New insights into allergic rhinitis treatment: MSC nanovesicles targeting dendritic cells.

Allergic rhinitis (AR) is a condition with limited treatment options. This study investigates the potential use of mesenchymal stem cell (MSC) nanovesicles as a novel therapy for AR. Specifically, the study explores the underlying mechanisms of MSC nanovesicle therapy by targeting dendritic cells (DCs). The researchers fabricated DC-targeted P-D2-EVs nanovesicles and characterized their properties. Transcriptomic sequencing and single-cell sequencing analyses were performed to study the impact of P-D2-EVs on AR mice, identifying core genes involved in the treatment. In vitro cell experiments were conducted to validate the effects of P-D2-EVs on DC metabolism, Th2 differentiation, and ILC2 activation. The results showed that P-D2-EVs efficiently targeted DCs. Transcriptomic sequencing analysis revealed differential expression of 948 genes in nasal tissue DCs of mice treated with P-D2-EVs. Single-cell sequencing further revealed that P-D2-EVs had inhibitory effects on DC activation, Th2 differentiation, and ILC2 activation, with Fut1 identified as the core gene. Validation experiments demonstrated that P-D2-EVs improved IL10 metabolism in DCs by downregulating Fut1 expression, thereby suppressing Th2 differentiation and ILC2 activation. Animal experiments confirmed the inhibitory effects of P-D2-EVs and their ability to ameliorate AR symptoms in mice. The study suggests that P-D2-EVs reshape DC metabolism and suppress Th2 differentiation and ILC2 activation through the inhibition of the Fut1/ICAM1/P38 MAPK signaling pathway, providing a potential therapeutic approach for AR.

LncRNA H19 inhibits oxidative stress injury of cochlear hair cells by regulating miR-653-5p/SIRT1 axis.

Oxidative stress is one of the important mechanisms of inner ear cell damage, which can lead to age-related hearing loss (ARHL). LncRNA H19 is significantly downregulated in the cochlea of old mouse, however, the role of H19 in the development of ARHL remains unclear. In this study, we aim to investigate the expression and function of H19 in oxidative stress injury of cochlear hair cells induced by HO. RT-qPCR and western blot analysis confirms that HEI-OC1 cells stimulated with HO decreases the expressions of H19 and SIRT1, but increases the expression of miR-653-5p. Overexpression of H19 could increase cell viability, ATP level and mitochondrial membrane potential, but reduce mitochondrial ROS generation and cell apoptosis ratio in HO-stimulated HEI-OC1 cells. MiR-653-5p is a target of H19, which can bind to the 3'-UTR of SIRT1. H19 is found to regulate the expression of SIRT1 through miR-653-5p. Further experiments demonstrates that H19 regulates HEI-OC1 cell viability, ATP level, mitochondrial membrane potential, mitochondrial ROS generation, and cell apoptosis ratio via the miR-653-5p/SIRT1 axis. In conclusion, lncRNA H19 inhibits oxidative stress injury of cochlear hair cells via the miR-653-5p/SIRT1 axis.

Parotidectomy in the management of squamous cell carcinoma of the external auditory canal.

PURPOSE: To investigate optimal approaches for appropriate removal of the parotid gland in the management of squamous cell carcinoma (SCC) of the external auditory canal (EAC) at different tumor stages. METHODS: In total, 39 patients with SCC of EAC treated at the Second Affiliated Hospital of Nanchang University between September 2003 and April 2019 were enrolled in this study. All patients underwent lateral temporal bone resection or subtotal temporal bone resection. Total parotidectomy was performed in patients with direct parotid invasion. Superficial parotidectomy was performed in patients with parotid node metastasis and patients with advanced stages without evidence of parotid involvement. RESULTS: The mean follow-up period was 68.7 months. Local recurrences or distant metastases occurred in five patients (12.8%). The 5-year overall survival rate was 78.4%. The 5-year survival rate was 100% in early stage (T1 and T2) patients, and 58.9 and 50.0% in patients staged III and IV, respectively. Direct parotid invasion was observed in only advanced-stage patients, while parotid node metastasis was noted in both early and advanced-stage patients preoperatively. There were no significant differences (χ2 = 0.1026; p = 0.749) between different tumor primary locations. However, soft tissue or preauricular organs became vulnerable once the anterior wall was infiltrated or eroded. CONCLUSION: Parotid management is important for achieving safer and wider tumor-free margins. Total parotidectomy should be mandatory for all advanced-staged (T3 and T4) patients. An optimal decision for parotid management in early stages depends on the infiltration or erosion of the anterior wall of the EAC.

CD47 is a Potential Target for the Treatment of Laryngeal Squamous Cell Carcinoma.

BACKGROUND/AIMS: This study aims to investigate the effect of CD47 on the development of laryngeal squamous cell carcinoma (LSCC) and the therapeutic potential of monoclonal antibody against CD47 and its ligand SIRPα in the treatment of LSCC. METHODS: We firstly detected the expressions of CD47 mRNA and protein in LSCC and para-carcinoma tissues, introduced the most efficient CD47siRNA sequence into LSCC cells by lentiviral transfection and employed three monoclonal antibodies to evaluate their anti-LSCC effects in vitro and in vivo. RESULTS: We observed that the mRNA and protein expressions of CD47 in LSCC tissue had significant increase in LSCC tissues compared with those in para-carcinoma tissue (p < 0.05). After the treatments of three monoclonal antibodies, i.e. anti-SIRPα, anti-CD47 BRIC126, anti-CD47 B6H12.2, in rats transfected with Hep-2 cell, it has been showed that the mRNA and protein expressions of CD47 in LSCC tissue decreased, macrophage efficiency was promoted when anti-SIRPα and/or CD47siRNA were used, the amounts, viabilities and expressions of CD47 protein of tumor cell were significantly inhibited. Additionally, combined use of CD47siRNA and anti-SIRPα seemed more efficient than solo use of CD47siRNA/anti-SIRPα. CONCLUSION: The results suggested a critical role of CD47 in LSCC development and the promising treatment of antiCD47/SIRPα and/or CD47siRNA in LSCC.

CCR3 gene knockout inhibits proliferation, differentiation, and migration of eosinophils in allergic rhinitis model mice.

Allergic rhinitis (AR) is characterized by various bothersome clinical symptoms of the nasal mucosa that impaired the quality of daily life. Different chemokine receptors play a crucial role in the recruitment of inflammatory cells in AR. However, the effect of CC chemokine receptor (CCR) 3 on the function of eosinophils (EOS) is still unclear. We investigated the effect of CCR3 on EOS in a murine model of OVA-mediated allergic rhinitis using CCR3-deficient (CCR3-/-) mice. In vitro, bone marrow of CCR3-/- and wild-type (WT) mice were used to investigate the induction and development of EOS. In vivo, Allergic rhinitis was initiated in CCR3-/- and wild-type (WT) mice by passive transfer OVA, followed by detecting the eosinophil infiltration of the nasal mucosa and bone marrow. Then CD34+ progenitor cells in bone marrow and blood were evaluated by IHC analysis. Furthermore, the degranulation proteins of EOS in nasal mucosa, marrow, blood and NALF were determined by IHC, real-time PCR analysis and Western blot. We found that CCR3 gene can regulate the growth and development of primary cultured eosinophils. Knockout CCR3 gene can inhibit the proliferation and degranulation of EOS. The infiltration of eosinophils in the nasal mucosa following OVA-challenged, was significantly higher in WT mice compared with those stimulated with phosphate-buffered saline (PBS) for WT, but that was not seen in similarly treated CCR3-/- mice. Besides, the number of CD34+ progenitor cells in bone marrow and blood were also suppressed in CCR3-/- mice. The degranulation proteins of EOS expressed in nasal mucosa, marrow, blood and NALF were decreased in CCR3-/- AR mice compared with WT-AR mice. And the clinical symptoms were significantly alleviated. The expression of granulation proteins in NALF were not detected in both untreated CCR3-/- mice and WT mice. These results demonstrate a contribution of CCR3 to both the growth, migration, and degranulation of EOS during allergic rhinitis.

LncRNA ANRIL Promotes Autophagy Activation Through miR-16-5p/TLR4 Axis in Allergic Rhinitis.

BACKGROUND: Allergic rhinitis (AR) is an allergic disease of nasal mucosa. LncRNAs are key modulators affecting AR development. Neverthelss, the impact of lncRNA ANRIL in AR is not clear. OBJECTIVE: This work decided to study the mechanism underlying the impact of ANRIL on TLR4 expression through targeting miR-16-5p during autophagy and epithelial barrier dysfunction in the progression of AR. METHODS: Human nasal epithelial cells were exposed to TNF-α to establish AR cell model, AR mice model was constructed by ovalbumin (OVA) treatment. QRT-PCR or western blot assays were applied to measure the levels of mRNA and proteins. Dual-luciferase reporter gene detection and RIP assay were conducted to verify the association between ANRIL and miR-16-5p. Autophagy flux assessment by mRFP-GFP-LC3 method was performed to detect autophagy level. RESULTS: AR progression could induce the autophagy, and the expressions of tight junction proteins were downregulated in AR cell model. Moreover, knockdown of ANRIL reversed the effect of AR on autophagy-related protein and tight junction proteins MiR-16-5p was found to be bound with ANRIL and miR-16-5p inhibitor could reverse ANRIL knockdown-induced downregulation of autophagy-related proteins and epithelial barrier dysfunction. In addition, miR-16-5p directly targeted TLR4. Furthermore, knockdown of ANRIL reversed miR-16-5p and TLR4 expression, autophagy level, and tight junction protein levels in nasal mucosa of AR mice. CONCLUSION: This study illustrated that ANRIL acted as a promotion factor in AR induced autophagy and epithelial barrier dysfunction by enhancing the expression of TLR4 via interacting with miR-16-5p.

Upregulation of miR-155 regulates group 2 innate lymphoid cells by targeting c-maf in allergic rhinitis.

Group 2 innate lymphoid cells (ILC2s) and Th2 type immune response are critically involved in the pathogenesis of allergic rhinitis (AR), and this pathological process is influenced by microRNAs-mediated post-transcriptional regulation. The present study investigated the adaptation and function of miR-155 in AR patients and mouse model. We found that significantly increased miR-155 expression (1.63 ± 0.12 vs. 0.92 ± 0.11 in human, and 1.68 ± 0.15 vs. 1.06 ± 0.06 in mice) and ILC2s activity in nasal mucosa and serum in AR patients and mice. Administration of miR-155 antagomir significantly reduced the activity of ILC2s in nasal mucosa, suppressed the production of Th2 cytokines in serum and nasal mucosa, and alleviated the airway inflammation and allergic symptoms in AR mice, while miR-155 agomir increased ILC2s activity and production of Th2 cytokines and induced airway inflammation and allergic symptoms in control mice. Meanwhile, the expression of transcriptional factor c-Maf (0.57 ± 0.05 vs. 0.37 ± 0.04) in nasal mucosa in AR mice, which was significantly recovered by miR-155 antagomir (0.56 ± 0.04). Treatment with miR-155 agomir decreased c-Maf expression in nasal mucosa in control mice. This synchronized with the similar pattern in the current observations that miR-155 regulated Th2 cytokine (IL-4, IL-5, IL-9 and IL-13) production, airway inflammation and allergic symptoms in AR mice. Together, upregulation miR-155 suppressed the expression of transcriptional factor c-Maf and was critically involved in the ILC2s activation, which contributed to the airway inflammation and allergic symptoms in AR.

Long noncoding RNA DRAIC acts as a microRNA-122 sponge to facilitate nasopharyngeal carcinoma cell proliferation, migration and invasion via regulating SATB1.

Increasing evidences have revealed that long noncoding RNAs (lncRNAs) are frequently involved in various cancers. However, the expression and function of lncRNA DRAIC in nasopharyngeal carcinoma (NPC) remain unknown. In this study, we found that DRAIC was significantly increased in NPC tissues. Increased expression of DRAIC was positively correlated with advanced clinical stages of NPC patients. Functional assays revealed that ectopic expression of DRAIC enhances NPC cell growth, migration and invasion. DRAIC knockdown represses NPC cell growth, migration and invasion. Mechanistically, we identified two miR-122 binding sites on DRAIC. RNA pull-down, RNA immunoprecipitation, and dual-luciferase reporter assays confirmed the binding of DRAIC to miR-122. Via binding of miR-122, DRAIC upregulated the expression of miR-122 target SATB1, which was abolished by the mutation of miR-122 binding sites on SATB1. Moreover, the oncogenic roles of DRAIC on NPC were reversed by the mutation of miR-122 binding sites on SATB1, simultaneous overexpression of miR-122, or depletion of SATB1. In addition, the expression of SATB1 was also increased and positively associated with that of DRAIC in NPC tissues. In conclusion, these findings revealed the important roles of DRAIC-miR-122-SATB1 axis in NPC and suggested that DRAIC may be a potential therapeutic target for NPC.

[A systematic review of adenoidectomy in the treatment of otitis media with effusion in children].

OBJECTIVE: Systematic reviews and Meta-analysis were conducted to assess the efficacy and security of adenoidectomy for the treatment of otitis media with effusion in children. METHOD: Based on the principles and methods of Cochrane systematic reviews, literature was searched in PubMed, Medline, Elisevier, Ovid, CBM, CNKI, VIP and Wanfang datebases. Randomized controlled trials about treatment of otitis media with effusion in children using adenoidectomy were included. Meta-analysis was performed for the result of homogeneous studies using RevMan 5.2 software. RESULT: Adenoidectomy (combined with myringotomy or puncture) was superior to non-surgical (combined with myringotomy or puncture) treatment in reducing the incidence of acute otitis media and removing the middle ear effusion. Adenoidectomy combined with tympanostomy tube was superior to tympanostomy tube alone in the removal of the middle ear effusion and improvement of hearing level. Three trials described some postoperative complications including haemorrhage, incipient malignant hyperthermia, postoperative pneumonia and velopharyngeal insufficiency. CONCLUSION: Our research shows a benefit of adenoidectomy in the removal of middle ear effusion in children with OME. Adenoidectomy combined with tympanostomy tube was superior to tympanostomy tube alone in improving hearing level. At present, there is no evidence of serious postoperative complications after adenoidectomy.

[A systematic review of vasodilators for sudden sensorineural hearing loss].

OBJECTIVE: To evaluate the efficacy and safety of vasodilators for sudden sensorineural hearing loss. METHOD: Based on the principles and methods of Cocharne Systematic Reviews, we searched the cochrane central register of controlled trials, PubMed, Embase, ISI, the China biological medicine datebase, VIP, CNKI and Wangfang database. Randomized controlled trials about using vasodilators to treat sudden sensorineural hearing loss were included. Meta-analysis was performed for the results of homogeneous studies using RevMan software. RESULT: Twenty eight randomized control trials met the inclusion criteria. Seven studies showed vasodilators was not more effective than placebo. From 14 studies comparing vasodilators with vasodilators and 9 studies comparing vasodilators with other drugs, no definite conclusion could be drawn. CONCLUSION: The evidence currently available does not support the use of vasodilators in the treatment of sudden sensorineural hearing loss. Further randomized, double-blind, placebo-controlled trials are needed in order to define the efficacy and acceptability of vasodilators in the treatment of sudden sensorineural hearing loss.