www.HearingLossTreatmentReport.com
https://www.frontiersin.org/articles/10.3389/fncel.2021.735723/full
The Expression and Roles of the Super Elongation Complex in Mouse Cochlear Lgr5+ Progenitor Cells
Super Elongation Complex might play important roles in regulating inner ear progenitors and regulating hair cell regeneration.
https://www.cell.com/stem-cell-reports/fulltext/S2213-6711(21)00428-8
High-throughput screening on cochlear organoids identifies VEGFR-MEK-TGFB1 signaling promoting hair cell reprogramming
VEGFR-MEK-TGFB1 signaling crosstalk as a potential target for hair cell regeneration and hearing restoration.
CATEGORY:
Research
SCREENSHOT:
TITLE:
miR-153/KCNQ4 axis contributes to noise-induced hearing loss in a mouse model
CONTENT:
J Physiol Sci. 2021 Sep 3;71(1):28. doi: 10.1186/s12576-021-00814-0.
ABSTRACT
Damage to the cochlear sensory epithelium is a key contributor to noise-induced sensorineural hearing loss (SNHL). KCNQ4 plays an important role in the cochlear potassium circulation and outer hair cells survival. As miR-153 can target and regulate KCNQ4, we sought to study the role of miR-153 in SNHL. 12-week-old male CBA/J mice were exposed to 2-20 kHz broadband noise at 96 dB SPL to induce temporary threshold shifts and 101 dB SPL to induce permanent threshold shifts. Hearing loss was determined by auditory brainstem responses (ABR). Relative expression of miR-153 and KCNQ4 in mice cochlea were determined by Real-Time quantitative PCR. miR-153 mimics were co-transfected with wild type or mutated KCNQ4 into HEK293 cells. Luciferase reporter assay was used to validate the binding between miR-153 and KCNQ4. AAV-sp-153 was constructed and administrated intra-peritoneally 24- and 2-h prior and immediately after noise exposure to knockdown miR-153. The KCNQ4 is mainly expressed in outer hair cells (OHCs). We showed that the expression of KCNQ4 in mice cochlea was reduced and miR-153 expression was significantly increased after noise exposure compared to control. miR-153 bound to 3’UTR of KNCQ4, and the knockdown of miR-153 with the AAV-sp-153 administration restored KCNQ4 mRNA and protein expression. In addition, the knockdown of miR-153 reduced ABR threshold shifts at 8, 16, and 32 kHz after permanent threshold shifts (PTS) noise exposure. Correspondingly, OHC losses were attenuated with inhibition of miR-153. This study demonstrates that miR-153 inhibition significantly restores KNCQ4 in cochlea after noise exposure, which attenuates SNHL. Our study provides a new potential therapeutic target in the prevention and treatment of SNHL.
PMID:34479475 | DOI:10.1186/s12576-021-00814-0
SOURCE:
The journal of physiological sciences : JPS
PUBLISHER:
PMID:
pubmed:34479475
ID:
0b58ea4968e09ff10f4e1238c494f316pubmed:34479475
DOI:
10.1186/s12576-021-00814-0
DATE – PUBLISHED:
Sat, 04 Sep 2021 06:00:00 -0400
DATE – DOI:
2021-09-03T15:08:12Z
DATE – ADDED:
09/04/21 09:14AM
LINK – PUBMED:
https://pubmed.ncbi.nlm.nih.gov/34479475/
LINK – DOI:
https://doi.org/10.1186/s12576-021-00814-0
LINK – PUBLISHER:
https://jps.biomedcentral.com/articles/10.1186/s12576-021-00814-0?utm_source=hearinglosstreatmentreport.com
IMAGE:
REFERENCE:
Hearing Loss Treatment Report, Urgent Research, 2021-09-04T13:14:45+00:00, https://www.hearinglosstreatmentreport.com.
CATEGORY:
Research
SCREENSHOT:
TITLE:
The expression of PHB2 in the cochlea: possible relation to age-related hearing loss
CONTENT:
Cell Biol Int. 2021 Aug 26. doi: 10.1002/cbin.11693. Online ahead of print.
ABSTRACT
Age-related hearing loss (ARHL) is the most prevalent sensory deficit in the elderly, but its mechanism remains unclear. Scaffold protein Prohibitin 2 (PHB2) has been widely involved in aging and neurodegeneration. However, the role of PHB2 in ARHL is undeciphered to date. To investigate the expression pattern and the role of PHB2 in ARHL, we used C57BL/6 mice and HEI-OC1 cell line as models. In our study, we have found PHB2 exists in the cochlea and is expressed in hair cells, spiral ganglion neurons and HEI-OC1 cells. In mice with ARHL, mitophagy is reduced and correspondingly the expression level of PHB2 is decreased. Moreover, after H2 O2 treatment the mitophagy is activated and the PHB2 expression is increased. These findings indicate that PHB2 may exert an important role in ARHL through mitophagy. Findings from this work will be helpful for elucidating the mechanism underlying the ARHL and for providing a new target for ARHL treatment. This article is protected by copyright. All rights reserved.
PMID:34435719 | DOI:10.1002/cbin.11693
SOURCE:
Cell biology international
PUBLISHER:
PMID:
pubmed:34435719
ID:
0b58ea4968e09ff10f4e1238c494f316pubmed:34435719
DOI:
10.1002/cbin.11693
DATE – PUBLISHED:
Thu, 26 Aug 2021 06:00:00 -0400
DATE – DOI:
2021-08-26T11:36:01Z
DATE – ADDED:
08/26/21 02:11PM
LINK – PUBMED:
https://pubmed.ncbi.nlm.nih.gov/34435719/
LINK – DOI:
https://doi.org/10.1002/cbin.11693
LINK – PUBLISHER:
https://onlinelibrary.wiley.com/doi/10.1002/cbin.11693?utm_source=hearinglosstreatmentreport.com
IMAGE:
REFERENCE:
Hearing Loss Treatment Report, Urgent Research, 2021-08-26T18:11:08+00:00, https://www.hearinglosstreatmentreport.com.
https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC8417573/
Research Progress on the Mechanism of Cochlear Hair Cell Regeneration
CATEGORY:
Research
SCREENSHOT:
TITLE:
Downregulation of Cav3.1 T-type Calcium Channel Expression in Age-related Hearing Loss Model
CONTENT:
Curr Med Sci. 2021 Aug;41(4):680-686. doi: 10.1007/s11596-021-2416-0. Epub 2021 Aug 17.
ABSTRACT
OBJECTIVE: Age-related hearing loss (AHL), characterized by degeneration of cochlea structures, is the most common sensory disorder among the elderly worldwide. The calcium channel is considered to contribute to normal hearing. However, the role of the T-type voltage-activated calcium channel, Cav3.1, remains unclear in AHL. Here, we investigate the age-related change of Cav3.1 expression in the cochlea and D-gal-induced senescent HEI-OC1 cells.
METHODS: Cochleae from C57BL/6 mice at 2 months and 12 months of age were assessed. Senescence in House Ear Institute-Organ of Corti 1 (HEI-OC1) cells was induced by D-gal treatment. The immunofluorescence technique was employed to investigate the distribution of Cav3.1 in vivo and in vitro. Quantitative assessment was achieved by Western blotting and real-time PCR.
RESULTS: In comparison with 2-month-old animals, 12-month old C57BL/6 mice exhibited great loss of hair cells and elevated auditory brainstem threshold. The Cav3.1 was located in hair cells, spiral ganglion cells, lateral walls, and the expression of Cav3.1 protein and mRNA decreased in the aged cochleae. D-gal-induced senescence assay confirmed the down-regulation of Cav3.1 expression in senescent HEI-OC1 cells.
CONCLUSION: Our results show that age-related down-regulated expression of Cav3.1 in the cochleae is associated with AHL and may contribute to the pathogenesis of AHL.
PMID:34403092 | DOI:10.1007/s11596-021-2416-0
SOURCE:
Current medical science
PUBLISHER:
PMID:
pubmed:34403092
ID:
0b58ea4968e09ff10f4e1238c494f316pubmed:34403092
DOI:
10.1007/s11596-021-2416-0
DATE – PUBLISHED:
Tue, 17 Aug 2021 06:00:00 -0400
DATE – DOI:
2021-08-17T10:36:41Z
DATE – ADDED:
08/17/21 07:00PM
LINK – PUBMED:
https://pubmed.ncbi.nlm.nih.gov/34403092/
LINK – DOI:
https://doi.org/10.1007/s11596-021-2416-0
LINK – PUBLISHER:
https://link.springer.com/10.1007/s11596-021-2416-0?utm_source=hearinglosstreatmentreport.com
IMAGE:
REFERENCE:
Hearing Loss Treatment Report, Urgent Research, 2021-08-17T23:00:52+00:00, https://www.hearinglosstreatmentreport.com.
https://www.sciencedirect.com/science/article/abs/pii/S1534580721005591?via%3Dihub
Enhancer decommissioning imposes an epigenetic barrier to sensory hair cell regeneration
https://www.cell.com/molecular-therapy-family/molecular-therapy/pdf/S1525-0016(21)00367-1.pdf
https://www.frontiersin.org/articles/10.3389/fncel.2021.666706/full
https://www.hindawi.com/journals/np/2021/4784385/
Noise-Induced Hearing Loss: Updates on Molecular Targets and Potential Interventions
Reestablishing Neural Plasticity in Regenerated Spiral Ganglion Neurons and Sensory Hair Cells for Hearing Loss
CATEGORY:
Research
SCREENSHOT:
TITLE:
mTOR Signaling in the Inner Ear as Potential Target to Treat Hearing Loss
CONTENT:
Int J Mol Sci. 2021 Jun 14;22(12):6368. doi: 10.3390/ijms22126368.
ABSTRACT
Hearing loss affects many people worldwide and occurs often as a result of age, ototoxic drugs and/or excessive noise exposure. With a growing number of elderly people, the number of people suffering from hearing loss will also increase in the future. Despite the high number of affected people, for most patients there is no curative therapy for hearing loss and hearing aids or cochlea implants remain the only option. Important treatment approaches for hearing loss include the development of regenerative therapies or the inhibition of cell death/promotion of cell survival pathways. The mammalian target of rapamycin (mTOR) pathway is a central regulator of cell growth, is involved in cell survival, and has been shown to be implicated in many age-related diseases. In the inner ear, mTOR signaling has also started to gain attention recently. In this review, we will emphasize recent discoveries of mTOR signaling in the inner ear and discuss implications for possible treatments for hearing restoration.
PMID:34198685 | DOI:10.3390/ijms22126368
SOURCE:
International journal of molecular sciences
PUBLISHER:
PMID:
pubmed:34198685
ID:
0b58ea4968e09ff10f4e1238c494f316pubmed:34198685
DOI:
10.3390/ijms22126368
DATE – PUBLISHED:
Fri, 02 Jul 2021 06:00:00 -0400
DATE – DOI:
2021-06-15T02:31:04Z
DATE – ADDED:
07/02/21 08:07AM
LINK – PUBMED:
https://pubmed.ncbi.nlm.nih.gov/34198685/
LINK – DOI:
https://doi.org/10.3390/ijms22126368
LINK – PUBLISHER:
https://www.mdpi.com/1422-0067/22/12/6368?utm_source=hearinglosstreatmentreport.com
IMAGE:
REFERENCE:
Hearing Loss Treatment Report, Urgent Research, 2021-07-02T12:07:25+00:00, https://www.hearinglosstreatmentreport.com.
https://www.mdpi.com/1422-0067/22/11/6158/htm
Roles of Key Ion Channels and Transport Proteins in Age-Related Hearing Loss
CATEGORY:
Research
SCREENSHOT:
TITLE:
Inhalation of Molecular Hydrogen, a Rescue Treatment for Noise-Induced Hearing Loss
CONTENT:
Front Cell Neurosci. 2021 Jun 1;15:658662. doi: 10.3389/fncel.2021.658662. eCollection 2021.
ABSTRACT
Noise exposure is the most important external factor causing acquired hearing loss in humans, and it is strongly associated with the production of reactive oxygen species (ROS) in the cochlea. Several studies reported that the administration of various compounds with antioxidant effects can treat oxidative stress-induced hearing loss. However, traditional systemic drug administration to the human inner ear is problematic and has not been successful in a clinical setting. Thus, there is an urgent need to develop rescue treatment for patients with acute acoustic injuries. Hydrogen gas has antioxidant effects, rapid distribution, and distributes systemically after inhalation.The purpose of this study was to determine the protective efficacy of a single dose of molecular hydrogen (H2 ) on cochlear structures. Guinea pigs were divided into six groups and sacrificed immediately after or at 1 or 2 weeks. The animals were exposed to broadband noise for 2 h directly followed by 1-h inhalation of 2% H2 or room air. Electrophysiological hearing thresholds using frequency-specific auditory brainstem response (ABR) were measured prior to noise exposure and before sacrifice. ABR thresholds were significantly lower in H2 -treated animals at 2 weeks after exposure, with significant preservation of outer hair cells in the entire cochlea. Quantification of synaptophysin immunoreactivity revealed that H2 inhalation protected the cochlear inner hair cell synaptic structures containing synaptophysin. The inflammatory response was greater in the stria vascularis, showing increased Iba1 due to H2 inhalation.Repeated administration of H2 inhalation may further improve the therapeutic effect. This animal model does not reproduce conditions in humans, highlighting the need for additional real-life studies in humans.
PMID:34140880 | PMC:PMC8205059 | DOI:10.3389/fncel.2021.658662
SOURCE:
Frontiers in cellular neuroscience
PUBLISHER:
PMID:
pubmed:34140880
ID:
0b58ea4968e09ff10f4e1238c494f316pubmed:34140880
DOI:
10.3389/fncel.2021.658662
DATE – PUBLISHED:
Fri, 18 Jun 2021 06:00:00 -0400
DATE – DOI:
2021-06-01T05:34:01Z
DATE – ADDED:
06/18/21 01:25PM
LINK – PUBMED:
https://pubmed.ncbi.nlm.nih.gov/34140880/
LINK – DOI:
https://doi.org/10.3389/fncel.2021.658662
LINK – PUBLISHER:
https://www.frontiersin.org/articles/10.3389/fncel.2021.658662/full?utm_source=hearinglosstreatmentreport.com
IMAGE:
REFERENCE:
Hearing Loss Treatment Report, Urgent Research, 2021-06-18T17:25:36+00:00, https://www.hearinglosstreatmentreport.com.
CATEGORY:
Research
SCREENSHOT:
TITLE:
Effects of Insulin-Like Growth Factor (IGF-1) in Patients with Sensorineural Hearing Loss
CONTENT:
J Int Adv Otol. 2021 May;17(3):207-214. doi: 10.5152/iao.2021.8549.
ABSTRACT
OBJECTIVES: (1) To test the effect of local administration of insulin-like growth factor-1 (IGF-1) in patients with sensorineural hearing loss (SNHL). (2) To test the effect of local administration of IGF-1 in patients with ototoxicity.
METHODS: Forty patients with SNHL were included in the study. Their hearing thresholds at different frequencies (0.5, 1, 2, and 4 kHz) along with the average hearing threshold were noted. The patients were then randomly allocated to 2 groups and were treated with IGF-1 via one of the following routes: (1) intratympanic injection and (2) Gelfoam. Patients were followed-up at weekly intervals for 6 weeks but follow-up PTA was done at 3 weeks, 6 weeks, and 6 months only.
RESULTS: Forty patients (25 male, 15 female) participated in the study. Their age ranged from 13 to 63 years, with a mean of 31.3 years. Nineteen (47.5%) patients exhibited some degree of recovery after 6 months of follow-up, while 21 (52.5%) did not exhibit any recovery. Fourteen (35%) patients showed slight recovery (SR), 1 (4%) patient showed marked recovery, and complete recovery was observed in 4 (10%) patients. Twelve of the 20 patients who underwent treatment using Gelfoam showed improvement in hearing (measured as a reduction in hearing threshold), while only 7 of the 20 patients who underwent intratympanic injection showed such improvement. Among adverse reactions, the most common was pain (88%) which typically did not last beyond 3 days. Other adverse reactions observed were dizziness (24%) and headache (20%). One patient suffered from acute suppurative otitis media (ASOM) and had a perforation in the tympanic membrane. However, this was treated successfully with medications.
CONCLUSION: Intratympanic IGF-1 is a novel drug that has shown early promise in controlling and reversing SNHL.
PMID:34100744 | DOI:10.5152/iao.2021.8549
SOURCE:
The journal of international advanced otology
PUBLISHER:
PMID:
pubmed:34100744
ID:
0b58ea4968e09ff10f4e1238c494f316pubmed:34100744
DOI:
10.5152/iao.2021.8549
DATE – PUBLISHED:
Tue, 08 Jun 2021 06:00:00 -0400
DATE – DOI:
2021-06-04T13:09:30Z
DATE – ADDED:
06/08/21 02:54PM
LINK – PUBMED:
https://pubmed.ncbi.nlm.nih.gov/34100744/
LINK – DOI:
https://doi.org/10.5152/iao.2021.8549
LINK – PUBLISHER:
https://www.advancedotology.org/en/effects-of-insulin-like-growth-factor-igf-1-in-patients-with-sensorineural-hearing-loss-131632?utm_source=hearinglosstreatmentreport.com
IMAGE:
REFERENCE:
Hearing Loss Treatment Report, Urgent Research, 2021-06-08T18:54:02+00:00, https://www.hearinglosstreatmentreport.com.
https://pubmed.ncbi.nlm.nih.gov/34034344/
https://www.thieme-connect.de/products/ejournals/abstract/10.1055/s-0041-1728677
Advancements in Stem Cell Technology and Organoids for the Restoration of Sensorineural Hearing Loss
CATEGORY:
Research
SCREENSHOT:
TITLE:
FOXG1 promotes aging inner ear hair cell survival through activation of the autophagy pathway
CONTENT:
Autophagy. 2021 May 19:1-22. doi: 10.1080/15548627.2021.1916194. Online ahead of print.
ABSTRACT
Presbycusis is the cumulative effect of aging on hearing. Recent studies have shown that common mitochondrial gene deletions are closely related to deafness caused by degenerative changes in the auditory system, and some of these nuclear factors are proposed to participate in the regulation of mitochondrial function. However, the detailed mechanisms involved in age-related degeneration of the auditory systems have not yet been fully elucidated. In this study, we found that FOXG1 plays an important role in the auditory degeneration process through regulation of macroautophagy/autophagy. Inhibition of FOXG1 decreased the autophagy activity and led to the accumulation of reactive oxygen species and subsequent apoptosis of cochlear hair cells. Recent clinical studies have found that aspirin plays important roles in the prevention and treatment of various diseases by regulating autophagy and mitochondria function. In this study, we found that aspirin increased the expression of FOXG1, which further activated autophagy and reduced the production of reactive oxygen species and inhibited apoptosis, and thus promoted the survival of mimetic aging HCs and HC-like OC-1 cells. This study demonstrates the regulatory function of the FOXG1 transcription factor through the autophagy pathway during hair cell degeneration in presbycusis, and it provides a new molecular approach for the treatment of age-related hearing loss.Abbreviations : AHL: age-related hearing loss; baf: bafilomycin A1; CD: common deletion; D-gal: D-galactose; GO: glucose oxidase; HC: hair cells; mtDNA: mitochondrial DNA; RAP: rapamycin; ROS: reactive oxygen species; TMRE: tetramethylrhodamine, ethyl ester.
PMID:34006186 | DOI:10.1080/15548627.2021.1916194
SOURCE:
Autophagy
PUBLISHER:
PMID:
pubmed:34006186
ID:
0b58ea4968e09ff10f4e1238c494f316pubmed:34006186
DOI:
10.1080/15548627.2021.1916194
DATE – PUBLISHED:
Wed, 19 May 2021 06:00:00 -0400
DATE – DOI:
2021-05-19T07:55:51Z
DATE – ADDED:
05/19/21 12:19PM
LINK – PUBMED:
https://pubmed.ncbi.nlm.nih.gov/34006186/
LINK – DOI:
https://doi.org/10.1080/15548627.2021.1916194
LINK – PUBLISHER:
https://www.tandfonline.com/doi/full/10.1080/15548627.2021.1916194?utm_source=hearinglosstreatmentreport.com
IMAGE:
REFERENCE:
Hearing Loss Treatment Report, Urgent Research, 2021-05-19T16:19:43+00:00, https://www.hearinglosstreatmentreport.com.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8170689/
Neurog1, Neurod1, and Atoh1 are essential for spiral ganglia, cochlear nuclei, and cochlear hair cell development
https://www.biorxiv.org/content/10.1101/2021.05.05.442757v1.full
Drug distribution along the cochlea is strongly enhanced by low-frequency round window micro vibrations
Samuel M. Flaherty, View ORCID ProfileIan J. Russell, View ORCID ProfileAndrei N. Lukashkin
doi: https://doi.org/10.1101/2021.05.05.442757
https://www.jneurosci.org/content/early/2021/04/19/JNEUROSCI.3238-20.2021
Research Articles, Systems/Circuits
Primary Neural Degeneration in Noise-Exposed Human Cochleas: Correlations with Outer Hair Cell Loss and Word-Discrimination Scores
Journal of Neuroscience 21 April 2021, JN-RM-3238-20; DOI: https://doi.org/10.1523/JNEUROSCI.3238-20.2021
Abstract
Animal studies suggest that cochlear nerve degeneration precedes sensory cell degeneration in both noise-induced hearing loss (NIHL) and age-related hearing loss (ARHL), producing a hearing impairment that is not reflected in audiometric thresholds. Here, we investigated the histopathology of human ARHL and NIHL by comparing loss of auditory nerve fibers (ANFs), cochlear hair cells and the stria vascularis in a group of 52 cases with noise-exposure history against an age-matched control group. Although strial atrophy increased with age, there was no effect of noise history. Outer hair cell (OHC) loss also increased with age throughout the cochlea but was unaffected by noise history in the low-frequency region (<2 kHz), while greatly exacerbated at high frequencies (≥2 kHz). Inner hair cell (IHC) loss was primarily seen at high frequencies but was unaffected by noise at either low or high frequencies. ANF loss was substantial at all cochlear frequencies and was exacerbated by noise throughout. According to a multivariable regression model, this loss of neural channels contributes to poor word discrimination among those with similar audiometric threshold losses. The histopathological patterns observed also suggest that, whereas the low-frequency OHC loss may be an unavoidable consequence of aging, the high-frequency loss, which produces the classic down-sloping audiogram of ARHL, may be partially because of avoidable ear abuse, even among those without a documented history of acoustic overexposure.
Statement of Significance
As regenerative therapeutics in sensorineural hearing loss enter clinical trials, it becomes critical to infer which cochlear pathologies are present in addition to hair cell loss. Here, by analyzing human autopsy material, we show that acoustic injury accelerates age-related primary neural degeneration, but not strial degeneration, neither of which can be inferred from audiometric thresholds. It exacerbates outer hair cell (OHC) loss only in the high-frequency half of the cochlea, suggesting that the apical loss is age-related, whereas the basal loss is partially noise induced, and therefore avoidable. Statistical analysis suggests that neural loss helps explain differences in word-recognition ability among individuals with similar audiometric thresholds. The surprising correlation between neural loss and OHC loss in the cochlea’s speech region also implicates neural loss in the well-known decline in word scores as thresholds deteriorate with age.
Custom Title
Primary Neural Degeneration in Noise-Exposed Human Cochleas: Implications for Regenerative Therapeutics
CATEGORY:
Research
SCREENSHOT:
TITLE:
Nox3-derived superoxide in cochleae induces sensorineural hearing loss Mechanisms of Nox3-dependent hearing loss
CONTENT:
J Neurosci. 2021 Apr 13:JN-RM-2672-20. doi: 10.1523/JNEUROSCI.2672-20.2021. Online ahead of print.
ABSTRACT
Reactive oxygen species (ROS) produced by NADPH oxidases (Nox) contribute to the development of different types of sensorineural hearing loss (SNHL), a common impairment in humans with no established treatment. Although the essential role of Nox3 in otoconia biosynthesis and its possible involvement in hearing have been reported in rodents, immunohistological methods targeted at detecting Nox3 expression in inner ear cells reveal ambiguous results. Therefore, the mechanism underlying Nox3 -dependent SNHL remains unclear and warrants further investigation. We generated Nox3-Cre knock-in mice, in which Nox3 was replaced with Cre recombinase (Cre ). Using Nox3-Cre;tdTomato mice of either sex, in which tdTomato is expressed under the control of the Nox3 promoter, we determined Nox3-expressing regions and cell types in the inner ear. Nox3 -expressing cells in the cochlea included various types of supporting cells (SC), outer hair cells (OHC), inner hair cells (IHC), and spiral ganglion neurons (SGN). Nox3 expression increased with cisplatin, age, and noise insults. Moreover, increased Nox3 expression in SC and OHC, especially at the basal turn of the cochlea, played essential roles in ROS-related SNHL. The extent of Nox3 involvement in SNHL follows the following order: cisplatin-induced HL (CIHL) > age-related HL (ARHL) > noise-induced HL (NIHL). Here, on the basis of Nox3-Cre;tdTomato , which can be used as a reporter system (Nox3-Cre+/- ;tdTomato+/+ and Nox3-Cre+/+ ;tdTomato+/+ ), and Nox3 -KO (Nox3-Cre+/+ ;tdTomato+/+ ) mice, we demonstrate that Nox3 inhibition in the cochlea is a promising strategy for ROS-related SNHL, such as CIHL, ARHL, and NIHL.SIGNIFICANCE STATEMENT: We found Nox3-expressing regions and cell-types in the inner ear, especially in the cochlea, using Nox3-Cre;tdTomato mice, a reporter system generated in this study. Nox3 expression increased with cisplatin, age, and noise insults in specific cell-types in the cochlea and resulted in the loss (apoptosis) of outer hair cells. Thus, Nox3 might serve as a molecular target for the development of therapeutics for sensorineural hearing loss, particularly cisplatin-induced, age-related, and noise-induced hearing loss.
PMID:33849947 | DOI:10.1523/JNEUROSCI.2672-20.2021
SOURCE:
The Journal of neuroscience : the official journal of the Society for Neuroscience
PUBLISHER:
PMID:
pubmed:33849947
ID:
0b58ea4968e09ff10f4e1238c494f316pubmed:33849947
DOI:
10.1523/JNEUROSCI.2672-20.2021
DATE – PUBLISHED:
Wed, 14 Apr 2021 06:00:00 -0400
DATE – DOI:
2021-04-13T18:12:49Z
DATE – ADDED:
04/14/21 09:45AM
LINK – PUBMED:
https://pubmed.ncbi.nlm.nih.gov/33849947/
LINK – DOI:
https://doi.org/10.1523/JNEUROSCI.2672-20.2021
LINK – PUBLISHER:
http://www.jneurosci.org/lookup/doi/10.1523/JNEUROSCI.2672-20.2021?utm_source=hearinglosstreatmentreport.com
IMAGE:
REFERENCE:
Hearing Loss Treatment Report, Urgent Research, 2021-04-14T13:45:44+00:00, https://www.hearinglosstreatmentreport.com.
https://www.frontiersin.org/articles/10.3389/fncel.2021.658972/full
Rapamycin Added to Diet in Late Mid-Life Delays Age-Related Hearing Loss in UMHET4 Mice
PBM/NAC treatment may prevent hearing dysfunction caused by NIHL
CATEGORY:
Research
SCREENSHOT:
TITLE:
Combination photobiomodulation/N-acetyl-L-cysteine treatment appears to mitigate hair cell loss associated with noise-induced hearing loss in rats
CONTENT:
Lasers Med Sci. 2021 Apr 6. doi: 10.1007/s10103-021-03304-2. Online ahead of print.
ABSTRACT
Sensorineural hearing loss is an intractable disease. Acoustic overstimulation creates hearing loss; many patients exhibit social and emotional dysfunctions. In a model of noise-induced hearing loss (NIHL), low-level laser photobiomodulation (PBM) at a near-infrared wavelength significantly improved auditory brainstem response (ABR) thresholds. In addition, both N-acetyl-L-cysteine (NAC) and acetyl-L-carnitine (ALCAR) attenuated NIHL, reducing the effects of noise trauma in the cochlea and the central auditory system. Here, we combined PBM with antioxidants to explore hearing threshold recovery and morphological hair cell changes after rats were exposed to noise. The average auditory brainstem response thresholds after PBM/NAC combination treatment were reduced from the apex to the basal turn at all of 8, 16, and 32 kHz compared to the noise-only group. The PBM/NAC combination treated group exhibited intact outer hair cells in all turns, and significantly greater hair cell numbers in the middle and basal cochlear turns, than did controls. Thus, PBM/NAC treatment may prevent hearing dysfunction caused by NIHL.
PMID:33822307 | DOI:10.1007/s10103-021-03304-2
SOURCE:
Lasers in medical science
PUBLISHER:
PMID:
pubmed:33822307
ID:
0b58ea4968e09ff10f4e1238c494f316pubmed:33822307
DOI:
10.1007/s10103-021-03304-2
DATE – PUBLISHED:
Tue, 06 Apr 2021 06:00:00 -0400
DATE – DOI:
2021-04-06T07:04:00Z
DATE – ADDED:
04/06/21 07:30PM
LINK – PUBMED:
https://pubmed.ncbi.nlm.nih.gov/33822307/
LINK – DOI:
https://doi.org/10.1007/s10103-021-03304-2
LINK – PUBLISHER:
http://link.springer.com/10.1007/s10103-021-03304-2?utm_source=hearinglosstreatmentreport.com
IMAGE:
REFERENCE:
Hearing Loss Treatment Report, Urgent Research, 2021-04-06T23:30:28+00:00, https://www.hearinglosstreatmentreport.com.
CATEGORY:
Research
SCREENSHOT:
TITLE:
Protective Effects of N(1)-Methylnicotinamide Against High-Fat Diet- and Age-Induced Hearing Loss via Moderate Overexpression of Sirtuin 1 Protein
CONTENT:
Front Cell Neurosci. 2021 Apr 6;15:634868. doi: 10.3389/fncel.2021.634868. eCollection 2021.
ABSTRACT
Age-related hearing loss (ARHL) is the most common form of hearing loss and the predominant neurodegenerative disease associated with aging. Sirtuin 1 (SIRT1) is associated with the most complex physiological processes, including metabolism, cancer onset, and aging. SIRT1 protein levels are enhanced by the conversion of nicotinamide to N1 -methylnicotinamide (MNAM), independent of its mRNA levels. Moreover, MNAM has implications in increased longevity achieved through its mitohormetic effects. Nicotinamide N-methyltransferase (Nnmt) is an enzyme involved in MNAM metabolism, and its level increases under caloric restriction (CR) conditions. The CR condition has implications in delaying ARHL onset. In this study, we aimed to determine the relationship between diet, hearing function, SIRT1 and SIRT3 expression levels in the inner ear, and cochlear morphology. Mice fed with a high-fat diet (HFD), HFD + 1% MNAM, and low-fat diet (LFD) were monitored for age-related auditory-evoked brainstem responses, and changes in cochlear histology, metabolism, and protein and mRNA expressions were analyzed. Our results revealed that the HFD- and aging-mediated downregulated expression of SIRT1 and SIRT3 promoted hearing loss that was obfuscated by MNAM supplementation-induced upregulated expression of cochlear SIRT1 and SIRT3. Thus, our results suggest that MNAM can be used as a therapeutic agent for preventing ARHL.
PMID:33889076 | PMC:PMC8055820 | DOI:10.3389/fncel.2021.634868
SOURCE:
Frontiers in cellular neuroscience
PUBLISHER:
PMID:
pubmed:33889076
ID:
0b58ea4968e09ff10f4e1238c494f316pubmed:33889076
DOI:
10.3389/fncel.2021.634868
DATE – PUBLISHED:
Fri, 23 Apr 2021 06:00:00 -0400
DATE – DOI:
2021-04-06T04:35:29Z
DATE – ADDED:
04/23/21 01:45PM
LINK – PUBMED:
https://pubmed.ncbi.nlm.nih.gov/33889076/
LINK – DOI:
https://doi.org/10.3389/fncel.2021.634868
LINK – PUBLISHER:
https://www.frontiersin.org/articles/10.3389/fncel.2021.634868/full?utm_source=hearinglosstreatmentreport.com
IMAGE:
REFERENCE:
Hearing Loss Treatment Report, Urgent Research, 2021-04-23T17:45:47+00:00, https://www.hearinglosstreatmentreport.com.
CATEGORY:
Research
SCREENSHOT:
TITLE:
Protective effects of vitamins/antioxidants on occupational noise-induced hearing loss: A systematic review
CONTENT:
J Occup Health. 2021 Jan;63(1):e12217. doi: 10.1002/1348-9585.12217.
ABSTRACT
OBJECTIVES: Occupational noise-induced hearing loss (NIHL) due to industrial, military, and other job -related noise exposure can cause harmful health issues to occupied workers, but may also be potentially preventable. Vitamins/antioxidant have been studied as therapeutic strategies to prevent and/or delay the risks of human diseases as well as NIHL .So, this study was conducted to systematically review the protective effects of vitamins/antioxidants on occupational NIHL.
METHODS: Online databases including PubMed/Medline, Scopus, Web of Science, EMBASE, Science Direct, and Google Scholar were systematically searched up to 12 January 2021. Based on 6336 potentially relevant records identified through the initial search in the databases, 12 full-text publications were retrieved, one of which can be viewed as two separate trials, because it has studied the effects of two different antioxidants (ginseng and NAC) on NIHL, separately.
RESULTS: A review of the studies shows that vitamin B12, folic acid, and N-acetylcysteine (NAC) have a considerable protective effect on NIHL. However, these protective effects are not yet specified in different frequencies. The findings regarding the protective effects of other antioxidants are inconsistent in this field.
CONCLUSION: Vitamin B12, folic acid, and NAC may have a protective effect as an antioxidant on reducing occupational hearing loss. For a conclusive evidence of vitamin/antioxidant protective therapies, future studies with precise criteria for noise exposure and similar outcome parameters are required.
PMID:33788342 | DOI:10.1002/1348-9585.12217
SOURCE:
Journal of occupational health
PUBLISHER:
PMID:
pubmed:33788342
ID:
0b58ea4968e09ff10f4e1238c494f316pubmed:33788342
DOI:
10.1002/1348-9585.12217
DATE – PUBLISHED:
Wed, 31 Mar 2021 06:00:00 -0400
DATE – DOI:
2021-03-31T14:18:59Z
DATE – ADDED:
03/31/21 07:53PM
LINK – PUBMED:
https://pubmed.ncbi.nlm.nih.gov/33788342/
LINK – DOI:
https://doi.org/10.1002/1348-9585.12217
LINK – PUBLISHER:
https://onlinelibrary.wiley.com/doi/10.1002/1348-9585.12217?utm_source=hearinglosstreatmentreport.com
IMAGE:
REFERENCE:
Hearing Loss Treatment Report, Urgent Research, 2021-03-31T23:53:37+00:00, https://www.hearinglosstreatmentreport.com.
https://www.frontiersin.org/articles/10.3389/fncel.2021.660748/full
Front. Cell. Neurosci., 29 March 2021 | https://doi.org/10.3389/fncel.2021.660748
Transcription Factor Reprogramming in the Inner Ear: Turning on Cell Fate Switches to Regenerate Sensory Hair Cells
Abstract
Non-mammalian vertebrates can restore their auditory and vestibular hair cells naturally by triggering the regeneration of adjacent supporting cells. The transcription factor ATOH1 is a key regulator of hair cell development and regeneration in the inner ear. Following the death of hair cells, supporting cells upregulate ATOH1 and give rise to new hair cells. However, in the mature mammalian cochlea, such natural regeneration of hair cells is largely absent. Transcription factor reprogramming has been used in many tissues to convert one cell type into another, with the long-term hope of achieving tissue regeneration. Reprogramming transcription factors work by altering the transcriptomic and epigenetic landscapes in a target cell, resulting in a fate change to the desired cell type. Several studies have shown that ATOH1 is capable of reprogramming cochlear non-sensory tissue into cells resembling hair cells in young animals. However, the reprogramming ability of ATOH1 is lost with age, implying that the potency of individual hair cell-specific transcription factors may be reduced or lost over time by mechanisms that are still not clear. To circumvent this, combinations of key hair cell transcription factors have been used to promote hair cell regeneration in older animals. In this review, we summarize recent findings that have identified and studied these reprogramming factor combinations for hair cell regeneration. Finally, we discuss the important questions that emerge from these findings, particularly the feasibility of therapeutic strategies using reprogramming factors to restore human hearing in the future.
CATEGORY:
Research
SCREENSHOT:
TITLE:
Congenital Deafness and Recent Advances Towards Restoring Hearing Loss
CONTENT:
Curr Protoc. 2021 Mar;1(3):e76. doi: 10.1002/cpz1.76.
ABSTRACT
Congenital hearing loss is the most common birth defect, estimated to affect 2-3 in every 1000 births. Currently there is no cure for hearing loss. Treatment options are limited to hearing aids for mild and moderate cases, and cochlear implants for severe and profound hearing loss. Here we provide a literature overview of the environmental and genetic causes of congenital hearing loss, common animal models and methods used for hearing research, as well as recent advances towards developing therapies to treat congenital deafness. © 2021 The Authors.
PMID:33780161 | DOI:10.1002/cpz1.76
SOURCE:
Current protocols
PUBLISHER:
PMID:
pubmed:33780161
ID:
0b58ea4968e09ff10f4e1238c494f316pubmed:33780161
DOI:
10.1002/cpz1.76
DATE – PUBLISHED:
Mon, 29 Mar 2021 06:00:00 -0400
DATE – DOI:
2021-03-29T13:07:03Z
DATE – ADDED:
03/30/21 12:08AM
LINK – PUBMED:
https://pubmed.ncbi.nlm.nih.gov/33780161/
LINK – DOI:
https://doi.org/10.1002/cpz1.76
LINK – PUBLISHER:
https://onlinelibrary.wiley.com/doi/10.1002/cpz1.76?utm_source=hearinglosstreatmentreport.com
IMAGE:
REFERENCE:
Hearing Loss Treatment Report, Urgent Research, 2021-03-30T04:08:44+00:00, https://www.hearinglosstreatmentreport.com.
https://www.cell.com/stem-cell-reports/fulltext/S2213-6711(21)00131-4
HIC1 Represses Atoh1 Transcription and Hair Cell Differentiation in the Cochlea
CATEGORY:
Research
SCREENSHOT:
TITLE:
Oridonin ameliorates noise-induced hearing loss by blocking NLRP3 – NEK7 mediated inflammasome activation
CONTENT:
Int Immunopharmacol. 2021 Mar 23;95:107576. doi: 10.1016/j.intimp.2021.107576. Online ahead of print.
ABSTRACT
Inflammation is involved in noise-induced hearing loss (NIHL), but the mechanism is still unknown. The NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome, which triggers the inflammatory cascade, has been implicated in several inflammatory diseases in response to oxidative stress. However, whether the NLRP3 inflammasome is a key factor for permanent NIHL is still unknown. In this study, quantitative real-time polymerase chain reaction (qPCR), western blot, and enzyme-linked immunosorbent assays (ELISAs) demonstrated that the expression levels of activated caspase-1, interleukin (IL)-1β, IL-18, and NLRP3 were significantly increased in the cochleae of mice exposed to broadband noise (120 dB) for 4 h, compared with the control group. These results indicate that the activation of inflammasomes in the cochleae of mice during the pathological process of NIHL as well as NLRP3, a sensor protein of reactive oxygen species (ROS), may be key factors for inflammasome assembly and subsequent inflammation in cochleae. Moreover, many recent studies have revealed that NEK7 is an important component and regulator of NLRP3 inflammasomes by interacting with NLRP3 directly and that these interactions can be interrupted by oridonin. Here, we further determined that treatment with oridonin could indeed interrupt the interaction between NLRP3 and NEK7 as well as inhibit the downstream inflammasome activation in mouse cochleae after noise exposure. Furthermore, we tested anakinra, another inflammatory inhibitor, and it was shown to partially alleviate the degree of hearing impairment in some frequencies in an NIHL mouse model. These discoveries suggest that inhibiting NLRP3 inflammasomes and the downstream signaling pathway may provide a new strategy for the clinical treatment of NIHL.
PMID:33770730 | DOI:10.1016/j.intimp.2021.107576
SOURCE:
International immunopharmacology
PUBLISHER:
PMID:
pubmed:33770730
ID:
0b58ea4968e09ff10f4e1238c494f316pubmed:33770730
DOI:
10.1016/j.intimp.2021.107576
DATE – PUBLISHED:
Fri, 26 Mar 2021 06:00:00 -0400
DATE – DOI:
2021-03-23T12:47:43Z
DATE – ADDED:
03/27/21 10:05AM
LINK – PUBMED:
https://pubmed.ncbi.nlm.nih.gov/33770730/
LINK – DOI:
https://doi.org/10.1016/j.intimp.2021.107576
LINK – PUBLISHER:
https://linkinghub.elsevier.com/retrieve/pii/S1567576921002125?utm_source=hearinglosstreatmentreport.com
IMAGE:
REFERENCE:
Hearing Loss Treatment Report, Urgent Research, 2021-03-27T14:05:04+00:00, https://www.hearinglosstreatmentreport.com.
CATEGORY:
Research
SCREENSHOT:
TITLE:
Prevention of acquired sensorineural hearing loss in mice by in vivo Htra2 gene editing
CONTENT:
Genome Biol. 2021 Mar 22;22(1):86. doi: 10.1186/s13059-021-02311-4.
ABSTRACT
BACKGROUND: Aging, noise, infection, and ototoxic drugs are the major causes of human acquired sensorineural hearing loss, but treatment options are limited. CRISPR/Cas9 technology has tremendous potential to become a new therapeutic modality for acquired non-inherited sensorineural hearing loss. Here, we develop CRISPR/Cas9 strategies to prevent aminoglycoside-induced deafness, a common type of acquired non-inherited sensorineural hearing loss, via disrupting the Htra2 gene in the inner ear which is involved in apoptosis but has not been investigated in cochlear hair cell protection.
RESULTS: The results indicate that adeno-associated virus (AAV)-mediated delivery of CRISPR/SpCas9 system ameliorates neomycin-induced apoptosis, promotes hair cell survival, and significantly improves hearing function in neomycin-treated mice. The protective effect of the AAV-CRISPR/Cas9 system in vivo is sustained up to 8 weeks after neomycin exposure. For more efficient delivery of the whole CRISPR/Cas9 system, we also explore the AAV-CRISPR/SaCas9 system to prevent neomycin-induced deafness. The in vivo editing efficiency of the SaCas9 system is 1.73% on average. We observed significant improvement in auditory brainstem response thresholds in the injected ears compared with the non-injected ears. At 4 weeks after neomycin exposure, the protective effect of the AAV-CRISPR/SaCas9 system is still obvious, with the improvement in auditory brainstem response threshold up to 50 dB at 8 kHz.
CONCLUSIONS: These findings demonstrate the safe and effective prevention of aminoglycoside-induced deafness via Htra2 gene editing and support further development of the CRISPR/Cas9 technology in the treatment of non-inherited hearing loss as well as other non-inherited diseases.
PMID:33752742 | DOI:10.1186/s13059-021-02311-4
SOURCE:
Genome biology
PUBLISHER:
PMID:
pubmed:33752742
ID:
0b58ea4968e09ff10f4e1238c494f316pubmed:33752742
DOI:
10.1186/s13059-021-02311-4
DATE – PUBLISHED:
Tue, 23 Mar 2021 06:00:00 -0400
DATE – DOI:
2021-03-22T09:13:12Z
DATE – ADDED:
03/23/21 07:24AM
LINK – PUBMED:
https://pubmed.ncbi.nlm.nih.gov/33752742/
LINK – DOI:
https://doi.org/10.1186/s13059-021-02311-4
LINK – PUBLISHER:
https://genomebiology.biomedcentral.com/articles/10.1186/s13059-021-02311-4?utm_source=hearinglosstreatmentreport.com
IMAGE:
REFERENCE:
Hearing Loss Treatment Report, Urgent Research, 2021-03-23T11:24:13+00:00, https://www.hearinglosstreatmentreport.com.
CATEGORY:
Research
SCREENSHOT:
TITLE:
SCN11A gene deletion causes sensorineural hearing loss by impairing the ribbon synapses and auditory nerves
CONTENT:
BMC Neurosci. 2021 Mar 22;22(1):18. doi: 10.1186/s12868-021-00613-8.
ABSTRACT
BACKGROUND: The SCN11A gene, encoded Nav1.9 TTX resistant sodium channels, is a main effector in peripheral inflammation related pain in nociceptive neurons. The role of SCN11A gene in the auditory system has not been well characterized. We therefore examined the expression of SCN11A in the murine cochlea, the morphological and physiological features of Nav1.9 knockout (KO) ICR mice.
RESULTS: Nav1.9 expression was found in the primary afferent endings beneath the inner hair cells (IHCs). The relative quantitative expression of Nav1.9 mRNA in modiolus of wild-type (WT) mice remains unchanged from P0 to P60. The number of presynaptic CtBP2 puncta in Nav1.9 KO mice was significantly lower than WT. In addition, the number of SGNs in Nav1.9 KO mice was also less than WT in the basal turn, but not in the apical and middle turns. There was no lesion in the somas and stereocilia of hair cells in Nav1.9 KO mice. Furthermore, Nav1.9 KO mice showed higher and progressive elevated ABR threshold at 16 kHz, and a significant increase in CAP thresholds.
CONCLUSIONS: These data suggest a role of Nav1.9 in regulating the function of ribbon synapses and the auditory nerves. The impairment induced by Nav1.9 gene deletion mimics the characters of cochlear synaptopathy.
PMID:33752606 | DOI:10.1186/s12868-021-00613-8
SOURCE:
BMC neuroscience
PUBLISHER:
PMID:
pubmed:33752606
ID:
0b58ea4968e09ff10f4e1238c494f316pubmed:33752606
DOI:
10.1186/s12868-021-00613-8
DATE – PUBLISHED:
Tue, 23 Mar 2021 06:00:00 -0400
DATE – DOI:
2021-03-22T13:05:35Z
DATE – ADDED:
03/23/21 08:24AM
LINK – PUBMED:
https://pubmed.ncbi.nlm.nih.gov/33752606/
LINK – DOI:
https://doi.org/10.1186/s12868-021-00613-8
LINK – PUBLISHER:
https://bmcneurosci.biomedcentral.com/articles/10.1186/s12868-021-00613-8?utm_source=hearinglosstreatmentreport.com
IMAGE:
REFERENCE:
Hearing Loss Treatment Report, Urgent Research, 2021-03-23T12:24:36+00:00, https://www.hearinglosstreatmentreport.com.
CATEGORY:
Research
SCREENSHOT:
TITLE:
Endogenous Pituitary Adenylate Cyclase-Activating Polypeptide (PACAP) Plays a Protective Effect Against Noise-Induced Hearing Loss
CONTENT:
Front Cell Neurosci. 2021 Mar 22;15:658990. doi: 10.3389/fncel.2021.658990. eCollection 2021.
ABSTRACT
Pituitary adenylyl cyclase-activating polypeptide (PACAP) is a member of the vasoactive intestinal polypeptide (VIP)-the secretin-glucagon family of neuropeptides. They act through two classes of receptors: PACAP type 1 (PAC1) and type 2 (VPAC1 and VPAC2). Among their pleiotropic effects throughout the body, PACAP functions as neuromodulators and neuroprotectors, rescuing neurons from apoptosis, mostly through the PAC1 receptor. To explore the potential protective effect of endogenous PACAP against Noise-induced hearing loss (NIHL), we used a knockout mouse model lacking PAC1 receptor expression (PACR1-/- ) and a transgenic humanized mouse model expressing the human PAC1 receptor (TgHPAC1R). Based on complementary approaches combining electrophysiological, histochemical, and molecular biological evaluations, we show PAC1R expression in spiral ganglion neurons and in cochlear apical cells of the organ of Corti. Wild-type (WT), PAC1R-/- , and TgHPAC1R mice exhibit similar auditory thresholds. For most of the frequencies tested after acute noise damage, however, PAC1R-/- mice showed a larger elevation of the auditory threshold than did their WT counterparts. By contrast, in a transgene copy number-dependent fashion, TgHPAC1R mice showed smaller noise-induced elevations of auditory thresholds compared to their WT counterparts. Together, these findings suggest that PACAP could be a candidate for endogenous protection against noise-induced hearing loss.
PMID:33828461 | PMC:PMC8019930 | DOI:10.3389/fncel.2021.658990
SOURCE:
Frontiers in cellular neuroscience
PUBLISHER:
PMID:
pubmed:33828461
ID:
0b58ea4968e09ff10f4e1238c494f316pubmed:33828461
DOI:
10.3389/fncel.2021.658990
DATE – PUBLISHED:
Thu, 08 Apr 2021 06:00:00 -0400
DATE – DOI:
2021-03-22T06:42:56Z
DATE – ADDED:
04/08/21 01:18PM
LINK – PUBMED:
https://pubmed.ncbi.nlm.nih.gov/33828461/
LINK – DOI:
https://doi.org/10.3389/fncel.2021.658990
LINK – PUBLISHER:
https://www.frontiersin.org/articles/10.3389/fncel.2021.658990/full?utm_source=hearinglosstreatmentreport.com
IMAGE:
REFERENCE:
Hearing Loss Treatment Report, Urgent Research, 2021-04-08T17:18:29+00:00, https://www.hearinglosstreatmentreport.com.
CATEGORY:
Research
SCREENSHOT:
TITLE:
Expression of serum proteins in noise induced hearing loss workers of mining based industry
CONTENT:
J Proteomics. 2021 Mar 15:104185. doi: 10.1016/j.jprot.2021.104185. Online ahead of print.
ABSTRACT
Noise Induced Hearing Loss (NIHL) is caused by excessive noise exposure due to occupational activities thus affects communication and quality of life. Prolonged occupational and environmental exposure to loud noise damages key molecules present in the micro-machinery of the ear which are required for the mechano-electrical transduction of sound waves in cochlea. Specific proteins are known to be associated with hearing loss and related structural and functional disabilities in the human inner, outer hair cells and cochlea. Rationale of this study was to identify the cochlear proteins associated with the pathophysiology of NIHL using proteomic approaches in mining based industrial workers. Total (n = 210) samples were collected from mining based industrial workers of central India. Subjects were categorized based on audiometric analysis. Proteome changes of the host serum were investigated using one and two-dimensional electrophoresis in combination with LC-MS/MS and MALDI-TOF MS. Up-regulated 46 cochlear proteins among confirmed NIHL cases were identified by MASCOT. Shrinkage discriminant analysis provided top 25 discriminating feature proteins namely myosin, transthyretin, SERPIN, CCDC50, enkurin, transferin etc. The identified potential proteins may be used as biomarkers for early detection and to understand the pathogenic mechanism of NIHL. Evaluation of these biomarkers in follow-up cases may further aid in improving NIHL diagnosis. SIGNIFICANCE: Human proteome study in Noise Induced Hearing Loss (NIHL) cases has not been published till date. This study represents most comprehensive proteomic analysis in NIHL cases taken from Indian mine workers. The identified key twenty-five discriminating feature proteins which are upregulated when an individual develops (or is in stage of development of) NIHL, provides insights into the potential roles of these varied proteins in disease progression. The proteins thus identified by proteomic approach may be used as early diagnostic biomarker to predict the occurrence of disease at very early stage.
PMID:33737237 | DOI:10.1016/j.jprot.2021.104185
SOURCE:
Journal of proteomics
PUBLISHER:
PMID:
pubmed:33737237
ID:
0b58ea4968e09ff10f4e1238c494f316pubmed:33737237
DOI:
10.1016/j.jprot.2021.104185
DATE – PUBLISHED:
Fri, 19 Mar 2021 06:00:00 -0400
DATE – DOI:
2021-03-18T20:32:33Z
DATE – ADDED:
03/19/21 03:00PM
LINK – PUBMED:
https://pubmed.ncbi.nlm.nih.gov/33737237/
LINK – DOI:
https://doi.org/10.1016/j.jprot.2021.104185
LINK – PUBLISHER:
https://linkinghub.elsevier.com/retrieve/pii/S1874391921000841?utm_source=hearinglosstreatmentreport.com
IMAGE:
REFERENCE:
Hearing Loss Treatment Report, Urgent Research, 2021-03-19T19:00:02+00:00, https://www.hearinglosstreatmentreport.com.
CATEGORY:
Research
SCREENSHOT:
TITLE:
The DNA methylation inhibitor RG108 protects against noise-induced hearing loss
CONTENT:
Cell Biol Toxicol. 2021 Mar 15. doi: 10.1007/s10565-021-09596-y. Online ahead of print.
ABSTRACT
BACKGROUND: Noise-induced hearing loss represents a commonly diagnosed type of hearing disability, severely impacting the quality of life of individuals. The current work is aimed at assessing the effects of DNA methylation on noise-induced hearing loss.
METHODS: Blocking DNA methyltransferase 1 (DNMT1) activity with a selective inhibitor RG108 or silencing DNMT1 with siRNA was used in this study. Auditory brainstem responses were measured at baseline and 2 days after trauma in mice to assess auditory functions. Whole-mount immunofluorescent staining and confocal microcopy of mouse inner ear specimens were performed to analyze noise-induced damage in cochleae and the auditory nerve at 2 days after noise exposure.
RESULTS: The results showed that noise exposure caused threshold elevation of auditory brainstem responses and cochlear hair cell loss. Whole-mount cochlea staining revealed a reduction in the density of auditory ribbon synapses between inner hair cells and spiral ganglion neurons. Inhibition of DNA methyltransferase activity via a non-nucleoside specific pharmacological inhibitor, RG108, or silencing of DNA methyltransferase-1 with siRNA significantly attenuated ABR threshold elevation, hair cell damage, and the loss of auditory synapses.
CONCLUSIONS: This study suggests that inhibition of DNMT1 ameliorates noise-induced hearing loss and indicates that DNMT1 may be a promising therapeutic target. Graphical Headlights • RG108 protected against noise-induced hearing loss • RG108 administration protected against noise-induced hair cell loss and auditory neural damage. • RG108 administration attenuated oxidative stress-induced DNA damage and subsequent apoptosis-mediated cell loss in the cochlea after noise exposure.
PMID:33723744 | DOI:10.1007/s10565-021-09596-y
SOURCE:
Cell biology and toxicology
PUBLISHER:
PMID:
pubmed:33723744
ID:
0b58ea4968e09ff10f4e1238c494f316pubmed:33723744
DOI:
10.1007/s10565-021-09596-y
DATE – PUBLISHED:
Tue, 16 Mar 2021 06:00:00 -0400
DATE – DOI:
2021-03-15T18:03:14Z
DATE – ADDED:
03/16/21 02:49PM
LINK – PUBMED:
https://pubmed.ncbi.nlm.nih.gov/33723744/
LINK – DOI:
https://doi.org/10.1007/s10565-021-09596-y
LINK – PUBLISHER:
http://link.springer.com/10.1007/s10565-021-09596-y?utm_source=hearinglosstreatmentreport.com
IMAGE:
REFERENCE:
Hearing Loss Treatment Report, Urgent Research, 2021-03-16T18:49:43+00:00, https://www.hearinglosstreatmentreport.com.
CATEGORY:
Research
SCREENSHOT:
TITLE:
Treatment With Calcineurin Inhibitor FK506 Attenuates Noise-Induced Hearing Loss
CONTENT:
Front Cell Dev Biol. 2021 Mar 12;9:648461. doi: 10.3389/fcell.2021.648461. eCollection 2021.
ABSTRACT
Attenuation of noise-induced hair cell loss and noise-induced hearing loss (NIHL) by treatment with FK506 (tacrolimus), a calcineurin (CaN/PP2B) inhibitor used clinically as an immunosuppressant, has been previously reported, but the downstream mechanisms of FK506-attenuated NIHL remain unknown. Here we showed that CaN immunolabeling in outer hair cells (OHCs) and nuclear factor of activated T-cells isoform c4 (NFATc4/NFAT3) in OHC nuclei are significantly increased after moderate noise exposure in adult CBA/J mice. Consequently, treatment with FK506 significantly reduces moderate-noise-induced loss of OHCs and NIHL. Furthermore, induction of reactive oxygen species (ROS) by moderate noise was significantly diminished by treatment with FK506. In agreement with our previous finding that autophagy marker microtubule-associated protein light chain 3B (LC3B) does not change in OHCs under conditions of moderate-noise-induced permanent threshold shifts, treatment with FK506 increases LC3B immunolabeling in OHCs after exposure to moderate noise. Additionally, prevention of NIHL by treatment with FK506 was partially abolished by pretreatment with LC3B small interfering RNA. Taken together, these results indicate that attenuation of moderate-noise-induced OHC loss and hearing loss by FK506 treatment occurs not only via inhibition of CaN activity but also through inhibition of ROS and activation of autophagy.
PMID:33777956 | PMC:PMC7994600 | DOI:10.3389/fcell.2021.648461
SOURCE:
Frontiers in cell and developmental biology
PUBLISHER:
PMID:
pubmed:33777956
ID:
0b58ea4968e09ff10f4e1238c494f316pubmed:33777956
DOI:
10.3389/fcell.2021.648461
DATE – PUBLISHED:
Mon, 29 Mar 2021 06:00:00 -0400
DATE – DOI:
2021-03-12T06:50:17Z
DATE – ADDED:
03/29/21 01:57PM
LINK – PUBMED:
https://pubmed.ncbi.nlm.nih.gov/33777956/
LINK – DOI:
https://doi.org/10.3389/fcell.2021.648461
LINK – PUBLISHER:
https://www.frontiersin.org/articles/10.3389/fcell.2021.648461/full?utm_source=hearinglosstreatmentreport.com
IMAGE:
REFERENCE:
Hearing Loss Treatment Report, Urgent Research, 2021-03-29T17:57:07+00:00, https://www.hearinglosstreatmentreport.com.
CATEGORY:6
Research
SCREENSHOT:
TITLE:
Hidden hearing loss is associated with loss of ribbon synapses of cochlea inner hair cells
CONTENT:
Biosci Rep. 2021 Mar 18:BSR20201637. doi: 10.1042/BSR20201637. Online ahead of print.
ABSTRACT
This study aimed to observe the changes in the cochlea ribbon synapses after repeated exposure to moderate-to-high intensity noise. Guinea pigs received 95 dB SPL white noise exposure 4 hours a day for consecutive 7 days (we regarded it a medium-term and moderate-intensity noise, or MTMI noise). Animals were divided into 4 groups: Control, 1DPN (1-day post noise), 1WPN (1-week post noise), and 1MPN (1-month post noise). Auditory function analysis by ABR and CAP recordings, as well as ribbon synapse morphological analyses by immunohistochemistry (Ctbp2 and PSD95 staining) were performed one day, one week, and one month after noise exposure. After MTMI noise exposure, the amplitudes of auditory brainstem response (ABR) I and III waves were suppressed. The compound action potential (CAP) threshold was elevated, and CAP amplitude was reduced in the 1DPN group. No apparent changes in hair cell shape, arrangement or number were observed, but the number of ribbon synapse was reduced. The 1WPN and 1MPN groups showed that part of ABR and CAP changes recovered, as well as the synapse number. The defects in cochlea auditory function and synapse changes were observed mainly in the high-frequency region. Together, repeated exposure in MTMI noise can cause hidden hearing loss, which is partially reversible after leaving the noise environment; and MTMI noise induced hidden hearing loss is associated with inner hair cell ribbon synapses.
PMID:33734328 | DOI:10.1042/BSR20201637
SOURCE:
Bioscience reports
PUBLISHER:
PMID:
pubmed:33734328
ID:
0b58ea4968e09ff10f4e1238c494f316pubmed:33734328
DOI:
10.1042/BSR20201637
DATE – PUBLISHED:
Thu, 18 Mar 2021 06:00:00 -0400
DATE – DOI:
2021-03-18T15:54:01Z
DATE – ADDED:
03/18/21 07:41PM
LINK – PUBMED:
https://pubmed.ncbi.nlm.nih.gov/33734328/
LINK – DOI:
https://doi.org/10.1042/BSR20201637
LINK – PUBLISHER:
https://portlandpress.com/bioscirep/article/doi/10.1042/BSR20201637/228102/Hidden-hearing-loss-is-associated-with-loss-of?utm_source=hearinglosstreatmentreport.com
IMAGE:
REFERENCE:
Hearing Loss Treatment Report, Urgent Research, 2021-03-18T23:41:43+00:00, https://www.hearinglosstreatmentreport.com.
CATEGORY:
Research
SCREENSHOT:
TITLE:
Advances and challenges in adeno-associated viral inner-ear gene therapy for sensorineural hearing loss
CONTENT:
Mol Ther Methods Clin Dev. 2021 Mar 10;21:209-236. doi: 10.1016/j.omtm.2021.03.005. eCollection 2021 Jun 11.
ABSTRACT
There is growing attention and effort focused on treating the root cause of sensorineural hearing loss rather than managing associated secondary characteristic features. With recent substantial advances in understanding sensorineural hearing-loss mechanisms, gene delivery has emerged as a promising strategy for the biological treatment of hearing loss associated with genetic dysfunction. There are several successful and promising proof-of-principle examples of transgene deliveries in animal models; however, there remains substantial further progress to be made in these avenues before realizing their clinical application in humans. Herein, we review different aspects of development, ongoing preclinical studies, and challenges to the clinical transition of transgene delivery of the inner ear toward the restoration of lost auditory and vestibular function.
PMID:33850952 | PMC:PMC8010215 | DOI:10.1016/j.omtm.2021.03.005
SOURCE:
Molecular therapy. Methods & clinical development
PUBLISHER:
PMID:
pubmed:33850952
ID:
0b58ea4968e09ff10f4e1238c494f316pubmed:33850952
DOI:
10.1016/j.omtm.2021.03.005
DATE – PUBLISHED:
Wed, 14 Apr 2021 06:00:00 -0400
DATE – DOI:
2021-03-11T08:48:48Z
DATE – ADDED:
04/14/21 04:52PM
LINK – PUBMED:
https://pubmed.ncbi.nlm.nih.gov/33850952/
LINK – DOI:
https://doi.org/10.1016/j.omtm.2021.03.005
LINK – PUBLISHER:
https://linkinghub.elsevier.com/retrieve/pii/S2329050121000450?utm_source=hearinglosstreatmentreport.com
https://www.cell.com/molecular-therapy-family/methods/fulltext/S2329-0501(21)00045-0
IMAGE:
REFERENCE:
Hearing Loss Treatment Report, Urgent Research, 2021-04-14T20:52:40+00:00, https://www.hearinglosstreatmentreport.com.
https://www.biorxiv.org/content/10.1101/838649v2.full
ERBB2 is a Key Mediator in Hearing Restoration in Noise-Deafened Young Adult Mice
CATEGORY:
Research
SCREENSHOT:
TITLE:
VEGF-A165 gene therapy ameliorates blood-labyrinth barrier breakdown and hearing loss
CONTENT:
JCI Insight. 2021 Mar 9:143285. doi: 10.1172/jci.insight.143285. Online ahead of print.
ABSTRACT
AbstractMillions of people are affected by hearing loss. When hearing loss is caused by noise or aging, it is often associated with breakdown of the barrier between the cochlea and its blood vessels. Pericytes populate many small vessels in the adult inner ear, however, their role in different forms of hearing loss is largely unknown. Using an inducible and conditional pericyte depletion mouse model, we show that loss of pericytes leads to marked changes in vascular structure, resulting in poor blood circulation and hearing loss. In vitro, using advanced tissue explants from pericyte fluorescence reporter models in combination with exogenous donor pericytes, we show pericytes, signaled by endothelial growth factor isoform A165 (VEGF-A165), vigorously drives new vessel growth in both adult and neonatal mouse inner ear tissue. In vivo, the delivery of an adeno-associated virus serotype 1 (AAV1)-mediated VEGF-A165 viral vector to pericyte depleted animals regenerated lost pericytes, improved blood supply, reduced loss of sensory hair cells, and attenuated hearing loss. These studies provide the first clear-cut evidence that pericytes are critical for adult hearing and can regenerate cochlear vasculature. The restoration of vascular function in the damaged inner ear with AAV1-mediated VEGF-A165 gene therapy is a new strategy for ameliorating vascular associated hearing disorders, including common forms of age-related hearing loss.
PMID:33690221 | DOI:10.1172/jci.insight.143285
SOURCE:
JCI insight
PUBLISHER:
PMID:
pubmed:33690221
ID:
0b58ea4968e09ff10f4e1238c494f316pubmed:33690221
DOI:
10.1172/jci.insight.143285
DATE – PUBLISHED:
Wed, 10 Mar 2021 06:00:00 -0500
DATE – DOI:
2021-03-09T17:03:21Z
DATE – ADDED:
03/10/21 10:18PM
LINK – PUBMED:
https://pubmed.ncbi.nlm.nih.gov/33690221/
LINK – DOI:
https://doi.org/10.1172/jci.insight.143285
LINK – PUBLISHER:
http://insight.jci.org/articles/view/143285?utm_source=hearinglosstreatmentreport.com
IMAGE:
REFERENCE:
Hearing Loss Treatment Report, Urgent Research, 2021-03-11T03:18:27+00:00, https://www.hearinglosstreatmentreport.com.
CATEGORY:
Research
SCREENSHOT:
TITLE:
Treatment of Long-term Sudden Sensorineural Hearing Loss as an Otologic Migraine Phenomenon
CONTENT:
Otol Neurotol. 2021 Mar 5. doi: 10.1097/MAO.0000000000003111. Online ahead of print.
ABSTRACT
OBJECTIVES: To describe a cohort of patients presenting with long-term sudden sensorineural hearing loss (SSNHL) treated with prophylactic migraine and intratympanic steroid therapy.
METHODS: Patients presenting to a neurotology clinic at least 6 weeks from SSNHL onset were included. All patients received migraine prophylactic medication (nortriptyline, topiramate, and/or verapamil) and lifestyle changes for at least 6 weeks, as well as intratympanic steroid injections, if appropriate.
RESULTS: Twenty-one patients (43% female) with a mean age of 64 ± 11 years who presented 9 ± 8 months (median = 5) from symptom onset were included. Posttreatment hearing thresholds were significantly improved compared with pretreatment thresholds at 500 Hz (49 ± 19 dB versus 55 ± 20 dB, p = 0.01), 1000 Hz (52 ± 19 dB versus 57 ± 21 dB, p = 0.03), low-frequency pure-tone average (53 ± 15 dB versus 57 ± 17 dB, p = 0.01), and speech-frequency pure-tone average (57 ± 13 dB versus 60 ± 15 dB, p = 0.02). Posttreatment word-recognition-score (WRS) and speech-recognition-threshold (SRT) were also significantly improved (45 ± 28% versus 70 ± 28% and 57 ± 18 dB versus 50 ± 16 dB, respectively, both p < 0.01). Notably, ≥15% improvement in WRS and ≥10 dB improvement in SRT was observed in 13 (68%) and 8 (40%) patients, respectively. Of the 11 patients who presented with initial < 50% WRS, 8 (73%) had improved posttreatment >50% WRS with an average improvement of 39 ± 9%.
CONCLUSIONS: Migraine medications in addition to intratympanic steroid injections significantly improved SRT and hearing frequencies in 40% and 29% of SSNHL patients, respectively, while significant WRS recovery was observed in most (68%) patients. This suggests SSNHL may be an otologic migraine phenomenon, which may be at least partially reversible even after the traditional 30-day postonset window.
PMID:33710150 | DOI:10.1097/MAO.0000000000003111
SOURCE:
Otology & neurotology : official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology
PUBLISHER:
PMID:
pubmed:33710150
ID:
0b58ea4968e09ff10f4e1238c494f316pubmed:33710150
DOI:
10.1097/MAO.0000000000003111
DATE – PUBLISHED:
Fri, 12 Mar 2021 06:00:00 -0500
DATE – DOI:
2021-03-12T14:03:36Z
DATE – ADDED:
03/12/21 01:58PM
LINK – PUBMED:
https://pubmed.ncbi.nlm.nih.gov/33710150/
LINK – DOI:
https://doi.org/10.1097/MAO.0000000000003111
LINK – PUBLISHER:
https://journals.lww.com/10.1097/MAO.0000000000003111?utm_source=hearinglosstreatmentreport.com
IMAGE:
REFERENCE:
Hearing Loss Treatment Report, Urgent Research, 2021-03-12T18:58:06+00:00, https://www.hearinglosstreatmentreport.com.
CATEGORY:
Research
SCREENSHOT:
TITLE:
Activation of KCNQ4 as a Therapeutic Strategy to Treat Hearing Loss
CONTENT:
Int J Mol Sci. 2021 Mar 2;22(5):2510. doi: 10.3390/ijms22052510.
ABSTRACT
Potassium voltage-gated channel subfamily q member 4 (KCNQ4) is a voltage-gated potassium channel that plays essential roles in maintaining ion homeostasis and regulating hair cell membrane potential. Reduction of the activity of the KCNQ4 channel owing to genetic mutations is responsible for nonsyndromic hearing loss, a typically late-onset, initially high-frequency loss progressing over time. In addition, variants of KCNQ4 have also been associated with noise-induced hearing loss and age-related hearing loss. Therefore, the discovery of small compounds activating or potentiating KCNQ4 is an important strategy for the curative treatment of hearing loss. In this review, we updated the current concept of the physiological role of KCNQ4 in the inner ear and the pathologic mechanism underlying the role of KCNQ4 variants with regard to hearing loss. Finally, we focused on currently developed KCNQ4 activators and their pros and cons, paving the way for the future development of specific KCNQ4 activators as a remedy for hearing loss.
PMID:33801540 | DOI:10.3390/ijms22052510
SOURCE:
International journal of molecular sciences
PUBLISHER:
PMID:
pubmed:33801540
ID:
0b58ea4968e09ff10f4e1238c494f316pubmed:33801540
DOI:
10.3390/ijms22052510
DATE – PUBLISHED:
Sat, 03 Apr 2021 06:00:00 -0400
DATE – DOI:
2021-03-03T02:30:13Z
DATE – ADDED:
04/03/21 05:12PM
LINK – PUBMED:
https://pubmed.ncbi.nlm.nih.gov/33801540/
LINK – DOI:
https://doi.org/10.3390/ijms22052510
LINK – PUBLISHER:
https://www.mdpi.com/1422-0067/22/5/2510/htm
https://www.mdpi.com/1422-0067/22/5/2510?utm_source=hearinglosstreatmentreport.com
IMAGE:
REFERENCE:
Hearing Loss Treatment Report, Urgent Research, 2021-04-03T21:12:02+00:00, https://www.hearinglosstreatmentreport.com.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7959764/
https://www.frontiersin.org/articles/10.3389/fcell.2021.642946/full
Molecular Behavior of HMGB1 in the Cochlea Following Noise Exposure and in vitro
Abstract
Noise-induced hearing loss (NIHL) is characterized by cellular damage to the inner ear, which is exacerbated by inflammation. High-mobility group box 1 (HMGB1), a representative damage-associated molecular pattern (DAMP), acts as a mediator of inflammation or an intercellular messenger according to its cellular localization. Blocking or regulating HMGB1 offers an attractive approach in ameliorating NIHL. However, the precise therapeutic intervention must be based on a deeper understanding of its dynamic molecular distribution and function in cochlear pathogenesis after acoustic trauma. Here, we have presented the spatiotemporal dynamics of the expression of HMGB1, exhibiting distribution variability in specific cochlear regions and cells following noise exposure. After gene manipulation, we further investigated the characteristics of cellular HMGB1 in HEI-OC1 cells. The higher cell viability observed in the HMGB1 knocked-down group after stimulation with H2O2 indicated the possible negative effect of HMGB1 on cellular lifespan. In conclusion, this study demonstrated that HMGB1 is involved in NIHL pathogenesis and its molecular biology has essential and subtle influences, preserving a translational potential for pharmacological intervention.
https://journals.lww.com/otology-neurotology/Abstract/9000/Improved_Speech_Intelligibility_in_Subjects_With.95768.aspx
Improved Speech Intelligibility in Subjects With Stable Sensorineural Hearing Loss Following Intratympanic Dosing of FX-322 in a Phase 1b Study
CATEGORY:
Research
SCREENSHOT:
TITLE:
T2 relaxation time shortening in the cochlea of patients with sudden sensory neuronal hearing loss: a retrospective study using quantitative synthetic magnetic resonance imaging
CONTENT:
Eur Radiol. 2021 Feb 20. doi: 10.1007/s00330-021-07749-5. Online ahead of print.
ABSTRACT
OBJECTIVES: High cochlear signal intensity on three-dimensional (3D) T2 fluid-attenuated inversion recovery (FLAIR) sequences in patients with sudden sensorineural hearing loss (SSNHL) has been reported. Here, we evaluated the cochlear T2 relaxation time differences in patients with idiopathic SSNHL using quantitative synthetic MRI (SyMRI).
METHODS: Twenty-four patients with unilateral SSNHL who underwent precontrast conventional 3D FLAIR and SyMRI were retrospectively included. T1 and T2 relaxation times and the proton density (PD) of the bilateral ears were measured by manually drawn regions of interest. Wilcoxon signed-rank tests and intra- and interobserver correlation analyses were performed. Qualitative analysis was also performed to determine the presence and laterality of the asymmetric high signal intensity on synthetic FLAIR (SyFLAIR) images.
RESULTS: The T2 relaxation time was significantly lower in the affected (basal and apico-middle turns) than in the unaffected cochlea (basal turn: 519 ± 181.3 vs. 608.8 ± 203.6, p = 0.042; apico-middle turn: 410.8 ± 163.8 vs. 514.5 ± 186.3, p = 0.037). There were no significant differences in the T1 relaxation time and PD between the affected and unaffected ears (p > 0.05). Additionally, three patients without asymmetric signal intensity on conventional MRI showed asymmetric increased signal intensity in the affected ear on SyFLAIR.
CONCLUSIONS: The T2 relaxation time was significantly shorter in the affected than in the unaffected cochlea of patients with idiopathic SSNHL. The SyMRI-derived T2 relaxation time may be a promising imaging marker, suggesting that the changes in inner ear fluid composition are implicated in the idiopathic SSNHL development.
KEY POINTS: • T2 relaxation time was significantly lower in the affected than in the unaffected cochlea. • SyFLAIR showed increased lesion conspicuity compared to conventional 3D-FLAIR in detecting asymmetric high signal intensity of the affected side. • SyMRI-derived T2 relaxation time may be a promising imaging marker of the affected ear in patients with idiopathic SSNHL.
PMID:33609144 | DOI:10.1007/s00330-021-07749-5
SOURCE:
European radiology
PUBLISHER:
PMID:
pubmed:33609144
ID:
0b58ea4968e09ff10f4e1238c494f316pubmed:33609144
DOI:
10.1007/s00330-021-07749-5
DATE – PUBLISHED:
Sat, 20 Feb 2021 06:00:00 -0500
DATE – DOI:
2021-02-20T17:19:51Z
DATE – ADDED:
02/21/21 01:27AM
LINK – PUBMED:
https://pubmed.ncbi.nlm.nih.gov/33609144/
LINK – DOI:
https://doi.org/10.1007/s00330-021-07749-5
LINK – PUBLISHER:
http://link.springer.com/10.1007/s00330-021-07749-5
IMAGE:
REFERENCE:
Hearing Loss Treatment Report, Urgent Research, 2021-02-21T06:27:26+00:00, https://www.hearinglosstreatmentreport.com.
CATEGORY:
Research
SCREENSHOT:
TITLE:
Expression of alpha2-Na/K-ATPase in C57BL/6J Mice Inner Ear and Its Relationship with Age-related Hearing Loss
CONTENT:
Curr Med Sci. 2021 Feb;41(1):153-157. doi: 10.1007/s11596-021-2330-5. Epub 2021 Feb 13.
ABSTRACT
K+ cycling in the cochlea is critical to maintain hearing. Many sodium-potassium pumps are proved to participate in K+ cycling, such as Na/K-ATPase. The α2-Na/K-ATPase is an important isoform of Na/K-ATPase. The expression of α2-Na/K-ATPase in the cochlea is not clear. In this study, we used C57BL/6 mice as a model of presbycusis and implemented immunohistochemistry staining and quantitative real time-PCR, and the α2-Na/K-ATPase expression pattern was confirmed in the inner ear. It was found α2-Na/K-ATPase was expressed widely in cochlea and its mRNA and protein expression was gradually reduced with aging (4-, 14-, 26- and 48-weeks old mice). We suspected that, the down-regulation of α2-Na/K-ATPase expression might be associated with the remodeling of K+ cycling, degeneration of morphological structure and decrease of hearing function in aging C57 mice. In conclusion, we speculated that the reduction of α2-Na/K-ATPase might play an important role in the pathogenesis of age-related hearing loss.
PMID:33582920 | DOI:10.1007/s11596-021-2330-5
SOURCE:
Current medical science
PUBLISHER:
PMID:
pubmed:33582920
ID:
0b58ea4968e09ff10f4e1238c494f316pubmed:33582920
DOI:
10.1007/s11596-021-2330-5
DATE – PUBLISHED:
Sun, 14 Feb 2021 06:00:00 -0500
DATE – DOI:
2021-02-14T09:43:18Z
DATE – ADDED:
02/15/21 01:12AM
LINK – PUBMED:
https://pubmed.ncbi.nlm.nih.gov/33582920/
LINK – DOI:
https://doi.org/10.1007/s11596-021-2330-5
LINK – PUBLISHER:
http://link.springer.com/10.1007/s11596-021-2330-5
IMAGE:
REFERENCE:
Hearing Loss Treatment Report, Urgent Research, 2021-02-15T06:12:41+00:00, https://www.hearinglosstreatmentreport.com.
https://www.nature.com/articles/s41598-021-81294-5
An antibody to RGMa promotes regeneration of cochlear synapses after noise exposure
Treatment of noise-exposed animals with an anti-RGMa blocking antibody regenerated inner hair cell synapses and resulted in recovery of wave-I amplitude of the auditory brainstem response, indicating effective reversal of synaptopathy.
COMMENT: see preprint from July 2, 2020
https://www.biorxiv.org/content/10.1101/2020.07.01.183269v1.full
https://pubs.acs.org/doi/abs/10.1021/acsami.0c21151
ROS-Responsive Nanoparticle as a Berberine Carrier for OHC-Targeted Therapy of Noise-Induced Hearing Loss
This work suggested that PL-PPS/BBR may be a new potential treatment for noise-associated injury with clinical application
https://pubmed.ncbi.nlm.nih.gov/33522002/
Stem Cells
2021 Jan 31. doi: 10.1002/stem.3346. Online ahead of print.
A human induced pluripotent stem cell-based modular platform to challenge sensorineural hearing loss
PMID: 33522002 DOI: 10.1002/stem.3346
CATEGORY:
Research
SCREENSHOT:
TITLE:
Stem Cells and Gene Therapy in Progressive Hearing Loss: the State of the Art
CONTENT:
J Assoc Res Otolaryngol. 2021 Jan 28. doi: 10.1007/s10162-020-00781-0. Online ahead of print.
ABSTRACT
Progressive non-syndromic sensorineural hearing loss (PNSHL) is the most common cause of sensory impairment, affecting more than a third of individuals over the age of 65. PNSHL includes noise-induced hearing loss (NIHL) and inherited forms of deafness, among which is delayed-onset autosomal dominant hearing loss (AD PNSHL). PNSHL is a prime candidate for genetic therapies due to the fact that PNSHL has been studied extensively, and there is a potentially wide window between identification of the disorder and the onset of hearing loss. Several gene therapy strategies exist that show potential for targeting PNSHL, including viral and non-viral approaches, and gene editing versus gene-modulating approaches. To fully explore the potential of these therapy strategies, a faithful in vitro model of the human inner ear is needed. Such models may come from induced pluripotent stem cells (iPSCs). The development of new treatment modalities by combining iPSC modeling with novel and innovative gene therapy approaches will pave the way for future applications leading to improved quality of life for many affected individuals and their families.
PMID:33507440 | DOI:10.1007/s10162-020-00781-0
SOURCE:
Journal of the Association for Research in Otolaryngology : JARO
PUBLISHER:
PMID:
pubmed:33507440
ID:
0b58ea4968e09ff10f4e1238c494f316pubmed:33507440
DOI:
10.1007/s10162-020-00781-0
DATE – PUBLISHED:
Thu, 28 Jan 2021 06:00:00 -0500
DATE – DOI:
2021-01-28T16:56:11Z
DATE – ADDED:
01/28/21 11:57PM
LINK – PUBMED:
https://pubmed.ncbi.nlm.nih.gov/33507440/
LINK – DOI:
https://doi.org/10.1007/s10162-020-00781-0
LINK – PUBLISHER:
http://link.springer.com/10.1007/s10162-020-00781-0
IMAGE:
REFERENCE:
Hearing Loss Treatment Report, Urgent Research, 2021-01-29T04:57:19+00:00, https://www.hearinglosstreatmentreport.com.
https://www.biorxiv.org/content/10.1101/2021.01.21.427665v1.full
Dual expression of Atoh1 and Ikzf2 promotes transformation of adult cochlear supporting cells into outer hair cells
https://www.cell.com/cell-reports/fulltext/S2211-1247(20)31635-1
https://pubmed.ncbi.nlm.nih.gov/33472062/
Greater epithelial ridge cells are the principal organoid-forming progenitors of the mouse cochlea
Greater epithelial ridge cells display robust potential to generate inner ear organoids
https://www.nature.com/articles/s41598-020-79946-z
Steady streaming as a method for drug delivery to the inner ear
CATEGORY:
Research
SCREENSHOT:
TITLE:
Glucose Protects Cochlear Hair Cells Against Oxidative Stress and Attenuates Noise-Induced Hearing Loss in Mice
CONTENT:
Neurosci Bull. 2021 Jan 7. doi: 10.1007/s12264-020-00624-1. Online ahead of print.
ABSTRACT
Oxidative stress is the key determinant in the pathogenesis of noise-induced hearing loss (NIHL). Given that cellular defense against oxidative stress is an energy-consuming process, the aim of the present study was to investigate whether increasing energy availability by glucose supplementation protects cochlear hair cells against oxidative stress and attenuates NIHL. Our results revealed that glucose supplementation reduced the noise-induced formation of reactive oxygen species (ROS) and consequently attenuated noise-induced loss of outer hair cells, inner hair cell synaptic ribbons, and NIHL in CBA/J mice. In cochlear explants, glucose supplementation increased the levels of ATP and NADPH, as well as attenuating H2 O2 -induced ROS production and cytotoxicity. Moreover, pharmacological inhibition of glucose transporter type 1 activity abolished the protective effects of glucose against oxidative stress in HEI-OC1 cells. These findings suggest that energy availability is crucial for oxidative stress resistance and glucose supplementation offers a simple and effective approach for the protection of cochlear hair cells against oxidative stress and NIHL.
PMID:33415566 | DOI:10.1007/s12264-020-00624-1
SOURCE:
Neuroscience bulletin
PUBLISHER:
PMID:
pubmed:33415566
ID:
0b58ea4968e09ff10f4e1238c494f316pubmed:33415566
DOI:
10.1007/s12264-020-00624-1
DATE – PUBLISHED:
Fri, 08 Jan 2021 06:00:00 -0500
DATE – DOI:
2021-01-07T18:43:13Z
DATE – ADDED:
01/08/21 01:01PM
LINK – PUBMED:
https://pubmed.ncbi.nlm.nih.gov/33415566/
LINK – DOI:
https://doi.org/10.1007/s12264-020-00624-1
LINK – PUBLISHER:
http://link.springer.com/10.1007/s12264-020-00624-1
IMAGE:
REFERENCE:
Hearing Loss Treatment Report, Urgent Research, 2021-01-08T18:01:22+00:00, https://www.hearinglosstreatmentreport.com.
CATEGORY:
Research
SCREENSHOT:
TITLE:
Polymorphisms in the FAS gene are associated with susceptibility to noise-induced hearing loss
CONTENT:
Environ Sci Pollut Res Int. 2021 Jan 7. doi: 10.1007/s11356-020-12028-9. Online ahead of print.
ABSTRACT
This study investigated the relationship between genetic polymorphisms in the FAS gene and noise-induced hearing loss (NIHL) risk among Chinese workers exposed to occupational noise, and the molecular mechanism of NIHL caused by noise. In this case-control study, 692 NIHL workers and 650 controls were selected for genotyping of four single nucleotide polymorphisms (SNPs) of the FAS gene. Logistic regression was used to calculate the odds ratio (OR) and 95% confidence interval (CI) of the association of these genetic polymorphisms and NIHL. At the same time, a noise-exposed rat model was constructed to further clarify the effect of noise exposure on fas gene expression and the pathogenic mechanism of NIHL. Two polymorphisms, rs1468063 and rs2862833, were associated with NIHL in the case-control study. Individuals with the rs1468063-TT or rs2862833-AA genotypes had decreased NIHL risk (p < 0.01, p = 0.02, respectively). Compared with the control group, the hearing threshold of the case group of rats increased, while serum MDA, urine 8-OHdG, and fas gene expression increased, but let-7e expression decreased. Genetic polymorphisms in the FAS gene are related to the risk of NIHL in the Chinese population. Noise can cause a large amount of reactive oxygen species (ROS) in the cochlea tissue and blood, which lead to oxidative stress, lipid peroxidation, and DNA damage, further activating the FAS gene, and ultimately leading to hearing loss. PMID:33411277 | DOI:10.1007/s11356-020-12028-9 SOURCE: Environmental science and pollution research international PUBLISHER: PMID: pubmed:33411277 ID: 0b58ea4968e09ff10f4e1238c494f316pubmed:33411277 DOI: 10.1007/s11356-020-12028-9 DATE - PUBLISHED: Thu, 07 Jan 2021 06:00:00 -0500 DATE - DOI: 2021-01-07T08:06:27Z DATE - ADDED: 01/07/21 06:43PM LINK - PUBMED: https://pubmed.ncbi.nlm.nih.gov/33411277/ LINK - DOI: https://doi.org/10.1007/s11356-020-12028-9 LINK - PUBLISHER: http://link.springer.com/10.1007/s11356-020-12028-9 IMAGE: REFERENCE: Hearing Loss Treatment Report, Urgent Research, 2021-01-07T23:43:34+00:00, https://www.hearinglosstreatmentreport.com.
https://www.preprints.org/manuscript/202101.0099/v1
Zebrafish as a Biomedical Model for Stem Cells Research in Hearing Impairment
Salma Hafeez * ORCID logo
Version 1 : Received: 4 January 2021 / Approved: 5 January 2021 / Online: 5 January 2021 (14:23:23 CET)
CATEGORY:
Research
SCREENSHOT:
TITLE:
Therapeutic Application of Mesenchymal Stem Cells for Cochlear Regeneration
CONTENT:
In Vivo. 2021 Jan-Feb;35(1):13-22. doi: 10.21873/invivo.12227.
ABSTRACT
Hearing loss is one of the major worldwide health problems that seriously affects human social and cognitive development. In the auditory system, three components outer ear, middle ear and inner ear are essential for the hearing mechanism. In the inner ear, sensory hair cells and ganglion neuronal cells are the essential supporters for hearing mechanism. Damage to these cells can be caused by long-term exposure of excessive noise, ototoxic drugs (aminoglycosides), ear tumors, infections, heredity and aging. Since mammalian cochlear hair cells do not regenerate naturally, some therapeutic interventions may be required to replace the damaged or lost cells. Cochlear implants and hearing aids are the temporary solutions for people suffering from severe hearing loss. The current discoveries in gene therapy may provide a deeper understanding in essential genes for the inner ear regeneration. Stem cell migration, survival and differentiation to supporting cells, cochlear hair cells and spiral ganglion neurons are the important foundation in understanding stem cell therapy. Moreover, mesenchymal stem cells (MSCs) from different sources (bone marrow, umbilical cord, adipose tissue and placenta) could be used in inner ear therapy. Transplanted MSCs in the inner ear can recruit homing factors at the damaged sites to induce transdifferentiation into inner hair cells and ganglion neurons or regeneration of sensory hair cells, thus enhancing the cochlear function. This review summarizes the potential application of mesenchymal stem cells in hearing restoration and combining stem cell and molecular therapeutic strategies can also be used in the recovery of cochlear function.
PMID:33402445 | DOI:10.21873/invivo.12227
SOURCE:
In vivo (Athens, Greece)
PUBLISHER:
PMID:
pubmed:33402445
ID:
0b58ea4968e09ff10f4e1238c494f316pubmed:33402445
DOI:
10.21873/invivo.12227
DATE – PUBLISHED:
Wed, 06 Jan 2021 06:00:00 -0500
DATE – DOI:
2021-01-05T18:16:14Z
DATE – ADDED:
01/06/21 06:28AM
LINK – PUBMED:
https://pubmed.ncbi.nlm.nih.gov/33402445/
LINK – DOI:
https://doi.org/10.21873/invivo.12227
LINK – PUBLISHER:
http://iv.iiarjournals.org/lookup/doi/10.21873/invivo.12227
IMAGE:
REFERENCE:
Hearing Loss Treatment Report, Urgent Research, 2021-01-06T11:28:12+00:00, https://www.hearinglosstreatmentreport.com.
https://stemcellsjournals.onlinelibrary.wiley.com/doi/full/10.1002/stem.3315
Directed differentiation and direct reprogramming: Applying stem cell technologies to hearing research
Marta Roccio
First published: 30 December 2020 https://doi.org/10.1002/stem.3315
Funding information: Schmieder Bohrisch Foundation; Zürcher Stiftung für das Hören
CATEGORY:
Research
SCREENSHOT:
TITLE:
Trk agonist drugs rescue noise-induced hidden hearing loss
CONTENT:
JCI Insight. 2020 Dec 29:142572. doi: 10.1172/jci.insight.142572. Online ahead of print.
ABSTRACT
TrkB agonist drugs are shown here to have a significant effect on the regeneration of afferent cochlear synapses after noise-induced synaptopathy. The effects were consistent with regeneration of cochlear synapses that we observed in vitro after synaptic loss due to kainic acid-induced glutamate toxicity and were elicited by administration of TrkB agonists, amitriptyline and 7,8- dihydroxyflavone, directly into the cochlea via the posterior semicircular canal 48 h after exposure to noise. Synaptic counts at the inner hair cell and wave 1 amplitudes in the ABR were partially restored 2 weeks after drug treatment. Effects of amitriptyline on wave 1 amplitude and afferent auditory synapse numbers in noise-exposed ears after systemic (as opposed to local) delivery were profound and long-lasting; synapses in the treated animals remained intact one year after the treatment. However, the effect of systemically delivered amitriptyline on synaptic rescue was dependent on dose and the time window of administration: it was only effective when given before noise exposure at the highest injected dose. The long-lasting effect and the efficacy of post-exposure treatment indicate a potential broad application for the treatment of synaptopathy, which often goes undetected until well after the original damaging exposure(s).
PMID:33373328 | DOI:10.1172/jci.insight.142572
SOURCE:
JCI insight
PUBLISHER:
PMID:
pubmed:33373328
ID:
0b58ea4968e09ff10f4e1238c494f316pubmed:33373328
DOI:
10.1172/jci.insight.142572
DATE – PUBLISHED:
Tue, 29 Dec 2020 06:00:00 -0500
DATE – DOI:
2020-12-29T17:02:53Z
DATE – ADDED:
12/29/20 11:36PM
LINK – PUBMED:
https://pubmed.ncbi.nlm.nih.gov/33373328/
LINK – DOI:
https://doi.org/10.1172/jci.insight.142572
LINK – PUBLISHER:
http://insight.jci.org/articles/view/142572
IMAGE:
REFERENCE:
Hearing Loss Treatment Report, Urgent Research, 2020-12-30T04:36:21+00:00, https://www.hearinglosstreatmentreport.com.
https://www.mdpi.com/1422-0067/22/1/131/htm
https://pubmed.ncbi.nlm.nih.gov/33374462/
Molecular Aspects of the Development and Function of Auditory Neurons
https://www.mdpi.com/1422-0067/22/1/3/htm
Regulator of G Protein Signalling 4 (RGS4) as a Novel Target for the Treatment of Sensorineural Hearing Loss
This research represents a novel paradigm for the treatment of various forms of SNHL based on regulation of GPCR.
CATEGORY:
Research
SCREENSHOT:
TITLE:
Extracellular vesicles from human multipotent stromal cells protect against hearing loss after noise trauma in vivo
CONTENT:
Clin Transl Med. 2020 Dec;10(8):e262. doi: 10.1002/ctm2.262.
ABSTRACT
The lack of approved anti-inflammatory and neuroprotective therapies in otology has been acknowledged in the last decades and recent approaches are heralding a new era in the field. Extracellular vesicles (EVs) derived from human multipotent (mesenchymal) stromal cells (MSC) can be enriched in vesicular secretome fractions, which have been shown to exert effects (eg, neuroprotection and immunomodulation) of their parental cells. Hence, MSC-derived EVs may serve as novel drug candidates for several inner ear diseases. Here, we provide first evidence of a strong neuroprotective potential of human stromal cell-derived EVs on inner ear physiology. In vitro, MSC-EV preparations exerted immunomodulatory activity on T cells and microglial cells. Moreover, local application of MSC-EVs to the inner ear significantly attenuated hearing loss and protected auditory hair cells from noise-induced trauma in vivo. Thus, EVs derived from the vesicular secretome of human MSC may represent a next-generation biological drug that can exert protective therapeutic effects in a complex and nonregenerating organ like the inner ear.
PMID:33377658 | DOI:10.1002/ctm2.262
SOURCE:
Clinical and translational medicine
PUBLISHER:
PMID:
pubmed:33377658
ID:
0b58ea4968e09ff10f4e1238c494f316pubmed:33377658
DOI:
10.1002/ctm2.262
DATE – PUBLISHED:
Wed, 30 Dec 2020 06:00:00 -0500
DATE – DOI:
2020-12-22T14:56:50Z
DATE – ADDED:
12/30/20 05:51PM
LINK – PUBMED:
https://pubmed.ncbi.nlm.nih.gov/33377658/
LINK – DOI:
https://doi.org/10.1002/ctm2.262
LINK – PUBLISHER:
https://onlinelibrary.wiley.com/doi/10.1002/ctm2.262
IMAGE:
REFERENCE:
Hearing Loss Treatment Report, Urgent Research, 2020-12-30T22:51:39+00:00, https://www.hearinglosstreatmentreport.com.
CATEGORY:
Research
SCREENSHOT:
TITLE:
Age-related hearing loss pertaining to potassium ion channels in the cochlea and auditory pathway
CONTENT:
Pflugers Arch. 2020 Dec 17. doi: 10.1007/s00424-020-02496-w. Online ahead of print.
ABSTRACT
Age-related hearing loss (ARHL) is the most prevalent sensory deficit in the elderly and constitutes the third highest risk factor for dementia. Lifetime noise exposure, genetic predispositions for degeneration, and metabolic stress are assumed to be the major causes of ARHL. Both noise-induced and hereditary progressive hearing have been linked to decreased cell surface expression and impaired conductance of the potassium ion channel KV 7.4 (KCNQ4) in outer hair cells, inspiring future therapies to maintain or prevent the decline of potassium ion channel surface expression to reduce ARHL. In concert with KV 7.4 in outer hair cells, KV 7.1 (KCNQ1) in the stria vascularis, calcium-activated potassium channels BK (KCNMA1) and SK2 (KCNN2) in hair cells and efferent fiber synapses, and KV 3.1 (KCNC1) in the spiral ganglia and ascending auditory circuits share an upregulated expression or subcellular targeting during final differentiation at hearing onset. They also share a distinctive fragility for noise exposure and age-dependent shortfalls in energy supply required for sustained surface expression. Here, we review and discuss the possible contribution of select potassium ion channels in the cochlea and auditory pathway to ARHL. We postulate genes, proteins, or modulators that contribute to sustained ion currents or proper surface expressions of potassium channels under challenging conditions as key for future therapies of ARHL.
PMID:33336302 | DOI:10.1007/s00424-020-02496-w
SOURCE:
Pflugers Archiv : European journal of physiology
PUBLISHER:
PMID:
pubmed:33336302
ID:
0b58ea4968e09ff10f4e1238c494f316pubmed:33336302
DOI:
10.1007/s00424-020-02496-w
DATE – PUBLISHED:
Fri, 18 Dec 2020 06:00:00 -0500
DATE – DOI:
2020-12-17T23:03:30Z
DATE – ADDED:
12/18/20 11:55AM
LINK – PUBMED:
https://pubmed.ncbi.nlm.nih.gov/33336302/
LINK – DOI:
https://doi.org/10.1007/s00424-020-02496-w
LINK – PUBLISHER:
http://link.springer.com/10.1007/s00424-020-02496-w
IMAGE:
REFERENCE:
Hearing Loss Treatment Report, Urgent Research, 2020-12-18T16:55:45+00:00, https://www.hearinglosstreatmentreport.com.
https://www.nature.com/articles/s41418-020-00678-8
Building inner ears: recent advances and future challenges for in vitro organoid systems
Wouter H. van der Valk, Matthew R. Steinhart, Jingyuan Zhang & Karl R. Koehler
Cell Death & Differentiation volume 28, pages24–34(2021)Cite this article
https://www.frontiersin.org/articles/10.3389/fncel.2020.599152/full
Front. Cell. Neurosci., 09 December 2020 | https://doi.org/10.3389/fncel.2020.599152
Intrinsically Self-renewing Neuroprogenitors From the A/J Mouse Spiral Ganglion as Virtually Unlimited Source of Mature Auditory Neurons
https://www.biorxiv.org/content/10.1101/2020.12.03.409946v1
https://www.biorxiv.org/content/10.1101/2020.12.03.409946v1.full.pdf
Efferent control of hearing sensitivity and protection via inner ear supporting cells
https://www.frontiersin.org/articles/10.3389/fcell.2020.614954/full
REVIEW ARTICLE
Front. Cell Dev. Biol., 03 December 2020 | https://doi.org/10.3389/fcell.2020.614954
The Role of FoxG1 in the Inner Ear
CATEGORY:
Research
SCREENSHOT:
TITLE:
Weakening of Interaction Networks with Aging in Tip-Link Protein Induces Hearing Loss
CONTENT:
Biochem J. 2020 Dec 3:BCJ20200799. doi: 10.1042/BCJ20200799. Online ahead of print.
ABSTRACT
Age-related hearing loss (ARHL) is a common condition in humans marking the gradual decrease in hearing with age. Perturbations in the tip-link protein cadherin-23 that absorbs the mechanical tension from sound and maintains the integrity of hearing is associated with ARHL. Here, in search of molecular origins for ARHL, we dissect the conformational behavior of cadherin-23 along with the mutant S47P that progresses the hearing-loss drastically. Using an array of experimental and computational approaches, we highlight a lower thermodynamic stability, significant weakening in the hydrogen-bond network and inter-residue correlations among β-strands, due to the S47P mutation. The loss in correlated motions translates to not only a remarkable two orders of magnitude slower folding in the mutant but also to a proportionately complex unfolding mechanism. We thus propose that loss in correlated motions within cadherin-23 with aging may trigger ARHL, a molecular feature that likely holds true for other disease-mutations in β-strand-rich proteins.
PMID:33270084 | DOI:10.1042/BCJ20200799
SOURCE:
The Biochemical journal
PUBLISHER:
PMID:
pubmed:33270084
ID:
0b58ea4968e09ff10f4e1238c494f316pubmed:33270084
DOI:
10.1042/BCJ20200799
DATE – PUBLISHED:
Thu, 03 Dec 2020 06:00:00 -0500
DATE – DOI:
2020-12-03T14:31:41Z
DATE – ADDED:
12/03/20 08:09PM
LINK – PUBMED:
https://pubmed.ncbi.nlm.nih.gov/33270084/
LINK – DOI:
https://doi.org/10.1042/BCJ20200799
LINK – PUBLISHER:
https://portlandpress.com/biochemj/article/doi/10.1042/BCJ20200799/227128/Weakening-of-Interaction-Networks-with-Aging-in
IMAGE:
REFERENCE:
Hearing Loss Treatment Report, Urgent Research, 2020-12-04T01:09:05+00:00, https://www.hearinglosstreatmentreport.com.
CATEGORY:
Research
SCREENSHOT:
TITLE:
BRAF inhibition protects against hearing loss in mice
CONTENT:
Sci Adv. 2020 Dec 2;6(49):eabd0561. doi: 10.1126/sciadv.abd0561. Print 2020 Dec.
ABSTRACT
Hearing loss caused by noise, aging, antibiotics, and chemotherapy affects 10% of the world population, yet there are no Food and Drug Administration (FDA)-approved drugs to prevent it. Here, we screened 162 small-molecule kinase-specific inhibitors for reduction of cisplatin toxicity in an inner ear cell line and identified dabrafenib (TAFINLAR), a BRAF kinase inhibitor FDA-approved for cancer treatment. Dabrafenib and six additional kinase inhibitors in the BRAF/MEK/ERK cellular pathway mitigated cisplatin-induced hair cell death in the cell line and mouse cochlear explants. In adult mice, oral delivery of dabrafenib repressed ERK phosphorylation in cochlear cells, and protected from cisplatin- and noise-induced hearing loss. Full protection was achieved in mice with co-treatment with oral AZD5438, a CDK2 kinase inhibitor. Our study explores a previously unidentified cellular pathway and molecular target BRAF kinase for otoprotection and may advance dabrafenib into clinics to benefit patients with cisplatin- and noise-induced ototoxicity.
PMID:33268358 | DOI:10.1126/sciadv.abd0561
SOURCE:
Science advances
PUBLISHER:
PMID:
pubmed:33268358
ID:
0b58ea4968e09ff10f4e1238c494f316pubmed:33268358
DOI:
10.1126/sciadv.abd0561
DATE – PUBLISHED:
Thu, 03 Dec 2020 06:00:00 -0500
DATE – DOI:
2020-12-03T02:03:28Z
DATE – ADDED:
12/03/20 07:55AM
LINK – PUBMED:
https://pubmed.ncbi.nlm.nih.gov/33268358/
LINK – DOI:
https://doi.org/10.1126/sciadv.abd0561
LINK – PUBLISHER:
https://advances.sciencemag.org/lookup/doi/10.1126/sciadv.abd0561
IMAGE:
REFERENCE:
Hearing Loss Treatment Report, Urgent Research, 2020-12-03T12:55:04+00:00, https://www.hearinglosstreatmentreport.com.
CATEGORY:
Research
SCREENSHOT:
TITLE:
Mutations of MAP1B encoding a microtubule-associated phosphoprotein cause sensorineural hearing loss
CONTENT:
JCI Insight. 2020 Dec 3;5(23):136046. doi: 10.1172/jci.insight.136046.
ABSTRACT
The pathophysiology underlying spiral ganglion cell defect-induced deafness remains elusive. Using the whole exome sequencing approach, in combination with functional assays and a mouse disease model, we identified the potentially novel deafness-causative MAP1B gene encoding a highly conserved microtubule-associated protein. Three novel heterozygous MAP1B mutations (c.4198A>G, p.1400S>G; c.2768T>C, p.923I>T; c.5512T>C, p.1838F>L) were cosegregated with autosomal dominant inheritance of nonsyndromic sensorineural hearing loss in 3 unrelated Chinese families. Here, we show that MAP1B is highly expressed in the spiral ganglion neurons in the mouse cochlea. Using otic sensory neuron-like cells, generated by pluripotent stem cells from patients carrying the MAP1B mutation and control subject, we demonstrated that the p.1400S>G mutation caused the reduced levels and deficient phosphorylation of MAP1B, which are involved in the microtubule stability and dynamics. Strikingly, otic sensory neuron-like cells exhibited disturbed dynamics of microtubules, axonal elongation, and defects in electrophysiological properties. Dysfunctions of these derived otic sensory neuron-like cells were rescued by genetically correcting MAP1B mutation using CRISPR/Cas9 technology. Involvement of MAP1B in hearing was confirmed by audiometric evaluation of Map1b heterozygous KO mice. These mutant mice displayed late-onset progressive sensorineural hearing loss that was more pronounced in the high frequencies. The spiral ganglion neurons isolated from Map1b mutant mice exhibited the deficient phosphorylation and disturbed dynamics of microtubules. Map1b deficiency yielded defects in the morphology and electrophysiology of spiral ganglion neurons, but it did not affect the morphologies of cochlea in mice. Therefore, our data demonstrate that dysfunctions of spiral ganglion neurons induced by MAP1B deficiency caused hearing loss.
PMID:33268592 | DOI:10.1172/jci.insight.136046
SOURCE:
JCI insight
PUBLISHER:
PMID:
pubmed:33268592
ID:
0b58ea4968e09ff10f4e1238c494f316pubmed:33268592
DOI:
10.1172/jci.insight.136046
DATE – PUBLISHED:
Thu, 03 Dec 2020 06:00:00 -0500
DATE – DOI:
2020-12-02T16:04:40Z
DATE – ADDED:
12/03/20 07:55AM
LINK – PUBMED:
https://pubmed.ncbi.nlm.nih.gov/33268592/
LINK – DOI:
https://doi.org/10.1172/jci.insight.136046
LINK – PUBLISHER:
https://insight.jci.org/articles/view/136046
IMAGE:
REFERENCE:
Hearing Loss Treatment Report, Urgent Research, 2020-12-03T12:55:03+00:00, https://www.hearinglosstreatmentreport.com.
CATEGORY:
Research
TITLE:
Noise Exposures Causing Hearing Loss Generate Proteotoxic Stress and Activate the Proteostasis Network
DESCRIPTION:
Exposure to excessive sound causes noise-induced hearing loss through complex mechanisms and represents a common and unmet neurological condition. We investigate how noise insults affect the cochlea with proteomics and functional assays. Quantitative proteomics reveals that exposure to loud noise causes proteotoxicity. We identify and confirm hundreds of proteins that accumulate, including cytoskeletal proteins, and several nodes of the proteostasis network. Transcriptomic analysis reveals that…
CONTENT:
Cell Rep. 2020 Nov 24;33(8):108431. doi: 10.1016/j.celrep.2020.108431.
ABSTRACT
Exposure to excessive sound causes noise-induced hearing loss through complex mechanisms and represents a common and unmet neurological condition. We investigate how noise insults affect the cochlea with proteomics and functional assays. Quantitative proteomics reveals that exposure to loud noise causes proteotoxicity. We identify and confirm hundreds of proteins that accumulate, including cytoskeletal proteins, and several nodes of the proteostasis network. Transcriptomic analysis reveals that a subset of the genes encoding these proteins also increases acutely after noise exposure, including numerous proteasome subunits. Global cochlear protein ubiquitylation levels build up after exposure to excess noise, and we map numerous posttranslationally modified lysines residues. Several collagen proteins decrease in abundance, and Col9a1 specifically localizes to pillar cell heads. After two weeks of recovery, the cochlea selectively elevates the abundance of the protein synthesis machinery. We report that overstimulation of the auditory system drives a robust cochlear proteotoxic stress response.
PMID:33238128 | DOI:10.1016/j.celrep.2020.108431
SOURCE:
Cell reports
DATE – PUBLISHED:
24 Nov 2020
DATE – ADDED:
Wed, 25 Nov 2020 06:00:00 -0500
DATE – FOUND:
11/26/20 05:57AM
PUBMED ID:
pubmed:33238128
DOI:
10.1016/j.celrep.2020.108431
PUBMED LINK:
https://pubmed.ncbi.nlm.nih.gov/33238128/
DOI LINK:
https://doi.org/10.1016/j.celrep.2020.108431
PUBLISHER LINK:
https://linkinghub.elsevier.com/retrieve/pii/S2211124720314200
JOURNAL LINK:
https://www.cell.com/cell-reports/fulltext/S2211-1247(20)31420-0
TITLE:
Endoscopic-Assisted Drug Delivery for Inner Ear Regeneration
DESCRIPTION:
Sensorineural hearing loss is caused by irreversible loss of auditory hair cells and/or neurons and is increasing in prevalence. Hair cells and neurons do not regenerate after damage, but novel regeneration therapies based on small molecule drugs, gene therapy, and cell replacement strategies offer promising therapeutic options. Endogenous and exogenous regeneration techniques are discussed in context of their feasibility for hair cell and neuron regeneration. Gene therapy and treatment of…
CONTENT:
Otolaryngol Clin North Am . 2021 Feb;54(1):189-200. doi: 10.1016/j.otc.2020.09.022.
ABSTRACT
Sensorineural hearing loss is caused by irreversible loss of auditory hair cells and/or neurons and is increasing in prevalence. Hair cells and neurons do not regenerate after damage, but novel regeneration therapies based on small molecule drugs, gene therapy, and cell replacement strategies offer promising therapeutic options. Endogenous and exogenous regeneration techniques are discussed in context of their feasibility for hair cell and neuron regeneration. Gene therapy and treatment of synaptopathy represent promising future therapies. Minimally invasive endoscopic ear surgery offers a viable approach to aid in delivery of pharmacologic compounds, cells, or viral vectors to the inner ear for all of these techniques.
PMID:33243375 | DOI:10.1016/j.otc.2020.09.022
IDENTIFIER:
pmid:33243375,doi:10.1016/j.otc.2020.09.022
PMID:
pubmed:33243375
ID:
5aa6076e0127310720e03f8fa09545b5pubmed:33243375
DOI:
10.1016/j.otc.2020.09.022
DATE – PUBLISHED:
Fri, 27 Nov 2020 06:00:00 -0500
DATE – DOI:
2020-11-23T09:13:42Z
DATE – RETRIEVED:
11/27/20 06:17AM
LINK – PUBMED:
https://pubmed.ncbi.nlm.nih.gov/33243375/
LINK – DOI:
https://doi.org/10.1016/j.otc.2020.09.022
LINK – PUBLISHER:
https://linkinghub.elsevier.com/retrieve/pii/S0030666520366962
CATEGORY:
Research
TITLE:
G6PD overexpression protects from oxidative stress and age-related hearing loss
DESCRIPTION:
Aging of the auditory system is associated with the incremental production of reactive oxygen species (ROS) and the accumulation of oxidative damage in macromolecules, which contributes to cellular malfunction, compromises cell viability, and, ultimately, leads to functional decline. Cellular detoxification relies in part on the production of NADPH, which is an important cofactor for major cellular antioxidant systems. NADPH is produced principally by the housekeeping enzyme glucose-6-phosphate…
CONTENT:
Aging Cell. 2020 Nov 22:e13275. doi: 10.1111/acel.13275. Online ahead of print.
ABSTRACT
Aging of the auditory system is associated with the incremental production of reactive oxygen species (ROS) and the accumulation of oxidative damage in macromolecules, which contributes to cellular malfunction, compromises cell viability, and, ultimately, leads to functional decline. Cellular detoxification relies in part on the production of NADPH, which is an important cofactor for major cellular antioxidant systems. NADPH is produced principally by the housekeeping enzyme glucose-6-phosphate dehydrogenase (G6PD), which catalyzes the rate-limiting step in the pentose phosphate pathway. We show here that G6PD transgenic mice (G6PD-Tg), which show enhanced constitutive G6PD activity and NADPH production along life, have lower auditory thresholds than wild-type mice during aging, together with preserved inner hair cell (IHC) and outer hair cell (OHC), OHC innervation, and a conserved number of synapses per IHC. Gene expression of antioxidant enzymes was higher in 3-month-old G6PD-Tg mice than in wild-type counterparts, whereas the levels of pro-apoptotic proteins were lower. Consequently, nitration of proteins, mitochondrial damage, and TUNEL+ apoptotic cells were all lower in 9-month-old G6PD-Tg than in wild-type counterparts. Unexpectedly, G6PD overexpression triggered low-grade inflammation that was effectively resolved in young mice, as shown by the absence of cochlear cellular damage and macrophage infiltration. Our results lead us to propose that NADPH overproduction from an early stage is an efficient mechanism to maintain the balance between the production of ROS and cellular detoxification power along aging and thus prevents hearing loss progression.
PMID:33222382 | DOI:10.1111/acel.13275
SOURCE:
Aging cell
DATE – PUBLISHED:
22 Nov 2020
DATE – ADDED:
Sun, 22 Nov 2020 06:00:00 -0500
DATE – FOUND:
11/23/20 05:39AM
PUBMED ID:
pubmed:33222382
DOI:
10.1111/acel.13275
PUBMED LINK:
https://pubmed.ncbi.nlm.nih.gov/33222382/
DOI LINK:
https://doi.org/10.1111/acel.13275
PUBLISHER LINK:
https://onlinelibrary.wiley.com/doi/10.1111/acel.13275
https://www.biorxiv.org/content/10.1101/2020.11.17.387001v1
https://www.biorxiv.org/content/10.1101/2020.11.17.387001v1?utm_source=hearinglosstreatmentreport.com
Towards personalized auditory models: predicting individual sensorineural-hearing-loss profiles from recorded human auditory physiology
Sarineh Keshishzadeh, Markus Garrett, Sarah Verhulst
doi: https://doi.org/10.1101/2020.11.17.387001
https://www.nature.com/articles/s41598-020-76553-w
https://pubmed.ncbi.nlm.nih.gov/33203940/
Synaptic migration and reorganization after noise exposure suggests regeneration in a mature mammalian cochlea
https://www.mdpi.com/1422-0067/21/22/8649/htm
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7696585/
https://pubmed.ncbi.nlm.nih.gov/33212773/
Generation of Cochlear Hair Cells from Sox2 Positive Supporting Cells via DNA Demethylation
https://www.pnas.org/content/early/2020/11/13/2016858117
Proc Natl Acad Sci U S A
2020 Nov 16;202016858. doi: 10.1073/pnas.2016858117. Online ahead of print.
Fast recovery of disrupted tip links induced by mechanical displacement of hair bundles
CATEGORY:
Research
TITLE:
Single and dual vector gene therapy with AAV9-PHP.B rescues hearing in Tmc1 mutant mice
DESCRIPTION:
AAV-mediated gene therapy is a promising approach for treating genetic hearing loss. Replacement or editing of the Tmc1 gene, encoding hair cell mechanosensory ion channels, is effective for hearing restoration in mice with some limitations. Efficient rescue of outer hair cell function, as well as lack of hearing recovery with later stage treatment, remain issues to be solved. Exogenous genes delivered with the AAV9-PHP.B capsid via the utricle transduce both inner and outer hair cells of the…
CONTENT:
Mol Ther. 2020 Nov 16:S1525-0016(20)30614-6. doi: 10.1016/j.ymthe.2020.11.016. Online ahead of print.
ABSTRACT
AAV-mediated gene therapy is a promising approach for treating genetic hearing loss. Replacement or editing of the Tmc1 gene, encoding hair cell mechanosensory ion channels, is effective for hearing restoration in mice with some limitations. Efficient rescue of outer hair cell function, as well as lack of hearing recovery with later stage treatment, remain issues to be solved. Exogenous genes delivered with the AAV9-PHP.B capsid via the utricle transduce both inner and outer hair cells of the mouse cochlea with high efficacy. Here we demonstrate that AAV9-PHP.B gene therapy can promote hair cell survival and successfully rescues hearing in three distinct mouse models of hearing loss. Tmc1 replacement with AAV9-PHP.B in a Tmc1 knockout mouse rescues hearing and promotes hair cell survival with equal efficacy in inner and outer hair cells. The same treatment in a recessive Tmc1 hearing loss model, Baringo, partially recovers hearing even with later stage treatment. Finally, dual delivery of SpCas9 and gRNA in separate AAV9-PHP.B vectors selectively disrupts a dominant Tmc1 allele and preserves hearing in Beethoven mice, a model of dominant, progressive hearing loss. Tmc1-targeted gene therapies using single or dual AAV9-PHP.B vectors offer potent and versatile approaches for treating dominant and recessive deafness.
PMID:33212302 | DOI:10.1016/j.ymthe.2020.11.016
SOURCE:
Molecular therapy : the journal of the American Society of Gene Therapy
DATE – PUBLISHED:
16 Nov 2020
DATE – ADDED:
Thu, 19 Nov 2020 06:00:00 -0500
DATE – FOUND:
11/20/20 05:29AM
PUBMED ID:
pubmed:33212302
DOI:
10.1016/j.ymthe.2020.11.016
PUBMED LINK:
https://pubmed.ncbi.nlm.nih.gov/33212302/
DOI LINK:
https://doi.org/10.1016/j.ymthe.2020.11.016
PUBLISHER LINK:
https://linkinghub.elsevier.com/retrieve/pii/S1525001620306146
https://journals.lww.com/otology-neurotology/Abstract/9000/Access_to_the_Apical_Cochlear_Modiolus_for.95934.aspx
Access to the Apical Cochlear Modiolus for Possible Stem Cell-Based and Gene Therapy of the Auditory Nerve
Wrobel, Christian*,†; Bevis, Nicholas F.*; Meyer, Alexander C.*; Beutner, Dirk*Author Information
Otology & Neurotology: November 06, 2020 – Volume Publish Ahead of Print – Issue –
doi: 10.1097/MAO.0000000000002941
CATEGORY:
Research
TITLE:
Protection of Cochlear Ribbon Synapses and Prevention of Hidden Hearing Loss
DESCRIPTION:
In the auditory system, ribbon synapses are vesicle-associated structures located between inner hair cells (IHCs) and spiral ganglion neurons that are implicated in the modulation of trafficking and fusion of synaptic vesicles at the presynaptic terminals. Synapse loss may result in hearing loss and difficulties with understanding speech in a noisy environment. This phenomenon happens without permanent hearing loss; that is, the cochlear synaptopathy is “hidden.” Recent studies have reported…
DATE – PUBLISHED:
Mon, 02 Nov 2020 22:35:10 +0000
LINK – PUBLISHER:
https://www.hindawi.com/journals/np/2020/8815990/
https://faseb.onlinelibrary.wiley.com/doi/10.1096/fj.202000939R
https://pubmed.ncbi.nlm.nih.gov/33131093/
Adenosine A2B receptor: A pathogenic factor and a therapeutic target for sensorineural hearing loss
Jeanne M. Manalo Hong Liu Dalian Ding John Hicks Hong Sun Richard Salvi Rodney E. Kellems Fred A. Pereira Yang Xia
CATEGORY:
Research
TITLE:
BDNF Outperforms TrkB Agonist 7,8,3′-THF in Preserving the Auditory Nerve in Deafened Guinea Pigs
DESCRIPTION:
In deaf subjects using a cochlear implant (CI) for hearing restoration, the auditory nerve is subject to degeneration, which may negatively impact CI effectiveness. This nerve degeneration can be reduced by neurotrophic treatment. Here, we compare the preservative effects of the naturally occurring tyrosine receptor kinase B (TrkB) agonist brain-derived neurotrophic factor (BDNF) and the small-molecule TrkB agonist 7,8,3′-trihydroxyflavone (THF) on the auditory nerve in deafened guinea pigs. THF…
CONTENT:
Brain Sci. 2020 Oct 28;10(11):E787. doi: 10.3390/brainsci10110787.
ABSTRACT
In deaf subjects using a cochlear implant (CI) for hearing restoration, the auditory nerve is subject to degeneration, which may negatively impact CI effectiveness. This nerve degeneration can be reduced by neurotrophic treatment. Here, we compare the preservative effects of the naturally occurring tyrosine receptor kinase B (TrkB) agonist brain-derived neurotrophic factor (BDNF) and the small-molecule TrkB agonist 7,8,3′-trihydroxyflavone (THF) on the auditory nerve in deafened guinea pigs. THF may be more effective than BDNF throughout the cochlea because of better pharmacokinetic properties. The neurotrophic compounds were delivered by placement of a gelatin sponge on the perforated round window membrane. To complement the histology of spiral ganglion cells (SGCs), electrically evoked compound action potential (eCAP) recordings were performed four weeks after treatment initiation. We analyzed the eCAP inter-phase gap (IPG) effect and measures derived from pulse-train evoked eCAPs, both indicative of SGC healthiness. BDNF but not THF yielded a significantly higher survival of SGCs in the basal cochlear turn than untreated controls. Regarding IPG effect and pulse-train responses, the BDNF-treated animals exhibited more normal responses than both untreated and THF-treated animals. We have thus confirmed the protective effect of BDNF, but we have not confirmed previously reported protective effects of THF with our clinically applicable delivery method.
PMID:33126525 | DOI:10.3390/brainsci10110787
SOURCE:
Brain sciences
DATE – PUBLISHED:
28 Oct 2020
DATE – ADDED:
Sat, 31 Oct 2020 06:00:00 -0400
DATE – FOUND:
10/31/20 12:11PM
PUBMED ID:
pubmed:33126525
DOI:
10.3390/brainsci10110787
PUBMED LINK:
https://pubmed.ncbi.nlm.nih.gov/33126525/
DOI LINK:
https://doi.org/10.3390/brainsci10110787
PUBLISHER LINK:
https://www.mdpi.com/2076-3425/10/11/787
CATEGORY:
Research
SCREENSHOT:
TITLE:
Analysis of related factors between sudden sensorineural hearing loss and serum indices base on artificial intelligence and big data
CONTENT:
Lin Chung Er Bi Yan Hou Tou Jing Wai Ke Za Zhi. 2020 Nov;34(11):977-980. doi: 10.13201/j.issn.2096-7993.2020.11.004.
ABSTRACT
Objective: The etiology and pathophysiologic mechanism of sudden sensorineural hearing loss are undefined. We will use artificial intelligence and big data methods to explore the correlation between sudden sensorineural hearing loss and serum indices. Method: A total of 1218 patients with sudden deafness admitted to Sun Yat-sen Memorial Hospital were selected as the experimental group, 95 861 healthy subjects were randomly selected as the control group at the same period. Serum biochemical indexes in two groups were collected and analyzed by TreeNet and CART machine learning algorithms, to screen out highly correlated indicators with sudden sensorineural hearing loss and dig out a set of clinical features for people with high risk of sudden sensorineural hearing loss. Result: It was found that high prevalence rate of sudden sensorineural hearing loss is related to eosinophils, reticulocyte and fibrinogen. The areas under the receiver operator characteristic curves（ROC-AUC） were exploited to evaluate the prediction performance of TreeNet model. Overall the TreeNet model has provided high predictive ability by ROC curve, achieving AUC of 0.99, both recall and accuracy rate of 99.90%. Conclusion: There is significant difference between sudden deadness and normal people in serum biochemical indexes. Eosinophil is the first important indicator to distinguish sudden sensorineural hearing loss. Treenet model has important referenced significance for the screening and diagnosis of sudden sensorineural hearing loss.
PMID:33254313 | DOI:10.13201/j.issn.2096-7993.2020.11.004
SOURCE:
Lin chuang er bi yan hou tou jing wai ke za zhi = Journal of clinical otorhinolaryngology, head, and neck surgery
PUBLISHER:
基于人工智能下突发性聋与血清指标的相关因素分析
PMID:
pubmed:33254313
ID:
0b58ea4968e09ff10f4e1238c494f316pubmed:33254313
DOI:
10.13201/j.issn.2096-7993.2020.11.004
DATE – PUBLISHED:
Mon, 30 Nov 2020 06:00:00 -0500
DATE – DOI:
2020-10-27T07:21:43Z
DATE – ADDED:
12/01/20 05:32AM
LINK – PUBMED:
https://pubmed.ncbi.nlm.nih.gov/33254313/
LINK – DOI:
https://doi.org/10.13201/j.issn.2096-7993.2020.11.004
LINK – PUBLISHER:
http://kns.cnki.net/kcms/detail/detail.aspx?doi=10.13201/j.issn.2096-7993.2020.11.004
IMAGE:
https://piccache.cnki.net/kdn/index/kns7/nimages/logo_xl.png
https://kns.cnki.net/kcms/Detail/resource/gb/images/icon-qrcode-download.jpg,https://kns.cnki.net/kcms/Detail/resource/gb/images/icon-pop-sample.jpg,https://piccache.cnki.net/kdn/index/kns7/nimages/logo_xl.png,https://piccache.cnki.net/kdn/index/kns7/nimages/logo_tx.png,https://piccache.cnki.net/kdn/index/kns7/nimages/foot-logo.png,https://piccache.cnki.net/kdn/index/kns7/nimages/kxwz.jpg
REFERENCE:
Hearing Loss Treatment Report, Urgent Research, 2020-12-01T10:32:32+00:00, https://www.hearinglosstreatmentreport.com.
CATEGORY:
Research
SCREENSHOT:
TITLE:
Outcome of otolith organ function after treatment of sudden sensorineural hearing loss
CONTENT:
Lin Chung Er Bi Yan Hou Tou Jing Wai Ke Za Zhi. 2020 Nov;34(11):993-998. doi: 10.13201/j.issn.2096-7993.2020.11.008.
ABSTRACT
Objective: This study aimed to assess the clinical practice value of ocular vestibular evoked myogenic potential（oVEMP） and cervical vestibular evoked myogenic potential（cVEMP） in monitoring the rehabilitation of vestibular function in patients with suddensen sorineural hearing loss（SSHL）. Method: Twenty-four patients with SSHL were retrospectively enrolled， showing no VEMP response on the affected side but exhibiting VEMP responses after therapies We analyzed the improvement and the restoration of hearing and the parameters of VEMP response. Result: After treatment, seven patients showed VEMP recovery, including three cases with both oVEMP and cVEMP recovery, three cases with oVEMP recovery, and one case with cVEMP recovery. Between VEMP recoved group and VEMP unrecoved group, before treatment, no significant difference was found in the thresholds of pure-tone audiometry（PTA）. However, after treatment, VEMP recoved group exhibited lower PTA thresholds and better PTA shift （P <0.01）. Multivariate analysis revealed that recovery of VEMP was the independent risk factor for the therapeutic effect of SSHL. Conclusion: The Combination of oVEMP and cVEMP is an objective tool for assessing vestibular otolithic end organ function during dynamic functional recovery in SSHL and the recovery of VEMP could predict the auditory improvement. PMID:33254317 | DOI:10.13201/j.issn.2096-7993.2020.11.008 SOURCE: Lin chuang er bi yan hou tou jing wai ke za zhi = Journal of clinical otorhinolaryngology, head, and neck surgery PUBLISHER: 突发性聋治疗后耳石器功能转归 PMID: pubmed:33254317 ID: 0b58ea4968e09ff10f4e1238c494f316pubmed:33254317 DOI: 10.13201/j.issn.2096-7993.2020.11.008 DATE - PUBLISHED: Mon, 30 Nov 2020 06:00:00 -0500 DATE - DOI: 2020-10-27T07:21:43Z DATE - ADDED: 12/01/20 05:32AM LINK - PUBMED: https://pubmed.ncbi.nlm.nih.gov/33254317/ LINK - DOI: https://doi.org/10.13201/j.issn.2096-7993.2020.11.008 LINK - PUBLISHER: http://kns.cnki.net/kcms/detail/detail.aspx?doi=10.13201/j.issn.2096-7993.2020.11.008 IMAGE: https://piccache.cnki.net/kdn/index/kns7/nimages/logo_xl.png https://kns.cnki.net/kcms/Detail/resource/gb/images/icon-qrcode-download.jpg,https://kns.cnki.net/kcms/Detail/resource/gb/images/icon-pop-sample.jpg,https://piccache.cnki.net/kdn/index/kns7/nimages/logo_xl.png,https://piccache.cnki.net/kdn/index/kns7/nimages/logo_tx.png,https://piccache.cnki.net/kdn/index/kns7/nimages/foot-logo.png,https://piccache.cnki.net/kdn/index/kns7/nimages/kxwz.jpg REFERENCE: Hearing Loss Treatment Report, Urgent Research, 2020-12-01T10:32:34+00:00, https://www.hearinglosstreatmentreport.com.
CATEGORY:
Research
TITLE:
Perspectives on Human Hearing Loss, Cochlear Regeneration, and the Potential for Hearing Restoration Therapies
DESCRIPTION:
Most adults who acquire hearing loss find it to be a disability that is poorly corrected by current prosthetics. This gap drives current research in cochlear mechanosensory hair cell regeneration and in hearing restoration. Birds and fish can spontaneously regenerate lost hair cells through a process that has become better defined in the last few years. Findings from these studies have informed new research on hair cell regeneration in the mammalian cochlea. Hair cell regeneration is one part of…
CONTENT:
Brain Sci. 2020 Oct 20;10(10):E756. doi: 10.3390/brainsci10100756.
ABSTRACT
Most adults who acquire hearing loss find it to be a disability that is poorly corrected by current prosthetics. This gap drives current research in cochlear mechanosensory hair cell regeneration and in hearing restoration. Birds and fish can spontaneously regenerate lost hair cells through a process that has become better defined in the last few years. Findings from these studies have informed new research on hair cell regeneration in the mammalian cochlea. Hair cell regeneration is one part of the greater problem of hearing restoration, as hearing loss can stem from a myriad of causes. This review discusses these issues and recent findings, and places them in the greater social context of need and community.
PMID:33092183 | DOI:10.3390/brainsci10100756
SOURCE:
Brain sciences
DATE – PUBLISHED:
20 Oct 2020
DATE – ADDED:
Fri, 23 Oct 2020 06:00:00 -0400
DATE – FOUND:
10/23/20 07:18AM
PUBMED ID:
pubmed:33092183
DOI:
10.3390/brainsci10100756
PUBMED LINK:
https://pubmed.ncbi.nlm.nih.gov/33092183/
DOI LINK:
https://doi.org/10.3390/brainsci10100756
PUBLISHER LINK:
https://www.mdpi.com/2076-3425/10/10/756
CATEGORY:
Research
TITLE:
Progenitor cell therapy for acquired pediatric nervous system injury: Traumatic brain injury and acquired sensorineural hearing loss
DESCRIPTION:
While cell therapies hold remarkable promise for replacing injured cells and repairing damaged tissues, cell replacement is not the only means by which these therapies can achieve therapeutic effect. For example, recent publications show that treatment with varieties of adult, multipotent stem cells can improve outcomes in patients with neurological conditions such as traumatic brain injury and hearing loss without directly replacing damaged or lost cells. As the immune system plays a central…
CONTENT:
Stem Cells Transl Med. 2020 Oct 9. doi: 10.1002/sctm.20-0026. Online ahead of print.
ABSTRACT
While cell therapies hold remarkable promise for replacing injured cells and repairing damaged tissues, cell replacement is not the only means by which these therapies can achieve therapeutic effect. For example, recent publications show that treatment with varieties of adult, multipotent stem cells can improve outcomes in patients with neurological conditions such as traumatic brain injury and hearing loss without directly replacing damaged or lost cells. As the immune system plays a central role in injury response and tissue repair, we here suggest that multipotent stem cell therapies achieve therapeutic effect by altering the immune response to injury, thereby limiting damage due to inflammation and possibly promoting repair. These findings argue for a broader understanding of the mechanisms by which cell therapies can benefit patients.
PMID:33034162 | DOI:10.1002/sctm.20-0026
SOURCE:
Stem cells translational medicine
DATE – PUBLISHED:
9 Oct 2020
DATE – ADDED:
Fri, 09 Oct 2020 06:00:00 -0400
DATE – FOUND:
10/09/20 07:09AM
PUBMED ID:
pubmed:33034162
DOI:
10.1002/sctm.20-0026
PUBMED LINK:
https://pubmed.ncbi.nlm.nih.gov/33034162/
DOI LINK:
https://doi.org/10.1002/sctm.20-0026
PUBLISHER LINK:
https://onlinelibrary.wiley.com/doi/10.1002/sctm.20-0026
CATEGORY:
Research
TITLE:
GRβ Regulates Glucocorticoid Resistance in Sudden Sensorineural Hearing Loss
DESCRIPTION:
CONCLUSION: We clarified the mechanisms of high expression of GRβ in glucocorticoid-resistant sudden sensorineural hearing loss, and proved that the inhibition of SRp30c may act as a new treatment way of glucocorticoid-resistant sudden sensorineural hearing loss.
CONTENT:
Curr Pharm Biotechnol. 2020 Oct 8. doi: 10.2174/1389201021666201008163534. Online ahead of print.
ABSTRACT
BACKGROUND: In recent years, the incidence of sudden deafness has gradually increased, with a very limited understanding of the etiology and the pathogenesis. Glucocorticoids are the first choice for the treatment, but some hormoneresistant patients are not sensitive to glucocorticoid therapy. The pathogenesis is not yet known. In this study, we aim to construct HEI-OC1 cell line stably overexpressing glucocorticoid receptor beta (GRβ), and identify its exact role in the cases of glucocorticoid-resistant sudden deafness.
METHOD: We used the endotoxin lipopolysaccharide-stimulated cochlear hair cells (HEI-OC1) to investigate the relationship of inflammation factor IL-2, TNF alpha, and SRp30c with the high expression GRβ. We build a stable GRβ high expression HEI-OC1 cell line and clarified its effects on the therapeutic effect from Dexamethasone. MTT assay, colony formation assay, CCK-8 assay, Western blot, and RT-qPCR were utilized for the characterizations.
RESULTS: Dexamethasone reduced LPS-induced inflammatory response in HEI-OC1 cells (p<0.05), detected by MTT assay. Dexamethasone could protect HEI-OC1 cells, but its protective effect was weakened due to the transfection of SRp30c overexpression plasmid (p<0.05). The transfection of SRp30c over-expression plasmid in HEI-OC1 cells could elevate the expressions of GRβ (p<0.05). CONCLUSION: We clarified the mechanisms of high expression of GRβ in glucocorticoid-resistant sudden sensorineural hearing loss, and proved that the inhibition of SRp30c may act as a new treatment way of glucocorticoid-resistant sudden sensorineural hearing loss. PMID:33032506 | DOI:10.2174/1389201021666201008163534 SOURCE: Current pharmaceutical biotechnology DATE - PUBLISHED: 8 Oct 2020 DATE - ADDED: Fri, 09 Oct 2020 06:00:00 -0400 DATE - FOUND: 10/09/20 07:09AM PUBMED ID: pubmed:33032506 DOI: 10.2174/1389201021666201008163534 PUBMED LINK: https://pubmed.ncbi.nlm.nih.gov/33032506/ DOI LINK: https://doi.org/10.2174/1389201021666201008163534 PUBLISHER LINK: https://www.eurekaselect.com/186752/article
CATEGORY:
Research
TITLE:
Altered outer hair cell mitochondrial and subsurface cisternae connectomics are candidate mechanisms for hearing-loss in mice
DESCRIPTION:
Organelle crosstalk is vital for cellular functions. The propinquity of mitochondria, endoplasmic reticulum (ER), and plasma membrane promote regulation of multiple functions, which include intracellular Ca^(2+) flux, and cellular biogenesis. Although the purposes of apposing mitochondria and ER have been described, an understanding of altered organelle connectomics related to disease states is emerging. Since inner ear outer hair cell (OHC) degeneration is a common trait of age-related hearing…
CONTENT:
J Neurosci. 2020 Oct 5:JN-RM-2901-19. doi: 10.1523/JNEUROSCI.2901-19.2020. Online ahead of print.
ABSTRACT
Organelle crosstalk is vital for cellular functions. The propinquity of mitochondria, endoplasmic reticulum (ER), and plasma membrane promote regulation of multiple functions, which include intracellular Ca2+ flux, and cellular biogenesis. Although the purposes of apposing mitochondria and ER have been described, an understanding of altered organelle connectomics related to disease states is emerging. Since inner ear outer hair cell (OHC) degeneration is a common trait of age-related hearing loss, the objective of this study was to investigate whether the structural and functional coupling of mitochondria with subsurface cisternae (SSC), was affected by aging. We applied functional and structural probes to equal numbers of male and female mice with a hearing phenotype akin to human aging. We discovered the polarization of cristae and crista junctions in mitochondria tethered to the SSC in OHCs. Aging was associated with SSC stress and decoupling of mitochondria with the SSC, mitochondrial fission/fusion imbalance, a remarkable reduction in mitochondrial and cytoplasmic Ca2+ levels, reduced K+ -induced Ca2+ uptake, and marked plasticity of cristae membranes. A model of structure-based ATP production predicts profound energy stress in older OHCs. This report provides data suggesting that altered membrane organelle connectomics may result in progressive hearing loss.SIGNIFICANCE STATEMENT We address the question, “Do aged OHCs exhibit detectable changes in organelle connectomics that would help us better understand human hearing loss in a relevant mouse model?” Because of the close association of mitochondria SSC over much of the OHC inner surface, mitochondria-SSC connectomics appears to play a central role in hearing. In polarized cells such as OHCs, where there is functional segregation of apical versus basal regions, the relationship between altered organelle connectomics and hearing loss is unknown. We propose a mechanism of mitochondria-SSC dysregulation related to aging and OHC degeneration, showing distinct altered mitochondrial and cytoplasmic Ca2+ regulation, mitochondrial polarization, and fission/fusion imbalance, mitochondrial-SSC decoupling, and SSC and cellular energy stress.
PMID:33020216 | DOI:10.1523/JNEUROSCI.2901-19.2020
SOURCE:
The Journal of neuroscience : the official journal of the Society for Neuroscience
DATE – PUBLISHED:
5 Oct 2020
DATE – ADDED:
Tue, 06 Oct 2020 06:00:00 -0400
DATE – FOUND:
10/06/20 07:06AM
PUBMED ID:
pubmed:33020216
DOI:
10.1523/JNEUROSCI.2901-19.2020
PUBMED LINK:
https://pubmed.ncbi.nlm.nih.gov/33020216/
DOI LINK:
https://doi.org/10.1523/JNEUROSCI.2901-19.2020
PUBLISHER LINK:
http://www.jneurosci.org/lookup/doi/10.1523/JNEUROSCI.2901-19.2020
CATEGORY:
Research
TITLE:
Biomarkers Suggesting Favorable Prognostic Outcomes in Sudden Sensorineural Hearing Loss
DESCRIPTION:
Sudden sensorineural hearing loss (SSNHL) is a medical emergency, making detailed examination to determine possible causes and early treatment important. However, etiological examinations in SSNHL do not always reveal a cause, and several factors have been found to affect treatment outcomes. Various studies are being performed to determine the prognosis and effects of treatment in patients who experience sudden hearing loss, and to identify biomarkers associated with this condition. Embase,…
CONTENT:
Int J Mol Sci. 2020 Sep 30;21(19):E7248. doi: 10.3390/ijms21197248.
ABSTRACT
Sudden sensorineural hearing loss (SSNHL) is a medical emergency, making detailed examination to determine possible causes and early treatment important. However, etiological examinations in SSNHL do not always reveal a cause, and several factors have been found to affect treatment outcomes. Various studies are being performed to determine the prognosis and effects of treatment in patients who experience sudden hearing loss, and to identify biomarkers associated with this condition. Embase, PubMed, and the Cochrane database were searched using the key words SSNHL, prognostic, and biomarker. This search identified 4 articles in Embase, 28 articles in PubMed, and 36 in the Cochrane database. Of these 68 articles, 3 were duplicates and 37 were unrelated to the research topic. After excluding these articles, the remaining 28 articles were reviewed. Factors associated with SSNHL were divided into six categories: metabolic, hemostatic, inflammatory, immunologic, oxidative, and other factors. The associations between these factors with the occurrence of SSNHL and with patient prognosis were analyzed. Low monocyte counts, low neutrophil/lymphocyte ratio (NLR) and monocyte/high-density lipoproteins (HDL) cholesterol ratio (MHR), and low concentrations of fibrinogen, platelet glycoprotein (GP) IIIa, and TNF-α were found to be associated with good prognosis. However, these factors alone could not completely determine the onset of and recovery from SSNHL, suggesting the need for future basic and clinical studies.
PMID:33008090 | DOI:10.3390/ijms21197248
SOURCE:
International journal of molecular sciences
DATE – PUBLISHED:
30 Sep 2020
DATE – ADDED:
Sat, 03 Oct 2020 06:00:00 -0400
DATE – FOUND:
10/04/20 02:17AM
PUBMED ID:
pubmed:33008090
DOI:
10.3390/ijms21197248
PUBMED LINK:
https://pubmed.ncbi.nlm.nih.gov/33008090/
DOI LINK:
https://doi.org/10.3390/ijms21197248
PUBLISHER LINK:
https://www.mdpi.com/1422-0067/21/19/7248
https://www.mdpi.com/1422-0067/21/19/7248/htm
https://www.biorxiv.org/content/10.1101/2020.09.28.314922v1.full
Macrophages respond rapidly to ototoxic injury of lateral line hair cells but are not required for hair cell regeneration
View ORCID ProfileMark E. Warchol, Angela Schrader, View ORCID ProfileLavinia Sheets
doi: https://doi.org/10.1101/2020.09.28.314922
https://www.biorxiv.org/content/10.1101/2020.10.04.324335v1.full
Contrasting mechanisms for hidden hearing loss: synaptopathy vs myelin defects
Maral Budak, Karl Grosh, View ORCID ProfileGabriel Corfas, Michal Zochowski, Victoria Booth
doi: https://doi.org/10.1101/2020.10.04.324335
CATEGORY:
Research
TITLE:
Altered Brain Activity and Functional Connectivity in Unilateral Sudden Sensorineural Hearing Loss
DESCRIPTION:
CONCLUSION: SSNHL causes functional alterations in brain regions, mainly in the striatum, auditory cortex, visual cortex, MTG, AG, precuneus, and limbic lobes within the acute period of hearing loss.
CONTENT:
Neural Plast. 2020 Sep 22;2020:9460364. doi: 10.1155/2020/9460364. eCollection 2020.
ABSTRACT
BACKGROUND: Sudden sensorineural hearing loss (SSNHL) is an otologic emergency and could lead to social difficulties and mental disorders in some patients. Although many studies have analyzed altered brain function in populations with hearing loss, little information is available about patients with idiopathic SSNHL. This study is aimed at investigating brain functional changes in SSNHL via functional magnetic resonance imaging (fMRI).
METHODS: Thirty-six patients with SSNHL and thirty well-matched normal hearing individuals underwent resting-state fMRI. Amplitude of low-frequency fluctuation (ALFF), fractional ALFF (fALFF), and functional connectivity (FC) values were calculated.
RESULTS: In the SSNHL patients, ALFF and fALFF were significantly increased in the bilateral putamen but decreased in the right calcarine cortex, right middle temporal gyrus (MTG), and right precentral gyrus. Widespread increases in FC were observed between brain regions, mainly including the bilateral auditory cortex, bilateral visual cortex, left striatum, left angular gyrus (AG), bilateral precuneus, and bilateral limbic lobes in patients with SSNHL. No decreased FC was observed.
CONCLUSION: SSNHL causes functional alterations in brain regions, mainly in the striatum, auditory cortex, visual cortex, MTG, AG, precuneus, and limbic lobes within the acute period of hearing loss.
PMID:33029130 | PMC:PMC7527900 | DOI:10.1155/2020/9460364
SOURCE:
Neural plasticity
DATE – PUBLISHED:
22 Sep 2020
DATE – ADDED:
Thu, 08 Oct 2020 06:00:00 -0400
DATE – FOUND:
10/08/20 06:42AM
PUBMED ID:
pubmed:33029130
DOI:
10.1155/2020/9460364
PUBMED LINK:
https://pubmed.ncbi.nlm.nih.gov/33029130/
DOI LINK:
https://doi.org/10.1155/2020/9460364
PUBLISHER LINK:
https://www.hindawi.com/journals/np/2020/9460364/
https://www.researchsquare.com/article/rs-46143/v1
SCN11A Gene Deletion Causes Sensorineural Hearing Loss by Impairing the Ribbon Synapses and Auditory Nerves
Mian Zu, Wei-wei Guo, Tao Cong, Fei Ji, Shi-li Zhang, Yue Zhang, Xin Song, Wei Sun, David Z.Z. He, Wei-guo Shi, Shiming Yang
DOI:
10.21203/rs.3.rs-46143/v1
https://www.dovepress.com/effects-of-growth-factors-and-the-microrna-183-family-on-differentiati-peer-reviewed-fulltext-article-SCCAA
https://doi.org/10.2147/SCCAA.S248526
Effects of Growth Factors and the MicroRNA-183 Family on Differentiation of Human Bone Marrow-Derived Mesenchymal Stem Cells Towards Auditory Neuron-Like Cells
Authors Farnoosh G, Mahmoudian-Sani MR
Published 10 September 2020 Volume 2020:13 Pages 79—89
DOI https://doi.org/10.2147/SCCAA.S248526
https://www.frontiersin.org/articles/10.3389/fcell.2020.576654/full
ORIGINAL RESEARCH ARTICLE
Front. Cell Dev. Biol., 08 September 2020 | https://doi.org/10.3389/fcell.2020.576654
Bromodomain Protein BRD4 Is Essential for Hair Cell Function and Survival
https://link.springer.com/article/10.1007/s12035-020-02092-0
Combined Atoh1 and Neurod1 Deletion Reveals Autonomous Growth of Auditory Nerve Fibers
https://www.tandfonline.com/doi/abs/10.1080/00016489.2020.1810859?journalCode=ioto20
https://www.ncbi.nlm.nih.gov/pubmed/32876518?dopt=Abstract
Related Articles
Circulating microRNAs as potentially new diagnostic biomarkers of idiopathic sudden sensorineural hearing loss.
Acta Otolaryngol. 2020 Sep 02;:1-8
Authors: Ha SM, Hwang KR, Park IH, Park S, Choi JS, Park DJ, Park JE, Lee SH, Lee HY, Seo YJ
Abstract
BACKGROUND: Early detection of inner ear cell damage can reduce the chances of permanent damage to hearing ability. However, current inner ear cell damage detection methods can detect damage only after the patient has lost hearing ability. MicroRNA expression levels in circulating systems are affected in diseases or conditions arising from the distant lesions. Therefore, detection of circulating microRNA expression levels could be one of the best ways to obtain information on inaccessible lesion sites.
AIMS/OBJECTIVES: This study aims to establish a method for monitoring idiopathic sudden sensorineural hearing loss (ISSNHL) by analyzing circulating microRNA expression levels. 21 ISSNHL patients and 24 healthy controls were enrolled.
MATERIAL AND METHODS: Real-time quantitative polymerase chain reaction was performed for detecting expression levels of circulating microRNAs.
RESULTS: Among eight circulating microRNAs, expression levels of five circulating microRNAs significantly differed between ISSNHL patients and healthy controls. circulating microRNA expression levels correlates with treatment outcomes and hearing ability.
CONCLUSIONS AND SIGNIFICANCE: Using methods combining the evaluation of miR-183, miR-210, miR-18b, and miR-23a cut-off values identified in ISSNHL patients and healthy controls during receiver operating characteristic curve analysis, sensitivity and specificity of 80.95% (17/21) and 87.50% (21/24) were obtained, respectively.
PMID: 32876518 [PubMed – as supplied by publisher]
https://www.mdpi.com/1660-4601/17/17/6336/htm
https://pubmed.ncbi.nlm.nih.gov/32878128/
Open Access
Article
Dextromethorphan Attenuates Sensorineural Hearing Loss in an Animal Model and Population-Based Cohort Study
Int. J. Environ. Res. Public Health 2020, 17(17), 6336; https://doi.org/10.3390/ijerph17176336
Received: 31 July 2020 / Revised: 27 August 2020 / Accepted: 28 August 2020 / Published: 31 August 2020
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https://journals.sagepub.com/doi/10.1177/0145561320952501
https://www.ncbi.nlm.nih.gov/pubmed/32865463?dopt=Abstract
Related Articles
The Role of Anti-Endothelial Cell Autoantibodies and Immune Response in Acute Low-Tone Hearing Loss.
Ear Nose Throat J. 2020 Aug 31;:145561320952501
Authors: Chen D, Wang Z, Jia G, Mao H, Ni Y
Abstract
OBJECTIVE: Immunity is associated with acute low tone hearing loss. However, the exact pathophysiology of immunity-mediated acute low tone hearing loss remains unknown. In this study, we evaluated the presence, therapeutic effectiveness, and immunopathological mechanisms of anti-endothelial cell autoantibodies (AECEs) in patients with acute low-frequency hearing loss.
MATERIAL AND METHODS: Forty-nine patients who were treated as inpatients having acute low-frequency hearing loss and additional symptoms, such as ear fullness, tinnitus, dizziness, or hyperacusis, were enrolled in this study. Serum samples from these patients were collected for laboratory serum autoimmunity detection, including AECAs, antinuclear antibodies, immunoglobulin, and circular immune complex. Therapeutic responses to combination therapy in short-term outcome and serum cytokine levels were compared between AECA-positive and AECA-negative patients.
RESULTS: Anti-endothelial cell autoantibodies-positive patients tended to show significantly less response to standard therapy compared with AECAs controls (P < .05). Moreover, some serum cytokine levels elevated in both AECAs- and AECAs+ groups. Positive ratio of interleukin-8 and concentrations of macrophage inflammatory protein-1α were found higher in AECAs+ groups (P < .05). CONCLUSION: The results supported that AECAs might wield influence on the short-term outcome of acute low-tone hearing loss (ALHL) treatment. Furthermore, AECA-mediated acute low-frequency hearing loss possibly involved dysregulation of inflammation process and release of cytokines. PMID: 32865463 [PubMed - as supplied by publisher]
https://www.sciencedirect.com/science/article/abs/pii/S0006291X2031562X?via%3Dihub
https://pubmed.ncbi.nlm.nih.gov/32868078/
Loss of RAD6B induces degeneration of the cochlea in mice
Yangping Ma 1, Yanfeng Song 1, Rong Shen 1, Panpan Li 1, Han Ding 1, Zhao Guo 1, Xiangwen Liu 1, Degui Wang 2
Affiliations expand
PMID: 32868078 DOI: 10.1016/j.bbrc.2020.08.017
Abstract
Presbycusis is a form of age-related hearing loss (AHL). Many studies have shown that the degeneration of various structures in the cochlea of the inner ear is related to AHL, and DNA damage is an important factor leading to the above process. As an E2 ubiquitin-conjugated enzyme, RAD6B plays an important role in DNA damage repair (DDR) through histone ubiquitination. However, the molecular mechanism is still unclear. In this study, we investigated the role of RAD6B in the morphological changes and DDR mechanisms in aging-related degeneration of the cochlea of mice. We observed that the hair cells, stria vascularis and spiral ganglion in the cochlea of the RAD6B knockout mice showed significant degenerative changes and abnormal expression of proteins associated with DDR mechanisms compared with those of the littermate wild-type mice. In conclusion, our results suggest that the deletion of RAD6B may lead to abnormalities in DDR, thereby accelerating the degeneration of various structures in the cochlea and senescence and apoptosis of cochlea cells.
Keywords: Cochlea; DNA damage; Degeneration; RAD6B; Ubiquitin.
CATEGORY:
Research
TITLE:
Systematic Transcriptome Analysis of Noise-Induced Hearing Loss Pathogenesis Suggests Inflammatory Activities and Multiple Susceptible Molecules and Pathways
DESCRIPTION:
Noise-induced hearing loss (NIHL) is characterized by damage to cochlear neurons and associated hair cells; however, a systematic evaluation of NIHL pathogenesis is still lacking. Here, we systematically evaluated differentially expressed genes of 22 cochlear samples in an NIHL mouse model. We performed Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis and weighted gene co-expression network analysis (WGCNA). Core modules were detected using protein-protein interactions…
CONTENT:
Front Genet. 2020 Aug 28;11:968. doi: 10.3389/fgene.2020.00968. eCollection 2020.
ABSTRACT
Noise-induced hearing loss (NIHL) is characterized by damage to cochlear neurons and associated hair cells; however, a systematic evaluation of NIHL pathogenesis is still lacking. Here, we systematically evaluated differentially expressed genes of 22 cochlear samples in an NIHL mouse model. We performed Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis and weighted gene co-expression network analysis (WGCNA). Core modules were detected using protein-protein interactions and WGCNA with functional annotation, diagnostic value evaluation, and experimental validation. Pooled functional annotation suggested the involvement of multiple inflammatory pathways, including the TNF signaling pathway, IL-17 signaling pathway, NF-kappa B signaling pathway, rheumatoid arthritis, and p53 signaling pathway. The core modules suggested that responses to cytokines, heat, cAMP, ATP, mechanical stimuli, and immune responses were important in NIHL pathogenesis. These activities primarily occurred on the external side of the plasma membrane, the extracellular region, and the nucleus. Binding activities, including CCR2 receptor binding, protein binding, and transcription factor binding, may be important. Additionally, the hub molecules with diagnostic value included Relb, Hspa1b, Ccl2, Ptgs2, Ldlr, Plat, and Ccl17. An evaluation of Relb and Hspa1b protein levels showed that Relb was upregulated in spiral ganglion neurons, which might have diagnostic value. In conclusion, this study indicates that the inflammatory response is involved in auditory organ changes in NIHL pathogenesis; moreover, several molecules and activities have essential and subtle influences that have translational potential for pharmacological intervention.
PMID:33005175 | PMC:PMC7483666 | DOI:10.3389/fgene.2020.00968
SOURCE:
Frontiers in genetics
DATE – PUBLISHED:
28 Aug 2020
DATE – ADDED:
Fri, 02 Oct 2020 06:00:00 -0400
DATE – FOUND:
10/02/20 07:34AM
PUBMED ID:
pubmed:33005175
DOI:
10.3389/fgene.2020.00968
PUBMED LINK:
https://pubmed.ncbi.nlm.nih.gov/33005175/
DOI LINK:
https://doi.org/10.3389/fgene.2020.00968
PUBLISHER LINK:
https://www.frontiersin.org/article/10.3389/fgene.2020.00968/full
https://www.tandfonline.com/doi/abs/10.1080/17460441.2020.1806232?journalCode=iedc20
https://pubmed.ncbi.nlm.nih.gov/32838572/
Drug development for noise-induced hearing loss
Isabel Varela-Nieto ,Silvia Murillo-Cuesta,Miryam Calvino,Rafael Cediel &Luis Lassaletta
Received 23 Mar 2020, Accepted 03 Aug 2020, Published online: 25 Aug 2020
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