Hsp70/Bmi1-FoxO1-SOD Signaling Pathway Contributes to the Protective Effect of Sound Conditioning against Acute Acoustic Trauma in a Rat Model.

Sound conditioning (SC) is defined as "toughening" to lower levels of sound over time, which reduces a subsequent noise-induced threshold shift. Although the protective effect of SC in mammals is generally understood, the exact mechanisms involved have not yet been elucidated. To confirm the protective effect of SC against noise exposure (NE) and the stress-related signaling pathway of its rescue, we observed target molecule changes caused by SC of low frequency prior to NE as well as histology analysis in vivo and verified the suggested mechanisms in SGNs in vitro. Further, we investigated the potential role of Hsp70 and Bmi1 in SC by targeting SOD1 and SOD2 which are regulated by the FoxO1 signaling pathway based on mitochondrial function and reactive oxygen species (ROS) levels. Finally, we sought to identify the possible molecular mechanisms associated with the beneficial effects of SC against noise-induced trauma. Data from the rat model were evaluated by western blot, immunofluorescence, and RT-PCR. The results revealed that SC upregulated Hsp70, Bmi1, FoxO1, SOD1, and SOD2 expression in spiral ganglion neurons (SGNs). Moreover, the auditory brainstem responses (ABRs) and electron microscopy revealed that SC could protect against acute acoustic trauma (AAT) based on a significant reduction of hearing impairment and visible reduction in outer hair cell loss as well as ultrastructural changes in OHCs and SGNs. Collectively, these results suggested that the contribution of Bmi1 toward decreased sensitivity to noise-induced trauma following SC was triggered by Hsp70 induction and associated with enhancement of the antioxidant system and decreased mitochondrial superoxide accumulation. This contribution of Bmi1 was achieved by direct targeting of SOD1 and SOD2, which was regulated by FoxO1. Therefore, the Hsp70/Bmi1-FoxO1-SOD signaling pathway might contribute to the protective effect of SC against AAT in a rat model.

[A modified STOP-Bang questionnaire for OSA screening in the young, middle-age women].

Objective:The STOP-Bang（S-B） questionnaire is widely used for screening patients with OSA. However, BMI and NC cutoff value in the original S-B questionnaire is 35 kg/m²and 40cm, the BMI and NC value in the young and middle-aged female patients in China is lower than that. We aimed to establish a more appropriate modified STOP-Bang（MS-B） questionnaire. Method:A total of 523 cases with suspected OSA in the young and middle-aged female were included in this study. All patients were asked to completed the S-B, MS-B questionnaire and undergo overnight polysomnography（PSG）. The BMI and NC value of the MS-B were determined by the optimal operating points of the ROC. The ability of S-B and MS-B were assessed by ROC and McNemar's test. Result:BMI=28 kg/m²and NC=36 cm as alternative cutoff is to refine S-B questionnaire. When taking apnea hypopnea index（AHI） ≥5 times/h, ≥15 times/h and ≥30 times/h as cut-offs, MS-B had higher sensitivity（88.7% vs 86.7%, 92.8% vs 87.7%, 95.0% vs 90.1%, respectively） and the area under the curve（0.74 vs 0.706, 0.734 vs 0.703, 0.739 vs 0.699, respectively） than S-B. There were significant differences in McNemar test（P<0.05）. Conclusion:This study examined the clinical utility of MS-B. MS-B may improve predictive performance of S-B questionnaire in the young and middle-aged female with OSA.

Noise alters guinea pig's blood-labyrinth barrier ultrastructure and permeability along with a decrease of cochlear Claudin-5 and Occludin.

BACKGROUND: Noise exposure (NE) is a severe modern health hazard that induces hearing impairment. However, the noise-induced ultrastructural changes of blood-labyrinth barrier (BLB) and the potential involvements of tight junction proteins (TJP) remain inconclusive. We investigated the effects of NE on not only the ultrastructure of cochlea and permeability of BLB but also the expression of TJP within the guinea pig cochlea. RESULTS: Male albino guinea pigs were exposed to white noise for 4 h or 2 consecutive days (115 dB sound pressure level, 6 hours per day) and the hearing impairments and light microscopic change of BLB were evaluated with auditory brainstem responses (ABR) and the cochlear sensory epithelia surface preparation, respectively. The cochlear ultrastructure and BLB permeability after NE 2d were revealed with transmission electron microscope (TEM) and lanthanum nitrate-tracing techniques, respectively. The potential alterations of TJPs Claudin-5 and Occludin were quantified with immunohistochemistry and western blot. NE induced significant hearing impairment and NE 2d contributed to significant outer hair cell (OHC) loss that is most severe in the first row of outer hair cells. Furthermore, the loosen TJ and an obvious leakage of lanthanum nitrate particles beneath the basal lamina were revealed with TEM. Moreover, a dose-dependent decrease of Claudin-5 and Occludin was observed in the cochlea after NE. CONCLUSIONS: All these findings suggest that both decrease of Claudin-5 and Occludin and increased BLB permeability are involved in the pathologic process of noise-induced hearing impairment; however, the causal relationship and underlying mechanisms should be further investigated.