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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-ß1 and ß2) 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-ß2 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-ß2 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.

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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-1ß, 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.

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BACKGROUND: Transcranial direct current stimulation (tDCS) and foot drop stimulators (FDS) are widely used for stroke rehabilitation. However, no study has investigated if tDCS could boost the effects of FDS and gait training in improving clinical parameters and neuroplasticity biomarkers of chronic post-stroke subjects. OBJECTIVE: To investigate the effects of combining tDCS and FDS on motor impairment, functional mobility, and brain-derived neurotrophic factor (BDNF) serum levels. Also, to evaluate the effects of this protocol on the insulin-like growth factor-1 (IGF-1), insulin growth factor-binding proteins-3 (IGFBP-3), interleukin (IL) 6 and 10, and tumor necrosis factor-α (TNF-α) levels. METHODS: Thirty-two chronic post-stroke individuals were randomized to tDCS plus FDS or sham tDCS plus FDS groups. Both groups underwent ten gait training sessions for two weeks using a FDS device and real or sham tDCS. Blood samples and clinical data were acquired before and after the intervention. Motor impairment was assessed by the Fugl-Meyer Assessment and functional mobility using the Timed up and Go test. RESULTS: Both groups improved the motor impairment and functional mobility and increased the BDNF levels. Both groups also increased the IL-10 and decreased the cortisol, IL-6, and TNF-α levels. No difference was observed between groups. CONCLUSION: tDCS did not add effect to FDS and gait training in improving clinical parameters and neuroplasticity biomarkers in chronic post-stroke individuals. Only FDS and gait training might be enough for people with chronic stroke to modify some clinical parameters and neuroplasticity biomarkers.

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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.

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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/m2 were randomly assigned to receive PROs (Lactobacillus acidophilus 1 × 109 colony forming units and Bifidobacterium lactis 1 × 109 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.

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Objetivo: Verificar os efeitos da acupuntura e fitoterapia chinesa na qualidade de vida e nos marcadores inflamatórios de pacientes asmáticos, registrando possíveis efeitos adversos durante o tratamento. Design: Aleatoriamente 30 indivíduos foram alocados em 3 grupos: controle, acupuntura e fitoterapia chinesa sham (Placebo) e acupuntura e fitoterapia chinesa intervenção. Métodos: Os indivíduos receberam 4 sessões de igual duração com avaliação pré e pós-tratamento da qualidade de vida e marcadores inflamatórios. O uso de medicamentos também foi registrado. Resultados: Encontrou-se diferença estatisticamente significativa no questionário de qualidade de vida, indicador de Vitalidade (RSVIT) apresentou um p < 0,005 e o indicador de Aspectos Sociais (RSAS) apresentou um p < 0,004, em comparação ao momento pré (p < 0,05) nos grupos controle, sham e intervenção; os Aspectos Emocionais (RSEM) com p < 0,003 e a Saúde Mental (RSSM) com p < 0,01 obtiveram diferença estatística apenas nos grupos Sham e Intervenção. Utilizou-se ANOVA de duas vias de medidas repetidas. Os demais não apresentaram diferenças e não houve efeitos adversos. Conclusão: A acupuntura e a fitoterapia chinesa são intervenções seguras, mas produziram efeito apenas na qualidade de vida ao longo de 4 semanas. São necessários mais estudos, verificando o efeito nos marcadores inflamatórios e na avaliação do tempo de intervenção.

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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.

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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-DRlow monocytes frequency than controls. Moreover, severe COVID-19 patients presented higher NF-κB p65 phosphorylation in CD14 + HLA-DRlow, as well as higher expression of TLR-4 and NF-κB p65 phosphorylation in CD14 + HLA-DRhigh 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-DRlow 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.

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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.

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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.

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