Δευτέρα 3 Ιανουαρίου 2022

lncRNA HOTAIR mediates OGD/R-induced cell injury and angiogenesis in a EZH2-dependent manner

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Exp Ther Med. 2022 Jan;23(1):99. doi: 10.3892/etm.2021.11022. Epub 2021 Dec 1.

ABSTRACT

Long non-coding RNAs (lncRNA) serve an important role in neonatal hypoxic-ischemic encephalopathy (HIE) have been reported to regulate the activity of HIE-associated proteins. The present study aimed to elucidate the role of Hox transcript antisense intergenic RNA (HOTAIR) in oxygen-glucose deprivation/reperfusion (OGD/R)-induced injury in human brain microvascular endothelial cells (hBMVECs). The levels of HOTAIR were evaluated in the serum of neonatal patients with HIE, and the effects of HOTAIR were evaluated using in vitro assays, such as reverse transcription-quantitative PCR to detect lncRNA and mRNA levels and western blot analysis to determine protein levels. Moreover, RNA immunoprecipitation assays were used to evaluate the association between HOTAIR and enhancer of zeste homolog 2 (EZH2), Cell Counting Kit-8 was used to detect cell viability, an endothelial monolayer cell permeability assay was used to analyze cell viability, TUNEL staining was used to detect the levels of apoptosis, a Transwell assay was used to evaluate cell invasion and a tube formation assay was used to analyze tube formation ability. In addition, the effects of HOTAIR and EZH2 on cell apoptosis and the invasive and tube formation abilities of hBMVECs were investigated using TUNEL, Transwell and tube formation assays, respectively. The results showed that the expression levels of HOTAIR were markedly increased both in neonatal HIE patients and in the OGD/R injury in vitro model. HOTAIR knockdown reduced hBMVEC viability, enhanced cell permeability and apoptosis, in addition to decreasing the expression levels of tight junction-related proteins, such as zonula occludens-1, occluden, Claudin5 and vascular endothelial-cadherin. However, EZH2 overexpression reversed the effects of HOTAIR silencing on hBMVECs. Additionally, HOTAIR knockd own enhanced the migratory and tube formation abilities of OGD/R-induced hBMVECs, which were also reversed by EZH2 overexpression. Overall, the present study revealed an association between the HOTAIR/EZH2 axis and brain microvascular endothelial cell injury and angiogenesis, which provides a novel insight into the molecular mechanism underlying stroke or the development of new pharmacotherapies.

PMID:34976141 | PMC:PMC8674968 | DOI:10.3892/etm.2021.11022

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Screening for Eustachian Tube Dysfunction in Clinical Practice Using the Eustachian Tube Dysfunction Questionnaire‐7

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https://entsurrey.com/Download/Questionaires/Eustachian_Tube_Dysfunction_(ETDQ_7).pdf

Objectives/Hypothesis

To evaluate the ability of the Eustachian Tube Dysfunction Questionnaire-7 (ETDQ-7) to discriminate between patients with Eustachian tube dysfunction (ETD) and Non-ETD diagnoses, and identify symptom information to improve ability to discriminate these groups.

Study Design

Cohort study.

Methods

Pilot retrospective study with consecutive adult patients presenting to otology clinics and one general otolaryngology clinic in an academic health system. Patients were administered ETDQ-7 with eight additional symptom items. Electronic health records were reviewed for demographic and diagnostic information. Patients were grouped into diagnosis categories: 1) True ETD, 2) experiencing ear fullness (EF) not due to ETD, and 3) Control patients without ETD-related disorders or EF. ETDQ-7 and symptom item scores were compared by the diagnosis group. Receiver-operative characteristics curves and area under the curve (AUC) were generated for each ETD diagnosis group based on ETDQ-7 and symptom scores.

Results

Of the 108 patients included in this study 74 (68.5%) were diagnosed with ETD. Patients with ETD had higher (indicating worse symptom burden) overall ETDQ-7 scores than Control group (Median [Q1, Q3] 3.0, [1.7, 4.1]; versus 1.5 [1.0, 3.4] P = .008). There was no statistically significant difference between overall ETDQ-7 scores for ETD and Non-ETD EF patients (P = .389). The AUC for the ETDQ-7 in discriminating ETD from other conditions that cause EF was 0.569; the addition of 8 symptom questions to the ETDQ-7 improved AUC to 0.801.

Conclusion

Additional patient-reported symptom information may improve the ability to discriminate ETD from other similarly presenting diagnoses when using ETDQ-7.

Level of Evidence

3 Laryngoscope, 2022

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A clinical analysis of oropharyngeal squamous cell carcinoma: a single-institution's experience

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Eur Arch Otorhinolaryngol. 2022 Jan 3. doi: 10.1007/s00405-021-07236-z. Online ahead of print.

ABSTRACT

PURPOSE: We herein report the treatment outcome of oropharyngeal squamous cell carcinoma (OPSCC) at Kyushu University Hospital, the total number of OPSCC cases, and changes in the proportion of human papilloma virus (HPV)-related carcinomas over time.

METHOD: We performed a retrospective analysis of 237 cases treated for OPSCC at Kyushu University Hospital between 2013 and 2019. We performed HPV-mRNA in situ hybridization and p16 immunohistochemistry.

RESULT: This study included 197 males (82.1%) and 40 females (17.9%). The disease-specific, progression-free and overall survival (OS) were 69%, 62% and 61%, respectively, over the decade-long study period. p16-Immunohistochemistory and highrisk HPV mRNA in situ hybridization were positive in 114 (48.1%) and 105 (44.3%) cases, respectively. The number of HPV-related OPSCC ca ses increased according to an annual analysis. HPV+ cases had a significantly better prognosis than HPV- cases. In addition, p16+/HPV- cases had a significantly worse prognosis than p16+/HPV+ cases (OS: p = 0.0484). HPV+ OPSCC cases were associated with a younger age (< 60 years old) (p = 0.0429), non-smoker (p = 0.0001), lateral tumor site (< 0.00001), lymphoid metastasis (< 0.0001) and low clinical stage (< 0.0001).

CONCLUSION: The frequency of HPV-related OPSCC cases is increasing in Japan as well as worldwide, and such cases are characterized by no smoking habit, a young age, and a good prognosis. Even in p16+ OPSCC, HPV- cases had a poor prognosis, suggesting the importance of accurate HPV determination. To determine the intensity of treatment for HPV-related and non-related OPSCC, it is necessary to accumulate cases for the accurate HPV determination and compari son of treatment effects.

PMID:34978590 | DOI:10.1007/s00405-021-07236-z

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