Curcumina e um novo complexo Ruteno(II)curcumina : caracterização e avaliação das suas potencialidades biológicas

Mestrado em Bioquímica - Métodos BiomolecularesA curcumina é um pigmento de cor amarela, da família dos polifenóis, obtido a partir dos rizomas da planta Curcuma longa. É dotada de diversas propriedades biológicas que se relacionam com a vasta gama de alvos moleculares que possui, sendo de destacar a sua atividade anticancerígena já provada em diversas linhas celulares cancerígenas. No entanto, a atividade biológica da curcumina é limitada pela sua baixa biodisponibilidade que se deve principalmente à sua fraca solubilidade e rápida degradação em condições fisiológicas. Uma estratégia para contornar as limitações terapêuticas da curcumina é a sua complexação com iões metálicos, nomeadamente com complexos de ruténio(II). Neste trabalho foi preparado um novo complexo de curcumina com ruténio(II) e tritiaciclononano [9anoS3] com o objetivo de aumentar a solubilidade da curcumina em meio fisiológico. A curcumina foi extraída e purificada a partir de rizomas secos e pulverizados de Curcuma longa sendo depois desprotonada e coordenada com o precursor [Ru(II)(9anoS3)(DMSO)Cl2] (DMSO=dimetilsulfóxido). A estrutura e pureza do complexo formado, [Ru(II)(9aneS3)(curcumina)(S-DMSO)]Cl foi avaliada por Ressonância Magnética Nuclear de 1H e 13C, espectrometria de massa e análise elementar. A afinidade do novo complexo para ligação ao ácido desoxirribonucleico (ADN) foi estudada por ensaios de titulação e por determinação da variação na temperatura de desnaturação do ADN de esperma de salmão. Este estudo permitiu determinar que o complexo tem a capacidade de intercalar com o ADN com uma constante de ligação comparável aos intercaladores de ADN já conhecidos (4.00x105 M-1). A atividade citotóxica deste complexo contra o cancro de próstata foi estudada in vitro, usando como controlo positivo a curcumina. Mais ainda, aproveitando o potencial fotossensibilizador da curcumina, os ensaios foram feitos na presença e na ausência de luz. Para isso, usaram-se culturas celulares humanas isoladas de carcinoma de próstata (PC-3) e a toxicidade foi avaliada em linhas celulares prostáticas não tumorais (PNT-2). Com estes ensaios verificou-se que o complexo preparado não tem efeito citotóxico nem fototóxico nas concentrações usadas para as linhas celulares estudas. Mais, observou-se que a curcumina apresenta, no escuro, efeito citotóxico nas concentrações usadas e ainda, que este efeito é fortemente potenciado na presença de luz, sendo um potencial agente para terapia fotodinâmica em cancro de próstata.Curcumin is a yellow pigment, of the family of polyphenols, obtained from the rhizomes of the Curcuma longa. It is provided with several biological properties which relate with the wide range of molecular targets that possesses, especially the anticancer activity already proven in various cell lines. However, the biological activity of curcumin is limited by their low bioavailability which is mainly because their poor solubility and rapid degradation in physiological conditions. One promising strategy to circumvent the therapeutic limitations of curcumin is the binding with metal ions, namely with ruthenium(II) complexes. In this work, was prepared a new complex of curcumin with ruthenium(II) and trithiacyclononane (9aneS3) with the aim of increasing the solubility of curcumin in physiological medium. The curcumina was extracted and purified from the powder rhizomes of Curcuma longa being after deprotonated and coordinated with the precursor [Ru(II)(9aneS3)(DMSO)Cl2] (DMSO=dimethylsulfoxide). The structure and purity of the prepared complex, [Ru(II)(9aneS3)(curcumina)(S-DMSO)]Cl was evaluated by 1H and 13C Nuclear Magnetic Resonance spectroscopies, mass spectrometry and elemental analysis. The affinity of the new complex to bind to deoxyribonucleic acid (DNA) was studied by titration assays and determination of the variation on sperm salmon DNA melting temperature. This study allowed to determine that the complex has ability to intercalate with DNA with a binding constant comparable with classical intercalators. The cytotoxic activity of this complex against prostate cancer was studied in vitro, using curcumin as a positive control. Moreover, taking advantage of the photosensitizer potential of curcumin, the assays were made under dark and light conditions. For this, human cell cultures were used isolated from prostate carcinoma (PC-3) and the toxicity was evaluated in non-tumour prostate cells (PNT-2). With these tests, it was found that the new complex do not have any cytotoxic or phototoxic effect in the same concentrations range tested for cell lines studied. Further, was observed that the curcumin presents, in dark, cytotoxic effect and, that this effect is strongly potentiated by light presence, with a potential for photodynamic therapy in prostate cancer

Rising rural body-mass index is the main driver of the global obesity epidemic in adults

Body-mass index (BMI) has increased steadily in most countries in parallel with a rise in the proportion of the population who live in cities(.)(1,2) This has led to a widely reported view that urbanization is one of the most important drivers of the global rise in obesity(3-6). Here we use 2,009 population-based studies, with measurements of height and weight in more than 112 million adults, to report national, regional and global trends in mean BMI segregated by place of residence (a rural or urban area) from 1985 to 2017. We show that, contrary to the dominant paradigm, more than 55% of the global rise in mean BMI from 1985 to 2017-and more than 80% in some low- and middle-income regions-was due to increases in BMI in rural areas. This large contribution stems from the fact that, with the exception of women in sub-Saharan Africa, BMI is increasing at the same rate or faster in rural areas than in cities in low- and middle-income regions. These trends have in turn resulted in a closing-and in some countries reversal-of the gap in BMI between urban and rural areas in low- and middle-income countries, especially for women. In high-income and industrialized countries, we noted a persistently higher rural BMI, especially for women. There is an urgent need for an integrated approach to rural nutrition that enhances financial and physical access to healthy foods, to avoid replacing the rural undernutrition disadvantage in poor countries with a more general malnutrition disadvantage that entails excessive consumption of low-quality calories.Peer reviewe

Height and body-mass index trajectories of school-aged children and adolescents from 1985 to 2019 in 200 countries and territories: a pooled analysis of 2181 population-based studies with 65 million participants

Summary Background Comparable global data on health and nutrition of school-aged children and adolescents are scarce. We aimed to estimate age trajectories and time trends in mean height and mean body-mass index (BMI), which measures weight gain beyond what is expected from height gain, for school-aged children and adolescents. Methods For this pooled analysis, we used a database of cardiometabolic risk factors collated by the Non-Communicable Disease Risk Factor Collaboration. We applied a Bayesian hierarchical model to estimate trends from 1985 to 2019 in mean height and mean BMI in 1-year age groups for ages 5–19 years. The model allowed for non-linear changes over time in mean height and mean BMI and for non-linear changes with age of children and adolescents, including periods of rapid growth during adolescence. Findings We pooled data from 2181 population-based studies, with measurements of height and weight in 65 million participants in 200 countries and territories. In 2019, we estimated a difference of 20 cm or higher in mean height of 19-year-old adolescents between countries with the tallest populations (the Netherlands, Montenegro, Estonia, and Bosnia and Herzegovina for boys; and the Netherlands, Montenegro, Denmark, and Iceland for girls) and those with the shortest populations (Timor-Leste, Laos, Solomon Islands, and Papua New Guinea for boys; and Guatemala, Bangladesh, Nepal, and Timor-Leste for girls). In the same year, the difference between the highest mean BMI (in Pacific island countries, Kuwait, Bahrain, The Bahamas, Chile, the USA, and New Zealand for both boys and girls and in South Africa for girls) and lowest mean BMI (in India, Bangladesh, Timor-Leste, Ethiopia, and Chad for boys and girls; and in Japan and Romania for girls) was approximately 9–10 kg/m2. In some countries, children aged 5 years started with healthier height or BMI than the global median and, in some cases, as healthy as the best performing countries, but they became progressively less healthy compared with their comparators as they grew older by not growing as tall (eg, boys in Austria and Barbados, and girls in Belgium and Puerto Rico) or gaining too much weight for their height (eg, girls and boys in Kuwait, Bahrain, Fiji, Jamaica, and Mexico; and girls in South Africa and New Zealand). In other countries, growing children overtook the height of their comparators (eg, Latvia, Czech Republic, Morocco, and Iran) or curbed their weight gain (eg, Italy, France, and Croatia) in late childhood and adolescence. When changes in both height and BMI were considered, girls in South Korea, Vietnam, Saudi Arabia, Turkey, and some central Asian countries (eg, Armenia and Azerbaijan), and boys in central and western Europe (eg, Portugal, Denmark, Poland, and Montenegro) had the healthiest changes in anthropometric status over the past 3·5 decades because, compared with children and adolescents in other countries, they had a much larger gain in height than they did in BMI. The unhealthiest changes—gaining too little height, too much weight for their height compared with children in other countries, or both—occurred in many countries in sub-Saharan Africa, New Zealand, and the USA for boys and girls; in Malaysia and some Pacific island nations for boys; and in Mexico for girls. Interpretation The height and BMI trajectories over age and time of school-aged children and adolescents are highly variable across countries, which indicates heterogeneous nutritional quality and lifelong health advantages and risks

Heterogeneous contributions of change in population distribution of body mass index to change in obesity and underweight NCD Risk Factor Collaboration (NCD-RisC)

From 1985 to 2016, the prevalence of underweight decreased, and that of obesity and severe obesity increased, in most regions, with significant variation in the magnitude of these changes across regions. We investigated how much change in mean body mass index (BMI) explains changes in the prevalence of underweight, obesity, and severe obesity in different regions using data from 2896 population-based studies with 187 million participants. Changes in the prevalence of underweight and total obesity, and to a lesser extent severe obesity, are largely driven by shifts in the distribution of BMI, with smaller contributions from changes in the shape of the distribution. In East and Southeast Asia and sub-Saharan Africa, the underweight tail of the BMI distribution was left behind as the distribution shifted. There is a need for policies that address all forms of malnutrition by making healthy foods accessible and affordable, while restricting unhealthy foods through fiscal and regulatory restrictions