Potential involvement of circulating extracellular vesicles and particles on exercise effects in malignancies

Physical activity and exercise have been widely related to prevention, treatment, and control for several non-communicable diseases. In this context, there are innumerous pre-clinical and clinical evidence indicating the potential role of exercise, beyond cancer prevention and survival, improved quality of life, including on psychological components, bone health and cachexia, from cancer survivors is described as well. This mini-review raises the potential role of circulating extracellular and particles vesicles (EVPs) cargo, as exerkines, conducting several positive effects on adjacent and/or distant tissues such as tumor, immune, bone and muscle cells. We highlighted new perspectives about microRNAs into EVPs changes induced by exercise and its benefits on malignancies, since microRNAs can be implicated with intricated physiopathological processes. Potential microRNAs into EVPs were pointed out here as players spreading beneficial effects of exercise, such as miR-150- 5p, miR-124, miR-486, and miRNA-320a, which have previous findings on involvement with clinical outcomes and as well as tumor microenvironment, regulating intercellular communication and tumor growth. For example, highintensity interval aerobic exercise program seems to increase miR‐150 contents in circulating EVPs obtained from women with normal weight or overweight. In accordance circulating EVPs miR-150-5p content is correlated with prognosis colorectal cancer, and ectopic expression of miR-150 may reduce cell proliferation, invasion and metastasis. Beyond the involvement of bioactive miRNAs into circulating EVPs and their pathways related to clinical and preclinical findings, this mini review intends to support further studies on EVPs cargo and exercise effects in oncology

Epigenetic marks are modulated by gender and time of the day in the hippocampi of adolescent rats : a preliminary study

Although the involvement of gender in epigenetic machinery in peripheral tissues during the neonatal period has been suggested, the gender-related epigenetic profile of brain areas during the adolescent period is rarely exploited. Furthermore, the influence of time of day on hippocampal acetylation marks has been demonstrated in young adult and aged rats; however, there are no studies reporting epigenetic changes in the adolescent period. Therefore, this study aimed to investigate the effects of gender on hippocampal DNA methyltransferase 1 content and histone deacetylase (HDAC) activity of adolescent rats at different time points, specifically early morning and afternoon. Both epigenetic markers increased significantly in the hippocampi of female rats compared to the male group, an indicator of reduced transcriptional activity. In addition, HDAC activity during the early morning was higher compared to afternoon groups in both male and female rats, while DNA methyltransferase 1 content was not altered by the time of day. Our findings demonstrate that hippocampal DNA methylation and histone acetylation status can be influenced by gender during the adolescent period, while the time of the day impacts HDAC activity

Circulating extracellular vesicles and particles derived from adipocytes : the potential role in spreading microRNAs associated with cellular senescence

Aging is associated with adipose tissue dysfunction and is recognized as a risk factor for shortened life span. Considering that in vitro findings have shown the involvement of microRNA in extracellular vesicles and particles (EVPs) on senescence, we hypothesized that circulating EVPs derived from adipocytes can be involved in the aging process via their microRNA cargo. We aimed to determine the microRNA profiles of circulating EVPs derived from adipocytes (FABP4+) from aged and young adult animals and to perform in silico prediction of their downstream signaling effects. Plasma was obtained from Wistar rats (3 and 21 months old), and adipocyte-derived EVPs were isolated using the commercially available kit. Fatty acid-binding protein 4 (FABP4) was used for adipocyte-derived EVPs isolation; microRNA isolation and microarray expression analysis were performed. The analysis revealed 728 miRNAs, 32 were differentially between groups (p < 0.05; fold change ≥ |1.1|), of which 15 miRNAs were upregulated and 17 were downregulated in circulating EVPs from aged animals compared to young adults. A conservative filter was applied, and 18 microRNAs had experimentally validated and highly conserved predicted mRNA targets, with a total of 2,228 mRNAs. Canonical pathways, disease and functions, and upstream regulator analyses were performed using IPA-QIAGEN, allowing a global and interconnected evaluation. IPA categories impacted negatively were cell cycle, cellular development, cellular growth and proliferation, and tissue development, while those impacted positively were “digestive system cancer” and “endocrine gland tumor.” Interestingly, the upregulated miR-15-5p targets several cyclins, such as CCND1 and CCND2, and miR-24-3p seems to target CDK4 (cyclin-dependent kinase 4); then potentially inhibiting their expression, both miRNAs can induce a negative regulation of cell cycle progression. In contrast, silencing of negative cell cycle checkpoint regulators, such as p21 and p16, can be predicted, which can induce impairment in response to genotoxic stressors. In addition, predicted targets, such as SMAD family members, seem to be involved in the positive control of digestive and endocrine tumors. Taken together, this exploratory study indicates that miRNA signature in circulating adipocyte-derived EVPs may be involved with the double-edged sword of cellular senescence, including irreversible proliferation arrest and tissue-dependent cancer, and seems to be suitable for further validation and confirmatory studies

Efeito do exercício físico em ambiente aquático ou terrestre sobre marcadores de estado oxidativo em plasma de pacientes diabéticos

O Diabetes Mellitus, em especial o tipo 2 (DMT2), é uma doença metabólica crônica associada a inúmeras comorbidades e complicações. Estudos recentes têm associado às complicações relacionadas ao diabetes a um estado de desequilíbrio entre as defesas antioxidantes do organismo e as espécies reativas circulantes. Atualmente propõe-se o uso de estratégias não farmacológicas a fim amenizar os sintomas do DMT2. O exercício físico vem ganhando um papel de grande destaque entre estas estratégias. No entanto estudos que avaliem os efeitos bioquímicos e fisiológicos do exercício físico nesta população ainda são escassos, principalmente em ambiente aquático. A partir disso o objetivo deste trabalho foi avaliar os efeitos do exercício em ambiente aquático ou terrestre sobre marcadores de estado oxidativo em plasma de pacientes diabéticos. Para tanto foram selecionados 24 indivíduos diabéticos tipo 2, sedentários, de ambos os sexos, para participarem de 12 semanas de treinamento aeróbio. Os indivíduos foram divididos em grupo terra ou grupo água e os protocolos mantiveram periodização de treinamento similar. As coletas das amostras foram realizadas antes e após a primeira e última sessão de treinamento. A partir destas amostras foram analisados diversos marcadores de estado oxidativo. Os resultados obtidos não mostraram diferenças significativas tanto no grupo água quanto no grupo terra em parâmetros oxidativos como: conteúdo de radicais livres, substâncias fluorescentes solúveis em água e a oxidação de resíduos de aminoácidos. A atividade da superóxido dismutase e o potencial antioxidante total também não foram alterados. Apesar disso, foi possível observar que o ambiente no qual o treinamento é realizado pode sim impactar diferentemente na resposta obtida uma vez que os níveis de isoprostanos se mostraram reduzidos somente no grupo que realizou o exercício em terra. Embora os resultados obtidos tenham revelado somente efeito do treinamento em terra, não podemos excluir os efeitos benéficos da água sobre estes indivíduos. Podemos sugerir que o ambiente aquático possa estar envolvido na modulação de outros mecanismos fisiológicos. Os dados obtidos suportam a ideia de que o exercício com intensidade similar, variando somente o ambiente de treinamento, possa alterar diferentemente os níveis de isoprostanos em indivíduos diabéticos tipo 2