Evidence suggests that physical exercise has effects on neuronal plasticity as well as overall brain health. This effect has been linked to exercise capacity in modulating the antioxidant status, when the oxidative stress is usually linked to the neuronal damage. Although high-intensity interval training (HIIT) is the training-trend worldwide, its effect on brain function is still unclear. Thus, we aimed to assess the neuroplasticity, mitochondrial, and redox status after one-week HIIT training. Male (C57Bl/6) mice were assigned to non-trained or HIIT groups. The HIIT protocol consisted of three days with short bouts at 130% of maximum speed (Vmax), intercalated with moderate-intensity continuous exercise sessions of 30 min at 60% Vmax. The mass spectrometry analyses showed that one-week of HIIT increased minichromosome maintenance complex component 2 (MCM2), brain derived neutrophic factor (BDNF), doublecortin (DCX) and voltage-dependent anion-selective channel protein 2 (VDAC), and decreased mitochondrial superoxide dismutase 2 (SOD 2) in the hippocampus. In addition, one-week of HIIT promoted no changes in H2O2 production and carbonylated protein concentration in the hippocampus as well as in superoxide anion production in the dentate gyrus. In conclusion, our one-week HIIT protocol increased neuroplasticity and mitochondrial content regardless of changes in redox status, adding new insights into the neuronal modulation induced by new training models.

Triple-negative breast cancer (TNBC) stands out for its aggressiveness and accelerated rate of proliferation. Evidence shows that exercise may exert antitumorigenic effects, but the biochemical mechanisms underlying them remain unclear. Our objective was to evaluate the ability of exercise to modulate tumor growth and energy metabolism in an experimental TNBC model. Female BALB/c mice were sedentary or trained for 12 weeks and inoculated with 1 × 104 4T1 cells in the eighth week. Analyzes of macronutrient oxidation, mitochondrial respiration, and expression of genes related to cell metabolism were performed. The results showed that the trained group had a smaller tumor mass and the mitochondria in the tumors presented lower respiratory rates in the state of maximum electron transport capacity. Additionally, the tumors of the exercised group showed a higher expression of genes related to tumor suppressors, while the genes linked with cellular growth were similar between groups. Furthermore, the training modulated the corporal macronutrient oxidation to almost exclusive carbohydrate oxidation, while the sedentary condition metabolized both carbohydrate and lipids. Therefore, the exercise reduced tumor growth, with an impact on mitochondrial and macronutrient metabolism. Our results shed light on the understanding of the antitumorigenic effects of physical exercise, particularly regarding the metabolic transformations in TNBC.

Sepsis is a syndrome characterized by a dysregulated inflammatory response, cellular stress, and organ injury. Sepsis is the main cause of death in intensive care units worldwide, creating need for research and new therapeutic strategies. Heat shock protein (HSP) analyses have recently been developed in the context of sepsis. HSPs have a cytoprotection role in stress conditions, signal to immune cells, and activate the inflammatory response. Hence, HSP analyses have become an important focus in sepsis research, including the investigation of HSPs targeted by therapeutic agents used in sepsis treatment. Many therapeutic agents have been tested, and their HSP modulation showed promising results. Nonetheless, the heterogeneity in experimental designs and the diversity in therapeutic agents used make it difficult to understand their efficacy in sepsis treatment. Therefore, future investigations should include the analysis of parameters related to the early and late immune response in sepsis, HSP localization (intra or extracellular), and time to the onset of treatment after sepsis. They also should consider the differences in experimental sepsis models. In this review, we present the main results of studies on therapeutic agents in targeting HSPs in sepsis treatment. We also discuss limitations and possibilities for future investigations regarding HSP modulators.

DEDICATÓRIA Dedico este trabalho aos meus pais, Nelson e Renilda, por todo estímulo à aprendizagem e conhecimento, sobretudo, pela minha formação como ser humano. "...é sempre bom saber um pouco de cada coisa!" me diziam quando criança. Talvez tenha levado à serio demais a frase, mas o dia que não aprendo nada, para mim, é um dia desperdiçado. À minha irmã Mônica e meu cunhado Diego, pelo companheirismo e conversas sempre agradáveis. Dedico também este trabalho a todas as mulheres, em especial àquelas diagnosticadas com câncer de mama. Mulheres fortes, guerreiras e que mesmo diante desta batalha, são mães, companheiras enamoradas, amigas e mantêm sua graciosidade, delicadeza e amor! Obrigado pelo exemplo de humanidade! AGRADECIMENTOS Você não pode mudar o vento, mas pode ajustar as velas do barco para chegar onde quer. (Confúcio) Gosto de pensar que Ciência é mar aberto... No qual navegamos com a ambição da descoberta. Mas a navegação exige chegadas e partidas... É assim que vejo o agora, o momento de içar velas e navegar águas desconhecidas novamente, tendo agora na bagagem, aquilo que vocês gentilmente compartilharam comigo.

Purpose. Cardiovascular fitness (maximal oxygen uptake [VO 2 max]) is linked with health indicators and the 2 subunit of the AMP-activated protein kinase (AMPK 2), encoded by the PRKAA2 gene, is an important metabolic sensor and can mediate part of exercise effect. It has been proposed that changes in the metabolic process bound with exercise might occur through epigenetic regulations. However, how VO 2 max can influence the epigenetic mechanism and consequently health is still unknown. the aim of this study was to investigate the PRKAA2 gene methylation profile and its relation to metabolic variables in normoglycemic monozygotic twins discordant for VO 2 max. Methods. Nine pairs of monozygotic twins were studied, with the intra-pair VO 2 max difference 10 ml • kg-1 • min-1. An oral glucose tolerance test was used, and blood samples were collected for biochemical and DNA methylation analyses. Results. No DNA methylation differences were observed between the groups. the low-cardiorespiratory-fitness group demonstrated a positive correlation between the methylation profile and low-density lipoprotein (CpG1, r = 0.714) and total cholesterol (CpG1, r = 0.723; CpG3, r = 0.678). Only the high-cardiorespiratory-fitness group showed correlations between glucose and insulin variables. Conclusions. Our data suggest a link between high cardiorespiratory fitness and glucose-insulin correlation. the results provide important insights for future studies about the mechanisms through which VO 2 max can influence glucose metabolism.