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    Can Environmental Enrichment Modulate Epigenetic Processes in the Central Nervous System Under Adverse Environmental Conditions? A Systematic Review
    (Springer/Plenum Publishers, 2024) Fernandes, Matheus Santos de Sousa; Costa, Moara Rodrigues; Badicu, Georgian; Yagin, Fatma Hilal; Santos, Gabriela Carvalho Jurema; da Costa, Jonathan Manoel; de Souza, Raphael Fabricio
    The aim of this paper is to summarize the available evidence in the literature regarding the effects generated by exposure to an enriched environment (EE) on the modulation of epigenetic processes in the central nervous system under adverse environmental conditions. Searches were conducted in three databases: PubMed/Medline (1053 articles), Scopus (121 articles), and Embase (52 articles), which were subjected to eligibility criteria. Of the 1226 articles found, 173 duplicates were removed. After evaluating titles/abstracts, 904 studies were excluded, resulting in 49 articles, of which 14 were included in this systematic review. EE was performed using different inanimate objects. Adverse environmental conditions included CUMS, sepsis, nicotine exposure, PCP exposure, early stress, WAS, high fructose intake, TBI, and sevoflurane exposure. Regarding microRNA expression, after exposure to EE, an increase in the expression of miR-221 and miR-483 was observed in the prefrontal cortex, and a reduction in the expression of miR-92a-3p and miR-134 in the hippocampus. Regarding histone modifications, in the hippocampus, there was a reduction of HAT, HDAC/HDAC4, H3 (acetyl K14), H4 (acetyl K15), H3K4me3, K3k27me3, and HDAC2/3/5. In the cortex, there was a reduction of HDAC2, and in the prefrontal cortex, there was an increase in acetylated H3. Regarding DNA modifications, there was a reduction of DNMT in the hippocampus. This systematic review concludes that the benefits of EE on the brain and behavior of animals are directly related to different epigenetic mechanisms, reflecting in cell growth and neuroplasticity. EE may be a non-pharmacological and easy-to-apply alternative to prevent symptoms in disorders affecting brain tissue.
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    Does Quercetin Supplementation Promote Biological Changes and Performance in Athletes? A Systematic Review
    (Biolife Publisher, 2024) Fernandes, Matheus Santos de Sousa; Ferreira, Diorginis José Soares; Yagin, Fatma Hilal; Badicu, Georgian; Silva, Clarice Beatriz Gonçalves; Costa, Jonathan Manoel da; Santos, Gabriela Carvalho Jurema
    Background: Summarize the available evidence in the literature regarding the repercussions generated by quercetin supplementation in amateur and professional athletes. Methods: Searches were conducted in four databases, Cochrane Library (23 articles), PubMed/Medline (37 articles), Scopus (70 articles), and Excerpta Medica Database (EMBASE) (72 articles), which were subjected to eligibility criteria. Results: Out of 202 articles found, 95 duplicates were removed, and 107 articles were analyzed for the inclusion process. Then, 784 studies were excluded after title/abstract evaluation, resulting in 17 articles of which 13 were included in this systematic review. After quercetin supplementation, alterations in aspects related to the inflammatory response were observed, mainly through modifications in the formation of interleukin (IL)-1β, interleukin 2 (IL-2), interleukin 8 (IL-8), interleukin 10 (IL-10), interleukin 12 (IL-12), and tumor necrosis factor alpha (TNF-α). Responses were also observed in biochemical parameters, such as reduction of xanthine oxidase, and plasma free radicals. There were also changes related to anthropometry and body composition, in lean body mass (LBM). Some repercussions on performance were also observed, such as an increase in Sprint time (s), and training efficacy, a decrease post-run muscular pain through the Visual Analog Score (VAS), and recovery time in hours. Conclusion: This systematic review indicates that quercetin supplementation does not improve exercise performance, but may exert positive effects on training development, which might trigger better performance as training progresses. On the inflammatory and oxidative-related parameters, just a few evidence pointed to an improved biochemical profile, wherein the slight enhancement may not justify the supplementation costs. © 2024 The Author(s).
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    The impact of enriched environments on cerebral oxidative balance in rodents: a systematic review of environmental variability effects
    (Frontiers Media Sa, 2024) Ramos, Tiago Lacerda; Fernandes, Matheus Santos de Sousa; Fidelis, Debora Eduarda da Silva; Santos, Gabriela Carvalho Jurema; Albuquerque, Renata B.; Ferreira, Diorginis Jose Soares; de Souza, Raphael Fabricio
    Introduction The present review aimed to systematically summarize the impacts of environmental enrichment (EE) on cerebral oxidative balance in rodents exposed to normal and unfavorable environmental conditions. Methods In this systematic review, four databases were used: PubMed (830 articles), Scopus (126 articles), Embase (127 articles), and Science Direct (794 articles). Eligibility criteria were applied based on the Population, Intervention, Comparison, Outcomes, and Study (PICOS) strategy to reduce the risk of bias. The searches were carried out by two independent researchers; in case of disagreement, a third participant was requested. After the selection and inclusion of articles, data related to sample characteristics and the EE protocol (time of exposure to EE, number of animals, and size of the environment) were extracted, as well as data related to brain tissues and biomarkers of oxidative balance, including carbonyls, malondialdehyde, nitrotyrosine, oxygen-reactive species, and glutathione (reduced/oxidized). Results A total of 1,877 articles were found in the four databases, of which 16 studies were included in this systematic review. The results showed that different EE protocols were able to produce a global increase in antioxidant capacity, both enzymatic and non-enzymatic, which are the main factors for the neuroprotective effects in the central nervous system (CNS) subjected to unfavorable conditions. Furthermore, it was possible to notice a slowdown in neural dysfunction associated with oxidative damage, especially in the prefrontal structure in mice. Discussion In conclusion, EE protocols were determined to be valid tools for improving oxidative balance in the CNS. The global decrease in oxidative stress biomarkers indicates refinement in reactive oxygen species detoxification, triggering an improvement in the antioxidant network.
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    Is environmental enrichment effective in modulating autophagy markers in the brain exposed to adverse conditions? A systematic review
    (Frontiers Media Sa, 2025) Silva, Clarice Beatriz Goncalves; de Sousa Fernandes, Matheus Santos; Cerqueira, Debora Dantas Nucci; Santos, Gabriela Carvalho Jurema; Yagin, Fatma Hilal; Aygun, Yalin; Badicu, Georgian
    Autophagy is a key regulator of cellular homeostasis and neuronal survival, particularly under adverse physiological conditions. Environmental enrichment (EE), a non-pharmacological intervention providing enhanced sensory, cognitive, and motor stimulation, may modulate autophagic processes in the brain. This systematic review aimed to synthesize preclinical findings on the effects of EE on autophagy markers in rodent models subjected to diverse adverse conditions. A literature search across PubMed, Scopus, ScienceDirect, and embase yielded eight eligible studies meeting inclusion criteria. EE was found to be generally associated with upregulation of key autophagic markers such as Beclin-1, LC3-II/LC3-I ratio, cathepsins, p62, p-TFEB, and LAMP-1 across brain regions including the cortex, hippocampus, and penumbral area. However, reductions in some markers were also observed, indicating that the modulatory effects of EE are context-dependent and may vary with disease model, brain region, or EE protocol duration. These findings suggest that EE holds promise as an adjunctive strategy to modulate autophagy and mitigate neurodegeneration, though heterogeneity in study design and outcomes warrants caution during interpretation. Further mechanistic and sex-specific studies are needed to clarify the therapeutic relevance of EE-induced autophagic modulation.
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    Polyunsaturated Fatty Acid Supplementation in Athletes: A Systematic Review
    (Biolife Publisher, 2024) Fernandes, Matheus Santos de Sousa; da Costa, Jonathan Manoel; Badicu, Georgian; Santos, Gabriela Carvalho Jurema; Silva, Deyvison Guilherme Martins; Lagranha, Claudia Jacques; Yagin, Fatma Hilal
    Background: This study aims to summarize the evidence regarding the effects of polyunsaturated fatty acids (PUFAs) supple-mentation on both amateur and professional athletes. Objective: The aim is to elucidate the impacts of PUFAs supplementation on physical performance, inflammatory response, biochemical profile, anthropometric/body composition, and performance outcomes in athletes. Methods: Articles published up to December 2023 were retrieved from databases including Cochrane Library, PubMed/Medline, Scopus, and Embase. Selected articles met eligibility criteria and quality methodology. Data on inflammatory response, biochemical markers, anthropometric/body composition, and neuromuscular indicators were extracted. Results: Twenty-one studies were included in this systematic review. PUFAs supplementation resulted in decreased levels of certain inflammatory markers (interferon-gamma, interleukin 1, prostaglandin E2, and tumor necrosis factor alpha). However, no significant differences were observed in interleukin 4, 6, 8, 10, and matrix metalloproteinase 9. Additionally, there were no differences in glycemic (glucose and insulin) and lipid metabolism (high density lipoprotein (HDL)) cholesterol, low density lipoprotein (LDL), triglycerides). A reduction in reactive oxygen species levels was noted. No significant differences were found in muscle fatigue markers and anthropometry. Some performance parameters (neuromuscular and aerobic) improved following supplementation, including performance on the Yo-Yo distance test, resting energy expenditure, exercise time to exhaustion, and maximum oxygen consumption/maximum heart rate. Conclusion: Supplementation with PUFAs (600–3150 mg) in athletes led to reductions in inflammation and oxidative stress markers, as well as improvements in specific aerobic performance parameters. However, no significant effects were observed on glycemic and lipid profiles, anthropometric profiles, or body composition. © 2024 The Author(s).