Central role of obesity in endothelial cell dysfunction and cardiovascular risk

Atherosclerosis is the leading cause of mortality in the contemporary world. The critical role of the endothelial cells (EC) in vascular homeostasis, the metabolic changes that take place when the cell is activated, and the elements involved in these processes have been widely explored over the past years. Obesity and its impact, promoting a rise in blood levels of free fatty acids (FAs) are often associated with atherosclerosis and cardiovascular mortality. However, the mechanisms that promote cardiovascular structural changes and adaptive changes in the ECs, particularly in the context of obesity, are little known. Here, we reviewed studies that assessed the metabolic adaptations of healthy and dysfunctional ECs during exposure to FAs, as well as the epidemiological perspectives of cardiovascular structural changes in obesity. Finally, we explored the role of new agents - sphingolipids, dietary unsaturated fatty acids and sodium-glucose cotransporter-2 inhibitors (iSGLT2) - in atherosclerosis and their relationship with obesity.651879

The partial inhibition of hypothalamic IRX3 exacerbates obesity

The Iroquois homeobox 3 (Irx3) gene has been identified as a functional long-range target of obesity-associated variants within the fat mass and obesity-associated protein (FTO) gene. It is highly expressed in the hypothalamus, and both whole-body knockout and hypothalamic restricted abrogation of its expression results in a lean phenotype, which is mostly explained by the resulting increased energy expenditure in the brown adipose tissue. Because of its potential implication in the pathogenesis of obesity, we evaluated the hypothalamic cell distribution of Irx3 and the outcomes of inhibiting its expression in a rodent model of diet-induced obesity. Methods: Bioinformatics tools were used to evaluate the correlations between hypothalamic Irx3 and neurotransmitters, markers of thermogenesis and obesity related phenotypes. Droplet-sequencing analysis in >20,000 hypothalamic cells was used to explore the types of hypothalamic cells expressing Irx3. Lentivirus was used to inhibit hypothalamic Irx3 and the resulting phenotype was studied. Findings: IRX3 is expressed predominantly in POMC neurons. Its expression is inhibited during prolonged fasting, as well as when mice are fed a high-fat diet. The partial inhibition of hypothalamic Irx3 using a lentivirus resulted in increased diet-induced body mass gain and adiposity due to increased caloric intake and reduced energy expenditure. Interpretation: Contrary to the results obtained when lean mice are submitted to complete inhibition of Irx3, partial inhibition of hypothalamic Irx3 in obese mice causes an exacerbation of the obese phenotype. These data suggest that at least some of the Irx3 functions in the hypothalamus are regulated according to a hormetic pattern, and modulation of its expression can be a novel approach to modifying the body's energy-handling regulation.39448460FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESP2013/07607-8; 2017/02983-

Low-Level Laser Application in the Early Myocardial Infarction Stage Has No Beneficial Role in Heart Failure

Low-level laser therapy (LLLT) has been targeted as a promising approach that can mitigate post infarction cardiac remodeling. There is some interesting evidence showing that the beneficial role of the LLLT could persist long-term even after the end of the application, but it remains to be systematically evaluated. Therefore, the present study aimed to test the hypothesis that LLLT beneficial effects in the early post-infarction cardiac remodeling could remain in overt heart failure even with the disruption of irradiations. Female Wistar rats were subjected to the coronary occlusion to induce myocardial infarction or Sham operation. A single LLLT application was carried out after 60 s and 3 days post-coronary occlusion, respectively. Echocardiography was performed 3 days and at the end of the experiment (5 weeks) to evaluate cardiac function. After the last echocardiographic examination. LV hemodynamic evaluation was performed at baseline and on sudden afterload increases. Compared with the Sham group, infarcted rats showed increased systolic and diastolic internal diameter as well as a depressed shortening fraction of LV. The only benefit of the LLLT was a higher shortening fraction after 3 days of infarction. However, treated-LLLT rats show a lower shortening fraction in the 5th week of study when compared with Sham and non-irradiated rats. A worsening of cardiac function was confirmed in the hemodynamic analysis as evidenced by the higher LV end-diastolic pressure and lower +dP/dt and dP/dt with five weeks of study. Cardiac functional reserve was also impaired by infarction as evidenced by an attenuated response of stroke work index and cardiac output to a sudden afterload stress, without LLLT repercussions. No significant differences were found in the myocardial expression of Akti NEGF pathway. Collectively, these findings illustrate that LLLT improves LV systolic function in the early post-infarction cardiac remodeling. However, this beneficial effect may be dependent on the maintenance of phototherapy. Long-term studies with LLLT application are needed to establish whether these effects ultimately translate into improved cardiac remodeling.Conselho Nacional de Desenvolvimento Cientifico e TecnologicoFAPESPNove de Julho Univ, Lab Biophoton, Sao Paulo, SP, BrazilUniv Fed Sao Paulo, Lab Cardiac Physiol, Sao Paulo, SP, BrazilNove de Julho Univ, Program Med, Sao Paulo, BrazilUniv Sao Judas Tadeu, Brazil Phys Educ & Aging Sci Program, Translat Physiol Lab, Sao Paulo, BrazilUniv Fed Sao Paulo, Lab Cardiac Physiol, Sao Paulo, SP, BrazilCNPq: 4400851/2014-8FAPESP: 09-54225/8FAPESP: 15/11028-9Web of Scienc

INVENTÁRIO E DIAGNÓSTICO DA ARBORIZAÇÃO URBANA VIÁRIA DE RIO BRANCO, AC

O presente trabalho foi desenvolvido dentro do perímetro urbano da cidade de Rio BrancoAC, localizada entre as coordenadas geográficas de 9°58’29’’ de latitude sul e 67°48’36’’ de longitude oeste. Teve como objetivo geral o levantamento e diagnóstico da arborização viária. A metodologia estatística utilizada foi definida tomando-se como unidade amostral o quarteirão. Encontrou-se pouquíssimos espécimes nas calçadas dos quarteirões amostrados, totalizando 292 indivíduos distribuídos por 39 espécies, sendo 11 nativas e 28 exóticas. A média por quarteirão foi de 1,83 árvores, e por quilômetro de calçada foi de 4,57 árvores. Concluiu-se que o número de árvores existentes nas calçadas foi muito pequeno, tendo-se como referência 100 árvores por quilômetro de calçada como ideal. A maioria das espécies encontrada era exótica (78,57%), a despeito da cidade encontrar-se numa região com uma das maiores diversidades de espécies arbóreas do planeta. Quanto ao estado físico, a copa normal foi predominante, exceto na região central. As recomendações indicadas foram primeiramente de se elaborar um plano de arborização urbana para o município, contendo referências técnicas para escolha das espécies, técnicas de manejo e programa de educação ambiental

Whole-genome sequencing of 1,171 elderly admixed individuals from Brazil

As whole-genome sequencing (WGS) becomes the gold standard tool for studying population genomics and medical applications, data on diverse non-European and admixed individuals are still scarce. Here, we present a high-coverage WGS dataset of 1,171 highly admixed elderly Brazilians from a census-based cohort, providing over 76 million variants, of which ~2 million are absent from large public databases. WGS enables identification of ~2,000 previously undescribed mobile element insertions without previous description, nearly 5 Mb of genomic segments absent from the human genome reference, and over 140 alleles from HLA genes absent from public resources. We reclassify and curate pathogenicity assertions for nearly four hundred variants in genes associated with dominantly-inherited Mendelian disorders and calculate the incidence for selected recessive disorders, demonstrating the clinical usefulness of the present study. Finally, we observe that whole-genome and HLA imputation could be significantly improved compared to available datasets since rare variation represents the largest proportion of input from WGS. These results demonstrate that even smaller sample sizes of underrepresented populations bring relevant data for genomic studies, especially when exploring analyses allowed only by WGS

A social and ecological assessment of tropical land uses at multiple scales: the Sustainable Amazon Network

Science has a critical role to play in guiding more sustainable development trajectories. Here, we present the Sustainable Amazon Network (Rede Amazonia Sustentavel, RAS): a multidisciplinary research initiative involving more than 30 partner organizations working to assess both social and ecological dimensions of land-use sustainability in eastern Brazilian Amazonia. The research approach adopted by RAS offers three advantages for addressing land-use sustainability problems: (i) the collection of synchronized and co-located ecological and socioeconomic data across broad gradients of past and present human use; (ii) a nested sampling design to aid comparison of ecological and socioeconomic conditions associated with different land uses across local, landscape and regional scales; and (iii) a strong engagement with a wide variety of actors and non-research institutions. Here, we elaborate on these key features, and identify the ways in which RAS can help in highlighting those problems in most urgent need of attention, and in guiding improvements in land-use sustainability in Amazonia and elsewhere in the tropics. We also discuss some of the practical lessons, limitations and realities faced during the development of the RAS initiative so far.Keywords: Social–ecological systems, Tropical forests, Land use, Interdisciplinary research, Sustainability, Trade-off

Associação entre a ooforectomia bilateral precoce e o desenvolvimento do parkinsonismo e Doença de Parkinson em mulheres na pré-menopausa

O parkinsonismo é um distúrbio do sistema nervoso de maior incidência masculina do que feminina, visto que, por mecanismos fisiológicos, o estrogênio possui efeitos neuroprotetores, com funções como aumento da dopamina, um neurotransmissor essencial para o controle das funções motoras. Além disso, previne a formação dos corpúsculos de Lewy e da agregação da α-sinucleína, responsáveis pela progressão da Doença de Parkinson. Por isso, a doença se apresenta diferentemente nas mulheres. A remoção cirúrgica de ambos os ovários em mulheres na pré-menopausa para a prevenção do câncer de ovário parece favorecer o surgimento da doença, tendo em vista a perda da produção do hormônio protetor. Assim, o objetivo do estudo é analisar a associação entre a ooforectomia bilateral precoce e o desenvolvimento de parkinsonismo e Doença de Parkinson em mulheres na pré-menopausa. Trata-se de uma revisão bibliográfica sistemática, do tipo quantitativa, que utilizou as plataformas do PubMed, SciELO e Cochrane Library como bases de dados para seleção dos artigos, todos na língua inglesa. Foram utilizadas literaturas publicadas com recorte temporal de 2017 a 2022. De acordo com as literaturas analisadas, a ooforectomia bilateral precoce em mulheres na pré-menopausa aumenta o risco do desenvolvimento de parkinsonismo. Desse modo, a diminuição dos procedimentos cirúrgicos profiláticos para câncer de ovário nas pacientes com risco médio de malignidade reduziria o risco dessa condição