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PURPOSE: The purpose of this review is to systematically summarize the application of organoids in the field of otolaryngology and head and neck surgery. It aims to shed light on the current advancements and future potential of organoid technology in these areas, particularly in addressing challenges like hearing loss, cancer research, and organ regeneration. METHODS: Review of current literature regrading organoids in the field of otolaryngology and head and neck surgery. RESULTS: The review highlights several advancements in the field. In otology, the development of organoid replacement therapies offers new avenues for treating hearing loss. In nasal science, the creation of specific organoid models aids in studying nasopharyngeal carcinoma and respiratory viruses. In head and neck surgery, innovative approaches for squamous cell carcinoma prediction and thyroid regeneration using organoids have been developed. CONCLUSION: Organoid research in otolaryngology-head and neck surgery is still at an early stage. This review underscores the potential of this technology in advancing our understanding and treatment of various conditions, predicting a transformative impact on future medical practices in these fields.
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Carcinoma de Células Escamosas , Pérdida Auditiva , Otolaringología , Humanos , Organoides , NarizRESUMEN
The coronavirus disease 2019(COVID-19) pandemic poses a severe threat to global health.As an emerging infectious disease mainly attacking the respiratory tract,it has severely challenged the management of chronic non-infectious respiratory diseases including obstructive sleep apnea(OSA) and asthma.This article reviews the impact of OSA on the incidence of COVID-19 and the underlying pathophysiological mechanism,as well as the effects of OSA on the hospitalization risk and the prognosis and outcome of COVID-19 patients,which will provide novel ideas for the management of OSA during the COVID-19 pandemic.
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Asma , COVID-19 , Apnea Obstructiva del Sueño , Humanos , COVID-19/epidemiología , Pandemias , Factores de Riesgo , Apnea Obstructiva del Sueño/terapiaRESUMEN
The mitochondrial 1555A>G mutation plays a critical role in aminoglycoside-induced and non-syndromic hearing loss (AINSHL). Previous studies have suggested that mitochondrial secondary variants may modulate the clinical expression of m.1555A>G-induced deafness, but the molecular mechanism has remained largely undetermined. In this study, we investigated the contribution of a deafness-associated tRNAGln 4394C>T mutation to the clinical expression of the m.1555A>G mutation. Interestingly, a three-generation family with both the m.1555A>G and m.4394C>T mutations exhibited a higher penetrance of hearing loss than another family harboring only the m.1555A>G mutation. At the molecular level, the m.4394C>T mutation resides within a very conserved nucleotide of tRNAGln, which forms a new base-pairing (7T-66A) and may affect tRNA structure and function. Using trans-mitochondrial cybrid cells derived from three subjects with both the m.1555A>G and m.4394C>T mutations, three patients with only the m.1555A>G mutation and three control subjects without these primary mutations, we observed that cells with both the m.1555A>G and m.4394C>T mutations exhibited more severely impaired mitochondrial functions than those with only the m.1555A>G mutation. Furthermore, a marked decrease in mitochondrial RNA transcripts and respiratory chain enzymes was observed in cells harboring both the m.1555A>G and m.4394C>T mutations. Thus, our data suggest that the m.4394C>T mutation may play a synergistic role in the m.1555A>G mutation, enhancing mitochondrial dysfunctions and contributing to a high penetrance of hearing loss in families with both mtDNA pathogenic mutations.
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Sordera , Pérdida Auditiva , Humanos , ARN Mitocondrial , ARN de Transferencia de Glutamina , Sordera/inducido químicamente , Sordera/genética , Mutación , Pérdida Auditiva/inducido químicamente , Pérdida Auditiva/genética , Aminoglicósidos , ADN Mitocondrial/genética , Nucleótidos/efectos adversosRESUMEN
Benzo[a]pyrene (BaP), a representative polycyclic aromatic hydrocarbon compound, is a carcinogen that causes head and neck cancers. Despite intensive research, the molecular mechanism of BaP in the development of oral squamous cell carcinoma (OSCC) remains largely unknown. In the present study, the SCC-9 human OSCC cell line was cultured in vitro, separated into treatment groups, and treated with dimethyl sulfoxide or BaP at various concentrations. The malignant behavior ascribed to the BaP treatment was investigated by cell proliferation, clony formation assay, and Transwell assays. Furthermore, transcriptome sequencing was performed to detect the differentially expressed genes, followed by quantitative real-time PCR to measure the expression levels of nine of these genes. Moreover, the Gene Ontology (GO) term and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses showed the biological processes and signaling pathways in which the target genes were involved. Significant effects on SCC-9 cell proliferation, tumorigenicity, cell migration, and invasion were observed after exposure to 8 µM BaP. Additional results revealed that BaP inhibited apoptosis in a dose-dependent manner. The transcriptome sequencing results showed 137 upregulated genes and 135 downregulated genes induced by BaP, associated with tumor-related biological processes and signaling pathways, mainly including transcriptional dysregulation in cancer, the tumor necrosis factor signaling pathway, metabolism of xenobiotics by cytochrome P450, mitogen-activated protein kinase signaling pathway, and so forth. Our study demonstrates that BaP may regulate the expression of certain genes involved in tumor-associated signaling pathways, thereby promoting the proliferative, tumorigenic, and metastatic behaviors of OSCC cells while suppressing their apoptosis.
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Neoplasias de la Boca , Hidrocarburos Policíclicos Aromáticos , Carcinoma de Células Escamosas de Cabeza y Cuello , Benzo(a)pireno/toxicidad , Carcinógenos , Proliferación Celular , Dimetilsulfóxido , Perfilación de la Expresión Génica , Humanos , Proteínas Quinasas Activadas por Mitógenos/genética , Neoplasias de la Boca/genética , RNA-Seq , Carcinoma de Células Escamosas de Cabeza y Cuello/genética , Transcriptoma , Factores de Necrosis Tumoral/genética , XenobióticosRESUMEN
Long noncoding RNAs (lncRNAs) are a novel class of potential biomarkers and therapeutic targets for the treatment of neoplasms. The purpose of this study was to explore the expression profile, potential functions, and diagnostic and clinical significance of lncRNAs in sinonasal inverted papilloma (SNIP). The expression profiles of lncRNAs and mRNAs were analyzed using a microarray. The potential functions and clinical implications of specific lncRNAs were further analyzed by bioinformatics and statistical methods. Microarray analysis identified 1,668 significantly upregulated and 1,767 downregulated lncRNAs in SNIP. Several mRNAs coexpressed with lncRNAs were enriched in some biological processes and cellular signaling pathways related to tumorigenesis. Lnc-AKTIP might interact with a variety of tumor-associated proteins and transcription factors, such as PCBP2, IRF-1, and p53. Receiver operating characteristic curve analysis for lnc-AKTIP showed an area under the curve of 0.939. Notably, its expression level was significantly decreased in SNIP tissues versus normal tissues and was associated with SNIP staging. Lnc-AKTIP may serve as a valuable diagnostic biomarker and a therapeutic target for SNIP.
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Age-related hearing loss (ARHL) is the most prevalent sensory deficit in the elderly, but its mechanism remains unclear. Scaffold protein prohibitin 2 (PHB2) has been widely involved in aging and neurodegeneration. However, the role of PHB2 in ARHL is undeciphered to date. To investigate the expression pattern and the role of PHB2 in ARHL, we used C57BL/6 mice and HEI-OC1 cell line as models. In our study, we have found PHB2 exists in the cochlea and is expressed in hair cells, spiral ganglion neurons, and HEI-OC1 cells. In mice with ARHL, mitophagy is reduced and correspondingly the expression level of PHB2 is decreased. Moreover, after H2 O2 treatment the mitophagy is activated and the PHB2 expression is increased. These findings indicate that PHB2 may exert an important role in ARHL through mitophagy. Findings from this study will be helpful for elucidating the mechanism underlying the ARHL and for providing a new target for ARHL treatment.
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Envejecimiento/metabolismo , Cóclea/metabolismo , Pérdida Auditiva/metabolismo , Prohibitinas/metabolismo , Animales , Células Cultivadas , Ratones , Ratones Endogámicos C57BL , Mitocondrias/metabolismo , Mitofagia/fisiología , Neuronas/metabolismo , Presbiacusia/metabolismo , Ganglio Espiral de la Cóclea/metabolismoRESUMEN
In addition to acute respiratory symptoms,coronavirus disease 2019(COVID-19)could cause olfactory dysfunction,which becomes the only clinical manifestation of COVID-19 in some cases.We review the epidemiological characteristics,pathological mechanism,screening value,treatment and prognosis of olfactory dysfunction in patients with COVID-19,aiming to achieve an in-depth understanding of the early diagnosis,quarantine,scientific treatment and prognosis of COVID-19.
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COVID-19 , Trastornos del Olfato , Diagnóstico Precoz , Humanos , Trastornos del Olfato/diagnóstico , Trastornos del Olfato/etiología , SARS-CoV-2 , OlfatoRESUMEN
Tuberculous otitis media (TOM) is a rare disease. This study presents our experience in the diagnosis and treatment of TOM. A 49-year-old female had repeated ear discharge, vertigo, and severe hearing loss for six years, and underwent mastoid surgery four times because she was misdiagnosed with chronic suppurative otitis media. The patient had left-sided facial paralysis for two weeks when she was admitted to our hospital and was managed with radical mastoidectomy and facial nerve decompression. After surgery, facial nerve function gradually improved from grade V to grade II, and the patient was diagnosed with an unusual primary bilateral TOM after tuberculosis smear culture, pathologic examination, and tuberculosis DNA testing by the PCR technique. After anti-tuberculosis therapy, the operative mastoid cavity in the patient was eventually epithelialized and dry. Therefore, this study suggests that, TOM should be actively excluded in patients with uncontrollable ear leakage, massive white granulation tissue and dead bone formation in the ear. Surgical decompression is recommended to prevent permanent facial paralysis, since opening the facial nerve sheath effectively relieves facial nerve compression and edema due to the TOM-induced persistent inflammation and granulation tissue formation.
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Cytoplasmic p27 plays an important role in regulating the cell cycle. Recent studies have revealed p27 protein translocation from the nucleus to the cytoplasm in many tumour cells. The aim of this study was to investigate the role and molecular mechanisms of cytoplasmic p27 in the progression of nasopharyngeal carcinoma (NPC) and to explore its prognostic value. We found increased cytoplasmic p27 expression by immunohistochemistry in NPC tissues, and its expression level was significantly correlated with the T classification and TNM clinical stage of NPC. The survival rate was significantly lower for NPC patients with cytoplasmic p27 immunopositivity than for NPC patients with cytoplasmic p27 immunonegativity, and cytoplasmic p27 was an independent risk factor that affected the prognosis of patients with NPC. Cytoplasmic p27 promoted the proliferation, cell cycle progression, migration, and invasion of NPC cells, increased Bim-1 and Twist1 protein levels, and decreased RhoA-GTP level. Collectively, these findings suggest that cytoplasmic relocalization of p27 is involved in the pathogenesis of NPC and is closely related to the unfavourable prognosis of patients with NPC. Therefore, cytoplasmic p27 might be a useful prognostic factor and potential therapeutic target for patients with NPC.
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Biomarcadores de Tumor/metabolismo , Inhibidor p27 de las Quinasas Dependientes de la Ciclina/metabolismo , Citoplasma/metabolismo , Carcinoma Nasofaríngeo/metabolismo , Neoplasias Nasofaríngeas/metabolismo , Adulto , Anciano , Línea Celular Tumoral , Citoplasma/patología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Carcinoma Nasofaríngeo/diagnóstico , Carcinoma Nasofaríngeo/patología , Neoplasias Nasofaríngeas/diagnóstico , Neoplasias Nasofaríngeas/patología , PronósticoRESUMEN
Background: Closed reduction is an effective treatment for arytenoid dislocation. The treatment is usually given more than once to obtain normal voice. However, when to perform the next closed reduction remains controversial.Objective: This study aimed to observe the regularity of the voice recovery and the arytenoid motion in patients with arytenoid dislocation after closed reduction.Material and methods: Thirty-one patients were recruited from September 2017 to April 2019. Results of their clinical data were reviewed retrospectively.Results: Among the thirty-one patients, their VHI scores, F0, jitter%, shimmer%, glottal-to-noise excitation %(GNE), maximum phonation time (MPT) and GRBAS Scale (G, R, B, A) improved significantly (p < .05), but there was no statistically significant difference for GRBAS Scale (S) (p>.05). The duration between last closed reduction and the restoring normal voice ranged from 1-8 days, with a mean of 4.65 ± 0.57 days, at the same time the glottis was completely closed.Conclusions and significance: Closed reduction for patients with arytenoid dislocation is an effective procedure. A time window between 4.08th and 5.22th day (at a confidence level of 95%) after the last closed reduction was identified to be critical for voice recovery.
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Cartílago Aritenoides/lesiones , Cartílago Aritenoides/fisiopatología , Enfermedades de la Laringe/cirugía , Voz , Adulto , Anciano , Cartílago Aritenoides/diagnóstico por imagen , Femenino , Humanos , Enfermedades de la Laringe/diagnóstico por imagen , Enfermedades de la Laringe/etiología , Laringoscopía , Masculino , Persona de Mediana Edad , Recuperación de la Función , Estudios Retrospectivos , Tiempo de Tratamiento , Resultado del Tratamiento , Adulto JovenRESUMEN
Dysregulated microRNAs (miRNAs) play crucial roles in the occurrence and development of multiple tumours, but their roles in the progression of nasal squamous cell carcinoma (NSCC) remain unknown. The aim of our study was to investigate the potential function and molecular mechanism of miR-143-3p in NSCC. Expression of miRNA and mRNA was detected by quantitative real-time reverse transcription-PCR (qRT-PCR). Forced overexpression of miR-143-3p was established by transfecting mimics into NSCC cell line. Then, we investigated the role of miR-143-3p in human NSCC cell proliferation, apoptosis, cycle and migration by using MTT, flow cytometry and transwell assays. Bioinformatics analysis, qRT-PCR, Western blot and luciferase reporter analysis were performed to validate the relationship between miR-143-3p and its potential targets. We found that miR-143-3p was substantially downregulated in human NSCC tissues and cell line. Forced upregulation of miR-143-3p significantly attenuated cell proliferation and migration. Furthermore, this change could induce apoptosis and G1-phase arrest of NSCC cells. Mechanistically, miR-143-3p directly targeted and significantly suppressed Bcl-2 and IGF1R expression. In summary, miR-143-3p regulation of the proliferation, apoptosis, cell cycle and migration of NSCC probably partly depends on inhibition of Bcl-2 and IGF1R, indicating that miR-143-3p may be a novel molecular therapeutic target for NSCC.
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Carcinoma de Células Escamosas/genética , MicroARNs/genética , Neoplasias Nasales/genética , Proteínas Proto-Oncogénicas c-bcl-2/genética , Receptor IGF Tipo 1/genética , Carcinoma de Células Escamosas/patología , Línea Celular Tumoral , Movimiento Celular , Proliferación Celular , Progresión de la Enfermedad , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Masculino , Persona de Mediana Edad , Neoplasias Nasales/patologíaRESUMEN
By fusing the extracellular domain of the natural killer (NK) cell receptor NKG2D to DAP12, we constructed a chimeric antigen receptor (CAR) to improve NK cell tumor responses. An RNA electroporation approach that provides transient expression of the CAR was adopted as a risk mitigation strategy. Expression of the NKG2D RNA CAR significantly augmented the cytolytic activity of NK cells against several solid tumor cell lines in vitro and provided a clear therapeutic benefit to mice with established solid tumors. Three patients with metastatic colorectal cancer were then treated with local infusion of the CAR-NK cells. Reduction of ascites generation and a marked decrease in number of tumor cells in ascites samples were observed in the first two patients treated with intraperitoneal infusion of low doses of the CAR-NK cells. The third patient with metastatic tumor sites in the liver was treated with ultrasound-guided percutaneous injection, followed by intraperitoneal infusion of the CAR-NK cells. Rapid tumor regression in the liver region was observed with Doppler ultrasound imaging and complete metabolic response in the treated liver lesions was confirmed by positron emission tomography (PET)- computed tomographic (CT) scanning. Our results highlight a promising therapeutic potential of using RNA CAR-modified NK cells to treat metastatic colorectal cancer.
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Traslado Adoptivo/métodos , Trasplante de Células/métodos , Neoplasias Colorrectales/terapia , Células Asesinas Naturales/inmunología , Células Asesinas Naturales/trasplante , Subfamilia K de Receptores Similares a Lectina de Células NK/genética , Receptores Quiméricos de Antígenos/inmunología , Traslado Adoptivo/efectos adversos , Animales , Ingeniería Celular/métodos , Trasplante de Células/efectos adversos , Neoplasias Colorrectales/mortalidad , Neoplasias Colorrectales/patología , Citotoxicidad Inmunológica/genética , Estudios de Factibilidad , Femenino , Vectores Genéticos , Células HCT116 , Humanos , Células Asesinas Naturales/metabolismo , Activación de Linfocitos , Masculino , Ratones , Ratones Endogámicos NOD , Ratones SCID , Persona de Mediana Edad , Proyectos Piloto , ARN Mensajero/genética , Receptores Quiméricos de Antígenos/genética , Receptores Quiméricos de Antígenos/metabolismo , Resultado del Tratamiento , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
BACKGROUND: Mutations in mitochondrial tRNA (mt-tRNA) genes have been found to be associated with both syndromic and non-syndromic hearing impairment. However, the pathophysiology underlying mt-tRNA mutations in clinical expression of hearing loss remains poorly understood. OBJECTIVE: The aim of this study was to explore the potential association between mttRNA mutations and hearing loss. METHODS AND RESULTS: We reported here the molecular features of a pedigree with maternally transmitted non-syndromic hearing loss. Among 12 matrilineal relatives, five of them suffered variable degree of hearing impairment, but none of them had any medical history of using aminoglycosides antibiotics (AmAn). Genetic screening of the complete mitochondrial genomes from the matrilineal relatives identified the coexistence of mt-tRNAHis G12192A and mt-tRNAThr G15927A mutations, together with a set of polymorphisms belonging to human mitochondrial haplogroup B5b1b. Interestingly, the G12192A mutation occurred 2-bp from the 3' end of the TψC loop of mt-tRNAHis, which was evolutionarily conserved from various species. In addition, the well-known G15927A mutation, which disrupted the highly conserved C-G base-pairing at the anticodon stem of mt-tRNAThr, may lead to the failure in mt-tRNA metabolism. Furthermore, a significant decreased in ATP production and an increased ROS generation were observed in polymononuclear leukocytes (PMNs) which were isolated from the deaf patients carrying these mt-tRNA mutations, suggested that the G12192A and G15927A mutations may cause mitochondrial dysfunction that was responsible for deafness. However, the absence of any functional mutations/variants in GJB2, GJB3, GJB6 and TRMU genes suggested that the nuclear genes may not play important roles in the clinical expression of non-syndromic hearing loss in this family. CONCLUSION: Our data indicated that mt-tRNAHis G12192A mutation may increase the penetrance and expressivity of deafness-associated m-tRNAThr G15927A mutation in this family.
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Pueblo Asiatico/genética , Sordera/genética , Sordera/fisiopatología , Mitocondrias/genética , Mutación , ARN de Transferencia de Histidina/genética , ARN de Transferencia de Treonina/genética , Adulto , Secuencia de Bases , ADN Mitocondrial/análisis , Femenino , Genes Mitocondriales , Humanos , Masculino , Persona de Mediana Edad , Linaje , Penetrancia , FenotipoRESUMEN
AIM: To analyze the expression profile, diagnostic and clinicopathological significances of miRNAs in sinonasal inverted papilloma (SNIP). MATERIALS & METHODS: The expression profile of miRNAs was analyzed using a miRNA microarray approach. The potential functions and clinical significances of specific miRNAs were further analyzed by bioinformatics and statistical methods. RESULTS: The microarray assay identified 37 significantly upregulated and 21 downregulated miRNAs in SNIP. Of nine miRNAs randomly selected, the expression levels of seven miRNAs were confirmed by quantitative real-time PCR. The potential target genes of several candidate miRNAs were enriched in some biological processes and cellular signaling pathways related to tumorigenesis. Receiever operating characteristic curve analysis for miR-214-3p indicated an area under the curve of 0.932. Notably, its expression level was significantly decreased in SNIP tissues and associated with SNIP staging and recurrence. CONCLUSION: MiR-214-3p can possibly serve as a valuable biomarker and a therapeutic target for SNIP.
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Biomarcadores de Tumor/genética , Regulación Neoplásica de la Expresión Génica/genética , MicroARNs/genética , Neoplasias Nasales/genética , Papiloma Invertido/genética , Adulto , Anciano , Anciano de 80 o más Años , Carcinogénesis , Biología Computacional , Regulación hacia Abajo , Femenino , Humanos , Masculino , Persona de Mediana Edad , Regulación hacia ArribaRESUMEN
The objective of the present study was to investigate the clinical application of magnetic resonance imaging (MRI)-respiratory gating technology for assessing illness severity in children with obstructive sleep apnea hypopnea syndrome (OSAHS).MRI-respiratory gating technology was used to scan the nasopharyngeal cavities of 51 children diagnosed with OSAHS during 6 respiratory phases. Correlations between the ratio of the area of the adenoid to the area of the nasopalatine pharyngeal cavity (Sa/Snp), with the main indexes of polysomnography (PSG), were analyzed. Receiver operator characteristic (ROC) curve and Kappa analysis were used to determine the diagnostic accuracy of Sa/Snp in pediatric OSAHS.The Sa/Snp was positively correlated with the apnea hypopnea index (AHI) (Pâ<â.001) and negatively correlated with the lowest oxygen saturation of blood during sleep (LaSO2) (Pâ<â.001). ROC analysis in the 6 respiratory phases showed that the area under the curve (AUC) of the Sa/Snp in the end-expiratory phase was the largest (0.992, Pâ<â.001), providing a threshold of 69.5% for the diagnosis of severe versus slight-moderate OSAHS in children. Consistency analysis with the AHI showed a diagnosis accordance rate of 96.0% in severe pediatric OSAHS and 96.2% in slight-moderate pediatric OSAHS (Kappaâ=â0.922, Pâ<â.001).Stenosis of the nasopalatine pharyngeal cavity in children with adenoidal hypertrophy was greatest at the end-expiration phase during sleep. The end-expiratory Sa/Snp obtained by a combination of MRI and respiratory gating technology has potential as an important imaging index for diagnosing and evaluating severity in pediatric OSAHS.
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Imagen por Resonancia Magnética/métodos , Técnicas de Imagen Sincronizada Respiratorias/métodos , Apnea Obstructiva del Sueño/diagnóstico por imagen , Tonsila Faríngea/diagnóstico por imagen , Tonsila Faríngea/fisiopatología , Adolescente , Área Bajo la Curva , Niño , Preescolar , Femenino , Humanos , Masculino , Nasofaringe/diagnóstico por imagen , Nasofaringe/fisiopatología , Polisomnografía , Curva ROC , Respiración , Índice de Severidad de la Enfermedad , SueñoRESUMEN
Sinonasal teratocarcinosarcoma (SNTCS) is a rare malignancy characterized by potent invasiveness, rapid growth, and a poor prognosis. Due to its diverse histopathological morphology, complex components, and insidious growth sites, as well as inadequate biopsies, SNTCS is often misdiagnosed as other tumors, and this misdiagnosis directly affects the treatment and prognosis of patients. Here, we report a case of an elderly SNTCS patient who underwent intranasal endoscopic tumor resection under systemic anesthesia. His preoperative diagnosis and intraoperative frozen sections both led to a misdiagnosis of olfactory neuroblastoma (ONB). However, after surgeries, the patient was diagnosed with SNTCS based on routine histopathology and immunohistochemical staining. He then underwent follow-up but died of tumor recurrence six months later.
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Long non-coding RNAs (lncRNAs) have been proved to play important roles in a variety of human immune diseases. However, their pathological effects on the development of allergic rhinitis (AR) have not been clearly understood. The aim of this study was to determine the expression profile of lncRNAs in nasal mucosa of AR patients by lncRNA microarray and to predict potential roles of specific lncRNAs in the pathogenic mechanisms of AR by analysis of lncRNA-mRNA co-expression network, Gene Ontology (GO) and pathway. The lncRNA microarray analysis showed that a total of 2,259 lncRNAs (1,033 up-regulated and 1,226 down-regulated) and 704 mRNAs (157 up-regulated and 547 down-regulated) were significantly differentially expressed in the nasal mucosa samples from 4 AR patients as compared to those from 4 non-allergic subjects (fold change > 2; P < 0.05). In addition, the lncRNA-mRNA co-expression network contained 143 network nodes including 76 lncRNAs and 67 mRNAs, in which 117 significant correlation pairs presented as positive, and 108 pairs presented as negative. The results from GO and pathway analysis indicated that the lncRNAs-coexpressed mRNAs were enriched in several biological processes and cellular signaling pathways related to AR development, such as positive regulation of interleukin-13 secretion, Fc epsilon RI signaling pathway and NF-kappa B signaling pathway. To summary, our study provides important information on the molecular mechanisms and biological functions of these AR-related lncRNAs, which could be utilized for developing novel therapeutic strategies for AR.
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Perfilación de la Expresión Génica , Mucosa Nasal/metabolismo , Mucosa Nasal/patología , ARN Largo no Codificante/genética , Rinitis Alérgica/genética , Adulto , Femenino , Redes Reguladoras de Genes , Humanos , Masculino , Persona de Mediana Edad , ARN Largo no Codificante/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismo , Reacción en Cadena en Tiempo Real de la Polimerasa , Reproducibilidad de los Resultados , Rinitis Alérgica/patología , Adulto JovenRESUMEN
Mutations in mitochondrial genome have been found to be associated with hearing loss. Of these, the mitochondrial 12S rRNA and tRNASer(UCN) are the hot spots for pathogenic mutations associated with deafness. To understand the putative role of mitochondrial DNA (mtDNA) mutations in hearing loss, we recently initiated a mutational screening for the mtDNA mutations in Hangzhou area from Zhejiang Province. In this study, we described a maternally inherited Han Chinese family with high penetrance of hearing loss, notably, the penetrances of hearing loss in this family were 80% and 40%, when the aminoglycoside was included or excluded. Three matrilineal relatives in this pedigree exhibited different levels of hearing loss with different age at onset. In addition, sequence analysis of the complete mitochondrial genome showed the presence of the well-known C1494T mutation in 12S rRNA gene and the G7444A mutation in the COI/tRNASer(UCN). The C1494T mutation had been reported to be a pathogenic mutation associated with aminoglycoside-induced and non-syndromic hearing loss. While the G7444A mutation was considered as a secondary mutation associated with deafness. However, the lack of functional variants in GJB2 and TRMU genes suggested that nuclear modified genes may not play important roles in deafness expression. Thus, the combination of G7444A and C1494T mutations in mitochondrial genome may account for the high penetrance of hearing loss in this Chinese family.
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Genetic polymorphisms in grainyheadlike 2 (GRHL2) variants were examined for their suspected association with sudden sensorineural hearing loss (SSHL). Between January 2009 and April 2014, 190 patients with SSHL, who were diagnosed at the Departments of Otorhinolaryngology Head and Neck Surgery at Kaihua People's Hospital and Hangzhou First People's Hospital, were selected for the present study and defined as the SSHL group. A group of 210 healthy individuals were defined as the control group. Polymerase chain reaction (PCR)restriction fragment length polymorphism was used to detect GRHL2 genotypes, using genomic DNA isolated from peripheral blood as PCR templates. GRHL2 rs611419 genetic polymorphisms conferred a protective effect against SSHL (AT+TT vs. AA: OR=0.63, 95% CI=0.410.98, P=0.038). In addition, rs10955255 polymorphisms were associated with a reduced risk of SSHL (AA vs. GG: OR=0.54, 95% CI=0.310.95, P=0.032; GA+AA vs. GG: OR=0.58, 95% CI=0.380.89, P=0.012). Combined genotypes of rs611419, rs10955255 and rs6989650 in the GRHL2 gene are also associated with a reduced risk of SSHL (P=0.035). In subjects who consumed alcohol, cooccurrence of 38 variant alleles conferred increased resistance to SSHL, compared with the occurrence of 02 variant alleles (OR=0.40, 95% CI=0.210.76, P=0.004). GRHL2 genetic polymorphisms, rs611419 and rs10955255, have a protective role against SSHL and reduce the risk of SSHL. However, rs6989650 is not associated with SSHL.
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Proteínas de Unión al ADN/genética , Pérdida Auditiva Sensorineural/genética , Factores de Transcripción/genética , Adulto , Estudios de Casos y Controles , Resistencia a la Enfermedad , Femenino , Frecuencia de los Genes , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Humanos , Desequilibrio de Ligamiento , Masculino , Polimorfismo de Nucleótido Simple , Factores Protectores , RiesgoRESUMEN
BACKGROUND/AIMS: MicroRNAs (miRNAs) are critical regulators of immune responses and immunologic disorders. However, little is known about miRNA expression and function during mast cell differentiation, proliferation and activation. This study aimed to determine the miRNA expression profiles in mast cells stimulated by immunoglobulin E (IgE) and antigen and to analyze the potential functions of specific miRNAs. METHODS: Bone marrow-derived mast cells (BMMCs) generated from differentiated mouse bone marrow cells were untreated (Unstimu) or stimulated with IgE-antigen complexes for 1 h or 6 h (Stimu). The miRNA profiles were evaluated by miRNA microarray. MiRNA target gene prediction and enrichment analyses were performed using bioinformatics. RESULTS: Seven significantly up-regulated and 10 down-regulated miRNAs were identified in the 1 h Stimu group relative to the Unstimu group (fold change>2; P<0.05). Of 8 miRNAs randomly selected from the 17 identified, the expression levels of 6 were confirmed by quantitative real-time PCR (qRT-PCR). The potential target genes of several candidate miRNAs were enriched in FcεRI signaling, response to stimulus and cellular exocytosis. CONCLUSION: The expression of many miRNAs changes following IgE-FcεRI cross-linking in activated mast cells, and these miRNAs probably play key regulatory roles in core signaling pathways and biological behaviors. Evaluating the functions of these characteristic miRNAs will further our understanding of IgE-associated allergic disease pathogenesis and the development of therapeutic strategies.