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Objective: To analyze the etiology, diagnosis, and treatment of unexplained conductive hearing loss (UCHL) with intact tympanic membrane. Methods: A systematic review was conducted based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A total of 642 articles were retrieved from databases such as PubMed, Embase, Web of Science, and Cochrane. Fifty-four research articles and 21 case reports were screened out according to the inclusion and exclusion criteria for analysis of the etiology of UCHL. Seven research articles with UCHL who underwent exploratory tympanotomy were selected for data extraction and analysis of clinical characteristics. Results: UCHL is a common manifestation of various diseases, including congenital ossicular anomalies (COA), otosclerosis (OTS), congenital middle ear cholesteatoma (CMEC), oval window atresia, superior semicircular-canal dehiscence, congenital stapedial footplate fixation, middle ear osteoma or adenoma, congenital ossification of stapedial tendon, and so on. A total of 522 patients were included in the 7 articles; among whom OTS showed a tendency to increase with age. The main symptoms were hearing loss, followed by tinnitus, dizziness, ear fullness, ear pain, facial paralysis. A total of 87.5% to 93.0% patients with COA manifested as nonprogressive deafness that occurred since childhood, with tinnitus incidence of 15.6% to 30.2%, and 86.4% to 96.4% patients with OTS presented with progressive hearing loss, with tinnitus incidence of 60.1% to 90.9%. The diagnosis positive rate of high-resolution computed tomography (HRCT) was 33.8% to 87.1%, and CMEC was higher than that of COA (83.3%-100% vs 28.6%-64%). All the articles reported good hearing recovery. The most common surgical complications included taste abnormalities, tinnitus, and dizziness. Conclusion: UCHL presents with similar clinical manifestations and poses challenges in preoperative diagnosis. Exploratory tympanotomy is the primary method for diagnosis and treatment, with good prognosis after removing the lesion and reconstructing hearing during the operation. Children can also safely undergo the surgery.
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Eustachian tube dysfunction (ETD) is a condition where the Eustachian tube (ET) fails to function normally, resulting in symptoms such as aural fullness, tinnitus, autophony, and hearing loss. ETD can further lead to middle ear diseases such as otitis media effusion and adhesive otitis media, which is becoming more common in the field of otology. Although the pathogenesis of ETD remains unclear, recent animal studies and clinical experiments have found allergic reactions and allergic diseases are closely related to the occurrence of ETD. As the mucosa of the ET is continuous with that of the nasopharynx and tympanic cavity, it is reasonable to assume that the immunological basis of the ET itself is similar to that of respiratory allergic diseases. However, due to the special anatomical location and complex pathogenesis of the ET, there is still no unified diagnostic gold standard. Additionally, there is an ongoing debate regarding whether ETD can be classified as a distinct disease or even an allergic disease. Furthermore, the effectiveness of anti-allergic therapy in patients with ETD is yet to be fully understood. Therefore, this review elaborates on the possible mechanisms of allergic reactions in the occurrence and development of ETD, and explores the potential role of anti-allergic therapy in managing this condition, in order to provide new insights into the pathogenesis and prevention of ETD.
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N6-methyl adenosine (m6A) modification is known to play a crucial role in various aging-related diseases. However, its involvement in presbycusis, a type of age-related hearing loss, is not yet clear. We examined the changes in oxidative stress levels in both plasma of presbycusis patients and mice. To determine the expression of m6A and its functional enzymes, we used liquid chromatography tandem-mass spectrometry (LC-MS/MS), enzyme-linked immunosorbent assay (ELISA), and RT-PCR to analyze the total RNA of presbycusis patients blood cells (n = 8). Additionally, we detected the expression of m6A functional enzymes in the cochlea of presbycusis mice using immunohistochemistry. We assessed the effects of m6A methyltransferase METTL3 on SIRT1 protein expression, reactive oxygen species (ROS) levels, and apoptosis in an oxidative stress model of organ of Corti 1 (OC1) cells. To observe the effect on SIRT1 protein expression, we interfered with the m6A recognition protein IGF2BP3 using siRNA. In both presbycusis patients and mice, there was an increased level of oxidative stress in plasma.There was a decrease in the expression of m6A, METTL3, and IGF2BP3 in presbycusis patients blood cells. The expression of METTL3 and IGF2BP3 was also reduced in the cochlea of presbycusis mice. In OC1 cells, METTL3 positively regulated SIRT1 protein levels, while reversely regulated the level of ROS and apoptosis. IGF2BP3 was found to be involved in the regulation of SIRT1 protein expression. In addition, METTL3 may play a protective role in oxidative stress-induced injury of OC1 cells, while both METTL3 and IGF2BP3 cooperatively regulate the level of m6A and the fate of SIRT1 mRNA in OC1 cells.
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Presbiacusia , Sirtuína 1 , Animais , Camundongos , Adenosina/metabolismo , Apoptose , Cromatografia Líquida , Metiltransferases/genética , Metiltransferases/metabolismo , Estresse Oxidativo , Espécies Reativas de Oxigênio , RNA Mensageiro/metabolismo , Sirtuína 1/metabolismo , Espectrometria de Massas em Tandem , HumanosRESUMO
Animal experiments play an important role in the study of the pathogenesis of human diseases and new methods of diagnosis and treatment. Due to the great differences in the anatomical structure and physiology of the upper airway between animals and humans, there is currently no animal model that can fully simulate the pathological anatomy and pathophysiological characteristics of human obstructive sleep apnea (OSA) patients. Herein, we summarizes the construction methods of several OSA animal models that have been widely used in the studies published in the last 5 years, the advantages and limitations of each model as well as related evaluation techniques are described. This information has potential to provide further guide for the development of OSA related animal experiments.
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Cisplatin is highly effective for killing tumor cells. However, as one of its side effects, ototoxicity limits the clinical application of cisplatin. The mechanisms of cisplatin-induced ototoxicity have not been fully clarified yet. SIRT3 is a deacetylated protein mainly located in mitochondria, which regulates a variety of physiological processes in cells. The role of SIRT3 in cisplatin-induced hair cell injury has not been founded. In this study, primary cultured cochlear explants exposed to 5 µM cisplatin, as well as OC-1 cells exposed to 10 µM cisplatin, were used to establish models of cisplatin-induced ototoxicity in vitro. We found that when combined with cisplatin, metformin (75 µM) significantly up-regulated the expression of SIRT3 and alleviated cisplatin-induced apoptosis of hair cells. We regulated the expression of SIRT3 to explore the role of SIRT3 in cisplatin-induced auditory hair cell injury. Overexpression of SIRT3 promoted the survival of auditory hair cells and alleviated the apoptosis of auditory hair cells. In contrast, knockdown of SIRT3 impaired the protective effect of metformin and exacerbated cisplatin injury. In addition, we found that the protective effect of SIRT3 may be achieved by regulating GLUT4 translocation and rescuing impaired glucose uptake caused by cisplatin. Our study confirmed that upregulation of SIRT3 may antagonize cisplatin-induced ototoxicity, and provided a new perspective for the study of cisplatin-induced ototoxicity.
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Antineoplásicos , Metformina , Ototoxicidade , Sirtuína 3 , Humanos , Cisplatino/toxicidade , Antineoplásicos/toxicidade , Sirtuína 3/genética , Ototoxicidade/etiologia , Ototoxicidade/prevenção & controle , Metformina/farmacologia , ApoptoseRESUMO
Cisplatin is a widely used chemotherapeutic agent. However, its clinical application remains limited due to the high incidence of severe ototoxicity. It has been reported that the unfolded protein response (UPR) is involved in cisplatin-induced ototoxicity. However, the specific mechanism underlying its effect remains unclear. Therefore, the present study aimed to explore the sequential changes in the key UPR signaling branch and its potential pro-apoptotic role in cisplatin-induced ototoxicity. The hair cell-like OC-1 cells were treated with cisplatin for different periods and then the expression levels of the UPR- and apoptosis-related proteins were determined. The results showed that the apoptotic rate of cells was gradually increased with prolonged cisplatin treatment. Furthermore, the sequential changes in three UPR signaling branches were evaluated. The expression levels of activating transcription factor 4 (ATF4) and C/EBP homologous protein (CHOP) were gradually increased with up to 12 h of cisplatin treatment. The aforementioned expression profile was consistent with that observed for the apoptosis-related proteins. Subsequently, the proportion of apoptotic cells was notably decreased in CHOP-silenced hair cell-like OC-1 cells following treatment with cisplatin. Moreover, we found significant hair cells loss and a higher level of CHOP in cisplatin-treated cochlear explants in a time-dependent manner. Overall, the present study demonstrated that the protein kinase RNAlike endoplasmic reticulum kinase (PERK)/ATF4/CHOP signaling branch could play an important role in cisplatin-induced cell apoptosis. Furthermore, the current study suggested that CHOP may be considered as a promising therapeutic target for cisplatin-induced ototoxicity.
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Cisplatino , Ototoxicidade , Humanos , Cisplatino/toxicidade , Fator 4 Ativador da Transcrição/genética , Fator 4 Ativador da Transcrição/metabolismo , Fator 4 Ativador da Transcrição/farmacologia , Estresse do Retículo Endoplasmático/fisiologia , RNA/metabolismo , RNA/farmacologia , Ototoxicidade/metabolismo , Resposta a Proteínas não Dobradas , Retículo Endoplasmático/metabolismoRESUMO
The fatty acid metabolism (FAM) is known to impact tumorigenesis, tumor progression and treatment resistance via enhancing lipid synthesis, storage and catabolism. However, the role of FAM in head and neck squamous cell carcinoma (HNSCC) has remained elusive. In the present study, we obtained a total of 69 differentially expressed FAM-related genes between 502 HNSCC samples and 44 normal samples from The Cancer Genome Atlas (TCGA) database. The HNSCC samples were divided into 2 clusters according to 69 differentially expressed genes (DEGs) via cluster analysis. Then DEGs in the two clusters were found, and 137 prognostic DEGs were identified by univariate analysis. Subsequently, combined with the clinical information of 546 HNSCC patients from TCGA database, a 12-gene prognostic risk model was established (FEPHX3, SPINK7, FCRLA, MASP1, ZNF541, CD5, BEST2 and ZAP70 were down-regulation, ADPRHL1, DYNC1I1, KCNG1 and LINC00460 were up-regulation) using multivariate Cox regression and LASSO regression analysis. The risk scores of 546 HNSCC samples were calculated. According to the median risk score, 546 HNSCC patients were divided into the high- and low-risk (high- and low score) groups. The Kaplan-Meier survival analysis showed that the survival time of HNSCC patients was significantly shorter in the high-risk group than that in the low-risk group (p < 0.001). The same conclusion was obtained in the Gene Expression Omnibus (GEO) dataset. After that, the multivariate Cox regression analysis indicated that the risk score was an independent factor for patients with HNSCC in the TCGA cohort. In addition, single-sample gene set enrichment analysis (ssGSEA) indicated that the level of infiltrating immune cells was relatively low in the high-risk group compared with the low-risk group. In summary, FAM-related gene expression-based risk signature could predict the prognosis of HNSCC independently.
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With the COVID-19 pandemic, the usage of personal protective equipment (PPE) has become 'the new normal'. Both surgical masks and N95 masks with a face shield are widely used in healthcare settings to reduce virus transmission, but the use of these masks has a negative impact on speech perception. Therefore, transparent masks are recommended to solve this dilemma. However, there is a lack of quantitative studies regarding the effect of PPE on speech perception. This study aims to compare the effect on speech perception of different types of PPE (surgical masks, N95 masks with face shield and transparent masks) in healthcare settings, for listeners with normal hearing in the audiovisual or auditory-only modality. The Bamford-Kowal-Bench (BKB)-like Mandarin speech stimuli were digitally recorded by a G.R.A.S KEMAR manikin without and with masks (surgical masks, N95 masks with face shield and transparent masks). Two variants of video display were created (with or without visual cues) and tagged to the corresponding audio recordings. The speech recording and video were presented to listeners simultaneously in each of four conditions: unattenuated speech with visual cues (no mask); surgical mask attenuated speech without visual cues; N95 mask with face shield attenuated speech without visual cues; and transparent mask attenuated speech with visual cues. The signal-to-noise ratio for 50 % correct scores (SNR50) threshold in noise was measured for each condition in the presence of four-talker babble. Twenty-four subjects completed the experiment. Acoustic spectra obtained from all types of masks were primarily attenuated at high frequencies, beyond 3 kHz, but to different extents. The mean SNR50 thresholds of the two auditory-only conditions (surgical mask and N95 mask with face shield) were higher than those of the audiovisual conditions (no mask and transparent mask). SNR50 thresholds in the surgical-mask conditions were significantly lower than those for the N95 masks with face shield. No significant difference was observed between the two audiovisual conditions. The results confirm that wearing a surgical mask or an N95 mask with face shield has a negative impact on speech perception. However, wearing a transparent mask improved speech perception to a similar level as unmasked condition for young normal-hearing listeners.
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Better understanding the mechanism of cisplatin-induced ototoxicity is of great significance for clinical prevention and treatment of cisplatin-related hearing loss. However, the mechanism of cisplatin-induced inflammatory response in cochlear stria vascularis and the mechanism of marginal cell (MC) damage have not been fully clarified. In this study, a stable model of cisplatin-induced MC damage was established in vitro, and the results of PCR and Western blotting showed increased expressions of NLRP3, Caspase-1, IL-1ß, and GSDMD in MCs. Incomplete cell membranes including many small pores appearing on the membrane were also observed under transmission electron microscopy and scanning electron microscopy. In addition, downregulation of NLRP3 by small interfering RNA can alleviate cisplatin-induced MC pyroptosis, and reducing the expression level of TXNIP possesses the inhibition effect on NLRP3 inflammasome activation and its mediated pyroptosis. Taken together, our results suggest that NLRP3 inflammasome activation may mediate cisplatin-induced MC pyroptosis in cochlear stria vascularis, and TXNIP is a possible upstream regulator, which may be a promising therapeutic target for alleviating cisplatin-induced hearing loss.
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Proteína 3 que Contém Domínio de Pirina da Família NLR , Piroptose , Caspase 1/metabolismo , Cisplatino/efeitos adversos , Inflamassomos/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismoRESUMO
Purpose: This study aimed to construct a prognostic signature consisting of immune-related RNA-binding proteins (RBPs) to predict the prognosis of patients with head and neck squamous cell carcinoma (HNSCC) effectively. Methods: The transcriptome and clinical data of HNSCC were downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. First, we ascertained the immunological differences in HNSCC, through single-sample gene set enrichment analysis, stromal and immune cells in malignant tumor tissues using expression data (ESTIMATE), and cell-type identification by estimating relative subsets of RNA transcripts (CIBERSORT) deconvolution algorithm. Then we used univariate proportional hazards (Cox) regression analysis and least absolute shrinkage and selection operator (LASSO) Cox regression analysis to screen immune-related RBPs and acquire the risk score of each sample. Subsequently, we further investigated the difference in prognosis, immune status, and tumor mutation burden in high- and low-risk groups. Finally, the efficacy of immunotherapy was measured by the tumor immune dysfunction and exclusion (TIDE) score. Results: We derived 15 immune-related RBPs, including FRMD4A, ASNS, RAB11FIP1, FAM120C, CFLAR, CTTN, PLEKHO1, SELENBP1, CHCHD2, NPM3, ATP2A3, CFDP1, IGF2BP2, NQO1, and DENND2D. There were significant differences in the prognoses of patients in the high- and low-risk groups in the training set (p < 0.001) and the validation set (p < 0.01). Furthermore, there were statistical differences between the high-risk group and low-risk group in immune cell infiltration and pathway and tumor mutation load (p < 0.001). In the end, we found that patients in the low-risk group were more sensitive to immunotherapy (p < 0.001), and then we screened 14 small-molecule chemotherapeutics with higher sensitivity to the high-risk group (p < 0.001). Conclusion: The study constructed a prognostic signature of HNSCC, which might guide clinical immunotherapy in the future.
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Sensorineural hearing loss is a common sensory impairment in humans caused by abnormalities in the inner ear. The stria vascularis is regarded as a major cochlear structure that can independently degenerate and influence the degree of hearing loss. This review summarizes the current literature on the role of the stria vascularis in the pathogenesis of sensorineural hearing loss resulting from different etiologies, focusing on both molecular events and signaling pathways, and further attempts to explore the underlying mechanisms at the cellular and molecular biological levels. In addition, the deficiencies and limitations of this field are discussed. With the rapid progress in scientific technology, new opportunities are arising to fully understand the role of the stria vascularis in the pathogenesis of sensorineural hearing loss, which, in the future, will hopefully lead to the prevention, early diagnosis, and improved treatment of sensorineural hearing loss.
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Laryngeal squamous cell carcinoma (LSCC) is the main type of laryngeal cancer with poor prognosis. Incidence of LSCC increases every year, posing a great threat to human health. The underlying mechanism needs further study. Neutrophils are the most prevalent type of immune cells, which play vital roles in crosstalk between the microenvironment and cancer cells. In our study, we aim to figure out the complex regulation between neutrophils and LSCC. Our experiments showed that LSCC cells could promote the activation and mobility of neutrophils. And, in return, neutrophils enhanced the proliferation, migration, and invasion of LSCC. The subsequent results showed that IL-17 was highly expressed in neutrophil conditioned medium. Block of IL-17 could effectively inhibit the progression of LSCC induced by neutrophils. What is more, the results showed that IL-17 activated the JAK/STAT3 pathway in LSCC. Inhibition of the JAK/STAT3 pathway could significantly block neutrophil-induced LSCC progression. Our research reveals the complex interaction between neutrophils and LSCC cells, providing new ideas for the treatment of LSCC.
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Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Interleucina-17/metabolismo , Janus Quinases/metabolismo , Neoplasias Laríngeas/metabolismo , Neoplasias Laríngeas/patologia , Neutrófilos/metabolismo , Fator de Transcrição STAT3/metabolismo , Carcinoma de Células Escamosas/etiologia , Linhagem Celular Tumoral , Movimento Celular/genética , Movimento Celular/imunologia , Citocinas/metabolismo , Humanos , Neoplasias Laríngeas/etiologia , Ativação de Neutrófilo/genética , Ativação de Neutrófilo/imunologia , Neutrófilos/imunologia , Transdução de Sinais , Microambiente TumoralRESUMO
Background: N6-methyladenosine (m6A), 5-methylcytosine (m5C) and N1-methyladenosine (m1A) are the main RNA methylation modifications involved in the progression of cancer. However, it is still unclear whether m6A/m5C/m1A-related long non-coding RNAs (lncRNAs) affect the prognosis of head and neck squamous cell carcinoma (HNSCC). Methods: We summarized 52 m6A/m5C/m1A-related genes, downloaded 44 normal samples and 501 HNSCC tumor samples with RNA-seq data and clinical information from The Cancer Genome Atlas (TCGA) database, and then searched for m6A/m5C/m1A-related genes co-expressed lncRNAs. We adopt the least absolute shrinkage and selection operator (LASSO) Cox regression to obtain m6A/m5C/m1A-related lncRNAs to construct a prognostic signature of HNSCC. Results: This prognostic signature is based on six m6A/m5C/m1A-related lncRNAs (AL035587.1, AC009121.3, AF131215.5, FMR1-IT1, AC106820.5, PTOV1-AS2). It was found that the high-risk subgroup has worse overall survival (OS) than the low-risk subgroup. Moreover, the results showed that most immune checkpoint genes were significantly different between the two risk groups (p < 0.05). Immunity microenvironment analysis showed that the contents of NK cell resting, macrophages M2, and neutrophils in samples of low-risk group were significantly lower than those of high-risk group (p < 0.05), while the contents of B cells navie, plasma cells, and T cells regulatory (Tregs) were on the contrary (p < 0.05). In addition, patients with high tumor mutational burden (TMB) had the worse overall survival than those with low tumor mutational burden. Conclusion: Our study elucidated how m6A/m5C/m1A-related lncRNAs are related to the prognosis, immune microenvironment, and TMB of HNSCC. In the future, these m6A/m5C/m1A-related lncRNAs may become a new choice for immunotherapy of HNSCC.
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PURPOSE: To construct a prognostic signature composed of DNA repair genes to effectively predict the prognosis of patients with head and neck squamous cell carcinoma (HNSCC). METHODS: After downloading the transcriptome and clinical data of HNSCC from the Cancer Genome Atlas (TCGA), 499 patients with HNSCC were equally divided into training and testing sets. In the training set, 13 DNA repair genes were screened using univariate proportional hazard (Cox) regression analysis and least absolute shrinkage and selection operator (LASSO) Cox regression analysis to construct a risk model, which was validated in the testing set. RESULTS: In the training and testing sets, there were significant differences in the clinical outcomes of patients in the high- and low-risk groups showed by Kaplan-Meier survival curves (P < 0.001). Univariate and multivariate Cox regression analyses showed that the risk score had independent prognostic predictive ability (P < 0.001). At the same time, the immune cell infiltration, immune score, immune-related gene expression, and tumor mutation burden (TMB) of patients with HNSCC were also different between the high- and low-risk groups (P < 0.05). Finally, we screened several chemotherapeutics for HNSCC, which showed significant differences in drug sensitivity between the high- and low-risk groups (P < 0.05). CONCLUSION: This study constructed a 13-DNA-repair-gene signature for the prognosis of HNSCC, which could accurately and independently predict the clinical outcome of the patient. We then revealed the immune landscape, TMB, and sensitivity to chemotherapy drugs in different risk groups, which might be used to guide clinical treatment decisions.
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Cisplatin-induced ototoxicity is one of the important reasons that limit the drug's clinical application, and its mechanism has not been fully elucidated so far. The aim of this study was to explore the attenuate effect of tauroursodeoxycholic acid (TUDCA), a proteostasis promoter, on cisplatin-induced ototoxicity in vivo and in vitro, and to explore its possible mechanism. Auditory brainstem response (ABR) was measured to identify the attenuate effects of TUDCA administered subcutaneously [500 mg/kg/d × 3d, cisplatin: 4.6 mg/kg/d × 3d, intraperitoneal injection (i.p.)] or trans-tympanically (0.5 mg/mL, cisplatin: 12 mg/kg, i.p. with a pump) in Sprague-Dawley (SD) rats subjected to cisplatin-induced hearing loss. The cochlear explants of neonatal rats and OC1 auditory hair cell-like cell lines cultured in vitro were used to observe the number of apoptotic cells and the endoplasmic reticulum (ER) stress in the control, cisplatin (5 µM for 48 h for cochlear explants, 10 µM for 24 h for OC1 cells), and cisplatin + TUDCA (1 mM for 24 h for cochlear explants, 1.6 mM for 24 h for OC1 cells) groups. Differences in the expression of key proteins in the ER protein quality control (ERQC) system were detected. The changes in the attenuate effect of TUDCA on cisplatin-induced ototoxicity after down-regulating calreticulin (CRT), UDP-glucose ceramide glucosyltransferase-like 1 (UGGT1), and OS9 ER lectin (OS9) were also measured. The effect of TUDCA (10 mM) on stabilizing unfolded or misfolded proteins (UFP/MFP) was analyzed in a cell-free 0.2 % bovine serum albumin (BSA) aggregation system in vitro. Both the subcutaneous and trans-tympanic TUDCA administration alleviated cisplatin-induced increase in ABR thresholds in rats. TUDCA was able to reduce cisplatin-induced apoptosis and alleviate ER stress in cochlear explants and OC1 cells. Under the cisplatin treatment, the expression levels of CRT, UGGT1, and OS9 in the auditory hair cell increased, and the expression of total ubiquitinated proteins decreased. TUDCA attenuated the effect of cisplatin on UGGT1 and OS9, and recovered the protein ubiquitination levels. After down-regulating CRT, UGGT1, or OS9, the protective effect of TUDCA decreased. In the cell-free experimental system, TUDCA inhibited the aggregation of denatured BSA molecules. In summary, TUDCA can attenuate cisplatin-induced ototoxicity, possibly by inhibiting the accumulation and aggregation of UFP/MFP and the associated ER stress.
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Cisplatino/toxicidade , Retículo Endoplasmático/efeitos dos fármacos , Ototoxicidade/prevenção & controle , Agregados Proteicos/efeitos dos fármacos , Dobramento de Proteína/efeitos dos fármacos , Ácido Tauroquenodesoxicólico/uso terapêutico , Animais , Antineoplásicos/toxicidade , Linhagem Celular Transformada , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/fisiologia , Relação Dose-Resposta a Droga , Retículo Endoplasmático/patologia , Células Ciliadas Auditivas/efeitos dos fármacos , Células Ciliadas Auditivas/patologia , Masculino , Ototoxicidade/patologia , Agregados Proteicos/fisiologia , Ratos , Ratos Sprague-Dawley , Ácido Tauroquenodesoxicólico/farmacologiaRESUMO
BACKGROUND: Studies have shown that Helicobacter pylori (H. pylori) infection may be associated with the occurrence of otitis media with effusion (OME) in children. OBJECTIVE: This is a systematic review of the relevant published literature to explore the relationship between H. pylori infection and OME in children. METHOD: Articles published before October 30, 2019 in the PubMed, Web of Science, Ovid, the China National Knowledge Infrastructure (CNKI) database, and Wanfang databases were retrieved. Articles were screened based on prespecified inclusion and exclusion criteria. Quality assessment was applied to the included studies. Data in the included studies were extracted and classified for qualitative analysis. RESULTS: Ten studies, which enrolled a total of 397 cases and 334 controls, were included; all were case-control studies of varying quality. We summarized and compared H. pylori infections in different specimens from pediatric patients with OME. Due to the apparent heterogeneity between the included studies, meta-analysis was not appropriate, hence we carried out only a qualitative analysis. CONCLUSION: The detection rate of H. pylori in the middle ear, tonsil and gastric juice in children with OME was higher than that in children without OME. There is no clear and reliable conclusion as to whether there is a difference in the detection rate of H. pylori in adenoid specimens of children with or without OME. Eradication of H. pylori may improve symptoms of drug-resistant OME. Nevertheless, more studies of higher quality are needed to improve the conclusions.
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Infecções por Helicobacter/epidemiologia , Helicobacter pylori/isolamento & purificação , Otite Média com Derrame/epidemiologia , Adolescente , Estudos de Casos e Controles , Criança , Pré-Escolar , Orelha Média/microbiologia , Suco Gástrico/microbiologia , Humanos , Lactente , Tonsila Palatina/microbiologiaRESUMO
Previous study reported that either selective GSK-3ß inhibitor or up-regulating autophagy can alleviate cisplatin-induced ototoxicity. Other studies indicate that the activity of GSK-3ß is closely associated with the autophagy level. The purpose of this study is to primarily explore the role of autophagy in the alleviation effect of GSK-3ß inhibition on cisplatin-induced ototoxicity in vivo and in vitro. We observed the autophagy changes induced by GSK-3ß inhibitor in outer hair cells (OHCs) in a cisplatin-induced ototoxicity rat model. In addition, autophagy inhibitor 3-MA was used in vitro experiments to observe the influence of autophagy inhibition on the cell protection effect due to GSK-3ß inactivation. The relationship among autophagy, GSK-3ß and cell damage were inferred. Negative regulation of GSK-3ß significantly enhanced autophagy and alleviated cisplatin-induced hearing loss, OHC death in vivo and apoptosis in vitro. The autophagy inhibitor 3-MA inverted the protective effect of negative regulation of GSK-3ß. These results indicated that enhancing autophagy may be a key downstream effect of GSK-3ß inhibition in the alleviation of cisplatin-induced ototoxicity both in vivo and in vitro.
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Autofagia/efeitos dos fármacos , Cisplatino , Otopatias/tratamento farmacológico , Glicogênio Sintase Quinase 3 beta/metabolismo , Células Ciliadas Auditivas/efeitos dos fármacos , Cloreto de Lítio/farmacologia , Animais , Fadiga Auditiva/efeitos dos fármacos , Linhagem Celular , Modelos Animais de Doenças , Regulação para Baixo , Otopatias/induzido quimicamente , Otopatias/enzimologia , Otopatias/patologia , Potenciais Evocados Auditivos do Tronco Encefálico/efeitos dos fármacos , Células Ciliadas Auditivas/enzimologia , Células Ciliadas Auditivas/patologia , Masculino , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacosRESUMO
BACKGROUND: Recent reports have shown that laser myringotomy (LM) is increasingly used to treat otitis media with effusion (OME), with higher effectiveness, fewer complications, and lower recurrence rate. OBJECTIVE: A systematic review of the published literature was conducted to assess the efficacy of LM compared with incisional myringotomy (IM) with or without tympanostomy ventilation tube (VT) for the surgical treatment of OME in pediatric patients (age ≤ 18 years). METHODS: We searched the PubMed, Web of Science, Ovid, VIP Chinese, China National Knowledge Infrastructure (CNKI), and Wanfang Chinese databases for articles published before Nov 20, 2018. All relevant articles were reviewed and selectively collected according to inclusion and exclusion criteria. The quality of the included studies was assessed. The data in the eligible studies were extracted and analyzed. RESULTS: A total of 8 studies, including 698 patients and 1262 ears, were included. The types of studies examined include randomized controlled trials (RCTs) and case-control studies of varying quality. The outcomes and complications of LM and IM with or without VT were charted and compared. No quantitative meta-analysis could be performed. CONCLUSIONS: LM, characterized by much higher recurrence of OME and less complications, is less effective than IM+VT in keeping the middle ear ventilated and relieving middle ear effusion, but more effective than IM alone. The different interventions seem to show no significant differences in hearing improvement. Nevertheless, additional high-quality research is needed to perform more advanced analyses and to confirm and update our results and conclusions.
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Terapia a Laser , Ventilação da Orelha Média/métodos , Otite Média com Derrame/cirurgia , Adolescente , Criança , Pré-Escolar , Humanos , Resultado do TratamentoRESUMO
Acquired sensorineural hearing loss (SNHL), including age-related hearing loss (ARHL), noise-induced hearing loss (NIHL), drug-induced hearing loss (DIHL) and sudden sensorineural hearing loss (SSHL), is one of the most common sensory deficits in humans. Several studies have reported that antioxidant gene glutathione s-transferase M1 and T1 (GST M1 and T1) polymorphisms have a close relationship with the susceptibility to acquired SNHL, but other articles have reported opposite results. This meta-analysis aims to identify whether an association exists between GST M1 and T1 polymorphisms and the susceptibility to acquired SNHL. Seventeen independent studies containing 1749 cases and 2018 controls were included. According to the I2 value of the heterogeneity test, random-effects model was selected to calculate the pooled odds ratios (ORs) with their 95% confidence intervals (95% CIs) and p values. The pooled ORs (95% CI, p-value) of GST M1 and T1 were 1.186(0.955-1.473, p = 0.122) and 1.107(0.841-1.458, p = 1.467), respectively. In addition, subgroup analyses according to the type of SNHL and ethnicity showed no relationship between GST M1 and T1 polymorphisms and the susceptibility to acquired SNHL. Our results suggest that no significant relationship was found between GST M1 and T1 polymorphisms and the susceptibility to acquired SNHL.
Assuntos
Predisposição Genética para Doença/genética , Glutationa Transferase/genética , Perda Auditiva Neurossensorial/genética , Estudos de Associação Genética , Humanos , Estresse Oxidativo/fisiologia , Polimorfismo de Nucleotídeo Único/genética , Fatores de RiscoRESUMO
BACKGROUND: Several case-control studies reported the relationship between single nucleotide polymorphisms (SNPs) in HSP70 genes and noise-induced hearing loss (NIHL). However, their conclusions are conflicting. This meta-analysis aims to identify the association of HSP70 variants and NIHL susceptibility. METHOD: A systematical literature search was performed in PubMed, Web of Science, EMBASE, and Wanfang Chinese database. The pooled odds radio (OR), 95% confidence interval (CI) and p value were calculated in fixed- or random-effects model according to the I2 value in the heterogeneity test. RESULTS: Four articles containing five studies, including 633 cases and 926 controls, were included. Under the allele, homozygote and dominant model, the pooled ORs (95%CI, p-value) of rs1061581 were 1.32 (1.06-1.67, p = 0.019), 1.93 (1.10-3.36, p = 0.021) and 1.455 (1.408-2.019, p = 0.025), respectively. In addition, a significant association was found between rs2227956 in Caucasians and the NIHL susceptibility under all five genetic models. We did not discover evidence sufficient to prove the associations between the other three SNPs (rs1043618, rs2763979 and rs2075800) and the NIHL susceptibility. CONCLUSION: This meta-analysis indicated that the two HSP70 variants, rs1061581 and rs2227956, may serve as genetic susceptibility factors for NIHL. Larger scale studies are required to further update the results.