Curcumin promotes apoptosis of human melanoma cells by caspase 3.

Cutaneous melanoma (CM) is a malignant neoplasm with a high metastatic rate that shows poor response to systemic treatments in patients with advanced stages. Recently, studies have highlighted the antineoplastic potential of natural compounds, such as polyphenols, in the adjuvant therapy context to treat CM. The objective of the present study was to evaluate the effect of different concentrations of curcumin (0.1-100 µM) on the metastatic CM cell line SK-MEL-28. The cells were treated for 6 and 24 h with different concentrations of curcumin. Cell viability was assessed by 3-(4,5-dimethyl-2thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay and fluorescence microscopy. The apoptotic-inducing potential was detected by annexin V flow cytometry. The wound healing assay was used to verify cell migration after the curcumin exposition. The redox profile was evaluated by levels of the pro-oxidant markers reactive oxygen species (ROS) and Nitric oxide (NOx) and antioxidants of total thiols (PSH) and nonprotein thiols. The gene expression and enzymatic activity of caspase 3 were evaluated by reverse transcription-quantitative polymerase chain reaction and a sensitive fluorescence assay, respectively. Curcumin significantly decreased the cell viability of SK-MEL-28 cells at both exposure times. It also induced apoptosis at the highest concentration tested (p < .0001). SK-MEL-28 cell migration was inhibited by curcumin after treatment with 10 µM (p < .0001) and 100 µM (p < .0001) for 6 and 24 h (p = .0006 and p < .0001, respectively). Furthermore, curcumin significantly increased levels of ROS and NOx. Finally, curcumin was capable of increasing the gene expression at 10 µM (p = .0344) and 100 µM (p = .0067) and enzymatic activity at 10 µM (p = .0086) and 100 µM (p < .0001) of caspase 3 after 24 h. For the first time, we elucidated in our study that curcumin increases ROS levels, promoting oxidative stress that activates the caspase pathway and culminates in SK-MEL-28 metastatic CM cell death.

Resistance training reduces platelet activation in hypertensive women: the role of purinergic signaling.

BACKGROUND AND AIM: Essential arterial hypertension is a risk factor for stroke, myocardial infarction, heart failure, and arterial aneurysm, which are related to the activation of platelets. Purinergic signaling has a central role in platelet aggregation. Although ATP and ADP can act as a proaggregant agent, adenosine inhibits platelet aggregation and reduces vascular injury. Physical exercise exhibits antiaggregant properties and can modulate purinergic system. The aim of this study was to evaluate the effect of 6 months of resistance training on purinergic system components in platelets and on platelet activation, hemodynamic and anthropometric parameters in hypertensive woman. METHOD: A total of 31 hypertensive and 28 normotensive middle-aged sedentary women were submitted to 6 months of resistance training. Purinergic enzymes activities were assessed in platelets; ATP and Tromboxane B2 (TXB2) levels were measured in serum. Blood pressure (BP), BMI, and body fat were also measured. All variables were statistically analyzed, considering P value less than 0.05. RESULTS: Six months of resistance training was able to significantly reduce BP, ATP, and TXB2 levels as well as NTPDase, ecto-5'nucleotidase, and ADA activities in hypertensive group. After 6 months of resistance training, purinergic system components and TXB2 of hypertensive group were similar to normotensive group in platelets, demonstrating that resistance training was able to modulate platelet activation. A positive correlation was found between BP, enzyme activities, and levels of ATP and TXB2. CONCLUSION: Our findings demonstrated the relationship between purinergic signaling and platelet activation in hypertension and suggests that resistance training serve as tool to reduce platelet aggregation in hypertensive woman by modulating purinergic system.

Antineoplastic properties of polyphenols in TPC-1 human papillary thyroid carcinoma cell line: a systematic review

ABSTRACT Thyroid cancer usually responds to surgical and ablative therapy, but when it's refractory the alternative lies in tyrosine kinase inhibitors that, in addition to harmful side effects, acts only in a palliative way. The concern for other therapeutic possibilities brought evidence on flavonoids, hypothesizing a possible strategy. This review aimed to organize a compilation of in vitro studies using polyphenol substances in TPC-1 (human papillary thyroid carcinoma cell line) summarizing it's results and describing the metabolic pathways involved. Articles were selected on PubMed, Google Scholar, LILACS, BVS and SciELO, using keywords "thyroid cancer", "flavonoids" and "TPC-1", until June 2022. 185 studies were selected. After identification and exclusion of duplicates and exclusion criteria applied, 11 original articles were evaluated. Of these, the findings of flavonoids added to TPC-1 were: inhibition of cell growth and viability, promotion of cell cycle arrest and induction of apoptosis. Polyphenolic compounds have antineoplastic properties by different mechanisms as shown in vitro, but the concentrations needed are above usual dietary consumption and the findings are limited to experimental cellular studies. Despite that, these results should be useful to guide further analysis aiming to reveal the real safety and efficacy of polyphenols in this scenario.

Refletindo sobre o Pet-Saúde/Gradua-SUS no contexto da trajetória do pró-saúde: onde avançamos e onde precisamos avançar?

A formação profissional em saúde, apesar dos avanços inegáveis, ainda não consegue dar conta de um de seus papéis sociais centrais, o de aproximar os(as) graduandos(as) das reais necessidades do Sistema Único de Saúde (SUS), de seus atores e protagonistas na gestão/educação/cuidado/pesquisa, e sobretudo de seus(suas) usuários(as). Na contramão dessa lacuna, a academia não problematiza a realidade pois vem sendo conduzida a partir de referenciais pedagógicos bancários e acríticos. Já que não a tem na graduação (onde deveria constar, independente de projetos “paralelos”), essa aproximação crítico-reflexiva com a realidade social vem sendo aos poucos introduzida/reforçada, além de experiências pontuais e pulverizadas Brasil afora, também por iniciativas governamentais como o PET-Saúde GraduaSUS (Programa de Educação pelo Trabalho para Saúde), estratégia atual para continuidade nos esforços já iniciados pelo Pró-Saúde (Programa Nacional de Reorientação da Formação Profissional em Saúde). Neste contexto, este trabalho tem como objetivo geral refletir sobre a trajetória do PET-Saúde / Gradua-SUS em relação ao seu histórico no contexto do Pró-Saúde. Trata-se de um estudo na modalidade relato de experiência, onde se considera a experiência de uma equipe do PET-Saúde / Gradua-SUS no Oeste Catarinense, desenvolvida em parceria entre a Secretaria Municipal de Saúde de Chapecó-SC (SESAU) e os cursos de Medicina e Enfermagem da Universidade Federal da Fronteira Sul (UFFS), Campus Chapecó-SC. Como resultados, tem-se que o atual modelo de PET-Saúde é benéfico no sentido da continuidade à uma proposta ainda considerada necessária por proporcionar espaços de vivências insubstituíveis pelas vigentes paredes das salas de aula tradicionais, além de contribuir para consolidação da integração ensino-serviço-comunidade tão almejada desde a Reforma Sanitária. Contudo, há uma lacuna considerável, que pode ser encarada até como retrocesso, no sentido do esmorecimento quanto ao estímulo anterior muito claro à interdisciplinaridade e até à transdisciplinaridade, lógica pulsante nos editais passados irradiados do Pró-Saúde, evidenciado pelo fato de agora os grupos tutoriais caminharem majoritariamente separados em sua composição e atuação (no caso estudado, um grupo de Enfermagem e outro de Medicina), reforçando a lógica disciplinar e de fragmentação da equipe de saúde vigentes no cotidiano dos serviços. Outro aspecto a melhorar seria o necessário retorno do PET-Saúde à lógica maior que semeou sua origem (o Pró-Saúde), pois muito além da concessão de bolsas que estimulariam a permanência de alguns atores nesse processo para dinamizar os(as) demais, o eixo estruturante de todas estas iniciativas parece que vem sendo ofuscado pelos incentivos financeiros temporários, a despeito do ideal em se capilarizar movimentos de ensinar e aprender entre todos(as) os(as) profissionais de saúde, enquanto Educadores(as) natos(as) em sintonia com as incumbências trazidos para o SUS pela Lei 8.080/1990, Constituição Federal, e diversas outras legislações e documentos com alusões ao SUS como campo obrigatório para formação de recursos humanos. Por conseguinte, sugere-se que haja uma retomada nos valores formativos presentes no Pró-Saúde, nas Diretrizes Curriculares Nacionais (DNC) dos cursos da área de saúde, e também uma melhor articulação do PET-Saúde com os demais dispositivos formativos, como o VER-SUS (constante no edital vigente), Projeto Rondon, PROVAB, e Programa Mais Médicos.