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SDF-1α-aligned SF nanofiber promoted regeneration of urethral mucosa, submucosal smooth muscles, and microvasculature, increased cellular proliferation, and reduced collagen deposition. SDF-1α expression was increased in reconstructed urethra at 3 months post-surgery in SDF-1α-aligned SF group. SDF-1α-aligned SF microfiber/3D-BAMG scaffolds may be used to repair and reconstruct long urethral defects because they accelerate urethral regeneration. © 2020 Wiley Periodicals, Inc.Mesoporous bioactive glass nanoparticles (MBGNs) based on the SiO2 -P2 O5 -CaO system have demonstrated promising properties for the local delivery of therapeutically active ions with the aim to improve their osteogenic properties. Manganese (Mn) has been identified as a candidate ion for local application in bone tissue engineering applications. It remains unknown how SiO2 -P2 O5 -CaO-based MBGNs influence human bone marrow-derived mesenchymal stromal cells (BMSCs) in terms of viability, proliferation, and differentiation and how these features can be modified by the addition of Mn to the MBGNs' composition. Therefore, in this study, MBGNs (composition in mol% 50 SiO2 , 40 CaO, 10 P2 O5 ) and its Mn-doped derivate 5Mn-MBGNs (composition in mol% 50 SiO2 , 35 CaO, 10 P2 O5 , 5 MnO) were applied to a culture of BMSCs in two different concentrations. With increasing concentration, 5Mn-MBGNs supported osteogenic differentiation and enhanced the upregulation of genes encoding for extracellular matrix proteins but also negatively influenced cell viability and proliferation. When applied in lower concentrations, MBGNs showed not only viability- and growth-enhancing effects but also significant pro-osteogenic features-however, these positive properties deteriorated with increasing concentration. Two major conclusions can be drawn from this study (a) supplementation with Mn enhances the osteogenic properties of MBGNs in a dose-dependent manner and (b) MBGNs constitute an attractive vector for therapeutically active ions since it exhibits an intrinsic pro-osteogenic potential that can be improved and/or modified by incorporation of therapeutically active ions. Future studies should focus on the evaluation of further candidate ions that are known to influence osteogenic differentiation positively. © 2020 The Authors. Journal of Biomedical Materials Research Part A published by Wiley Periodicals, Inc.The aim of this study was to assess the effect of adalimumab on the expression level of mRNA and protein TNF-α, IFN-γ, IL-17, IL12A, IL12B, IL23A in the culture of normal human fibroblasts, in which the LPS inflammation process was induced. The NHDF culture was exposed to the effect of LPS in the concentrations of 1μg/ml,2μg/ml and 10μg/ml for 2,8 and 24 hour periods, and then adalimumab was added at the concentration of 8μg/ml, it was then incubated for 2,8 and 24 hours. Cells unexposed to LPS and adalimumab constituted the control. The microarray expression techniques, RTqPCR, and ELISA assay were used. Irrespectively of the concentration of LPS used and the incubation time of it with cells overexpression of the analyzed genes is present, with increasing factor concentration used to induce inflammation and incubation time with it, expression of the assessed genes was greater. In turn, adding the anti-TNF drug to the culture caused the silencing of the expression of the mRNAs and proteins. It was confirmed that LPS and adalimumab above all affect the expression of genes and proteins dependent on the interaction of IL-12 with receptors, which are TNF-α and IFN-γ, and to a lesser extent also modulate IL-17. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.AIMS Diabetic nephropathy, a pathologically diagnosed microvascular complication of diabetes, is a strong risk factor for cardiovascular events, which mainly involve arteries larger than those affected in diabetic nephropathy. However, the association between diabetic nephropathy pathological findings and cardiovascular events has not been well studied. We aimed to investigate whether the pathological findings in diabetic nephropathy are closely associated with cardiovascular event development. METHODS This retrospective cohort study analysed 377 people with type 2 diabetes and biopsy-proven diabetic nephropathy, with a median follow-up of 5.9 years (interquartile range 2.0 to 13.5). We investigated how cardiovascular events were impacted by two vascular diabetic nephropathy lesions, namely arteriolar hyalinosis and arterial intimal thickening, and by glomerular and interstitial lesions. RESULTS Of the 377 people with diabetic nephropathy, 331 (88%) and 295 (78%) had arteriolar hyalinosis and arterial intimal thickening, respectively. During the entire follow-up period, those with arteriolar hyalinosis had higher cardiovascular event rates in the crude Kaplan-Meier analysis than those without these lesions (P = 0.005, log-rank test). When fully adjusted for clinically relevant confounders, arteriolar hyalinosis independently predicted cardiovascular events [hazard ratio (HR) 1.99; 95% confidence interval (CI) 1.12, 3.86], but we did not find any relationship between arterial intimal thickening and cardiovascular events (HR 0.89; 95% CI 0.60, 1.37). Additionally, neither glomerular nor interstitial lesions were independently associated with cardiovascular events in the fully adjusted model. CONCLUSIONS Arteriolar hyalinosis, but not intimal thickening of large arteries, was strongly associated with cardiovascular events in people with diabetic nephropathy. A1155463 This article is protected by copyright. All rights reserved.It is important to improve the understanding of the interactions between the trees and pathogens and integrate this knowledge about disease resistance into tree breeding programs. The conifer Norway spruce (Picea abies) is an important species for the forest industry in Europe. Its major pathogen is Heterobasidion parviporum, causing stem and root-rot. In this study, we identified eleven Norway spruce QTLs (Quantitative trait loci) that correlate with variation in resistance to H. parviporum in a population of 466 trees by association genetics. Individual QTLs explained between 2.1% and 5.2% of the phenotypic variance. The expression of candidate genes associated with the QTLs were analysed in silico and in response to H. parviporum hypothesizing that i) candidate genes linked to control of fungal sapwood growth are more commonly expressed in sapwood, and; ii) candidate genes associated with induced defences are respond to H. parviporum inoculation. The Norway spruce laccase PaLAC5 associated with control of lesion length development is likely to be involved in the induced defences.
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