Search Results (98)

Recreational noise-induced hearing loss (RNIHL) is a significant factor contributing to hearing loss in young people. Its process is irreversible, and early symptoms are hidden. Therefore, early identification is of great significance. Otoacoustic emissions (OAEs) are commonly used to detect the function of outer hair cells. It is widely used for early diagnosis of occupational noise-induced hearing loss, but it remains underutilized in RNIHL detection. In order to explore the characteristics of RNIHL and the early detection value of different types of OAEs, this study reviewed the detection results of OAEs in previous studies on noise-induced hearing loss and analyzed the differences and causes among the studies. The study found that, through the detection of distortion product otoacoustic emissions (DPOAEs), there were differences in the sensitive frequency bands of outer hair cell damage between recreational noise and occupational noise, particularly in the high-frequency region. Transient-evoked otoacoustic emissions (TEOAEs) can fully reflect the damage to cochlear outer hair cells caused by RNIHL. This study indicates that OAEs, particularly TEOAEs, can serve as a highly sensitive and objective detection tool for RNIHL, whereas DPOAEs are more appropriate for the early screening of occupational noise-induced hearing loss. Full article

Background/Objectives: Cochlear “injury” is thought to be a significant cause of tinnitus in patients with hearing loss. Interestingly, individuals with normal hearing may also experience tinnitus. This study evaluates otoacoustic distortion product emissions (DPOAEs) in individuals with normal hearing who experience tinnitus perception. Methods: In this prospective study, the tinnitus group (TG) consisted of 34 subjects with tinnitus (four unilaterally) and normal hearing (threshold ≤ 25 dBHL at 0.25–8 kHz). The control group (CG) comprised 10 healthy volunteers (20 ears) without tinnitus and normal hearing. Medical history was recorded, and all participants underwent a complete otolaryngological examination, pure tone audiometry, and DPOAE recording (DP-gram, L1 = 55 dB, L2 = 65 dB, for F2: 619–10,000 Hz). Moreover, participants in the TG completed a detailed tinnitus history (with self-rated loudness scoring) and the Tinnitus Handicap Inventory (Greek-version THI-G) and underwent tinnitus analysis. Results: The recorded mean DPOAE values during the DP-gram of the CG were significantly larger in amplitude at low (t-test, Bonferroni-corrected p < 0.09) and high frequencies (t-test, Bonferroni-corrected p < 0.02) compared with the TG. Tinnitus assessment showed tinnitus pitch matching at the frequency area in the DP-gram, where the acceptance recording criteria were not met. There were no statistically significant differences in tinnitus onset, self-rated loudness scores of >70, and severe disability (THI-G > 58) for TG subjects in whom DPOAEs were not recorded at frequencies of ≤1000 Hz. Participants with abnormal DPOAEs at around 4000 Hz had tinnitus of sudden onset and severe disability (THI-G > 58). Finally, those with pathological recordings of DPOAEs at ≥6000 Hz had gradual onset tinnitus (Pearson Chi-square test, p < 0.05). Conclusions: DPOAEs in normal hearing individuals with tinnitus show lower amplitudes in low and high frequencies compared with normal hearing individuals without tinnitus. The tinnitus matched-frequency coincided with the frequency area where DPOAEs were abnormal. Full article

Hair follicle stem cells (HFSCs) are pluripotent stem cells located in the bulges of hair follicles. Apoptosis regulates tissue homeostasis by eliminating unnecessary or damaged cells during development and aging. VDAC2, located in the outer mitochondrial membrane (MOM), is a key apoptosis regulator, but its role in cashmere goat hair follicles remains unclear. In previous studies, through proteomic sequencing, we found that VDAC2 was significantly differentially expressed in the anagen, catagen, and telogen phases of the hair follicles of Albas cashmere goats. This study aimed to explore the role of VDAC2 in secondary hair follicle stem cells (SHFSCs) and preliminarily investigate its regulatory mechanism through RNA-seq. Overexpression of VDAC2 promoted apoptosis in SHFSCs, while knockdown had the opposite effect. RNA-seq analysis, together with expression validation of downstream genes, indicates that the P53 signaling pathway may be involved in VDAC2-mediated SHFSC regulation. RT-qPCR and Western blotting confirmed that VDAC2 activated the P53 signaling pathway in SHFSCs. Furthermore, the use of a P53 inhibitor after VDAC2 overexpression partially rescued the apoptosis of cells caused by VDAC2. These results demonstrate that VDAC2 plays an important role in SHFSC apoptosis. Our findings greatly enhance our understanding of the role of VDAC2 in SHFSC apoptosis and hair follicle growth. Full article

Background/Objectives: Obesity is a risk factor for several diseases; however, less has been researched about how diet-induced obesity may affect the auditory system. In this sense, the purpose of this study was to evaluate the effect of diet-induced obesity on the functionality and integrity of the outer hair cells, a key component of the organ of Corti, inside the cochlea. Furthermore, we hypothesized that adipose tissue (AT) status is associated with impaired outer hair cell auditory amplification in young C57BL/6 mice, contributing to increased vulnerability to hearing damage. Methods: Weaning male C57BL/6J mice (7 weeks old) weighing 22–23 g were divided into two diet groups: (i) a control diet or (ii) a high-fat diet (HFD) for 12 or 16 weeks. Metabolic parameters (body and AT weight, glucose tolerance test), AT dysfunction markers (AT remodeling, adipocyte size, crown-like structures), and outer hair cell function (distortion products otoacoustic emissions (DPOAEs) threshold and amplitudes) and integrity (hair cells cell count) were evaluated. Results: We observed that mice fed an HFD for 16 weeks showed a higher DPOAE threshold against stimuli at 16 KHz and a lower count of outer hair cells in the medial section of the cochlea. These results demonstrate a correlation between body and AT weight specifically at 16 weeks of treatment, the time point at which we observed a marked AT dysfunction. Conclusions: Taken together, our results suggest that obese mice with AT dysfunction have an altered auditory efferent system, characterized by a higher DPOAE threshold and a lower outer hair cell count in the medial section, which may impact signal transduction. Full article

Noise-induced hearing loss (NIHL) is a common type of sensorineural hearing loss caused by exposure to high-intensity noise that leads to irreversible cochlear damage. Despite extensive research on cochlear pathophysiology, the precise mechanisms remain unclear, and no established treatment exists. This is due to the challenges in imaging and the inability to perform biopsies in human patients. Consequently, animal models, particularly mice, have been widely used to study NIHL. Clinically, NIHL presents as either a temporary threshold shift, in which hearing recovers, or a permanent threshold shift, which results in an irreversible loss. Histopathological studies have identified the key features of NIHL, including outer hair cell loss, auditory nerve degeneration, and synaptic impairment. Recent findings suggest that oxidative stress and inflammation are major contributors to NIHL, highlighting the potential for therapeutic interventions, such as antioxidants and anti-inflammatory agents. Given the increasing prevalence of NIHL owing to occupational noise exposure and personal audio device use, addressing this issue is a pressing public health challenge. This review summarizes the clinical features, underlying mechanisms, and emerging treatment strategies for NIHL while identifying current knowledge gaps and future research directions. Full article

Outer bulge (OB) hair follicle stem cells (HFSCs) play a crucial role in maintaining hair follicle structural stability and regulating the hair follicle cycle. Previous studies demonstrated that keratin 24 (Krt24) exhibits spatiotemporally restricted expression in OB HFSCs. Here, we report the generation of the Krt24-Cre^ERT2 mouse line. When crossed with Rosa26^LSL-tdTomato or Rosa26^LSL-DTR reporter lines, offspring exhibited specific labeling (Krt24-Cre^ERT2;Rosa26^LSL-tdTomato) or ablation (Krt24-Cre^ERT2;Rosa26^LSL-DTR) of Krt24⁺ cells. In Krt24-Cre^ERT2;Rosa26^LSL-tdTomato mice, phase-specific tamoxifen (TAM) administration demonstrated spatiotemporal fidelity of Cre activity to endogenous Krt24 expression patterns. Lineage tracing revealed that tdTomato-labeled Krt24⁺ cells differentiated into the outer root sheath (ORS) during the anagen phase and persisted when hair follicles reentered telogen. Ablation of Krt24⁺ cells via diphtheria toxin (DT) administration significantly delayed anagen initiation. Mice under continuous depletion of Krt24⁺ HFSCs experienced substantial mortality after ionizing irradiation. Notably, ionizing radiation triggered a marked expansion of tdTomato-labeled Krt24⁺ cells, accompanied by maintained hair follicle homeostasis. Taken together, this study established a Krt24-Cre^ERT2 mouse line targeting OB HFSCs, which are essential for hair follicle development and damage repair. Full article

The inner ear and/or lateral line are responsible for hearing and balance of vertebrate. The otic sensory hair cells (HCs) employ cilium organelles, namely stereocilia and/or kinocilia, to mediate mechanical stimuli to electrical signal transition. Tektins (Tekts) are known as the cilium microtubule stabilizer and inner-space filler, and four Tekt(1-4)-encoding genes are identified in zebrafish HCs, but the subcellular location of Tekts in HCs remains unknown. In the present study, we first found that tekt3 is expressed in the inner ear and lateral line neuromast. Antibody staining revealed that Tekt3 is present in neuromast and utricular HCs. It is absent in the saccule, the authentic hearing end-organ of zebrafish and the crista of semi-circular canals. Furthermore, Tekt3 were enriched at the apical side of neuromast and utricular HCs, mainly in the cytosol. Similar subcellular distribution of Tekt3 was also evident in the outer HCs of mature mouse cochlea, which are not directly linked to the hearing sense. However, only neuromast HCs exerted morphological defect of kinocilia in tekt3 mutant. The disrupted or distorted HC kinocilia of mutant neuromast ultimately resulted in slower vital dye intake, delayed HC regeneration after neomycin treatment, and reduced startle response to vibration stimulation. All functional defects of tekt3 mutant were largely rescued by wild-type tekt3 mRNA. Our study thus suggests that zebrafish Tekt3 maintains the integrity and function of neuromast kinocilia to against surrounding and persistent low-frequency noises, perhaps via the intracellular distribution of Tekt3. Nevertheless, TEKT3/Tekt3 could be used to clarify HC sub-types in both zebrafish and mice, to highlight the non-hearing HCs. Full article

Hair follicle stem cells, located in the bulge region of the outer root sheath, are multipotent epithelial stem cells capable of differentiating into epidermal, sebaceous gland, and hair shaft cells. Efficient culturing of these cells is crucial for advancements in dermatology, regenerative medicine, and skin model development. This investigation aimed to develop a protocol for isolating enriched bulge-derived epithelial cells from scalp specimens to produce tissue-engineered substitutes. The epithelium, including hair follicles, was separated from the dermis using thermolysin, followed by microdissection of the bulge region. Epithelial stem cells were isolated using enzymatic dissociation to create a single-cell suspension and compared with the direct explant culture and a benchmark method which isolates cells from the epidermis and pilosebaceous units. After 8 days of culture, the enzymatic digestion of microdissected bulges yielded 5.3 times more epithelial cells compared to explant cultures and proliferated faster than the benchmark method. Cells cultured from all methods exhibited comparable morphology and growth rates. The fully stratified epidermis of tissue-engineered skin was similar, indicating comparable differentiation potential. This enzymatic digestion method improved early-stage cell recovery and expansion while maintaining keratinocyte functionality, offering an efficient hair bulge cell-extraction technique for tissue engineering and regenerative medicine applications. Full article

Cisplatin (cis-diclorodiamminoplatin, CDDP) is a common chemotherapeutic agent for solid tumors, but its use is limited by severe side effects such as ototoxicity and nephrotoxicity. Variability in CDDP dosing and administration, along with high mortality and sensitivity in animal models, complicates experimental approaches. This study aimed to evaluate ototoxic damage in rats by comparing a single bolus versus three divided CDDP injections, also considering nephrotoxic effects. Twenty-four Sprague-Dawley rats were divided into three groups: eight received a single intraperitoneal injection of CDDP (14 mg/kg), eight received three injections (4.6 mg/kg/day), and eight were untreated controls. All CDDP-treated rats showed significant high-frequency hearing loss and morphological damage, including cochlear outer hair cell loss and renal glomerular atrophy with proximal tubule necrosis. Oxidative stress markers (nitrotyrosine and SOD1 expression) confirmed cochlear and renal alterations. Notably, the single bolus group had a 25% mortality rate and significant weight loss among survivors, unlike the other groups. This study introduces the novel finding that cumulative administration of three doses reduces mortality and weight loss while maintaining similar ototoxic and nephrotoxic effects. Therefore, cumulative administration is recommended for future studies to mitigate ototoxic and nephrotoxic damage, offering a potentially improved protocol for the administration of cisplatin. Full article

Saline–alkali environments restrict soybean production in China. Wild soybean genes can be used to improve the alkaline tolerance of cultivated soybean in molecular breeding. The expansin protein family promotes cell wall expansion. In this study, the relative expression levels of expansin family genes in wild soybean treated with 50 mM NaHCO₃ were measured at 0, 3, 6, and 12 h, and the relative expression of GsEXPA8 was found to be higher at 12 h. Wild soybean was treated with abscisic acid (ABA), indole-3-acetic acid (IAA), gibberellic acid (GA), and jasmonic acid (JA), and GsEXPA8 was found to respond to ABA and IAA signals. Sequence analysis shows that GsEXPA8 has DPBB_EXPA and expansin domains. Subcellular localization analysis shows that GsEXPA8 was localized in the cytoplasm in protoplasts and the cell membrane or wall in tobacco, indicating that it has nuclear membrane localization signals. GsEXPA8 overexpression reduced the malondialdehyde content in transgenic plants treated with NaHCO₃ and increased peroxidase activity before treatment. After the transformation of soybean roots from hair roots, GsEXPA8 was found to be expressed in the outer root cells and promote the development of thicker, shorter roots, thereby improving the plant’s alkaline tolerance. Stable GsEXPA8 transformation improved saline alkaline tolerance via the regulation of the alkali stress-related genes GmKIN1, GmRD22, GmDnaJA6, GmNFYC1, and GmMYB14. These findings provide support for further research on alkali-tolerance regulation pathways and molecular breeding for alkali tolerance. Full article

COVID-19 is an infectious disease caused by the SARS-CoV-2 virus. During and after COVID-19, audiovestibular symptoms and impairments have been reported. Objectives: This study aimed to investigate the impacts of COVID-19 on the peripheral and central auditory systems of children and adolescents following the acute COVID-19 phase based on behavioral, electroacoustic, and electrophysiological audiological assessments. Methods: This is a primary, prospective, observational, and cross-sectional study of 23 children aged 8 to 15 years who acquired confirmed COVID-19 and who, before infection, had not had any auditory complaints or school complications. The results were compared with pre-pandemic data collected from a similar group of 23 children who had normal peripheral and central hearing and good school performance. Each participant answered a questionnaire about child development, school, and health history and underwent tests including pure-tone audiometry and high-frequency audiometry, imitanciometry, transient evoked otoacoustic emissions, and distortion product otoacoustic emissions. They also received tests of Brainstem Auditory Evoked Potentials, Long Latency Auditory Evoked Potentials, Dichotic Digits Test, Sentence Identification Test, Dichotic Consonant–Vowel Test, Frequency Pattern Test, and Gaps-In-Noise Test. Results: Significant differences were observed between the groups, with the study group showing worse thresholds compared to the control group at both standard audiometric frequencies and at higher frequencies, although both groups were still within normal limits (p ≤ 0.05). In addition, the study group had a higher prevalence of absent responses, as identified by otoacoustic emissions and acoustic reflexes. In terms of central auditory performance, the study group showed ABRs with significantly longer latencies of waves I, III, and V compared to the control group. The study group also performed less well on the Dichotic Digits and Pediatric Speech Identification tests. Conclusions: COVID-19 appears to alter the auditory system, both peripherally at the level of the outer hair cells and more centrally. Full article

Cisplatin-induced ototoxicity occurs in approximately half of patients treated with cisplatin, and pediatric patients are more likely to be affected than adults. The oxidative stress elicited by cisplatin is a key contributor to the pathogenesis of ototoxicity. Notoginsenoside R1 (NGR1), the main bioactive compound of Panax notoginseng saponins, has antioxidant and antiapoptotic effects. This study investigated the ability of NGR1 to protect against cisplatin-induced damage in auditory HEI-OC1 cells and neonatal murine cochlear explants. The viability of HEI-OC1 cells treated with NGR1 and cisplatin was greater than that of cells treated with cisplatin alone. The results of Western blots and immunostaining for cleaved caspase-3 revealed that the level of cleaved caspase-3 in the cells treated with cisplatin was repressed by NGR1. NGR1 attenuated cisplatin-induced cytotoxicity in HEI-OC1 cells. Intracellular reactive oxygen species (ROS) were detected with a DCFDA assay and immunostaining for 4-HNE. The result revealed that its expression was induced by cisplatin and was significantly reduced by NGR1. Moreover, NGR1 can promote heme oxygenase-1 (HO-1) expression at both the mRNA and protein levels. ZNPPIX, an HO-1 inhibitor, was administered to cisplatin-treated cells to investigate the role of HO-1 in the protective effect of NGR1. The suppression of HO-1 activity by ZNPPIX markedly abolished the protective effect of NGR1 on cisplatin-treated cells. Therefore, NGR1 protects cells from cisplatin-induced damage by activating HO-1 and its antioxidative activity. In cochlear explants, NGR1 protects cochlear hair cells and attenuates cisplatin-induced ototoxicity by inhibiting ROS generation. In the group treated with cisplatin alone, prominent loss of outer hair cells and severe damage to the structure of the stereociliary bundles of inner and outer hair cells were observed. Compared with the group treated with cisplatin alone, less loss of outer hair cells (p = 0.009) and better preservation of the stereociliary bundles of hair cells were observed in the group treated with cisplatin and NGR1. In conclusion, these findings indicate that NGR1 can protect against cisplatin-induced ototoxicity by inducing HO-1 expression and suppressing oxidative stress. Full article

Sound vibrations generate electrical signals called cochlear potentials, which can reflect cochlear stereocilia movement and outer hair cells (OHC) mechanical activity. However, because the cochlear structure is delicate and complex, it is difficult for existing measurement techniques to pinpoint the origin of potentials. This limitation in measurement capability makes it difficult to fully understand the contribution of stereocilia and transduction channels to cochlear potentials. In view of this, firstly, this article obtains the stereocilia movement generated by basilar membrane (BM) vibration based on the positional relationship between the various structures of the organ Corti. Secondly, Kirchhoff’s law is used to establish an electric field model of the cochlear cavity, and the stereocilia movement is embedded in the electric field by combining the gated spring model. Finally, a force-electric coupling mathematical model of the cochlea is established. The results indicated that the resistance variation between different cavities in the cochlea leads to a sharp tuning curve. As the displacement of the BM increased, the longitudinal potential along the cochlea continued to move toward the base. The decrease in stereocilia stiffness reduced the deflection angle, thereby reducing the transduction current and lymphatic potential. Full article

Hearing loss is a health crisis that affects more than 60 million Americans. Currently, sodium thiosulfate is the only drug approved by the Food and Drug Administration (FDA) to counter hearing loss. Sirtuins were proposed as therapeutic targets in the search for new compounds or drugs to prevent or cure age-, noise-, or drug-induced hearing loss. Sirtuins are proteins involved in metabolic regulation with the potential to ameliorate sensorineural hearing loss. The mammalian sirtuin family includes seven members, SIRT1-7. This paper is a literature review on the sirtuins and their protective roles in sensorineural hearing loss. Literature search on the NCBI PubMed database and NUsearch included the keywords ‘sirtuin’ and ‘hearing’. Studies on sirtuins without relevance to hearing and studies on hearing without relevance to sirtuins were excluded. Only primary research articles with data on sirtuin expression and physiologic auditory tests were considered. The literature review identified 183 records on sirtuins and hearing. After removing duplicates, eighty-one records remained. After screening for eligibility criteria, there were forty-eight primary research articles with statistically significant data relevant to sirtuins and hearing. Overall, SIRT1 (n = 29) was the most studied sirtuin paralog. Over the last two decades, research on sirtuins and hearing has largely focused on age-, noise-, and drug-induced hearing loss. Past and current studies highlight the role of sirtuins as a mediator of redox homeostasis. However, more studies need to be conducted on the involvement of SIRT2 and SIRT4-7 in hearing protection. Full article

Sonic hedgehog (Shh) is a component of the Hedgehog signaling pathway, playing an important role in regulating cell proliferation, differentiation, apoptosis, and the repair of damaged organisms. To further clarify the expression pattern of Shh gene in the secondary hair follicle growth cycle of cashmere goats and its mechanism of action on secondary hair follicle papilla cells, and improve cashmere quality, in this study, we took Inner Mongolia Albas white cashmere goats as the research objects and collected skin samples at different growth stages to obtain secondary hair follicles, detected Shh and its gene expression by RT-qPCR, Western blot, immunohistochemistry, and other techniques, while we also cultured DPCs in vitro. Shh gene overexpression and interference vectors were constructed, and the effects of Shh gene on the proliferation and apoptosis of DPCs were studied through cell transfection technology. The results showed that there are significant differences in Shh and its gene expression in the secondary hair follicle growth cycle skins of cashmere goats, with the highest expression level in anagen, followed by catagen, and the lowest expression level in telogen. Shh was mainly expressed in the inner root sheath, outer root sheath, and secondary hair follicle papilla. After the overexpression of Shh gene, the proliferation and vitality of the hair papilla cells were enhanced compared to the interference group. After Shh gene interference, the apoptosis rate of the cells increased, indicating that Shh gene can regulate downstream Ptch, Smo, and Gli2 gene expression to promote the proliferation of DPCs, and thus form its expression pattern in the secondary hair follicle growth cycle of cashmere goats. Full article