Exosome miR-552 Promotes Laryngocarcinoma Cells Malignant Progression via the PTEN/TOB1 Axis.

INTRODUCTION: Tumor exosome-derived miRNAs play important roles in the human laryngocarcinoma. However, it is still unknown if exosome miR-552 is involved in the laryngocarcinoma. The aim of the current study was to explore exosome miR-552's role in laryngocarcinoma and its underlying mechanisms. METHODS: Hep-2 exosome was characterized by transmission electron microscopy and nanoparticle tracking technology. CCK-8 was used to determine cell viability, and a xenograft animal model was used to determine the tumorigenicity. qPCR and Western blotting were used to measure the changes in target biomarkers. Luciferase reporter assay was used to evaluate the interactions between miR-552 and PTEN. miRNA sequencing was used to check the changes in miRNA profiles. RESULTS: miR-552 was upregulated in the laryngocarcinoma patients and was positively correlated to the cell proliferation and tumor growth. PTEN was identified as a direct target of miR-552. Hep-2 exosome is featured by high expression of miR-552 and treatment of Hep-2 exosome enhanced cell proliferation and tumorigenicity. The underlying mechanisms revealed that treatment of exosomes enhanced the malignant transformation of recipient cells in part by regulating epithelial-mesenchymal transition. CONCLUSION: Exosome miR-552 promotes laryngocarcinoma cells' malignant progression in part by the regulation of the PTEN/TOB1 axis.

MiR-5189-3p Suppresses cell Proliferation, Invasion and Migration Through Targeting EIF5A2 in Laryngeal Squamous Cell Carcinoma.

A growing body of evidence suggests that miR-5189-3p plays a critical role in multiple diseases. This study aimed to investigate the function of miR-5189-3p in laryngeal squamous cell carcinoma (LSCC) and explore its underlying mechanisms. qRT-PCR was designed to determine the expression levels of miR-5189-3p and eukaryotic translation initiation factor 5A2 (EIF5A2), while CCK-8 assay was performed to measure the effects of miR-5189-3p on cell proliferation. Transwell assay was performed to evaluate cell invasion as well as migration, and wound healing assay was applied to demonstrate cell migratory ability. Target gene prediction and luciferase reporter assay were developed to screen the possible target gene of miR-5189-3p, and Western blot was designed to measure EIF5A2 protein expression. MiR-5189-3p was down-regulated in LSCC tissues and cell lines. Up-regulation of miR-5189-3p notably inhibited cell proliferation, invasion, and migration in HEP2 and FADU cells. EIF5A2 was the potential downstream gene of miR-5189-3p, and overexpression of miR-5189-3p apparently reduced EIF5A2 expression. Moreover, reintroduction of EIF5A2 rescued the tumor suppressive effects of miR-5189-3p. MiR-5189-3p functions as a tumor inhibitor in LSCC progression via directly regulating EIF5A2 and may be a potential therapeutic target for LSCC.

Luteolin ameliorates inflammation and Th1/Th2 imbalance via regulating the TLR4/NF-κB pathway in allergic rhinitis rats.

OBJECTIVE: Luteolin has an anti-allergic effect but its mechanism is not clear. This study attempted to determine the mechanisms of luteolin in rhinitis. METHODS: Allergic rhinitis rat model was established by ovalbumin (OVA) stimulation. Then, the rats were treated with normal saline, luteolin, or lipopolysaccharide (LPS) for 14 days. Nasal symptoms were scored; the histopathological changes of nasal mucosa were detected by hematoxylin-eosin staining. Serum levels of Th1 type cytokines (IFN-γ, IL-2), Th2 type cytokines (IL-4, IL-5, IL-13), and OVA-specific IgE (sIgE) were determined by ELISA. The expressions of Toll-like receptor 4 (TLR4) and p65 in nasal mucosa were detected by Western blot or immunohistochemistry. RESULTS: Luteolin decreased symptom scores, specifically, the scores in control group, model group, model + 0.1 mg/kg luteolin, model + 1 mg/kg luteolin, and model + 10 mg/kg luteolin groups were 0.63 ± 0.52, 7.88 ± 0.83, 1.38 ± 0.52, 2.75 ± 0.46, and 5.00 ± 0.53, respectively. Luteolin ameliorated nasal mucosa inflammation by promoting the down-regulated levels of Th1 type cytokines, and suppressing the up-regulated levels of Th2 type cytokines, OVE-sIgE, TLR4, and p65. LPS further increased symptom scores, aggravated nasal mucosa inflammation, improved the unbalance of Th1/Th2 type cytokines, and lowered the expressions of OVE-sIgE, TLR4, and p65. Moreover, LPS reversed the effect of luteolin on allergic rhinitis rats. CONCLUSION: Luteolin ameliorated inflammation and Th1/Th2 imbalance via regulating the TLR4/NF-κB pathway in allergic rhinitis rats. This study provided novel evidence that luteolin could be used as a candidate drug in allergic rhinitis treatment.

Silencing of miR-17-5p suppresses cell proliferation and promotes cell apoptosis by directly targeting PIK3R1 in laryngeal squamous cell carcinoma.

BACKGROUND: Increasing evidence has suggested that microRNAs (miRNAs) act as key post-transcriptional regulators in tumor progression. Previous studies have confirmed that miR-17-5p functions as an oncogene in multiple cancers and contributes to tumor progression. However, the role and biological functions of miR-17-5p in the development of laryngeal squamous cell carcinoma (LSCC) still remain unknown. METHODS: qRT-PCR was used to detect miRNA and mRNA expression levels in LSCC tissues and cell lines. CCK-8 assay was used to measure cell viability and flow cytometry was performed to evaluate cell apoptosis. Western blot analysis was used to detect the protein levels of BAX, BCL-2, cleaved Caspase-3, PIK3R1 and AKT. Luciferase reporter assay was used to detect the effect of miR-17-5p on PIK3R1 expression. Xenograft animal model was used to test the effect of miR-17-5p on LSCC cell in vivo. RESULTS: In the present study, we found that miR-17-5p expression level was upregulated in LSCC tissues and cell lines. Depletion of miR-17-5p in LSCC cells significantly reduced cell proliferation and promoted cell apoptosis in vitro and in vivo. Mechanically, knockdown of miR-17-5p in LSCC cells inhibited BCL-2 expression while enhanced BAX and cleaved Caspase-3 protein expression. Moreover, depletion of miR-17-5p in LSCC cells suppressed AKT phosphorylation but did not influence PTEN expression. Importantly, miR-17-5p positively regulated PIK3R1 expression by directly binding to its 3'-untranslated region (UTR). Additionally, PIK3R1, which expression was downregulated in LSCC tissues and cell lines, was involved in LSCC cell survival by modulating the activation of AKT signal pathway. Dysregulation of miR-17-5p/PIK3R1 axis was participated in LSCC cell proliferation and apoptosis by inhibiting the activation of the PI3K/AKT signaling pathway. CONCLUSIONS: In conclusion, our study indicates that the miR-17-5p/PIK3R1 axis plays an essential role in the development of LSCC and provides a potential therapeutic target for LSCC treatment.

Upregulation of circFLNA contributes to laryngeal squamous cell carcinoma migration by circFLNA-miR-486-3p-FLNA axis.

BACKGROUND: Accumulating evidence shows that circular RNAs (circRNAs) plays vital roles in tumor progression. However, the biological functions of circRNAs in laryngeal squamous cell carcinoma (LSCC) metastasis is still unclear. METHODS: qRT-PCR was used to detect circFLNA, miRNAs and FLNA mRNA expression. Transwell assay and western blot were performed to evaluate cell migration ability and to detect FLNA, MMP2 and MLK1 protein expression, respectively. RNA pull-down analysis was used to find the binding-miRNAs of circFLNA. Luciferase reporter assay was used to examine the effect of circFLNA on miRNAs and miR-486-3p on FLNA expression. RESULTS: In this study, we confirmed that a Filamin A (FLNA)-derived hsa_circ_0092012 known as circFLNA, was upregulated in LSCC, and the higher expression of circFLNA was correlated with LSCC lymph node metastasis. Increased circFLNA facilitates LSCC cell migration ability through upregulating FLNA and MMP2 protein expression. Mechanistically, we find that circFLNA sponges miR-486-3p in LSCC cells, relieving miR-486-3p-induced repression of FLNA which promotes LSCC cell migration. Accordingly, FLNA mRNA is overexpressed in LSCC tissues and a higher FLNA level is correlated with poor survival. Dysregulation of the circFLNA/miR-486-3p/FLNA regulatory pathway contributes to LSCC migration. CONCLUSIONS: In summary, our study sheds light on the regulatory mechanism of circFLNA in LSCC migration via sponging miR-486-3p, which downregulates the FLNA protein expression. Targeting circFLNA/miR-486-3p/FLAN axis provides a potential therapeutic target for aggressive LSCC.

lncRNA FLJ20021 regulates CDK1-mediated PANoptosis in a ZBP1-dependent manner to increase the sensitivity of laryngeal cancer-resistant cells to cisplatin.

In this study, we investigated the role of the newly discovered lncRNA FLJ20021 in laryngeal cancer (LC) and its resistance to cisplatin treatment. We initially observed elevated lncRNA FLJ20021 levels in cisplatin-resistant LC cells (Hep-2/R). To explore its function, we transfected lncRNA FLJ20021 and cyclin-dependent kinase 1 (CDK1) into Hep-2/R cells, assessing their impact on cisplatin sensitivity and PANoptosis. Silencing lncRNA FLJ20021 effectively reduced cisplatin resistance and induced PANoptosis in Hep-2/R cells. Mechanistically, lncRNA FLJ20021 primarily localized in the nucleus and interacted with CDK1 mRNA, thereby enhancing its transcriptional stability. CDK1, in turn, promoted panapoptosis in a ZBP1-dependent manner, which helped overcome cisplatin resistance in Hep-2/R cells. This study suggests that targeting lncRNA FLJ20021 can be a promising approach to combat cisplatin resistance in laryngeal cancer by regulating CDK1 and promoting PANoptosis via the ZBP1 pathway. These findings open up possibilities for lncRNA-based therapies in the context of laryngeal cancer.

Incidence and prognosis of olfactory and gustatory dysfunctions related to SARS-CoV-2 Omicron strain infection in China: A national multicenter survey of 35,566 individuals.

Objective: This cross-sectional study aimed to determine the epidemiology of olfactory and gustatory dysfunctions related to COVID-19 in China. Methods: This study was conducted by 45 tertiary Grade-A hospitals in China. Online and offline questionnaire data were obtained from patients infected with COVID-19 between December 28, 2022, and February 21, 2023. The collected information included basic demographics, medical history, smoking and drinking history, vaccination history, changes in olfactory and gustatory functions before and after infection, and other postinfection symptoms, as well as the duration and improvement status of olfactory and gustatory disorders. Results: Complete questionnaires were obtained from 35,566 subjects. The overall incidence of olfactory and taste dysfunction was 67.75%. Being female or being a cigarette smoker increased the likelihood of developing olfactory and taste dysfunction. Having received four doses of the vaccine or having good oral health or being a alcohol drinker decreased the risk of such dysfunction. Before infection, the average olfactory and taste VAS scores were 8.41 and 8.51, respectively; after infection, they decreased to 3.69 and 4.29 and recovered to 5.83 and 6.55 by the time of the survey. The median duration of dysosmia and dysgeusia was 15 and 12 days, respectively, with 0.5% of patients having symptoms lasting for more than 28 days. The overall self-reported improvement rate was 59.16%. Recovery was higher in males, never smokers, those who received two or three vaccine doses, and those that had never experienced dental health issues, or chronic accompanying symptoms. Conclusions: The incidence of dysosmia and dysgeusia following infection with the SARS-CoV-2 virus is high in China. Incidence and prognosis are influenced by several factors, including sex, SARS-CoV-2 vaccination, history of head-facial trauma, nasal and oral health status, smoking and drinking history, and the persistence of accompanying symptoms.

Individual exposure of ambient particulate matters and eosinophilic chronic rhinosinusitis with nasal Polyps: Dose-Response, mediation effects and recurrence prediction.

PURPOSE: We evaluated the association between ambient particulate matter (PM) exposure and eosinophilic chronic rhinosinusitis with nasal polyps (CRSwNP), and predicted the CRSwNP recurrence risk using machine learning algorithms. METHODS: In total, 1,086 patients with CRSwNP were recruited from nine hospitals in China during 2014-2019. The average annual concentrations of ambient PMs before surgery were assessed using satellite-based daily concentrations of PM2.5 and PM10 for a 1 × 1-km2 area. Linear regression and logistic regression models were used to evaluate the associations of PM exposure with eosinophilia and risks of eosinophilic CRSwNPs. In addition, mediation effect analysis was used to validate the interrelationships of the aforementioned factors. Finally, machine learning algorithms were used to predict the recurrence risks of CRSwNPs. RESULTS: There was a significantly increased risk of eosinophilic CRSwNPs with each 10 µg/m3 increase in PMs, with odds ratios (ORs) of 1.039 (95% confidence interval [CI] = 1.007-1.073) for PM10 and 1.058 (95% CI = 1.007- 1.112) for PM2.5. Eosinophils had a significant mediation effect, which accounted for 52% and 35% of the relationships of CRSwNP recurrence with PM10 and PM2.5, respectively. Finally, we developed a naïve Bayesian model to predict the risk of CRSwNP recurrence based on PM exposure, inflammatory data, and patients' demographic factors. CONCLUSIONS: Increased PM exposure is associated with an increased risk of eosinophilic CRSwNP in China. Therefore, patients with eosinophilic CRSwNP should reduce PM exposure to mitigate its harmful impacts.

Preliminary dynamic observation of wound healing after low-temperature plasma radiofrequency ablation for laryngeal leukoplakia.

BACKGROUND: Low-temperature plasma ablation (LTPA) is an emerging technique for laryngeal leukoplakia (LL). OBJECTIVE: To initially observe the healing process of trauma after LTPA for LL. MATERIALS AND METHODS: Seventeen patients who underwent LTPA for LL were collected, and the degrees of wound healing were analyzed. RESULTS: Only 1 patient in who dysbiosis of the pharyngeal flora was induced by self-administered hormone nebulization treatment during the follow-up period. In the remaining patients, the wound healing was characterized by a crater-shaped defect on the vocal folds surface with pseudo-membranes, congestion, and mild edema on postoperative day 1. These symptoms became worse on postoperative day 7. On postoperative day 15, the pseudo-membrane was fully formed and some patients had granulomatous swelling of the vocal cords. These symptoms became better and better on postoperative day 30 and day 45. On postoperative day 60, the mucosa of the vocal folds had essentially returned to normal. On postoperative day 90, the vocal folds morphology and function had recovered well. CONCLUSION: It takes 2-3 months for the wound to heal completely after LTPA for LL. SIGNIFICANCE: A proper understanding of the wound healing process can reduce unnecessary surgical and pharmacologic interventions and avoid excessive treatment.

Exosomes Derived from microRNA-21 Overexpressing Neural Progenitor Cells Prevent Hearing Loss from Ischemia-Reperfusion Injury in Mice via Inhibiting the Inflammatory Process in the Cochlea.

Both exosomes derived from neural progenitor cells (NPCs) can suppress inflammation. Whether exosomes derived from miR-21-transfected NPCs (miR-21-Exo) could be utilized to alleviate hearing loss is investigated. NPCs were transfected with lentiviral vectors overexpressing miR-21, and miR-21-Exo was purified. Morphology and exosome membrane markers were examined with nanoparticle tracking analysis, transmission electron microscopy, and Western blot. After incubation with different concentrations of miR-21-Exo, the viability of RAW 264.7 cells and the relative expressions of miR-21 and IL-10 were determined. The ischemia and reperfusion (I/R) model of C57BL/6 J mice was constructed, and the treatment benefit of miR-21-Exo was revealed by the auditory brainstem response (ABR) test. Immunofluorescence staining of caspase-3 and parvalbumin was used to detect apoptosis hair cells in the cochlea, and Western blot was utilized to detect the relative expressions of P53 and inflammatory cytokines in the cochlea. Isolated exosomes were confirmed by the size of 96 ± 25 nm, single membrane, and positive expression of CD9 and Tsg101. Upregulated miR-21 expression was detected in miR-21-transfected NPCs and miR-21-Exo. miR-21-Exo incubation demonstrated no cytotoxicity but upregulated miR-21 and IL-10 expressions in RAW 264.7 cells. The administration of miR-21-Exo inhibited the increased ABR threshold under 8, 16, and 32 kHz frequencies in cochlea-I/R injury mice and diminished the mean fluorescent intensity of caspase-3/parvalbumin. Moreover, miR-21-Exo treatment increased the IL-10 expression and prevented the increased TNF-α and IL-1ß expressions in the cochlea of I/R mice both in mRNA and protein levels. Inner ear administration of miR-21-Exo effectively improved hearing damage caused by I/R.

High mobility group box 1 inhibition by BoxA attenuates ovalbumin-induced allergic rhinitis in mice.

This study was designed to evaluate the effects of BoxA on allergic rhinitis (AR). Ovalbumin (OVA)-induced AR mice model was employed and BoxA was administered to AR mice. AR symptoms, levels of cytokines and chemokines, and the expression of high mobility group box 1 (HMGB1), TLR2, and TLR4 were measured. BoxA treatment significantly ameliorated AR symptoms, decreased level of histamine, OVA-specific antibodies, suppressed the infiltration of immune cells in nasal tissues, inhibited the expression of IL-4, IL-6, IL-5, TNF-α, IL-13, IL-17, IL-2 while promoting the expression of IL-10, suppressed the expression of HMGB1, TLR2, and TLR4 in AR mice. BoxA ameliorated allergic rhinitis in mice by inhibiting HMGB1.

Circular RNA ZNF609 promotes laryngeal squamous cell carcinoma progression by upregulating epidermal growth factor receptor via sponging microRNA-134-5p.

Emerging evidence has revealed that aberrantly expressed circular RNAs (circRNAs) play vital roles in tumorigenesis and progression of diverse human malignancies. CircZNF609 was found to be involved in hepatocellular carcinoma, but the role and underlying mechanism of circZNF609 in laryngeal squamous cell carcinoma (LSCC) remain unclear. This study aimed to explore the molecular mechanism of circZNF609 in LSCC. qRT-qPCR was performed to detect the expression of circZNF609 and microRNA-134-5p (miR-134-5p) in LSCC. Colony formation assay, CCK-8 assay, BrdU incorporation assay, clone formation assay, transwell invasion assay and Western blot analysis were performed to evaluate LSCC cell proliferation, as well as the expression of proliferating cell nuclear antigen (PCNA) and MMP-2. Luciferase reporter assay, target gene prediction and screening were used to validate downstream target genes of circZNF609 and miR-134-5p. EGFR expression was detected by Western blot analysis and RT-qPCR. Nude mice were used to detect tumor changes. CircZNF609 was upregulated in LSCC and associated with poor survival of LSCC patients. Knockdown of circZNF609 inhibited LSCC proliferation, invasion and the expression of PCNA and matrix matalloproteinases-2 (MMP-2). CircZNF609 can regulate miR-134-5p to upregulate epidermal growth factor receptor (EGFR). In addition, knockdown of EGFR or overexpression of miR-134-5p could reverse the tumor-promoting effects of circZNF609 in LSCC. In LSCC tissues, circZNF609 was negatively correlated with miR-134-5p and positively correlated with EGFR. CircZNF609 promotes the progression of LSCC via the miR-134-5p/EGFR axis, which might be the therapeutic target of LSCC.

Intranasal budesonide for rhinitis during a high airborne pollution period: a randomized controlled trial.

BACKGROUND: Air pollution may induce or reinforce nasal inflammation regardless of allergy status. There is limited direct clinical evidence informing the treatment of airborne pollution-related rhinitis. OBJECTIVE: To assess the effectiveness of intranasal budesonide in adults with self-reported rhinitis symptoms triggered/worsened by airborne pollution. METHODS: Adults in northern China with self-reported rhinitis symptoms triggered or worsened by airborne pollution were randomized to budesonide 256 µg/day or placebo for 10 days in pollution season (October 2019 to February 2020). The primary endpoint was the mean change from baseline in 24-h reflective total nasal symptom score (rTNSS) averaged over 10 days. The secondary endpoints were subject-assessed Global Impression of Change (SGIC), mean change from baseline in individual nasal symptom severity, and mean change from baseline in individual non-nasal symptoms of cough and postnasal drip severity. One-sided P < 0.0125 was considered statistically significant. RESULTS: After an interruption by COVID-19, an interim analysis showed that the study could be ended for efficacy with n = 206 participants (103/group) since the primary efficacy endpoint demonstrated significant results. The final efficacy results showed that the 10-day-averaged rTNSS change in the budesonide group was greater than with placebo (- 2.20 vs - 1.72, P = 0.0107). Budesonide also significantly improved 10-day-averaged itching/sneezing change (- 0.75 vs - 0.51, P = 0.0009). Results for SGIC and all other individual symptoms did not show significant differences between the two groups. CONCLUSIONS: Intranasal budesonide 256 µg once daily improved the total nasal symptoms and itching/sneezing over 10 days in adults with rhinitis triggered/worsened by airborne pollution.

Factors associated with the quality of life for hospitalized patients with HPV-associated oropharyngeal squamous cell carcinoma.

PURPOSE: Oropharynx squamous cell cancer (OPSCC) is a type of head and neck squamous cell carcinoma. The raising OPSCC incidence is mainly attributed to human papillomavirus (HPV). HPV-related OPSCC has a relatively good prognosis, the concerns are focused on the improvement of quality-of-life (QOL). We aimed to figure out the factors which may affect the QOL of HPV-related OPSCC patients after treatment. METHODS: This study included patients with HPV-related OPSCC. The QOL of the patients were analyzed through the administration of European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (EORTC QLQ-C30)-Chinese version, the European Organization for Research and Treatment of Cancer Head and Neck Cancer Module-35 (EORTC QLQ-H&N-35)-Chinese version, and Eating Assessment Tool-10 (EAT-10). Multivariable regression analysis was employed to detect the influence of predictor variables on the QOL of patients. RESULTS: A total of 294 HPV-related OPSCC patients were involved in this research. The results of EORTC QLQ-C30, EORTC QLQ-H&N-35, and EAT-10 demonstrated that the treatment decreased the QOL of HPV-related OPSCC patients. Several different factors including marital status, consumption of tobacco and alcohol, tumor sites, clinical stages, therapeutic strategies, and neck dissection were proved to have influence on QOL of HPV-related OPSCC after treatment. CONCLUSION: Based on the analyzation of the QOL at baseline and after treatment, we demonstrated several factors which influenced the QOL of HPV-associated OPSCC patients after treatment. These results can make a great contribution to the improvement of the QOL after treatment.

Low-temperature radiofrequency coblation reduces treatment interval and post-operative pain of laryngotracheal recurrent respiratory papillomatosis.

Laryngeal papillomatosis is a benign disease in the larynx but with the potential to develop into significant complications as a result of its high recurrence rate. CO2 laser and radiofrequency controlled ablation (coblation) have been used to treat recurrent respiratory papillomatosis, but detailed comparisons of their respective treatment outcomes are not fully investigated. This retrospective study examines the procedure time, time interval between interventions, blood loss during operation, post-operative complications and pain scores among patients who received either CO2 laser or radiofrequency coblation interventions for laryngotracheal recurrent respiratory papillomatosis. Compared with CO2 laser intervention, radiofrequency coblation significantly reduced operation time, time interval between interventions, blood loss during operation and number of times bipolar electrocoagulation needed in each procedure. Post-operatively, pain scores after radiofrequency coblation were significantly lower than those after CO2 laser intervention. Incidence rates of post-operative complications, in terms of palate pharyngeal mucosa damage, bleeding and subcutaneous emphysema, were also significantly reduced after radiofrequency coblation. Low-temperature radiofrequency coblation is a superior intervention compared with CO2 laser against laryngotracheal recurrent respiratory papillomatosis.

MicroRNA-892a regulates laryngocarcinoma cell proliferation via Dicer.

IMPACT STATEMENT: This work expanded the knowledge of the molecular mechanisms underlying LC progression by exploring the role of miR-892a in the viability of TU212 and M4E cells. The results showed that miR-892a, which exhibited elevated expression in LC cells and tissue specimens of patients with LC, exerted an inhibitory effect on Dicer expression, whereas silencing of miR-892a in TU212 and M4E cells hindered cell proliferation and growth and promoted apoptosis. Furthermore, miR-892a was demonstrated to directly target Dicer 3'-UTR and inhibit its expression. These findings demonstrated that miR-892a acted as an LC oncogene via its action on Dicer, which further confirmed that miR-892a can serve as a diagnostic indicator or promising agent for LC treatment.

Long Noncoding RNA Linc00632 Inhibits Interleukin-13-Induced Inflammatory Cytokine and Mucus Production in Nasal Epithelial Cells.

Allergic rhinitis (AR) is an allergic disease characterized as (immunoglobulin E)-mediated type I hypersensitivity disorder. The interleukin-13 (IL-13) signaling pathway has been implicated in the pathogenesis of AR. In the present study, we investigated the regulatory role and mechanism of long noncoding RNA Linc00632 in IL-13-induced inflammatory cytokine and mucus production in nasal epithelial cells (NECs) from AR patients. We evaluated the expression of Linc00632 in nasal tissues from AR patients and in IL-13-treated NECs. We explored the role of Linc00632 in granulocyte-macrophage colony-stimulating factor (GM-CSF), eotaxin, and MUAC5AC production in IL-13-treated NECs. We searched for the potential target of Linc00632. Downregulation of Linc00632 was identified in nasal tissues of AR patients and in IL-13-treated NECs. Linc00632 inhibited IL-13-induced GM-CSF, eotaxin, and MUAC5AC production. Linc00632 targeted miR-498 and negatively regulated its expression. MiR-498 targeted IL1RN and inhibition of miR-498 suppressed IL-13-induced GM-CSF, eotaxin, and MUC5AC expression. The regulation of IL-13-induced dysfunction of NECs by Linc00632 depended on miR-498. Linc00632 inhibited IL-13-induced GM-CSF, eotaxin, and MUAC5AC production in IL-13-treated NECs by targeting miR-498.

Effects of GPR81 silencing combined with cisplatin stimulation on biological function in hypopharyngeal squamous cell carcinoma.

Hypopharyngeal squamous cell carcinoma (HSCC) is a malignant tumor found in the head and neck region. Lactate receptor 1, also known as G protein­coupled receptor81 (GPR81), has been reported to play a vital role in cancer growth and metabolism. However, the function of GPR81 in HSCC remains largely unknown. The present study investigated the effect of GPR81 on cell survival and GPR81­mediated energy metabolism under cisplatin treatment in HSCC. GPR81 knockdown reduced the proliferation and invasion of the human HSCC cell line FaDu. Furthermore, GPR81 silencing combined with cisplatin treatment increased the expression of translocase of outer mitochondrial membrane 20 at the mRNA and protein levels (P<0.05). mRNA and protein expression of phosphofructokinase 1 in mRNA appeared to be downregulated in GPR81 knockdown FaDu cells treated with cisplatin, although this was not statistically significant. GPR81 silencing and cisplatin challenge showed no significant upregulation compared with the control, but significant downregulation in mRNA and protein levels compared with the shRNA­scramble group. Apoptosis was measured by flow cytometry with annexin V and 7­aminoactinomycin D. GPR81 silencing and cisplatin led to an increased apoptotic rate. Moreover, absence of GPR81 combined with cisplatin exposure increased caspase­3 expression and decreased Bcl­2 levels. The results of the present study suggested that GPR81 and cisplatin sensitivity played an important role in HSCC growth and metabolism.

Prognostic Value of Programmed Cell Death Ligand-1 Expression in Nasopharyngeal Carcinoma: A Meta-Analysis of 1,315 Patients.

Background: The prognostic value of programmed cell death ligand-1 (PD-L1) in patients with nasopharyngeal carcinoma (NPC) remains controversial. Therefore, we conducted this meta-analysis to understand the role of PD-L1 in NPC. Method: We searched PubMed, Embase, Web of Science, and Cochrane Library up to April 2019. We determined the pooled hazard ratio (HR) and 95% confidence intervals (CIs) to assess the relationship between PD-L1 and various survival outcomes. Begg's funnel plot was used to assess any publication bias. Results: Eleven studies involving 1,315 patients were included in this meta-analysis. For overall survival (OS), the HR was 1.48 and 95% CI was 1.00-2.18 (p = 0.049). For disease-free survival (DFS), the HR was 1.51 and 95% CI was 0.85-2.69 (p = 0.162). For distant metastasis-free survival (DMFS), the HR was 1.75 and 95% CI was 0.64-4.79 (p = 0.277). For local recurrence-free survival (LRFS), the HR was 0.67 and 95% CI was 0.06-8.16 (p = 0.756). The results of prognosis of PD-L1 and OS were more significant after sensitivity analysis. The pooled odds ratio indicated that PD-L1 expression was not associated with T stage, N stage, M stage, overall stage, sex, age, smoking, or alcohol intake. No publication bias was found. Conclusion: Our meta-analysis showed that PD-L1 overexpression in NPC was associated with a poor OS and may be useful as a novel prognostic factor for NPC.

Tauroursodeoxycholic acid attenuates gentamicin-induced cochlear hair cell death in vitro.

Gentamycin is one of the most clinically used aminoglycoside antibiotics which induce intrinsic apoptosis of hair cells. Tauroursodeoxycholic acid (TUDCA) is known as safe cell-protective agent in disorders associated with apoptosis. We aimed to investigate the protective effects of TUDCA against gentamicin-induced ototoxicity. House Ear Institute-Organ of Corti 1(HEI-OC1) cells and explanted cochlear tissue were treated with gentamicin and TUDCA, followed by serial analyses including cell viability assay, hair cell staining, qPCR, ELISA and western blotting to determine the cell damage by the parameters relevant to cell apoptosis and endoplasmic reticulum stress. TUDCA significantly attenuated gentamicin-induced cell damage in cultured HEI-OC1 cells and explanted cochlear hair cells. TUDCA alleviated gentamicin-induced cell apoptosis, supported by the decreased Bax/Bcl2 ratio compared with that of gentamicin treated alone. TUDCA decreased gentamicin-induced nitric oxide production and protein nitration in both models. In addition, TUDCA suppressed gentamicin-induced endoplasmic reticulum stress as reflected by inversing the expression levels of Binding immunoglobulin protein (Bip), CCAAT/-enhancer-binding protein homologous protein (CHOP) and Caspase 3. TUDCA attenuated gentamicin-induced hair cell death by inhibiting protein nitration activation and ER stress, providing new insights into the new potential therapies for sensorineural deafness.