Synthesis and cytotoxicity evaluation of thiosemicarbazones and their thiazole derivatives

O estudo teve como objetivo a síntese de uma série de tiossemicarbazonas e seus derivados tiazólicos e a avaliação da atividade citotóxica contra três linhagens de células tumorais humanas e células normais (Vero), a fim de se avaliar o potencial pró-apoptótico dos compostos mais ativos. As tiossemicarbazonas foram obtidas por reação entre um aldeído aromático e tiossemicarbazida (rend. 71-96%), as quais foram submetidas à ciclização com α-bromoacetofenona, fornecendo os heterociclos tiazólicos desejados (rend. 63-100%). Todos os compostos sintetizados foram testados na concentração de 50 µM contra três linhagens de células tumorais: HL60 (leucemia promielocítica), Jurkat (leucemia linfoblástica aguda) e MCF-7 (câncer de mama). O efeito pró-apoptótico foi avaliado por citometria de fluxo como porcentagem de células com DNA hipodiplóide. Três compostos tiazólicos foram ativos contra, pelo menos, uma linhagem tumoral (CI50=43-76 µM), com baixa citotoxicidade contra células Vero (CI50 >; 100 M). O composto mais ativo dessa série induziu fragmentação do DNA de 91% e 51% nas linhagens HL60 e MCF-7, respectivamente, sugerindo que este composto ativou a apoptose nessas células. Dentre os compostos sintetizados, um em particular apresentou atividade antiproliferativa e pró-apoptótica em células tumorais e pode ser considerado composto protótipo promissor na busca por novos análogos com atividade melhorada.The aims of this study were to synthesize a series of thiosemicarbazones and their thiazole derivatives, to investigate their cytotoxic activity against three human cancers and normal (Vero cells) cell lines, and to evaluate the pro-apoptotic potential of the most active compounds. Materials and Methods: The thiosemicarbazones were obtained by reacting an aromatic aldehyde with thiosemicarbazide (yield 71-96%), which were subjected to a cyclization with α-bromoacetophenone to yield the required thiazole heterocycles (yield 63-100%). All the synthesized compounds were screened at 50 µM concentration against three cell lines representing HL60 (promyelocytic leukemia), Jurkat (acute lymphoblastic leukemia), and MCF-7 (breast cancer). The pro-apoptotic effect was measured by flow cytometry as the percentage of cells with hypodiploid DNA. Results: Three thiazole compounds showed activity against at least one tumor cell line (IC50 = 43-76 µM) and low cytotoxicity against Vero cells (IC50 >; 100 M). The most active compound of this series induced 91% and 51% DNA fragmentation in HL60 and MCF-7 cell lines, respectively, suggesting that this compound triggered apoptosis in these cells. Conclusion: Among the synthesized compounds, one in particular was found to exert antiproliferative and pro-apoptotic activity on tumor cells and can be considered promising as a lead molecule for the design of new analogues with improved activity

The Antioxidant Role of Xanthurenic Acid in the Aedes aegypti Midgut during Digestion of a Blood Meal

In the midgut of the mosquito Aedes aegypti, a vector of dengue and yellow fever, an intense release of heme and iron takes place during the digestion of a blood meal. Here, we demonstrated via chromatography, light absorption and mass spectrometry that xanthurenic acid (XA), a product of the oxidative metabolism of tryptophan, is produced in the digestive apparatus after the ingestion of a blood meal and reaches milimolar levels after 24 h, the period of maximal digestive activity. XA formation does not occur in the White Eye (WE) strain, which lacks kynurenine hydroxylase and accumulates kynurenic acid. The formation of XA can be diminished by feeding the insect with 3,4-dimethoxy-N-[4-(3-nitrophenyl)thiazol-2-yl] benzenesulfonamide (Ro-61-8048), an inhibitor of XA biosynthesis. Moreover, XA inhibits the phospholipid oxidation induced by heme or iron. A major fraction of this antioxidant activity is due to the capacity of XA to bind both heme and iron, which occurs at a slightly alkaline pH (7.5-8.0), a condition found in the insect midgut. The midgut epithelial cells of the WE mosquito has a marked increase in occurrence of cell death, which is reversed to levels similar to the wild type mosquitoes by feeding the insects with blood supplemented with XA, confirming the protective role of this molecule. Collectively, these results suggest a new role for XA as a heme and iron chelator that provides protection as an antioxidant and may help these animals adapt to a blood feeding habit

Predicting animal abundance through local ecological knowledge: An internal validation using consensus analysis

Given the ongoing environmental degradation from local to global scales, it is fundamental to develop more efficient means of gathering data on species and ecosystems. Local ecological knowledge, in which local communities can consistently provide information on the status of animal species over time, has been shown to be effective. Several studies demonstrate that data gathered using local ecological knowledge (LEK)-based methods are comparable with data obtained from conventional methods (such as line transects and camera traps). Here, we employ a consensus analysis to validate and evaluate the accuracy of interview data on LEK. Additionally, we investigate the influence of social and bioecological variables on enhancing data quality. We interviewed 323 persons in 19 villages in the Western and Central Amazon to determine the level of consensus on the abundance of hunted and non-hunted forest species. These villages varied in size, socio-economic characteristics and in the experience with wildlife of their dwellers. Interviewees estimated the relative abundance of 101 species with a broad spectrum of bioecological characteristics using a four-point Likert scale. High consensus was found for species population abundance in all sampled villages and for 79.6% of interviewees. The village consensus of all species abundance pooled was negatively correlated with village population size. The consensus level was high regardless of the interviewees' hunting experience. Species that are more frequently hunted or are more apparent had greater consensus values; only two species presented a low consensus level, which are rare and solitary species. We show in our study in the Amazon that information gathered by local peoples, Indigenous as well as non-Indigenous, can be useful in understanding the status of animal species found within their environment. The high level of cultural consensus we describe likely arises from knowledge sharing and the strong connection between the persons interviewed and the forest. We suggest that consensus analysis can be used to validate LEK-generated data instead of comparing these types of data with information obtained by conventional methods

Congruence of local ecological knowledge (LEK)-based methods and line-transect surveys in estimating wildlife abundance in tropical forests

Effective estimation of wildlife population abundance is an important component of population monitoring, and ultimately essential for the development of conservation actions. Diurnal line-transect surveys are one of the most applied methods for abundance estimations. Local ecological knowledge (LEK) is empirically acquired through the observation of ecological processes by local people. LEK-based methods have only been recognized as valid scientific methods for surveying fauna abundance in the last three decades. However, the agreement between both methods has not been extensively analysed. We compared concomitant abundance data for 91 wild species (mammals, birds and tortoises) from diurnal line transects (9,221 km of trails) and a LEK-based method (291 structured interviews) at 18 sites in Central and Western Amazonia. We used biological and socioecological factors to assess the agreements and divergences between abundance indices obtained from both methods. We found a significant agreement of population abundance indices for diurnal and game species. This relationship was also positive regardless of species sociality (solitary or social), body size and locomotion mode (terrestrial and arboreal); and of sampled forest type (upland and flooded forests). Conversely, we did not find significant abundance covariances for nocturnal and non-game species. Despite the general agreement between methods, line transects were not effective at surveying many species occurring in the area, with 40.2% and 39.8% of all species being rarely and never detected in at least one of the survey sites. On the other hand, these species were widely reported by local informants to occur at intermediate to high abundances. Although LEK-based methods have been long neglected by ecologists, our comparative study demonstrated their effectiveness for estimating vertebrate abundance of a wide diversity of taxa and forest environments. This can be used simultaneously with line-transect surveys to calibrate abundance estimates and record species that are rarely sighted during surveys on foot, but that are often observed by local people during their daily extractive activities. Thus, the combination of local and scientific knowledge is a potential tool to improve our knowledge of tropical forest species and foster the development of effective strategies to meet biodiversity conservation goals

Predicting animal abundance through local ecological knowledge: An internal validation using consensus analysis

Given the ongoing environmental degradation from local to global scales, it is fundamental to develop more efficient means of gathering data on species and ecosystems. Local ecological knowledge, in which local communities can consistently provide information on the status of animal species over time, has been shown to be effective. Several studies demonstrate that data gathered using local ecological knowledge (LEK)‐based methods are comparable with data obtained from conventional methods (such as line transects and camera traps). Here, we employ a consensus analysis to validate and evaluate the accuracy of interview data on LEK. Additionally, we investigate the influence of social and bioecological variables on enhancing data quality. We interviewed 323 persons in 19 villages in the Western and Central Amazon to determine the level of consensus on the abundance of hunted and non‐hunted forest species. These villages varied in size, socio‐economic characteristics and in the experience with wildlife of their dwellers. Interviewees estimated the relative abundance of 101 species with a broad spectrum of bioecological characteristics using a four‐point Likert scale. High consensus was found for species population abundance in all sampled villages and for 79.6% of interviewees. The village consensus of all species abundance pooled was negatively correlated with village population size. The consensus level was high regardless of the interviewees' hunting experience. Species that are more frequently hunted or are more apparent had greater consensus values; only two species presented a low consensus level, which are rare and solitary species. We show in our study in the Amazon that information gathered by local peoples, Indigenous as well as non‐Indigenous, can be useful in understanding the status of animal species found within their environment. The high level of cultural consensus we describe likely arises from knowledge sharing and the strong connection between the persons interviewed and the forest. We suggest that consensus analysis can be used to validate LEK‐generated data instead of comparing these types of data with information obtained by conventional methods. Read the free Plain Language Summary for this article on the Journal blog

Fluid challenges in intensive care: the FENICE study A global inception cohort study

Fluid challenges (FCs) are one of the most commonly used therapies in critically ill patients and represent the cornerstone of hemodynamic management in intensive care units. There are clear benefits and harms from fluid therapy. Limited data on the indication, type, amount and rate of an FC in critically ill patients exist in the literature. The primary aim was to evaluate how physicians conduct FCs in terms of type, volume, and rate of given fluid; the secondary aim was to evaluate variables used to trigger an FC and to compare the proportion of patients receiving further fluid administration based on the response to the FC.This was an observational study conducted in ICUs around the world. Each participating unit entered a maximum of 20 patients with one FC.2213 patients were enrolled and analyzed in the study. The median [interquartile range] amount of fluid given during an FC was 500 ml (500-1000). The median time was 24 min (40-60 min), and the median rate of FC was 1000 [500-1333] ml/h. The main indication for FC was hypotension in 1211 (59 %, CI 57-61 %). In 43 % (CI 41-45 %) of the cases no hemodynamic variable was used. Static markers of preload were used in 785 of 2213 cases (36 %, CI 34-37 %). Dynamic indices of preload responsiveness were used in 483 of 2213 cases (22 %, CI 20-24 %). No safety variable for the FC was used in 72 % (CI 70-74 %) of the cases. There was no statistically significant difference in the proportion of patients who received further fluids after the FC between those with a positive, with an uncertain or with a negatively judged response.The current practice and evaluation of FC in critically ill patients are highly variable. Prediction of fluid responsiveness is not used routinely, safety limits are rarely used, and information from previous failed FCs is not always taken into account

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