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Tranylcypromine upregulates Sestrin 2 expression to ameliorate NLRP3-related noise-induced hearing loss

Neural Regeneration Research 2025年第5期20卷 1483-1494页

作者： Xihang Chen Zhifeng Chen Menghua Li Weiwei Guo Shuolong Yuan Liangwei Xu Chang Lin Xi Shi Wei Chen Shiming Yang Senior department of Otolaryngology Head and Neck Surgery Chinese PLA General HospitalChinese PLA Medical SchoolBeijingChina State Key Laboratory of hearing and Balance Science BeijingChina National Clinical Research Center for Otolaryngologic Diseases BeijingChina Key Laboratory of hearing Science Ministry of EducationBeijingChina Beijing Key Laboratory of hearing Impairment Prevention and Treatment BeijingChina department of Otorhinolaryngology Head and Neck Surgery The First Affiliated Hospital of Fujian Medical UniversityFuzhouFujian ProvinceChina department of Otolaryngology Head and Neck Surgery The 940th Hospital of Joint Logistics Support Force of Chinese PLALanzhouGansu ProvinceChina Key Laboratory of Tropical Biological Resources of Ministry of Education School of Pharmaceutical SciencesHainan UniversityHaikouHainan ProvinceChina Academician Workstation of Hainan University School of Pharmaceutical SciencesYazhou BaySanyaHainan ProvinceChina

Noise-induced hearing loss is the primary non-genetic factor contributing to auditory ***,there are currently no effective pharmacological interventions for patients with noise-induced hearing ***,we present evidence suggesting that the lysine-specific demethylase 1 inhibitor–tranylcypromine is an otoprotective agent that could be used to treat noise-induced hearing loss,and elucidate its underlying regulatory *** established a mouse model of permanent threshold shift hearing loss by exposing the mice to white broadband noise at a sound pressure level of 120 d B for 4 *** found that tranylcypromine treatment led to the upregulation of Sestrin2(SESN2)and activation of the autophagy markers light chain 3B and lysosome-associated membrane glycoprotein 1 in the cochleae of mice treated with *** noise exposure group treated with tranylcypromine showed significantly lower average auditory brainstem response hearing thresholds at click,4,8,and 16 k Hz frequencies compared with the noise exposure group treated with *** findings indicate that tranylcypromine treatment resulted in increased SESN2,light chain 3B,and lysosome-associated membrane glycoprotein 1 expression after noise exposure,leading to a reduction in levels of 4-hydroxynonenal and cleaved caspase-3,thereby reducing noise-induced hair cell ***,immunoblot analysis demonstrated that treatment with tranylcypromine upregulated SESN2 expression via the autophagy *** treatment also reduced the production of NOD-like receptor family pyrin domaincontaining 3(NLRP3)*** conclusion,our results showed that tranylcypromine treatment ameliorated cochlear inflammation by promoting the expression of SESN2,which induced autophagy,thereby restricting NLRP3-related inflammasome signaling,alleviating cochlear hair cell loss,and protecting hearing *** findings suggest that inhibiting lysine-specific demethylase 1 is a

关键词： 4-hydroxynonenal apoptosis autophagy cleaved caspase-3 inflammation NOD-like receptor family pyrin domain-containing 3(NLRP3) noise-induced hearing loss oxidative stress Sestrin2 tranylcypromine

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Small molecule inhibitor DDQ-treated hippocampal neuronal cells show improved neurite outgrowth and synaptic branching

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Neural Regeneration Research 2025年第9期20卷 2624-2632页

作者： Jangampalli Adi Pradeepkiran Priyanka Rawat Arubala P.Reddy Erika Orlov PHemachandra Reddy department of Internal Medicine Texas Tech University Health Sciences CenterLubbockTXUSA department of Nutritional Sciences College of Human SciencesTexas Tech UniversityLubbockTXUSA department of Pharmacology&Neuroscience Texas Tech University Health Sciences CenterLubbockTXUSA department of Neurology Texas Tech University Health Sciences CenterLubbockTXUSA department of Speech Language and Hearing SciencesTexas Tech University Health Sciences CenterLubbockTXUSA department of Public Health Texas Tech University Health Sciences CenterLubbockTXUSA

The process of neurite outgrowth and branching is a crucial aspect of neuronal development and *** and dendrites,sometimes referred to as neurites,are extensions of a neuron's cellular body that are used to start *** we explored the effects of diethyl(3,4-dihydroxyphenethylamino)(quinolin-4-yl)methylphosphonate(DDQ)on neurite developmental features in HT22 neuronal *** this work,we examined the protective effects of DDQ on neuronal processes and synaptic outgrowth in differentiated HT22cells expressing mutant Tau(mTau)*** investigate DDQ chara cteristics,cell viability,biochemical,molecular,western blotting,and immunocytochemistry were *** outgrowth is evaluated through the segmentation and measurement of neural *** neural processes can be seen and measured with a fluorescence microscope by manually tracing and measuring the length of the neurite *** neuronal processes can be observed and quantified with a fluorescent microscope by manually tracing and measuring the length of the neuronal ***-treated mTau-HT22 cells(HT22 cells transfected with cDNA mutant Tau)were seen to display increased levels of synaptophysin,MAP-2,andβ-***,we confirmed and noted reduced levels of both total and p-Tau,as well as elevated levels of microtubule-associated protein 2,β-tubulin,synaptophysin,vesicular acetylcholine transporter,and the mitochondrial biogenesis protein-pe roxisome prolife rator-activated receptor-gamma coactivator-1α.In mTa u-expressed HT22 neurons,we observed DDQ enhanced the neurite characteristics and improved neurite development through increased synaptic *** findings conclude that mTa u-HT22(Alzheimer's disease)cells treated with DDQ have functional neurite developmental chara *** key finding is that,in mTa u-HT22 cells,DDQ preserves neuronal structure and may even enhance nerve development function with mTa u inhibition.

关键词： diethyl(3 4-dihydroxyphenethylamino)(quinolin-4-yl)methylphosphonate(DDQ) hippocampal neuronal cells HT22 neurite outgrowth neuronal development small molecule

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Gain adjustment at tinnitus pitch to manage both tinnitus and speech perception in noise

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Journal of Otology 2019年第4期14卷 141-148页

作者： Hemanth Narayan Shetty Jijo Mathai Pottackal department of Audiology All India Institute of Speech and HearingMysuru570006India department of Speech and hearing JSS Institute of Speech and HearingDharwad580007India

To investigate how much gain variation is required from prescription to effect tinnitus percept,and if this revised prescription affects speech *** participants who experienced catastrophic tinnitus even after fitted with hearing aid were *** were grouped based on their tinnitus pitch and the prescriptive formula used to fit hearing *** were evaluated for handicap from tinnitus using Tinnitus Handicap Inventory(THI).hearing aid was programmed using either NAL-NL2 or DSL(I/o)v5 prescriptive formula and gain at tinnitus pitch was adjusted till the tinnitus get *** 50 was determined soon after fitted with hearing aid and 30 days of hearing aid ***,THI and international outcome inventory for hearing aid(IOI-HA)were determined after 30 days of hearing aid use.A significant higher gain adjustment was needed at tinnitus pitch to reduce tinnitus precept using NAL-NL2 than DSL(I/o)v5 prescriptive ***,SNR 50 was not affected by either tinnitus pitch or revised prescription ***,SNR 50 improved after 30 days of hearing aid use.A 76% of the participants’experienced habituation to perception after 30 days of hearing aid use,10% had slight,10% had mild,and 4% had a moderate degree of tinnitus on *** IOA-HA,96%(N=19)of participants have reported satisfactory,and 4%(N=1)reported moderate benefit from hearing *** of prescriptive formula adjusting gain at tinnitus pitch is an efficient method to reduce tinnitus symptoms and improve speech perception.

关键词： Amplification hearing loss Tinnitus Speech perception hearing aid

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Enhanced auditory evoked potentials in musicians:A review of recent findings

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Journal of Otology 2016年第2期11卷 63-72页

作者： Himanshu Kumar Sanju Prawin Kumar All India Institute of Speech and hearing department of Audiology All India Institute of Speech and Hearing

Auditory evoked potentials serve as an objective mode for assessment to check the functioning of the auditory system and *** has reported enhanced electrophysiological responses in musicians, which shows neuroplasticity in musicians. Various databases including Pub Med, Google, Google Scholar and Medline were searched for references related to auditory evoked potentials in musicians from 1994 till date. Different auditory evoked potentials in musicians have been summarized in the present article. The findings of various studies may support as evidences for music-induced neuroplasticity which can be used for the treatment of various clinical disorders. The search results showed enhanced auditory evoked potentials in musicians compared to non-musicians from brainstem to cortical levels. Also, the present review showed enhanced attentive and pre-attentive skills in musicians compared to non-musicians.

关键词： Neuroplasticity Auditory evoked potential Review Musicians Electrophysiological

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Pre-attentive auditory discrimination skill in Indian classical vocal musicians and non-musicians

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Journal of Otology 2016年第3期11卷 102-110页

作者： Himanshu Kumar Sanju Prawin Kumar All India Institute of Speech and hearing department of Audiology All India Institute of Speech and Hearing

Objective:To test for pre-attentive auditory discrimination skills in Indian classical vocal musicians and ***:Mismatch negativity(MMN) was recorded to test for pre-attentive auditory discrimination skills with a pair of stimuli of /1000 Hz/ and/1100 Hz/,with /1000 Hz/ as the frequent stimulus and /1100 Hz/ as the infrequent ***,offset and peak latencies were the considered latency parameters,whereas peak amplitude and area under the curve were considered for amplitude *** sample:Exactly 50 participants,out of which the experimental group had 25 adult Indian classical vocal musicians and 25 age-matched non-musicians served as the control group,were included in the *** group participants had a minimum professional music experience in Indian classic vocal music of 10 ***,control group participants did not have any formal training in ***:Descriptive statistics showed better waveform morphology in the experimental group as compared to the *** showed significantly better onset latency,peak amplitude and area under the curve in the experimental group but no significant difference in the offset and peak latencies between the two ***:The present study probably points towards the enhancement of pre-attentive auditory discrimination skills in Indian classical vocal musicians compared to *** indicates that Indian classical musical training enhances pre-attentive auditory discrimination skills in musicians,leading to higher peak amplitude and a greater area under the curve compared to non-musicians.

关键词： Neuronal plasticity Event-related potentials Music

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Adaptive hearing in the vocal plainfin midshipman fish:getting in tune for the breeding season and implications for acoustic communication

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Integrative Zoology 2009年第1期4卷 33-42页

作者： Joseph A.SISNEROS department of Psychology the Department of Biology and the Virginia Merrill Bloedel Hearing Research CenterUniversity of WashingtonSeattleUSA

The plainfin midshipman fish(Porichthys notatus Girard,1854)is a vocal species of batrachoidid fish that gen-erates acoustic signals for intraspecific communication during social and reproductive activity and has become a good model for investigating the neural and endocrine mechanisms of vocal-acoustic ***-tively active female plainfin midshipman fish use their auditory sense to detect and locate“singing”males,which produce a multiharmonic advertisement call to attract females for *** seasonal onset of male adver-tisement calling in the midshipman fish coincides with an increase in the range of frequency sensitivity of the female’s inner ear saccule,the main organ of hearing,thus leading to enhanced encoding of the dominant frequency components of male advertisement ***-reproductive females treated with either testosterone or 17β-estradiol exhibit a dramatic increase in the inner ear’s frequency sensitivity that mimics the reproductive fe-male’s auditory phenotype and leads to an increased detection of the male’s advertisement *** novel form of auditory plasticity provides an adaptable mechanism that enhances coupling between sender and receiver in vocal *** review focuses on recent evidence for seasonal reproductive-state and steroid-dependent plasticity of auditory frequency sensitivity in the peripheral auditory system of the midshipman *** potential steroid-dependent mechanism(s)that lead to this novel form of auditory and behavioral plasticity are also dis-cussed.

关键词： auditory plasticity hair cells saccule sex steroids tuning.

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Shrinkage of ipsilateral taste buds and hyperplasia of contralateral taste buds following chorda tympani nerve transection

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Neural Regeneration Research 2015年第6期10卷 989-995页

作者： Yi-ke Li Juan-mei Yang Yi-bo Huang Dong-dong Ren Fang-lu Chi department of Otology and Skull Base Surgery Eye Ear Nose & Throat HospitalFudan University Shanghai Auditory Medical Center Key Laboratory of hearing Science Ministry of Health department of hearing and Speech Sciences Vanderbilt University

The morphological changes that occur in the taste buds after denervation are not well under- stood in rats, especially in the contralateral tongue epithelium. In this study, we investigated the time course of morphological changes in the taste buds following unilateral nerve transection. The role of the trigeminal component of the lingual nerve in maintaining the structural integrity of the taste buds was also examined. Twenty-four Sprague-Dawley rats were randomly divided into three groups： control, unilateral chorda tympani nerve transection and unilateral chorda tympani nerve transection ＋ lingual nerve transection. Rats were allowed up to 42 days of re- covery before being euthanized. The taste buds were visualized using a cytokeratin 8 antibody. Taste bud counts, volumes and taste receptor cell numbers were quantified and compared among groups. No significant difference was detected between the chorda tympani nerve transection and chorda tympani nerve transection ＋ lingual nerve transection groups. Taste bud counts, volumes and taste receptor cell numbers on the ipsilateral side all decreased significantly compared with control. On the contralateral side, the number of taste buds remained unchanged over time, but they were larger, and taste receptor cells were more numerous postoperatively. There was no evidence for a role of the trigeminal branch of the lingual nerve in maintaining the structural integrity of the anterior taste buds.

关键词： nerve regeneration gustation cytokeratin tongue epithelium immunohistochemistry taste bud trigeminal nerve disorder NSFC grants neural regeneration

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The relationship between age,acceptable noise level,and listening effort in middle-aged and older-aged individuals

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Journal of Otology 2023年第4期18卷 220-229页

作者： Hemanth Narayan Shetty Suma Raju Sanjana Singh S department of Audiology JSS Institute of Speech and HearingMysuruKarnatakaIndia department of Speech-Language Pathology JSS Institute of Speech and HearingMysuruKarnatakaIndia

Objective:The purpose of the study was to evaluate listening effort in adults who experience varied annoyance towards *** and methods:Fifty native Kannada-speaking adults aged 41e68 years *** evaluated the participant's acceptable noise level while listening to ***,a sentence-final wordidentification and recall test at 0 dB SNR(less favorable condition)and 4 dB SNR(relatively favorable condition)was used to assess listening *** repeat and recall scores were obtained for each ***:The regression model revealed that the listening effort increased by 0.6%at 0 dB SNR and by 0.5%at 4 dB SNR with every one-year advancement in *** effort increased by 0.9%at 0 dB SNR and by 0.7%at 4 dB SNR with every one dB change in the value of Acceptable Noise Level(ANL).At 0 dB SNR and 4 dB SNR,a moderate and mild negative correlation was noted respectively between listening effort and annoyance towards noise when the factor age was ***:Listening effort increases with age,and its effect is more in less favorable than in relatively favorable ***,if the annoyance towards noise was controlled,the impact of age on listening effort was *** effort correlated with the level of annoyance once the age effect was ***,the listening effort was predicted from the ANL to a moderate degree.

关键词： Listening effort Acceptable noise level Cognitive reservoir Repeat and recall task

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Binaural integration abilities in bilateral cochlear implant user

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Journal of Otology 2015年第4期10卷 150-153页

作者： Chie Obuchi Masae Shiroma Sayaka Ogane Kimitaka Kaga department of Speech and hearing Sciences International University of Health and Welfare

Bilateral Cochlear implants (CIs) improved speech intelligibility, speech perception in background noise, and sound localization in quiet and noisy situations. However, it is unclear whether these advantages essentially result in binaural integration of acoustic stimuli from each ear. In this study, we investigated the effectiveness of binaural integration by bilateral CIs placement using binaural hearing tests and subjective auditory perceptual assessment. A 61-year-old bilateral CIs subject underwent the following four tests:the Japanese hearing in Noise Test (HINT-J), the dichotic listening test (DLT), the Rapidly Alternating Speech Perception (RASP) test, and subjective auditory perceptual assessment. The HINT-J score was significantly higher for bilateral CIs than for a unilateral CI. However, DLT and the RASP test revealed contradictory results. Subjective auditory perceptual assessment revealed active and bright impressions for bilateral hearing, which were also noisy and strong compared with those for unilateral hearing. The results of this study revealed that bilateral CIs improved speech perception in background noise and an improved auditory impression, although the bilateral integration abilities were not improved. This was probably because the patient was required to combine information from the two ears into a single perception in DLT and the RASP test. More longitudinal data should be collected and analyzed in future studies to evaluate the long-term effects of bilateral CIs. Copyright ? 2016, PLA General Hospital department of Otolaryngology Head and Neck Surgery. Production and hosting by Elsevier (Singapore) Pte Ltd. This is an open access article under the CC BY-NC-ND license (http://***/licenses/by-nc-nd/4.0/).

关键词： Bilateral cochlear implants Binaural integration ability Subjective auditory perceptual assessment

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A systematic review on the imaging findings in auditory neuropathy spectrum disorder

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Journal of Otology 2024年第3期19卷 166-172页

作者： Supriya Mathew Chandni Jain department of Audiology All India Institute of Speech and HearingMysuruKarnatakaIndia

Purpose:The present systematic review examined imaging findings in the Auditory Neuropathy Spectrum Disorder(ANSD)***:Electronic databases such as Pub Med,Google Scholar,J Gate,and Science Direct were used to conduct a literature *** articles retrieved through the literature search were assessed in two *** the first stage,title and abstract screening were done;in the second stage,a full-length article review was *** the 379 shortlisted records,19 articles were chosen for the full-length ***:The selected articles performed imaging using Computerized tomography(CT)and magnetic resonance imaging(MRI).In most studies,cochlear nerve deficiency(CND)was the most prevalent anomaly in the ANSD ***,MRI was the imaging modality of choice recommended in most *** was also noted that CND was a characteristic feature of unilateral ***:From this systematic review,it is clear that integrating imaging studies into diagnostic protocol would help to understand the underlying pathology better and expedite decision-making and intervention for ANSD patients.

关键词： ANSD Imaging Computerized tomography Magnetic resonance imaging Cochlear nerve deficiency

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