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1.
Otol Neurotol ; 45(7): e509-e516, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-38918071

RESUMO

OBJECTIVE: The purpose of this study was to evaluate the value of asymmetry values, gain, and pathological saccades of the video head impulse test (vHIT) in sudden sensorineural hearing loss (SSNHL). STUDY DESIGN: Retrospective study. SETTING: Tertiary referral center. PATIENTS: A total of 226 individuals diagnosed with unilateral definite SSNHL were hospitalized. The assessment included a comprehensive evaluation of medical history, pure-tone test, acoustic impedance, positional test, video nystagmography (VNG), vHIT, vestibular evoked myogenic potentials (VEMPs) and magnetic resonance. INTERVENTIONS: vHIT, VNG, cVEMP, oVEMP. Statistical analysis was performed with SPSS version 22.0 for Windows. MAIN OUTCOME MEASURES: The asymmetry values, gain, and pathological saccades of the vHIT. RESULTS: The abnormal gain of vHIT in anterior, horizontal, and posterior canal in SSNHL patients with vertigo were revealed in 20 of 112 (17.9%), 24 of 112 (21.4%), and 60 of 112 (53.6%), respectively. The vHIT pathological saccades (overt + covert) of anterior, horizontal, and posterior canal in SSNHL patients with vertigo were observed in 5 of 112 (4.6%), 52 of 112 (46.4%), and 58 of 112 (51.8%), respectively. Multivariate analysis indicated that the prognosis of patients with vertigo was correlated with vHIT gain of posterior canal, pathological saccade in horizontal canal, asymmetric ratio of horizontal canal gain, asymmetric ratio of posterior canal gain, Canal paresis (%) on caloric test and spontaneous nystagmus. CONCLUSION: In the vHIT of patients with SSNHL with vertigo, the posterior canal is most easily affected. Reduced gain of posterior canal, pathological saccade of horizontal canal, and larger asymmetric gain of posterior canal and horizontal canal may be negative prognostic factors.


Assuntos
Teste do Impulso da Cabeça , Perda Auditiva Neurossensorial , Perda Auditiva Súbita , Movimentos Sacádicos , Potenciais Evocados Miogênicos Vestibulares , Humanos , Teste do Impulso da Cabeça/métodos , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Movimentos Sacádicos/fisiologia , Estudos Retrospectivos , Perda Auditiva Neurossensorial/fisiopatologia , Perda Auditiva Neurossensorial/diagnóstico , Idoso , Perda Auditiva Súbita/fisiopatologia , Perda Auditiva Súbita/diagnóstico , Potenciais Evocados Miogênicos Vestibulares/fisiologia , Adolescente , Vertigem/fisiopatologia , Vertigem/diagnóstico , Adulto Jovem , Imageamento por Ressonância Magnética , Idoso de 80 Anos ou mais
2.
Front Neurol ; 14: 1269545, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38090267

RESUMO

Background: Observational studies have indicated a potential association between thyroid dysfunction and the risk of sudden sensorineural hearing loss (SSNHL). However, the precise causal relationship between the two remains uncertain. The objective of our study was to assess the causal influence of thyroid function on SSNHL by employing a bidirectional and multivariable Mendelian randomization (MR) approach. Methods: Single-nucleotide polymorphisms (SNPs) associated with free thyroid (FT4) and thyroid stimulating hormone (TSH) were selected from the summary data of a large genome-wide association study (GWAS) conducted on European individuals. The summary-level data of SSNHL were also obtained from a GWAS, which included 196,592 participants (1,491 cases and 195,101 controls). The MR analysis primarily utilized the inverse variance weighted (IVW) method, with sensitivity analyses performed using the weighted median, MR-Egger, and MR-PRESSO approaches. Results: In the IVW method, an elevated genetically predicted FT4 level was found to effectively reduce the risk of SSNHL (OR = 0.747, 95% CI = 0.565-0.987, P = 0.04). These findings were consistent when conducting multivariate MR analysis, which adjusted for TSH levels (OR = 0.929, 95% CI = 0.867-0.995, P = 0.036). However, genetically predicted TSH levels did not emerge as a risk factor for SSNHL (OR = 1.409, 95% CI = 0.895-1.230, P = 0.547). Furthermore, even after adjusting for FT4 levels in the multivariate MR analysis, no evidence of a direct causal relationship between TSH levels and the risk of SSNHL was observed (OR = 1.011, 95% CI = 0.880-1.161, P = 0.867). The reverse MR analysis showed that there was no evidence of a direct causal relationship between SSNHL and the risk of FT4 level (OR = 1.026, 95% CI = 0.999-1.054, P = 0.056) or TSH level (OR = 1.002, 95% CI = 0.989-1.015, P = 0.702). Conclusion: Within the normal range, genetic variants associated with higher FT4 levels demonstrate a potential protective effect against SSNHL, whereas there is no direct causal relationship between TSH levels and the risk of SSNHL.

3.
Curr Treat Options Oncol ; 24(10): 1392-1407, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37556048

RESUMO

OPINION STATEMENT: Temporal bone paragangliomas (TBPs) are indolent, classically benign and highly vascular neoplasms of the temporal bone. There are two types of TBPs, tympanomastoid paragangliomas (TMPs) and tympanojugular paragangliomas (TJPs). The most common symptoms are hearing loss and pulsatile tinnitus. Diagnostic workup, besides conventional physical and laboratory examinations, includes biochemical testing of catecholamine and genetic testing of SDHx gene mutations as well as radiological examination. Although surgery is traditionally the mainstay of treatment, it is challenging due to the close proximity of tumor to critical neurovascular structures and thus the high risk of complications, especially in patients with advanced lesions. Radiotherapy and active surveillance have been increasingly recommended for selected patients. Decision on treatment should be made comprehensively. Curative effect depends on various factors. Long-term follow-up with clinical, laboratory, and radiological examinations is essential for all patients.


Assuntos
Neoplasias de Cabeça e Pescoço , Paraganglioma , Humanos , Paraganglioma/diagnóstico , Paraganglioma/etiologia , Paraganglioma/terapia , Osso Temporal , Mutação , Testes Genéticos , Estudos Retrospectivos , Neoplasias de Cabeça e Pescoço/genética
4.
Front Public Health ; 11: 1184262, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37304124

RESUMO

Objective: To report the otologic symptoms that present in patients with COVID-19 infection and investigate the pathogenic characteristics during the period of the pandemic. Materials and methods: This cross-sectional descriptive study included participants with COVID-19 infection. COVID-19 infection was verified in these patients by nucleic acid test or antigen test. An online questionnaire was developed to analyze the association between the COVID-19 pandemic and the characteristics of otologic symptoms. Results: This study included 2,247 participants, of which nearly half had one or more otologic symptoms. The presents of otologic symptoms were associated with gender (OR = 1.575, p < 0.0001), age (OR = 0.972, p < 0.0001), and occupation (healthcare worker: p < 0.0001; personnel of enterprises or institutions: OR = 1.792, p < 0.0001; student: OR = 0.712, p < 0.044). The otologic symptoms following COVID-19 infection in order were vertigo (25.95%), tinnitus (19.05%), otalgia (19.00%), aural fullness (17.18%), hearing loss (11.62%), otorrhea (1.25%), and facial paralysis (0.27%). Conclusion: The present study shows that otologic symptoms are common among the COVID-19 infected participants and that these symptoms mostly recover spontaneously. During the corona-virus pandemic, the involvement of the cochleovestibular system and facial nerve should not be overlooked while treating the COVID-19 infected individuals.


Assuntos
COVID-19 , Ácidos Nucleicos , Humanos , COVID-19/epidemiologia , Estudos Transversais , Pandemias , Pessoal de Saúde
5.
Front Neurol ; 14: 1121324, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36908605

RESUMO

Introduction: Although sudden sensorineural hearing loss (SSNHL) has been attempted to be understood for 70 years, diagnosis and treatment strategies still have strong heterogeneity worldwide, which are reflected in the guidelines issued by countries and the clinical practice of otolaryngologists. Methods: Questionnaires were sent to registered otolaryngologists nationwide via an online questionnaire system. We investigated the current views and clinical practices of otolaryngologists in mainland China about the diagnosis, examination, and treatment strategies of SSNHL. Results: Most otolaryngologists supported diagnostic classification via audiograms. Regional economic situation and hospital grade affected application strategies for differential diagnosis. Regarding corticosteroid therapy, 54.9% of respondents opted to discontinue the drug 5 days after systemic administration. Both intratympanic therapy and post-auricular injections were selected by more than half of the respondents as initial and salvage treatments. Discussion: Chinese otolaryngologists exhibit heterogeneity in clinical practices for SSNHL, including distinct approaches to combination therapy and local application of steroids. This study pointed out Chinese doctors' similarities, differences, and unique strategies in diagnosing and treating SSNHL and analyzed the possible reasons to help the world understand the current otolaryngology practices in China.

6.
BMC Bioinformatics ; 24(1): 56, 2023 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-36803022

RESUMO

Sudden sensorineural hearing loss is a common and frequently occurring condition in otolaryngology. Existing studies have shown that sudden sensorineural hearing loss is closely associated with mutations in genes for inherited deafness. To identify these genes associated with deafness, researchers have mostly used biological experiments, which are accurate but time-consuming and laborious. In this paper, we proposed a computational method based on machine learning to predict deafness-associated genes. The model is based on several basic backpropagation neural networks (BPNNs), which were cascaded as multiple-level BPNN models. The cascaded BPNN model showed a stronger ability for screening deafness-associated genes than the conventional BPNN. A total of 211 of 214 deafness-associated genes from the deafness variant database (DVD v9.0) were used as positive data, and 2110 genes extracted from chromosomes were used as negative data to train our model. The test achieved a mean AUC higher than 0.98. Furthermore, to illustrate the predictive performance of the model for suspected deafness-associated genes, we analyzed the remaining 17,711 genes in the human genome and screened the 20 genes with the highest scores as highly suspected deafness-associated genes. Among these 20 predicted genes, three genes were mentioned as deafness-associated genes in the literature. The analysis showed that our approach has the potential to screen out highly suspected deafness-associated genes from a large number of genes, and our predictions could be valuable for future research and discovery of deafness-associated genes.


Assuntos
Surdez , Perda Auditiva Neurossensorial , Humanos , Surdez/genética , Perda Auditiva Neurossensorial/diagnóstico , Perda Auditiva Neurossensorial/genética , Testes Genéticos , Mutação , Redes Neurais de Computação
7.
Eur J Med Res ; 28(1): 26, 2023 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-36639782

RESUMO

BACKGROUND: Aldosterone relieves transcriptional repression of epithelial sodium channel (ENaC) by inhibiting Dot1a and Af9 expression and their interaction with ENaC promoter in various tissues. Expressions of ENaC and Af9 in inner ear have been identified. However, it is not known how Dot1l is regulated by aldosterone in inner ear. METHODS: Twenty-eight adult guinea pigs were randomly divided into the control group and treatment group. Aldosterone 1 mg/kg/d was injected intraperitoneally in the treatment group and saline in the control group for 7 days. Animals were killed 1 month later following auditory brainstem response examination. Histomorphology of cochlea was detected with hematoxylin-eosin staining, and Dot1l expression was examined with immunohistochemistry and Western blot. RESULTS: There was no significant difference in ABR thresholds before and after injection of aldosterone or saline in either group. Endolymphatic hydrops was found in 75% of animals in the treatment group. Dot1l was found in both groups in the stria vascularis, Reissner's membrane, spiral limbus, organ of Corti and spiral ligament. Dot1l expression in the treatment group was decreased by aldosterone. CONCLUSIONS: Dot1l in guinea pig cochlea is inhibited by aldosterone with induction of endolymphatic hydrops. Dot1l may be closely related to endolymph regulation by aldosterone and to pathogenesis of Meniere's disease.


Assuntos
Hidropisia Endolinfática , Doença de Meniere , Cobaias , Animais , Aldosterona/farmacologia , Aldosterona/metabolismo , Cóclea/metabolismo , Cóclea/patologia , Hidropisia Endolinfática/etiologia , Hidropisia Endolinfática/metabolismo , Hidropisia Endolinfática/patologia , Doença de Meniere/complicações , Doença de Meniere/metabolismo , Doença de Meniere/patologia
8.
Biomed Res Int ; 2023: 1733100, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36718148

RESUMO

Laryngeal squamous cell cancer (LSCC) is a common malignant tumor with a high degree of malignancy, and its etiology remains unclear. Therefore, screening potential biomarkers is necessary to facilitate the treatment and diagnosis of LSCC. Robust rank aggregation (RRA) analysis was used to integrate two gene expression datasets of LSCC patients from the Gene Expression Omnibus (GEO) database and identify differentially expressed genes (DEGs) between LSCC and nonneoplastic tissues. A gene coexpression network was constructed using weighted gene correlation network analysis (WGCNA) to explore potential associations between the module genes and clinical features of LSCC. Combining differential gene expression analysis and survival analysis, we screened potential hub genes, including CDK1, SPC24, HOXB7, and SELENBP1. Subsequently, western blotting and immunohistochemistry were used to test the protein levels in clinical specimens to verify our findings. Finally, four candidate diagnostic and prognostic biomarkers (CDK1, SPC24, HOXB7, and SELENBP1) were identified. We propose, for the first time, that SPC24 is a gene that may associate with LSCC malignancy and is a novel therapeutic target. These findings may provide important mechanistic insight of LSCC.


Assuntos
Neoplasias de Cabeça e Pescoço , Neoplasias Laríngeas , Neoplasias de Células Escamosas , Humanos , Neoplasias Laríngeas/diagnóstico , Neoplasias Laríngeas/genética , Neoplasias Laríngeas/metabolismo , Prognóstico , Carcinoma de Células Escamosas de Cabeça e Pescoço/diagnóstico , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Neoplasias de Cabeça e Pescoço/genética , Ciclo Celular/genética , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Regulação Neoplásica da Expressão Gênica/genética , Proteínas Associadas aos Microtúbulos/genética , Proteínas de Homeodomínio/genética
9.
Front Genet ; 13: 931037, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35754831

RESUMO

[This corrects the article DOI: 10.3389/fgene.2021.659517.].

10.
Curr Treat Options Oncol ; 23(1): 43-53, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35167009

RESUMO

OPINION STATEMENT: Malignant tumors of the external auditory canal (EAC) are rare tumors in the head and neck. Delayed diagnosis is not uncommon because the symptoms of early tumors are nonspecific. Various surgical and oncological treatment modalities have been reported. Decision-making depends on pathological feature and stage of the lesions, patient's general condition and preference, and physician's experience and skill. Radical surgery is widely accepted as the primary treatment of choice. Postoperative radiotherapy is used more often to improve local and regional control of the disease. Chemotherapy is usually recommended for advanced disease, residual disease, and metastasis. Prognosis is affected by multiple factors such as TNM stage, surgical margin, pathological type and differentiation of tumor, involvement of facial nerve, and so on. Although the survival rate is improved significantly over the past several decades with the development of skull base surgery, neuroradiology, anesthesiology, and oncology, it remains challenging to diagnose and treat EAC malignancies due to the rarity, the local anatomical complexity of temporal bone, and the lack of standard TNM staging system.


Assuntos
Carcinoma de Células Escamosas , Neoplasias da Orelha , Carcinoma de Células Escamosas/patologia , Meato Acústico Externo/patologia , Meato Acústico Externo/cirurgia , Neoplasias da Orelha/diagnóstico , Neoplasias da Orelha/patologia , Neoplasias da Orelha/terapia , Humanos , Estadiamento de Neoplasias , Estudos Retrospectivos , Resultado do Tratamento
11.
Bioelectromagnetics ; 43(2): 106-118, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35066900

RESUMO

Numerous studies have shown that radiofrequency electromagnetic radiation (RF-EMR) may negatively affect human health. We detected the effect of 3500 MHz RF-EMR on anxiety-like behavior and the auditory cortex (ACx) in guinea pigs. Forty male guinea pigs were randomly divided into four groups and exposed to a continuous wave of 3500 MHz RF-EMF at an average specific absorption rate (SAR) of 0, 2, 4, or 10 W/kg for 72 h. After exposure, malondialdehyde (MDA) levels, antioxidant enzyme activity, anxiety-like behavior, hearing thresholds, cell ultrastructure, and apoptosis were detected. Our results revealed that hearing thresholds and basic indexes of animal behavior did not change significantly after exposure (P > 0.05). However, the MDA levels of ACx were increased (P < 0.05), and catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GSH-px) activities were decreased (P < 0.05) in the exposure groups compared to the sham group. Ultrastructural changes of ACx, including swollen mitochondria and layered myelin sheaths, were observed. Cytochrome-c relocalization, caspase-9, and cleaved caspase-3 activation were detected in the exposure groups. In conclusion, these results suggest that oxidative stress is an important mechanism underlying the biological effects of RF-EMR, which can induce ultrastructural damage to the ACx and cell apoptosis through a mitochondria-dependent mechanism. Moreover, oxidative stress, apoptosis induction and ultrastructural damage increase in a SAR-dependent manner. However, RF-EMR does not increase hearing thresholds or induce anxiety. Bioelectromagnetics. 43:106-118, 2022. © 2021 Bioelectromagnetics Society.


Assuntos
Córtex Auditivo , Telefone Celular , Animais , Antioxidantes/metabolismo , Ansiedade/etiologia , Córtex Auditivo/metabolismo , Campos Eletromagnéticos/efeitos adversos , Radiação Eletromagnética , Cobaias , Masculino , Estresse Oxidativo
12.
J Int Med Res ; 49(2): 300060521990983, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33630715

RESUMO

OBJECTIVE: To analyze the etiologies, treatments, and outcomes of sensorineural hearing loss (SSNHL) during pregnancy. STUDY DESIGN: Retrospective chart review of 25 pregnant patients treated for SSNHL between January 2012 and September 2019. Forty-nine age matched non-pregnant women with severe and profound hearing loss diagnosed with SSNHL during the same period served as controls. Data were recorded on age, symptoms, onset of hearing loss, audiometric results, treatments, and outcomes. RESULTS: The mean age was 29.6 years (range 23-38 years). Intratympanic steroids (ITS) were administered in 15 (60.0%) pregnant women with SSNHL. Three women were treated with postauricular steroids only, while another woman was treated with intravenous ginkgo leaf extract and dipyridamole. The remaining six women received no medications. More than half (8/15, 53.3%) of pregnant women with SSNHL receiving ITS experienced hearing improvement. Pregnant women with profound hearing loss who received no medication had no hearing improvement. Most pregnant women with SSNHL (12/15, 80.0%) had higher fibrinogen levels than controls (mean values 3.77±0.71 g/L and 2.54±0.48 g/L, respectively). CONCLUSION: Fibrinogen could be a risk factor for SSNHL during pregnancy. ITS may benefit pregnant women with severe and profound SSNHL.


Assuntos
Perda Auditiva Neurossensorial , Perda Auditiva Súbita , Adulto , Audiometria , Feminino , Perda Auditiva Neurossensorial/tratamento farmacológico , Perda Auditiva Neurossensorial/etiologia , Perda Auditiva Súbita/diagnóstico , Perda Auditiva Súbita/tratamento farmacológico , Perda Auditiva Súbita/etiologia , Humanos , Injeção Intratimpânica , Gravidez , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
13.
Front Genet ; 12: 659517, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-35024042

RESUMO

Objective: The etiology of sudden sensorineural hearing loss (SSNHL) is still unknown. It has been demonstrated that normal endolymph metabolism is essential for inner ear function and that epithelial sodium channels (ENaC) may play an important role in the regulation of endolymphatic Na+. This study aimed to explore the potential association between αENaC p. Ala663Thr gene polymorphism and SSNHL. Methods: Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to examine the genotype and allele frequency of the αENaC p. Ala663Thr polymorphism in 20 cases of low-frequency SSNHL (LF-SSNHL), 19 cases of high-frequency SSNHL (HF-SSNHL), 31 cases of all frequency SSNHL (AF-SSNHL), 42 cases of profound deafness SSNHL (PD-SSNHL), and 115 normal controls. Results: The T663 allele was found to be significantly associated with an increased risk of LF-SSNHL (p = 0.046, OR = 2.16, 95% CI = 1.01-4.62). The TT genotype and T663 allele, on the other hand, conferred a protective effect for PD-SSNHL (AA vs. TT: p = 0.012, OR = 0.25, 95% CI = 0.08-0.74; A vs. T: p = 0.001, OR = 0.36, 95% CI = 0.21-0.61). However, there was no statistically significant difference in genotype or allele frequency between the two groups (HF-SSNHL and AF-SSNHL) and the control group. Conclusion: The αENaC p. Ala663Thr gene polymorphism plays different roles in different types of SSNHL.

14.
Eur Arch Otorhinolaryngol ; 278(9): 3193-3202, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32979119

RESUMO

OBJECTIVE: Temporal bone squamous cell carcinoma (TBSCC) is a rare, aggressive tumor. Surgery, alone or combined with radiotherapy, represent the mainstay of treatment. To report our experience in the treatment of TBSCC and evaluate the disease-specific survival, identifying the factors influencing this outcome. MATERIALS AND METHODS: A retrospective study was performed on 66 patients between 1993 and 2018. Patients were staged according to the University of Pittsburgh-modified TNM staging system. Nine cases (13.6%) were Stage I, 7 cases (10.6%) Stage II, 20 cases (30.3%) Stage III and 30 cases (45.5%) Stage IV. Twenty-four patients underwent lateral temporal bone resection (LTBR) and 42 patients underwent subtotal temporal bone resection (STBR). RESULTS: One hundred percent of Stage I and II patients showed no evidence of disease (NED) after a median follow-up of 101 months (range 1-289 months). NED resulted in 88.2% of Stage III (mean follow-up 80.3 months; range 8-257) and 46.4% of stage IV (mean follow-up 50.6 months; range 3-217). Pittsburgh Stage or involvement of mastoid, facial nerve, medial wall of the middle ear, temporomandibular joint and middle fossa dura emerged as negative prognostic factors. The highest mortality rate occurred in the first 2 years after treatment, due to local recurrence. CONCLUSIONS: Prognosis of TBSCC can be excellent in early stage tumors, employing a LTBR. In more advanced cases, prognosis is poor. STBR with adjuvant radiotherapy represents the treatment of choice, offering acceptable survival rates. Given the rarity of the pathology, many controversies still exist concerning optimal management.


Assuntos
Carcinoma de Células Escamosas , Recidiva Local de Neoplasia , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/cirurgia , Humanos , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Osso Temporal/patologia , Osso Temporal/cirurgia , Resultado do Tratamento
15.
Bioelectromagnetics ; 41(3): 219-229, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32072661

RESUMO

To investigate the possible mechanisms for biological effects of 1,800 MHz mobile radiofrequency radiation (RFR), the radiation-specific absorption rate was applied at 2 and 4 W/kg, and the exposure mode was 5 min on and 10 min off (conversation mode). Exposure time was 24 h short-term exposure. Following exposure, to detect cell DNA damage, cell apoptosis, and reactive oxygen species (ROS) generation, the Comet assay test, flow cytometry, DAPI (4',6-diamidino-2-phenylindole dihydrochloride) staining, and a fluorescent probe were used, respectively. Our experiments revealed that mobile phone RFR did not cause DNA damage in marginal cells, and the rate of cell apoptosis did not increase (P > 0.05). However, the production of ROS in the 4 W/kg exposure group was greater than that in the control group (P < 0.05). In conclusion, these results suggest that mobile phone energy was insufficient to cause cell DNA damage and cell apoptosis following short-term exposure, but the cumulative effect of mobile phone radiation still requires further confirmation. Activation of the ROS system plays a significant role in the biological effects of RFR. Bioelectromagnetics. © 2020 The Authors. Bioelectromagnetics published by Wiley Periodicals, Inc.


Assuntos
Telefone Celular , Ondas de Rádio/efeitos adversos , Estria Vascular/citologia , Animais , Apoptose , Células Cultivadas , Dano ao DNA , Feminino , Masculino , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/metabolismo , Estria Vascular/patologia , Estria Vascular/fisiologia
16.
J Cell Mol Med ; 24(4): 2444-2450, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31957270

RESUMO

Radioresistance causes a major problem for improvement of outcomes of patients treated with radiation. Targeting for DNA repair deficient mechanisms is a hallmark of sensitization to resistance. We tested whether Olaparib, a (poly) ADP-ribose polymerase (PARP) inhibitor, can sensitize the radioresistant FaDu cells to radiotherapy. Radioresistant FaDu cells, called FaDu-RR cells, were used as the radioresistant hypopharyngeal cancer models. The expression of PARP1 was detected in both FaDu and FaDu-RR cells. The role of Olaparib in radiosensitization was analysed with several assays including clonogenic cell survival, cell proliferation and cell cycle, and radioresistant xenograft. High expression of PARP1 had a significant effect on enhancing radioresistance in FaDu-RR cells compared with FaDu cells. After treatment of Olaparib, FaDu-RR cells showed significantly less and smaller surviving colonies, lower proliferation ability and G2/M arrest than those in the group without treatment. Moreover, Olaparib significantly reduced growth of tumours in FaDu-RR cell xenografts treated with ionizing radiation. Olaparib can significantly inhibit PARP1 expression and consequently has significant effects on radiosensitization in FaDu-RR cells. These results indicate that Olaparib may help individualize treatment and improve their outcomes of hypopharyngeal cancer patients treated with radiation.


Assuntos
Ftalazinas/farmacologia , Piperazinas/farmacologia , Inibidores de Poli(ADP-Ribose) Polimerases/farmacologia , Poli(ADP-Ribose) Polimerases/metabolismo , Tolerância a Radiação/efeitos dos fármacos , Animais , Antineoplásicos/farmacologia , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Divisão Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Reparo do DNA/efeitos dos fármacos , Fase G2/efeitos dos fármacos , Humanos , Masculino , Camundongos , Camundongos Nus , Ensaios Antitumorais Modelo de Xenoenxerto/métodos
17.
Oral Oncol ; 100: 104469, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31756687

RESUMO

BACKGROUND: Radiotherapy is a central treatment option for hypopharyngeal squamous cell carcinoma, but the prognoses of patients treated with radiotherapy only are not satisfactory due to radioresistance. The underlying molecular mechanisms remain largely elusive, and mechanism-derived predictive markers of radioresistance are currently unavailable. METHODS: In this study, we first established a specifically radioresistant FaDu cell line by repeated exposure to ionizing radiation with a total dose of 60 Gy (FaDu-RR). The validation of FaDu-RR cells was performed by clonogenic cell survival assay and cell proliferation assay. Microarrays and bioinformatics were analyzed to determine the differentially expressed mRNAs and their functions. DNA-repair capabilities were tested by cell cycle analysis and comet assay. The expressions of four key proteins in homologous recombination pathways, including BRCA1, BRCA2, RPA1, and Rad51, were detected both in FaDu-RR cells and radioresistant xenograft. RESULTS: We established the specifically radioresistant FaDu cell line. Through microarrays and bioinformatics, homologous recombination pathways were suggested to play important roles in radioresistant mechanisms. High expression levels of key proteins in homologous recombination pathways were then detected both in FaDu-RR cells and radioresistant xenograft. Silencing RPA1 could reduce the radioresistance of FaDu-RR cells. CONCLUSION: Our results provided strong evidence that homologous recombination enhances the radioresistance in hypopharyngeal carcinoma. Proteins in homologous recombination pathways may be potential biomarkers to predict hypopharyngeal carcinoma response to radiotherapy, establishing a basis for their utility in clinical practice.


Assuntos
Carcinoma de Células Escamosas/genética , Reparo do DNA/efeitos da radiação , Recombinação Homóloga , Neoplasias Hipofaríngeas/genética , Tolerância a Radiação , Animais , Proteína BRCA1/genética , Proteína BRCA2/genética , Carcinoma de Células Escamosas/radioterapia , Linhagem Celular Tumoral , Proliferação de Células , Sobrevivência Celular , Perfilação da Expressão Gênica/métodos , Regulação Neoplásica da Expressão Gênica/efeitos da radiação , Humanos , Neoplasias Hipofaríngeas/radioterapia , Masculino , Camundongos , Análise de Sequência com Séries de Oligonucleotídeos , Rad51 Recombinase/genética , Proteína de Replicação A/genética , Regulação para Cima , Ensaios Antitumorais Modelo de Xenoenxerto
18.
J Biomed Sci ; 26(1): 14, 2019 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-30717758

RESUMO

BACKGROUND: Nasopharyngeal carcinoma (NPC), a highly invasive tumor, exhibits a distinctive racial and geographic distribution. As options of agents for effective combination chemoradiotherapy for advanced NPC are limited, novel therapeutic approaches are desperately needed. Here the potential of silencing NFBD1 in combination with PARP inhibition as a novel therapeutic strategy for NPC was investigated. METHODS: To investigate the function of NFBD1, we created NFBD1-depleted NPC cell lines via lentivirus mediated shRNA, and the colony formation, MTS assay, comet assay and apoptosis analysis were used to evaluate the sensitivity of NFBD1 knockdown on PARP inhibition. The signaling change was assessed by western blot, Immunofluorescence and flow cytometry. Furthermore, Xenografts model was used to evaluate the role of silencing NFBD1 in combination with PARP inhibition. RESULTS: We find that silencing NFBD1 in combination with PARP inhibition significantly inhibits the cell proliferation and cell cycle checkpoint activity, and increases the apoptosis and DNA damage. Mechanistic studies reveal that NFBD1 loss blocks olaparib-induced homologous recombination repair by decreasing the formation of BRCA1, BRCA2 and RAD51 foci. Furthermore, the xenograft tumor model demonstrated significantly increases sensitivity towards PARP inhibition under NFBD1 deficiency. CONCLUSIONS: We show that NFBD1 depletion may possess sensitizing effects of PARP inhibitor, and consequently offers novel therapeutic options for a significant subset of patients.


Assuntos
Inativação Gênica , Carcinoma Nasofaríngeo/terapia , Proteínas Nucleares/genética , Inibidores de Poli(ADP-Ribose) Polimerases/metabolismo , Reparo de DNA por Recombinação/genética , Transativadores/genética , Proteínas Adaptadoras de Transdução de Sinal , Apoptose/fisiologia , Proteínas de Ciclo Celular , Linhagem Celular Tumoral , Técnicas de Silenciamento de Genes , Humanos , Proteínas Nucleares/metabolismo , Transativadores/metabolismo
19.
Otol Neurotol ; 39(8): 1018-1024, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-30063499

RESUMO

OBJECTIVE: To investigate the characteristics, treatment, and prognostic factors of sudden sensorineural hearing loss (SSNHL) in children. METHODS: Seventy-five cases (78 ears) of SSNHL in children from February 2011 to June 2016 were retrospectively analyzed. We scrutinized the clinical manifestations, audiological assessments, and serologic examinations of these pediatric cases by univariate and multivariate logistic analysis methods. The patients were divided into four groups according to their audiometric curve type: ascending, descending, flat, and profound. RESULTS: Of the 75 patients (78 ears), 25 patients were in the ascending group (32.00%), 9 patients were in the descending group (12.00%), 17 patients were in the flat group (22.67%), and 24 patients were in the profound group (32.32%). The overall recovery rates (complete + partial + slight) of the different groups were as follows: ascending group, 96.00%; flat group, 76.47%; profound group, 50.00%; and descending group, 44.44%. The overall recovery rate of all patients was 70.67%. The multivariate logistic analysis showed that the type of audiometric curve and the interval from onset to intervention were two independent risk factors that correlated with the prognosis of SSNHL in children. Some children had positive cytomegaoviyns, rubella virus, and herpes simplex virus immunoglobulin G antibodies. Twenty-one children were treated with additional intratympanic methylprednisolone as salvage therapy and 13 of these children showed improved (complete + partial + slight) recoveries. Three children had postauricular compound betamethasone injections, but none of them showed improvement. One of three children recovered slightly after treatment with intratympanic methylprednisolone combined with postauricular betamethasone injection. CONCLUSIONS: The prognosis of SSNHL in children is closely related to the type of audiometric curve and the onset of treatment. Intratympanic methylprednisolone and compound betamethasone injected postauricularly could be effective for SSNHL in children.


Assuntos
Glucocorticoides/uso terapêutico , Perda Auditiva Neurossensorial/diagnóstico , Perda Auditiva Súbita/diagnóstico , Metilprednisolona/uso terapêutico , Adolescente , Audiometria , Criança , Pré-Escolar , Feminino , Glucocorticoides/administração & dosagem , Perda Auditiva Neurossensorial/tratamento farmacológico , Perda Auditiva Súbita/tratamento farmacológico , Humanos , Lactente , Injeção Intratimpânica , Masculino , Metilprednisolona/administração & dosagem , Prognóstico , Estudos Retrospectivos
20.
Acta Otolaryngol ; 137(9): 903-909, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28399691

RESUMO

CONCLUSIONS: Af9 protein in cochlea may be closely related to endolymph regulation by aldosterone and thus may be involved in pathogenesis of endolymphatic hydrops (EH). OBJECTIVES: EH is the pathological characteristic of Ménière's disease (MD). Aldosterone could induce EH, but its relationship with MD is still controversial. The aim of the present study is to investigate the Af9 protein expression in guinea pig cochlea and regulation of Af9 expression and cochlear function by aldosterone. The role of Af9 in pathogenesis of EH is discussed. METHODS: Thirty guinea pigs were randomly divided into two groups. The treatment group was intraperitoneally injected with aldosterone 0.1 mg/kg/d for 5 days, while the control group was done with saline. Hearing and histomorphology of cochlea were examined. In addition, expression of Af9 protein was studied. RESULTS: The hearing threshold of the treatment group was increased. EH was induced in 73% of guinea pigs in the treatment group, and no EH was found in the control group. Af9 protein was found in spiral limbus, stria vascularis, Reissner's membrane, organ of Corti and spiral ganglion in both groups. Af9 expression in cochlea decreased significantly at protein level after treatment by aldosterone.


Assuntos
Aldosterona/fisiologia , Cóclea/metabolismo , Hidropisia Endolinfática/metabolismo , Animais , Cóclea/patologia , Cóclea/fisiopatologia , Hidropisia Endolinfática/etiologia , Hidropisia Endolinfática/patologia , Hidropisia Endolinfática/fisiopatologia , Potenciais Evocados Auditivos do Tronco Encefálico , Cobaias , Distribuição Aleatória
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