Antioxidative Stress-Induced Destruction to Cochlear Cells Caused by Blind Antioxidant Therapy.

OBJECTIVE: Verification that blind and excessive use of antioxidants leads to antioxidant stress which exacerbates cochlear cell damage. STUDY DESIGN: Basic research. SETTING: The Third Affiliated Hospital of Sun Yat-Sen University. METHODS: We compared and quantified hair cell-like house ear institute-organ of corti 1 (HEI-OC1) cell density, cell viability, and apoptosis caused by different concentrations of N-acetylcysteine (NAC) via Hoechst staining, Cell Counting Kit 8, Hoechst with propidium iodide staining, and Annexin V with propidium iodide (PI) staining. Apoptosis induced by high concentrations of M40403 and coenzyme Q10 in cochlear explants was analyzed and compared by cochlear dissection and activated caspase 3 labeling. RESULTS: With the increase of NAC concentration (0-1000 µmol/L), cell density decreased consequently and reached the lowest at 1000 µmol/L (****P ≤ .0001). Cell viability is also declining (**P < .01). The number of Annexin V-fluorescein isothiocyanate-labeled cells and PI-labeled cells increased with increasing NAC concentration after treatment of HEI-OC1 cells for 48 hours. The proportion of apoptotic cells also rose (*P < .05, **P < .01). Cochlear hair cells (HCs) treated with low concentrations of M40403 and coenzyme Q10 for 48 hours showed no damage. When the concentrations of M40403 and coenzyme Q10 were increased (concentrations＞30 µmol/L), HC damage began, followed by a dose-dependent increase in HC loss (*P < .001, **P < .0001). Activated caspase-3 was clearly apparent in cochlear explants treated with 50 µmol/L M40403 and coenzyme Q10 compared with cochlear explants without added M40403 and coenzyme Q10. CONCLUSION: These experimental results suggest that inappropriate application of antioxidants can cause severe damage to normal cochlear HCs.

Cobalt-induced apoptosis of cochlear organotypic cultures and HEI-OC1 cells is mediated by Dicer.

Cobalt is widely used in the medical industry, mainly including cobalt alloy joint implants and cobalt-chromium porcelain crowns. However, unexplained ototoxicity and neurotoxicity often occur in the clinical use of cobalt agents at present, which limits the development of the cobalt industry. In this study, based on the clinical problem of cobalt ototoxicity, we first conducted an extensive search and collation of related theories, and on this basis, prepared an HEI-OC1 cell model and basilar membrane organotypic cultures after cobalt treatment. We used immunofluorescence staining, western blot, CCK8, and si-RNA to investigate the mechanism of cobalt ototoxicity, to discover its potential therapeutic targets. After comparing the reactive oxygen species, mitochondrial transmembrane potential, apoptosis-related protein expression, and cell viability of different treatment groups, the following conclusions were drawn: cobalt causes oxidative stress in the inner ear, which leads to apoptosis of inner ear cells; inhibition of oxidative stress and apoptosis can alleviate the damage of cobalt on inner ear cells; and the Dicer protein plays a role in the mechanism of inner ear damage and is a potential target for the treatment of cobalt-induced inner ear damage. Taken together, these results suggest that cobalt-induced ototoxicity triggered by oxidative stress activates a cascade of apoptotic events where cCaspase-3 decreases Dicer levels and amplifies this apoptotic pathway. It may be possible to prevent and treat cobalt ototoxicity by targeting this mechanism.

Nanomaterials for Inner Ear Diseases: Challenges, Limitations and Opportunities.

The inner ear is located deep in the temporal bone and has a complex anatomy. It is difficult to observe and obtain pathological tissues directly. Therefore, the diagnosis and treatment of inner ear diseases have always been a major clinical problem. The onset of inner ear disease can be accompanied by symptoms such as hearing loss, dizziness and tinnitus, which seriously affect people's lives. Nanoparticles have the characteristics of small size, high bioavailability and strong plasticity. With the development of related research on nanoparticles in inner ear diseases, nanoparticles have gradually become a research hotspot in inner ear diseases. This review briefly summarizes the research progress, opportunities and challenges of the application of nanoparticles in inner ear diseases.

Corrigendum: ß-Cyclodextrin and Oligoarginine Peptide-Based Dendrimer-Entrapped Gold Nanoparticles for Improving Drug Delivery to the Inner Ear.

[This corrects the article DOI: 10.3389/fbioe.2022.844177.].

ß-Cyclodextrin and Oligoarginine Peptide-Based Dendrimer-Entrapped Gold Nanoparticles for Improving Drug Delivery to the Inner Ear.

Here, we developed a safe and highly effective nanocarrier using ß-cyclodextrin (ß-CD) and oligoarginine peptide (Arg8)-modified dendrimer-entrapped gold nanoparticles (Au@CD-PAMAM-Arg8), with a diameter of 5 nm, for improved delivery of dexamethasone (Dex) to the inner ear. The properties and in vivo distribution of the Au@CD-PAMAM-Arg8 were assessed in vitro, and a streptomycin (SM) ototoxicity model was used in vivo. Flow cytometry analysis of HEIOC1 cells treated with Au@CD-PAMAM-Arg8 and Au @CD-PAMAM at different time intervals indicated that cell uptake efficiency of the drug delivery carrier Au@CD-PAMAM-Arg8 was higher than that of Au @CD-PAMAM. Au@CD-PAMAM-Arg8 carrying Dex (Au@CD-PAMAM-Arg8/Dex) were mainly distributed in hair cells, the spiral ganglion, lateral wall, and nerve fibers and had stronger protective effects on the inner ear than Dex administration alone. In vivo tracer tests revealed that tympanic injection was significantly more effective than posterior ear injection, muscle injection, and tail vein injection, whereas clinical retro-auricular injection could not increase the efficiency of drug delivery into the ear. Electrocochleography results showed that Au@CD-PAMAM-Arg8/Dex significantly improved hearing in C57/BL6 mice after SM exposure. These findings indicate that Au@CD-PAMAM-Arg8 may be the useful drug carriers for the treatment of inner ear diseases.

Composition and Distribution of Aliphatic Hydrocarbon Compounds and Biomarkers in Seafloor Sediments from Offshore of the Leizhou Peninsula (South China).

The offshore of Leizhou Peninsula (LP, China), which contains unique ecosystems such as mangroves, seagrass beds, and coral reefs, is an environmentally sensitive area. For this reason, the levels of aliphatic hydrocarbon including biomarkers (hopanes, steranes) in the offshore seafloor sediments were analyzed in terms of their composition, distribution, and input sources and aimed to evaluate the extent of possible petroleum hydrocarbon contamination in the sediments of coastal areas. The total aliphatic hydrocarbons (TAH) fraction, the content of total n-alkanes (nC14-nC37) (∑n-alkanes), and content of hopane + sterane are in the range of 13.76-99.53, 1.22-8.33, and 0.02-0.23 µg/g dw, respectively. The presence of unresolved complex mixture (UCM) hydrocarbons hump and petrogenic steranes and hopanes in these seafloor sediments suggest that petrogenic sourced hydrocarbon inputs were present. The stations on the peninsula's southwest side had the lowest values of UCM/resolved aliphatic compounds (UCM/R) and UCM/n-alkanes. These findings suggest that seafloor sediments from the southwest offshore of the peninsula were likely contaminated by recently inputted petroleum hydrocarbons. The presence of relatively high ∑n-alkanes content in seafloor sediments from southwest offshore of the LP, combined with relatively low natural n-alkane ratios (NARs), indicates an increased influence of petrogenic hydrocarbons. The elevated levels of recent petrogenic hydrocarbon contamination in the sediments from the LP's southwestern offshore were likely related to petroleum exploitation in the Beibu Gulf's Maichen and Wushi sags.

Experimental animal models of drug-induced sensorineural hearing loss: a narrative review.

OBJECTIVE: This narrative review describes experimental animal models of sensorineural hearing loss (SNHL) caused by ototoxic agents. BACKGROUND: SNHL primarily results from damage to the sensory organ within the inner ear or the vestibulocochlear nerve (cranial nerve VIII). The main etiology of SNHL includes genetic diseases, presbycusis, ototoxic agents, infection, and noise exposure. Animal models with functional and anatomic damage to the sensory organ within the inner ear or the vestibulocochlear nerve mimicking the damage seen in humans are employed to explore the mechanism and potential treatment of SNHL. These animal models of SNHL are commonly established using ototoxic agents. METHODS: A literature search of PubMed, Embase, and Web of Science was performed for research articles on hearing loss and ototoxic agents in animal models of hearing loss. CONCLUSIONS: Common ototoxic medications such as aminoglycoside antibiotics (AABs) and platinum antitumor drugs are extensively used to induce SNHL in experimental animals. The effect of ototoxic agents in vivo is influenced by the chemical mechanisms of the ototoxic agents, the species of animal, routes of administration of the ototoxic agents, and the dosage of ototoxic agents. Animal models of drug-induced SNHL contribute to understanding the hearing mechanism and reveal the function of different parts of the auditory system in humans.

Application of Enhanced Recovery After Surgery in Perioperative Period of Tympanoplasty and Mastoidectomy.

INTRODUCTION: Enhanced recovery after surgery (ERAS) protocols are a series of perioperative care to optimize preoperative preparation, prevent postoperative complications, minimize stress, and speedup recovery. Tympanoplasty and mastoidectomy are common surgical procedures for chronic suppurative otitis media. OBJECTIVE: To compare the efficacy and safety between ERAS and conventional recovery after surgery in the perioperative period of chronic suppurative otitis media. METHODS: From April 2018 to February 2019, a total of 84 patients scheduled for tympanoplasty and/or mastoidectomy due to chronic suppurative otitis media were involved and randomly divided into the ERAS group and the control group. The patients' preoperative anxiety, postoperative pain, and comfort level were determined by comparing the results of Self-Rating Anxiety Scale (SAS), Visual Analog Scale (VAS) and General Comfort Questionnaire (GCQ). The postoperative complications, postoperative hospital stay, and hospitalization cost were calculated. RESULTS: The ERAS group showed a lower SAS score (30 [28-31.5] vs 35 [30-43], P < .05], a higher GCQ score (88 [84-100] vs 83 [78.25-92.25], P < .05), and a lower VAS score (0 [0-0] vs 1 [0-2], P < .05] after surgery. No significant difference (P > .05) was observed between the ERAS group and the control group in postoperative complications, postoperative hospitalization time, and hospitalization cost, respectively. CONCLUSION: Enhanced recovery after surgery can reduce pain and improve comfort in the perioperative period of chronic suppurative otitis media.

Impacts of different methylprednisolone administration routes in patients with sudden hearing loss or Meniere's disease.

BACKGROUND: Evidence suggests that glucocorticoids are important in the treatment of sudden hearing loss (SHL) and Meniere's disease (MD). However, different glucocorticoid administration methods may have a significant impact on treatment outcomes. OBJECTIVE: This study aimed to investigate effects of different glucocorticoid administration methods on sudden hearing loss and Meniere's disease. METHODS: In this study, glucocorticoids were administered orally in 18 patients, by retroauricular injection in 15 patients and by intratympanic injection in 15 patients. White blood cell (WBC) count, serum K+, fasting plasma glucose (FPG), body temperature, heart rate and blood pressure were used to evaluate effects of glucocorticoids on patients with hearing loss. Visual analog scale (VAS) of pain and sleep disorders were also surveyed, and pure tone audiometry (PTA) results were compared among groups to evaluate efficacy of different glucocorticoids administration methods. RESULT: WBC count, heart rate and blood pressure were higher in patients taking oral glucocorticoids, while body temperature, serum K+ and FPG levels did not change in all three groups. However, patients who received intratympanic injection of glucocorticoids experienced more pain, while those taking oral glucocorticoids reported more sleep impairment. Treatment efficacy on hearing loss was not significantly different among the three groups. CONCLUSION: These findings suggest that systemic glucocorticoid administration can result in greater whole body responses than local administration, but with similar hearing treatment efficacy.

Analysis of Click and Swept-Tone Auditory Brainstem Response Results for Moderate and Severe Sensorineural Hearing Loss.

INTRODUCTION: Auditory brainstem response (ABR) is one of the commonly used methods in clinical settings to evaluate the hearing sensitivity and auditory function. The current ABR measurement usually adopts click sound as the stimuli. However, there may be partial ABR amplitude attenuation due to the delay characteristics of the cochlear traveling wave along the basilar membrane. To solve that problem, a swept-tone method was proposed, in which the show-up time of different frequency components was adjusted to compensate the delay characteristics of the cochlear basilar membrane; therefore, different ABR subcomponents of different frequencies were synchronized. METHODS: The normal hearing group, moderate sensorineural hearing loss group, and severe sensorineural hearing loss group underwent click ABR and swept-tone ABR with different stimulus intensities. The latencies and amplitudes of waves I, III, and V in 2 detections were recorded. RESULTS: It was found that the latency of each of the recorded I, III, and V waves detected by swept-tone ABR was shorter than that by click ABR in both the control group and experimental groups. In addition, the amplitude of each of the recorded I, III, and V waves, except V waves under 60 dB nHL in the moderate sensorineural hearing loss group, detected by swept-tone ABR was larger than that by click ABR. The results also showed that the swept-tone ABR could measure the visible V waves at lower stimulus levels in the severe sensorineural hearing loss group. CONCLUSION: Swept-tone improves the ABR waveforms and helps to obtain more accurate threshold to some extent. Therefore, the proposed swept-tone ABR may provide a new solution for better morphology of ABR waveform, which can help to make more accurate diagnosis about the hearing functionality in the clinic.

Balloon dilation of Eustachian tube combined with tympanostomy tube insertion and middle ear pressure equalization therapy for recurrent secretory otitis media.

Objective to report outcomes of balloon dilation Eustachian tuboplasty combined with tympanostomy tube insertion and middle ear pressure equalization therapy in treatment of recurrent secretory otitis media. Methods Fifty one patients with recurrent secretory otitis media (62 ears) underwent balloon dilation of Eustachian tube and tympanic tube insertion under general anesthesia, followed by long term middle ear pressure equalization therapies. The Eustachian tube score (ETS) and Eustachian tube function questionnaire (ETDQ-7) were used for pre- and postoperative (up to 12 months) evaluation of Eustachian tube functions. Results The mean ETS score was 2.34 ±â€¯0.97 preoperatively, and 6.17 ±â€¯1.54, 7.23 ±â€¯1.62, 8.24 ±â€¯1.97, and 7.63 ±â€¯1.86 at 1, 3, 6 and 12 months postoperatively, respectively (P < 0.05). The ETDQ-7 score was 4.82 ±â€¯1.07 preoperatively, and 2.20 ±â€¯0.54, 2.32 ±â€¯0.68, 2.53 ±â€¯0.79, and 2.67 ±â€¯0.76 at 1, 3, 6 and 12 months postoperatively, respectively (P < 0.05). Conclusion Balloon dilation of Eustachian tube combined with tympanostomy and catheterization resulted in significant improvement of subjective symptoms and objective evaluation of Eustachian tube functions in most patients with recurrent secretory otitis media, as indicated by the ETS and ETDQ-7 scores, demonstrating high levels of efficacy and patient satisfaction.

Comparing Auditory Brainstem Responses evoked by Click and Sweep-Tone in Normal-Hearing Adults.

Auditory brainstem response (ABR) is an objective method via which hearing loss could be detected. ABR induced by click, a broadband signal, is generally considered as the gold standard. However, due to the inherent delay of the cochlear traveling wave, click cannot excite the entire cochlear basement membrane at the same time, leading to the attenuation of the induced ABR waveform. In order to resolve this limitation, a sweep-tone-based stimulus that reconstructs the arrival time of different frequency components with respect to the delay characteristics of cochlear basement membrane was designed and used to induce ABR in this study. Subsequently, we compared the performance of the proposed sweep-tone-induced ABR method and the commonly adopted click induced ABR at different test levels and different stimulus rates. And the obtained results showed that the waveform morphology of sweep-tone-induced ABR was significantly better than that of click induced ABR across different test levels and stimulus rates. Moreover, compared to the click induced ABR at different sweeps, we found that the proposed sweep-tone-induced ABR effectively induced the ABR waveform at a relatively faster rate. Hence, the proposed sweep-tone-induced ABR approach provides a new method to improve the sensitivity of ABR detection in hearing loss.

Flexible Non-contact Electrodes for Bioelectrical Signal Monitoring.

Physiological signals such as ECG and EMG are closely related with human health and a long term monitoring of the physiological signals would be beneficial to detect possible disorders at the early stage. The wet electrodes currently used in the clinics require adhesives gels to record high-quality signals, which might cause discomfort of the patients and introduce some risk of skin allergy. Non-contact capacitive electrodes that can be operated without skin contact have been developed in previous studies, but these electrodes were rigid with electronic components on the back, which might not be an optimal solution for long term healthcare monitoring. In this study, a flexible non-contact electrode without any electronic components on both sides was designed for the long term acquisition of bioelectrical signals to maximize subject comfort. The flexible electrode was made up of multi-layer flexible printed circuits (FPC) materials and could be bent according to the local shape to achieve better non-contact capacitive coupling with the skin. The performance of the proposed flexible electrode was compared with that of the conventional wet electrodes in different signal recording conditions. The results showed that the proposed non-contact flexible electrode can capture high quality ECG and EMG signals, and its performance was comparable to the commonly used wet electrodes. This study might provide a reliable solution with great patient comfort for the long-term monitoring of biological signals.

Using Muscle Synergy to Evaluate the Neck Muscular Activities during Normal Swallowing.

Swallowing is an extremely complex motion controlled by multiple muscles on the front neck region. Normal swallowing is dependent on orderly activation and co-coordination of the associated neck muscles, known as muscle synergy. However, evidence for muscle synergy during normal swallowing is rarely investigated. In this study, we studied the muscle synergy associated with swallowing saliva based on high-density (HD) surface electromyography (sEMG) signals acquired from four healthy subjects. The non-negative matrix factorization algorithm was applied to reconstruct the muscle activation patterns, and the values of variance accounted for (VAF) coefficients were computed to determine the number of muscle synergies. The results showed that the VAF values raised with the increase in the number of synergies on both the left and right sides of the neck. And the variation tendency of the VAF values was almost similar between the left and right area with a significant correlation ($\text{r}=0.9902 \pm 0.0046$, $\mathrm {p}<0.05)$. Furthermore, it was observed that an average of 5 muscle synergies was the minimum number required to sufficiently reconstruct the spatial characteristics of the synergism between both sides of the neck. These results suggest that the muscle synergy approach could serve as a promising candidate to evaluate the muscular co-contractions during swallowing, and it might be a useful method for dysphagia monitoring and diagnoses.