RESUMO
The identification of new drugs with few or no adverse effects is of great interest worldwide. In cancer therapy, natural products have been used as chemopreventive and chemotherapeutic agents. Plants from the Brazilian savannah belonging to the Byrsonima genus are popularly known as muricis and have attracted much attention due to their various pharmacological activities. However, there are currently no data on these plants concerning their use as chemopreventive or chemotherapeutic agents in human cell lines. The present study assessed the potential of B. correifolia, B. verbascifolia, B. crassifolia, and B. intermedia extracts as natural alternatives in the prevention and/or treatment of cancer. The chemical constituents present in each extract were analyzed by electrospray ionization-mass spectrometry (ESI-MSN). The mutagenic/antimutagenic (micronucleus assay), genotoxic/antigenotoxic (comet assay), apoptotic/necrotic (acridine orange/ethidium bromide uptake), and oxidative/antioxidative (CM-H2DCFDA) effects of the extracts and their influence on gene expression (RTqPCR) were investigated in nonmetabolizing gastric (MNP01) and metabolizing hepatocarcinoma (HepG2) epithelial cells to evaluate the effects of metabolism on the biological activities of the extracts. The genotoxicity, mutagenicity, and apoptotic effects observed in HepG2 cells with B. correifolia and B. verbascifolia extracts are probably associated with the presence of proanthocyanidins and amentoflavone. In MNP01 cells, none of the four extracts showed mutagenic effects. B. crassifolia and B. intermedia extracts exhibited strong antimutagenicity and enhanced detoxification in HepG2 cells and antioxidant capacities in both types of cells, possibly due to the presence of gallic and quinic acids, which possess chemopreventive properties. This study identifies for the first time B. correifolia and B. verbascifolia extracts as potential agents against hepatocarcinoma and B. crassifolia and B. intermedia extracts as putative chemopreventive agents.
Assuntos
Anticarcinógenos , Antimutagênicos , Humanos , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Brasil , Plantas , Antioxidantes/farmacologia , Mutagênicos/toxicidade , Instabilidade Genômica , Antimutagênicos/farmacologiaRESUMO
The synthetic peptide p-BTX-I is based on the native peptide (formed by glutamic acid, valine and tryptophan) isolated from Bothrops atrox venom. We have previously demonstrated its neuroprotective and neurotrophic properties in PC12 cells treated with the dopaminergic neurotoxin 1-methyl-4-phenylpyridinium (MPP+). Now, we have investigated the neuroprotective effects and mechanisms of p-BTX-I against the toxicity of acrolein in PC12 cells. Studies have demonstrated that acrolein might play an important role in the etiology of Alzheimer's disease (AD), which is characterized by neuronal and synaptic loss. Our results showed that not only acrolein reduced cell differentiation and cell viability, but also altered the expression of markers of synaptic communication (synapsin I), energy metabolism (AMPK-α, Sirt I and glucose uptake), and cytoskeleton (ß-III-tubulin). Treatment with p-BTX-I increased the percentage of differentiation in cells treated with acrolein and significantly attenuated cell viability loss, besides counteracting the negative effects of acrolein on synapsin I, AMPK-α, Sirt I, glucose uptake, and ß-III-tubulin. Additionally, p-BTX-I alone increased the expression of apolipoprotein E (apoE) gene, associated with the proteolytic degradation of ß-amyloid peptide aggregates, a hallmark of AD. Taken together, these findings demonstrate that p-BTX-I protects against acrolein-induced neurotoxicity and might be a tool for the development of novel drugs for the treatment of neurodegenerative diseases.
Assuntos
Proteínas Quinases Ativadas por AMP/biossíntese , Acroleína/antagonistas & inibidores , Metabolismo Energético/efeitos dos fármacos , Glucose/metabolismo , Plasticidade Neuronal/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Sirtuína 1/biossíntese , Sinapsinas/biossíntese , Tubulina (Proteína)/biossíntese , Acroleína/toxicidade , Animais , Apolipoproteínas E/biossíntese , Biomarcadores/metabolismo , Diferenciação Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células PC12 , Peptídeos/farmacologia , RatosRESUMO
OBJECTIVE: This study proposed to use the nanotechnology to deliver glycoalkaloidic extract (AE) to bladder cancer cells, evaluating their activity in 2D and 3D models and the biological mechanism of cell death. METHODS: NPs were prepared by nanoprecipitation method using polylactic acid (PLA) and characterized considering their size, charge, particle concentration and stability. The cytotoxicity was evaluated in 2D and 3D model, and the apoptosis and cell cycle were investigated using flow cytometry. KEY FINDINGS: NPs loading AE (NP-AE) had diameter around 125 ± 6 nm (PdI <0.1) and negative charge. The encapsulation efficiency of SM and SS was higher than 85% for both compounds. The obtained formulation showed a significant in-vitro cytotoxic effect against RT4 cells in a dose-dependent manner with IC50 two fold lower than the free AE. The cytotoxic effect of NP-AE was mediated by apoptosis and cell cycle arrested in the S phase. RT4 cells cultured under 3D conditions exhibited a higher resistance to the treatments (IC50 ~ three fold higher than in 2D cell culture). CONCLUSION: The NP-AE might be a promising nanocarrier to load and deliver glycoalkaloids against bladder cancer.
Assuntos
Alcaloides/química , Alcaloides/farmacologia , Nanopartículas/química , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Neoplasias da Bexiga Urinária/tratamento farmacológico , Antineoplásicos/química , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Portadores de Fármacos/química , Humanos , Nanotecnologia/métodos , Tamanho da Partícula , Poliésteres/química , Fase S/efeitos dos fármacos , Bexiga Urinária/efeitos dos fármacosRESUMO
ABSTRACT In general, students have few opportunities to address their emotions under the guidance of an experienced physician, which can undermine their self-confidence to deal with real patients in stressful situations. Emotional detachment and cynicism are defense mechanisms, which can emerge as a consequence. The consolidation of a professional identity committed to patients' interests can become a challenge when medical students are not comfortable in their role as caregivers. In general, we consider that the undergraduate medical curriculum has been insufficient in providing appropriate environments for students to reflect on professional identity formation and on the future challenges of their profession. Objective: To develop an in-depth debriefing to address students' emotions and professional identity formation in the context of a simulation activity with simulated patients at a medical school in Brazil. Methods: The authors conducted a simulated medical consultation activity using standardized patients (SPs) with an in-depth debriefing based on the feelings of the patient and the student. During each encounter the formation and consolidation of professional identity was discussed. Fourth- and sixth-year medical students (n=551) participated and answered a questionnaire about the activity and the learning outcome. Results: The students felt comfortable during the activity, due to "openness to dialogue", "proximity with colleagues and teachers" and the "judgment-free environment". More than 90% reported that what they had learned would be useful in their professional and personal lives, providing a greater "understanding of emotions", "empathy", "ability to listen" and "ability to deal with conflicts". More than half of them were motivated to study, especially "doctor-patient relationship", "treatment", "common diseases" and "medicine in general". Students considered the activity important for retrieving the initial reasons that had led them to embarking on the medical profession in the first place. Conclusions: Reflecting on disease and its impact on patients' daily life may motivate learning in medicine, allowing for the recovery of the personal and social meaning of its practice. In-depth debriefing was important to nurture professional identity committed to empathy and patients' interests. Activities planned to discuss the influence and importance of emotions in medical practice can help students to reconcile personal and professional identities.
RESUMO Em geral, os estudantes de medicina têm poucas oportunidades para refletir sobre suas emoções guiados por um médico mais experiente, e isto pode levar a uma diminuição da sua autoconfiança para lidar com pacientes reais, particularmente em situações de estresse. Como consequência podem surgir o distanciamento emocional e o cinismo. Neste contexto, a consolidação de uma identidade profissional comprometida com os interesses do paciente pode ser um desafio se os estudantes não estiverem confortáveis em seus papéis de cuidadores. Muitas vezes, o currículo médico não cria oportunidades suficientes para refletir sobre o desenvolvimento da identidade profissional e sobre os desafios da prática médica futura. Objetivo: Desenvolver um debriefing estendido e profundo para abordar a dimensão afetiva das consultas médicas e a formação da identidade profissional no contexto de uma atividade de simulação com pacientes padronizados em uma escola médica no Brasil. Métodos: Os autores conduziram uma atividade de simulação de consultas médicas com paciente padronizado com um debriefing estendido baseado nas emoções do paciente e do estudante. Durante cada um dos encontros a formação e consolidação da identidade profissional foram abordadas. Alunos do quarto e sexto ano médicos (n=551) participaram das atividades e responderam um questionário sobre a atividade e sobre os objetivos alcançados. Resultados: Os estudantes sentiram-se confortáveis durante a atividade devido a "abertura para o diálogo", "proximidade com professores e colegas" e um "ambiente livre de julgamentos". Mais de 90% dos estudantes considerou que o aprendizado será aplicado tanto em suas vidas profissionais como em suas vidas pessoais, por um maior "entendimento das emoções", "empatia", "habilidade para ouvir" e "habilidade para lidar com conflitos". Mais da metade dos estudantes sentiu-se motivada a estudar, especialmente "relação médico-paciente", "tratamento", "doenças comuns" e "medicina em geral". A atividade foi considerada importante para resgatar a motivação inicial que os levaram a escolher o curso médico. Conclusões: Refletir sobre as doenças e seus impactos na vida dos pacientes pode motivar os estudantes a aprender medicina, permitindo o resgate do significado pessoal e social de sua prática. O aprofundamento do debriefing foi importante para nutrir uma identidade profissional comprometida com a empatia e com os interesses dos pacientes. Atividades planejadas para abordar a influência e a importância das emoções na prática médica podem ajudar os estudantes no processo de reconciliação entre suas identidades pessoal e profissional.
RESUMO
Informações recentes sobre a associação de aspectos moleculares e funcionais em bubalinos criaram novas oportunidades para estudar da regulação da reprodução nesta espécie e seu papel na fisiologia e, consequentemente, eficiência produtiva. Tem sido apontada interação de um "coquetel molecular" que opera de modo independente ou interdependente às funções celulares, hormonais e maturacionais relacionadas à fertilidade animal, uma vez que há genes cujos padrões de diversidade, mutações e polimorfismos estão diretamente associados às características reprodutivas em bubalinos. Nesta revisão serão evidenciadas algumas pesquisas, em sua maioria realizadas com a espécie bubalina, cujos resultados e considerações representam as ideias e paradigmas de vários autores. Considerando a importância deste tema, objetiva-se com este manuscrito, descrever alguns mecanismos moleculares já conhecidos e especular sobre as perspectivas futuras da pesquisa para encontrar links entre a biologia molecular e a eficiência reprodutiva observada no campo.(AU)
Recent researches on the association of molecular and functional aspects in buffaloes has created new opportunities to study of reproductive regulation and its role in physiology and, consequently, productive efficiency. Have been described a "molecular cocktail" that controls independently or interdependently the cellular, hormonal and maturational functions related to animal fertility, since there are genes whose diversity patterns, mutations and polymorphisms, are directly associated with reproductive traits in buffaloes. In this review, will be emphasized some results and considerations that represent the ideas and paradigms of several authors. The aim of this manuscript is to describe some molecular mechanisms already known and to speculate on the future prospects to find links between molecular biology and reproductive efficiency observed in the field.(AU)
Assuntos
Animais , Búfalos/genética , Polimorfismo Genético , Biologia Molecular , Búfalos/fisiologia , Reprodução/genética , Reprodução/fisiologiaRESUMO
Informações recentes sobre a associação de aspectos moleculares e funcionais em bubalinos criaram novas oportunidades para estudar da regulação da reprodução nesta espécie e seu papel na fisiologia e, consequentemente, eficiência produtiva. Tem sido apontada interação de um "coquetel molecular" que opera de modo independente ou interdependente às funções celulares, hormonais e maturacionais relacionadas à fertilidade animal, uma vez que há genes cujos padrões de diversidade, mutações e polimorfismos estão diretamente associados às características reprodutivas em bubalinos. Nesta revisão serão evidenciadas algumas pesquisas, em sua maioria realizadas com a espécie bubalina, cujos resultados e considerações representam as ideias e paradigmas de vários autores. Considerando a importância deste tema, objetiva-se com este manuscrito, descrever alguns mecanismos moleculares já conhecidos e especular sobre as perspectivas futuras da pesquisa para encontrar links entre a biologia molecular e a eficiência reprodutiva observada no campo.
Recent researches on the association of molecular and functional aspects in buffaloes has created new opportunities to study of reproductive regulation and its role in physiology and, consequently, productive efficiency. Have been described a "molecular cocktail" that controls independently or interdependently the cellular, hormonal and maturational functions related to animal fertility, since there are genes whose diversity patterns, mutations and polymorphisms, are directly associated with reproductive traits in buffaloes. In this review, will be emphasized some results and considerations that represent the ideas and paradigms of several authors. The aim of this manuscript is to describe some molecular mechanisms already known and to speculate on the future prospects to find links between molecular biology and reproductive efficiency observed in the field.
Assuntos
Animais , Biologia Molecular , Búfalos/fisiologia , Búfalos/genética , Polimorfismo Genético , Reprodução/fisiologia , Reprodução/genéticaRESUMO
Brazilian flora biodiversity has been widely investigated to identify effective and safe phytotherapeutic compounds. Among the investigated plant species, the Byrsonima genus exhibits promising biological activities. This study aimed at evaluating the cytotoxicity of B. correifolia, B. verbascifolia, B. fagifolia and B. intermedia extracts using different assays in two cell lines (primary gastric and HepG2 cells). The different extract concentrations effects on cell viability were assayed using the MTT, aquabluer, neutral red and LDH assays. Non-cytotoxic concentrations were selected to generate cell proliferation curves and to assess cell cycle kinetics by flow cytometry. Byrsonima extracts differentially affected cell viability depending on the metabolic cellular state and the biological parameter evaluated. B. fagifolia and B. intermedia extracts exhibited lower cytotoxic effects than B. correifolia and B. verbascifolia in all assays. The results obtained with LDH and flow cytometry assays were more reliable, suggesting that they can be useful in the screening for herbal medicine and to further characterize these extracts as phytotherapeutic compounds.
RESUMO
BACKGROUND: Lung ultrasound (US) is an excellent tool to assess lung edema in a myriad of different clinical situations. We hypothesized that lung US might also be a good prognostic and management instrument in septic patients, regardless of disease severity. METHODS: This was a prospective observational cohort study at an urban academic emergency department (ED). Inclusion criteria were as follows: septic patients, at least 18 years old, admitted at the ED of a tertiary hospital. A simplified lung edema scoring system (SLESS) was developed, and 6 thoracic regions were evaluated. Four different lung US patterns were considered, from normal aeration to total consolidation. To evaluate disease severity, the SLESS was compared with the Mortality in Emergency Department Sepsis Score and the third version of the Simplified Acute Physiology Score scoring systems. Aiming to assess the effect of the lung edema in the gas exchange, the SLESS was compared with the Pao2/fraction of inspired oxygen ratio. RESULTS: Sixty-one patients were enrolled in a 3-month period. The SLESS had a good correlation with the Mortality in Emergency Department Sepsis Score and Simplified Acute Physiology Score (r = 0.53 and r = 0.55, respectively; P < .001 for both) and a negative correlation with the Pao2/fraction of inspired oxygen ratio (r = -0.62; P < .001). The SLESS also showed correlation with the respiratory rate (r = 0.45; P = .0003). The odds ratio for death related to the SLESS was 1.370 (95% confidence interval, 1.109-1.691; P = .0035). CONCLUSION: The SLESS is an easy and practical scoring system. It might be a useful tool to predict severity of disease in sepsis patients. The SLESS might also be able to be correlated with the oxygen exchange.