RESUMO
Anxiety is a remarkably common condition among patients with pharyngitis, but the relationship between these disorders has received little research attention, and the underlying neural mechanisms remain unknown. Here, we show that the densely innervated pharynx transmits signals induced by pharyngeal inflammation to glossopharyngeal and vagal sensory neurons of the nodose/jugular/petrosal (NJP) superganglia in mice. Specifically, the NJP superganglia project to norepinephrinergic neurons in the nucleus of the solitary tract (NTSNE). These NTSNE neurons project to the ventral bed nucleus of the stria terminalis (vBNST) that induces anxiety-like behaviors in a murine model of pharyngeal inflammation. Inhibiting this pharynxâNJPâNTSNEâvBNST circuit can alleviate anxiety-like behaviors associated with pharyngeal inflammation. This study thus defines a pharynx-to-brain axis that mechanistically links pharyngeal inflammation and emotional response.
Assuntos
Faringite , Faringe , Humanos , Animais , Camundongos , Ansiedade , Encéfalo , Células Receptoras Sensoriais , InflamaçãoRESUMO
OBJECTIVES: To investigate the incidence and characteristics of adult otitis media with effusion (OME) before, during, and after the COVID-19 pandemic. METHODS: A retrospective descriptive study was conducted. The incidence, age, sex, affected ear side, time of OME onset according to COVID-19 and days of improvement after conservative treatment were determined to assess the clinical features of adult OME in different periods of the COVID-19 pandemic. RESULTS: The incidence of adult OME during these periods was 3.17%, 2.30%, 6.18%, and 3.68%, respectively. Unilateral ear involvement and male sex were more common. The onset of adult OME occurred 7.80 ± 3.97 days after COVID-19 diagnosis, and improvement was observed after 12.24 ± 5.08 days of conservative treatment. Patients in the post-pandemic period were older than those in the non-pandemic period. CONCLUSION: The incidence of adult OME in China showed a tendency to decrease, recover, and decrease again following the COVID-19 outbreak. Pandemic prevention and control measures have had a certain impact on reducing the incidence, but the elderly are more prone to this disease.
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COVID-19 , Otite Média com Derrame , Adulto , Humanos , Masculino , Idoso , Recém-Nascido , Otite Média com Derrame/cirurgia , Pandemias , Estudos Retrospectivos , Incidência , Teste para COVID-19 , COVID-19/epidemiologiaRESUMO
PURPOSE: To investigate the effect of the interval between bilateral cochlear implantation on the development of bilateral peripheral auditory pathways as revealed by the electrically evoked auditory brainstem response (EABR). METHODS: Fifty-eight children with profound bilateral sensorineural hearing loss were recruited. Among them, 33 children received sequential bilateral cochlear implants (CIs), and 25 children received simultaneous bilateral CIs. The bilateral EABRs evoked by electrical stimulation from the CI electrode were recorded on the day of second-side CI activation. RESULTS: The latencies of wave III (eIII) and wave V (eV) were significantly shorter on the first CI side than on the second CI side in children with sequential bilateral CIs but were similar between the two sides in children with simultaneous bilateral CIs. Furthermore, the latencies were prolonged from apical to basal channels along the cochlea in the two groups. In children with sequential CIs, the inter-implant interval was negatively correlated with the eV latency on the first CI side and was positively correlated with bilateral differences in the eIII and eV latencies. CONCLUSIONS: Unilateral CI use promotes the maturation of ipsilateral auditory conduction function. However, a longer inter-implant interval results in more unbalanced development of bilateral auditory brainstem pathways. Bilateral cochlear implantation with no or a short interval is recommended.
Assuntos
Implante Coclear , Implantes Cocleares , Surdez , Perda Auditiva Neurossensorial , Criança , Humanos , Perda Auditiva Neurossensorial/cirurgia , Potenciais Evocados Auditivos do Tronco Encefálico/fisiologia , Tronco Encefálico/cirurgia , Surdez/cirurgiaRESUMO
Predictions, the bridge between the internal and external worlds, are established by prior experience and updated by sensory stimuli. Responses to omitted but unexpected stimuli, known as omission responses, can break the one-to-one mapping of stimulus-response and can expose predictions established by the preceding stimulus built up. While research into exogenous predictions (driven by external stimuli) is often reported, that into endogenous predictions (driven by internal percepts) is rarely available in the literature. Here, we report evidence for endogenous predictions established by the Zwicker tone illusion, a phantom pure-tone-like auditory percept following notch noises. We found that MMN, P300, and theta oscillations could be recorded using an omission paradigm in subjects who can perceive Zwicker tone illusions, but could not in those who cannot. The MMN and P300 responses relied on attention, but theta oscillations did not. In-depth analysis shows that an increase in single-trial theta power, including total and induced theta, with the endogenous prediction, is lateralized to the left frontal brain areas. Our study depicts that the brain automatically analyzes internal perception, progressively establishes predictions and yields prediction errors in the left frontal region when a violation occurs.
Assuntos
Ilusões , Humanos , Ilusões/fisiologia , Som , Atenção/fisiologia , Córtex Cerebral/fisiologia , Lobo Frontal/fisiologia , Estimulação Acústica , Percepção Auditiva/fisiologia , Eletroencefalografia , Potenciais Evocados Auditivos/fisiologiaRESUMO
PURPOSE: To investigate the auditory pathway functions in deaf patients with Mondini malformation using the electrically evoked auditory brainstem response (EABR) during cochlear implantation (CI). METHODS: A total of 58 patients with severe to profound sensorineural hearing loss (SNHL) were included in this study. Of these patients, 27 cases had Mondini malformation and 31 control cases had no inner ear malformations (IEMs). Intraoperative EABRs evoked by electrical stimulation at the round window niche (RWN) and round window membrane (RWM) were recorded. RESULTS: Patients with Mondini malformation showed significantly lower EABR extraction rates than those with no IEMs did. However, for patients who showed EABRs, no significant difference in EABR thresholds, wave III (eIII) latencies, wave V (eV) latencies or eIII-eV latency intervals was found between two groups. CONCLUSION: The physiological functions of the peripheral auditory system in patients with Mondini malformation may divide into opposite extremes, as revealed by a robust EABR and the absence of the EABR, respectively. The auditory conduction function should be objectively and individually evaluated for patients with Mondini malformation by the EABR.
Assuntos
Implante Coclear , Implantes Cocleares , Perda Auditiva Neurossensorial , Limiar Auditivo , Potenciais Evocados Auditivos do Tronco Encefálico/fisiologia , Feminino , Audição , Perda Auditiva Neurossensorial/cirurgia , Humanos , GravidezRESUMO
ABSTRACT: Teratomas are germline tumors commonly composed of multiple cell types derived from embryonic germ cell layers. Teratomas in head and neck region are exceptionally rare and present during the neonatal and infantile period. We describe a male adult with a mature teratoma originating from sphenoid body. A 24-year-old male patient presented with left-sided intermitted headache and facial numbness. Radiographic imaging showed a 3 cm × 2.3âcm mass with heterogeneous density in the sphenoid region. The endoscopic sphenoid sinus opening surgery was performed through endonasal transpterygoid approach. The final pathologic diagnosis was confirmed as mature teratoma. The patient has been followed-up for 18 months without recurrence. We suggest endonasal transpterygoid approach could be an effective and safe treatment for patients with mature teratoma in the sphenoid bone.
Assuntos
Neoplasias Ósseas , Teratoma , Neoplasias Ósseas/diagnóstico por imagem , Neoplasias Ósseas/cirurgia , Endoscopia , Humanos , Masculino , Recidiva Local de Neoplasia , Base do Crânio , Osso Esfenoide/diagnóstico por imagem , Osso Esfenoide/cirurgia , Teratoma/diagnóstico por imagem , Teratoma/cirurgia , Adulto JovemRESUMO
BACKGROUND: Allergic rhinitis (AR) is one of the most prevalent allergic diseases in children. This study aimed to investigate the association between serum concentrations of vitamin E and AR to determine if the vitamin E level is correlated with the occurrence and severity of AR. METHODS: A total of 113 children were enrolled in this cross-sectional study. Sixty-five children in the outpatient group were diagnosed with AR, and 48 healthy children were recruited as controls. All subjects underwent serum vitamin E (adjusted for total cholesterol and triglycerides) measurements. Serum to total IgE (tIgE), the five most common allergen-specific IgE (sIgE) levels and skin prick test (SPT) were measured in children with AR. The severity of AR was assessed with the nasal symptoms score, and the situation of exposure to passive smoking were inquired. RESULTS: Serum vitamin E levels were significantly lower in the AR group than in the normal children (P < 0.001). A significant negative correlation was observed between serum vitamin E levels and sIgE as well as the SPT grade. Serum vitamin E levels were also inversely related to the nasal symptoms score; however, statistical significance was not found. CONCLUSIONS: A significantly lower vitamin E level was found in children with AR. Lower serum vitamin E levels may have correlation with the occurrence of AR in children. However, serum vitamin E levels were not statistically correlated with the severity of AR.
Assuntos
Rinite Alérgica , Vitamina E , Criança , Estudos Transversais , Humanos , Imunoglobulina E , Rinite Alérgica/diagnóstico , Testes CutâneosRESUMO
BACKGROUND: Few studies focused on the prognosis of unilateral idiopathic sudden sensorineural hearing loss (UISSNHL) with vertigo. OBJECTIVES: To describe how the semicircular canal (SCC) function tests may prove helpful in the diagnosis of UISSNHL with vertigo. MATERIAL AND METHODS: 59 UISSNHL patients underwent audiometry, caloric test and video head impulse test (vHIT). The correlation between hearing loss and SCC dysfunction was analyzed. RESULTS: The results showed significant differences of hearing loss grades (p = 0.004) and hearing loss configurations (p = 0.009) between UISSNHL patients with and without vertigo. In vHIT, the gains of horizontal canal (HC) and posterior canal (PC) were more frequently impaired compared with that of anterior canal (AC). The abnormal rate of caloric test was the highest, followed by the abnormal rates of HC and PC gain. A significant difference of abnormal rate of HC gain was only found between the mild and moderate UISSNHL patients with and without vertigo (p = 0.029). CONCLUSION: Abnormal SCC function happens frequently in patients with profound hearing loss. Ipsilesional abnormal vHIT (especially the HC gain) in the presence of abnormal caloric test is a pattern of findings observed in mild and moderate UISSNHL patients with vertigo.
Assuntos
Audiometria , Testes Calóricos , Teste do Impulso da Cabeça , Perda Auditiva Neurossensorial/diagnóstico , Perda Auditiva Súbita/diagnóstico , Vertigem/complicações , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Canais Semicirculares/fisiopatologia , Índice de Gravidade de Doença , Adulto JovemRESUMO
BACKGROUND: Yes-associated protein (YAP) plays a crucial role in tumour development and it is the main effector of the Hippo signalling pathway. However, the mechanism underlying YAP downregulation in laryngeal cancer is still unclear. In our previous study, we found that YAP, compared with adjacent tissues, was expressed higher in laryngeal cancer and was also closely associated with histological differentiation, TNM stage and poor prognosis. METHODS: In this study, we attempted to determine whether silenced YAP could downregulate human laryngeal carcinoma Hep-2 cells progression. YAP was downregulated in Hep-2 cells by shRNA, and the malignant ability of Hep-2 was assessed in vitro and in vivo. RESULTS: In vitro, CCK-8, colony formation and wound healing assays showed that downregulation of YAP significantly reduced the rates of proliferation, migration, and invasion in Hep-2 cells. Downregulation of YAP distinctly induced G2/M cycle arrest and increased the rate of apoptosis. Accordingly, western blot assay suggested that the expression of DKK1, vimentin and ß-catenin was significantly decreased after YAP downregulated treatment, thereby indicating that YAP mediated the EMT programme and the Wnt/ß-catenin signalling pathway in carcinoma of the larynx. Furthermore, silencing of YAP suppressed Hep-2 cell tumourigenesis and metastasis in vivo. CONCLUSION: In summary, our findings demonstrated the proliferation of YAP downregulation and the invasion of Hep-2 cells via downregulating the Wnt/ß-catenin pathway in vitro and in vivo, suggesting that YAP may provide a potential therapeutic strategy for the treatment of laryngeal cancer.
Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Neoplasias Laríngeas/metabolismo , Neoplasias Laríngeas/patologia , Fosfoproteínas/metabolismo , beta Catenina/metabolismo , Animais , Apoptose , Movimento Celular , Proliferação de Células , Regulação para Baixo , Pontos de Checagem da Fase G2 do Ciclo Celular , Técnicas de Silenciamento de Genes , Pontos de Checagem da Fase M do Ciclo Celular , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Invasividade Neoplásica , Estadiamento de Neoplasias , RNA Interferente Pequeno , Sincalida , Fatores de Transcrição , Ensaio Tumoral de Célula-Tronco , Vimentina/metabolismo , Via de Sinalização Wnt , Cicatrização , Proteínas de Sinalização YAPRESUMO
The purpose of the present study was to determine the crucial role of microRNAs (miRNAs/miRs) involved in the proliferation and migration of nasopharyngeal carcinoma (NPC) and to investigate their underlying mechanisms. In this study, we focused on the expression and function of miR-200c in NPC. First, we found the expression level of miR-200c in NPC cells and tissues was upregulated, and it was suggested that the high expression of miR-200c accelerated the proliferation and migration of NPC cells in vitro. Notably, a result of the present study was that the cell fate determination factor dachshund family transcription factor 1 (DACH1) was identified as a direct target of miR-200c. Suppression of miR-200c expression in NPC cells increased endogenous DACH1 mRNA and protein levels, which was negatively correlated with miR-200c. Meanwhile, DACH1 was shown to regulate the Wnt/ß-catenin signaling pathway. Accordingly, it was concluded that miR-200c exerted a tumor-promoting role in NPC development by targeting DACH1, which may contribute to the increase in the rates of NPC proliferation and migration. miR-200c may be a potential diagnostic and prognostic biomarker for NPC.
Assuntos
Movimento Celular , Proliferação de Células , Proteínas do Olho/metabolismo , MicroRNAs/genética , Carcinoma Nasofaríngeo/patologia , Fatores de Transcrição/metabolismo , Proteínas Wnt/metabolismo , beta Catenina/metabolismo , Apoptose , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Proteínas do Olho/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Carcinoma Nasofaríngeo/genética , Carcinoma Nasofaríngeo/metabolismo , Neoplasias Nasofaríngeas/genética , Neoplasias Nasofaríngeas/metabolismo , Neoplasias Nasofaríngeas/patologia , Prognóstico , Fatores de Transcrição/genética , Células Tumorais CultivadasRESUMO
This study aims to elucidate the prognostic and predictive biomarker of miR-495 and Stat3 in peripheral blood in relation to lower extremity deep venous thrombosis (DVT). Patients with lower limb fractures were assigned into case and control groups. Rats were allocated into blank (normal rats), sham (normal rats), DVT, miR-495 mimic, miR-495 inhibitor, over-Stat3, and si-Stat3 groups. ELISA was used to detect levels of prothrombin time (PT), endothelin-1 (ET-1), Human Fibrinogen (FIB), D-Dimer, blood coagulation factors V and VIII, tissue type plasminogen activator (t-PA), platelet activating factor (PAF), protein C and Stat3. qRT-PCR was employed for the evaluation of the expressions of miR-495 and Stat3, while receiver operating characteristic (ROC) curve was constructed to assess the predictive value of miR-495 and Stat3 as well as the treatment outcomes of patients with lower limb fractures. Logistic regression analyses were conducted in order to correlate indexes and lower extremity DVT. miR-495 overexpression, t-PA, PAF, and protein C were confirmed to be protective factors, while Stat3 overexpression, PT, ET-1, FIB, D-Dimer, blood coagulation factor V, and VIII were all ultimately considered to be risk factors of lower extremity DVT. Stat3 was confirmed to be the target gene of miR-495. Compared with the blank group, the length and weight of the thrombus as well as the ratio between length and weight, mRNA and protein expression of Stat3 were reduced in the miR-495 mimic and si-Stat3 groups. Our findings suggest that through the suppression of Stat3 expression, miR-495 prohibits lower extremity DVT in peripheral blood.
Assuntos
Biomarcadores/sangue , MicroRNA Circulante/análise , Extremidade Inferior/patologia , MicroRNAs/genética , Fator de Transcrição STAT3/metabolismo , Trombose Venosa/diagnóstico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Ratos , Ratos Sprague-Dawley , Fator de Transcrição STAT3/genética , Trombose Venosa/sangue , Trombose Venosa/genética , Adulto JovemRESUMO
Acoustic trauma is being reported to damage the auditory periphery and central system, and the compromised cortical inhibition is involved in auditory disorders, such as hyperacusis and tinnitus. Parvalbumin-containing neurons (PV neurons), a subset of GABAergic neurons, greatly shape and synchronize neural network activities. However, the change of PV neurons following acoustic trauma remains to be elucidated. The present study investigated how auditory cortical PV neurons change following unilateral 1 hour noise exposure (left ear, one octave band noise centered at 16 kHz, 116 dB SPL). Noise exposure elevated the auditory brainstem response threshold of the exposed ear when examined 7 days later. More detectable PV neurons were observed in both sides of the auditory cortex of noise-exposed rats when compared to control. The detectable PV neurons of the left auditory cortex (ipsilateral to the exposed ear) to noise exposure outnumbered those of the right auditory cortex (contralateral to the exposed ear). Quantification of Western blotted bands revealed higher expression level of PV protein in the left cortex. These findings of more active PV neurons in noise-exposed rats suggested that a compensatory mechanism might be initiated to maintain a stable state of the brain.
Assuntos
Córtex Auditivo/fisiopatologia , Neurônios GABAérgicos/metabolismo , Ruído/efeitos adversos , Estimulação Acústica , Animais , Córtex Auditivo/metabolismo , Potenciais Evocados Auditivos do Tronco Encefálico , Masculino , Parvalbuminas/metabolismo , Ratos Sprague-DawleyRESUMO
An external approach for resection of sinonasal tumors is associated with increased morbidity. Therefore, we employed a modified transnasal endoscopic maxillectomy combined with pre and/or postoperative radiotherapy for early stage maxillary carcinomas. It aims to evaluate our early experience with endoscopic resection of selected malignant sinonasal tumors. The medical and radiology records of patients who underwent endonasal endoscopic resection of malignant sinonasal tumors between 2008 and 2012 were retrospectively reviewed. Ten cases of selected malignant tumor were performed to resect by modified transnasal endoscopic maxillectomy. All the patients were without evidence of disease at a mean follow-up of 26.8 months. No major complications were recorded. The mean hospitalization stay was 6.6 days. In very carefully selected cases of malignant tumors, modified transnasal endoscopic maxillectomy is acceptable. The postoperative complication rate is low, cosmetic outcome is excellent and patients do not require a long hospitalization.
Assuntos
Carcinoma/cirurgia , Neoplasias do Seio Maxilar/cirurgia , Cirurgia Endoscópica por Orifício Natural/métodos , Adulto , Idoso , Carcinoma/patologia , Carcinoma/radioterapia , Feminino , Humanos , Tempo de Internação , Masculino , Neoplasias do Seio Maxilar/patologia , Neoplasias do Seio Maxilar/radioterapia , Pessoa de Meia-Idade , Radioterapia Adjuvante , Estudos Retrospectivos , Resultado do TratamentoRESUMO
The objective of this study was to review our experience on intracranial complications (ICC) secondary to chronic otitis media (COM), and to investigate its clinical characteristics and treatment approaches. From January 1996 to December 2012, 17 patients with ICC secondary to COM were identified and included in this study, and were analyzed retrospectively. 13 out of these 17 cases (76.4 %) have cholesteatoma. The most common intracranial complication is brain abscesses (52.9 %), followed by meningitis (29.4 %), perisinus abscess (11.7 %), and epidural abscess (6 %). All patients underwent emergency mastoidectomy within the first 24 h after clear diagnosis. 7 patients underwent brain abscess drainage or abscess excision at the time of ear surgery. The mortality rates are 0 %. No recurrence was found in the 24-month follow-up period. Cholesteatoma was strongly associated with ICC. An early diagnosis and active surgical intervention in collaboration with proper antibiotic treatment is the key to cure.
Assuntos
Otite Média/complicações , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Abscesso Encefálico/etiologia , Abscesso Encefálico/cirurgia , Criança , Doença Crônica , Drenagem , Humanos , Trombose Intracraniana/etiologia , Trombose Intracraniana/cirurgia , Processo Mastoide/cirurgia , Meningite/etiologia , Meningite/cirurgia , Pessoa de Meia-Idade , Otite Média/cirurgia , Adulto JovemRESUMO
AIMS: To discuss indications and surgical techniques for cochlear implantation (CI) in children with profound sensorineural hearing loss and otitis media with effusion (OME). METHODS: Between January 2003 and May 2013, a total of 550 patients received cochlear implants at the Anhui Provincial Hospital, Hefei, China. Of these, 30 children with OME underwent CI with round window insertion in one stage. RESULTS: One-stage operations of CI with round window insertion were carried out in 30 children with OME. All electrodes were implanted successfully. CI was performed without complications and the electrode arrays were protected well. All implant devices worked normally and all patients performed well during an average follow-up period of 12 months. None of the patients experienced any immediate or delayed postoperative infection-related complications. CONCLUSIONS: CI with round window insertion could be safely and effectively performed in one stage in children with profound sensorineural hearing loss and OME. It is unnecessary to delay implantation to control OME, but it remains a challenging problem in operation.
Assuntos
Implante Coclear/métodos , Implantes Cocleares , Perda Auditiva Neurossensorial/cirurgia , Otite Média com Derrame/cirurgia , Janela da Cóclea/cirurgia , Criança , Pré-Escolar , China , Feminino , Humanos , Lactente , Masculino , Resultado do TratamentoRESUMO
An 8-week feeding experiment was conducted on the juvenile turbot (Scophthalmus maximus) to evaluate the influence of yeast extract (YE) supplementation in the diet on growth performance, feed utilization, body composition, nutrient digestibility, intestinal histology, and antioxidant capacity. Four experimental diets were formulated with graded levels of yeast extract 0 (YE0), 1% (YE1), 3% (YE3), and 5% (YE5) and fed to turbots (initial body weight: 4.2 ± 0.1 g) with three replicates per diet and 200 fish in each replicate, respectively. The results showed that turbots fed with diets YE1 and YE3 displayed a significantly higher specific growth rate and protein efficiency rate than those fed with diets YE0 and YE5, while the feed conversion ratios in YE1 and YE3 groups were lower than those in YE0 and YE5. Fish fed with diets YE3 and YE5 showed higher body crude protein contents than those in groups YE0 and YE1. The highest apparent digestibility coefficients for dry matter and crude protein, digestive enzyme activities (trypsin, lipase, and amylase), and the height of the intestinal fold were observed in the YE3 group. YE3 treatment displayed a significantly higher superoxide dismutase (SOD) activity than the YE0 group, while the malondialdehyde (MDA) content in YE1 was significantly lower than those in YE0 and YE5. No significant difference was observed in serum physiological and biochemical parameters among all treatments. Overall, appropriate dietary supplementation of the yeast extract could improve the growth performance, digestibility, and antioxidant capacity of the juvenile turbot, and the recommended yeast extract level in the feed is 2.47%.
RESUMO
Laryngeal carcinoma (LC) is a common cancer of the respiratory tract. This study aims to investigate the role of RNA-binding motif protein 15 (RBM15) in the cisplatin (DDP) resistance of LC cells. LC-DDP-resistant cells were constructed. RBM15, lysine-specific demethylase 5B (KDM5B), lncRNA Fer-1 like family member 4 (FER1L4), lncRNA KCNQ1 overlapping transcript 1 (KCNQ1OT1), glutathione peroxidase 4 (GPX4), and Acyl-CoA synthetase long-chain family (ACSL4) was examined. Cell viability, IC50, and proliferation were assessed after RBM15 downregulation. The enrichment of insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3) and N6-methyladenosine (m6A) on KDM5B was analyzed. KDM5B mRNA stability was measured after actinomycin D treatment. A tumor xenograft assay was conducted to verify the role of RBM15 in LC. Results showed that RBM15 was upregulated in LC and its knockdown decreased IC50, cell viability, proliferation, glutathione, and upregulated iron ion content, ROS, malondialdehyde, ACSL4, and ferroptosis. Mechanistically, RBM15 improved KDM5B stability in an IGF2BP3-dependent manner, resulting in FER1L4 downregulation and GPX4 upregulation. KDM5B increased KCNQ1OT1 and inhibited ACSL4. KDM5B/KCNQ1OT1 overexpression or FER1L4 knockdown promoted DDP resistance in LC by inhibiting ferroptosis. In conclusion, RBM15 promoted KDM5B expression, and KDM5B upregulation inhibited ferroptosis and promoted DDP resistance in LC by downregulating FER1L4 and upregulating GPX4, as well as by upregulating KCNQ1OT1 and inhibiting ACSL4. Silencing RBM15 inhibited tumor growth in vivo.
Assuntos
Cisplatino , Resistencia a Medicamentos Antineoplásicos , Epigênese Genética , Ferroptose , Neoplasias Laríngeas , Proteínas de Ligação a RNA , Ferroptose/genética , Cisplatino/farmacologia , Resistencia a Medicamentos Antineoplásicos/genética , Humanos , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismo , Linhagem Celular Tumoral , Camundongos , Animais , Neoplasias Laríngeas/genética , Neoplasias Laríngeas/metabolismo , Camundongos Nus , Regulação Neoplásica da Expressão Gênica , Proliferação de Células/efeitos dos fármacos , Antineoplásicos/farmacologia , Coenzima A Ligases/genética , Coenzima A Ligases/metabolismoRESUMO
BACKGROUND: Deaf children with cochlear nerve canal stenosis (CNCs) are always considered poor candidates for cochlear implantation. OBJECTIVES: To investigate the function of the peripheral auditory pathway in deaf children with CNCs, as revealed by the electrically evoked auditory brainstem response (EABR), and postoperative cochlear implants (CIs) outcomes. MATERIALS AND METHODS: Thirteen children with CNCs and 13 children with no inner ear malformations (IEMs) who received CIs were recruited. The EABR evoked by electrical stimulation from the CI electrode was recorded. Postoperative CI outcomes were assessed using Categories of Auditory Performance (CAP) and Speech Intelligibility Rate (SIR). RESULTS: Compared with children with no IEMs, children with CNCs showed lower EABR extraction rates, higher thresholds, a longer wave V (eV) latency and lower CAP and SIR scores. The auditory and speech performance was positively correlated with the diameter of the cochlear nerve canal and the number of channels showing wave III (eIII) and eV in children with CNCs. CONCLUSIONS AND SIGNIFICANCE: The physiological function of the peripheral auditory pathway in children with CNCs is poorer than that in children with no IEMs. Postoperative auditory and speech abilities may depend on the severity of cochlear nerve malformation and auditory conduction function.