Background:There is an ongoing discussion concerning the potential origins of chronic rhinosinusitis with nasal polyposis (CRSwNP).Objective:The aim of this study was to quantify subpopulations of T cells in peripheral blood and nasal polyps in CRSwNP to examine their influence on the etiology of this disease.Methods:Tissue and blood samples were collected from 11 patients who underwent nasal sinus surgery, and these samples were analyzed by multicolor flow cytometry.Results:There was a significantly lower frequency of CD4+ T-helper (Th) cells and a significantly higher frequency of CD8+ T cells among lymphocytes isolated from nasal polyps compared with peripheral blood mononuclear cells (PBMC). In both T-cell subpopulations, a shift mainly from naive T cells among peripheral blood lymphocytes toward an effector memory and terminally differentiated subtype predominance in nasal polyps was observed. Among CD4+ T cells, the frequencies of cluster of differentiation (CD) 45RA- Forkhead-Box-Protein P3high (FoxP3high) cytotoxic T-lymphocyte-associated Protein 4high (CTLA-4high) activated regulatory T (Treg) cells, and CD45RA- Forkhead-Box-Protein P3low (FoxP3low) memory T cells were significantly increased in nasal polyps compared with PBMC.Conclusion:In this study, we presented a detailed characterization of CD4+ and CD8+ T-cell subpopulations in patients with CRSwNP. CD8+ T cells were more prominent in nasal polyps than in CD4+ T cells. Both nasal CD8+ T cells and CD4+ T cells predominantly had an effector memory phenotype. Among CD4+ T cells, activated Treg cells were increased in nasal polyps compared with PBMC. The data point toward a local regulation of T-cell composition within the microenvironment of nasal polyps, which might be further exploited in the future to develop novel immunotherapeutic strategies.
Zinc oxide nanoparticles (ZnO-NP) are widely spread in consumer products. Data about the toxicological characteristics of ZnO-NP is still under controversial discussion. The human skin is the most important organ concerning ZnO-NP exposure. Intact skin was demonstrated to be a sufficient barrier against NPs; however, defect skin may allow NP contact to proliferating cells. Within these cells, stem cells are the most important toxicological target for NPs. The aim of this study was to evaluate the genotoxic and cytotoxic effects of ZnO-NP at low-dose concentrations after long-term and repetitive exposure to human mesenchymal stem cells (hMSC). Cytotoxic effects of ZnO-NP were measured by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. Furthermore, genotoxicity was evaluated by the comet assay. For long-term observation over 6 weeks, transmission electron microscopy (TEM) was applied. The results of the study indicated cytotoxic effects of ZnO-NP beginning at high concentrations of 50 μg/mL and genotoxic effects in hMSC exposed to 1 and 10 μg/mL ZnO-NP. Repetitive exposure enhanced cyto- but not genotoxicity. Intracellular NP accumulation was observed up to 6 weeks. The results suggest cytotoxic and genotoxic potential of ZnO-NP. Even low doses of ZnO-NP may induce toxic effects as a result of repetitive exposure and long-term cellular accumulation. This data should be considered before using ZnO-NP on damaged skin.
The increasing usage of zinc oxide nanoparticles (ZnO-NPs) in industrial applications as well as in consumer products raises concern regarding their potential adverse effects to a greater extend. Numerous studies have demonstrated toxic properties of NPs, however there is still a lack of knowledge concerning the underlying mechanisms. This study was designed to systematically investigate cytotoxicity, apoptosis, cell cycle alterations, and genotoxicity induced by ZnO-NP. Moreover, it was an aim of the investigations to specify the diverse effects of nanoparticle exposure in malignant in comparison with non-malignant cells. Therefore, human head and neck squamous cell carcinoma-derived FaDu cells were incubated with 4-20 µg/ml of ZnO-NPs for 1-48 hr and tested for cell viability, cell cycle alterations, apoptosis and caspase-3 gene expression as a sensitive marker of molecular apoptotic processes with regard to time- and dose-dependent effects. Human mesenchymal bone marrow stem cells were used as non-malignant representatives to examine oxidative stress-related genotoxicity. Results showed a significant reduction in cell viability as well as dose- and time-dependent increase of apoptotic cells following nanoparticle treatment. Likewise, caspase-3 gene expression enhanced already before first apoptotic cells were detectable. It could be observed that doses that were cytotoxic in tumor cells did not reduce viability in stem cells. However, the same concentrations already induced significant DNA damage. The findings of the study suggest to keep a more critical eye on the use of nanoparticles as anti-cancer agents. Yet, additional in vivo studies are needed to assess safety concerns for consumers and patients. Environ. Mol. Mutagen. 59:247-259, 2018. © 2017 Wiley Periodicals, Inc.
Asthma and allergies are both major global health problems with an increasing prevalence, and environmental data implicate an influence of air pollutants on their development. The present study focuses on the influence of nitrogen dioxide (NO2) and the major allergen of the house dust mite Der p 1 on human nasal epithelial cells of nonallergic patients in vitro. Nasal epithelial mucosa samples of 11 donors were harvested during nasal air passage surgery and cultured as an air-liquid interface. Exposure to 0.1, 1 and 10 ppm NO2 or synthetic air as a control was performed for 1 h. Subsequently, the cells were exposed to Der p 1 for 24 h. The release of interleukin (IL)-6 and IL-8 was measured by ELISA, and the production of IL-6 mRNA and IL-8 mRNA was measured by RT-PCR. NO2 exposure resulted in a concentration-dependent release of IL-6, but not IL-8 release. The coexposure of 0.1 ppm NO2 and Der p 1, or 1 ppm NO2 and Der p 1 significantly increased both IL-6 and IL-8 release. Exposure to NO2, Der p 1, or their combination, did not significantly influence the production of IL-6 or IL-8 mRNA. In conclusion, NO2 increases the release of inflammatory cytokines in human nasal epithelial cells, especially in coexposure with Der p 1, as a mechanism of allergotoxicology.
Although potentially biased by a relatively small number of patients, our study provides evidence that TSH after single-port cholecystectomy is (i) not less frequent when compared with standard laparoscopy, (ii) not as infrequent as suggested by the current literature, and (iii) not only associated with technical failure or patients' comorbidity.
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