TFIIB-related factor 2 regulates glucose-regulated protein 78 expression in acquired middle ear cholesteatoma.

Acquired middle ear cholesteatoma leads to hearing loss, ear discharge, ear pain, and more serious intracranial complications. However, there is still no effective treatment other than surgery. TFIIB-related factor 2 (BRF2) acted as a redox sensor overexpressing in oxidative stress which linked endoplasmic reticulum (ER) stress, while glucose-regulated protein 78 (GRP78) was a biomarker of ER stress in cancer, atherosclerosis and inflammation. In our study, we investigated the roles of BRF2 and GRP78 in acquired middle ear cholesteatoma. Our results revealed that the expression of BRF2 was significant increased in acquired middle ear cholesteatoma, and which was positively correlated with the expression of GRP78. In addition, BRF2 and GRP78 showed colocalization in epithelium of acquired middle ear cholesteatomas and HaCaT cells. Prolongation of LPS stimulation in HaCaT cells escalated the expression of BRF2 and GRP78. To confirm the role of BRF2 and GRP78, we transfected si-BRF2 into HaCaT cells. All results indicated that BRF2 expression positively regulates the expression of GRP78 and may participate in the pathogenesis of acquire middle ear cholesteatoma.

Preliminary study on the feasibility of a two-stage screening strategy for otitis media with effusion in children.

AIM: To evaluate the feasibility of a two-stage screening strategy for otitis media with effusion (OME) in pre-school and school children. The risk factors of OME were also studied. METHODS: One hundred and eighty-nine children aged 4-8 years were recruited. The two-stage screening consisted of an on-site screening with a portable otoscopy along with a questionnaire to both diagnose children with OME and identify children at risk, and a standard screening performed at a regional hospital for final diagnosis. The prevalence detected from the two-stage screening approach was compared to the actual prevalence. RESULTS: The detection rate of OME through the two-stage screening approach was not significantly different from the actual prevalence rate (12.7% vs. 13.4%, P = 0.847). Children from the urban area had a lower risk for OME than that from the rural area (P = 0.007, odds ratio (OR) = 0.28, 95% confidence interval (CI): 0.11-0.74). Compared to childcare dining, family dining helped to reduce the chance of OME (P < 0.001, OR = 0.15, 95% CI: 0.06-0.38). CONCLUSIONS: The two-stage screening strategy was effective for screening for OME among pre-school and school children. It can be used in rural areas that have a high prevalence of OME and limited medical resources.

The evolution of function within the Nudix homology clan.

The Nudix homology clan encompasses over 80,000 protein domains from all three domains of life, defined by homology to each other. Proteins with a domain from this clan fall into four general functional classes: pyrophosphohydrolases, isopentenyl diphosphate isomerases (IDIs), adenine/guanine mismatch-specific adenine glycosylases (A/G-specific adenine glycosylases), and nonenzymatic activities such as protein/protein interaction and transcriptional regulation. The largest group, pyrophosphohydrolases, encompasses more than 100 distinct hydrolase specificities. To understand the evolution of this vast number of activities, we assembled and analyzed experimental and structural data for 205 Nudix proteins collected from the literature. We corrected erroneous functions or provided more appropriate descriptions for 53 annotations described in the Gene Ontology Annotation database in this family, and propose 275 new experimentally-based annotations. We manually constructed a structure-guided sequence alignment of 78 Nudix proteins. Using the structural alignment as a seed, we then made an alignment of 347 "select" Nudix homology domains, curated from structurally determined, functionally characterized, or phylogenetically important Nudix domains. Based on our review of Nudix pyrophosphohydrolase structures and specificities, we further analyzed a loop region downstream of the Nudix hydrolase motif previously shown to contact the substrate molecule and possess known functional motifs. This loop region provides a potential structural basis for the functional radiation and evolution of substrate specificity within the hydrolase family. Finally, phylogenetic analyses of the 347 select protein domains and of the complete Nudix homology clan revealed general monophyly with regard to function and a few instances of probable homoplasy. Proteins 2017; 85:775-811. © 2016 Wiley Periodicals, Inc.

Short-wavelength infrared laser activates the auditory neurons: comparing the effect of 980 vs. 810 nm wavelength.

Research on auditory neural triggering by optical stimulus has been developed as an emerging technique to elicit the auditory neural response, which may provide an alternative method to the cochlear implants. However, most previous studies have been focused on using longer-wavelength near-infrared (>1800 nm) laser. The effect comparison of different laser wavelengths in short-wavelength infrared (SWIR) range on the auditory neural stimulation has not been previously explored. In this study, the pulsed 980- and 810-nm SWIR lasers were applied as optical stimuli to irradiate the auditory neurons in the cochlea of five deafened guinea pigs and the neural response under the two laser wavelengths was compared by recording the evoked optical auditory brainstem responses (OABRs). In addition, the effect of radiant exposure, laser pulse width, and threshold with the two laser wavelengths was further investigated and compared. The one-way analysis of variance (ANOVA) was used to analyze those data. Results showed that the OABR amplitude with the 980-nm laser is higher than the amplitude with the 810-nm laser under the same radiant exposure from 10 to 102 mJ/cm2. And the laser stimulation of 980 nm wavelength has lower threshold radiant exposure than the 810 nm wavelength at varied pulse duration in 20-500 µs range. Moreover, the 810-nm laser has a wider optimized pulse duration range than the 980-nm laser for the auditory neural stimulation.

Substrate specificity characterization for eight putative nudix hydrolases. Evaluation of criteria for substrate identification within the Nudix family.

The nearly 50,000 known Nudix proteins have a diverse array of functions, of which the most extensively studied is the catalyzed hydrolysis of aberrant nucleotide triphosphates. The functions of 171 Nudix proteins have been characterized to some degree, although physiological relevance of the assayed activities has not always been conclusively demonstrated. We investigated substrate specificity for eight structurally characterized Nudix proteins, whose functions were unknown. These proteins were screened for hydrolase activity against a 74-compound library of known Nudix enzyme substrates. We found substrates for four enzymes with kcat /Km values >10,000 M-1  s-1 : Q92EH0_LISIN of Listeria innocua serovar 6a against ADP-ribose, Q5LBB1_BACFN of Bacillus fragilis against 5-Me-CTP, and Q0TTC5_CLOP1 and Q0TS82_CLOP1 of Clostridium perfringens against 8-oxo-dATP and 3'-dGTP, respectively. To ascertain whether these identified substrates were physiologically relevant, we surveyed all reported Nudix hydrolytic activities against NTPs. Twenty-two Nudix enzymes are reported to have activity against canonical NTPs. With a single exception, we find that the reported kcat /Km values exhibited against these canonical substrates are well under 105 M-1  s-1 . By contrast, several Nudix enzymes show much larger kcat /Km values (in the range of 105 to >107 M-1  s-1 ) against noncanonical NTPs. We therefore conclude that hydrolytic activities exhibited by these enzymes against canonical NTPs are not likely their physiological function, but rather the result of unavoidable collateral damage occasioned by the enzymes' inability to distinguish completely between similar substrate structures. Proteins 2016; 84:1810-1822. © 2016 Wiley Periodicals, Inc.

A continuous fluorescence assay for the characterization of Nudix hydrolases.

The common substrate structure for the functionally diverse Nudix protein superfamily is nucleotide-diphosphate-X, where X is a large variety of leaving groups. The substrate specificity is known for less than 1% of the 29,400 known members. Most activities result in the release of an inorganic phosphate ion or of a product bearing a terminal phosphate moiety. Reactions have typically been monitored by a modification of the discontinuous Fiske-SubbaRow assay, which is relatively insensitive and slow. We report here the development of a continuous fluorescence assay that enables the rapid and accurate determination of substrate specificities in a 96-well format. We used this novel assay to confirm the reported substrate characterizations of MutT and NudD of Escherichia coli and to characterize DR_1025 of Deinococcus radiodurans and MM_0920 of Methanosarcina mazei. Novel findings enabled by the new assay include the following. First, in addition to the well-characterized hydrolysis of 8-oxo-dGTP at the α-ß position, MutT cleaves at the ß-γ phosphate bond at a rate of 3% of that recorded for hydrolysis at the α-ß position. Second, MutT also catalyzes the hydrolysis of 5-methyl-dCTP. Third, 8-oxo-dGTP was observed to be the best substrate for DR_1025 of the 41 compounds screened.

Effect of speaking rate on recognition of synthetic and natural speech by normal-hearing and cochlear implant listeners.

OBJECTIVE: Most studies have evaluated cochlear implant (CI) performance using "clear" speech materials, which are highly intelligible and well articulated. CI users may encounter much greater variability in speech patterns in the "real world," including synthetic speech. In this study, the authors measured sentence recognition with multiple talkers and speaking rates, and with naturally produced and synthetic speech in listeners with normal hearing (NH) and CIs. DESIGN: NH and CI subjects were asked to recognize naturally produced or synthetic sentences, presented at a slow, normal, or fast speaking rate. Natural speech was produced by one male and one female talker; synthetic speech was generated to simulate a male and female talker. For natural speech, the speaking rate was time-scaled while preserving voice pitch and formant frequency information. For synthetic speech, the speaking rate was adjusted within the speech synthesis engine. NH subjects were tested while listening to unprocessed speech or to an eight-channel acoustic CI simulation. CI subjects were tested while listening with their clinical processors and the recommended microphone sensitivity and volume settings. RESULTS: The NH group performed significantly better than did the CI-simulation group, and the CI-simulation group performed significantly better than did the CI group. For all subject groups, sentence recognition was significantly better with natural speech than with synthetic speech. The performance deficit with synthetic speech was relatively small for NH subjects listening to unprocessed speech. However, the performance deficit with synthetic speech was much greater for CI subjects and for CI-simulation subjects. There was significant effect of talker gender, with slightly better performance with the female talker for CI subjects and slightly better performance with the male talker for the CI simulations. For all subject groups, sentence recognition was significantly poorer only at the fast rate. CI performance was very poor (approximately 10% correct) at the fast rate. CONCLUSIONS: CI listeners are susceptible to variability in speech patterns caused by speaking rate and production style (natural versus synthetic). CI performance with clear speech materials may overestimate performance in real-world listening conditions. The poorer CI performance may be because of other factors besides reduced spectro-temporal resolution, such the quality of electric stimulation, duration of deafness, or cortical processing. Optimizing the input or training may improve CI users' tolerance for variability in speech patterns.

Whole transcriptome sequencing analysis of blood plasma-derived exosomes from immune-related hearing loss.

BACKGROUND: Early diagnosis of immune-related hearing loss and timely treatment can prevent structural damage to the inner ear and contribute to hearing retention. Exosomal miRNAs, lncRNAs and proteins have great prospects as novel biomarkers for clinical diagnosis. Our study aimed to investigate the molecular mechanisms of exosomes or exosomal ceRNA regulatory networks in immune-related hearing loss. METHODS: An immune-related hearing loss mice model was constructed by injection with inner ear antigen, and then the blood plasma samples of the mice were collected for exosomes isolation by ultra-centrifugation. Subsequently, the different exosomes were sent for whole transcriptome sequencing using Illumina platform. Finally, a ceRNA pair was chosen for validation by RT-qPCR and dual luciferase reporter gene assay. RESULTS: The exosomes were successfully extracted from the blood samples of the control and the immune-related hearing loss mice. After sequencing, 94 differentially expressed (DE) lncRNAs, 612 DEmRNAs, and 100 DEmiRNAs were found in the immune-related hearing loss-associated exosomes. Afterwards, ceRNA regulatory networks consisting of 74 lncRNAs, 28 miRNAs and 256 mRNAs were proposed, and the genes in the ceRNA regulatory networks were significantly enriched in 34 GO terms of biological processes and 9 KEGG pathways. Finally, Gm9866 and Dusp7 were significantly up-regulated, while miR-185-5p level was declined in the exosomes from immune-related hearing loss, and Gm9866, miR-185-5p and Dusp7 interacted with each other. CONCLUSIONS: Gm9866-miR-185-5p-Dusp7 was confirmed to be closely correlated with the occurrence and progression of immune-related hearing loss.

Analysis of the vestibular aqueduct development on the risk for suffering from idiopathic sudden sensorineural hearing loss.

OBJECTIVE: Large vestibular aqueduct syndrome (LVAS) is one of the etiology of hearing loss. Clinically, we observed that the VA size of patients with idiopathic sudden sensorineural hearing loss (ISSNHL) did not meet the diagnostic criteria of VA enlargement, but there were individual variations. Through this study, we want to understand the VA development and explore its risk for suffering from ISSNHL. METHODS: 74 patients with ISSNHL were retrospectively reviewed in our department from June 2018 to September 2021. Meanwhile, 57 people with no ear diseases were randomly selected as the control group. All their clinical information were systematically collected. The axial thin-slice CT images of temporal bone were used to observe and measure the VA in ISSNHL and controls. ISSNHL were classified as different types and grades according to pure tone audiometry and the degree of hearing loss, respectively. Logistic regression analysis was adopted to evaluate the risk factors of different types and grades of ISSNHL. RESULTS: The operculum morphology could be funnel-shaped, tubular and invisible, but they had no statistical difference in the morbidity of ISSNHL. The operculum width of the affected sides in the case group was significantly wider than that of the matched sides in the control group (0.84±0.35mm vs 0.68±0.34mm, p=0.009), but the midpoint width had no statistical difference (p=0.447). The operculum width was an independent risk factor for the total hearing loss type (p=0.036, OR=4.49, 95% CI=1.10-18.29), moderate (p=0.013, OR=17.62, 95% CI=1.82-170.95) and profound (p=0.031, OR=4.50, 95% CI=1.14-17.67) grade of ISSNHL. Hypertension was an independent risk factor for the severe grade (p=0.004, OR=12.44, 95% CI=2.19-70.64) of ISSNHL. Both the operculum width (p=0.048, OR=7.14, 95% CI=1.02-50.26) and hypertension (p=0.014, OR=6.73, 95% CI=1.46-30.97) were the risk factors for the flat type of ISSNHL. The midpoint width of the VA, gender, age, diabetes mellitus, hyperlipidemia, and plasma fibrinogen concentration had no significant effect on the risk for suffering from ISSNHL. CONCLUSION: The development of the VA operculum is a risk factor for some types and grades of ISSNHL. Hypertension remained a risk factor for ISSNHL.

Melatonin Attenuates Cisplatin-Induced Ototoxicity via Regulating the Cell Apoptosis of the Inner Ear.

Objective: The mechanism of ototoxicity caused by cisplatin is currently unclear, and the induced apoptosis may play an important role in inner ear injury. Melatonin has high antioxidant and antiapoptotic effects. This study is aimed at clarifying the protective effect on the inner ear and the underlying mechanism of melatonin. Design: The mice and HEI-OC1 cells were randomly separated into four groups: control group, cisplatin group, melatonin group, and cisplatin exposure after melatonin pretreatment group. Place and Duration of the Study. From September 2018 to September 2021, all experiments were completed at the Second Hospital of Shandong University. And the study was approved by the Ethics Committee of the Second Hospital of Shandong University (KYLL-2020 (KJ) A-0191). Methodology. Mice were pretreated with peritoneal injection of melatonin prior to the application of cisplatin. Auditory Brainstem Response (ABR) test was performed before and after treatment, then the temporal bones were collected for histology investigation. HEI-OC1 cells were pretreated with melatonin before adding cisplatin. The apoptosis of HEI-OC1 cells was observed by MTS, TUNEL, and flow cytometry, respectively. Moreover, the mRNA expression of apoptosis-related factors was detected by qRT-PCR. Results: ABR and morphological analysis showed that cisplatin caused damage to the function and structure of the inner ear. MTS, TUNEL, and flow cytometry showed that the application of cisplatin caused a significant increase in the apoptosis level of HEI-OC1 cells, and melatonin pretreatment reduced this damage. Moreover, melatonin pretreatment reversed the mRNA expression changes of apoptosis-related factors induced by cisplatin. Conclusions: Apoptosis is involved in the inner ear dysfunction caused by cisplatin. Melatonin reduces the ototoxicity of cisplatin by regulating the induced apoptosis response.

MiR-142-5p directly targets cyclin-dependent kinase 5-mediated upregulation of the inflammatory process in acquired middle ear cholesteatoma.

MicroRNAs (miRNAs) play important roles in the regulation of cell proliferation, differentiation, apoptosis, and inflammatory responses. MiR-142-5p is an important inflammation-associated miRNA, whose abnormal expression has been associated with a variety of inflammation-related diseases. However, the role and signaling pathways targeted by miR-142-5p in acquired middle ear cholesteatoma (AMEC) have not been fully elucidated. Cyclin-dependent kinase 5 (CDK5), a special member of the CDK family compared with classic cyclins that plays a critical role in the inflammatory response. In this study, we investigated the roles of miR-142-5p and CDK5 in inflammatory responses in AMEC. Our results revealed that the expression of miR-142-5p was significantly reduced in AMEC, and was negatively correlated with the expression of CDK5 (r=-0.5451). We also found that miR-142-5p can inhibit CDK5 expression by directly target 3' untranslated region (UTR) of CDK5. Additionally, our findings indicated that the increased expression of CDK5 induces the secretion of inflammatory cytokines. In order to further confirm the involvement of miR-142-5p in the regulation of the inflammatory response in AMEC through its inhibitory effect on CDK5 expression, we studied the inflammatory response in HaCaT cells transfected with small interfering RNA against CDK5 (si-CDK5) and a miR-142-5p inhibitor. The results confirmed that miR-142-5p regulates the inflammatory response in AMEC by downregulating CDK5. In summary, miR-142-5p directly inhibits the CDK5-mediated upregulation of inflammatory cytokines in AMEC, which makes it a potential therapeutic target in this disease.

Hidden hearing loss is associated with loss of ribbon synapses of cochlea inner hair cells.

The present study aimed to observe the changes in the cochlea ribbon synapses after repeated exposure to moderate-to-high intensity noise. Guinea pigs received 95 dB SPL white noise exposure 4 h a day for consecutive 7 days (we regarded it a medium-term and moderate-intensity noise, or MTMI noise). Animals were divided into four groups: Control, 1DPN (1-day post noise), 1WPN (1-week post noise), and 1MPN (1-month post noise). Auditory function analysis by auditory brainstem response (ABR) and compound action potential (CAP) recordings, as well as ribbon synapse morphological analyses by immunohistochemistry (Ctbp2 and PSD95 staining) were performed 1 day, 1 week, and 1 month after noise exposure. After MTMI noise exposure, the amplitudes of ABR I and III waves were suppressed. The CAP threshold was elevated, and CAP amplitude was reduced in the 1DPN group. No apparent changes in hair cell shape, arrangement, or number were observed, but the number of ribbon synapse was reduced. The 1WPN and 1MPN groups showed that part of ABR and CAP changes recovered, as well as the synapse number. The defects in cochlea auditory function and synapse changes were observed mainly in the high-frequency region. Together, repeated exposure in MTMI noise can cause hidden hearing loss (HHL), which is partially reversible after leaving the noise environment; and MTMI noise-induced HHL is associated with inner hair cell ribbon synapses.

Analysis of related factors of recurrence in horizontal semicircular canal benign paroxysmal positional vertigo: a pilot study.

Background: Whether the abnormal caloric test (C-test) affects recurrence rate in horizontal semicircular canal benign paroxysmal positional vertigo (HSC-BPPV) with residual dizziness (RD) is not clear.Objectives: 1) Analyze the association of the cycles of canalith repositioning procedure (CRP), C-test and RD after CRP and 2) determine which affects the recurrence rate in idiopathic HSC-BPPV.Materials and methods: Eighty-four patients with HSC-BPPV (canal type) were included in this work. The cycles of CRP, C-test, the RD after CRP and HSC-BPPV recurrence rate were recorded. Depending on the times of CRP and patients who presented dizziness after treatment, patients were divided into four groups, the relationship between abnormal C-test and RD was analyzed. The outcomes of recurrence rate were compared between groups, respectively.Results: (1) The abnormal C-test prevalence among the HSC-BPPV patients with RD was 36% while in no RD group was 14.7%. The difference was statistically significant (p = .045). (2) The recurrence rate was 11.8% in no RD group but in RD group the rate was higher (32%, p = .039). When patients combined with abnormal C-test, the recurrence rate was significantly higher (77.8% vs. 20%) (p = .033).Conclusions: A weak correlation between RD and abnormal C-test is noted. Presence of RD and abnormal C-test in patients with HSC-BPPV predicts a higher recurrence rate.

Identification of Key Modules, Hub Genes, and Noncoding RNAs in Chronic Rhinosinusitis with Nasal Polyps by Weighted Gene Coexpression Network Analysis.

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a chronic inflammatory disease with relatively easy recurrence. However, the precise molecular mechanisms of this disease are poorly known. Based on gene sequencing data obtained from the Gene Expression Omnibus (GEO) database, we constructed coexpression networks by weighted gene coexpression network analysis (WGCNA). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed by the Database for Annotation, Visualization, and Integrated Discovery (DAVID). The core gene of pathogenesis, CRSwNP, was screened by protein-protein interaction data (PPI) from the HPRD database. Unsupervised clustering was applied to screen hub genes related to the phenotype of CRSwNP. Blue and turquoise modules were found to be most significantly related to the pathogenicity of CRSwNP. Functional enrichment analysis showed that cell proliferation in the blue modules, the apoptotic process in the turquoise module, and the cancer pathway in both modules were mostly significantly correlated with the development of CRSwNP. The noncoding RNAs (long noncoding RNA and microRNA) and the top 10 core genes in each module were found to be associated with the pathogenesis of CRSwNP. A total of nine hub genes were identified to be related to the CRSwNP phenotype. By qRT-PCR analysis, AKT1, CDH1, PIK3R1, CBL, LRP1, MALAT1, and XIST were proven to be associated with the pathogenesis of CRSwNP. AGR2, FAM3D, PIP, DSE, and TMC were identified to be related to the CRSwNP phenotype. Further exploration of these genes will reveal more important information about the mechanisms of CRSwNP.

Analysis of the developmental trajectory and influencing factors of auditory and speech functions after cochlear implantation in Mandarin Chinese speaking children.

Background: The auditory and speech development of the children with cochlear implants (CIs) are influenced by many factors.Objective: To study the developmental trajectory and influencing factors of auditory and speech functions for the Mandarin Chinese speaking children with CIs.Material and methods: The children with CIs undergoing rehabilitation in the same institution from June 2016 to June 2019 were followed up. Their closed monosyllables and disyllables recognition rate, closed average language age, categories of auditory performance (CAP) and speech intelligibility rating (SIR) were evaluated at 0, 1, 3, 6, 12 and 24 months of rehabilitation. The results were analyzed by SPSS 23.0.Results: 49 children were followed up for 1 year, 29 children for 2 years. The evaluated indicators of auditory and speech functions were improved with the prolongation of rehabilitation and influenced by the age of cochlear implantation, the use of hearing aids before surgery, guardian's educational degree, the relationship between guardian and child.Conclusions and significance: The auditory and speech functions of the children with CIs were improved significantly with the prolongation of rehabilitation and influenced by many factors, which can help us to predict the effect of CI more accurately and develop an individualized rehabilitation program.

A unique radioprotective effect of resolvin E1 reduces irradiation-induced damage to the inner ear by inhibiting the inflammatory response.

BACKGROUND: In addition to the direct effects of irradiation, the induced inflammatory response may play an important role in the damage to the inner ear caused by radiotherapy for the treatment of head and neck cancers. Resolvin E1 (RvE1) has anti-inflammatory activity, acting by reducing neutrophil infiltration and proinflammatory cytokine expression. Therefore, in this study we sought to confirm whether the inflammation induced by irradiation was involved in damage to the inner ear after radiotherapy and to investigate the protective effect and underlying mechanism of RvE1 using mouse models. METHODS: A dose of RvE1 was delivered by intraperitoneal injection to mice before irradiation. Changes in the auditory brainstem response (ABR), relative balance ability, inner ear morphology and the expression levels of inflammatory factors in the inner ear were analyzed on days 7 and 14 after irradiation and compared among different experimental groups. RESULTS: Changes of ABR and relative balance ability showed the inner functions of experimental mice presented severe damage after irradiation, but the damage was significantly alleviated after RvE1 pretreatment compared to irradiation alone. Morphological analysis of the inner ear showed severe damage to the cochlea and vestibule after irradiation. In contrast, damage to the cochlea and vestibule was significantly reduced in the RvE1-pretreated group compared to that in the irradiation alone group. Along with these functional and morphological changes, the mRNA expression level of anti-inflammatory factors interleukin-2 was significantly increased, while those of proinflammatory factors interleukin-6 and tumor necrosis factor-α were significantly decreased in the inner ear of mice after RvE1 pretreatment compared to irradiation alone. CONCLUSIONS: We believe that inflammation induced by irradiation is involved in the damage to the inner ear caused by radiotherapy, and that RvE1 reduces the damage caused by irradiation to the inner ear by regulating the induced inflammatory response.

miR­10b­3p, miR­8112 and let­7j as potential biomarkers for autoimmune inner ear diseases.

Circulating microRNAs (miRNAs) have been suggested as non­invasive biomarkers for the diagnosis of several autoimmune diseases. However, to the best of our knowledge, no studies have yet examined the miRNA expression profiles in autoimmune inner ear disease (AIED). The present study aimed to use an miRNA sequencing assay to detect the miRNA expression profiles of serum samples from 3 control mice and 3 antigen­induced AIED model mice. Differentially expressed miRNAs (DE­miRNAs) were screened using a t­test. miRNA target prediction was performed using TargetScan Mouse. Then, the miRNA­target gene interaction network was constructed and visualized using Cytoscape software. The underlying functions of the target genes of the DE­miRNAs were predicted using the clusterProfiler package. As a result, 22 miRNAs were identified as DE­miRNAs between AIED and control mice, including 10 upregulated and 12 downregulated genes. Based on the TargetScan Mouse prediction, 1,958 genes were identified as the targets for the 22 DE­miRNAs. Functional analysis indicated that only the target genes of 8 miRNAs were respectively enriched for Gene Ontology terms and Kyoto Encyclopedia of Genes and Genomes pathways, among which miR­10b­3p, let­7j and miR­8112 were shared between the two pathway analyses. These 3 miRNAs may be involved in AIED by affecting inflammatory chemokine (miR­10b­3p­C­C motif chemokine 12), Wnt signaling (miR­8112­Wnt9b/Wnt 3a/Wnt2b) and Mucin type O­glycan biosynthesis pathways (let­7j­Galnt2/Galnt12). In conclusion, miR­10b­3p, miR­8112 and let­7j may be underlying biomarkers for diagnosing AIED.

Cmah deficiency may lead to age-related hearing loss by influencing miRNA-PPAR mediated signaling pathway.

BACKGROUND: Previous evidence has indicated CMP-Neu5Ac hydroxylase (Cmah) disruption inducesaging-related hearing loss (AHL). However, its function mechanisms remain unclear. This study was to explore the mechanisms of AHL by using microarray analysis in the Cmah deficiency animal model. METHODS: Microarray dataset GSE70659 was available from the Gene Expression Omnibus database, including cochlear tissues from wild-type and Cmah-null C57BL/6J mice with old age (12 months, n = 3). Differentially expressed genes (DEGs) were identified using the Linear Models for Microarray data method and a protein-protein interaction (PPI) network was constructed using data from the Search Tool for the Retrieval of Interacting Genes database followed by module analysis. Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis was performed using the Database for Annotation, Visualization and Integrated Discovery. The upstream miRNAs and potential small-molecule drugs were predicted by miRwalk2.0 and Connectivity Map, respectively. RESULTS: A total of 799 DEGs (449 upregulated and 350 downregulated) were identified. Upregulated DEGs were involved in Cell adhesion molecules (ICAM1, intercellular adhesion molecule 1) and tumor necrosis factor (TNF) signaling pathway (FOS, FBJ osteosarcoma oncogene; ICAM1), while downregulated DEGs participated in PPAR signaling pathway (PPARG, peroxisome proliferator-activated receptor gamma). A PPI network was constructed, in which FOS, ICAM1 and PPARG were ranked as hub genes and PPARG was a transcription factor to regulate other target genes (ICAM1, FOS). Function analysis of two significant modules further demonstrated PPAR signaling pathway was especially important. Furthermore, mmu-miR-130b-3p, mmu-miR-27a-3p, mmu-miR-27b-3p and mmu-miR-721 were predicted to regulate PPARG. Topiramate were speculated to be a potential small-molecule drug to reverse DEGs in AHL. CONCLUSIONS: PPAR mediated signaling pathway may be an important mechanism for AHL. Downregulation of the above miRNAs and use of topiramate may be potential treatment strategies for ALH by upregulating PPARG.

The variation of superior semicircular canal bone thickness in relation to age and gender.

BACKGROUND: Superior semicircular canal dehiscence syndrome (SSCD) is a current diagnosis that is due to a loss of bone covering the superior semicircular canal (SSC). This results in pressure-/sound- induced vertigo and oscillopsia. OBJECTIVE: To find the variation of the thickness of the bone that covers the Superior Semicircular Canal with relation to age and gender among the Chinese descents. MATERIALS AND METHODS: Three hundred and eleven temporal bone Cone Beam Computed Tomography (CBCT) images of patients who attended Otology clinic at Second Hospital of Shandong University from January, 2017 to April, 2018 were retrospectively studied. The images were reconstructed in the line of Poschl and the thinnest area of the bone covering the SSC was taken. RESULTS: We included 172 (55.31%) females and 139 (44.69%) males. Mean age was 41 years. Overall mean difference in thickness was found to be -0.0210. There was no significant difference between the female and male bone thickness (p = .7113). With age the mean difference was 0.0801 (p = .1557) which was not statistically significant. CONCLUSION AND SIGNIFICANCE: There was no significant change in bone thickness with advancing age. CBCT is the best method of assessing SSCD.

Expression of VEGF, iNOS, and eNOS is increased in cochlea of diabetic rat.

CONCLUSION: The results of this study indicate that diabetes causes up-regulation of vascular endothelial growth factor (VEGF), inducible nitric oxide synthase (iNOS), and endothelial nitric oxide synthase (eNOS), which may be involved in the pathogenesis of cochlea functional loss. OBJECTIVE: To investigate the underlying mechanisms that may be responsible for diabetic microangiopathy in the inner ear, we studied the expression of VEGF, iNOS, and eNOS in the streptozotocin (STZ)-induced diabetic rat cochlea. MATERIALS AND METHODS: The immunofluorescence studies were performed by using FITC-labelled specific antibodies to VEGF, iNOS, and eNOS on paraffin sections of the cochlea. The expression levels of VEGF, iNOS, and eNOS were quantified by means of Western blot analysis of cochlea protein extracts. Evans blue (EB) was used to investigate blood-labyrinth barrier (BLB) permeability in the cochlea. RESULTS: Increased cochlear expression of VEGF, iNOS, and eNOS was detected in the diabetic rat. Furthermore, increased permeability of BLB was evidenced by increased cochlear EB extravasation in the diabetic rat.