Modernist Toilette: Degas, Woolf, Lawrence

<p>COPD animals were submitted to therapeutic protocols as described in materials and methods. Further, all animals were euthanized, lungs were obtained and sections were stained by PAS (Periodic Acid Schiff) as described in methods. In A) representative graphs and B) photomicrographs of PAS stained sections. Data representative of two experiments. n = 5–8 animals per group. One-way ANOVA.</p

Effect of photobiomodulation in the balance between effector and regulatory T cells in an experimental model of COPD

IntroductionCurrently, Chronic Obstructive Pulmonary Disease (COPD) has a high impact on morbidity and mortality worldwide. The increase of CD4+, CD8+ cells expressing NF-κB, STAT4, IFN-γ and perforin are related to smoking habit, smoking history, airflow rate, obstruction and pulmonary emphysema. Furthermore, a deficiency in CD4+CD25+Foxp3+ regulatory T cells (Tregs) may impair the normal function of the immune system and lead to respiratory immune disease. On the other hand, the anti-inflammatory cytokine IL-10, produced by Treg cells and macrophages, inhibits the synthesis of several pro-inflammatory cytokines that are expressed in COPD. Therefore, immunotherapeutic strategies, such as Photobiomodulation (PBM), aim to regulate the levels of cytokines, chemokines and transcription factors in COPD. Consequently, the objective of this study was to evaluate CD4+STAT4 and CD4+CD25+Foxp3+ cells as well as the production of CD4+IFN- γ and CD4+CD25+IL-10 in the lung after PBM therapy in a COPD mice model.MethodsWe induced COPD in C57BL/6 mice through an orotracheal application of cigarette smoke extract. PMB treatment was applied for the entire 7 weeks and Bronchoalveolar lavage (BAL) and lungs were collected to study production of IFN- γ and IL-10 in the lung. After the last administration with cigarette smoke extract (end of 7 weeks), 24 h later, the animals were euthanized. One-way ANOVA followed by NewmanKeuls test were used for statistical analysis with significance levels adjusted to 5% (p &lt; 0.05).ResultsThis result showed that PBM improves COPD symptomatology, reducing the number of inflammatory cells (macrophages, neutrophils and lymphocytes), the levels of IFN-γ among others, and increased IL-10. We also observed a decrease of collagen, mucus, bronchoconstriction index, alveolar enlargement, CD4+, CD8+, CD4+STAT4+, and CD4+IFN-γ+ cells. In addition, in the treated group, we found an increase in CD4+CD25+Foxp3+ and CD4+IL-10+ T cells.ConclusionThis study suggests that PBM treatment could be applied as an immunotherapeutic strategy for COPD

Effect of Low-Level Laser Therapy (LLLT) in Pulmonary Inflammation in Asthma Induced by House Dust Mite (HDM): Dosimetry Study

Asthma is characterized by chronic inflammation in the airways. Several models have been proposed for the discovery of new therapies. Low-Level Laser Therapy (LLLT) is relatively new and effective, very low cost, with no side effects. However, there is still no consensus on the optimal dose to be used. In this sense, the objective of the present study was to evaluate the best dose in an experimental model of asthma induced by House Dust Mite (HDM). Balb/c mice received administration of 100 ug/animal HDM and LLLT applications (diode laser: 660 nm, 100 mW and four different energies 1J, 3J, 5J, and 7.5J) for 16 days. After 24 hours, we studied inflammatory, functional, and structural parameters. The results showed that LBI was able to modulate the pulmonary inflammation observed by reducing the number of cells in Bronchoalveolar Lavage Fluid (BALF) as well as reducing the percentage of neutrophils, eosinophils and T lymphocytes. On the other hand, LLLT increased the level of IL-10 and reduced levels of IL-4, IL-5 and IL-13 in BALF. LLLT was able to reduce the production of mucus, peribronchial eosinophils, collagen deposition, bronchoconstriction index, and bronchial and muscular thickening in the airways. We concluded that the use of LLLT in the treatment of chronic inflammation of the airways attenuated the inflammatory process and functional and structural parameters. We emphasize, in general, that the 1J and 3J laser presented better results. Thus, photobiomodulation may be considered a promising tool for the treatment of chronic pulmonary allergic inflammation observed in asthma

Exercise Inhibits the Effects of Smoke-Induced COPD Involving Modulation of STAT3

Purpose. Evaluate the participation of STAT3 in the effects of aerobic exercise (AE) in a model of smoke-induced COPD. Methods. C57Bl/6 male mice were divided into control, Exe, COPD, and COPD+Exe groups. Smoke were administered during 90 days. Treadmill aerobic training begun on day 61 until day 90. Pulmonary inflammation, systemic inflammation, the level of lung emphysema, and the airway remodeling were evaluated. Analysis of integral and phosphorylated expression of STAT3 by airway epithelial cells, peribronchial leukocytes, and parenchymal leukocytes was performed. Results. AE inhibited smoke-induced accumulation of total cells (p<0.001), lymphocytes (p<0.001), and neutrophils (p<0.001) in BAL, as well as BAL levels of IL-1β (p<0.001), CXCL1 (p<0.001), IL-17 (p<0.001), and TNF-α (p<0.05), while increased the levels of IL-10 (p<0.001). AE also inhibited smoke-induced increases in total leukocytes (p<0.001), neutrophils (p<0.05), lymphocytes (p<0.001), and monocytes (p<0.01) in blood, as well as serum levels of IL-1β (p<0.01), CXCL1 (p<0.01), IL-17 (p<0.05), and TNF-α (p<0.01), while increased the levels of IL-10 (p<0.001). AE reduced smoke-induced emphysema (p<0.001) and collagen fiber accumulation in the airways (p<0.001). AE reduced smoke-induced STAT3 and phospho-STAT3 expression in airway epithelial cells (p<0.001), peribronchial leukocytes (p<0.001), and parenchymal leukocytes (p<0.001). Conclusions. AE reduces smoke-induced COPD phenotype involving STAT3

Human Tubal-Derived Mesenchymal Stromal Cells Associated with Low Level Laser Therapy Significantly Reduces Cigarette Smoke-Induced COPD in C57BL/6 mice.

Cigarette smoke-induced chronic obstructive pulmonary disease is a very debilitating disease, with a very high prevalence worldwide, which results in a expressive economic and social burden. Therefore, new therapeutic approaches to treat these patients are of unquestionable relevance. The use of mesenchymal stromal cells (MSCs) is an innovative and yet accessible approach for pulmonary acute and chronic diseases, mainly due to its important immunoregulatory, anti-fibrogenic, anti-apoptotic and pro-angiogenic. Besides, the use of adjuvant therapies, whose aim is to boost or synergize with their function should be tested. Low level laser (LLL) therapy is a relatively new and promising approach, with very low cost, no invasiveness and no side effects. Here, we aimed to study the effectiveness of human tube derived MSCs (htMSCs) cell therapy associated with a 30mW/3J-660 nm LLL irradiation in experimental cigarette smoke-induced chronic obstructive pulmonary disease. Thus, C57BL/6 mice were exposed to cigarette smoke for 75 days (twice a day) and all experiments were performed on day 76. Experimental groups receive htMSCS either intraperitoneally or intranasally and/or LLL irradiation either alone or in association. We show that co-therapy greatly reduces lung inflammation, lowering the cellular infiltrate and pro-inflammatory cytokine secretion (IL-1β, IL-6, TNF-α and KC), which were followed by decreased mucus production, collagen accumulation and tissue damage. These findings seemed to be secondary to the reduction of both NF-κB and NF-AT activation in lung tissues with a concomitant increase in IL-10. In summary, our data suggests that the concomitant use of MSCs + LLLT may be a promising therapeutic approach for lung inflammatory diseases as COPD

Reduction of T CD4⁺ and T CD8⁺ T cells infiltration in the lungs of htMSC and/or LLLT treated animals.

<p>COPD animals were submitted to therapeutic protocols as described in materials and methods. Further, all animals were euthanized and BAL obtained for flow cytometric analysis of the frequency of CD4⁺ and CD8⁺ T cells. In (A and B), dot plots depict the gates used. In (C and D), graphs of the percentage of CD4⁺ and CD8⁺ T cells, respectively. In (E and F),graphs of the absolute numbers of CD4⁺ and CD8⁺ T cells, respectively. Data representative of two independent experiments. n = 5–8 animals per group. One-way ANOVA.</p

Reduced total NF-B staining in the lungs of htMSC i.n and/or LLLT treated animals.

<p>COPD animals were submitted to therapeutic protocols as described in materials and methods. Further, all animals were euthanized, lungs obtained and sections were stained with anti-NF-B In A) representative graphs and B) photomicrographs of immunohistochemistry stained sections. Data representative of two experiments. n = 5–8 animals per group. One-way ANOVA.</p

Reduced cellular infiltration in the lungs of htMSC and LLLT treated COPD animals.

<p>COPD animals were submitted to therapeutic protocols as described in materials and methods. Further, all animals were euthanized and BAL obtained for cytospin and the quantification of total cells (A), macrophages (B), neutrophils (C) and lymphocytes (D). Data representative of three independent experiments. n = 5–8 animals per group. One-way ANOVA.</p