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Objective: Chronic rhinosinusitis (CRS), a common disease in otorhinolaryngology, seriously affects the life quality of patients. The existing therapy has certain limitations, and it is very urgent to deeply explore the pathogenesis and classification of CRS. Microbiome and inflammation are considered the causes of CRS, but the precise roles and the associations between these two factors in the pathogenesis of CRS remain controversial. Methods: Secretions were collected from the middle nasal canal, maxillary sinus and ethmoid sinus in CRS patients, then subjected to 16 S rRNA gene sequencing to profile microbiota community. Operational Taxonomic Units clustering and species annotation were adopted to obtain species diversity, prevalence rate and average relative abundance. Comparisons were performed at the level of microbial species and genus between CRS and control using NMDS, Anosim and MetaStat analysis. Th1 cytokines and Th2 cytokines were detected by ELISA. Spearman analysis were adopted to probe into the correlation between Th cytokines and microbial species in CRS. Results: Thirty-seven patients were enrolled, among them 22 with CRS and 15 were controls. The most abundant genera were Corynebacterium and Staphylococcus no matter in CRS patients or control. Corynebacterium propinquum was significant decreased in CRS patients no matter with nasal polyp or not. The abundances of Prevotella birria and Carnobacterium maltaromaticum were significantly different between CRSsNP and CRSwNP group. The levels of cytokines IL-2, TNF-α, IFN-É£, IL-4, IL-6, IL-10 were all increased in CRS patients. The cytokines levels were associated with specific microbial species in nasal tissue. Conclusion: The changes of species richness and complexity in nasal microbiome were obvious in CRS patients with nasal polyps or not. The different cytokines levels and microbiome between CRS patients without nasal polyps and patients with nasal polyps suggest heterogeneity in pathogenesis of chronic rhinosinusitis. Distinct microbiota and different cytokines were strongly linked in CRS. Level of Evidence: NA.
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BACKGROUND: Emerging evidence shows that long non-coding RNAs (lncRNAs) play a crucial role in tumor development by regulating biological behavior in various cancer cells. Several lncRNAs act as miRNA sponges by binding miRNA sequences and thus regulating mRNA expression. The lncRNA maternally expressed gene 3 (MEG3) has decreased expression levels in many cancer cells and acts as a tumor suppressor in different cancers. MEG3 also showed decreased expression in nasopharyngeal carcinoma (NPC) and plays a role in tumor suppression; however, the detailed mechanism of tumor suppression in NPC cells has not been reported. This paper aimed to explore the function and molecular mechanisms of MEG3 in the development of NPC. METHODS: MEG3 and miR-543 levels in NPC cells were detected by quantitative real-time PCR (qRT-PCR). The regulatory role of MEG3 in NPC cells was examined using knockdown and overexpression of MEG3 in C666-1 cells. Cell proliferation was analyzed by the cell counting kit-8 (CCK-8) assay, cell migration and invasion capacities were evaluated using Transwell assay, and cell apoptosis was assessed using flow cytometry. The relationship between MEG3 and miR-543 was investigated by luciferase reporter assay. MEG3- and Krüppel like factor 4 (KLF4)-mediated changes in NPC cell proliferation and apoptosis were analyzed, and KLF4, Bcl-2 and Bax protein expression levels were measured by western blotting. RESULTS: The results showed that MEG3 was decreased and miR-543 was increased in NPC cell lines, and upregulated MEG3 inhibited cell proliferation, migration, and invasion and promoted apoptosis, suggesting that MEG3 acts as a tumor suppressor in NPC cells. Furthermore, a luciferase reporter assay and western blotting indicated that MEG3 regulated KLF4 expression by sponging miR-543. Functionally, overexpression of MEG3 suppressed cell proliferation, promoted cell apoptosis and affected Bcl-2 and Bax protein levels via regulation of KLF4 expression mediated by sponging miR-543. CONCLUSIONS: These findings show that lncRNA MEG3 inhibits the development of NPC by sponging miR-543 targeting KLF4 and that MEG3 can serve as a new novel target for NPC therapeutics.
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OBJECTIVE: To study the therapeutic effect of photocatalytic nano-TiO2 on nasopharyngeal carcinoma xenograft in nude mice and underlying mechanism. METHODS: Nude mice bearing human nasopharyngeal carcinoma xenograft were randomly divided into six groups: nano-TiO2 + UV irradiation (with gradient concentration of nano-TiO2); nano-TiO2 alone and UV irradiation alone and blank control. The nano-TiO2 suspension was injected into xenografts, and 24 h after UV light with the wave length of 330 - 400 nm, all the xenografts were removed and sectioned for HE staining. Ultrastructure and apoptosis of tumor cells in the xenografts were observed by transmission electron microscope (TEM). The expression of Caspase-3 was examined immunohistochemical staining and the apoptosis was detected with TUNEL. RESULTS: Pathological analysis showed significant inflammatory responses (grade II and III) with local necrosis occurred in tumor tissues after nano-TiO2 photodynamic therapy, but not in the negative control and blank control. TEM showed the nano-TiO2 particles entered into the cytoplasm and the nucleus of tumor cells and many tumor cells had morphological changes for apoptosis. Significant positive expression of Caspase-3 and TUNEL-positive cells were found in the the xenografts with the treatments of nano-TiO2 + UV irradiation compared to control (P < 0.01), which were enhanced with the increases in nano-TiO2 concentration (P < 0.01). CONCLUSION: Photocatalytic nano-TiO2 can inhibit the growth of nasopharyngeal carcinoma xenograft in nude mice by inducing Caspase-3 expression and apoptosis in the tumor cells.