No abstract

No abstract

RATIONALE: Human olfactory mucosa-derived mesenchymal stem cells (hOM-MSCs) are promising for treatment of immune diseases. The immunomodulatory activities of hOM-MSCs are partially ascribed to CD4 + T and B-lymphocytes, macrophages, and dendritic cells. The effect of the hOM-MSCs on function of CD8 + cytotoxic lymphocytes (CTLs) and natural killer cells (NKCs) was assessed. METHODS: hOM-MSC were generated from biopsies of patients (n53) with non-inflammatory diseases of the nasal cavity. Peripheral blood mononuclear cells (PBMCs) (n57) were cultured over hOM-MSCs in 10:1 ratio for 3 days. Expression of perforin, granzyme B and CD107a were analyzed in both CTLs and NKCs subsets. Jurkat cells were used as target cells. PBMCs and Jurkat were co-cultured in a 5:1 ratio for 2 h. Necrosis and apoptosis were detected by Annexin V (FITC) / To-PRO-3 staining. RESULTS: The hOM-MSCs reduced granzyme B and perforin expression in NKCs, but not in CTLs. The hOM-MSCs suppressed both spontaneous and tumor cell-stimulated degranulation detected by CD107a expression in both CTLs and NKCs. The Viability assay showed that hOM-MSC-treated PBMCs possessed reduced ability to induce apoptosis in target cells (MSCs-treated group-22.2 [range 18.2-27.3]%, control-13.3 [range 12.0-15.4]%; p50.02). CONCLUSIONS: hOM-MSCs suppressed cytotoxic functions of CTLs and NKCs affecting expression of perforin, granzyme B, CD107a, which eventually led to the reduced ability to induce apoptosis in target tumor cells. The development of MSC-based cell therapy may be useful for diseases associated with excessive cytotoxicity.

Magnetic resonance imaging (MRI), as a diagnostic tool in tissue engineering, has received widespread attention because of its ability to consistently provide degradation and absorption of implants in vivo. For some specific human tissues and organs, such as nerves, muscles and myocardium, their regeneration requires tissue engineering scaffolds have a good electrical conductivity. Graphene oxide (GO) has been extensively studied as a conductive biomaterial having mechanical reinforcement. Based on the above, we propose an MRI conductive scaffold containing gelatin (Gel)/gelatin-polycaprolactone (Gel-PCL)/ultra-small paramagnetic iron oxide (USPIO)/graphene oxide (GO) (Gel/Gel-PCL/USPIO/GO). Their physical and chemical properties as well as biocompatibility are measured in vitro. The purpose of doping USPIO was developed for non-invasive monitoring of tissue engineered implants and tissue reconstruction. Functional modification of GO to match electrophysiological requirement. Co-culture with bone marrow mesenchymal stem cells showed good biocompatibility. Blood experiments have also demonstrated the feasibility of scaffolds as tissue engineered implants. The USPIO-labeled conductive scaffold, as an effective image-guided and electrically stimulating implant, appears to be a reconstruction platform for specific tissues and organs.

No abstract

The advanced analysis of immune parameters describing differentiation profile, activation and exhaustion of lymphocytes, monocytes and granulocytes of patients with moderate and severe/critical COVID-19 pneumonia was performed.

RATIONALE: Aspirin Exacerbated Respiratory Disease (AERD) is defined by the triad of asthma, chronic rhinosinusitis with nasal polyps (CRSwNP), and an intolerance to cyclooxygenase-1 inhibitors. AERD patients tend to have more severe respiratory disease than aspirin-tolerant patients with CRSwNP. The underlying mechanisms contributing to enhanced disease in AERD are not understood, but a dysregulation in arachidonic acid metabolism is important. We investigated the 15lipoxygenase (15-LO) pathway in AERD pathogenesis. METHODS: We examined expression levels of genes important for the synthesis and function of arachidonic acid metabolites in AERD and CRSwNP NP by single-cell RNA sequencing using the 10X Genomics platform and by traditional RT-PCR. Lipid mediators were measured in sinonasal tissue by mass spectrometry. Immunofluorescence was used to examine localization of specific enzymes within NP. RESULTS: ALOX15 expression was significantly elevated in AERD compared to CRSwNP NP (p<0.05) and control tissue (p<0.001) and was predominantly expressed in epithelial cells. ALOX15expression significantly correlated with radiographic sinus disease severity (r50.56, p<0.001) and was associated with comorbid asthma in CRSwNP. 15oxo-ETE, a downstream product of 15-LO, was significantly elevated in CRSwNP (27.93 pg/mg tissue) and AERD (61.03 pg/mg tissue) NP compared to control (7.17 pg/mg tissue, p<0.001). Hydroxyprostaglandin dehydrogenase, an enzyme required for 15-oxo-ETE synthesis, was predominantly expressed in mast cells and, by immunofluorescence, localized near 15-LO + epithelium in AERD NP. CONCLUSIONS: Epithelial and mast cell interactions, leading to the synthesis of 15-oxo-ETE, may contribute to the dysregulation of arachidonic acid metabolism via the 15-LO pathway as well as to the enhanced sinonasal disease severity observed in AERD.

No abstract