Flavonoids from the Brazilian plant Croton betulaster inhibit the growth of human glioblastoma cells and induce apoptosis

This study investigated the effects of the flavonoids 5-hydroxy-7,4′-dimethoxyflavone, casticin, and penduletin, isolated from Croton betulaster Müll Arg., Euphorbiaceae, a plant utilized in popular medicine in Brazil, on the growth and viability of the human glioblastoma cell line GL-15. We observed that 5-hydroxy-7,4′-dimethoxyflavone and casticin were not toxic to GL-15 cells after 24 h of exposure. However, casticin and penduletin inhibited the metabolic activity of glioblastoma cells significantly at a concentration of 10 μM (p ≤ 0.05). Flavonoids casticin and penduletin also induced a significant and dose-dependent growth inhibition beginning at 24 h of exposure, and the most potent flavonoid was penduletin. It was also observed that penduletin and casticin induced an enlargement of the cell body and a reduction of cellular processes, accompanied by changes in the pattern of expression of the cytoskeletal protein vimentin. Signs of apoptosis, such as the externalization of membrane phosphatidyl serine residues, nuclear condensation, and fragmentation, were also detected in cells treated with 50–100 μM flavonoids. Our results indicate that flavonoids extracted from C. betulaster present antitumoral activity to glioblastoma cells, with penduletin proving to be the most potent of the tested flavonoids. Our results also suggest that these molecules may be promising supplementary drugs for glioblastoma treatment

Pervasive gaps in Amazonian ecological research

Biodiversity loss is one of the main challenges of our time,1,2 and attempts to address it require a clear un derstanding of how ecological communities respond to environmental change across time and space.3,4 While the increasing availability of global databases on ecological communities has advanced our knowledge of biodiversity sensitivity to environmental changes,5–7 vast areas of the tropics remain understudied.8–11 In the American tropics, Amazonia stands out as the world’s most diverse rainforest and the primary source of Neotropical biodiversity,12 but it remains among the least known forests in America and is often underrepre sented in biodiversity databases.13–15 To worsen this situation, human-induced modifications16,17 may elim inate pieces of the Amazon’s biodiversity puzzle before we can use them to understand how ecological com munities are responding. To increase generalization and applicability of biodiversity knowledge,18,19 it is thus crucial to reduce biases in ecological research, particularly in regions projected to face the most pronounced environmental changes. We integrate ecological community metadata of 7,694 sampling sites for multiple or ganism groups in a machine learning model framework to map the research probability across the Brazilian Amazonia, while identifying the region’s vulnerability to environmental change. 15%–18% of the most ne glected areas in ecological research are expected to experience severe climate or land use changes by 2050. This means that unless we take immediate action, we will not be able to establish their current status, much less monitor how it is changing and what is being lostinfo:eu-repo/semantics/publishedVersio

Os aspectos semiológicos do acidente vascular encefálico: uma abordagem neurológica

O Acidente Vascular Encefálico (AVC) é um evento neurológico súbito, com um foco de isquemia ou hemorragia. Ambos, qualificados pelo déficit neurológico focal abrupto. Ressaltando, que estes déficits podem ocorrer, sendo a ocorrência espontânea, perduração de 15 minutos, autoresolutiva é denominada como Ataque Isquêmico Transitório (AIT), no entanto, toda insuficiência neural que não melhorar pós esse período deve ser manejado como AVC. O artigo objetivou descrever os principais aspectos clínicos do AVC. O AVC é uma emergência para a saúde pública, em razão de ser um potencial em gerar morbimortalidades para os portadores e prejuízos para os sistemas de saúde. O AVC do tipo isquêmico representa a maioria das ocorrências, o quadro clínico do paciente é correspondente ao tecido neural afetado, inicialmente a tomografia computadorizada sem contraste é o primeiro exame, por ser crucial para descartar a etiologia hemorrágica, a condução terapêutica se baseia em medidas neuroprotetoras através da estabilização da glicemia, temperatura e sódio, adequar os níveis pressóricos, mediante o prazo estipulado impor terapia antitrombótica. A manifestação hemorrágica, pode ocorrer por torção de aneurisma sacular originando o sangramento subaracnóideo ou por hipertensão gerando o sangramento intraparenquimatoso. A partir da análise das informações coletadas, elucida-se que o diagnóstico precoce e o período transcorrido até o manejo terapêutico são cruciais para o desfecho clínico do portador, ou seja, é possível a normalização ou ocorrer sequelas neurais e óbito

Pervasive gaps in Amazonian ecological research

Biodiversity loss is one of the main challenges of our time,1,2 and attempts to address it require a clear understanding of how ecological communities respond to environmental change across time and space.3,4 While the increasing availability of global databases on ecological communities has advanced our knowledge of biodiversity sensitivity to environmental changes,5,6,7 vast areas of the tropics remain understudied.8,9,10,11 In the American tropics, Amazonia stands out as the world's most diverse rainforest and the primary source of Neotropical biodiversity,12 but it remains among the least known forests in America and is often underrepresented in biodiversity databases.13,14,15 To worsen this situation, human-induced modifications16,17 may eliminate pieces of the Amazon's biodiversity puzzle before we can use them to understand how ecological communities are responding. To increase generalization and applicability of biodiversity knowledge,18,19 it is thus crucial to reduce biases in ecological research, particularly in regions projected to face the most pronounced environmental changes. We integrate ecological community metadata of 7,694 sampling sites for multiple organism groups in a machine learning model framework to map the research probability across the Brazilian Amazonia, while identifying the region's vulnerability to environmental change. 15%–18% of the most neglected areas in ecological research are expected to experience severe climate or land use changes by 2050. This means that unless we take immediate action, we will not be able to establish their current status, much less monitor how it is changing and what is being lost

Pervasive gaps in Amazonian ecological research

Biodiversity loss is one of the main challenges of our time,1,2 and attempts to address it require a clear understanding of how ecological communities respond to environmental change across time and space.3,4 While the increasing availability of global databases on ecological communities has advanced our knowledge of biodiversity sensitivity to environmental changes,5,6,7 vast areas of the tropics remain understudied.8,9,10,11 In the American tropics, Amazonia stands out as the world's most diverse rainforest and the primary source of Neotropical biodiversity,12 but it remains among the least known forests in America and is often underrepresented in biodiversity databases.13,14,15 To worsen this situation, human-induced modifications16,17 may eliminate pieces of the Amazon's biodiversity puzzle before we can use them to understand how ecological communities are responding. To increase generalization and applicability of biodiversity knowledge,18,19 it is thus crucial to reduce biases in ecological research, particularly in regions projected to face the most pronounced environmental changes. We integrate ecological community metadata of 7,694 sampling sites for multiple organism groups in a machine learning model framework to map the research probability across the Brazilian Amazonia, while identifying the region's vulnerability to environmental change. 15%–18% of the most neglected areas in ecological research are expected to experience severe climate or land use changes by 2050. This means that unless we take immediate action, we will not be able to establish their current status, much less monitor how it is changing and what is being lost

O estresse nosso de cada dia: estudo de caso sobre o estresse no trabalho em órgãos da administração pública

Since the second half of the XXth century, the approach of the mental load of job and stress drew attention organizations and researchers in search of a better understanding of the manners of reducing the pressures which affect the operators. Models for surveillance and prevention of the situations of stress at job were developed as tools of help to the dyking of this illness and how they can contribute to the visualization of stress to ameliorate situations. In the present study is introduced empirical researches led with public agencies of the State of Sao Paulo to prove working conditions of the civil servants, and to define borders for the observation of stress.A partir da segunda metade do século XX, a abordagem sobre as cargas psíquicas do trabalho e sobre o estresse vem atraindo a atenção de organizações e pesquisadores, em busca de uma maior compreensão sobre meios de reduzir os constrangimentos que afligem que os operadores. Modelos para prevenção e acompanhamento de situações de estresse no trabalho foram elaborados como ferramentas de auxílio na contensão dessa patologia, e podem contribuir para visualização de situações potencializadoras do estresse. No presente estudo serão apresentadas investigações empíricas realizadas junto a órgãos da administração pública do Estado de São Paulo, para verificação das condições de trabalho dos servidores públicos, delimitando fronteiras para a observação de situações de estresse

O estresse nosso de cada dia: estudo de caso sobre o estresse no trabalho em órgãos da administração pública

Since the second half of the XXth century, the approach of the mental load of job and stress drew attention organizations and researchers in search of a better understanding of the manners of reducing the pressures which affect the operators. Models for surveillance and prevention of the situations of stress at job were developed as tools of help to the dyking of this illness and how they can contribute to the visualization of stress to ameliorate situations. In the present study is introduced empirical researches led with public agencies of the State of Sao Paulo to prove working conditions of the civil servants, and to define borders for the observation of stress.A partir da segunda metade do século XX, a abordagem sobre as cargas psíquicas do trabalho e sobre o estresse vem atraindo a atenção de organizações e pesquisadores, em busca de uma maior compreensão sobre meios de reduzir os constrangimentos que afligem que os operadores. Modelos para prevenção e acompanhamento de situações de estresse no trabalho foram elaborados como ferramentas de auxílio na contensão dessa patologia, e podem contribuir para visualização de situações potencializadoras do estresse. No presente estudo serão apresentadas investigações empíricas realizadas junto a órgãos da administração pública do Estado de São Paulo, para verificação das condições de trabalho dos servidores públicos, delimitando fronteiras para a observação de situações de estresse

The anti-hypertensive drug prazosin inhibits glioblastoma growth via the PKC-dependent inhibition of the AKT pathway

International audienceA variety of drugs targeting monoamine receptors are routinely used in human pharmacology. We assessed the effect of these drugs on the viability of tumor-initiating cells isolated from patients with glioblastoma. Among the drugs targeting monoamine receptors, we identified prazosin, an 1- and 2B-adrenergic receptor antagonist, as the most potent inducer of patient-derived glioblastoma-initiating cell death. Prazosin triggered apoptosis of glioblastoma-initiating cells and of their differentiated progeny, inhibited glioblastoma growth in orthotopic xenografts of patient-derived glioblastoma-initiating cells, and increased survival of glioblastoma-bearing mice. We found that prazosin acted in glioblastoma-initiating cells independently from adrenergic receptors. Its off-target activity occurred via a PKC-dependent inhibition of the AKT pathway, which resulted in caspase-3 activation. Blockade of PKC activation prevented all molecular changes observed in prazosin-treated glioblastoma-initiating cells, as well as prazosin-induced apoptosis. Based on these data, we conclude that prazosin, an FDA-approved drug for the control of hypertension, inhibits glioblastoma growth through a PKC-dependent mechanism. These findings open up promising prospects for the use of prazosin as an adjuvant therapy for glioblastoma patients

The anti-hypertensive drug prazosin inhibits glioblastoma growth via the PKCd-dependent inhibition of the AKT pathway

Published onlineInternational audienceA variety of drugs targeting monoamine receptors are routinely used in human pharmacology. We assessed the effect of these drugs on the viability of tumor-initiating cells isolated from patients with glioblastoma. Among the drugs targeting monoamine receptors, we identified prazosin, an a1-and a2B-adrenergic receptor antagonist, as the most potent inducer of patient-derived glioblastoma-initiating cell death. Prazosin triggered apoptosis of glioblastoma-initiating cells and of their differentiated progeny, inhibited glioblastoma growth in orthotopic xenografts of patient-derived glioblastoma-initiating cells, and increased survival of glioblastoma-bearing mice. We found that prazosin acted in glioblastoma-initiating cells independently from adrenergic receptors. Its off-target activity occurred via a PKCd-dependent inhibition of the AKT pathway, which resulted in caspase-3 activation. Blockade of PKCd activation prevented all molecular changes observed in prazosin-treated glioblastoma-initiating cells, as well as prazosin-induced apoptosis. Based on these data, we conclude that prazosin, an FDA-approved drug for the control of hyperten-sion, inhibits glioblastoma growth through a PKCd-dependent mechanism. These findings open up promising prospects for the use of prazosin as an adjuvant therapy for glioblastoma patients