m6A-related lncRNA signature for predicting prognosis and immune response in head and neck squamous cell carcinoma.

OBJECTIVES: N6-methyladenosine (m6A) and long non-coding RNAs (lncRNAs) significantly impact the prognosis and the response to immunotherapy in head and neck squamous cell carcinoma (HNSCC). Therefore, this study aimed to develop an m6A-related lncRNA (m6AlncRNA) model for predicting the prognosis and the immunotherapeutic response in HNSCC. METHODS: We identified the m6AlncRNAs and constructed a risk assessment signature by using univariable Cox, Least Absolute Shrinkage and Selection Operator (LASSO), and multivariate Cox regression analyses. The Kaplan-Meier analysis, receiver-operating characteristic (ROC) curves, principal component analysis (PCA), decision curve analysis (DCA), consistency index (C-index), and nomogram were applied to assess the risk model. Finally, we investigated the predictability of this model in prognosis and response to immunotherapy and evaluated various novel compounds for the clinical treatment of HNSCC. RESULTS: HNSCC patients were assigned to high- and low-risk groups based on the median risk scores, and the high- and low-risk groups had different clinical features, tumor immune infiltration status, tumor immune dysfunction and exclusion (TIDE), tumor mutational burden (TMB), sensitivity to novel potential compounds, and immunotherapeutic response. CONCLUSIONS: The model we developed was accurate and efficient in predicting the prognosis of patients with HNSCC. It was also sensitive in stratifying HNSCC patients with good response to immunotherapy. Therefore, our study provided insight into elucidating the processes and mechanisms of m6AlncRNAs.

Identification of molecular classification and gene signature for predicting prognosis and immunotherapy response in HNSCC using cell differentiation trajectories.

Head and neck squamous cell carcinoma (HNSCC) is a highly heterogeneous malignancy with poor prognosis. This article aims to explore the clinical significance of cell differentiation trajectory in HNSCC, identify different molecular subtypes by consensus clustering analysis, and develop a prognostic risk model on the basis of differentiation-related genes (DRGs) for predicting the prognosis of HNSCC patients. Firstly, cell trajectory analysis was performed on single-cell RNA sequencing (scRNA-seq) data, four molecular subtypes were identified from bulk RNA-seq data, and the molecular subtypes were predictive of patient survival, clinical features, immune infiltration status, and expression of immune checkpoint genes (ICGs)s. Secondly, we developed a 10-DRG signature for predicting the prognosis of HNSCC patients by using weighted correlation network analysis (WGCNA), differential expression analysis, univariate Cox regression analysis, and multivariate Cox regression analysis. Then, a nomogram integrating the risk assessment model and clinical features can successfully predict prognosis with favorable predictive performance and superior accuracy. We projected the response to immunotherapy and the sensitivity of commonly used antitumor drugs between the different groups. Finally, we used the quantitative Reverse Transcription-Polymerase Chain Reaction (qRT-PCR) analysis and western blot to verify the signature. In conclusion, we identified distinct molecular subtypes by cell differentiation trajectory and constructed a novel signature based on differentially expressed prognostic DRGs, which could predict the prognosis and response to immunotherapy for patients and may provide valuable clinical applications in the treatment of HNSCC.

Astragalus Polysaccharide Relieves Inflammatory Responses in Guinea Pigs with Allergic Rhinitis via Ameliorating NF-kB-Mediated Treg/Th17 Imbalance.

BACKGROUND: Allergic rhinitis (AR) is regarded as a prevalent and non-infectious inflammation in nasal mucosa, and astragalus polysaccharide (APS) could mitigate inflammation. OBJECTIVES: Herein, this study probed the specific mechanism of APS in inflammatory responses in AR. METHODS: Firstly, AR guinea pig models were established through the stimulation and sensitization of ovalbumin (OVA) and received APS treatment. Changes in nasal symptoms were assessed through counting the sneezing and rubbing times of guinea pigs. The change patterns of OVA-specific immunoglobulin-E (OVA-sIgE), OVA-specific immunoglobulin-G1 (OVA-sIgG1), tumor necrosis factor (TNF)-α, and interleukin (IL)-6 in guinea pig serum were identified. Meanwhile, the levels of IL-17, transforming growth factor (TGF)-ß, IL-10, and forkhead box protein P3 (Foxp3) in the guinea pig tissues or serum were examined, and CD25+Foxp3+Treg or CD4+IL17+Th17 cell proportion was detected. Afterwards, nuclear factor-kappa B (NF-kB) expression in guinea pig nasal mucosa tissues were examined. Rescue experiments were designed to probe the role of NF-kB overexpression in inflammatory responses and Treg/Th17 imbalance in AR guinea pigs. RESULTS: APS treatment reduced sneezing and rubbing times of AR guinea pigs and suppressed OVA-sIgE, OVA-sIgG1, TNF-α, and IL-6 levels in guinea pig serum, and meanwhile, increased CD25+Foxp3+Treg cell proportion while reduced CD4+IL17+Th17 cell proportion in AR guinea pig serum or tissues, in a dose-dependent manner. NF-kB was highly-expressed in AR guinea pigs and down-regulated after APS treatment. NF-kB overexpression facilitated inflammatory responses and Treg/Th17 imbalance in AR. CONCLUSION: APS reduced Treg/Th17 imbalance via suppressing NF-kB expression, thereby ameliorating inflammatory responses in AR.

miR-96-5p Suppresses the Progression of Nasopharyngeal Carcinoma by Targeting CDK1.

BACKGROUND: Nasopharyngeal carcinoma (NPC) is a malignant tumor that occurs in the nasopharyngeal mucosa. Clinically, radiotherapy is the preferred treatment for NPC, and cervical lymph node metastasis is easy to emerge in the early stage. Therefore, this study aimed to investigate the role and potential molecular mechanisms of miR-96-5p in NPC cells to develop new therapeutic horizons. METHODS: The expression of miR-96-5p and CDK1 was measured by RT-qPCR or Western blot. The target relationship between miR-96-5p and CDK1 was confirmed by luciferase reporter assay. CCK-8, sphere formation, flow cytometry and colony formation assay were employed to examine cell viability, stem-like property, apoptosis and cycle, respectively. Male BALB/c nude mice model (6-8 weeks, weigh 18-20 g) was used to evaluate the effect of miR-96-5p on tumor growth in vivo. RESULTS: miR-96-5p was lowly expressed and CDK1 was highly expressed in NPC tissues and cell lines. CDK1 was identified as a direct target of miR-96-5p, and its expression was negatively regulated by miR-96-5p. By targeting CDK1, miR-96-5p overexpression significantly inhibited tumor sphere formation, promoted apoptosis and cell cycle arrest in CNE-2Z cells. Importantly, CCK-8 and colony formation assay demonstrated that elevated miR-96-5p enhanced the radiotherapy and chemotherapy sensitivity of CNE-2Z cells. Animal experiments showed that the overexpression of miR-96-5p reduced tumor weight and size in tumor-bearing mice and inhibited the expression of stem-like marker proteins and apoptosis-related proteins. CONCLUSION: These results, together, suggested that miR-96-5p induced cell cycle arrest and apoptosis, inhibited stem-like property, and enhanced the radiochemical sensitivity of NPC by targeting CDK1. In short, miR-96-5p may be a diagnostic and therapeutic target for NPC.

Effects of Qing Qiao Capsule in the treatment of chronic secretory otitis media and the levels of serum inflammatory factors.

To explore the effects of Qing Qiao Capsule in the treatment of chronic secretory otitis media and the levels of serum inflammatory factors, a total of 50 chronic secretory otitis media patients in the control group were subjected to caefaclor capsule, while the total of 50 cases in the observation group were treated with Qing Qiao Capsule. The traditional Chinese medicine (TCM) syndrome scores, therapeutic effects, and the levels of inflammatory factors were evaluated. After treatment, the scores of deafness, hearing loss, dizziness, soreness and weakness of the waist and knees, and fever is hens in palms and soles were significantly decreased in both groups (all P value <0.05). However, each score in the observation group was markedly less than that of the control group (all P value <0.05). Moreover, the C-reactive protein (CRP), procalcitonin (PCT) and tumor necrosis factor-α (TNF-α) levels measured after treatment were significantly lowered than those before treatment (all P value <0.05). Also, the levels of CRP, PCT and TNF-α in the observation group were obviously less than that of the control group (all P value <0.05). And the total therapeutic efficacy of the observation group was significantly higher than that of the control group (P<0.05). But no significant difference was observed in the rates of adverse reactions between both groups (P>0.05). Application of Qing Qiao Capsule in the treatment of chronic secretory otitis media yields better results, lowers TCM syndrome scores, and alleviates the body's inflammatory response, which is a safe drug in clinical use.

Apigenin enhances the antitumor effects of cetuximab in nasopharyngeal carcinoma by inhibiting EGFR signaling.

Nasopharyngeal carcinoma (NPC) is a type of head and neck cancers with poor prognosis. Despite that platinum-based chemotherapy concurrent with radiotherapy have made great achievements for the treatment of NPC, the therapeutic reaction and toxicity varies dramatically among individuals. Apigenin (API), a naturally occurring plant flavone, is considered to have anti-cancer effect. Cetuximab (CET), a well known epidermal growth factor receptor (EGFR) inhibitor, is widely used in various cancers, especially head and neck cancers. The aim of our study was to measure the combination of API and CET for the treatment of NPC in vitro and in vivo. Results demonstrated that combining API and CET could better suppress the viability of the human nasopharyngeal carcinoma cell lines (HONE1 and CNE2) and inhibit the growth of NPC than API or CET used alone. Besides, the combination of API with CET produced greater pro-apoptosis effect. Moreover, the increased G2/M phase arrest caused by CET could be remarkably enhanced by adding API in HONE1 and CNE2 cells. Although, both API and CET could decrease the expressions of p-EGFR, p-Akt, p-STAT3 and Cyclin D1. Combining them produced greater inhibition effect. These results suggested that the combination of API and CET may be a promising therapeutic approach for the treatment of NPC.