Asthma is characterized by chronic lung inflammation and airway hyperresponsiveness. Despite recent advances in the understanding of its pathophysiology, asthma remains a major public health problem and, at present, there are no effective interventions capable of reversing airway remodeling. Mesenchymal stromal cell (MSC)-based therapy mitigates lung inflammation in experimental allergic asthma; however, its ability to reduce airway remodeling is limited. We aimed to investigate whether pre-treatment with eicosapentaenoic acid (EPA) potentiates the therapeutic properties of MSCs in experimental allergic asthma. Seventy-two C57BL/6 mice were used. House dust mite (HDM) extract was intranasally administered to induce severe allergic asthma in mice. Unstimulated or EPA-stimulated MSCs were administered intratracheally 24 h after final HDM challenge. Lung mechanics, histology, protein levels of biomarkers, and cellularity in bronchoalveolar lavage fluid (BALF), thymus, lymph nodes, and bone marrow were analyzed. Furthermore, the effects of EPA on lipid body formation and secretion of resolvin-D1 (RvD1), prostaglandin E2 (PGE2), interleukin (IL)-10, and transforming growth factor (TGF)-β1 by MSCs were evaluated in vitro. EPA-stimulated MSCs, compared to unstimulated MSCs, yielded greater therapeutic effects by further reducing bronchoconstriction, alveolar collapse, total cell counts (in BALF, bone marrow, and lymph nodes), and collagen fiber content in airways, while increasing IL-10 levels in BALF and M2 macrophage counts in lungs. In conclusion, EPA potentiated MSC-based therapy in experimental allergic asthma, leading to increased secretion of pro-resolution and anti-inflammatory mediators (RvD1, PGE2, IL-10, and TGF-β), modulation of macrophages toward an anti-inflammatory phenotype, and reduction in the remodeling process. Taken together, these modifications may explain the greater improvement in lung mechanics obtained. This may be a promising novel strategy to potentiate MSCs effects.

Asthma is a chronic inflammatory disease characterized by airway inflammation and remodeling, which can lead to progressive decline of lung function. Although mesenchymal stromal cells (MSCs) have shown beneficial immunomodulatory properties in preclinical models of allergic asthma, effects on airway remodeling have been limited. Mounting evidence suggests that prior exposure of MSCs to specific inflammatory stimuli or environments can enhance their immunomodulatory properties. Therefore, we investigated whether stimulating MSCs with bronchoalveolar lavage fluid (BALF) or serum from asthmatic mice could potentiate their therapeutic properties in experimental asthma. In a house dust mite (HDM) extract asthma model in mice, unstimulated, asthmatic BALF‐stimulated, or asthmatic serum‐stimulated MSCs were administered intratracheally 24 hours after the final HDM challenge. Lung mechanics and histology; BALF protein, cellularity, and biomarker levels; and lymph‐node and bone marrow cellularity were assessed. Compared with unstimulated or BALF‐stimulated MSCs, serum‐stimulated MSCs further reduced BALF levels of interleukin (IL)‐4, IL‐13, and eotaxin, total and differential cellularity in BALF, bone marrow and lymph nodes, and collagen fiber content, while increasing BALF IL‐10 levels and improving lung function. Serum stimulation led to higher MSC apoptosis, expression of various mediators (transforming growth factor‐β, interferon‐γ, IL‐10, tumor necrosis factor‐α‐stimulated gene 6 protein, indoleamine 2,3‐dioxygenase‐1, and IL‐1 receptor antagonist), and polarization of macrophages to M2 phenotype. In conclusion, asthmatic serum may be a novel strategy to potentiate therapeutic effects of MSCs in experimental asthma, leading to further reductions in both inflammation and remodeling than can be achieved with unstimulated MSCs. Stem Cells Translational Medicine 2019;8:301&312

Recebido em 23 de setembro de 2015. Aceito em 8 de novembro de 2015Usando as triangulações propostas pelo antigo astrônomo Aristarco, obtivemos neste trabalho o tempo total e a duração do máximo dos eclipses solares e calculamos o tempo total dos eclipses lunares. Para isso, usamos os valores do período orbital da Lua e os valores das razões entre as distâncias Terra-Lua e o diâmetro da Terra. Combinamos esses valores com outros dois parâmetros geométricos, conseguidos a partir do tratamento das imagens dos eclipses do Sol e da Lua. Os resultados foram comparados com valores atuais. Palavras-chave: Aristarco, eclipse, anel de fogo.Using triangulations proposed by the ancient astronomer Aristarchus, we obtained in this work the total time to lunar and solar eclipses and the maximum duration of solar eclipses. For this purpose, we used the values of the orbital period of the Moon and the values of the ratio between the Earth-Moon distance and the Earth's diameter. We combined them with two other geometric parameters obtained from the processing of images of the Sun and Moon eclipses. The results were compared with current values. Keywords: Aristarchus, eclipse, ring of fire. IntroduçãoRevisitar os trabalhos de Aristarco (∼300 aC)é realizar um estudo das características geométricas do Sol, da Lua, da Terra e das configurações entre eles, em especial os eclipses lunar e solar [1][2][3]. Para resgatar as ideias e os trabalhos deste cientista antigo, adotaremos um ponto de vista atual, na qual conhecemos com grande precisão o valor do diâmetro da Terra, 1 as distâncias Terra-Lua e o período de revolução da Lua em torno da Terra [4]. Seus valores numéricos se encontram organizados na Tabela 1.Na primeira razão da Tabela 1, d P T L se refere aquela distância onde a Lua está no perigeu (periélio), ou seja, na posição mais próxima da Terra. Na segunda razão, d TLé a distância média entre a Terra e Lua e na terceira, d A T Lé a distância relativa ao apogeu (afélio), queé a posição mais afastada da Lua na suaórbita. O denominador (D T ) destas * Endereço de correspondência: acbertuola@gmail.com. 1 O diâmetro da Terra foi estimado por Eratóstenes (∼ 225 aC) com razoável precisão. O valor utilizado neste trabalhoé DT = 12740 km.Tabela 1: Grandezas astronômicas a respeito da Lua. RazõesPeríodo da Lua (dias)

Although bone marrow-derived mesenchymal stromal cells (BM-MSCs) from patients with chronic obstructive pulmonary disease (COPD) appear to be phenotypically and functionally similar to BM-MSCs from healthy sources in vitro, the impact of COPD on MSC metabolism and mitochondrial function has not been evaluated. In this study, we aimed to comparatively characterize MSCs from healthy and emphysematous donors (H-MSCs and E-MSCs) in vitro and to assess the therapeutic potential of these MSCs and their extracellular vesicles (H-EVs and E-EVs) in an in vivo model of severe emphysema. For this purpose, C57BL/6 mice received intratracheal porcine pancreatic elastase once weekly for 4 weeks to induce emphysema; control animals received saline under the same protocol. Twenty-four hours after the last instillation, animals received saline, H-MSCs, E-MSCs, H-EVs, or E-EVs intravenously. In vitro characterization demonstrated that E-MSCs present downregulation of anti-inflammatory (TSG-6, VEGF, TGF-β, and HGF) and anti-oxidant (CAT, SOD, Nrf2, and GSH) genes, and their EVs had larger median diameter and lower average concentration. Compared with H-MSC, E-MSC mitochondria also exhibited a higher respiration rate, were morphologically elongated, expressed less dynamin-related protein-1, and produced more superoxide. When co-cultured with alveolar macrophages, both H-MSCs and E-MSCs induced an increase in iNOS and arginase-1 levels, but only H-MSCs and their EVs were able to enhance IL-10 levels. In vivo, emphysematous mice treated with E-MSCs or E-EVs demonstrated no amelioration in cardiorespiratory dysfunction. On the other hand, H-EVs, but not H-MSCs, were able to reduce the neutrophil count, the mean linear intercept, and IL-1β and TGF-β levels in lung tissue, as well as reduce pulmonary arterial hypertension and increase the right ventricular area in a murine model of elastase-induced severe emphysema. In conclusion, E-MSCs and E-EVs were unable to reverse cardiorespiratory dysfunction, whereas H-EVs administration was associated with a reduction in cardiovascular and respiratory damage in experimental severe emphysema.

High accuracy in estimating energy expenditure is essential for enhancing sports performance. The resting metabolic rate (RMR), as a primary component of total energy expenditure (TEE), is commonly estimated using predictive equations. However, these references may not be applicable to adolescent athletes. The purpose of this cross-sectional study was to analyse the differences between predicted RMR in relation to energy expenditure measured by indirect calorimetry (IC) among 45 Brazilian male adolescent football athletes. Indirect calorimetry (IC) and anthropometric (bioimpedance) measurements were recorded at a single visit to the laboratory after fasting overnight. The mean age was 15.6 ± 1.14 years, body mass was 63.05 ± 7.8 kg, and height was 172 ± 7.5 cm. The RMR values predicted by equations proposed by the Food and Agriculture Organization (FAO) (United Nations), Henry and Rees (HR), Harris Benedict (HB), and Cunningham (CUN) were compared with IC RMR values, by correlation analysis. The FAO and HR predictive equations yielded different values from IC (IC: 1716.26 ± 202.58, HR: 1864.87 ± 147.78, FAO: 1854.28 ± 130.19, p = 0.001). A moderate correlation of 0.504 was found between the results of HB and IC. In the survival-agreement model, the CUN equation showed low disagreement with the IC RMR, with error values between 200 and 300 kcal/day. The results showed that HB and CUN yielded similar values as IC, with the CUN equation showing low disagreement with IC; hence, adolescent athletes should undergo evaluation with precise laboratory methods to ensure that accurate information about RMR is recorded.