Early and late effects of bone marrow-derived mononuclear cell therapy on lung and distal organs in experimental sepsis

Abstract We tested the hypothesis that bone marrow-derived mononuclear cells (BMDMCs) at an early phase of cecal ligation and puncture (CLP)-induced sepsis may have lasting effects on: (1) lung mechanics and histology, (2) the structural remodelling of lung parenchyma, (3) lung, kidney, and liver cell apoptosis, and (4) pro- and anti-inflammatory cytokines and growth factors. At day 1, BMDMC significantly reduced mortality, as well as caspase-3, interleukin (IL)-6 and IL-1\u3b2, vascular endothelial growth factor, platelet-derived growth factor, hepatocyte growth factor, and transforming growth factor-\u3b2, but increased IL-10 mRNA expression in lung tissue in septic mice contributing to endothelium and epithelium alveolar repair and improvement of lung mechanics. BMDMC also prevented the increase of apoptotic cells in lung, liver, and kidney. At day 7, these early functional and morphological effects were preserved or further improved. In conclusion, in the present model of sepsis, the beneficial effects of early administration of BMDMCs on lung and distal organs were preserved, possibly by paracrine mechanisms

N-acetylcysteine counteracts adipose tissue macrophage infiltration and insulin resistance elicited by advanced glycated albumin in healthy rats

Background: Advanced glycation endproducts elicit inflammation. However, their role in adipocyte macrophage infiltration and in the development of insulin resistance, especially in the absence of the deleterious biochemical pathways that coexist in diabetes mellitus, remains unknown. We investigated the effect of chronic administration of advanced glycated albumin (AGE-albumin) in healthy rats, associated or not with N-acetylcysteine (NAC) treatment, on insulin sensitivity, adipose tissue transcriptome and macrophage infiltration and polarization. Methods: Male Wistar rats were intraperitoneally injected with control (C) or AGE-albumin alone, or, together with NAC in the drinking water. Biochemical parameters, lipid peroxidation, gene expression and protein contents were, respectively, determined by enzymatic techniques, reactive thiobarbituric acid substances, RT-qPCR and immunohistochemistry or immunoblot. Carboxymethyllysine (CML) and pyrraline (PYR) were determined by LC/mass spectrometry (LC-MS/MS) and ELISA. Results: CML and PYR were higher in AGE-albumin as compared to C. Food consumption, body weight, systolic blood pressure, plasma lipids, glucose, hepatic and renal function, adipose tissue relative weight and adipocyte number were similar among groups. In AGE-treated animals, insulin resistance, adipose macrophage infiltration and Col12a1 mRNA were increased with no changes in M1 and M2 phenotypes as compared to C-albumin-treated rats. Total GLUT4 content was reduced by AGE-albumin as compared to C-albumin. NAC improved insulin sensitivity, reduced urine TBARS, adipose macrophage number and Itgam and Mrc mRNA and increased Slc2a4 and Ppara. CD11b, CD206, Ager, Ddost, Cd36, Nfkb1, Il6, Tnf, Adipoq, Retn, Arg, and Il12 expressions were similar among groups. Conclusions: AGE-albumin sensitizes adipose tissue to inflammation due to macrophage infiltration and reduces GLUT4, contributing to insulin resistance in healthy rats. NAC antagonizes AGE-albumin and prevents insulin resistance. Therefore, it may be a useful tool in the prevention of AGE action on insulin resistance and long-term complications of DM

Hálux valgo e pés planos: as forças plantares são iguais? Hallux valgus and flat feet: are plantar forces equal?

OBJETIVO: Este trabalho teve como objetivo estimar as forças plantares nos dedos dos pés de mulheres com hálux valgo e/ou pés planos. MÉTODOS: Trata-se de um estudo transversal envolvendo mulheres com hálux valgo e/ou pés planos confirmado através de análise radiográfica. Mediram-se as forças plantares, utilizando plataformas de forças. Coletaram-se estas forças com as mulheres descalças e em posição ereta, por três medidas sendo obtida uma média. Os dados foram adquiridos através da ponte amplificadora Spider 8 da HBM e analisados através do programa Catman®. Obtiveram-se as medidas de forças dos dedos de ambos os pés e as médias foram comparadas pelo teste t de Student segundo a presença de hálux valgo e pés planos; a associação entre essas deformidades foi estimada pelo teste exato de Fischer bicaudal, a significância estatística adotada foi alfa = 5%. RESULTADOS: Foram incluídas no estudo, vinte mulheres com presença ou não de hálux valgo. As forças médias encontradas mostraram-se maiores no 5º dedo em relação ao 1º dedo de ambos os pés (p< 0,05) em ambas as situações. CONCLUSÃO: Neste estudo encontraram-se, ao contrário de outros trabalhos, forças no 5º dedo maiores que no 1º em ambos os pés.<br>OBJECTIVE: to measure the plantar forces above the toes of women with hallux valgus and/or flat feet. METHODS: This study involved women with hallux valgus and/or flat feet confirmed by X-ray images. The plantar forces were measured utilizing force plates. Force was measured three times, which were taken with the women on barefoot and at upright position, recording the average for the three measurements. Data were acquired from Spider 8 system (HBM) and analyzed by using a Catman® software. The measurements for both feet's toes force were reported and the averages were compared by the Student's t-test according to the presence of hallux valgus and flat feet; the association between these deformities was estimated by using the two-tailed Fischer's exact test, the statistical significance adopted was alpha = 5%. RESULTS: For this study, 20 women with or without hallux valgus were included. The mean force values found showed to be higher on the fifth toe compared to first toe of both feet (p < 0.05) in both situations. CONCLUSION: in this study, we found strong forces on the fifth toe than on the first toe, contradicting some studies in literature

The p53 isoform, Δ133p53α, stimulates angiogenesis and tumour progression

International audienceThe tumour suppressor p53, involved in DNA repair, cell cycle arrest and apoptosis, also inhibits blood vessel formation, that is, angiogenesis, a process strongly contributing to tumour development. The p53 gene expresses 12 different proteins (isoforms), including TAp53 (p53 (or p53α), p53β and p53γ) and Δ133p53 isoforms (Δ133p53α, Δ133p53β and Δ133p53γ). The Δ133p53α isoform was shown to modulate p53 transcriptional activity and is overexpressed in various human tumours. However, its role in tumour progression is still unexplored. In the present study, we examined the involvement of Δ133p53 isoforms in tumoural angiogenesis and tumour growth in the highly angiogenic human glioblastoma U87. Our data show that conditioned media from U87 cells depleted for Δ133p53 isoforms block endothelial cell migration and tubulogenesis without affecting endothelial cell proliferation in vitro. The Δ133p53 depletion in U2OS osteosarcoma cells resulted in a similar angiogenesis blockade. Furthermore, using conditioned media from U87 cells ectopically expressing each Δ133p53 isoform, we determined that Δ133p53α and Δ133p53γ but not Δ133p53β, stimulate angiogenesis. Our in vivo data using the chicken chorio-allantoic membrane and mice xenografts establish that angiogenesis and growth of glioblastoma U87 tumours are inhibited upon depletion of Δ133p53 isoforms. By TaqMan low-density array, we show that alteration of expression ratio of Δ133p53 and TAp53 isoforms differentially regulates angiogenic gene expression with Δ133p53 isoforms inducing pro-angiogenic gene expression and repressing anti-angiogenic gene expression