Cisplatin is a first-line chemotherapeutic agent in the treatment of malignant tumors with remarkable clinical effects and low cost. However, the ototoxicity and neurotoxicity of cisplatin greatly limit its clinical application. This article reviews the possible pathways and molecular mechanisms of cisplatin trafficking from peripheral blood into the inner ear, the toxic response of cisplatin to inner ear cells, as well as the cascade reactions leading to cell death. Moreover, this article highlights the latest research progress in cisplatin resistance mechanism and cisplatin ototoxicity. Two effective protective mechanisms, anti-apoptosis and mitophagy activation, and their interaction in the inner ear are discussed. Additionally, the current clinical preventive measures and novel therapeutic agents for cisplatin ototoxicity are described. Finally, this article also forecasts the prospect of possible drug targets for mitigating cisplatin-induced ototoxicity. These include the use of antioxidants, inhibitors of transporter proteins, inhibitors of cellular pathways, combination drug delivery methods, and other mechanisms that have shown promise in preclinical studies. Further research is needed to evaluate the efficacy and safety of these approaches.

Myelin undergoes various changes after nerve injury, and c‐Jun has a close relationship with Schwann cells (SCs). However, it remains unclear whether c‐Jun can be involved in nerve repair by regulating ferroptosis. To explore this, we first set up a facial nerve injury model and detected the changes of ferroptosis‐related proteins and c‐Jun by immunofluorescence and Western blot. Then, we cultured RSC 96 and pSCs, and studied the potential regulatory relationships by a combination of experimental methods such as CCK‐8, ELISA, immunofluorescence, qRT‐PCR, Western blot and viral transfection. Finally, we corroborated the role of c‐Jun through animal experiments. Our experiments revealed that ferroptosis occurs after facial nerve injury. Erastin decreased GPX4, c‐Jun proteins and GSH content, while PTGS2, NRF2, HO‐1 proteins, MDA, Fe²⁺ and ROS contents increased. This effect was inhibited after c‐Jun overexpression but was reversed after the addition of c‐Jun siRNA. Besides, we proved in vivo that c‐Jun could inhibit ferroptosis and promote the recovery of facial nerve function. In conclusion, our study identified the relationship between c‐Jun and ferroptosis during peripheral nerve injury repair, which provides new ideas for studying peripheral nerve injury and repair.

Resveratrol is a non-flavonoid polyphenol compound that exists in many plants, and is considered an antitoxin. This study explores the effects from the regulation of miR-455-5p by resveratrol on cisplatin-induced ototoxicity via the PTEN–PI3K–AKT signaling pathway. For this, House Ear Institute–Organ of Corti 1 (HEI-OC1) cells were transfected with miR-455-5p inhibitor and treated with cisplatin and resveratrol, then cell proliferation, apoptosis, and oxidative stress were evaluated. A mouse model of hearing loss was established, and these mice were treated with cisplatin, resveratrol, or cisplatin combined with resveratrol, by intraperitoneal injection. The auditory brainstem response (ABR) threshold was measured, and hair cells were examined using immunofluorescence staining. The expression levels of miR-455-5p, PTEN, and PI3K/Akt proteins were examined. The results from our in-vitro experiments indicate that resveratrol promoted viability and reduced apoptosis and oxidative stress in cisplatin-induced HEI-OC1 cells. Resveratrol upregulated miR-455-5p, downregulated PTEN, and activated the PI3K–Akt axis. These effects of resveratrol were reversed by knock-down of miR-455-5p. The results from our in-vivo experiments indicate that resveratrol protected hearing and inhibited the hair-cell injury caused by cisplatin ototoxicity. Resveratrol also upregulated miR-455-5p, downregulated PTEN, and activated the PTEN–PI3K–Akt axis in cochlear tissues from cisplatin-treated mice. These results indicate that resveratrol upregulates miR-455-5p to target PTEN and activate the PI3K–Akt signaling pathway to counteract cisplatin ototoxicity.

Objective: Our aim was to determine the correlation between cognitive impairment and P300 event-related potential (ERP) in older adults with vertigo and imbalance, which further provides a reference for clinical diagnosis and patients’ rehabilitation. Methods: A total of 79 older adult patients with vertigo and imbalance in our outpatient department from January 2022 to December 2022 were selected and divided into the mild group (n = 20), moderate group (n = 39), and severe group (n = 20) according to the Dizziness Handicap Inventory (DHI). The auditory P300 component of event-related potentials (ERPs), Generalized Anxiety Disorder Questionnaire-7 (GAD-7), Patient Health Questionnaire-9 (PHQ-9), and Mini-Mental State Examination (MMSE) were used to evaluate depression, anxiety, and cognitive function in these patients, respectively. Results: The P300 latencies of the different severity groups were 292 ± 10 ms, 301 ± 8 ms, and 328 ± 5 ms, respectively, and the differences were statistically significant (p = 0.010). The P300 amplitudes of the different severity groups were 14.4 ± 2.6 μV, 3.9 ± 0.8 μV, and 5.1 ± 1.4 μV, respectively, and the differences were also statistically significant (p = 0.004). There was no statistically significant difference in the DHI evaluation or VAS visual simulation scoring between the two groups (p = 0.625, and 0.878, respectively). Compared with the short-course group, the long-course group showed prolonged P300 latency and decreased amplitude, higher scores in PHQ-9 and GAD-7, and lower scores in MMSE, and all the differences were statistically significant (p = 0.013, 0.021, 0.006, 0.004, and 0.018, respectively). Conclusion: Older patients with more severe symptoms of vertigo and imbalance are at higher risk of developing abnormal cognitive function. The P300 can be used as an objective neurophysiological test for the assessment of cognitive function relevant to elderly patients with vertigo and imbalance.