57 research outputs found
Synthesis, characterization, antibacterial and antitumoral activities of mononuclear zinc complexes containing tridentate amine based ligands with N3 or N2O donor groups
The synthesis and characterization of the four zinc(II) complexes [Zn(HL1)Cl-2] (1), [Zn(H2L2)Cl-2](2), [Zn(H2L3)Cl-2] (3) and[Zn(H2L4)Cl-2] (4), where HL1 = (bis-2-pyridylmethyl)amine, H2L2 = (2-hydroxybenzyl- 2-pyridylmethyl) amine, H2L3 = N-2[(pyridine-2-ylmethyl)amino)ethanol, H2L4 = 1-[(pyridine-2-ylmethyl)- amino]-propan-2-ol are reported; (3) and (4) are new while (2) was reported previously but its structure had not been determined. The complexes were characterized by elemental analysis, IR, UV-Vis and NMR spectroscopic, electrospray ionization mass spectrometry (ESI(+)-MS) and tandem mass spectrometry ESI(+)-MS/MS). X-ray diffraction studies were performed for complexes (1)-(3) revealing the presence of mononuclear structures in the solid state. The X-ray analyses of (1) and (3) demonstrate that HL1 and HL2 act as tridentate ligands, while the ligand H2L2 in (2) is bidentate. The cytotoxic properties of the ligands and of all the complexes were examined using human leukemia THP-1, U937 and Molt-4 cells. Complex (4) exhibited the highest cytotoxicity in this series with an IC50 value of 75 +/- 1 mu mol L (1) against U937 cells. Transmission electron microscopy (TEM) reveals ultrastructural changes typical of apoptotic cells. The induction of apoptosis was confirmed by the annexin V assay. The antimicrobial activity of complexes (1)-(4) was also investigated in vitro against four Gram-positive bacteria (ATCC10832, ATCC25923, COL) and the clinical Staphylococcus aureus isolate LSA88 (SEC/SEF/ TSST-1+). Complex (2) showed the most potent inhibitory activity, reaching almost 100% of inhibition against all strains tested. Morphological investigations using TEM indicate that the antibacterial activity of complex (2) may be associated with the inhibition of cell wall and therefore cell division. (C) 2014 Elsevier B. V. All rights reserved
Development and evaluation of an emulsion containing lycopene for combating acceleration of skin aging
Licopeno é um carotenóide com potente atividade antioxidante encontrado em grande quantidade no tomate e usado no combate a diversas doenças como doenças cardiovasculares e diferentes tipos de cânceres, incluindo o câncer de próstata. O objetivo desse trabalho foi desenvolver uma emulsão contendo extrato de licopeno obtido do tomate salada e avaliar a citotoxicidade do extrato, a estabilidade, o comportamento reológico, atividade antioxidante e permeação do fitocosmético. O cosmético foi desenvolvido utilizando fase oleosa contendo derivados de Karité e submetido à avaliação da estabilidade físico-química, espalhabilidade, análise térmica, comportamento reológico, qualidade microbiológica, citotoxicidade, atividade antioxidante e testes de permeação e retenção cutânea. Os resultados demonstraram que o fitocosmético é estável, apresenta comportamento reológico desejável para uma formulação tópica e é um produto promissor para ser utilizado no combate à aceleração do envelhecimento cutâneo.Lycopene, a carotenoid and potent antioxidant is found in large quantities in tomatoes. Lycopene combats diseases, such as cardiovascular disease and different types of cancer, including prostate cancer. However, its topical use in emulsion form for the combat of skin aging is under-explored. The aim of the present study was to develop an emulsion containing lycopene extracted from salad tomatoes and evaluate its cytotoxicity, stability, rheological behavior, antioxidant activity and phytocosmetic permeation. The developed cosmetic comprised an oil phase made up of shea derivatives and was evaluated in terms of its physiochemical stability, spreadability, thermal analysis, rheological behavior, microbiological quality, cytotoxicity, antioxidant activity, cutaneous permeation and retention. The results demonstrate that this phytocosmetic is stable, exhibits satisfactory rheological behavior for a topical formula and is a promising product for combating skin aging
Induction of apoptosis in leukemia cell lines by new copper(II) complexes containing naphthyl groups via interaction with death receptors
The synthesis, physico-chemical characterization and cytotoxicity of four new ligands and their respective copper(II) complexes toward two human leukemia cell lines (THP-1 and U937) are reported (i.e. [(HL1) Cu(mu-Cl)(2)Cu(HL1)]Cl-2 center dot H2O (1), [(H2L2)Cu(mu-Cl)(2)Cu(H2L2)]Cl-2 center dot 5H(2)O (2), [(HL3)Cu(mu-Cl)(2)Cu(HL3)]Cl-2 center dot 4H(2) (3), [(H2L4)Cu(mu-Cl)(2)Cu(H2L4)]Cl-2 center dot 6H(2)O (4)). Ligands HL1 and HL3 contain two pyridines, amine and alcohol moieties with a naphthyl pendant unit yielding a N3O coordination metal environment Ligands H2L2 and H2L4 have pyridine, phenol, amine and alcohol groups with a naphthyl pendant unit providing a N2O2 coordination metal environment These compounds are likely to be dinuclear in the solid state but form mononuclear species in solution. The complexes have an antiproliferative effect against both leukemia cell lines; complex (2) exhibits higher activity than cisplatin against U937 (8.20 vs 16.25 mu mol dm(-3)) and a comparable one against THP-1. These human neoplastic cells are also more susceptible than peripheral blood mononuclear cells (PBMCs) toward the tested compounds. Using C57BL/6 mice an LD50 of 55 mg kg(-1) was determined for complex (2), suggesting that this compound is almost four times less toxic than cisplatin (LD50 = 14.5 mg kg(-1)). The mechanism of cell death promoted by ligand H2L2 and by complexes (2) and (4) was investigated by a range of techniques demonstrating that the apoptosis signal triggered at least by complex (2) starts from an extrinsic pathway involving the activation of caspases 4 and 8. This signal is amplified by mitochondria with the concomitant release of cytochrome c and the activation of caspase 9. (C) 2015 Elsevier Inc. All rights reserved
Global age-sex-specific fertility, mortality, healthy life expectancy (HALE), and population estimates in 204 countries and territories, 1950-2019 : a comprehensive demographic analysis for the Global Burden of Disease Study 2019
Background: Accurate and up-to-date assessment of demographic metrics is crucial for understanding a wide range of social, economic, and public health issues that affect populations worldwide. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 produced updated and comprehensive demographic assessments of the key indicators of fertility, mortality, migration, and population for 204 countries and territories and selected subnational locations from 1950 to 2019.
Methods: 8078 country-years of vital registration and sample registration data, 938 surveys, 349 censuses, and 238 other sources were identified and used to estimate age-specific fertility. Spatiotemporal Gaussian process regression (ST-GPR) was used to generate age-specific fertility rates for 5-year age groups between ages 15 and 49 years. With extensions to age groups 10–14 and 50–54 years, the total fertility rate (TFR) was then aggregated using the estimated age-specific fertility between ages 10 and 54 years. 7417 sources were used for under-5 mortality estimation and 7355 for adult mortality. ST-GPR was used to synthesise data sources after correction for known biases. Adult mortality was measured as the probability of death between ages 15 and 60 years based on vital registration, sample registration, and sibling histories, and was also estimated using ST-GPR. HIV-free life tables were then estimated using estimates of under-5 and adult mortality rates using a relational model life table system created for GBD, which closely tracks observed age-specific mortality rates from complete vital registration when available. Independent estimates of HIV-specific mortality generated by an epidemiological analysis of HIV prevalence surveys and antenatal clinic serosurveillance and other sources were incorporated into the estimates in countries with large epidemics. Annual and single-year age estimates of net migration and population for each country and territory were generated using a Bayesian hierarchical cohort component model that analysed estimated age-specific fertility and mortality rates along with 1250 censuses and 747 population registry years. We classified location-years into seven categories on the basis of the natural rate of increase in population (calculated by subtracting the crude death rate from the crude birth rate) and the net migration rate. We computed healthy life expectancy (HALE) using years lived with disability (YLDs) per capita, life tables, and standard demographic methods. Uncertainty was propagated throughout the demographic estimation process, including fertility, mortality, and population, with 1000 draw-level estimates produced for each metric. Findings: The global TFR decreased from 2·72 (95% uncertainty interval [UI] 2·66–2·79) in 2000 to 2·31 (2·17–2·46) in 2019. Global annual livebirths increased from 134·5 million (131·5–137·8) in 2000 to a peak of 139·6 million (133·0–146·9) in 2016. Global livebirths then declined to 135·3 million (127·2–144·1) in 2019. Of the 204 countries and territories included in this study, in 2019, 102 had a TFR lower than 2·1, which is considered a good approximation of replacement-level fertility. All countries in sub-Saharan Africa had TFRs above replacement level in 2019 and accounted for 27·1% (95% UI 26·4–27·8) of global livebirths. Global life expectancy at birth increased from 67·2 years (95% UI 66·8–67·6) in 2000 to 73·5 years (72·8–74·3) in 2019. The total number of deaths increased from 50·7 million (49·5–51·9) in 2000 to 56·5 million (53·7–59·2) in 2019. Under-5 deaths declined from 9·6 million (9·1–10·3) in 2000 to 5·0 million (4·3–6·0) in 2019. Global population increased by 25·7%, from 6·2 billion (6·0–6·3) in 2000 to 7·7 billion (7·5–8·0) in 2019. In 2019, 34 countries had negative natural rates of increase; in 17 of these, the population declined because immigration was not sufficient to counteract the negative rate of decline. Globally, HALE increased from 58·6 years (56·1–60·8) in 2000 to 63·5 years (60·8–66·1) in 2019. HALE increased in 202 of 204 countries and territories between 2000 and 2019
Global burden of 369 diseases and injuries in 204 countries and territories, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019
Background: In an era of shifting global agendas and expanded emphasis on non-communicable diseases and injuries along with communicable diseases, sound evidence on trends by cause at the national level is essential. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) provides a systematic scientific assessment of published, publicly available, and contributed data on incidence, prevalence, and mortality for a mutually exclusive and collectively exhaustive list of diseases and injuries. Methods: GBD estimates incidence, prevalence, mortality, years of life lost (YLLs), years lived with disability (YLDs), and disability-adjusted life-years (DALYs) due to 369 diseases and injuries, for two sexes, and for 204 countries and territories. Input data were extracted from censuses, household surveys, civil registration and vital statistics, disease registries, health service use, air pollution monitors, satellite imaging, disease notifications, and other sources. Cause-specific death rates and cause fractions were calculated using the Cause of Death Ensemble model and spatiotemporal Gaussian process regression. Cause-specific deaths were adjusted to match the total all-cause deaths calculated as part of the GBD population, fertility, and mortality estimates. Deaths were multiplied by standard life expectancy at each age to calculate YLLs. A Bayesian meta-regression modelling tool, DisMod-MR 2.1, was used to ensure consistency between incidence, prevalence, remission, excess mortality, and cause-specific mortality for most causes. Prevalence estimates were multiplied by disability weights for mutually exclusive sequelae of diseases and injuries to calculate YLDs. We considered results in the context of the Socio-demographic Index (SDI), a composite indicator of income per capita, years of schooling, and fertility rate in females younger than 25 years. Uncertainty intervals (UIs) were generated for every metric using the 25th and 975th ordered 1000 draw values of the posterior distribution. Findings: Global health has steadily improved over the past 30 years as measured by age-standardised DALY rates. After taking into account population growth and ageing, the absolute number of DALYs has remained stable. Since 2010, the pace of decline in global age-standardised DALY rates has accelerated in age groups younger than 50 years compared with the 1990–2010 time period, with the greatest annualised rate of decline occurring in the 0–9-year age group. Six infectious diseases were among the top ten causes of DALYs in children younger than 10 years in 2019: lower respiratory infections (ranked second), diarrhoeal diseases (third), malaria (fifth), meningitis (sixth), whooping cough (ninth), and sexually transmitted infections (which, in this age group, is fully accounted for by congenital syphilis; ranked tenth). In adolescents aged 10–24 years, three injury causes were among the top causes of DALYs: road injuries (ranked first), self-harm (third), and interpersonal violence (fifth). Five of the causes that were in the top ten for ages 10–24 years were also in the top ten in the 25–49-year age group: road injuries (ranked first), HIV/AIDS (second), low back pain (fourth), headache disorders (fifth), and depressive disorders (sixth). In 2019, ischaemic heart disease and stroke were the top-ranked causes of DALYs in both the 50–74-year and 75-years-and-older age groups. Since 1990, there has been a marked shift towards a greater proportion of burden due to YLDs from non-communicable diseases and injuries. In 2019, there were 11 countries where non-communicable disease and injury YLDs constituted more than half of all disease burden. Decreases in age-standardised DALY rates have accelerated over the past decade in countries at the lower end of the SDI range, while improvements have started to stagnate or even reverse in countries with higher SDI. Interpretation: As disability becomes an increasingly large component of disease burden and a larger component of health expenditure, greater research and developm nt investment is needed to identify new, more effective intervention strategies. With a rapidly ageing global population, the demands on health services to deal with disabling outcomes, which increase with age, will require policy makers to anticipate these changes. The mix of universal and more geographically specific influences on health reinforces the need for regular reporting on population health in detail and by underlying cause to help decision makers to identify success stories of disease control to emulate, as well as opportunities to improve. Funding: Bill & Melinda Gates Foundation. © 2020 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 licens
The genetic architecture of the human cerebral cortex
The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder
Catálogo Taxonômico da Fauna do Brasil: setting the baseline knowledge on the animal diversity in Brazil
The limited temporal completeness and taxonomic accuracy of species lists, made available in a traditional manner in scientific publications, has always represented a problem. These lists are invariably limited to a few taxonomic groups and do not represent up-to-date knowledge of all species and classifications. In this context, the Brazilian megadiverse fauna is no exception, and the Catálogo Taxonômico da Fauna do Brasil (CTFB) (http://fauna.jbrj.gov.br/), made public in 2015, represents a database on biodiversity anchored on a list of valid and expertly recognized scientific names of animals in Brazil. The CTFB is updated in near real time by a team of more than 800 specialists. By January 1, 2024, the CTFB compiled 133,691 nominal species, with 125,138 that were considered valid. Most of the valid species were arthropods (82.3%, with more than 102,000 species) and chordates (7.69%, with over 11,000 species). These taxa were followed by a cluster composed of Mollusca (3,567 species), Platyhelminthes (2,292 species), Annelida (1,833 species), and Nematoda (1,447 species). All remaining groups had less than 1,000 species reported in Brazil, with Cnidaria (831 species), Porifera (628 species), Rotifera (606 species), and Bryozoa (520 species) representing those with more than 500 species. Analysis of the CTFB database can facilitate and direct efforts towards the discovery of new species in Brazil, but it is also fundamental in providing the best available list of valid nominal species to users, including those in science, health, conservation efforts, and any initiative involving animals. The importance of the CTFB is evidenced by the elevated number of citations in the scientific literature in diverse areas of biology, law, anthropology, education, forensic science, and veterinary science, among others
Mapping inequalities in exclusive breastfeeding in low- and middle-income countries, 2000–2018
Exclusive breastfeeding (EBF)—giving infants only breast-milk for the first 6 months of life—is a component of optimal breastfeeding practices effective in preventing child morbidity and mortality. EBF practices are known to vary by population and comparable subnational estimates of prevalence and progress across low- and middle-income countries (LMICs) are required for planning policy and interventions. Here we present a geospatial analysis of EBF prevalence estimates from 2000 to 2018 across 94 LMICs mapped to policy-relevant administrative units (for example, districts), quantify subnational inequalities and their changes over time, and estimate probabilities of meeting the World Health Organization’s Global Nutrition Target (WHO GNT) of ≥70% EBF prevalence by 2030. While six LMICs are projected to meet the WHO GNT of ≥70% EBF prevalence at a national scale, only three are predicted to meet the target in all their district-level units by 2030
Highly efficient synthetic iron-dependent nucleases activate both intrinsic and extrinsic apoptotic death pathways in leukemia cancer cells
The nuclease activity and the cytotoxicity toward human leukemia cancer cells of iron complexes, [Fe(HPClNOL) Cl-2]NO3 (1), [Cl(HPClNOL)Fe(mu-O)Fe(HPClNOL)Cl]Cl-2 center dot 2H(2)O (2), and [(SO4)(HPCINOL)Fe(mu-O)Fe(HPCINOL)(SO4)]center dot 6H(2)O (3) (HPCINOL = 1-(bis-pyridin-2-ylmethyl-amino)-3-chloropropan-2-ol), were investigated. Each complex was able to promote plasmid DNA cleavage and change the supercoiled form of the plasmid to circular and linear ones. Kinetic data revealed that (1), (2) and (3) increase the rate of DNA hydrolysis about 278, 192 and 339 million-fold, respectively. The activity of the complexes was inhibited by distamycin, indicating that they interact with the minor groove of the DNA. The cytotoxic activity of the complexes toward U937, HL-60, Jukart and THP-1 leukemia cancer cells was studied employing 3-(4,5-dimethythiazol-2-y1)-2,5-diphenyl tetrazolium bromide (MTT), fluorescence and electronic transmission microscopies, flow cytometry and a cytochrome C release assay. Compound (2) has the highest activity toward cancer cells and is the least toxic for normal ones (i.e. peripheral blood mononuclear cells (PBMCs)). In contrast, compound (1) is the least active toward cancer cells but displays the highest toxicity toward normal cells. Transmission electronic microscopy indicates that cell death shows features typical of apoptotic cells, which was confirmed using the annexin V-FITC/PI (fluorescein isothiocyanate/propidium iodide) assay. Furthermore, our data demonstrate that at an early stage during the treatment with complex (2) mitochondria lose their transmembrane potential, resulting in cytochrome C release. A quantification of caspases 3,9 (intrinsic apoptosis pathway) and caspase 8 (extrinsic apoptosis pathway) indicated that both the intrinsic (via mitochondria) and extrinsic (via death receptors) pathways are involved in the apoptotic stimuli. (C) 2013 Elsevier Inc. All rights reserved
Diversification of the forest beetle genus Tarphius in the Canary Islands, and the evolutionary origins of island endemics.
The flightless beetle genus Tarphius Erichson (Coleoptera: Colydiidae) is a distinctive element of the betle fauna of the Canary Islands with 29 species distributed across the five western islands. The majority of Tarphius species are rare and inimately associated with the monteverde forest and only two species occurr on more than one island. It this study we investigate the phylogeography of the Canary Island Tarphius, and their relationship to Tarphius from the more northerly archipelagos of Madera and the Azores using Maximum parsimony and bayesian inference analysis of mitochondrial cytochrome oxidase I and II sequence data. We use geological datings for the Canary Islands, Azores, and Madeira to calibrate specific nodes of the tree for the estimation of divergence times using a penalized likelihood method. Data suggest that the Canary Island species assumblage is of some antiquity, however, much of this species diversity is relatively recent is origin. The phylogencetic relationships of species inhabiting the younger islands of EI hierro and LaPalma indicate that coloniztion events between islands have probably been a significant factor in the evolutionary history of the Canary Island species assemblage. A comparison of molecular phylogenetic studies of arthropods on the Canary Island suggests that, in the evolution of the arthropod species species community of an island, the origin of endemic species is initially the result of colonizing lineages differentiating from their source populations. However, as an island matures a greater proportion of endemic species originate from intra-island speciation
- …