ROS., Conclusion: The results suggest the potential of 7-hydroxyfruticulin A (1) as well as the known demethylisofruticulin A (2),fruticulin A (3) and demethylfruticulin A (4) as candidates for use in further studies on the design of anti-leishmanial drugs., Competing Interests: Declaration of competing interest The authors declare that is no competing financial interest., (Copyright © 2024. Published by Elsevier GmbH.)

Sepsis is a potentially fatal clinical condition that results from an immune imbalance in the host during an infection. It presents systemic alterations due to excessive activation of pro-inflammatory mediators that contribute to inflammation, formation of reactive species, and tissue damage. Anti-inflammatory mediators are then extensively activated to regulate this process, leading to immune exhaustion and, consequently, immunosuppression of the host. Considering the biological activities of the nutraceutical Agaricus brasiliensis ( A. brasiliensis ), such as immunomodulatory, antioxidant, and antitumor activities, the present study investigated the therapeutic potential of the lipid fraction of A. brasiliensis (LF) in a model of lethal sepsis in mice ( Mus musculus ), induced by cecal ligation and perforation (CLP). The results showed that treatment of septic animals with LF or LF associated with ertapenem (LF-Erta) reduced systemic inflammation, promoting improvement in clinical parameters and increased survival. The data show a reduction in pro-inflammatory and oxidative stress markers, regulation of the anti-inflammatory response and oxidizing agents, and increased bacterial clearance in the peritoneal cavity and liver. Thus, it can be concluded that LF as a treatment, and in conjunction with antibiotic therapy, has shown promising effects as a hepatoprotective, antioxidant, antimicrobial, and immunomodulatory agent.

Background: Several risk factors have been involved in the poor clinical progression of coronavirus disease-19 (COVID-19), including ageing, and obesity. SARS-CoV-2 may compromise lung function through cell damage and paracrine inflammation; and obesity has been associated with premature immunosenescence, microbial translocation, and dysfunctional innate immune responses leading to poor immune response against a range of viruses and bacterial infections. Here, we have comprehensively characterized the immunosenescence, microbial translocation, and immune dysregulation established in hospitalized COVID-19 patients with different degrees of body weight., Results: Hospitalised COVID-19 patients with overweight and obesity had similarly higher plasma LPS and sCD14 levels than controls (all p < 0.01). Patients with obesity had higher leptin levels than controls. Obesity and overweight patients had similarly higher expansions of classical monocytes and immature natural killer (NK) cells (CD56 + CD16 - ) than controls. In contrast, reduced proportions of intermediate monocytes, mature NK cells (CD56 + CD16 + ), and NKT were found in both groups of patients than controls. As expected, COVID-19 patients had a robust expansion of plasmablasts, contrasting to lower proportions of major T-cell subsets (CD4 + and CD8+) than controls. Concerning T-cell activation, overweight and obese patients had lower proportions of CD4 + CD38 + cells than controls. Contrasting changes were reported in CD25 + CD127 low/neg regulatory T cells, with increased and decreased proportions found in CD4 + and CD8 + T cells, respectively. There were similar proportions of T cells expressing checkpoint inhibitors across all groups. We also investigated distinct stages of T-cell differentiation (early, intermediate, and late-differentiated - TEMRA). The intermediate-differentiated CD4 + T cells and TEMRA cells (CD4 + and CD8 + ) were expanded in patients compared to controls. Senescent T cells can also express NK receptors (NKG2A/D), and patients had a robust expansion of CD8 + CD57 + NKG2A + cells than controls. Unbiased immune profiling further confirmed the expansions of senescent T cells in COVID-19., Conclusions: These findings suggest that dysregulated immune cells, microbial translocation, and T-cell senescence may partially explain the increased vulnerability to COVID-19 in subjects with excess of body weight., (© 2024. The Author(s).)

Objective: To update the recommendations to support decisions regarding the pharmacological treatment of patients hospitalized with COVID-19 in Brazil., Methods: Experts, including representatives of the Ministry of Health and methodologists, created this guideline. The method used for the rapid development of guidelines was based on the adoption and/or adaptation of existing international guidelines (GRADE ADOLOPMENT) and supported by the e-COVID-19 RecMap platform. The quality of the evidence and the preparation of the recommendations followed the GRADE method., Results: Twenty-one recommendations were generated, including strong recommendations for the use of corticosteroids in patients using supplemental oxygen and conditional recommendations for the use of tocilizumab and baricitinib for patients on supplemental oxygen or on noninvasive ventilation and anticoagulants to prevent thromboembolism. Due to suspension of use authorization, it was not possible to make recommendations regarding the use of casirivimab + imdevimab. Strong recommendations against the use of azithromycin in patients without suspected bacterial infection, hydroxychloroquine, convalescent plasma, colchicine, and lopinavir + ritonavir and conditional recommendations against the use of ivermectin and remdesivir were made., Conclusion: New recommendations for the treatment of hospitalized patients with COVID-19 were generated, such as those for tocilizumab and baricitinib. Corticosteroids and prophylaxis for thromboembolism are still recommended, the latter with conditional recommendation. Several drugs were considered ineffective and should not be used to provide the best treatment according to the principles of evidence-based medicine and to promote resource economy.

Objective: To investigate the role of central obesity on immunometabolic response in peripheral blood mononuclear cells (PBMCs) from normal weight and overweight/obese young men., Methods: Eighteen individuals were classified as normal weight (NW; n = 9 - age: 25 ± 5 and BMI: 21.4 ± 1.7) and overweight/obese (OW; n = 9 - age: 29 ± 7 and BMI: 29.2 ± 2.7). The body composition was evaluated by dual-energy x-ray absorptiometry (DXA), waist circumference, and visceral and subcutaneous fat depots by ultrasound. Physical activity levels, metabolic parameters, immune phenotypic characterization, cytokine production by lipopolysaccharide (LPS) -stimulated whole blood cells and LPS or phorbol 12-myristate 13-acetate (PMA)-stimulated PBMC, and mitochondrial respiration in PBMCs were evaluated. Expression of AMP-activated protein kinase (AMPK), peroxisome proliferator-activated receptor gamma (PPAR-γ), nuclear factor-kappa B (NF-κB), toll-like receptor 4 (TLR-4), hypoxia-inducible factor-1 alpha (HIF-1α), and adrenergic receptor beta 1 and 2 (AR-β1 and β2) genes were evaluated in cultured PBMC using quantitative real-time polymerase chain reaction (qRT-PCR)., Results: Individuals with overweight/obese (OW) presented higher glucose (P = 0.009) and leptin (P = 0.010) than individuals with normal weight (NW). PBMCs of OW under stimulation with LPS presented a lower production of interleukin-10 (IL-10) (P = 0.011) and macrophage inflammatory protein-1alpha (MIP-1α) (P = 0.048) than NW. Mitochondrial respiration rates were not different between NW and OW subjects. Cultured PBMCs in LPS-stimulated condition indicated higher gene expression of AR-β2 in OW, while PMA-stimulated PBMCs presented lower expression of AMPK (P = 0.002) and higher expression of NF-κB (P=<0.0001) than NW. OW presented higher numbers of CD3 + CD4 + T cells (P = 0.009) and higher expression of programmed cell death protein 1 (PD-1) in CD8 + T cells (P = 0.001) than NW., Conclusion: Central obesity promoted reductions in interleukin 10 production response and increase in AR-β2 expressions in mitogen-stimulated PBMCs. Furthermore, central obesity altered the phenotype of PBMCs, also increasing the expression of PD-1 exhaustion markers in young adults., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2023 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.)

Obesity has been linked to cognitive decline and adverse effects on brain health. Zinc (Zn) is a mineral with important metabolic functions that can modulate obesity-related neurological impairment. Thus, the present study aimed to evaluate the effects of 12 weeks of Zn supplementation on the inflammatory profile, cognitive function, and mood of overweight or obese women through a double-blind, placebo-controlled study. The study included 42 women aged between 40 and 60, randomly divided into two groups: Zn supplementation (30 mg/day) or placebo for 12 weeks. Data regarding sociodemographic, anthropometric, dietary, and physical activity were collected. Mini-mental state examination (MMSE), verbal fluency test, clock drawing test, and Stroop test were performed. Anxiety and depression symptoms were assessed using the Beck anxiety inventory and the BDI-II, respectively. Saliva samples were collected to evaluate IL-1β, IL-6, TNF-α, insulin, nitrite, and Zn levels. Of the 42 participants (mean age 49.58 ± 6.46 years), 32 were included in the study analyses. Changes in body weight and macronutrient consumption were not different between placebo and Zn supplementation groups. Cognitive scores on the MMSE and Stroop tests were higher in the Zn supplementation group than in the placebo group. Salivary levels of IL-1b and Zn increased in the Zn group compared to placebo. There was no significant change in the adjusted means of the BDI-II and BECK scores between the zinc vs. placebo groups. Twelve weeks of Zn supplementation was able to partially improve the cognitive scores assessed in overweight or obese women, regardless of weight loss. These findings suggest that Zn supplementation can be considered an adjunct strategy to enhance cognitive health in overweight or obese women.

Aim: This study aimed to evaluate if physical activity is associated with systemic and cellular immunometabolic responses, in young adults after mild-to-moderate COVID-19 infection., Methods: Mild- to- moderate post-COVID-19 patients (70.50 ± 43.10 days of diagnosis; age: 29.4 (21.9- 34.9) years; BMI: 25.5 ± 4.3 kg m 2 n = 20) and healthy age-matched controls (age: 29.3 (21.2 - 32.6) years; BMI: 25.4 ± 4.7 kg m 2 ; n = 20) were evaluated. Physical activity levels (PAL), body composition, dietary habits, muscular and pulmonary function, mental health, sleep quality, metabolic parameters, immune phenotypic characterization, stimulated whole blood and PBMC culture (cytokine production), mRNA, and mitochondrial respiration in PBMCs were evaluated., Results: The post-COVID-19 group exhibited lower levels of moderate to vigorous physical activity (MVPA) (p = 0.038); therefore, all study comparisons were performed with adjustment for MVPA. Post-COVID-19 impacted the pulmonary function (FEV1, FEV1%pred, FVC, and FVC %pred) compared with the control (p adjusted by MVPA (p adj) <0.05). Post-COVID-19 exhibited lower levels of serum IL-6 (p adj <0.01), whereas it showed higher serum IL-10, triglyceride, leptin, IgG, ACE activity, TNFRSF1A, and PGE 2 (p adj <0.05) levels compared with controls. Post-COVID-19 presented a lower percentage of Treg cells (p adj = 0.03) and altered markers of lymphocyte activation and exhaustion (lower CD28 expression in CD8 + T cells (p adj = 0.014), whereas CD4 + T cells showed higher PD1 expression (p adj = 0.037)) compared with the control group. Finally, post- COVID-19 presented an increased LPS-stimulated whole- blood IL-10 concentration (p adj <0.01). When exploring mitochondrial respiration and gene expression in PBMCs, we observed a higher LEAK state value (p adj <0.01), lower OXPHOS activity (complex I) (p adj = 0.04), and expression of the Rev-Erb-α clock mRNA after LPS stimulation in the post-COVID-19 patients than in the control (p adj <0.01). Mainly, PAL was associated with changes in IL-10, triglyceride, and leptin levels in the plasma of post-COVID-19 patients. PAL was also associated with modulation of the peripheral frequency of Treg cells and the expression of PD-1 in CD8+ T cells, although it abrogated the statistical effect in the analysis of TNF-α and IL-6 production by LPS- and PMA-stimulated PBMC of post-COVID-19 patients., Conclusion: Young adults after mild-to-moderate SARS-CoV-2 infection appeared to have lower physical activity levels, which can be associated with clinical and immunometabolic responses in a complex manner., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Silva, Pereira, Minuzzi, Padilha, Figueiredo, Olean-Oliveira, dos Santos, von Ah Morano, Marchioto Júnior, Ribeiro, Dos Santos, Seelaender, Teixeira, Dos Santos, Lemos, Freire, Dorneles, Marmett, Olean-Oliveira, Teixeira, Seraphim, Caseiro, Pinho, Islam, Little, Krüger, Rosa-Neto, Coelho-E-Silva and Lira.)

The exposure to traffic-related air pollutants, such as NO 2 and O 3 , are associated with detrimental health effects, becoming one of the greatest public health issues worldwide. Exercising in polluted environments could result in harmful outcomes for health and may blunt the physiological adaptations of exercise training. This study aimed to investigate the influence of physical activity and O 3 exposure on redox status, an inflammatory marker, response to stress, and pulmonary toxicity of healthy young individuals. We performed a cross-sectional study with 100 individuals that, based on their exposure to O 3 and physical fitness (PF) level, were distributed in four groups: Low PF + Low O 3 ; Low PF + High O 3 ; High PF + Low O 3 ; High PF + High O 3 . We evaluated personal exposure to NO 2 and O 3, physical activity level, variables of oxidative stress (SOD, ROS, CAT, GSH, TBARS), pulmonary toxicity (CC16), and inflammatory mediators (IL-1β, IL-4, IL-6, IL-10, TNF-α, HSP70). Spearman correlation test to check the association among the variables was used and to compare groups we used one-way ANOVA followed by Bonferroni's post hoc and Kruskal Wallis test followed by Dunn's post hoc. O 3 levels correlated with physical activity (r = 0.25; p = 0.01) but not with age or markers of body composition (p > 0.05). The individuals with high physical fitness that were less exposed to O 3 presented higher CAT activity (p < 0.001), lower TBARS (p < 0.01) and IL-1β concentrations (p < 0.01), higher IL-6 (p < 0.05) and IL-10 concentrations (p < 0.05), lower IL-6:1L-10 ratio (p < 0.05), lower CC16 levels (p < 0.05), and higher HSP70 concentration (p < 0.05). Physical activity could result in higher exposure to O 3 that could partially blunt some exercise adaptations, while high physical fitness improved the antioxidant defense system, systemic inflammatory mediators, and pulmonary toxicity., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Promising results in improvement of nonalcoholic fatty liver disease and nonalcoholic steatohepatitis (NASH) have been identified following probiotic (PRO) treatment., Objectives: To evaluate PRO supplementation on hepatic fibrosis, inflammatory and metabolic markers, and gut microbiota in NASH patients., Methods: In a double-blind, placebo-controlled clinical trial, 48 patients with NASH with a median age of 58 y and median BMI of 32.7 kg/m 2 were randomly assigned to receive PROs (Lactobacillus acidophilus 1 × 10 9 colony forming units and Bifidobacterium lactis 1 × 10 9 colony forming units) or a placebo daily for 6 mo. Serum aminotransferases, total cholesterol and fractions, C-reactive protein, ferritin, interleukin-6, tumor necrosis factor-α, monocyte chemoattractant protein-1, and leptin were assessed. To evaluate liver fibrosis, Fibromax was used. In addition, 16S rRNA gene-based analysis was performed to evaluate gut microbiota composition. All assessments were performed at baseline and after 6 mo. For the assessment of outcomes after treatment, mixed generalized linear models were used to evaluate the main effects of the group-moment interaction. For multiple comparisons, Bonferroni correction was applied (α = 0.05/4 = 0.0125). Results for the outcomes are presented as mean and SE., Results: The AST to Platelet Ratio Index (APRI) score was the primary outcome that decreased over time in the PRO group. Aspartate aminotransferase presented a statistically significant result in the group-moment interaction analyses, but no statistical significance was found after the Bonferroni correction. Liver fibrosis, steatosis, and inflammatory activity presented no statistically significant differences between the groups. No major shifts in gut microbiota composition were identified between groups after PRO treatment., Conclusions: Patients with NASH who received PRO supplementation for 6 mo presented improvement in the APRI score after treatment. These results draw attention to clinical practice and suggest that supplementation with PROs alone is not sufficient to improve enzymatic liver markers, inflammatory parameters, and gut microbiota in patients with NASH. This trial was registered at clinicaltrials.gov as NCT02764047., (Copyright © 2023. Published by Elsevier Inc.)

Background: During the COVID-19 pandemic, the world experienced social distancing that resulted in changes in habits and lifestyle. Such changes can compromise healthy eating habits and the practice of physical activities, known risk factors for developing weight gain and obesity., Objective: The main objective of this study was to describe the change in eating habits, lifestyle, and cognition of the population of Rio Grande do Sul, a state in Southern Brazil, during social distancing due to COVID-19., Methods: The study was conducted from July 21 to August 10, 2020, through a structured online questionnaire that asked for sociodemographic information (age, gender, and education), anthropometric (reported weight and height), change in eating habits, lifestyle (sleep quality and physical activity), and cognition. Chi-square, McNemar tests, and univariate and multivariate analysis were used to evaluate the variables. Confidence intervals were calculated with a significance level of 5%., Results: Of a total of 1072 participants, 57.3% of respondents reported weight gain, and an increased percentage of people were classified as obese. Nearly half of the participants (46%) reported changes in their eating habits for the worse. Body mass index (BMI) was significantly associated with increased consumption of unhealthy foods. Our results identified high physical inactivity (46.9%) and obesity (19%) during social distancing. The changes in eating habits and lifestyle also increased the risk for decreased cognition., Conclusions: These findings highlighted that social distancing impacted eating habits and lifestyle, which increased obesity rates and might predispose to decreased cognition.

Objective: This study aimed to compare the influence of a high carbohydrate meal versus high-fat meal on the oxidation of substrates during an exercise incremental test., Materials and Methods: Ten untrained male subjects underwent two days of the protocol. Randomly, they received a high carbohydrate meal or a high-fat meal, receiving the other one in the next protocol. On both days, they performed an incremental treadmill test, with heart rate and maximal oxygen consumption to estimate the oxidation of substrates., Results: The high-fat meal showed an increase in the absolute amount of oxidized fat along with the incremental test ( P < 0.05; effect size = 0.9528), and a reduction in the respiratory exchange ratio at low intensities ( P < 0.05; effect size = 0.7765)., Conclusion: The meals presented no difference when compared to maximum oxidation point of substrates, the oxidation rate of substrates over time, and heart rate. A pre-test high-fat meal in untrained individuals was shown to be a modulating factor of total oxidized fats throughout the exercise, although it did not exert a significant effect on the rate of this oxidation over time.

The practice of physical activity (PA) is a non-pharmacological variable that alters the immune response through changes in cytokines and cellular immunity. Inversely latent cytomegalovirus (CMV) infection prematurely ages the immune system and contributes to the chronic inflammatory condition in several diseases and in aging. This study aimed to compare the association of the PA level and CMV serostatus on whole blood mitogen-stimulated cytokine production of young individuals. The resting blood samples were collected from 100 volunteers of both sexes assigned to one of six groups according to the degree of PA and CMV serostatus: sedentary CMV- (n = 15), moderate physical activity CMV- (moderate PA CMV -, n = 15), high physical activity CMV- (high PA CMV-, n = 15), sedentary CMV+ (n = 20), moderate physical activity CMV + (moderate PA CMV+, n = 20) and high physical activity CMV + (high PA CMV +, n = 20). The collected peripheral blood got diluted in supplemented RPMI-1640 culture medium and incubated for 48 h with a 2% concentration of phytohemagglutinin at 37ºC and CO2 at 5%. The supernatants were collected and used for the IL-6, IL-10, TNF-α, and INF-γ analysis by the ELISA method. The IL-10 concentration was higher in the Moderate PA and High PA groups when compared to the sedentary group, regardless of CMV status. The physically active (moderate and high PA) CMV+ individuals presented lower concentrations of IL-6 and TNF-α compared to CMV+ sedentary individuals, and the sedentary CMV+ subjects had a higher concentration of INF-γ compared to Sedentary CMV- subjects (p < 0.05). In summary, it is possible to infer that PA is key to controlling inflammation related to CMV infection. The stimulation of physical exercise is an important factor in controlling many diseases at the populational level., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest., (Copyright © 2023. Published by Elsevier B.V.)

Higher endotoxin in the circulation may indicate a compromised state of host immune response against coinfections in severe COVID-19 patients. We evaluated the inflammatory response of monocytes from COVID-19 patients after lipopolysaccharide (LPS) challenge. Whole blood samples of healthy controls, patients with mild COVID-19, and patients with severe COVID-19 were incubated with LPS for 2 h. Severe COVID-19 patients presented higher LPS and sCD14 levels in the plasma than healthy controls and mild COVID-19 patients. In non-stimulated in vitro condition, severe COVID-19 patients presented higher inflammatory cytokines and PGE-2 levels and CD14 + HLA-DR low monocytes frequency than controls. Moreover, severe COVID-19 patients presented higher NF-κB p65 phosphorylation in CD14 + HLA-DR low , as well as higher expression of TLR-4 and NF-κB p65 phosphorylation in CD14 + HLA-DR high compared to controls. The stimulation of LPS in whole blood of severe COVID-19 patients leads to lower cytokine production but higher PGE-2 levels compared to controls. Endotoxin challenge with both concentrations reduced the frequency of CD14 + HLA-DR low in severe COVID-19 patients, but the increases in TLR-4 expression and NF-κB p65 phosphorylation were more pronounced in both CD14 + monocytes of healthy controls and mild COVID-19 patients compared to severe COVID-19 group. We conclude that acute SARS-CoV-2 infection is associated with diminished endotoxin response in monocytes. KEY MESSAGES: Severe COVID-19 patients had higher levels of LPS and systemic IL-6 and TNF-α. Severe COVID-19 patients presented higher CD14+HLA-DRlow monocytes. Increased TLR-4/NF-κB axis was identified in monocytes of severe COVID-19. Blunted production of cytokines after whole blood LPS stimulation in severe COVID-19. Lower TLR-4/NF-κB activation in monocytes after LPS stimulation in severe COVID-19., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Sepsis is a severe global health problem, with high morbidity and mortality. In sepsis, one of the main affected organs is the liver. Hepatic alterations characterize a negative prognostic. Omega-3 fatty acids (ω3), eicosapentaenoic acid, and docosahexaenoic acid, are part of the main families of polyunsaturated fatty acids. ω3 has been used in studies as sepsis treatment and as a treatment for non-alcoholic liver disease., Aim: We aimed to evaluate the effects of treatment with fish oil (FO) rich in ω3 on liver changes and damage resulting from experimental sepsis., Methodology: A model of severe sepsis in Wistar rats was used. Oxidative stress in the liver tissue was evaluated by means of tests of thiobarbituric acid reactive substances, 2,7-dihydrodichlorofluorescein diacetate , catalase, and glutathione peroxidase, in the serum TBARS, DCF, thiols and, to assess liver dysfunction, alanine aminotransferase and aspartate aminotransferase. Hepatic tissue damage was evaluated using H&E histology., Results: In assessments of oxidative stress in liver tissue, a protective effect was observed in the tests of TBARS, DCF, CAT, and GPx, when compared the sepsis versus sepsis+ω3 groups. Regarding the oxidative stress in serum, a protective effect of treatment with ω3 was observed in the TBARS, DCF, and thiols assays, in the comparison between the sepsis and sepsis+ω3 groups. ω3 had also a beneficial effect on biochemical parameters in serum in the analysis of ALT, creatinine, urea, and lactate, observed in the comparison between the sepsis and sepsis+ω3 groups., Conclusion: The results suggest ω3 as a liver protector during sepsis with an antioxidant effect, alleviating injuries and dysfunctions., (© 2022 Indian National Association for Study of the Liver. Published by Elsevier B.V. All rights reserved.)

The aim of this study was to evaluate the systemic redox state and inflammatory markers in intensive care unit (ICU) or non-ICU severe COVID-19 patients during the hospitalization period. Blood samples were collected at hospital admission (T1) (Controls and COVID-19 patients), 5-7 days after admission (T2: 5-7 days after hospital admission), and at the discharge time from the hospital (T3: 0-72 h before leaving hospital or death) to analyze systemic oxidative stress markers and inflammatory variables. The reactive oxygen species (ROS) production and mitochondrial membrane potential (MMP) were analyzed in peripheral granulocytes and monocytes. THP-1 human monocytic cell line was incubated with plasma from non-ICU and ICU COVID-19 patients and cell viability and apoptosis rate were analyzed. Higher total antioxidant capacity, protein oxidation, lipid peroxidation, and IL-6 at hospital admission were identified in both non-ICU and ICU COVID-19 patients. ICU COVID-19 patients presented increased C-reactive protein, ROS levels, and protein oxidation over hospitalization period compared to non-ICU patients, despite increased antioxidant status. Granulocytes and monocytes of non-ICU and ICU COVID-19 patients presented lower MMP and higher ROS production compared to the healthy controls, with the highest values found in ICU COVID-19 group. Finally, the incubation of THP-1 cells with plasma acquired from ICU COVID-19 patients at T3 hospitalization period decreased cell viability and apoptosis rate. In conclusion, disturbance in redox state is a hallmark of severe COVID-19 and is associated with cell damage and death., (© 2022 John Wiley & Sons Ltd.)

Ozone (O 3 ) represents a great threat to human health, contributing to respiratory diseases and premature mortality. This pollutant is often considered a critical pollutant in regions of southern Brazil. Exposure to this pollutant during vigorous physical activity should be the subject of thorough investigations due to the increased ventilation rate and altered breathing pattern present during vigorous physical activity that result in greater inhalation of O 3 . Thus, this study aimed to evaluate the health risk of exposure to low, mean, and high concentrations of O 3 during different durations of exercise in the city of Rio Grande (southern Brazil). Healthy young men (n = 45) performed cardiopulmonary exercise testing, and ventilation rate data were collected to predict total ventilation and pollutant inhalation during a 5 km running session. The O 3 concentration in the city of Rio Grande was obtained from data reported by the Copernicus Atmosphere Monitoring Service (CAMS). The environmental health risk was calculated based on the potential intake dose. The lowest, mean, and highest concentrations of O 3 detected during the monitoring period were 32.5, 64.9, and 115.2 µg/m 3 , respectively. In all evaluated scenarios, there was a toxicological risk (RQ > 1), except when exercising when the O 3 concentration was lowest for the shortest length of time (p < 0.001). As the concentration of O 3 and the duration of the exposure increase, the health risk is increased. Therefore, O 3 concentration and duration of exposure are factors influencing the health risk of exercising. These findings are extremely relevant in cities that have high levels of O 3 , such as the city of Rio Grande., (© 2021. The Author(s), under exclusive licence to Springer Nature B.V.)

Purinergic signaling modulates immune function and is involved in the immunopathogenesis of several viral infections. This study aimed to investigate alterations in purinergic pathways in coronavirus disease 2019 (COVID-19) patients. Mild and severe COVID-19 patients had lower extracellular adenosine triphosphate and adenosine levels, and higher cytokines than healthy controls. Mild COVID-19 patients presented lower frequencies of CD4 + CD25 + CD39 + (activated/memory regulatory T cell [mTreg]) and increased frequencies of high-differentiated (CD27 - CD28 - ) CD8 + T cells compared with healthy controls. Severe COVID-19 patients also showed higher frequencies of CD4 + CD39 + , CD4 + CD25 - CD39 + (memory T effector cell), and high-differentiated CD8 + T cells (CD27 - CD28 - ), and diminished frequencies of CD4 + CD73 + , CD4 + CD25 + CD39 + mTreg cell, CD8 + CD73 + , and low-differentiated CD8 + T cells (CD27 + CD28 + ) in the blood in relation to mild COVID-19 patients and controls. Moreover, severe COVID-19 patients presented higher expression of PD-1 on low-differentiated CD8 + T cells. Both severe and mild COVID-19 patients presented higher frequencies of CD4 + Annexin-V + and CD8 + Annexin-V + T cells, indicating increased T-cell apoptosis. Plasma samples collected from severe COVID-19 patients were able to decrease the expression of CD73 on CD4 + and CD8 + T cells of a healthy donor. Interestingly, the in vitro incubation of peripheral blood mononuclear cell from severe COVID-19 patients with adenosine reduced the nuclear factor-κB activation in T cells and monocytes. Together, these data add new knowledge to the COVID-19 immunopathology through purinergic regulation., (© 2022 Wiley Periodicals LLC.)

Monocyte and lymphocyte subpopulations exhibit functions that vary between the anti- and pro-inflammatory spectrum, such as classic CD16- and non-classical CD16+monocytes, as well as T helper 2 lymphocytes (Th2), the Th1/Th17 lymphocytes ratio, and T regulatory lymphocytes (Treg). Metabolic disease-associated inflammation is accompanied by an imbalance in monocyte and lymphocyte phenotypes and functionality, as well as a stronger proportion of inflammatory subpopulations. These changes appear to be important for the development and progression of diseases like diabetes and cardiovascular disease. On the other hand, the regular practice of physical exercise is an important tool to restore the functionality of monocytes and lymphocytes, and to balance the subtypes ratio. However, key variables regarding exercise prescription, such as the type of exercise, intensity, and volume differentially impact on the acute and chronic immune response in individuals diagnosed with meta-inflammation diseases. Here, we discuss the impact of different physical exercise protocols, acutely and chronically, on monocytes and lymphocytes of individuals with metabolic disease-associated inflammation. In this review, we focus on the best effects of different exercise protocols to dose the "exercise pill" in different inflammatory status., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Aim: To evaluate the impact of exercise training plasma on in vitro prostate cancer cell viability and proliferation. Methods: PC3 prostate cancer cells were incubated with plasma obtained from young men with high and low physical fitness (PF) (high PF, n = 5; low PF, n = 5) and with the plasma collected from institutionalized older adults ( n = 8) before and after multimodal exercise training. Cell viability and proliferation, mitochondria membrane polarization, reactive oxygen species (ROS) generation, and apoptosis were evaluated after the cell treatment with plasma. Systemic cytokines were evaluated in the plasma of institutionalized older adults submitted to an exercise training protocol. Results: Plasma from high-PF men lowers both cell viability and proliferation after the incubation time. PC3 cells also presented lower cell viability and diminished rates of cell proliferation after the incubation with post-training plasma samples of the older adults. The incubation of PC3 cells with post-training plasma of older adults depolarized the mitochondrial membrane potential and increased mitochondrial reactive oxygen species production. Post-training plasma did not change apoptosis or necrosis rates in the PC3 cell line. Multimodal exercise training increased the plasma levels of IL-2, IL-10, IFN-α, and FGF-1 and decreased TNF-α concentrations in institutionalized older adults. Conclusion: Adaptations in blood factors of institutionalized older adults may alter cell viability and proliferation by targeting mitochondrial ROS in a prostate cancer cell line., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Peres, Branchini, Marmett, Nunes, Romão, Olean-Oliveira, Minuzzi, Cavalcante, Elsner, Lira and Dorneles.)

Monocytes play a major role in the initial innate immune response to SARS-CoV-2. Although viral load may correlate with several clinical outcomes in COVID-19, much less is known regarding their impact on innate immune phenotype. We evaluated the monocyte phenotype and mitochondrial function in severe COVID-19 patients (n = 22) with different viral burden (determined by the median of viral load of the patients) at hospital admission. Severe COVID-19 patients presented lower frequency of CD14 + CD16- classical monocytes and CD39 expression on CD14 + monocytes, and higher frequency of CD14 + CD16 + intermediate and CD14-CD16 + nonclassical monocytes as compared to healthy controls independently of viral load. COVID-19 patients with high viral load exhibited increased GM-CSF, PGE-2 and lower IFN-α as compared to severe COVID-19 patients with low viral load (p < 0.05). CD14 + monocytes of COVID-19 patients with high viral load presented higher expression of PD-1 but lower HLA-DR on the cell surface than severe COVID-19 patients with low viral load. All COVID-19 patients presented decreased monocyte mitochondria membrane polarization, but high SARS-CoV-2 viral load was associated with increased mitochondrial reactive oxygen species. In this sense, higher viral load induces mitochondrial reactive oxygen species generation associated with exhaustion profile in CD14 + monocytes of severe COVID-19 patients. Altogether, these data shed light on new pathological mechanisms involving SARS-CoV-2 viral load on monocyte activation and mitochondrial function, which were associated with COVID-19 severity., (Copyright © 2022. Published by Elsevier B.V.)

Background: Schizophrenia is a mental illness and its pharmacological treatment consists in the administration of antipsychotics like haloperidol. However, haloperidol often causes extrapyramidal motor disorders such as tardive dyskinesia (TD). So far, there is no effective treatment against TD and alternatives for it have been sought. Isoflafones have been studied as neuroprotector and inhibitor of monoamine oxidase enzyme. Thus, the objective is to evaluate the possible protective effect of isoflavones against the induction of involuntary movements induced by haloperidol in an animal model., Methods and Results: Male Wistar rats were treated with haloperidol (1 mg/kg/day) and/or isoflavones (80 mg/kg) for 28 days. Rats were submitted to behavioral evaluation to quantify vacuous chewing movements (VCM) and locomotor activity. In addition, the levels of pro-inflammatory cytokines were measured in the striatum. Haloperidol treatment reduced the locomotor activity and increased the number of VCM in rats. Co-treatment with isoflavones was able to reverse hypolocomotion and reduce the number of VCM. Besides, haloperidol caused significant increase in the proinflammatory cytokines (interleukin-1β:IL-1β, tumor necrosis factor-α: TNF-α and IL-6 and the co-treatment with isoflavones was able to reduce the levels of IL-1β and TNF-α, but not IL-6., Conclusions: It is believed that the beneficial effect found with this alternative treatment is related to its anti-inflammatory potential and to the action on estrogen receptors (based on scientific literature findings). Finally, further studies are needed to elucidate the mechanisms of isoflavones in reducing motor disorders induced by antipsychotics., (© 2021. The Author(s), under exclusive licence to Springer Nature B.V.)

The harmful effects of coronavirus disease 2019 (COVID-19) can reach the autonomic nervous system (ANS) and endothelial function. Therefore, the detrimental multiorgan effects of COVID-19 could be induced by deregulations in ANS that may persist after the acute SARS-CoV-2 infection. Additionally, investigating the differences in ANS response in overweight/obese, and physically inactive participants who had COVID-19 compared to those who did not have the disease is necessary. The aim of the study was to analyze the autonomic function of young adults after mild-to-moderate infection with SARS-CoV-2 and to assess whether body mass index (BMI) and levels of physical activity modulates autonomic function in participants with and without COVID-19. Patients previously infected with SARS-CoV-2 and healthy controls were recruited for this cross-sectional observational study. A general anamnesis was taken, and BMI and physical activity levels were assessed. The ANS was evaluated through heart rate variability. A total of 57 subjects were evaluated. Sympathetic nervous system activity in the post-COVID-19 group was increased (stress index; p = 0.0273). They also presented lower values of parasympathetic activity ( p < 0.05). Overweight/obese subjects in the post-COVID-19 group presented significantly lower parasympathetic activity and reduced global variability compared to non-obese in control group ( p < 0.05). Physically inactive subjects in the post-COVID-19 group presented significantly higher sympathetic activity than active subjects in the control group. Parasympathetic activity was significantly increased in physically active subjects in the control group compared to the physically inactive post-COVID-19 group ( p < 0.05). COVID-19 promotes changes in the ANS of young adults, and these changes are modulated by overweight/obesity and physical activity levels.

The C-C chemokine receptor type 5 (CCR5) plays a role in the immunopathogenesis of chronic kidney disease (CKD). Exercise has anti-inflammatory properties that may contribute to the rehabilitation of CKD patients. To date, the impact of the intradialytic exercise on CCR5 expression in monocytes and lymphocytes of CKD patients is unknown. We aimed to evaluate the effects of an acute intradialytic moderate-intensity exercise on CD4+CCR5+ T-cells and CD14+CCR5+ monocytes of elderly individuals with Chronic Kidney Disease (CKD). Eight CKD elderly patients performed a single bout of 20 min intradialytic exercise and a control hemodialysis (HD) session. Blood samples were collected at baseline, during and immediately after the trials. HD therapy increased the peripheral frequency of CD4+CCR5+ T-cells. The systemic CCL5 levels and the peripheral CD14+CCR5+ proportions increased during and after HD therapy. No significant alterations in CD4+CCR5+ and CD14+CCR5+ proportions or CCL5 levels were identified in CKD patients during and after intradialytic exercise. A negative correlation between the peripheral frequency of CD14+CCR5+ and the creatinine levels was identified in the intradialytic exercise session. A single moderate-intensity intradialytic exercise imposes an immunomodulatory impact in CKD elderly patients, preventing an excessive inflammatory response induced by hemodialysis.

Background: Long-term exposure to air pollution triggers metabolic alterations along with oxidative stress and inflammation, while exercise interventions are widely used to improve those parameters., Objective: Our study aimed to determine the effects of subchronic exposure to particulate matter 2.5 (PM 2.5 ) and endurance exercise training on glucose metabolism, oxidative stress, and inflammation of the heart and gastrocnemius muscle of rats., Material and Methods: Thirty-two male Wistar rats were assigned to 4 experimental groups: Untrained; Endurance training (ET); Untrained + PM 2.5 ; Endurance training + PM 2.5 . Rats exposed to air pollution received 50 µg of PM 2.5 via intranasal instillation daily for 12 weeks. Exercised groups underwent endurance training, consisting in running on an electronic treadmill (70% of maximal capacity, 5 days/week, 5 times/week) for 12 weeks. Glucose metabolism markers, redox state, and inflammatory variables were evaluated in the heart and gastrocnemius muscle., Results: ET and ET + PM 2.5 group had lower body mass gain and higher exercise capacity, and higher glycogen concentration in the heart and gastrocnemius muscle. In the heart, ET and ET + PM 2.5 groups had higher levels of GSH, and lower TBARS and TNF-α concentrations. In the gastrocnemius muscle, the ET group showed higher leptin and lower TBARS and IL-1β concentrations, ET and ET + PM 2.5 showed higher superoxide dismutase activity and ROS content., Conclusion: PM 2.5 exposure partially blunts metabolic and inflammatory adaptations in heart and gastrocnemius muscle tissues induced by exercise training.

Mucosal barrier alterations may play a role in the pathogenesis of several diseases, including COVID-19. In this study we evaluate the association between bacterial translocation markers and systemic inflammation at the earliest time-point after hospitalization and at the last 72 h of hospitalization in survivors and non-survivors COVID-19 patients. Sixty-six SARS-CoV-2 RT-PCR positive patients and nine non-COVID-19 pneumonia controls were admitted in this study. Blood samples were collected at hospital admission (T1) (Controls and COVID-19 patients) and 0-72 h before hospital discharge (T2, alive or dead) to analyze systemic cytokines and chemokines, lipopolysaccharide (LPS) concentrations and soluble CD14 (sCD14) levels. THP-1 human monocytic cell line was incubated with plasma from survivors and non-survivors COVID-19 patients and their phenotype, activation status, TLR4, and chemokine receptors were analyzed by flow cytometry. COVID-19 patients presented higher IL-6, IFN-γ, TNF-α, TGF-β1, CCL2/MCP-1, CCL4/MIP-1β, and CCL5/RANTES levels than controls. Moreover, LPS and sCD14 were higher at hospital admission in SARS-CoV-2-infected patients. Non-survivors COVID-19 patients had increased LPS levels concomitant with higher IL-6, TNF-α, CCL2/MCP-1, and CCL5/RANTES levels at T2. Increased expression of CD16 and CCR5 were identified in THP-1 cells incubated with the plasma of survivor patients obtained at T2. The incubation of THP-1 with T2 plasma of non-survivors COVID-19 leads to higher TLR4, CCR2, CCR5, CCR7, and CD69 expression. In conclusion, the coexistence of increased microbial translocation and hyperinflammation in patients with severe COVID-19 may lead to higher monocyte activation, which may be associated with worsening outcomes, such as death., (Copyright © 2021 Elsevier B.V. All rights reserved.)

We evaluated the impact of maximal exercise on oxidative stress and DNA damage in peripheral blood mononuclear cells (PBMC) from sedentary and exercised lean and obese men. PBMC were collected before, immediately and 1-h after exercise and exposed to hydrogen peroxide (H 2 O 2 ; 25 and 50 µM, 4 h). A leukocytosis was induced by maximal exercise immediately and 1-h after exercise in all groups. However, a lymphopenia was observed 1-h after exercise in the Sedentary obese group. In the control condition, low DNA damage index concomitant to increases in intracellular glutathione content (GSH) was identified immediately after exercise in all groups. However, higher DNA damage index and lipid peroxidation occurred 1-h after the bout in Sedentary and Exercised Obese groups. PBMC exposed to both H 2 O 2 25 and 50 µM experienced higher DNA damage and lipid peroxidation index immediately after exercise in all groups. Both lipid peroxidation and DNA damage index remained higher in PBMC of Sedentary Lean, Sedentary Obese, and Exercised obese groups obtained 1-h after exercise in both H 2 O 2 25 and 50 µM, with the highest values identified in PBMC from Sedentary Obese group. However, increases in GSH content were identified in treated PBMC from sedentary and exercised lean groups as well as exercised obese group 1-h after exercise. Habitual exercise confers increased resistance of PBMC to DNA damage induced by oxidative stress, reducing the detrimental effects of obesity.Keywords: Exercise, physical activity, DNA damage, obesity, mutagenesis, oxidative stress.

This study evaluated the effects of heat stress on the ex vivo inflammatory profile in untrained and trained men. Whole blood samples from untrained (UT) and trained (TR) individuals were incubated for 2 h at 37 °C or 40 °C. The whole blood of a subsample of the participants (n = 5 in both TR and UT groups) were stimulated with lipopolysaccharide (LPS, 10 ng/mL) concomitant to heat treatment (37 °C versus 40 °C). Flow cytometry was used to assess the intracellular NF-κB activation in CD4+ T cells and CD14+ monocytes, the expression of Toll-Like Receptor-4 (TLR-4), the frequencies of CD4+CD25-CD39+ and CD4+CD25+CD39+ T cells and monocyte subsets (CD14+CD16-; CD14+CD16+; CD14-CD16+), the mitochondrial membrane potential (MMP) and the reactive oxygen species (ROS) production by lymphocytes and monocytes. The production of interleukin (IL)-6, IL-10, and tumor necrosis factor-alpha (TNF-α) by LPS-stimulated whole blood were also evaluated. Heat treatment (40 °C) increased the proportions of CD14+CD16- and CD14+CD16+ monocytes and the lymphocyte MMP in the UT group. The frequencies of CD14-CD16+ monocytes and the activation of NF-κB in CD14+ monocytes decreased in UT and TR groups after heat treatment, while a reduction in CD4+CD25-CD39+ T-cells was observed only in the UT group. Higher TLR-4 and NF-κB activation were found in LPS-stimulated monocytes of UT men concomitant with higher TNF-α production and diminished IL-10 production after heat treatment. TR individuals presented lower NF- κB activation in LPS-stimulated monocytes after heat treatment. Our data suggest that the training status of individuals may impact on the anti-inflammatory response of heat treatment., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Illicit drug use can cause a variety of effects including alterations in the immune system. The aim of this study was to investigate the effects of illicit drugs on circulating lipopolysaccharide (LPS), systemic inflammation and oxidative stress markers in drug users. We evaluated the levels of soluble CD14 (sCD14), LPS, inflammatory (TNF-α and IL-6) and regulatory (IL-10) cytokines, as well as C-reactive protein (CRP), lipid peroxidation (TBARS) and total thiols in the peripheral blood of 81 men included in groups of cannabis (n = 21), cocaine (n = 12), cannabis-plus-cocaine users (n = 27), and non-drug users (n = 21). The use of cannabis plus cocaine leads to higher systemic levels of LPS, CRP, IL-6 and higher IL-6/IL-10 ratio, characterizing a proinflammatory profile. In contrast, a regulatory profile as viewed by lower systemic TNF-α and IL-6 levels and lower TNF-α/IL-10 ratio were observed in cannabis users compared to the control group. Moreover, cocaine users presented a lower content of non-enzymatic antioxidant thiol compared to control group, cannabis group and cannabis plus cocaine group. In conclusion, our results indicate that the use of cannabis contributes to an anti-inflammatory/or regulatory profile while the concomitant cannabis plus cocaine consumption coexists with increased circulating amounts of LPS and proinflammatory status., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Relationship between lymphocyte function and cardiorespiratory fitness (CRF) is well-documented at rest; however, upon mitogen stimulation the proliferation and cytokine production alters, but knowledge is incipient about lymphocyte responses after mitogen stimulus according to CRF. So, the purpose of the present study was to analyze the lymphocyte function according to the physical fitness status of healthy young men. The study is divided in two experiments being the first analyzing the lymphocyte phenotypes profile and the inflammatory responses, according to CRF, in lymphocyte cell cultures treated for 48 h with concanavalin A (ConA). The second experiment analyzed the proliferation, reactive oxygen species production, viability, and mitochondrial polarization state in lymphocytes treated with ConA in different concentrations, considering the CRF levels. The results showed a difference in the percentage of total lymphocytes expression between groups ( P = 0.011) observing a lower lymphocytes T expression in the group with high maximal oxygen consumption (V̇o 2max ) when compared with the moderate V̇o 2max group. When treated with ConA, the lymphocytes of the low V̇o 2max group released higher TNF-α concentration ( P = 0.032), reflecting an elevated TNF-α/IL-10 ratio ( P = 0.055), parallel with lower IL-6 production ( P = 0.027), mainly when compared with the moderate V̇o 2max group. In addition, there is a positive relationship between V̇o 2max and IL-6 production (r = 0.507; P = 0.016), whereas the percentage of total lymphocytes (LyT%) shows a negative trend with V̇o 2max (r = -0.497; P = 0.060). Also, individuals with lower V̇o 2max showed reduced absolute and relative ROS production, lower cell proliferation, and higher mitochondrial membrane depolarization. In conclusion, cardiorespiratory fitness degree exerts a strong impact on lymphocyte function after mitogen stimulation. NEW & NOTEWORTHY The innovation of the research is to elucidate the impact of different physical fitness status on metabolism, cell proliferation, and lymphocyte activity and, consequently, on the specific inflammatory response against a mitogen.

Sepsis is characterized by a dysregulated immune response to infection characterized by an early hyperinflammatory and oxidative response followed by a subsequent immunosuppression phase. Although there have been some advances in the treatment of sepsis, mortality rates remain high, urging for the search of new therapies. β -Lapachone ( β -Lap) is a natural compound obtained from Tabebuia avellanedae Lorentz ex Griseb. with several pharmacological properties including bactericidal, anti-inflammatory, and antioxidant activity. Thus, the aim of this study was to evaluate the effects of β -Lap in a mouse sepsis model. To this, we tested two therapeutic protocols in mice submitted to cecal ligation and puncture- (CLP-) induced sepsis. First, we found that in pretreated animals, β -Lap reduced the systemic inflammatory response and improved bacterial clearance and mouse survival. Moreover, β -Lap also decreased lipid peroxidation and increased the total antioxidant capacity in the serum and peritoneal cavity of septic animals. In the model of severe sepsis, the posttreatment with β -Lap was able to increase the survival of animals and maintain the antioxidant defense function. In conclusion, the β -Lap was able to increase the survival of septic animals by a mechanism involving immunomodulatory and antioxidant protective effects., Competing Interests: The authors declare no competing interests., (Copyright © 2020 Ana L. de B. Oliveira et al.)

In this study, we evaluated the effects of autologous serum collected after two types of exercise on the in vitro inflammatory profile and T cell phenotype of resting peripheral blood mononuclear cells (PBMCs) in obese men. Serum samples and PBMCs were obtained from eight obese men who performed two exercise bouts-high intensity interval exercise (HIIE) and exhaustive exercise session to voluntary fatigue-in a randomized cross-over trial. Pre-exercise PBMCs were incubated with 50% autologous serum (collected before and after each exercise bout) for 4 h. In vitro experiments revealed that post-HIIE serum reduced the histone H4 acetylation status and NF-κB content of PBMCs and suppressed the production of both TNF-α and IL-6 by PBMCs, while increasing IL-10 production. Post-exhaustive exercise serum induced histone H4 hyperacetylation and mitochondrial depolarization in lymphocytes and increased TNF-α production. In vitro post-HIIE serum incubation resulted in an increase in the frequencies of CD4 + CTLA-4 + and CD4 + CD25+ T cells expressing CD39 and CD73. Post-exhaustive exercise serum decreased the frequency of CD4 + CD25 + CD73+ T cells but increased CD4 + CD25-CD39 + T cell frequency. Both post-exercise serums increased the proportions of CD4 + PD-1 + and CD8 + PD-1+ T cells. Blood serum factors released during exercise altered the immune response and T cell phenotype. The type of exercise impacted the immunomodulatory activity of the post-exercise serum on PBMCs.

The aim of this study was to evaluate the inflammatory (peripheral and lipopolysaccharide (LPS)-stimulated released from whole blood) and metabolic (glucose and insulin) profile of inactive obese men in response to two isoenergetic models of aerobic exercise training (~300  kcal each exercise session). Twenty-two participants (28.7 ± 1.6 years; BMI = 34.4 ± 0.1 kg/m 2 ) were randomized into two groups: I) HIIT: high-intensity interval training (10× 1 bout: 1 min - 100% Maximal Aerobic Velocity) or II) MICT: moderate-intensity continuous training (65% Maximal Aerobic Velocity; kcal equal to HIIT). Both groups trained three times per week for 6-weeks. Fasting blood samples were collected before and 0, 30, and 60 min after exercise during the first and last training sessions for evaluation of: I) MIP-1ɑ, insulin, glucose, visceral and subcutaneous fat depots, oral glucose tolerance test, and homeostatic model assessment of insulin resistance (HOMA-IR) index; II) Peripheral (TNF-α, IL-6, and IL-10) and LPS-stimulated release of TNF-α and IL-10 were analyzed before, 0, and 60 min after sessions. IL-6 concentration remained elevated up to 60-min after the acute exercise session (p < 0.001), and IL-10 concentration was higher after 30 and 60-min (p = 0.001) compared to rest, independent of training period and protocol. AUC of IL-10 presented effect of type of training (p = 0.023) with MICT group showed significantly higher values than the HIIT. The ex-vivo assay showed higher IL-10 secretion in response to LPS immediately (p = 0.003) after both acute MICT and HIIT exercise sessions, independent of training period. Fifteen subjects presented decreased HOMA-IR after 6-weeks and seven presented an increase in this index. When we excluded the two least responsive subjects, it was possible to observe a decrease in HOMA-IR (p = 0.020) after training. Taken together, our results suggest that both HIIT and MICT (with same energy expenditure) promote similar effects on HOMA-IR and led to elevations in IL-10 production in LPS-stimulated whole blood, suggesting that leukocytes had an enhanced ability to secrete anti-inflammatory cytokines after the exercise bout., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

The urbanization process resulted in incredible achievements for society, unfortunately together with economic, social, and technological development it deteriorates air quality and encourages sedentary behavior. Air pollution inhalation is responsible for a massive negative health effect. The practice of regular physical exercise is strongly encouraged to achieve a healthy lifestyle. However, particularly during a physical exercise session, the respiratory system undergoes some physiological adaptations that lead to an increase in the volume of inhaled air, so exercising in a polluted environment would consequently augment the number of pollutants inhaled. In this scenario, would it be safer to stay physically inactive? Or to choose an indoor facility to exercise? Or to keep performing outdoor activities once the benefits achieved with exercise will overcome the possible damage caused by additional exposure to air pollution? Currently, these questions still do not have a decisive answer, so we designed a hypothesis to be tested in which exercise would be beneficial regardless of the chosen place. Outdoor and indoor pollution are both equally harmful to health, however, we do not know if it would have a difference to exercise in one of them., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Introduction: Some foods are also demonstrated benefits, such as anti-inflammatory, antioxidant, and ergogenic activity, similar to that of sports supplements. Grape juice has been considered an important source of polyphenols and these compounds could promote positive effects to the sports players. In this sense, the objective was to evaluate the effects of purple grape juice consumption on indicators of oxidative stress, inflammation, muscle damage, global histone H4 acetylation levels, and muscle strength and muscle power in volleyball athletes., Methods: This is a randomized double-blind clinical trial in which 12 male volleyball players (16 ± 0.6 years old) participated in three different moments with match simulation: control (without beverage) (WB), grape juice (GJ) and placebo (PLA) (400 mL/day of grape juice or placebo (maltodextrin) for 14 days in a cross-over model). Before and immediately after each match, blood collection for analysis of indicators of systemic redox status, systemic concentrations of Interferon-γ (IFN- γ) and Interleukin-4 (IL-4), muscle damage, by Creatine Kinase (CK-NAC) and levels of global histone H4 acetylation were performed, as well as handgrip strength (HG) and lower limb power tests., Results: Consumption of grape juice significantly reduced lipid peroxidation (p = 0.04) and Deoxyribonucleic Acid (DNA) damage (p = 0.01) after the match. IFN-γ levels, IL-4, CK-NAC, and histone H4 acetylation post-match did not alter with the grape juice consumption. Lower limb power improved after acute exercise in WB and GJ conditions (p < 0.001)., Conclusion: In this pilot trial, the intake of grape juice for two weeks seems to reduce the protein oxidation and DNA damage by intermittent physical exercise, without epigenetics influence., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Obesity and physical inactivity threaten human health, and both could be solved with exercise. However, a higher amount of pollutants is inhaled during exercise. Exposure to air pollution increases the incidence and progression of diseases. Therefore, the aim of the study was to investigate the rate of pollution inhalation of lean, overweight, and obese individuals in a low and high-intensity hypothetical exercise session. Healthy sedentary men (n = 135) classified as lean, overweight, or obese were enrolled in our study. All participants performed a cardiopulmonary exercise testing (CPX) to collect ventilation rate (VE) data, which was used to predict total ventilation and pollutant inhalation of a 5-km running session. Air pollutant concentration of São Paulo City, Brazil was evaluated and the toxicological risk was estimated based on the potential intake dose. The concentrations of PM 2.5 were 29.57 μg/m 3 and 51.71 μg/m 3 , PM 10 were 45.85 μg/m 3 and 74 μg/m 3 , NO 2 were 63.71 μg/m 3 and 66.65 μg/m 3 , and O 3 were 69 μg/m 3 and 37 μg/m 3 , respectively in the summer and winter. In the hypothetical exercise session, total VE and time in both the first and second threshold were increased in the obese group (p < 0.001) (p < 0.001). The inhalation of PM 2.5 , PM 10 , NO 2 , and O 3 , during the hypothetical session, was increased in obese individuals (p < 0.001). Obese individuals should be considered a susceptible population, once they are more exposed to air pollution during exercise.

Background and Aims: The main aim of this study was to analyze how the lipid accumulation affects the whole-body fat oxidation over a range of intensities during a submaximal incremental exercise test in post-menopausal overweight-obese women., Patients and Methods: The maximal fat oxidation (MFO), the intensity where the MFO occurs (FatMax), fat oxidation were measured over a range of intensities during a submaximal incremental exercise test through indirect calorimetry in 60 postmenopausal overweight-obese women (aged>49 years; body mass index 28.0 to 39.0 kg/m²). The metabolic profile of participants was evaluated and the LAP index was calculated (waist-58×triglycerides [mmol/L]). A cutoff point of 34.5 was adopted and participant were designed as low LAP index (n=30) or high LAP index (n=30)., Results: During submaximal exercise postmenopausal overweight-obese women with low LAP index showed a higher fat oxidation at 50% (0.53±0.05 vs. 0.45±0.12 g/min; p=0.01), 60% (0.40±0.06 vs. 0.31±0.16 g/min; p=0.02) and 70% (0.34±0.08 vs. 0.25±0.15 g/min; p=0.03) of VO 2Peak than those with high LAP index. No significant difference was observed in carbohydrate oxidation between groups (p>0.05) during exercise. Moreover, a significant difference in absolute MFO (p=0.018), MFO relative to free fat mass (p=0.043) and FatMax (p=0.002) was identified., Conclusion: Postmenopausal overweight-obese women who showed unhealthy metabolic phenotype evaluated through LAP index presented low fat oxidation during a submaximal incremental exercise., Competing Interests: No conflict of interest has been declared by the authors., (© Georg Thieme Verlag KG Stuttgart · New York.)

Background: Heart rate variability (HRV) a feasible predictor of prognosis in cardiovascular outcomes shown to be reduced in people living with HIV (PLWH)., Objective: This study sought to understand the effects of short-term aerobic training (AT) on the resting HRV and endothelial function in this population., Methods: PLWH performed 24 sessions of AT protocol. The protocol consists of 40 min of treadmill (60 to 80% of the VO 2max ), 3 times per week, for 8 weeks. HRV (standard deviation of all normal RR intervals - SDNN; root mean square of the successive differences - rMSSD; low frequency - LF; high frequency - HF; LF:HF ratio) and endothelial function parameters were evaluated by EndoPAT system pre and post intervention., Results: 7 men, the median age of the sample was 49 years (range, 38-68 years), completed the protocol. AT improved resting HRV parameters: SDNN (p = 0.02, power analysis (PA) 0.54), rMSSD (p = 0.02, PA = 0.99), LF (p = 0.02, PA = 0.85). HF, LF:HF ratio and endothelial function parameters showed no changes., Conclusions: The results suggest the short-term AT may improve HRV in men living with HIV.

The aim of this study was to evaluate the impact of high-intensity strength training (ST) or low-intensity strength training with blood flow restriction (ST-BFR) on monocyte subsets, the expression of C-C chemokine receptor 5 (CCR5), and CD16 on monocytes, and tumor necrosis factor alpha (TNF-α) production of overweight men. Thirty overweight men were randomly assigned to conventional ST or ST-BFR. Both groups performed exercises of knee extension and biceps curl with equal volume (3 sessions/week) over 8 weeks, and the peripheral frequency of monocytes (CD14+CD16-, classical monocytes; CD14+CD16+, intermediate monocytes; CD14-CD16+, nonclassical monocytes), the mean fluorescence intensity (MFI) of CCR5 and CD16 on CD14+ monocytes; and the production of TNF-α by lipopolysaccharide (LPS)-stimulated cells were quantified. Eight weeks of ST increased the frequency of CD14+CD16- monocytes ( p = 0.04) and reduced the percentage of CD14-CD16+ ( p = 0.02) and the production of TNF-α by LPS-stimulated cells ( p = 0.03). The MFI of CD16 on CD14+ monocytes decreased after the ST intervention ( p = 0.02). No difference in monocyte subsets, CCR5 or CD16 expression, and TNF-α production were identified after ST-BFR intervention ( p > 0.05). The adoption of ST promotes anti-inflammatory effects on monocyte subsets of overweight men, but this effect was lost when BFR was adopted. Novelty High-intensity strength training reduces the production of TNF-α and the peripheral frequency of CD16+ monocytes in overweight men. Blood flow restriction method blunts the strength training adaptations on monocyte subsets and pro-inflammatory TNF-α production in overweight men.

Immune cells are bioenergetically expensive during activation, which requires tightly regulated control of metabolic pathways. Both low and high glycemic conditions can modulate immune function. States of undernourishment depress the immune system, and in the same way, excessive intake of nutrients, such as an obesity state, compromise its functioning. Multicellular organisms depend on two mechanisms to survive: the regulation and ability to store energy to prevent starvation and the ability to fight against infection. Synergic interactions between metabolism and immunity affect many systems underpinning human health. In a chronic way, the breakdown of glycemic homeostasis in the body can influence cells of the immune system and consequently contribute to the onset of diseases such as type II diabetes, obesity, Alzheimer's, and fat and lean mass loss. On the contrary, exercise, recognized as a primary strategy to control hyperglycemic disorders, also induces a coordinated immune-neuro-endocrine response that acutely modulates cardiovascular, respiratory, and muscle functions and the immune response to exercise is widely dependent on the intensity and volume that may affect an immunodepressive state. These altered immune responses induced by exercise are modulated through the "stress hormones" adrenaline and cortisol, which are a threat to leukocyte metabolism. In this context, carbohydrates appear to have a positive acute response as a strategy to prevent depression of the immune system by maintaining plasma glucose concentrations to meet the energy demand from all systems involved during strenuous exercises. Therefore, herein, we discuss the mechanisms through which exercise may promotes changes on glycemic homeostasis in the metabolism and how it affects immune cell functions under higher or lower glucose conditions., (© 2019 Wiley Periodicals, Inc.)

Background: Obesity and low physical activity changes the redox state and neurotrophin secretion by leukocytes. However, the role of exercise on brain derived neurotrophic factor (BDNF) production and oxidative stress markers of peripheral blood mononuclear cells (PBMC) remains unknown. This study aimed to verify the impact of acute maximal exercise on oxidative stress markers and the BDNF production by stimulated PBMC from sedentary and physically active obese men., Methods: PBMC from twelve sedentary obese (SED group) and twelve regular exercisers (EXE group) obese men were collected before, immediately and 1-h after maximal exercise. PBMC were stimulated with lipopolysaccharide (LPS) to evaluate the BDNF and nitrite production, lipid peroxidation, and antioxidant enzymes catalase (CAT) and superoxide dismutase (SOD) activities., Results: PBMC from EXE group presented higher BDNF production (P=0.03) and lower TBARS levels than SED group at baseline. Maximal exercise increased BDNF and nitrite production, and lipid peroxidation immediately and 1-h after the bout in both groups. The EXE group presented higher superoxide dismutase activity immediately after bout and higher catalase activity 1-h after bout in PBMC. On the other hand, PBMC from SED group had lower superoxide dismutase activity immediately after exercise. Furthermore, PBMC from EXE group presented higher BDNF production and SOD activity and lower TBARS concentrations than SED group immediately after maximal exercise., Conclusions: Maximal exercise changes the redox state and enhances BDNF production by LPS-stimulated PBMC in obese individuals.

A lack of physical activity is linked to the development of many chronic diseases through a chronic low-grade inflammation state. It is now well accepted that the immune system plays a central role in the development of several chronic diseases, including insulin resistance, type 2 diabetes, atherosclerosis, heart failure and certain types of cancer. Exercise elicits a strong anti-inflammatory response independently of weight loss and can be a useful non-pharmacologic strategy to counteract the low-grade inflammation. The CD4+CD25+CD127- FoxP3+ Regulatory T (Treg) cells are a unique subset of helper T-cells, which regulate immune response and establish self-tolerance through the secretion of immunoregulatory cytokines, such as IL-10 and TGF-β, and the suppression of the function and activity of many immune effector cells (including monocytes/macrophages, dendritic cells, CD4+ and CD8+ T cells, and Natural Killers). The metabolic phenotype of Tregs are regulated by the transcription factor Foxp3, providing flexibility in fuel choice, but a preference for higher fatty acid oxidation. In this review, we focus on the mechanisms by which exercise - both acute and chronic - exerts its antiinflammatory effects through Treg cells mobilization. Furthermore, we discuss the implications of immunometabolic changes during exercise for the modulation of Treg phenotype and its immunosuppressive function. This narrative review focuses on the current knowledge regarding the role of Treg cells in the context of acute and chronic exercise using data from observational and experimental studies. Emerging evidence suggests that the immunomodulatory effects of exercise are mediated by the ability of exercise to adjust and improve Tregs number and function., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

This study investigated the peripheral frequency of monocytes, CD4 + T cell subsets and the systemic levels of cytokines in lean and obese men with different levels of cardiorespiratory fitness (CRF). Mononuclear cells were obtained from 45 lean and 45 obese men who were assigned into six groups according to their body mass index and CRF (low, moderate, or high VO 2Peak ) to analyze the frequency of monocyte subsets and subpopulations of CD4 + T cells (Treg cells, CD4 + CD25 high CD127 low ; mTeff, CD4 + CD25-CD39+; mTreg, CD4 + CD25+CD39+). The systemic levels of interleukin (IL)-6, IL-10, IL-17a, IL-33, leptin, and tumor necrosis factor-alpha (TNF-α) were also evaluated. Seven sedentary obese men performed one week of high-intensity interval training (HIIT, 3 sessions/week), and blood samples were collected before and 24 hours after the last session for phenotypic analysis of T cells and monocytes. Obese individuals presented an inflammatory profile characterized by lower frequencies of Treg and mTreg cells and higher proportions of proinflammatory monocytes. However, higher CRF status increased the frequencies of Treg cells and mTreg cells and decreased the percentage of CD4 + mTeff cells and intermediate and non-classical monocytes in the peripheral blood from lean and obese men. Systemic lower levels of proinflammatory (IL-6 and TNF-) cytokines and higher concentrations of IL-10 and IL-33 were observed in moderate and higher CRF in all subjects. HIIT increased the proportions of circulating mTreg and Treg cells in sedentary obese individuals. The immunoregulatory role of CRF contributes to the maintenance of low levels of inflammatory mediators., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objectives: To evaluate the influence of red wine exposure, alcohol, grape juice and resveratrol in the occurrence of spontaneous and ligature induced periodontitis as well as CRP, TNFα and IL-6 levels in Wistar rats., Methodology: 50 male Wistar rats were randomly assigned to 5 groups (Control, Red Wine, Grape Juice, 12% Alcohol and 0.05mg/mL Resveratrol). All groups were fed with laboratory rat chow and liquid intake according to group allocation. After 8 weeks, ligatures were placed around the maxillary right second molars. The contra-lateral molars remained as intra-group controls. After 14 days, animals were killed, blood samples collected and specimens prepared for analysis. Group comparisons were performed by ANOVA. A cut-off point in the 75th percentile in the side without ligature was used for definition of spontaneous periodontitis., Results: All animals completed the experiment. According to mean alveolar bone loss, no statistically significant differences were found. Animals exposed to red wine presented a lower occurrence of spontaneous periodontitis, lower levels of TNF-α (0.97 ng/mL) and CRP (0.29 mmol/μL) compared to controls (1.97 ng/mL, p = 0.008 and 0.45 mmol/ μL, p less than or equal to 0.05 respectively)., Conclusion: Red wine exposure potentially affects the occurrence of spontaneous periodontitis, CRP and TNF-α levels in Wistar rats., Competing Interests: The authors declare not to have conflicts of interest., (Copyright© by the International Academy of Periodontology.)

Objectives: To evaluate the effects of cannabis and/or cocaine use on inflammatory, oxidative stress status and circulating monocyte subsets in HIV-infected individuals under antiretroviral therapy., Design: Soluble CD14 (sCD14), intestinal fatty acid-binding protein (IFABP), tumor necrosis factor-alpha (TNF-α), interleukin (IL)-6, IL-8, IL-10, C-reactive protein (CRP) and oxidative stress markers were examined. The monocyte subsets and their activation and cytokine production by peripheral blood mononuclear cells (PBMCs) of HIV-1 infected individuals upon lipopolysaccharide (LPS)-stimulation were also investigated., Methods: sCD14, IFABP, TNF-α, IL-6, IL-8 and IL-10 levels were evaluated using ELISA, CRP by turbidimetry; lipid peroxidation (TBARS) spectrofluometrically and total thiol levels by using 5-5'-dithio-bis (2-nitrobenzoic acid) reagent. Monocyte subsets and activation were assessed by flow cytometry., Results: All HIV-infected drug user groups showed higher sCD14 levels compared with HIV+ nondrug users. IFABP was increased in HIV+ drug-users in relation to healthy individuals. Cannabis use lowered the percentages of inflammatory, nonclassical, activated-classic and activated-inflammatory monocytes. Cocaine users showed increased plasmatic TNF-α and TBARS levels, decreased thiols content and lower activated-classic and inflammatory-monocyte percentages. Cannabis-plus-cocaine use increased CRP, IL-8 and IL-6/IL-10 ratio, but decreased thiol content, and inflammatory and activated-classic monocyte percentages. PBMCs of cannabis and cannabis-plus-cocaine users showed low-potential cytokine production either spontaneously or under LPS-stimulation., Conclusion: In HIV infection, the use of cannabis induces predominantly an anti-inflammatory profile. The use of cocaine and cannabis-plus-cocaine showed a mixed pro-inflammatory and anti-inflammatory profile, with predominance of inflammatory status. Further studies are required to better understand the action of these drugs in HIV infection.

Our aim was to evaluate the impact of a single bout of exercise, consisting of a gait training session with body weight support (BWS), on histone acetylation status (global histone H4 and H3 acetylation levels), brain-derived neurotrophic factor (BDNF) levels, and oxidative stress markers in peripheral blood of individuals with chronic spinal cord injury (SCI). We also set out to compare these responses with those recorded after gait training performed using a walker and with no BWS. The subjects (nearly all with an incomplete spinal cord lesion) were each submitted to two 60-minute experimental sessions on separate days with a 1- week wash-out period between the interventions. The order of the sessions was randomized. Blood samples were collected before and after each experimental trial for measurement of biomarkers. The histone acetylation status and BDNF levels remained unchanged after both interventions. After the treadmill training, the participants showed a strong increase in levels of oxidative stress markers [plasma advanced oxidation protein products (AOPPs), nitrite and thiobarbituric acid-reactive substances] without changes in antioxidant mediators. Instead, elevations in AOPP and nitrite concentrations, in addition to increased levels of glutathione and catalase activity, were found after the walker training. A single bout of gait training, be it conducted on a treadmill with BWS or using a walker without BWS, is not able to alter BDNF levels and histone acetylation status in SCI patients. However, these trials can modulate oxidative stress parameters, seemingly in a protocol-dependent manner.

Aim: To investigate the impact of physical fitness on the mobilization of CD4 + CD25 - CD39 + and CD4 + CD25 + CD39 + T cells in response to acute exercise., Methods: Fifteen high physical fitness (25.3 ± 1.4 years) and 15 low physical fitness (26.1 ± 1.9 years) men performed a single bout of high-intensity interval exercise (HIIE, 10 bouts of 60 seconds at 85% HRmax intercepted by 75 seconds of recovery at 50% HRmax). Blood lymphocytes were isolated before, immediately after and 1 hour after exercise for assessment of cell surface expression of CD25, CD39, and CD73 on CD4 + T cells. Effector memory T cells (mTeff) were identified by CD4 + CD25 - CD39 + coexpression, and memory regulatory T cells (mTReg) were defined as CD4 + CD25 + CD39 + T cells., Results: Exercise increased CD4 + and CD4 + CD25 + T cell frequencies immediately after followed by a decrease bellow to baseline values at 1 hour after the bout in both low and high physical fitness groups. At baseline, the proportions of mTeff were higher, while mTreg were lower in low physical fitness individuals. The frequency of mTreg increased immediately after HIIE in both groups, and remained higher 1 hour after the bout. However, high physical fitness individuals presented higher mTreg frequency in all periods evaluated. A significantly mobilization of mTeff cells was identified in both groups immediately after HIIE. High physical fitness individuals displayed a decrease in mTeff cells bellow to baseline, while the frequency of mTeff remained higher in low physical fitness group 1 hour after the bout. The peripheral frequency of CD4 + CD25 + CD73 + T cells increased in a similar way immediately after the bout in both groups, returning to the baseline values 1 hour after exercise. No differences in CD4 + CD25 - CD73 + T cells were observed after HIIE in both groups., Conclusion: Our results highlight the impact of physical activity status in the redistribution of CD4 + T cells expressing ectonucleotidases in response to HIIE., (© 2019 Wiley Periodicals, Inc.)

The aim of this study was to evaluate the DNA damage in peripheral lymphocytes and the frequencies of CD8+ T cells expressing CD25, CD28 and CD45ro in aged individuals with inverted CD4:CD8 ratio. Blood samples of elderly individuals (aged >65) with normal CD4:CD8 ratio (n = 8) and inverted CD4:CD8 ratio (n = 8) were collected to identify the expression of CD25+, CD28+ and CD45ro+ in CD8+ T cells. DNA damage index was evaluated by the alkaline comet assay which was performed in lymphocytes treated with different concentrations of methyl methanesulfonate (MMS) (control non-treatment, 2 × 10 -5  M, 4 × 10 -5  M) for 1, 2 or 24 h. Elderly individuals with inverted CD4:CD8 ratio presented low frequency of CD8+ CD28+. Moreover, low DNA damage was observed in lymphocytes of elderly with inverted CD4:CD8 ratio in different doses of MMS. Aged individuals with inverted CD4:CD8 ratio presented lower DNA damage events in peripheral lymphocytes, suggesting a resistance for cell death in T cells of individuals with immune risk profile., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Pesticides are one of the most frequently investigated chemical, due to their multiple uses in agricultural and public health areas. This study evaluates lymphocytes CBMN (cytokinesis-block micronucleus cytome assay), inflammatory markers, inorganic elements in blood samples, and the relationship of these parameters with XRCC1Arg194Trp, OGG1Ser326Cys and PON1Gln192Arg polymorphisms in a population of tobacco farmers. The study population comprised 129 agricultural workers exposed to pesticides and 91 nonexposed. Farmers had significantly increased NPB (nuclear plasmatic bridge), MN (micronucleus) and NBUD (nuclear bud) frequencies, as well as IL-6 (interleukin 6) and TNF-α (tumor necrosis factor alpha) serum levels, and decreased cytokines CD4+/CD8+ ratio. In the exposed group, XRCC1 Trp/- was correlated with decreased NDI (nuclear division index), and OGG1 Cys/- was associated with higher levels of NPB and decreased levels of IL-6. The combined effects of PON1 Arg/- and XRCC1 Arg/Arg were associated with increased NPB frequencies. In addition, the combination of PON1 Arg/- with XRCC1 Trp/- or OGG1 Cys/- influenced in increased levels of necrosis in farmers. Furthermore, tobacco farmers showed a positive correlation between TNF-α levels and NPB, CD4+/CD8+ ratio and NBUD; and IL-6 levels with both MN and NDI. The duration of years of work at tobacco fields was correlated positively with NBUD frequency. Sulfur, chlorine and potassium were found at increased levels in the exposed group when compared to the nonexposed one. These findings provide evidence that tobacco farmers' exposure have increased DNA damage and alter the immune system's response, and that XRCC1 and OGG1 polymorphisms could influence both biomarkers results., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Aim: To evaluate the effects of acute fish oil supplementation (FOS) in DNA damage, lymphocyte phenotype and cytokines production after strenuous exercise in obese individuals., Methods: Sixteen sedentary obese (BMI >30.0 to <35.0 kg/m²) men performed two sessions of exhaustive exercise and consumed 2000 mg of either placebo or fish oil one hour before the exercise session; trials were separated by 14 days. Peripheral blood mononuclear cells were collected pre, immediately after and 1 h after both exercise sessions and stimulated in vitro with 2% phytohemagglutinin for cytokines secretion (IL-6, IL-8, TNF-α). Analysis of DNA damage index on total lymphocytes and the peripheral frequency of T helper CD4+ cells, T cytotoxic CD8+ cells, and CD19+ B cells were also performed., Results: FOS prevented the increase in serum cortisol levels and the production of TNF-α and IL-8 after strenuous exercise. The DNA damage index decreased 1 h after exercise in FOS trial. Moreover, a lymphocytosis, i.e. increases in the frequency of CD4+ and CD8+ T cells was observed immediately after exercise bout in both trials. Moreover, FOS prevented the decrease in CD8+ T cells below to baseline value 1 h after strenuous exercise., Conclusion: Acute supplementation with fish oil attenuates the proinflammatory cytokine response and diminished the DNA damage after strenuous exercise in obese individuals, suggesting a possible protective effect against the exacerbation of systemic damage induced by exhaustive exercise in obese individuals., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

The available chemotherapeutic drugs for the treatment of leishmaniasis present problems relating to efficacy, emergence of parasite resistance, and adverse effects and cost. Azole antifungal drugs have been repurposed for this proposition but the clinical response has been variable. In this sense, this study assessed the leishmanicidal and immunomodulatory activities of azoles-derived imidazolium salts (IS), being the ionic imidazole-derived equivalents: 1-n-butyl-3-methylimidazolium chloride (C 4 MImCl), 1-n-decyl-3-methylimidazolium chloride (C 10 MImCl), 1-n-hexadecyl-3-methylimidazolium chloride (C 16 MImCl), 1-n-hexadecyl-3-methylimidazolium methanesulfonate (C 16 MImMeS), 1-n-hexadecyl-3-methylimidazolium bis(trifluoromethanesulfonyl)imide (C 16 MImNTf 2 ) and 1-methyl-3-n-octadecylimidazolium chloride (C 18 MImCl). Promastigotes of Leishmania amazonensis were incubated with IS at concentrations ranging from 0.1 to 100 μM, and the parasite survival was monitored. The effects of IS on reactive oxygen species (ROS) production and mitochondrial membrane potential of promastigotes, as well as on cytotoxicity against peripheral blood mononuclear cells (PBMC) and human erythrocytes were determined. Besides, the activities of IS against amastigotes and nitric oxide production were also evaluated. The IS inhibited parasite growth and showed potent leishmanicidal activity against promastigotes of L. amazonensis. In addition, IS induced mitochondrial dysfunction and ROS production in parasites, and presented low cytotoxicity against PBMC and human erythrocytes. Furthermore, at very low concentration (0.5 μM), C 18 MImCl, C 16 MImMeS, C 16 MImCl, C 10 MImCl and C 16 MImNTf 2 were able to kill intramacrophage parasites at levels of 91.3, 100, 94.4, 95.3 and 35.6%, respectively. These results indicate that IS are promising candidates for the development of drugs against L. amazonensis., (Copyright © 2018 Elsevier B.V. All rights reserved.)