PurposeThe microbial environment is an important factor that contributes to the pathogenesis of atopic dermatitis (AD). Recently, it was revealed that not only bacteria itself but also extracellular vesicles (EVs) secreted from bacteria affect the allergic inflammation process. However, almost all research carried out so far was related to local microorganisms, not the systemic microbial distribution. We aimed to compare the bacterial EV composition between AD patients and healthy subjects and to experimentally find out the beneficial effect of some bacterial EV compositionMethodsTwenty-seven AD patients and 6 healthy control subjects were enrolled. After urine and serum were obtained, EVs were prepared from samples. Metagenomic analysis of 16s ribosomal DNA extracted from the EVs was performed, and bacteria showing the greatest difference between controls and patients were identified. In vitro and in vivo therapeutic effects of significant bacterial EV were evaluated with keratinocytes and with Staphylococcus aureus-induced mouse AD models, respectively.ResultsThe proportions of Lactococcus, Leuconostoc and Lactobacillus EVs were significantly higher and those of Alicyclobacillus and Propionibacterium were lower in the control group than in the AD patient group. Therefore, lactic acid bacteria were considered to be important ones that contribute to the difference between the patient and control groups. In vitro, interleukin (IL)-6 from keratinocytes and macrophages decreased and cell viability was restored with Lactobacillus plantarum-derived EV treatment prior to S. aureus EV treatment. In S. aureus-induced mouse AD models, L. plantarum-derived EV administration reduced epidermal thickening and the IL-4 level.ConclusionsWe suggested the protective role of lactic acid bacteria in AD based on metagenomic analysis. Experimental findings further suggest that L. plantarum-derived EV could help prevent skin inflammation.
The clinical utility of a small-caliber vascular graft is still limited, owing to the occlusion of graft by thrombosis and restenosis. A small-caliber vascular graft (diameter, 2.5 mm) fabricated by electrospinning with a polyurethane (PU) elastomer (Pellethane) and biofunctionalized with heparin and two cell-adhesive peptides, GRGDS and YIGSR, was developed for the purpose of preventing the thrombosis and restenosis through antithrombogenic activities and endothelialization. The vascular grafts showed slightly reduced adhesion of platelets and significantly decreased adsorption of fibrinogen. In vitro studies demonstrated that peptide treatment on a vascular graft enhanced the attachment of human umbilical vein endothelial cells (HUVECs), and the presence of heparin and peptides on the graft significantly increased the proliferation of HUVECs. In vivo implantation of heparin/peptides coimmobilized graft (PU-PEG-Hep/G+Y) and PU (control) grafts was performed using an abdominal aorta rabbit model for 60 days followed by angiographic monitoring and explanting for histological analyses. The patency was significantly higher for the modified PU grafts (71.4%) compared to the PU grafts (46.2%) at 9 weeks after implantation. The nontreated PU grafts showed higher levels of α-SMA expression compared to the modified grafts, and for both samples, the proximal and distal regions expressed higher levels compared to the middle region of the grafts. Moreover, immobilization of heparin and peptides and adequate porous structure were found to play important roles in endothelialization and cellular infiltration. Our results strongly encourage that the development of small-caliber vascular grafts is feasible.
Our study demonstrated that the RV pressure load prevented RV dilatation from chronic PR without systolic dysfunction. It is suggested that a proper relief of RVOT obstruction with acceptable residual stenosis is more advantageous than aggressive RVOT enlargement in the long-term outcome of repaired TOF.
PurposeAtopic dermatitis (AD) is an inflammatory skin disease, significantly affecting the quality of life. Using AD as a model system, we tested a successive identification of AD-associated microbes, followed by a culture-independent serum detection of the identified microbe.MethodsA total of 43 genomic DNA preparations from washing fluid of the cubital fossa of 6 healthy controls, skin lesions of 27 AD patients, 10 of which later received treatment (post-treatment), were subjected to high-throughput pyrosequencing on a Roche 454 GS-FLX platform.ResultsMicrobial diversity was decreased in AD, and was restored following treatment. AD was characterized by the domination of Staphylococcus, Pseudomonas, and Streptococcus, whereas Alcaligenaceae (f), Sediminibacterium, and Lactococcus were characteristic of healthy skin. An enzyme-linked immunosorbent assay (ELISA) showed that serum could be used as a source for the detection of Staphylococcus aureus extracellular vesicles (EVs). S. aureus EV-specific immunoglobulin G (IgG) and immunoglobulin E (IgE) were quantified in the serum.ConclusionsA metagenomic analysis together with a serum detection of pathogen-specific EVs provides a model for successive identification and diagnosis of pathogens of AD.
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