Stoutmcdonald0872

OBJECTIVE Lipocalin-type prostaglandin D synthase (L-PGDS) catalyzes the formation of prostaglandin D2 (PGD2), which has important roles in inflammation and cartilage metabolism. The aim of this study was to investigate the role of L-PGDS in the pathogenesis of OA using an experimental mouse model. METHODS Experimental OA was induced in wild-type (WT), and L-PGDS- deficient (L-PGDS-/-) mice (n = 10 per genotype) by destabilization of the medial meniscus (DMM). Cartilage degradation was evaluated by histology. The expression of MMP-13 and ADAMTS-5 was assessed by immunohistochemistry. Bone changes were determined by microcomputed tomography (µ-CT). Cartilage explants from L-PGDS-/- and WT mice (n = 6 per genotype) were treated with interleukin-1α (IL-1α) ex vivo, to evaluate proteoglycan degradation. Moreover, the effect of intra-articular injection of an adeno-associated virus (AAV) 2/5 encoding L-PGDS on OA progression was evaluated in WT mice (n = 9 per group). RESULTS Compared to WT mice, L-PGDS-/- mice had exacerbated cartilage degradation, and enhanced expression of MMP-13 and ADAMTS-5 (P  less then 0.05). Furthermore, L-PGDS-/- mice displayed increased synovitis and subchondral bone changes (P  less then 0.05). Cartilage explants from L-PGDS-/- mice showed enhanced proteoglycan degradation following treatment with IL-1α (P  less then 0.05). Intra-articular injection of AAV2/5 encoding L-PGDS attenuated the severity of DMM-induced OA-like changes in WT mice (P  less then 0.05). The level of L-PGDS was increased in OA tissues of WT mice (P  less then 0.05). CONCLUSION Collectively, these findings suggest a protective role of L-PGDS in OA, and therefore enhancing it level may constitute a promising therapeutic strategy. This article is protected by copyright. All rights reserved.Recently, minicircle (MC)-based cell therapy has been emerging as a novel technology for non-viral genetic modification. In this study, we investigated the characteristics of granulocyte chemotactic protein-2 (GCP-2)-overexpressing fibroblasts (GCP-2/MC) using MC microporation technology, as well as its therapeutic mechanism in wound healing. GCP-2 parent plasmid and MC containing GCP-2 were generated. Human dermal fibroblasts (HDF) were transfected with MC containing GCP-2. Quantitative reverse transcription polymerase chain reaction (qRT-PCR), scratch wound assay, and in vivo wound healing assay were performed. Gene and protein expression analysis revealed that GCP-2/MC highly expressed epithelialization growth factor, epidermal growth factor (EGF), chemokines, GCP-2, interleukin (IL)-8, as well as wound healing-associated genes such as insulin growth factor (IGF)-1 and hepatocyte growth factor (HGF). An in vitro scratch wound closure and matrigel tube formation assays demonstrated that the culture medium derived from GCP-2/MC substantially accelerated the wound closure and matrigel network formation. Wounds in nude mice were created by skin excisions followed by injections of GCP-2/MC. Results showed high cell survival potential and that GCP-2/MC transplantation highly accelerated skin wound closure by increasing re-epithelialization, capillary density and enhancing angiogenic factors, suggesting direct benefits for cutaneous closure. Taken together, these data suggest that MC-based GCP-2 overexpression could be a promising alternative strategy for promoting wound healing. This article is protected by copyright. All rights reserved.The 2019 European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) classification criteria for systemic lupus erythematosus (SLE) were developed to find an optimal balance between sensitivity and specificity while maintaining a relatively homogenous group of patients for inclusion in research studies and trials (1). In an early patient cohort study performed as part of Phase I (criteria generation) of the EULAR/ACR criteria project, 66.1% of SLE patients reported mucocutaneous findings in the first year of their disease (2). This article is protected by copyright. All rights reserved.Nerve defects are challenging to address clinically without satisfactory treatments. As a reliable alternative to autografts, decellularized nerve matrix scaffolds (DNM-Ss) have been widely used in clinics for surgical nerve repair. However, DNM-Ss remain inferior to autografts in their ability to support nerve regeneration for long nerve defects. In this study, we systematically and clearly presented the nano-architecture of nerve-specific structures, including the endoneurium, basement membrane and perineurium/epineurium in DNM-Ss. Furthermore, we modified the DNM-Ss by supplementing decellularized nerve matrix hydrogel (DNMG) and glial-derived neurotrophic factor (GDNF) and then bridged a 50-mm sciatic nerve defect in a beagle model. Fifteen beagles were randomly divided into three groups (5 per group) an autograft group, DNM-S group and GDNF-DNMG-modified DNM-S (DNM-S/GDNF@DNMG) group. DNM-S/GDNF@DNMGs, as optimized nerve grafts, were used to bridge nerve defects in the same manner as in the DNM-S group. The repair outcome was evaluated by behavioural observations, electrophysiological assessments, regenerated nerve tissue histology and reinnervated target muscle examinations. Compared with the DNM-S group, limb function, electrophysiological responses and histological findings were improved in the DNM-S/GDNF@DNMG group 6 months after grafting, reflecting a narrower gap between the effects of DNM-Ss and autografts. In conclusion, modification of DNM-Ss with DNMG and GDNF enhanced nerve regeneration and functional recovery, indicating that noncellular modification of DNM-Ss is a promising method for treating long nerve defects. This article is protected by copyright. All rights reserved.In the era of the "reproducibility crisis" and the "P-value controversy" new ways of presentation and interpretation of the results of a meta-analysis are desirable. One suggestion that has been made for single studies almost six decades ago and taken up now and then is the P-value function. For a given outcome, this function assigns a P-value to each possible hypothetical value, given the data. Moreover, the P-value function simultaneously provides two-sided confidence intervals for all possible alpha levels. An application to meta-analysis, while suggested early, has not been widely established. We introduce the drapery plot that presents the P-value function for all individual studies and pooled estimates in a meta-analysis as curves and the prediction range for a single future study. We also present a scaled variant with the test statistic on the y-axis. click here Both plots visualize the full information of a pairwise meta-analysis. We see a drapery plot as a complementary figure to a forest plot. It may be even an alternative in meta-analyses with many studies where forest plots tend to become very large and complex.