Liu X.,Eye |
Liu X.,Shanghai Auditory Medical Center |
Liu X.,Hearing Health Science |
Sheng H.-B.,Eye |
And 21 more authors.
Experimental and Therapeutic Medicine
Mucous cell metaplasia/hyperplasia in the middle ear epithelium is associated with the occurrence of otitis media with effusion during infections. However, the mechanism by which Notch signaling regulates cell fate in the middle ear epithelium is unclear. The aim of the present study was to elucidate this mechanism by investigating the localization of Notch receptors, such as Notch1 and Notch2, and Notch ligands, such as Jagged1, in the normal mouse middle ear epithelium (NMMEE) using immunofluorescence. Furthermore, the mRNA expression levels of Notch receptors and ligands were evaluated using reverse transcription polymerase chain reaction (PCR). The effects of the γ-secretase inhibitor N-[N-(3,5-difluorophenacetyl)-L-alanyl]-S-phenylglycine tert-butyl ester (DAPT) on epithelial cell proliferation were determined using 5-ethynyl-2'-deoxyuridine (EdU) staining and immunofluorescence staining of the apoptosis marker caspase-3 and the epithelial proliferation marker pan-cytokeratine. In addition, the differentiation of the NMMEE cells was characterized by evaluating the mRNA expression levels of the mucous cell-associated genes Arg2, Muc2, Spdef, Spink4 and Tff1 using quantitative PCR. Notch1, Notch2 and Jagged1 were observed to be co-localized throughout the mouse middle ear epithelium. Furthermore, Notch1-4, Jagged1, Jagged2, Dll1 and Dll4 mRNAs were expressed in the NMMEE cells. The inhibition of Notch by DAPT resulted in fewer EdU-positive cells and the upregulation of the expression levels of various mucous cell-associated genes. The results indicate that DAPT suppresses the proliferation of NMMEE cells while promoting their differentiation into mucous cells. Therefore, DAPT may provide a specific therapeutic strategy for the reversal of multiple pathological processes that are associated with epithelium thickening in the middle ear. © 2016, Spandidos Publications. All right reserved. Source
Gao N.,Fudan University |
Gao N.,Shanghai Auditory Medical Center |
Gao N.,Hearing Health Science |
Xu X.-D.,Fudan University |
And 22 more authors.
Conclusion: This study described objective and subjective evaluations of the Nurotron® Venus™ Cochlear Implant System and indicated that this system produced a satisfactory performance. Objective: To observe the performance of the Nurotron® Venus™ cochlear implant (CI) system via electrophysiological and psychophysical evaluations. Methods: A 26-electrode CI system was specially designed. The performance of MRI in animal and cadaveric head experiments, EABR in cats experiment, the correlation between ESRT and C level, and psychophysics evaluations in clinical trials were observed. Results: In the animal and cadaveric head experiments, magnet dislocation could not be prevented in the 1.5 T MRI without removal of the internal magnet. The EABR was clearly elicited in cat experiment. In the clinical trial, the ESRT was strongly correlated with C level (p < 0.001). The human clinical trial involving 57 post-lingually deafened native Mandarin-speaking patients was performed. Residual hearing protection in the implanted ear at each audiometric frequency was observed in 27.5-46.3% patients post-operatively. A pitch ranking test revealed that place pitches were generally ordered from apical to basal electrodes. The recognitions of the perceptions of 301 disyllabic words, environment sounds, disyllabic words, and numerals were significantly better than the pre-operative performance and reached plateaus. © 2015 Taylor & Francis. Source
Yang X.-Y.,Fudan University |
Yang X.-Y.,Shanghai Auditory Medical Center |
Yang X.-Y.,Hearing Health Science |
Jin K.,Fudan University |
And 23 more authors.
Planar cell polarity (PCP) signaling regulates cochlear extension and coordinates orientation of sensory hair cells in the inner ear. Retroviral-mediated introduction of the Math1 transcription factor leads to the transdifferentiation of some mature supporting cells into hair cells. Testosterone, a gonadal sex steroid hormone, is associated with neuroprotection and regeneration in Central Nervous System (CNS) development. Experiments were performed in vitro using Ad5-EGFP-Math1/Ad5-Math1 in neonatal mouse cochleas. Establishment of ectopic hair-cell like cell(HCLC) polarity in the lesser epithelial ridge (LER) with or without testosterone-3-(O-carboxymethyl) oxime bovine serum albumin (testosterone-BSA) treatment was investigated to determine the role of the PCP pathway in regulating ectopic regenerated (HCLCs) through induction by Math1 and testosterone treatment. After Math1 infection, new ectopic regenerated HCLCs were detected in the LER. After the HCLCs developed actin-rich stereocilia, the basal bodies moved from the center to the distal side. Moreover, the narrower, non-sensory LER region meant that the convergent extension (CE) was also established after transfection with Math1. After 9 days of in vitro testosterone-BSA treatment, more Edu(+), Sox2(+), and HCLC cells were observed in the LER with an accompanying downregulation of E-cadherin. Interestingly, the CE of the Ad5-EGFP-math1 treated LER is altered, but the intrinsic cellular polarity of the HCLCs is not obviously changed. In summary, our results indicate that PCP signaling is involved in the development of ectopic HCLCs and the CE of the ectopic sensory region is altered by testosterone-BSA through downregulation of cell-cell adhesion. Testosterone-BSA and Math1 treatment could promote an increase in HCLCs in the LER through proliferation and transdifferentiation. © 2015 Elsevier B.V. Source