RESUMEN
Oxidative stress is one of the important mechanisms of inner ear cell damage, which can lead to age-related hearing loss (ARHL). LncRNA H19 is significantly downregulated in the cochlea of old mouse, however, the role of H19 in the development of ARHL remains unclear. In this study, we aim to investigate the expression and function of H19 in oxidative stress injury of cochlear hair cells induced by HO. RT-qPCR and western blot analysis confirms that HEI-OC1 cells stimulated with HO decreases the expressions of H19 and SIRT1, but increases the expression of miR-653-5p. Overexpression of H19 could increase cell viability, ATP level and mitochondrial membrane potential, but reduce mitochondrial ROS generation and cell apoptosis ratio in HO-stimulated HEI-OC1 cells. MiR-653-5p is a target of H19, which can bind to the 3'-UTR of SIRT1. H19 is found to regulate the expression of SIRT1 through miR-653-5p. Further experiments demonstrates that H19 regulates HEI-OC1 cell viability, ATP level, mitochondrial membrane potential, mitochondrial ROS generation, and cell apoptosis ratio via the miR-653-5p/SIRT1 axis. In conclusion, lncRNA H19 inhibits oxidative stress injury of cochlear hair cells via the miR-653-5p/SIRT1 axis.
Asunto(s)
Células Ciliadas Auditivas , MicroARNs , ARN Largo no Codificante , Sirtuina 1 , Adenosina Trifosfato/metabolismo , Animales , Apoptosis/genética , Células Ciliadas Auditivas/metabolismo , Células Ciliadas Auditivas/patología , Ratones , MicroARNs/genética , MicroARNs/metabolismo , Estrés Oxidativo/genética , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Sirtuina 1/genética , Sirtuina 1/metabolismoRESUMEN
In this study, the adsorption method and micro-nano bubble (MNB) technology were combined to improve the efficiency of organic pollutant removal from dye wastewater. The adsorption properties of Congo red (CR) on raw coal and semi-coke (SC) with and without MNBs were studied. The mesoporosity of the coal strongly increased after the heat treatment, which was conducive to the adsorption of macromolecular organics, such as CR, and the specific surface area increased greatly from 2.787 m2/g to 80.512 m2/g. MNBs could improve the adsorption of both raw coal and SC under different pH levels, temperatures and dosages. With the use of MNBs, the adsorption capacity of SC reached 169.49 mg/g, which was much larger than that of the raw coal at 15.75 mg/g. The MNBs effectively reduced the adsorption time from 240 to 20 min. In addition, the MNBs could ensure the adsorbent maintained a good adsorption effect across a wide pH range. The removal rate was above 90% in an acidic environment and above 70% in an alkaline environment. MBs can effectively improve the rate of adsorption of pollutants by adsorbents. SC was obtained from low-rank coal through a rapid one-step heating treatment and was used as a kind of cheap adsorbent. The method is thus simple and easy to implement in the industrial context and has the potential for industrial promotion.
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Coque , Contaminantes Químicos del Agua , Adsorción , Carbón Mineral , Rojo Congo/química , Calor , Concentración de Iones de Hidrógeno , Cinética , Aguas Residuales/química , Contaminantes Químicos del Agua/químicaRESUMEN
With the continuous development of global industry and the increasing demand for lithium resources, recycling valuable lithium from industrial solid waste is necessary for sustainable development and environmental friendliness. Herein, we employed ion imprinting and capacitive deionization to prepare a new electrode material for lithium-ion selective recovery. The material morphology and structure were characterized using scanning electron microscopy, Fourier-transform infrared spectroscopy, and other characterization methods, and the adsorption mechanism and water clusters were correlated using the density functional theory. The electrode material exhibited a maximum adsorption capacity of 36.94 mg/g at a Li+ concentration of 600 mg/L. The selective separation factors for Na+, K+, Mg2+, and Al3+ in complex solution environments were 2.07, 9.82, 1.80, and 8.45, respectively. After undergoing five regeneration cycles, the material retained 91.81% of the initial Li+ adsorption capacity. Meanwhile, the electrochemical adsorption capacity for Li+ was more than twice the corresponding conventional physical adsorption capacity because electrochemical adsorption provides the energy needed for deprotonation, enabling exposure of the cavities of the crown ether molecules to enrich the active sites. The proposed environment-friendly separation approach offers excellent selectivity for Li+ recovery and addresses the growing demand for Li+ resources.
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Litio , Nitrógeno , Litio/química , Adsorción , Nitrógeno/química , Iones , Contaminantes Químicos del Agua/química , Espectroscopía Infrarroja por Transformada de FourierRESUMEN
Laryngocarcinoma is one of the most frequent malignancies occurring in the head and neck. The roles of spindle- and kinetochore-associated complex 1 (SKA1) in the malignant progression of several cancers have already been discussed. However, the precise significance and action's mechanism of SKA1 in laryngocarcinoma remain largely unknown. In this study, SKA1 was shown to be strongly expressed in laryngocarcinoma tissues and cells, and higher expression of SKA1 was associated with more severe tumor infiltration, larger tumor diameter, higher risk of lymphatic metastasis and later pathological stage. Additionally, loss-of-function assays in vitro suggested that SKA1 depletion caused a reduction in cell proliferation, migration, and colony formation as well as an increase in apoptosis. In animal experiments, tumors generated from AMC-HN-8 cells with SKA1 depletion exhibited declined tumor volume and weight. Similarly, the detection of Ki67 protein in xenograft tumor tissues reflected that knocking down SKA1 curbed tumor growth in vivo. Further exploration on downstream mechanism revealed that after treatment with Pifithrin-α, the suppression in proliferation level caused by SKA1 knockdown was reversed, while the increase of cell apoptosis was withdrawn; at the molecular level, Pifithrin-α treatment caused p-P53 and Bax diminished, while Bcl-2 ameliorated. In short, SKA1 promotes the development of laryngocarcinoma via activating the P53 signaling pathway.
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Cinetocoros , Proteína p53 Supresora de Tumor , Humanos , Línea Celular Tumoral , Proteína p53 Supresora de Tumor/genética , Proteína p53 Supresora de Tumor/metabolismo , Cinetocoros/metabolismo , Proliferación Celular/genética , Metástasis Linfática , Transducción de Señal , Proteínas Cromosómicas no Histona/genética , Proteínas Cromosómicas no Histona/metabolismoRESUMEN
Objectives: This study aimed to investigate the efficacy and safety of intratympanic or postauricular subperiosteal glucocorticoid injection combined with systemic glucocorticoid in the treatment of sudden sensorineural hearing loss (SSNHL). Methods: This study is a prospective randomized controlled study. This study included unilateral SSNHL patients who were hospitalized in our department between January 2020 and June 2021. Patients were randomly divided into three groups (groups A, B, and C). Patients in group A were treated with an intratympanic corticosteroid injection combined with systemic corticosteroid treatment, and patients in group B received a postauricular corticosteroid injection combined with systemic corticosteroid treatment. Patients in group C (control group) were treated with systemic corticosteroid alone. The case number of groups A, B, and C was 311, 375, and 369, respectively. Results: There was no significant difference in gender distribution, the proportion of left and right affected ears, and the average interval from onset to treatment among the three groups (P > 0.05). However, there were significant differences in their average age, distribution of audiogram type, and hearing loss levels among them (P < 0.01). Our study shows that there was no significant difference in average hearing threshold improvement before and after treatment in the three groups (P > 0.05). Regarding the complications, in group A, 33 patients (10.6%) had a transient vertigo attack during tympanic injection, which lasted for ~1-3 min. In group B, 20 patients (6.43%) complained of pain at the injection site, which disappeared after 1-3 days. No other complications occurred in all the other patients. Conclusion: The addition of intratympanic or postauricular corticosteroid to systemic steroids did not result in a significant effect on hearing recovery in SSNHL. No obvious complications occur in SSNHL patients treated with intratympanic injection or postauricular injection of corticosteroid. Clinical trial registration: [chictr.org.cn], registration number: ChiCTR2100048762.
RESUMEN
Sudden sensorineural hearing loss (SSNHL) is a multifactorial emergency disease. Until now, the etiology of SSNHL is still unknown. Previous studies regarding the etiology of SSNHL are clinical studies depending on clinical data collection and analysis. Due to the insufficient sample size or various selective bias in clinical studies, the results of these studies may be inaccurate. This prospective case-control study aimed at exploring the possible etiology and risk factors of SSNHL. We enrolled 255 SSNHL patients and 255 sex-, age- and residence-matched non-SSNHL subjects in the control group. Our study shows that there was no significant difference in the prevalence of comorbidities including hypertension and diabetes, as well as the incidence of smoking and drinking habits between the case and control groups (P > 0.05). In addition, the peripheral blood white blood cell count, neutrophil count, platelet-to-lymphocyte ratio (PLR) and fibrinogen level of the case group were significantly higher than those in the control group (P < 0.05). These findings suggest smoking, drinking, hypertension and diabetes may not be related to the onset of SSNHL. However, hypercoagulable state and inner ear vascular microthrombosis related to an elevated fibrinogen level might be the risk factors of the disease. In addition, inflammation play an important role of SSNHL onset.Trial Registration: Chinese Clinical Trial Registry. Registration number: ChiCTR2100048991.
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Diabetes Mellitus , Pérdida Auditiva Sensorineural , Pérdida Auditiva Súbita , Hipertensión , Humanos , Estudios de Casos y Controles , Pronóstico , Pérdida Auditiva Sensorineural/epidemiología , Pérdida Auditiva Sensorineural/etiología , Pérdida Auditiva Súbita/epidemiología , Pérdida Auditiva Súbita/etiología , Hipertensión/etiología , Hipertensión/complicaciones , FibrinógenoRESUMEN
The CCR3 gene plays a critical role in allergic airway inflammation, such as allergic rhinitis (AR), and there is an inflammatory signal link between the nasal cavity and the CCR3 gene in bone marrow. However, the effects of the CCR3 gene in bone marrow cells on AR are not clear. The present study investigated the roles and underlying mechanisms of the bone marrow CCR3 gene in AR mice. Conditional knockout of the bone marrow CCR3 gene (CKO) in mice was generated using the Cre-LoxP recombination system, and offspring genotypes were identified using polymerase chain reaction (PCR). An ovalbumin-induced AR model was established in CKO and wild-type mice to measure eosinophilic inflammation and the Th2 immune response. The following mechanisms were explored using a specific PI3K/AKT pathway inhibitor (Ly294002). We successfully constructed and bred homozygous CKO mice and confirmed a significant increase in CCR3 expression and PI3K/AKT pathway activity in AR mice. Deficiency of the bone marrow CCR3 gene caused a remarkable reduction of CCR3 expression and the PI3K/AKT signaling pathway activity, inhibited histopathological lesions and eosinophil infiltration of the nasal cavity, and reduced the production of Th2 cytokines in serum, which led to the remission of allergic symptoms in AR mice. Ly294002 treatment also decreased these inflammatory indexes in a concentration-dependent manner and blocked inflammatory signals from CCR3, but it did not affect the high expression of CCR3 in AR mice. Collectively, our results suggest that conditional knockout of the bone marrow CCR3 gene can reduce eosinophilic inflammation and the Th2 immune response, which may be due to inhibition of the PI3K/AKT pathway.
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Fosfatidilinositol 3-Quinasas , Rinitis Alérgica , Animales , Modelos Animales de Enfermedad , Técnicas de Silenciamiento del Gen , Inmunidad , Inflamación/patología , Ratones , Ratones Endogámicos BALB C , Mucosa Nasal/metabolismo , Fosfatidilinositol 3-Quinasas/genética , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Receptores CCR3/genética , Receptores CCR3/metabolismoRESUMEN
Ménière disease (MD) is an idiopathic inner ear disorder, and endolymphatic hydrops (EH) being considered to be its pathological basis. Currently, there is no gold standard for diagnosing MD. Previous study has reported visualized EH using MRI by intratympanic gadolinium-based contrast media (GBCM) administration (IT-Gd) in patients with MD, and this technique was gradually established for MD diagnosis. However, few studies reported their diagnostic sensitivity and specificity in clinical application. This prospective study aimed at investigating the clinical characteristics and magnetic resonance imaging (MRI) results of patients with MD, and analyzing the relationship between clinical results and MRI findings in MD patients. Our study shows that the diagnostic sensitivity and specificity of MRI were 79.2% and 80.7% respectively. Moreover, there was no significant correlation between hearing levels and cochlear grading scores, nor vestibular grading scores. The duration of disease was not significantly associated with cochlear or vestibular grading scores. These findings suggest that IT-Gd MRI offers reliable radiological diagnostic criteria for MD.
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Hidropesía Endolinfática/diagnóstico , Enfermedad de Meniere/diagnóstico , Adulto , Anciano , Anciano de 80 o más Años , Cóclea/diagnóstico por imagen , Cóclea/patología , Hidropesía Endolinfática/diagnóstico por imagen , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Enfermedad de Meniere/diagnóstico por imagen , Persona de Mediana Edad , Estudios Prospectivos , Vestíbulo del Laberinto/diagnóstico por imagen , Vestíbulo del Laberinto/patología , Adulto JovenRESUMEN
Mast cells (MCs) are the major effector cells of allergic rhinitis (AR). The present study aimed to investigate the effects of C-C chemokine receptor type 3 (CCR3) on the proliferation, apoptosis, chemotaxis and activated degranulation of mouse MCs. Mouse bone marrow-derived MCs were cultured in vitro, purified and identified using toluidine blue staining and flow cytometry. Three different CCR3-short hairpin (shRNA) lentiviral vectors were constructed and transfected into MCs, and the mRNA and protein expression levels of CCR3 were assessed by reverse transcription-quantitative PCR and western blotting. Proliferation and apoptosis of the MCs were measured using Cell Counting kit-8 (CCK-8) assays and flow cytometry, respectively. MC chemotaxis was assessed by Transwell assay and quantified using flow cytometry. The activation of MC degranulation was examined using ELISAs. The results demonstrated that MCs were appropriately isolated, and identified that CCR3-shRNA2 presented the higher knockdown effect among the three shRNAs tested. Following 96 h of transfection, the results of CCK-8 and flow cytometry assays demonstrated that CCR3-shRNA2 inhibited MC proliferation and promoted MC apoptosis. The results from the Transwell assay indicated that CCR3-shRNA2 restrained MC chemotaxis, whereas ELISA results demonstrated that CCR3-shRNA2 suppressed MC degranulation. In conclusion, CCR3-shRNA2 effectively downregulated CCR3 mRNA and protein expression levels in mouse MCs. In addition, CCR3-shRNA2 promoted MC apoptosis and suppressed the proliferation, chemotaxis and degranulation of mouse MCs, suggesting that CCR3-shRNA2 may serve as a therapeutic tool for the treatment of allergic rhinitis.
RESUMEN
The CC chemokine receptor 3 (CCR3) expressed by eosinophils, mast cells and Th2 cells is closely related to allergic diseases. The objective of this study was to explore whether silencing of CCR3 with short hairpin RNAs (shRNAs) delivered by a lentiviral vector could impact the function of mast cells in a murine model of allergic rhinitis (AR) in vivo. The murine model of allergic rhinitis (AR) inducing by ovalbumin (OVA) was constructed, and the BALB/c mice were divided into normal control group, AR group, controlshRNA treated group and lentiviral CCR3-shRNA treated group. The recombinant lentivirus vectors which express a short hairpin RNA (shRNA) targeting the CCR3 were dropped into the nasal cavity of OVA-sensitized mice before the challenges. Real-time fluorescence quantitative PCR and western blotting were performed to observe inhibitory effect of CCR3 gene. Nasal symptoms of mice and OVA-specific IgE in each group were assessed. Concentrations of histamine, tryptase and Prostaglandin D2 (PGD2) in bone marrow, peripheral blood and nasal mucosa were analyzed. Furthermore, histological analysis and electron microscopy analysis were applied to detect the histology changes of nasal mucosa and the infiltration of mast cells in nasal mucosa. The results showed that administration of CCR3shRNA could effectively inhibit the expression of the CCR3 gene in bone marrow, peripheral blood and nasal mucosa, which reduced the nasal symptoms, the level of OVA-specific IgE, the inflammatory cells and mast cells infiltration into nasal cavity, and relieved the histopathological changes of nasal mucosa. In addition, intervention of CCR3shRNA could reduce the levels of the histamine, tryptase and PGD2 in bone marrow, peripheral blood and nasal mucosa. These results suggest that inhibition of CCR3 gene expression by shRNAs lentiviral vectors can effectively attenuate migration, infiltration and degranulation of mast cells in local tissues and alleviate the inflammation of allergic rhinitis mice.
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Mastocitos/inmunología , Mucosa Nasal/inmunología , Receptores CCR3/genética , Rinitis Alérgica/terapia , Adyuvantes Inmunológicos/administración & dosificación , Hidróxido de Aluminio/administración & dosificación , Hidróxido de Aluminio/inmunología , Animales , Médula Ósea/patología , Degranulación de la Célula/genética , Degranulación de la Célula/inmunología , Movimiento Celular/genética , Movimiento Celular/inmunología , Modelos Animales de Enfermedad , Humanos , Lentivirus/genética , Masculino , Mastocitos/metabolismo , Ratones , Microscopía Electrónica , Mucosa Nasal/patología , Mucosa Nasal/ultraestructura , Ovalbúmina/administración & dosificación , Ovalbúmina/inmunología , Interferencia de ARN , ARN Interferente Pequeño/genética , ARN Interferente Pequeño/metabolismo , Receptores CCR3/inmunología , Receptores CCR3/metabolismo , Rinitis Alérgica/inmunología , Rinitis Alérgica/patologíaRESUMEN
The present study aimed to investigate the effects of CC chemokine receptor type 3 (CCR3) gene knockout on allergic rhinitis (AR) in mice, as well as the underlying molecular mechanisms. Ovalbumin was administrated to CCR3+/+ and CCR3/ BALB/c mice to establish an AR model. The mice were divided into four groups: i) Normal control (CG), ii) AR model (AR), iii) CCR3 knockout CG (CCR3/CG) and iv) AR model with CCR3 knockout (CCR3/AR). Histological sections of nasal mucosae were examined by hematoxylin and eosin staining, which revealed that CCR3 knockout suppressed the invasion of inflammatory cells and relieved the damage of nasal mucosae. Peripheral blood smear and nasalwashing smears were evaluated by Wright's staining. Eosinophil (EOS) numbers in nasal mucosae, peripheral blood, and nasal washings of the various groups were ranked in the order: AR>CCR3/AR>CG>CCR3/. mRNA expression levels of CCR3, EOS peroxidase (EPO), EOS cationic protein (ECP), and major basic protein (MBP) in the peripheral serum and nasal washings were detected by reverse transcriptionpolymerase chain reaction. Interferonγ (IFNγ), interleukin (IL)4, IL10, and immunoglobulin E (IgE) protein levels in the peripheral serum and nasal washings were investigated by ELISA. CCR3 mRNA expression was not detected in the CCR3/ and CCR3/AR groups, whereas expression levels in the AR group were markedly higher compared with expression in the CG group. Compared with the CGassociated groups (i.e., the CG and CCR3/CG groups), the levels of EPO, ECP, MBP, IL4, and IgE were significantly increased in the ARassociated groups (that is, R and CCR3/AR). In addition, the CCR3/AR group mice produced significantly lower levels of EPO, ECP, MBP, IL4 and IgE compared with the AR group, whereas the expression levels of IFNγ and IL10 were increased. CCR3 gene knockout may alleviate EOS invasion and the inflammatory response in AR model mice by reducing the expression levels of EPO, ECP, MBP, IL4, and IgE, and increasing the expression of IL10 and IFNγ.