Biological effects of trans, trans-farnesol in Leishmania amazonensis

IntroductionFarnesol, derived from farnesyl pyrophosphate in the sterols biosynthetic pathway, is a molecule with three unsaturations and four possible isomers. Candida albicans predominantly secretes the trans, trans-farnesol (t, t-FOH) isomer, known for its role in regulating the virulence of various fungi species and modulating morphological transition processes. Notably, the evolutionary divergence in sterol biosynthesis between fungi, including Candida albicans, and trypanosomatids resulted in the synthesis of sterols with the ergostane skeleton, distinct from cholesterol. This study aims to assess the impact of exogenously added trans, trans-farnesol on the proliferative ability of Leishmania amazonensis and to identify its presence in the lipid secretome of the parasite.MethodsThe study involved the addition of exogenous trans, trans-farnesol to evaluate its interference with the proliferation of L. amazonensis promastigotes. Proliferation, cell cycle, DNA fragmentation, and mitochondrial functionality were assessed as indicators of the effects of trans, trans-farnesol. Additionally, lipid secretome analysis was conducted, focusing on the detection of trans, trans-farnesol and related products derived from the precursor, farnesyl pyrophosphate. In silico analysis was employed to identify the sequence for the farnesene synthase gene responsible for producing these isoprenoids in the Leishmania genome.ResultsExogenously added trans, trans-farnesol was found to interfere with the proliferation of L. amazonensis promastigotes, inhibiting the cell cycle without causing DNA fragmentation or loss of mitochondrial functionality. Despite the absence of trans, trans-farnesol in the culture supernatant, other products derived from farnesyl pyrophosphate, specifically α-farnesene and β-farnesene, were detected starting on the fourth day of culture, continuing to increase until the tenth day. Furthermore, the identification of the farnesene synthase gene in the Leishmania genome through in silico analysis provided insights into the enzymatic basis of isoprenoid production.DiscussionThe findings collectively offer the first insights into the mechanism of action of farnesol on L. amazonensis. While trans, trans-farnesol was not detected in the lipid secretome, the presence of α-farnesene and β-farnesene suggests alternative pathways or modifications in the isoprenoid metabolism of the parasite. The inhibitory effects on proliferation and cell cycle without inducing DNA fragmentation or mitochondrial dysfunction raise questions about the specific targets and pathways affected by exogenous trans, trans-farnesol. The identification of the farnesene synthase gene provides a molecular basis for understanding the synthesis of related isoprenoids in Leishmania. Further exploration of these mechanisms may contribute to the development of novel therapeutic strategies against Leishmania infections

A relação dos fármacos agonistas de receptores GLP-1 e a proteção de doença renal para pacientes com Diabetes Mellitus

A diabetes mellitus compreende a incapacidade do organismo de desempenhar a função fisiológica da insulina, ocasionando uma grande carga de doenças, incluindo doença renal ou renal crônica e cardiovasculares. Os agonistas do receptor de GLP-1 são empregados em pacientes com diabetes tipo 2 como terapias de redução da glicose diversos à saúde destes pacientes. O objetivo deste estudo foi analisar a forma de ação dos agonistas de receptores GLP-1 como um fator de proteção à patologia renal crônica, em indivíduos portadores de diabetes mellitus do tipo 2, por meio de uma revisão bibliográfica sistemática. Os dados publicados demonstram que que agonistas do receptor GLP-1 reduzem a morte e incidência de doença renal terminal ou de insuficiência renal. Adicionalmente estes fármacos podem bloquear os mecanismos envolvidos em doenças renais, além de amenizar o estresse oxidativo e apoptose celular no rim. As terapias utilizadas com o uso de agonistas GLP-1 têm se mostrado agentes redutores da glicose e eficazes para pacientes com diabetes mellitus tipo 2, sendo recomendadas por instituições americanas e européias

Participação cidadã na sociedade civil global Citizen participation in the global civil society

O artigo discute a constituição de um espaço público global, focalizando sobretudo a ação de organizações não-governamentais que exercem pressão, em diferentes fóruns multilaterais, no sentido da constituição de um sistema internacional de prestação de contas com respeito a questões tais como as finanças internacionais, meio ambiente, qualidade de vida e segurança.<br>The article discusses the constitution of a global public space, with main focus on the action of non-governamental organizations which express in multiple international settings their concern with the creation of an international system of accountability directed to such questions as international finance, environment, quality of life and security

Santos e devotos no império ultramarino português

O artigo faz uma história da coleção de vilancicos de São Gonçalo de Amarante, que integram a Coleção Barbosa Machado na Biblioteca Nacional do Rio de Janeiro e, simultaneamente, apresenta reflexões sobre a relação santo-devoto no Império Ultramarino Português no século XVIII. Os vilancicos são identificados como um gênero retórico poético que evoca o santo e uma prática religiosa que contrastava com outras. Parte-se de uma perspectiva comparativa entre os vilancicos e outras evidências sobre a relação santo-devoto e, em particular, sobre o santo e sua festa na sociedade colonial escravista. O artigo dialoga com a historiografia centrada na noção de Império e com uma bibliografia da História e das Ciências Sociais voltada para a relação santodevoto, a santidade e as festas.<br>The paper produces a story of vilancicos for Saint Gonçalo do Amarante, that are part of the Rio de Janeiro National Library Barbosa Machado Collection and presents reflections on the relation saint-devotees in the Portuguese Overseas Empire during the 18th century. The vilancicos are identified as a rhetoric poetic genre that reminds the saint and a religious practice that contrasted with others. It starts from a comparative perspective between the vilancicos and other evidences about the relation saint-devotee, and in particular, about the saint and his feast in a colonial and proslavery society. The article deals with the historiography centered in the notion of Empire, and with a bibliography of History and Social Sciences pointed to the relation saint-devotee, the holiness and the feasts

NEOTROPICAL XENARTHRANS: a data set of occurrence of xenarthran species in the Neotropics

Xenarthrans—anteaters, sloths, and armadillos—have essential functions for ecosystem maintenance, such as insect control and nutrient cycling, playing key roles as ecosystem engineers. Because of habitat loss and fragmentation, hunting pressure, and conflicts with domestic dogs, these species have been threatened locally, regionally, or even across their full distribution ranges. The Neotropics harbor 21 species of armadillos, 10 anteaters, and 6 sloths. Our data set includes the families Chlamyphoridae (13), Dasypodidae (7), Myrmecophagidae (3), Bradypodidae (4), and Megalonychidae (2). We have no occurrence data on Dasypus pilosus (Dasypodidae). Regarding Cyclopedidae, until recently, only one species was recognized, but new genetic studies have revealed that the group is represented by seven species. In this data paper, we compiled a total of 42,528 records of 31 species, represented by occurrence and quantitative data, totaling 24,847 unique georeferenced records. The geographic range is from the southern United States, Mexico, and Caribbean countries at the northern portion of the Neotropics, to the austral distribution in Argentina, Paraguay, Chile, and Uruguay. Regarding anteaters, Myrmecophaga tridactyla has the most records (n = 5,941), and Cyclopes sp. have the fewest (n = 240). The armadillo species with the most data is Dasypus novemcinctus (n = 11,588), and the fewest data are recorded for Calyptophractus retusus (n = 33). With regard to sloth species, Bradypus variegatus has the most records (n = 962), and Bradypus pygmaeus has the fewest (n = 12). Our main objective with Neotropical Xenarthrans is to make occurrence and quantitative data available to facilitate more ecological research, particularly if we integrate the xenarthran data with other data sets of Neotropical Series that will become available very soon (i.e., Neotropical Carnivores, Neotropical Invasive Mammals, and Neotropical Hunters and Dogs). Therefore, studies on trophic cascades, hunting pressure, habitat loss, fragmentation effects, species invasion, and climate change effects will be possible with the Neotropical Xenarthrans data set. Please cite this data paper when using its data in publications. We also request that researchers and teachers inform us of how they are using these data