Enzyme Mechanism and Slow-Onset Inhibition of Plasmodium falciparum Enoyl-Acyl Carrier Protein Reductase by an Inorganic Complex

Malaria continues to be a major cause of children's morbidity and mortality worldwide, causing nearly one million deaths annually. The human malaria parasite, Plasmodium falciparum, synthesizes fatty acids employing the Type II fatty acid biosynthesis system (FAS II), unlike humans that rely on the Type I (FAS I) pathway. The FAS II system elongates acyl fatty acid precursors of the cell membrane in Plasmodium. Enoyl reductase (ENR) enzyme is a member of the FAS II system. Here we present steady-state kinetics, pre-steady-state kinetics, and equilibrium fluorescence spectroscopy data that allowed proposal of P. falciparum ENR (PfENR) enzyme mechanism. Moreover, building on previous results, the present study also evaluates the PfENR inhibition by the pentacyano(isoniazid)ferrateII compound. This inorganic complex represents a new class of lead compounds for the development of antimalarial agents focused on the inhibition of PfENR

In Vitro Antiplasmodial Activity of Flower Extracts from combretum leprosum mart (mofumbo)

Malaria is the cause of hundreds of deaths per year , besides putting billions of people at risk of developing disease. When it comes to its therapy, the drugs used currently are losing its efficacy due to increase inn the frequency of resistant strains of the parasite, highlight the importance for the serach of new classes of molecules prsentign antiplasmodial activity. In the present work, the antiplasmodial activities of five extracts from the flowers of Comretum leprosum are described. The method employed for obtaingine the extracts was silica gel column chromatography, and the techniques used for the analysis of antiplasmodial activity and citotoxicity were ELISA and MTT respectively, were a selectivitu index was calculated after the obtainign of these two values. The extract presenting the highest antiplasmodial activity was the chloroform extract, however, this extrac also presented the higther cytotoxicity and therefore the extract presenting the best overall activity was the hexane extract. The study deminstrated the plant Combretum leprosum has active substances against P. falciparum and therefore is a potential to be expored in funther pharmacological studies

Atividade antiplasmodial e citotóxica in vitro da entrecasca do caule de Maytenus guianensis Klotzsch Ex Reissek

Species of the Maytenus genus (Celastraceae) are commonly used in folk medicine in the Amazon region against cancer and as an anti-inflammatory agent. Maytenus guianensis, popularly known as “chichuá” or “xixuá”, is a widespread tree in the Amazon rainforest. In this study, we investigated the acetone extract of the inner bark of this species regarding its cytotoxic activity against HepG2 cells and its antiplasmodial activity against the 3D7 strain of Plasmodium falciparum. Cytotoxicity was determined by the colorimetric method (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) and the anti-P. falciparum activity was tested using anti-HRPII antibodies in an enzyme-linked immunosorbent assay. In the cytotoxicity assay, no cytotoxic activity was detected in any tested sample, according to the National Institute of Cancer standards. The results of the anti-P. falciparum  test, on the other hand, were promising (values expressed as IC50, in ng.mL-1): 253.02 ± 0.56 for the acetone extract of the inner bark, 292.23 ± 0.83 for the hexane fraction, 292.76 ± 0.51 for the chloroform fraction, 188.37 ± 0.74 for the acetone fraction, 837.04 ± 0.23 for friedelinol, and 950.25 ± 0.46 for 16 β-hydroxyfriedelin. Our results contributed with the chemotaxonomy of the Celastraceae and showed that M. guianensis may be an alternative source of compounds that could be used in prototypes of anti-malaria drugs.Espécies pertencentes ao gênero Maytenus (Celastraceae) são utilizadas na medicina tradicional na região Amazônica contra câncer, como anti-inflamatório. M. guianensis, popularmente conhecida como “chichuá e xixuá” é uma árvore muito difundida na floresta Amazônica. No presente estudo o extrato acetônico da entrecasca do caule desta espécie foi investigada acerca de sua atividade citotóxica nas células HepG2 e antiplasmodial no Plasmodium falciparum cepa 3D7. A citotoxicidade foi determinada através do método colorimétrico do (3-(4,5-dimetiltiazol-2-il)-2,5-difenil tetrazólio) e o teste anti-P. falciparum através do ensaio imunoenzimático anti-HRPII. Para o teste de atividade citotóxica nenhuma amostra testada apresentou citotoxicidade de acordo com o National Institute of Cancer. No teste anti-P. falciparum os resultados foram promissores e expressos em termos de IC50 (ng.mL-1), respectivamente: extrato acetônico da entrecasca do caule com 253,02 ± 0,56, fração hexânica com 292,23 ± 0,83, fração clorofórmica com 292,76 ± 0,01, fração acetônica com 188,37, friedelinol com 837,04 ± 0,05 e 16 β-hidroxifridelina com 950,25 ± 0,46. Os resultados obtidos contribuíram para o estudo quimiotaxonômico da família Celastraceae e mostrou que M. guianensis pode vir a ser uma fonte alternativa de compostos que poderão ser protótipos de drogas que atuarão frente à malária

Eficácia de intervenções imunomoduladoras para o tratamento da Esclerose Lateral Amiotrófica (ELA)

A esclerose lateral amiotrófica (ELA) é uma doença neurodegenerativa que afeta as células nervosas responsáveis pelo controle dos músculos voluntários, resultando em fraqueza muscular e atrofia. Nesse contexto, as intervenções imunomoduladoras têm como objetivo modular a resposta imune do organismo, ao reduzir a inflamação e possibilitar a neuroproteção, a partir do uso de anticorpos monoclonais, inibidores de citocinas e moduladores do sistema imunológico. No entanto, a eficácia de tais intervenções no tratamento da ELA ainda é incerta. Nesse sentido, o presente estudo tem como objetivo analisar a eficácia de intervenções imunomoduladoras para o tratamento da esclerose lateral amiotrófica. Para isso, foram selecionados cinco artigos que abordavam sobre a sua eficácia, por meio de uma estratégia de busca com recorte temporal entre 2017 e 2023, nas bases de dados PubMed (Medline), Cochrane Library e Embase. As intervenções imunomoduladoras, como o uso de inibidores de citocinas, têm demonstrado eficácia no tratamento da esclerose lateral amiotrófica (ELA). Além disso, há evidências de que a inflamação crônica pode estar envolvida em sua patogênese, o que sugere que a modulação do sistema imunológico pode ser uma abordagem terapêutica promissora. Em estudos clínicos recentes, a terapia com inibidores de citocinas mostrou-se capaz de reduzir a progressão da doença e melhorar a qualidade de vida dos pacientes com ELA. Ademais, há evidências que o uso de células-tronco pode melhorar o status funcional em pacientes com a doença. Entretanto, são necessários mais estudos, como ensaios clínicos randomizados e revisões sistemáticas com meta-análises, a fim de ratificar a eficácia das estratégias imunomoduladoras para a patologia

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