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1.
J Biol Chem ; 299(5): 104613, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36931391

RESUMO

Epstein-Barr virus (EBV) is a member of the lymphotropic virus family and is highly correlated with some human malignant tumors. It has been reported that envelope glycoprotein 110 (gp110) plays an essential role in viral fusion, DNA replication, and nucleocapsid assembly of EBV. However, it has not been established whether gp110 is involved in regulating the host's innate immunity. In this study, we found that gp110 inhibits tumor necrosis factor α-mediated NF- κB promoter activity and the downstream production of NF- κB-regulated cytokines under physiological conditions. Using dual-luciferase reporter assays, we showed that gp110 might impede the NF-κB promoter activation downstream of NF-κB transactivational subunit p65. Subsequently, we used coimmunoprecipitation assays to demonstrate that gp110 interacts with p65 during EBV lytic infection, and that the C-terminal cytoplasmic region of gp110 is the key interaction domain with p65. Furthermore, we determined that gp110 can bind to the N-terminal Rel homologous and C-terminal domains of p65. Alternatively, gp110 might not disturb the association of p65 with nontransactivational subunit p50, but we showed it restrains activational phosphorylation (at Ser536) and nuclear translocation of p65, which we also found to be executed by the C-terminal cytoplasmic region of gp110. Altogether, these data suggest that the surface protein gp110 may be a vital component for EBV to antagonize the host's innate immune response, which is also helpful for revealing the infectivity and pathogenesis of EBV.


Assuntos
Infecções por Vírus Epstein-Barr , NF-kappa B , Humanos , NF-kappa B/genética , NF-kappa B/metabolismo , Herpesvirus Humano 4/metabolismo , Infecções por Vírus Epstein-Barr/genética , Fator de Transcrição RelA/genética , Fator de Transcrição RelA/metabolismo , Transdução de Sinais , Transporte Proteico
2.
J Neurosci Res ; 102(1): e25281, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-38284861

RESUMO

Tinnitus is a widespread public health issue that imposes a significant social burden. The occurrence and maintenance of tinnitus have been shown to be associated with abnormal neuronal activity in the auditory pathway. Based on this view, neurobiological and pharmacological developments in tinnitus focus on ion channels and synaptic neurotransmitter receptors in neurons in the auditory pathway. With major breakthroughs in the pathophysiology and research methodology of tinnitus in recent years, the role of the largest family of ion channels, potassium ion channels, in modulating the excitability of neurons involved in tinnitus has been increasingly demonstrated. More and more potassium channels involved in the neural mechanism of tinnitus have been discovered, and corresponding drugs have been developed. In this article, we review animal (mouse, rat, hamster, and guinea-pig), human, and genetic studies on the different potassium channels involved in tinnitus, analyze the limitations of current clinical research on potassium channels, and propose future prospects. The aim of this review is to promote the understanding of the role of potassium ion channels in tinnitus and to advance the development of drugs targeting potassium ion channels for tinnitus.


Assuntos
Canais de Potássio , Zumbido , Cricetinae , Humanos , Animais , Cobaias , Camundongos , Ratos , Zumbido/tratamento farmacológico , Neurobiologia , Vias Auditivas , Neurônios
3.
Cell ; 136(3): 521-34, 2009 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-19203585

RESUMO

Amino acids are required for activation of the mammalian target of rapamycin (mTOR) kinase which regulates protein translation, cell growth, and autophagy. Cell surface transporters that allow amino acids to enter the cell and signal to mTOR are unknown. We show that cellular uptake of L-glutamine and its subsequent rapid efflux in the presence of essential amino acids (EAA) is the rate-limiting step that activates mTOR. L-glutamine uptake is regulated by SLC1A5 and loss of SLC1A5 function inhibits cell growth and activates autophagy. The molecular basis for L-glutamine sensitivity is due to SLC7A5/SLC3A2, a bidirectional transporter that regulates the simultaneous efflux of L-glutamine out of cells and transport of L-leucine/EAA into cells. Certain tumor cell lines with high basal cellular levels of L-glutamine bypass the need for L-glutamine uptake and are primed for mTOR activation. Thus, L-glutamine flux regulates mTOR, translation and autophagy to coordinate cell growth and proliferation.


Assuntos
Autofagia , Glutamina/metabolismo , Proteínas Quinases/metabolismo , Sistema ASC de Transporte de Aminoácidos/metabolismo , Animais , Linhagem Celular Tumoral , Drosophila melanogaster , Humanos , Leucina/metabolismo , Alvo Mecanístico do Complexo 1 de Rapamicina , Complexos Multiproteicos , Proteínas , Serina-Treonina Quinases TOR , Fatores de Transcrição/metabolismo
4.
Cereb Cortex ; 33(16): 9616-9626, 2023 08 08.
Artigo em Inglês | MEDLINE | ID: mdl-37381582

RESUMO

The aim of this study is to ascertain the mechanisms of cognitive reserve disorder in age-related hearing loss (ARHL), to study the correlation between ARHL and cognitive decline via EEG, and to reverse the adverse remodeling of auditory-cognitive connectivity with hearing aids (HAs). In this study, 32 participants were enrolled, including 12 with ARHLs, 9 with HAs, and 11 healthy controls (HCs), to undergo EEG, Pure Tone Average (PTA), Montreal Cognitive Assessment (MoCA), and other general cognitive tests. There were the lowest MoCA in the ARHL group (P = 0.001), especially in language and abstraction. In the ARHL group, power spectral density of the gamma in right middle temporal gyrus was significantly higher than HC and HA groups, while functional connectivity between superior frontal gyrus and cingulate gyrus was weaker than HC group (P = 0.036) and HA group (P = 0.021). In the HA group, superior temporal gyrus and cuneus had higher connectivity than in the HC group (P = 0.036). In the ARHL group, DeltaTM_DTA (P = 0.042) and CTB (P = 0.011) were more frequent than in the HC group, while there was less DeltaTM_CTA (P = 0.029). PTA was found to be associated with MoCA (r = -0.580) and language (r = -0.572), DeltaTM_CTB had a likewise correlation with MoCA (r = 0.483) and language (r = 0.493), while DeltaTM_DTA was related to abstraction (r = -0.458). Cognitive cortexes compensate for worse auditory perceptual processing in ARHL, which relates to cognitive decline. The impaired functional connectivity between auditory and cognitive cortexes can be remodeled by HAs. DeltaTM may serve as a biomarker for early cognitive decline and decreased auditory speech perception in ARHL.


Assuntos
Transtornos Cognitivos , Disfunção Cognitiva , Reserva Cognitiva , Perda Auditiva , Humanos , Disfunção Cognitiva/diagnóstico por imagem , Percepção Auditiva
5.
Org Biomol Chem ; 20(14): 2909-2921, 2022 04 06.
Artigo em Inglês | MEDLINE | ID: mdl-35322842

RESUMO

A new and highly stereoselective synthesis of chiral diol (S)-14, the common synthetic intermediate to (+)-(2R,4'R,8'R)-α-tocopherol (1), was accomplished in seven steps with 13.8% overall yield. This developed route featured a lipase-catalyzed desymmetric hydrolysis of prochiral diester 39a, which was prepared through a challenging Heck coupling, to chiral quaternary carbon-containing monoester (R)-37a of the correct configuration in 81% yield and 96.7% ee, to the best of our knowledge, leading to the most efficient enzymatic desymmetric synthesis of the chiral chroman skeleton of vitamin E members reported to date. Coupled with the modified preparation of the phytol-derived side chain, the chemoenzymatic total synthesis of 1 was completed in 15 longest linear steps with 3.1% overall yield.


Assuntos
Vitamina E , alfa-Tocoferol , Álcoois , Hidrólise , Estereoisomerismo
6.
Am J Otolaryngol ; 43(3): 103430, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35398741

RESUMO

OBJECTIVE: To analyze the audiological characteristics and surgical results in patients undergoing surgery for simple congenital ossicular chain malformation, and the effect of endoscopic surgery. METHODS: A retrospective review was performed on 86 patients who underwent surgery for the congenital malformation of the ossicular chain. Clinical characteristics and audiometric data were analyzed. Fifty-eight patients had detailed postoperative data, and the preoperative and postoperative audiometric results were compared. The subjects were further divided into endoscopic and microscopic groups, and their surgical effects were examined. RESULTS: The preoperative audiometry results in the low-frequency group were worse than those in the high-frequency group (P < 0.05). A postoperative air-bone gap closure to 20 dB or less was achieved in 73.33% of the 60 ears of patients postoperatively. The postoperative air conduction and air-bone gap were significantly better than the preoperative ones (P < 0.05), and the improvement effect was the best in class III patients (P < 0.05). Postoperative hearing had no significant differences between the endoscopic and microscopic groups. However, endoscopic surgery also was more advantageous in terms of operating time (P < 0.05). CONCLUSIONS: Preoperative pure tone audiometric results showed moderate or moderate-severe hearing loss, especially in the low-frequency area. The reconstruction of the auditory ossicle chain can achieve satisfactory results, especially in class III patients. Endoscopic and microscopic surgery in the treatment of simple congenital ossicular chain malformations can effectively improve postoperative hearing.


Assuntos
Ossículos da Orelha , Prótese Ossicular , Audiometria de Tons Puros , Ossículos da Orelha/cirurgia , Endoscopia/métodos , Audição , Humanos , Estudos Retrospectivos , Resultado do Tratamento
7.
J Neurophysiol ; 125(4): 1202-1212, 2021 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-33625942

RESUMO

Cisplatin is an antitumor drug that is widely used for the treatment of various solid tumors. Unfortunately, patients are often troubled by serious side effects, especially hearing loss. Up to now, there have been no clear and effective measures to prevent cisplatin-induced ototoxicity in clinical use. We explored the role of autophagy and the efficacy of metformin in cisplatin-induced ototoxicity in cells, zebrafish, and mice. Furthermore, the underlying molecular mechanism of how metformin affects cisplatin-induced ototoxicity was examined. In in vitro experiments, autophagy levels in HEI-OC1 cells were assessed using fluorescence and Western blot analyses. In in vivo experiments, whether metformin had a protective effect against cisplatin ototoxicity was validated in zebrafish and C57BL/6 mice. The results showed that cisplatin induced autophagy activation in HEI-OC1 cells. Metformin exerted antagonistic effects against cisplatin ototoxicity in HEI-OC1 cells, zebrafish, and mice. Notably, metformin activated autophagy and increased the expression levels of the adenosine monophosphate-activated protein kinase (AMPK) and the transcription factor Forkhead box protein O3 (FOXO3a), whereas cells with AMPK silencing displayed otherwise. Our findings indicate that metformin alleviates cisplatin-induced ototoxicity possibly through AMPK/FOXO3a-mediated autophagy machinery. This study underpins further researches on the prevention and treatment of cisplatin ototoxicity.NEW & NOTEWORTHY Cisplatin is an antitumor drug that is widely used for the treatment of various solid tumors. Up to now, there have been no clear and effective measures to prevent cisplatin-induced ototoxicity in clinical use. We investigated the protective effect of metformin on cisplatin ototoxicity in vitro and in vivo. Our findings indicate that metformin alleviates cisplatin-induced ototoxicity possibly through AMPK/FOXO3a-mediated autophagy machinery. This study underpins further researches on the prevention and treatment of cisplatin ototoxicity.


Assuntos
Antineoplásicos/toxicidade , Autofagia/efeitos dos fármacos , Cisplatino/toxicidade , Proteína Forkhead Box O3/efeitos dos fármacos , Células Ciliadas Auditivas/efeitos dos fármacos , Metformina/farmacologia , Fármacos Neuroprotetores/farmacologia , Ototoxicidade/tratamento farmacológico , Ototoxicidade/etiologia , Proteínas Quinases/efeitos dos fármacos , Quinases Proteína-Quinases Ativadas por AMP , Animais , Células Cultivadas , Modelos Animais de Doenças , Masculino , Metformina/administração & dosagem , Camundongos , Camundongos Endogâmicos C57BL , Fármacos Neuroprotetores/administração & dosagem , Peixe-Zebra
8.
Chem Rec ; 21(7): 1611-1630, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33835705

RESUMO

With the rapid development of genomic DNA sequencing, recombinant DNA expression, and protein engineering, biocatalysis has been increasingly and widely adopted in the synthesis of pharmaceuticals, bioactive molecules, fine chemicals, and agrochemicals. In this review, we have summarized the most recent advances achieved (2018-2020) in the research area of ketoreductase (KRED)-catalyzed asymmetric synthesis of chiral secondary alcohol intermediates to pharmaceuticals and bioactive molecules. In the first part, synthesis of chiral alcohols with one stereocenter through the bioreduction of four different ketone classes, namely acyclic aliphatic ketones, benzyl or phenylethyl ketones, cyclic aliphatic ketones, and aryl ketones, is discussed. In the second part, KRED-catalyzed dynamic reductive kinetic resolution and reductive desymmetrization are presented for the synthesis of chiral alcohols with two contiguous stereocenters.


Assuntos
Oxirredutases do Álcool/química , Álcoois/síntese química , Preparações Farmacêuticas/síntese química , Biocatálise , Cetonas/química , Oxirredução , Estereoisomerismo
9.
Nature ; 512(7512): 49-53, 2014 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-25043012

RESUMO

In the 1950s, the drug thalidomide, administered as a sedative to pregnant women, led to the birth of thousands of children with multiple defects. Despite the teratogenicity of thalidomide and its derivatives lenalidomide and pomalidomide, these immunomodulatory drugs (IMiDs) recently emerged as effective treatments for multiple myeloma and 5q-deletion-associated dysplasia. IMiDs target the E3 ubiquitin ligase CUL4-RBX1-DDB1-CRBN (known as CRL4(CRBN)) and promote the ubiquitination of the IKAROS family transcription factors IKZF1 and IKZF3 by CRL4(CRBN). Here we present crystal structures of the DDB1-CRBN complex bound to thalidomide, lenalidomide and pomalidomide. The structure establishes that CRBN is a substrate receptor within CRL4(CRBN) and enantioselectively binds IMiDs. Using an unbiased screen, we identified the homeobox transcription factor MEIS2 as an endogenous substrate of CRL4(CRBN). Our studies suggest that IMiDs block endogenous substrates (MEIS2) from binding to CRL4(CRBN) while the ligase complex is recruiting IKZF1 or IKZF3 for degradation. This dual activity implies that small molecules can modulate an E3 ubiquitin ligase and thereby upregulate or downregulate the ubiquitination of proteins.


Assuntos
Peptídeo Hidrolases/química , Talidomida/química , Ubiquitina-Proteína Ligases/química , Proteínas Adaptadoras de Transdução de Sinal , Cristalografia por Raios X , Proteínas de Ligação a DNA/agonistas , Proteínas de Ligação a DNA/antagonistas & inibidores , Proteínas de Ligação a DNA/química , Proteínas de Ligação a DNA/metabolismo , Proteínas de Homeodomínio/metabolismo , Humanos , Lenalidomida , Modelos Moleculares , Complexos Multiproteicos/agonistas , Complexos Multiproteicos/antagonistas & inibidores , Complexos Multiproteicos/química , Complexos Multiproteicos/metabolismo , Peptídeo Hidrolases/metabolismo , Ligação Proteica , Relação Estrutura-Atividade , Especificidade por Substrato , Talidomida/análogos & derivados , Talidomida/metabolismo , Fatores de Transcrição/metabolismo , Ubiquitina-Proteína Ligases/antagonistas & inibidores , Ubiquitina-Proteína Ligases/metabolismo
10.
BMC Psychiatry ; 20(1): 547, 2020 11 23.
Artigo em Inglês | MEDLINE | ID: mdl-33228598

RESUMO

BACKGROUND: Although the clinical efficacy and safety of repetitive transcranial magnetic stimulation (rTMS) in the treatment of chronic tinnitus have been frequently examined, the results remain contradictory. Therefore, we performed a systematic review and meta-analysed clinical trials examining the effects of rTMS to evaluate its clinical efficacy and safety. METHODS: Studies of rTMS for chronic tinnitus were retrieved from PubMed, Embase, and Cochrane Library through April 2020. Review Manager 5.3 software was employed for data synthesis, and Stata 13.0 software was used for analyses of publication bias and sensitivity. RESULTS: Twenty-nine randomized studies involving 1228 chronic tinnitus patients were included. Compared with sham-rTMS, rTMS exhibited significant improvements in the tinnitus handicap inventory (THI) scores at 1 week (mean difference [MD]: - 7.92, 95% confidence interval [CI]: - 14.18, - 1.66), 1 month (MD: -8.52, 95% CI: - 12.49, - 4.55), and 6 months (MD: -6.53, 95% CI: - 11.406, - 1.66) post intervention; there were significant mean changes in THI scores at 1 month (MD: -14.86, 95% CI: - 21.42, - 8.29) and 6 months (MD: -16.37, 95% CI: - 20.64, - 12.11) post intervention, and the tinnitus questionnaire (TQ) score at 1 week post intervention (MD: -8.54, 95% CI: - 15.56, - 1.52). Nonsignificant efficacy of rTMS was found regarding the THI score 2 weeks post intervention (MD: -1.51, 95% CI: - 13.42, - 10.40); the mean change in TQ scores 1 month post intervention (MD: -3.67, 95% CI: - 8.56, 1.22); TQ scores 1 (MD: -8.97, 95% CI: - 20.41, 2.48) and 6 months (MD: -7.02, 95% CI: - 18.18, 4.13) post intervention; and adverse events (odds ratios [OR]: 1.11, 95% CI: 0.51, 2.42). Egger's and Begg's tests indicated no publication bias (P = 0.925). CONCLUSION: This meta-analysis demonstrated that rTMS is effective for chronic tinnitus; however, its safety needs more validation. Restrained by the insufficient number of included studies and the small sample size, more large randomized double-blind multi-centre trials are needed for further verification.


Assuntos
Zumbido , Estimulação Magnética Transcraniana , Método Duplo-Cego , Humanos , Inquéritos e Questionários , Zumbido/terapia , Resultado do Tratamento
11.
ORL J Otorhinolaryngol Relat Spec ; 82(3): 150-162, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32203962

RESUMO

OBJECTIVE: To describe the feasibility of preserving the lesser occipital nerve (LON) and the great auricular nerve (GAN) in postauricular incision in ear surgery. METHODS: The distribution of the LON and the GAN was first identified in human cadavers. Then a clinical study was performed in 34 patients who underwent middle ear surgery between September 2016 and January 2017. Patients were divided into the conventional incision group and the modified incision group, according to incision types, and underwent sensory testing and subjective evaluation of auricular numbness after surgery at different times. RESULTS: Most frequently, the auricular branches of the LON went into the postauricular groove at the same height of inferior crus of antihelix. The vertical dimension from the intersection of the highest auricular branch of the GAN and postauricular groove to intertragic notch ranged from 5.7 to -4.2 mm. Preservation of the LON and the GAN reduced sensory loss in the modified incision group compared to the conventional incision group. CONCLUSION: Preservation of the LON and the GAN with modified postauricular incision can reduce postoperative auricular numbness.


Assuntos
Procedimentos Cirúrgicos Otológicos , Humanos , Período Pós-Operatório
12.
Int J Audiol ; 57(12): 892-899, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30261769

RESUMO

There is a lack of national studies on tinnitus in China and data based on a large sample size from multiple areas of the country. A cross-sectional study was carried out in Guangdong province from October 2015 to February 2016. In the study, tinnitus was defined as the presence of ringing, buzzing or other sounds in the ears in the past one year. Fourteen districts in Guangdong Province were selected as the first-level cluster by using the sampling method of probability proportional to size (PPS). Two sub-districts in each first-level cluster were randomly selected as the second-level cluster by PPS method. The sample consisted of 3705 eligible people aged over 18 years old, which were also selected by the PPS methods. The prevalence of tinnitus was 10.4% in Guangdong Province. Age, region, educational background, hearing impairment, ear trauma, otitis media and self-health report were the main risk factors for tinnitus. Tinnitus is a common condition and a large population suffers from tinnitus in Guangdong province, south of China. Greater public awareness and understanding of the associated factors are required for further interventions of prevention and management of tinnitus in China.


Assuntos
Zumbido/epidemiologia , Adolescente , Adulto , Distribuição por Idade , Fatores Etários , Idoso , China/epidemiologia , Estudos Transversais , Escolaridade , Feminino , Transtornos da Audição/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Otite Média/epidemiologia , Prevalência , Fatores de Risco , Distribuição por Sexo , Fatores de Tempo , Zumbido/diagnóstico , Adulto Jovem
13.
Audiol Neurootol ; 22(2): 96-103, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28817812

RESUMO

HYPOTHESIS: The miR-34a/Bcl-2 signaling pathway may play a role in the mechanisms related to age-related hearing loss (AHL) in the auditory cortex. BACKGROUND: The auditory cortex plays a key role in the recognition and processing of complex sound. It is difficult to explain why patients with AHL have poor speech recognition, so increasing numbers of studies have focused on its central change. Although micro (mi)RNAs in the central nervous system have recently been increasingly reported to be associated with age-related diseases, the molecular mechanisms of AHL in the auditory cortex are not fully understood. METHODS: The auditory brainstem response was used to assess the hearing ability of C57BL/6 mice, and q-PCR, immunohistochemistry, and Western blotting were used to detect the expression levels of miR-34a and Bcl-2 in the mouse auditory cortex. TUNEL and DNA fragmentation were adopted to detect the apoptosis of neurons in the auditory cortex. To verify the relationship of miR-34a and Bcl-2, we transfected an miR-34a mimic or miR-34a inhibitor into primary auditory cortex neurons. RESULTS: In this study, miR-34a/Bcl-2 signaling was examined in auditory cortex neurons during aging. miR-34a and apoptosis increased in the auditory cortex neurons of C57BL/6 mice with aging, whereas an age-related decrease in Bcl-2 was determined. In the primary neurons of the auditory cortex, miR-34a overexpression inhibited Bcl-2, leading to an increase in apoptosis. Moreover, miR-34a knockdown increased Bcl-2 expression and diminished apoptosis. CONCLUSION: Our results support a link between age-related apoptosis in auditory cortex neurons and miR-34a/Bcl-2 signaling, which may serve as a potential mechanism of the expression of AHL in the auditory cortex.


Assuntos
Apoptose/genética , Córtex Auditivo/metabolismo , MicroRNAs/genética , Neurônios/metabolismo , Presbiacusia/genética , Proteínas Proto-Oncogênicas c-bcl-2/genética , Animais , Córtex Auditivo/citologia , Córtex Auditivo/fisiopatologia , Potenciais Evocados Auditivos do Tronco Encefálico/genética , Potenciais Evocados Auditivos do Tronco Encefálico/fisiologia , Audição , Perda Auditiva , Camundongos , Camundongos Endogâmicos C57BL , MicroRNAs/metabolismo , Presbiacusia/metabolismo , Presbiacusia/fisiopatologia , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Transdução de Sinais/genética
14.
Audiol Neurootol ; 21(5): 326-332, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27925611

RESUMO

Bcl-2, the first gene shown to be involved in apoptosis, is a potent regulator of cell survival and known to have protective effects against a variety of age-related diseases. However, the possible relationship between hearing and Bcl-2 expression in the cochlea or auditory cortex of C57BL/6 mice, a mouse model of age-related hearing loss, is still unknown. Using RT-PCR, immunohistochemistry, and Western blot analysis, our results show that Bcl-2 is strongly expressed in the inner hair cells and spiral ganglion neurons of young mice. In addition, moderate Bcl-2 expression is also detected in the outer hair cells and in the neurons of the auditory cortex. A significant reduction of Bcl-2 expression in the cochlea or auditory cortex is also associated with elevated hearing thresholds and hair cell loss during aging. The expression pattern of Bcl-2 in the peripheral and central auditory systems suggests that Bcl-2 may play an important role in auditory function serving as a protective molecule against age-related hearing loss.


Assuntos
Envelhecimento/metabolismo , Córtex Auditivo/metabolismo , Células Ciliadas Auditivas Internas/metabolismo , Células Ciliadas Auditivas Externas/metabolismo , Neurônios/metabolismo , Presbiacusia/genética , Proteínas Proto-Oncogênicas c-bcl-2/genética , Gânglio Espiral da Cóclea/metabolismo , Animais , Córtex Auditivo/citologia , Limiar Auditivo , Western Blotting , Cóclea/metabolismo , Modelos Animais de Doenças , Potenciais Evocados Auditivos do Tronco Encefálico/fisiologia , Imuno-Histoquímica , Camundongos , Camundongos Endogâmicos C57BL , Presbiacusia/metabolismo , Presbiacusia/fisiopatologia , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Gânglio Espiral da Cóclea/citologia
15.
Neurol Sci ; 37(9): 1511-6, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27230393

RESUMO

Repetitive transcranial magnetic stimulation (rTMS) is one form of non-invasive brain stimulation and increasingly shows neuroprotection in multiple neurological disorders. However, the potential of rTMS for protective action on auditory function following acoustic trauma has not been investigated. Here, we examined effect of TMS on hearing conservation, neurons survival and brain-derived neurotrophin factor (BDNF) expression in the cochlea and auditory cortex following acoustic trauma in rats. Wistar rats were exposed to intense pure tone noise (10 kHz, 120 dB SPL for 2 h) followed by rTMS treatment or sham treatment (handling control) daily for 14 days. Auditory brainstem response revealed there was no significant difference in hearing threshold shifts between rTMS- and sham-treated rats, although rTMS-treated rats showed less neuron loss in the auditory cortex in comparison with sham rats. Additionally, acoustic trauma increased BDNF expression in the cochlea and auditory cortex, and this elevation could be attenuated by rTMS treatment. Our results suggest present regiment of rTMS does not protect hearing against acoustic trauma, but maybe have implications for tinnitus treatment.


Assuntos
Córtex Auditivo/metabolismo , Cóclea/metabolismo , Regulação da Expressão Gênica/fisiologia , Perda Auditiva Provocada por Ruído , Estimulação Magnética Transcraniana/métodos , Animais , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Modelos Animais de Doenças , Eletroencefalografia , Potenciais Evocados Auditivos do Tronco Encefálico/fisiologia , Feminino , Perda Auditiva Provocada por Ruído/patologia , Perda Auditiva Provocada por Ruído/fisiopatologia , Perda Auditiva Provocada por Ruído/terapia , Ruído/efeitos adversos , Ratos , Ratos Wistar
16.
Am J Otolaryngol ; 37(2): 99-102, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26954860

RESUMO

PURPOSE: Eustachian tube balloon dilation (ETBD) has been recently described as feasible treatment for patients with refractory Eustachian tube dysfunction (ETD). The aim of this study was to evaluate the efficacy of ETBD in the treatment of symptomatic Eustachian tube dysfunction (SETD) by subjective and objective analysis. MATERIALS AND METHODS: Forty patients who underwent ETBD were included in the study. Subjects' inclusion criteria were as follows: symptoms of ETD (aural fullness predominantly, with or without otalgia, muffle hearing and tinnitus), normal tympanic membrane, type A or C tympanograms, and without a history of any middle ear diseases. Main outcomes including subjective improvement, otoscopy, pure-tone audiometry, impedance audiometry, R-value in tubomanometry (TMM) at three pressure measurements (30, 40, and 50 mbar), Eustachian Tube Score (ETS) and the ability to perform a Valsalva maneuver were assessed preoperatively, 1 week, 3 months and 12 months postoperatively. RESULTS: All cases were dilated successfully. A significant effect of treatment was documented when measuring subjective improvement, impedance audiometry, R-value in TMM, ETS and the ability to perform a Valsalva maneuver 1 week, 3 months and 12 month postoperatively. Subjective symptoms were not relieved only in one patient. The overall success rate for all patients was 98%. CONCLUSIONS: ETBD can provide both short- and long-term benefits to those who are diagnosed SETD and refractory to medical management. SETD might be an optimal indication for ETBD in the treatment of ETD.


Assuntos
Cateterismo/métodos , Dilatação/métodos , Otopatias/terapia , Tuba Auditiva/fisiopatologia , Audição/fisiologia , Testes de Impedância Acústica , Adulto , Idoso , Otopatias/diagnóstico , Otopatias/fisiopatologia , Tuba Auditiva/diagnóstico por imagem , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Otoscopia , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
17.
Am J Otolaryngol ; 37(5): 442-6, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27221026

RESUMO

OBJECTIVE: To evaluate the effect of the combination of balloon Eustachian tuboplasty (BET) and tympanic paracentesis (TP) on intractable chronic otitis media with effusion (COME). METHODS: Ninety patients with intractable COME were included and randomly assigned to three groups: BET only (30 patients), BET+paracentesis (30 patients), and paracentesis only (30 patients). Otic endoscopic findings and tympanograms were recorded before the surgery and at the month 1, month 3, and month 6 follow-up evaluations. RESULTS: Both the BET only and BET+paracentesis groups achieved better outcomes than the paracentesis group. The BET+paracentesis group exhibited better otic endoscopic scores than the BET only group (p<0.05) at 1month post-operation. However, no significant difference was found at month 3 or month 6 post-operation. No significant difference in the tympanograms was observed between these two groups at month 1, month 3, or month 6 post-operation. The otic endoscopic sign scores improved from month 1 to month 6 in the BET only group and from month 1 to month 3 in the BET+paracentesis group. The conversion of type B tympanograms improved from month 1 to month 6 in the BET and BET+paracentesis groups but not in the paracentesis only group. CONCLUSIONS: Our results suggested that the combination of BET and TP was effective for intractable COME and can help shorten the recovery period for middle ear effusion.


Assuntos
Tuba Auditiva/cirurgia , Ventilação da Orelha Média , Otite Média com Derrame/cirurgia , Paracentese , Timpanoplastia , Adulto , Doença Crônica , Terapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Resultado do Tratamento , Adulto Jovem
18.
Eur Arch Otorhinolaryngol ; 273(9): 2451-9, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26611684

RESUMO

The purpose of this study was to investigate the effect of symmetrical, asymmetrical and unilateral hearing impairment on music quality perception. Six validated music pieces in the categories of classical music, folk music and pop music were used to assess music quality in terms of its 'pleasantness', 'naturalness', 'fullness', 'roughness' and 'sharpness'. 58 participants with sensorineural hearing loss [20 with unilateral hearing loss (UHL), 20 with bilateral symmetrical hearing loss (BSHL) and 18 with bilateral asymmetrical hearing loss (BAHL)] and 29 normal hearing (NH) subjects participated in the present study. Hearing impaired (HI) participants had greater difficulty in overall music quality perception than NH participants. Participants with BSHL rated music pleasantness and naturalness to be higher than participants with BAHL. Moreover, the hearing thresholds of the better ears from BSHL and BAHL participants as well as the hearing thresholds of the worse ears from BSHL participants were negatively correlated to the pleasantness and naturalness perception. HI participants rated the familiar music pieces higher than unfamiliar music pieces in the three music categories. Music quality perception in participants with hearing impairment appeared to be affected by symmetry of hearing loss, degree of hearing loss and music familiarity when they were assessed using the music quality rating test (MQRT). This indicates that binaural symmetrical hearing is important to achieve a high level of music quality perception in HI listeners. This emphasizes the importance of provision of bilateral hearing assistive devices for people with asymmetrical hearing impairment.


Assuntos
Percepção Auditiva/fisiologia , Perda Auditiva Bilateral/fisiopatologia , Perda Auditiva Neurossensorial/fisiopatologia , Perda Auditiva Unilateral/fisiopatologia , Música , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reconhecimento Psicológico
19.
Front Nutr ; 11: 1421605, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38962438

RESUMO

Background: Oxidative stress is associated with the occurrence of hearing loss and tinnitus. The oxidative balance score (OBS), a composite indicator evaluating the balance between antioxidant and pro-oxidative components across various dietary and lifestyle factors, indicates the overall oxidative balance status. However, the association of OBS with hearing loss and tinnitus has not been reported previously. Methods: Cross-sectional data from the National Health and Nutrition Examination Survey (NHANES) 1999-2018 were analyzed. Weighted multivariable logistic regression, weighted multivariable linear regression, and restricted cubic spline curve (RCS) regression were employed to explore the relationship between OBS and hearing loss at speech, low, and high frequencies, along with tinnitus. Subgroup analysis and sensitivity analysis were used to ascertain the consistency across subgroups and stability of the results. Results: We included 13,715 and 21,644 individuals to investigate the association between OBS and hearing loss, as well as between OBS and tinnitus, respectively. The second, third, and fourth quartiles of OBS were significantly associated with a lower risk of hearing loss at speech, low, and high frequencies, as well as tinnitus, compared to the lowest quartile. The RCS regression analysis indicated a negative linear association of OBS with hearing loss and tinnitus. Most associations were maintained in subgroup analysis and sensitivity analysis. Additionally, the dietary and lifestyle OBS independently contribute to the protection against hearing loss and tinnitus. Conclusion: OBS is negatively correlated with the risk of hearing loss and tinnitus. The findings suggest that combined antioxidant diet and lifestyle hold promise as potential strategies for reducing the prevalence of hearing loss and tinnitus.

20.
Acta Otolaryngol ; 144(2): 136-141, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38651889

RESUMO

BACKGROUND: Hearing loss is a common sequala of Streptococcus suis (S. suis) meningitis, but few have addressed cochlear implantation (CI) candidates with S. suis meningitis. OBJECTIVES: To assess the clinical characteristics and CI postoperative outcomes in S. suis meningitis patients. MATERIAL AND METHODS: Eight S. suis meningitis patients underwent CI at Sun Yat-sen Memorial Hospital between 2020 and 2023. Control groups included (1) non-Suis meningitis patients (n = 12) and (2) non-meningitis patients (n = 35). Electrode impedances and neural response telemetry (NRT) thresholds were recorded at one month after surgery. The auditory performance-II (CAP) and speech intelligibility rating (SIR) were recorded at the last visit. RESULTS: CAP scores of S. suis meningitis patients were significantly lower than those of non-Suis meningitis and non-meningitis patients (p = .019; p<.001). And NRT thresholds of S. suis meningitis patients were higher than those of non-Suis meningitis and non-meningitis patients (p = .006; p = .027). CONCLUSIONS AND SIGNIFICANCE: It is recommended for S. suis meningitis CI candidates to undergo CI promptly after controlling infection, preferably within four to six weeks. CI users with S. suis meningitis tend to exhibit suboptimal hearing rehabilitation outcomes, possibly associated with the more severe damage on spiral ganglion cells after S. suis meningitis.


Assuntos
Implante Coclear , Meningites Bacterianas , Infecções Estreptocócicas , Streptococcus suis , Humanos , Masculino , Feminino , Meningites Bacterianas/complicações , Adulto , Pessoa de Meia-Idade , Infecções Estreptocócicas/cirurgia , Infecções Estreptocócicas/complicações , Idoso , Adulto Jovem
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