Patients with chronic rhinosinusitis with nasal polyps (CRSwNP) and asthma comorbidity (ACRSwNP) present severe symptoms and are more likely to relapse. However, the pathogenesis of ACRSwNP is not fully understood. The aim of this study was to explore the underlying pathogenesis of ACRSwNP using bioinformatics approaches. ACRSwNP-related differentially expressed genes (DEGs) were identified by the analysis of the GSE23552 dataset. The clusterProfiler R package was used to carry out functional and pathway enrichment analysis. A protein–protein interaction (PPI) network was built using the STRING database to explore key genes in the pathogenesis of ACRSwNP. The bioinformatics analysis results were verified through qRT-PCR. The Connectivity Map (CMap) database was used to predict potential drugs for the treatment of ACRSwNP. A total of 36 DEGs were identified, which were mainly enriched in terms of regulation of immune response and detection sensory perception of taste. Thirteen hub genes including AZGP1, AQP9, GAPT, PIP, and PRR4 were identified as potential hub genes in ACRSwNP from the PPI network. Analysis of the GSE41861 dataset showed that upregulation of CST1 in nasal mucosa was associated with asthma. qRT-PCR detection confirmed the bioinformatics analysis results. Tacrolimus and spaglumic acid were identified as potential drugs for the treatment of ACRSwNP from the CMap database. The findings of this study provide insights into the pathogenesis of ACRSwNP and may provide a basis for the discovery of effective therapeutic modalities for ACRSwNP.
Background: Hypopharyngeal squamous cell carcinoma (HSCC) is a common malignant cancer characterized by high metastasis and infiltration. The development of new approaches for the early diagnosis and identification of new therapeutic targets is essential. TIPE2 is well known for a tumor suppressor and related to a favorable prognosis of HSCC. However, but the underlying mechanism remains unclear. Methods and Materials: TIPE2 expression was determined by immunohistochemistry and RT-qPCR. A TIPE2 overexpression stable cell line was generated by lentivirus infection. TIPE2 and other related protein levels were detected by western blotting. The cell cycle and apoptosis were performed by flow cytometric analysis. Cell proliferation was measured with a Cell Counting Kit-8 (CCK-8) assay, and the activity of caspase-3 and caspase-7 was assessed by Caspase-Glo® 3/7 Assay. All data were analyzed with SPSS 25 and GraphPad Prism 8.0. Results: TIPE2 expression was significantly downregulated in HSCC. Low TIPE2 expression may be associated with poor prognosis in HSCC. TIPE2 overexpression markedly inhibited tumor cell migration. Moreover, TIPE2 decreased cell proliferation but promoted apoptosis. TIPE2 suppressed tumor growth by activating Epithelial-Mesenchymal Transition (EMT) and the extrinsic apoptosis pathway. Conclusion: TIPE2 inhibited tumor progression by suppressing cell migration but promoting apoptosis. TIPE2 acted as a new therapeutic target in HSCC.
ObjectiveOlfactory impairment is a common complaint in patients with chronic rhinosinusitis with nasal polyps (CRSwNP), but the influence of endoscopic sinus surgery (ESS) on olfaction and the factors predicting olfactory impairment are not fully understood. This study aimed to assess the effect of ESS on improving olfactory dysfunction in patients with CRSwNP and to identify factors that predict prognosis.MethodsA total of 56 patients with CRSwNP reported their self-evaluated olfactory dysfunction score preoperatively and 1 month, 3 months, and 12 months after ESS. Preoperative clinical characteristics, computed tomography (CT) scan, and sinonasal endoscopy examination results were collected before surgery. Additionally, factors that predicted olfactory loss and affected the improvement of olfaction after ESS were evaluated.ResultsOlfactory improvement can be observed 1 month after ESS. A total of 73.2% (41/56) subjects experienced sustained recovery of subjective olfaction with the self-evaluated olfactory dysfunction score improving from 2.04 to 0.64 (P < 0.001) after 12 months. The Lund–Mackay scores (r = 0.593, P < 0.001) and Lund–Kennedy scores (r = 0.265, P < 0.05) correlated with the preoperative olfactory dysfunction score. Multivariate logistic regression analysis revealed that longer duration of olfactory dysfunction, blood eosinophilia, lower Lund–Mackay scores, and peripheral distribution of CT opacification were risk factors that adversely affected the recovery of olfactory function (P < 0.05).ConclusionESS improved self-evaluated olfactory function in patients with CRSwNP. Lund–Mackay scores and Lund–Kennedy scores were correlated with olfactory function prior to surgery, while a longer course of the disease, higher blood eosinophilia, lower Lund–Mackay scores, and peripheral distribution of CT opacification were risk factors for poor olfactory prognosis.
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