L-Arginine (L-ARG) supplementation has been suggested as a therapeutic option in several diseases, including Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-like syndrome (MELAS), arguably the most common mitochondrial disease. It is suggested that L-ARG, a nitric oxide (NO) precursor, can restore NO levels in blood vessels, improving cerebral blood flow. However, NO also participates in mitochondrial processes, such as mitochondrial biogenesis, the regulation of the respiratory chain, and oxidative stress. This study investigated the effects of L-ARG on mitochondrial function, nitric oxide synthesis, and nitro-oxidative stress in cell lines harboring the MELAS mitochondrial DNA (mtDNA) mutation (m.3243A>G). We evaluated mitochondrial enzyme activity, mitochondrial mass, NO concentration, and nitro-oxidative stress. Our results showed that m.3243A>G cells had increased NO levels and protein nitration at basal conditions. Treatment with L-ARG did not affect the mitochondrial function and mass but reduced the intracellular NO concentration and nitrated proteins in m.3243A>G cells. The same treatment led to opposite effects in control cells. In conclusion, we showed that the main effect of L-ARG was on protein nitration. Lowering protein nitration is probably involved in the mechanism related to L-ARG supplementation benefits in MELAS patients.

Males of Proechimys guyannensis, a rodent living in the Amazon rainforest are studied in biomedical research because of their antiepileptogenic mechanism. Females are usually taken from experimental designs, because of limited data of this sex. This study aimed to characterize the estrous cycle to include females together with males in research in a more balanced approach. The estrous cycle of P. guyannensis based through exfoliative cytology, determination of the vaginal occlusion membrane state, and hormonal analysis. In this study, cytological analyses of vaginal smears were performed for three months, three times a day. The observed length of the estrous cycle was 247 ± 81 h (mean ± SD) with a reproductive phase of 27.08 ± 17.39 h (estrus stage). We observed a frequent presence of both the open and closed states of the vaginal membrane in the estrus stage (fertile period) although only the open stage is a prerequisite for successful copulation. High levels of progesterone and estradiol were detected in proestrus. Levels of follicle-stimulating hormone peaked at the estrus stage. These data will establish the parameters and subsidies to set the grounds for future research either for investigating the biology of this species or to use P. guyannensis in research that previously excluded females. Information regarding female Proechimys is relevant to not only describe the species but also explain the interaction between sex hormones and physiological responses. Moreover, the present results will enhance rigor and reproducibility in preclinical studies. In conclusion, P. guyannensis reproductive cycles can occur spontaneously and cyclically independent of mating stimulation and the high levels of FSH in the estrus stage, suggest that ovulation occurs in the late phase of the estrus.

Este estudo visa a utilização de novas metodologias para geração de evidências através de dados eletrônicos, e requer esforço de todos os stakeholders da cadeia canábica que podem potencialmente utilizar esses dados para a tomada de decisões. Com a combinação de tecnologias e os avanços científicos disponíveis hoje, nunca houve um momento tão oportuno para tratar desse assunto e verificar o potencial da Cannabis para evolução socioambiental e científica na Saúde Única no Brasil. Através das recentes descobertas do Sistema Endocanabinoide e suas particularidades, o estudo de mundo real, torna-se de suma importância para obtermos dados consistentes no uso da Cannabis medicinal, podendo gerar valores sociais, econômicos, terapêuticos, ambientais e científicos através deste estudo. A insegurança dos profissionais de saúde com a falta de informações consistentes e regulamentação sobre as indicações, efeitos adversos e qualidade do produto disponível, exigem que novas pesquisas sejam implementadas. Apesar de evidências e pesquisas extensas que sustentam a eficácia e segurança no uso em diversas terapias, a regulamentação brasileira ainda é uma problemática. A utilização por humanos e animais, in natura ou de forma artesanal, há milhares de anos, para alívio da dor física, mental, emocional e espiritual, é contextualizada através da medicina tradicional e seu uso na atualidade pode nos trazer dados essenciais e complementares para a segurança, efetividade e indicações no seu uso, visando os produtos de Cannabis como um fitoterápico de grande valor. Esse estudo visa obter através de formulários em uma plataforma digital comercial, focada em terapias integrativas e interdisciplinares, dados de mundo real (DMR) para evidências de mundo real (EMR), no contexto medicinal, social e ambiental para promoção da saúde de humanos, animais e do meio ambiente. Garantido sigilo absoluto para segurança e integridade dos participantes da pesquisa, através da lei geral de proteção de dados e aprovação do conselho de ética, onde será aplicado o termo de consentimento livre e esclarecido e as respostas dos formulários interdisciplinares serão analisadas automaticamente, de forma percentual, sobre o uso de produtos de Cannabis de forma contínua, fomentando projeto social, criado para avaliar o impacto social e educacional ambiental a partir de lucros percentuais gerados com a plataforma comercial.

Mitochondrial diseases are complex disorders caused by nuclear or mitochondrial DNA mutations, leading to oxidative phosphorylation deficiency and excessive production of reactive oxygen species (ROS). While ROS have been well established in the pathogenesis of these diseases, the role of reactive nitrogen species (RNS) remains unclear. In this study, we performed a quantitative analysis of muscle fibers to investigate the relationship between protein nitration and mitochondrial abnormalities (mitochondrial proliferation and cytochrome-c oxidase (COX) deficiency) and factors like genotype, muscle damage, and age. A total of 1961 muscle fibers (303 from 4 controls and 1658 from 29 patients with mitochondrial diseases) were analyzed by immunostaining for nitro-tyrosine. Contrary to previous findings, which identified nitro-tyrosine only in small muscle vessels, we observed a broader distribution affecting the sarcolemma and sarcoplasm. Using multivariate techniques, we identified a significant correlation between protein nitration and mitochondrial proliferation but found no associations with COX deficiency, age, muscle damage, or genotype. These findings suggest that nitrative stress may contribute to mitochondrial dysfunction or play a role in signaling processes that induce mitochondrial biogenesis. Our results provide new insights into the molecular mechanisms of mitochondrial diseases and highlight the potential relevance of protein nitration.