Project description:Pemphigus vulgaris (PV) is a kind of IgG-mediated autoimmune blistering disease (AIBD). The peripheral immune system plays a vital role in the pathophysiology of pemphigus vulgaris. This study aimed to explore the changes of peripheral immune cells of the patient before and after medication administration.
Project description:Efforts are increasingly aiming to develop in vitro models that can provide effective alternatives to in vivo experiments. The main aim of this study was the establishment of an in vitro model of the non-keratinized mucous membrane that can be used as a standardized tool to evaluate biological and therapeutic effects of pharmaceuticals for mucosal wound healing. Performing histological and immunofluorescence analyses with known differentiation markers we proved that our model mimics the two distinctive layers of the mucous membrane – the stratified squamous epithelium and the lamina propria. In our study we used our model to investigate molecular effects of a dexpanthenol-containing ointment that is widely used in the wound treatment of the oral mucosa. For that purpose our model exhibits a unique feature in that dexpanthenol and proliferation enhancing additives that may interfere with our studies are not required for the maintenance of the model culture. After setting standardized lesions with a CO2 laser, topical treatment with the dexpanthenol-containing ointment enhanced wound closure in our non-keratinized mucous membrane model compared to placebo and untreated controls. Furthermore, microarray analysis revealed that the treatment of our laser wounded model with the dexpanthenol-containing ointment evoked an upregulated expression of various genes related to accelerated wound healing. Overall, we verified that our mucous membrane model can be utilized in future to monitor ex vivo effects of various topical therapies on mucosa morphology, physiology, and gene expression. Our findings confirm the potential of the non-keratinized mucous membrane model as an in vitro tool for the replacement of pharmacological in vivo studies regarding mucosal wound healing.
Project description:Efforts are increasingly aiming to develop in vitro models that can provide effective alternatives to in vivo experiments. The main aim of this study was the establishment of an in vitro model of the non-keratinized mucous membrane that can be used as a standardized tool to evaluate biological and therapeutic effects of pharmaceuticals for mucosal wound healing. Performing histological and immunofluorescence analyses with known differentiation markers we proved that our model mimics the two distinctive layers of the mucous membrane – the stratified squamous epithelium and the lamina propria. In our study we used our model to investigate molecular effects of a dexpanthenol-containing ointment that is widely used in the wound treatment of the oral mucosa. For that purpose our model exhibits a unique feature in that dexpanthenol and proliferation enhancing additives that may interfere with our studies are not required for the maintenance of the model culture. After setting standardized lesions with a CO2 laser, topical treatment with the dexpanthenol-containing ointment enhanced wound closure in our non-keratinized mucous membrane model compared to placebo and untreated controls. Furthermore, microarray analysis revealed that the treatment of our laser wounded model with the dexpanthenol-containing ointment evoked an upregulated expression of various genes related to accelerated wound healing. Overall, we verified that our mucous membrane model can be utilized in future to monitor ex vivo effects of various topical therapies on mucosa morphology, physiology, and gene expression. Our findings confirm the potential of the non-keratinized mucous membrane model as an in vitro tool for the replacement of pharmacological in vivo studies regarding mucosal wound healing.
Project description:The M3 muscarinic acetylcholine receptor (CHRM3) is predominantly expressed in the basal epidermal layer where it mediates the effects of the auto/paracrine cytotransmitter acetylcholine. Patients with the autoimmune blistering disease pemphigus develop autoantibodies to CHRM3 and show alterations in keratinocyte adhesion, proliferation and differentiation, suggesting that CHRM3 controls these cellular functions. Chrm3 mice display altered epidermal morphology resembling that seen in patients with pemphigus vulgaris. Here, we characterized the cellular and molecular mechanisms whereby CHRM3 controls epidermal structure and function. We used single cell (sc)RNA-seq to evaluate keratinocyte heterogeneity and identify differentially expressed genes in specific subpopulations of epidermal cells in Chrm3 KO neonatal mice.
Project description:Interventions: The experimental group:Specialized Nursing Intervention plan for stoma - Preoperative Skin Cleansing plan - Stoma mucous membrane disinfection plan;The control group:Routine nursing measures
Primary outcome(s): Infection rate of incision site after enterostomy retraction
Study Design: Parallel
Project description:Intravenous immunoglobulin (IVIg) is used to treat mucous membrane pemphigoid (MMP), although its therapeutic effectivity is not sufficiently supported by randomized controlled clinical trials and its mode of action is only insufficiently understood. We have examined the effect of IVIg in a mouse model of anti-laminin 332 MMP and found that IVIg ameliorates both cutaneous and mucosal inflammatory lesions. Our investigation into the modes of action of IVIg in MMP indicated effective antiinflammatory mechanisms beyond the enhanced degradation of IgG mediated through inhibition of the neonatal Fc receptor. Our results suggest that IVIg curbs the activation of neutrophils at several levels. This includes a direct, immediate inhibitory effect on neutrophil activation by immune complexes but not C5a which blunts the release of reactive oxygen species and leukotriene B4 from neutrophils. IVIg also suppresses the formation of neutrophil extracellular traps in response to Ca2+ ionophore. In vivo treatment with IVIg altered the transcriptome of blood leukocytes and bone marrow neutrophils towards less proinflammatory phenotypes. Collectively, our results support the effectivity of IVIg in the treatment of MMP and indicate that effects on neutrophils at multiple levels may significantly contribute to its therapeutic effects.
2024-04-10 | GSE263026 | GEO
Project description:Dominant Species in Membrane Bioreactors