BackgroundExtracellular adenosine triphosphate (ATP) is up-regulated in the airways of patients with chronic obstructive pulmonary disease (COPD), resulting in increased inflammation, bronchoconstriction, and cough. Although extracellular ATP levels are tightly controlled by nucleoside triphosphate diphosphohydrolase-1 (NTPDase1; also known as CD39) in the lungs, the role of CD39 in the pathology of COPD is unknown. We hypothesized that alterations in the expression and activity of CD39 could be part of the mechanisms for initiating and perpetuating the disease.MethodsWe analyzed CD39 gene and protein expression as well as ATPase enzyme activity in lung tissue samples of patients with COPD (n = 17), non-obstructed smokers (NOS) (n = 16), and never smokers (NS) (n = 13). Morphometry studies were performed to analyze pulmonary vascular remodeling.ResultsThere was significantly decreased CD39 gene expression in the lungs of the COPD group (1.17 [0.85–1.81]) compared with the NOS group (1.88 [1.35–4.41]) and NS group (3.32 [1.23–5.39]) (p = 0.037). This attenuation correlated with higher systemic inflammation and intimal thickening of muscular pulmonary arteries in the COPD group. Lung CD39 protein levels were also lower in the COPD group (0.34 [0.22–0.92]) compared with the NOS group (0.67 [0.32–1.06]) and NS group (0.95 [0.4–1.1) (p = 0.133). Immunohistochemistry showed that CD39 was downregulated in lung parenchyma, epithelial bronchial cells, and the endothelial cells of pulmonary muscular arteries in the COPD group. ATPase activity in human pulmonary structures was reduced in the lungs of patients with COPD.ConclusionAn attenuation of CD39 expression and activity is presented in lung tissue of stable COPD patients, which could lead to pulmonary ATP accumulation, favoring the development of pulmonary inflammation and emphysema. This may be a mechanism underlying the development of COPD.Electronic supplementary materialThe online version of this article (10.1186/s12931-018-0793-0) contains supplementary material, which is available to authorized users.

Three-dimensional porous scaffolds offer some advantages over conventional treatments for bone tissue engineering. Amongst all non-bioresorbable scaffolds, biocompatible metallic scaffolds are preferred over ceramic and polymeric scaffolds, as they can be used as electrodes with different electric field intensities (or voltages) for electric stimulation (ES). In the present work we have used a palladium-coated polymeric scaffold, generated by electroless deposition, as a bipolar electrode to electrically stimulate human osteoblast-like Saos-2 cells. Cells grown on palladium-coated polyurethane foams under ES presented higher proliferation than cells grown on foams without ES for up to 14 days. In addition, cells grown in both conditions were well adhered, with a flat appearance and a typical actin cytoskeleton distribution. However, after 28 days in culture, cells without ES were filling the entire structure, while cells under ES appeared rounded and not well adhered, a sign of cell death onset. Regarding osteoblast differentiation, ES seems to enhance the expression of early expressed genes. The results suggest that palladium-coated polyurethane foams may be good candidates for osteoblast scaffolds and demonstrate that ES enhances osteoblast proliferation up to 14 days and upregulate expression genes related to extracellular matrix formation.

Four novel transition metal-carborane photosensitisers were prepared by Sonogashira cross-coupling of 1-(4-ethynylbenzyl)-2-methyl-o-carborane (A-CB) with halogenated Ru(II)- or Ir(III)-phenanthroline complexes. The resulting boron-rich complexes with one (RuCB and IrCB) or two...

Growing evidence indicates that purinergic signalling is involved in the pathogenesis of chronic obstructive pulmonary disease (COPD) and in the vascular remodelling that occurs in other disorders; however, its role in initial vascular changes of COPD is not entirely known. We hypothesised that expression of genes regulating extracellular ATP and adenosine levels would be altered in the lung and systemic arteries of COPD patients. Quantitative real-time PCR was performed to analyse the relative expression of 17 genes associated with purinergic signalling and inflammation in lungs and intercostal arteries of never smokers (NS) (n = 16), non-obstructed smokers (NOS) (n = 17) and COPD patients (n = 21). Gene expression of ATP-degrading enzymes was decreased in both tissues of NOS and COPD patients compared to NS. NT5E expression (gene transcribing for an AMP hydrolyzing ectonucleotidase) was increased in both tissues in NOS compared to the other groups. P1 and P2 receptors did not show changes in expression. Expression of genes associated with inflammation (interleukin-13) was upregulated only in lung tissues of COPD. These findings suggest that the expression of different extracellular ATP-degrading enzymes is altered in smokers (NOS and COPD patients), promoting inflammation. However, the high NT5E expression found only in NOS could compensate this inflammatory environment.

A Ti-based alloy (Ti45Zr15Pd30Si5Nb5) with already proven excellent mechanical and biocompatibility features has been coated with piezoelectric zinc oxide (ZnO) to induce the electrical self-stimulation of cells. ZnO was grown onto the pristine alloy in two different morphologies: a flat dense film and an array of nanosheets. The effect of the combined material on osteoblasts (electrically stimulable cells) was analyzed in terms of proliferation, cell adhesion, expression of differentiation markers and induction of calcium transients. Although both ZnO structures were biocompatible and did not induce inflammatory response, only the array of ZnO nanosheets was able to induce calcium transients, which improved the proliferation of Saos-2 cells and enhanced the expression of some early differentiation expression genes. The usual motion of the cells imposes strain to the ZnO nanosheets, which, in turn, create local electric fields owing to their piezoelectric character. These electric fields cause the opening of calcium voltage gates and boost cell proliferation and early differentiation. Thus, the modification of the Ti45Zr15Pd30Si5Nb5 surface with an array of ZnO nanosheets endows the alloy with smart characteristics, making it capable of electric self-stimulation.

Nanogenerators are interesting for biomedical applications, with a great potential for electrical stimulation of excitable cells. Piezoelectric ZnO nanosheets present unique properties for tissue engineering. In this study, nanogenerator arrays based on ZnO nanosheets are fabricated on transparent coverslips to analyse the biocompatibility and the electromechanical interaction with two types of muscle cells, smooth and skeletal. Both cell types adhere, proliferate and differentiate on the ZnO nanogenerators. Interestingly, the amount of Zn ions released over time from the nanogenerators does not interfere with cell viability and does not trigger the associated inflammatory response, which is not triggered by the nanogenerators themselves either. The local electric field generated by the electromechanical nanogenerator–cell interaction stimulates smooth muscle cells by increasing cytosolic calcium ions, whereas no stimulation effect is observed on skeletal muscle cells. The random orientation of the ZnO nanogenerators, avoiding an overall action potential aligned along the muscle fibre, is hypothesised to be the cause of the cell-type dependent response. This demonstrates the need of optimizing the nanogenerator morphology, orientation and distribution according to the potential biomedical use. Thus, this study demonstrates the cell-scale stimulation triggered by biocompatible piezoelectric nanogenerators without using an external source on smooth muscle cells, although it remarks the cell type-dependent response.

In this work, porous FeMn(-xAg) alloys are fabricated through powder metallurgy methods. The effects of porosity and Ag addition on the microstructure, biodegradability, magnetic and mechanical properties of the alloys...

A series of porous metalloporphyrin frameworks prepared from the 5,10,15,20-tetra(4-pyridyl)porphyrin (H 2 TPyP) linker and four metal complexes, M(hfac) 2 M = Cu(II), Zn(II), Co(II), and Ni(II) (hfac: 1,1,1,5,5,5-hexafluoroacetylacetonate), were obtained using supercritical CO 2 (scCO 2 ) as a solvent. All the materials, named generically as [M-TPyP] n , formed porous metal− organic frameworks (MOFs), with surface areas of ∼450 m 2 g −1 . All MOFs were formed through the coordination of the metal to the exocyclic pyridine moieties in the porphyrin linker. For Cu(II), Zn(II), and Co(II), incomplete metal coordination of the inner pyrrole ring throughout the structure was observed, giving place to MOFs with substitutional defects and leading to a certain level of disorder and limited crystallinity. These samples, prepared using scCO 2 , were precipitated as nano-to micrometric powders. Separately, a layering technique from a mixture of organic solvents was used to crystallize high-quality crystals of the Co(II) based MOF, obtained with the formula [{Co(hfac) 2 } 2 H 2 TPyP] n . The crystal structure of this MOF was elucidated by single-crystal synchrotron X-ray diffraction. The Zn(II)-based MOF was selected as a potential photodynamic therapy drug in the SKBR-3 tumoral cell line showing outstanding performance. This MOF resulted to be nontoxic, but after 15 min of irradiation at 630 nm, using either 1 or 5 μM concentration of the product, almost 70% of tumor cells died after 72 h.