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1.
Exp Lung Res ; 47(1): 1-8, 2021 02.
Artículo en Inglés | MEDLINE | ID: mdl-33076710

RESUMEN

BACKGROUND: Inhaled capsaicin (8-methyl-N-vanillyl-6-nonenamide) has been used to induce cough in a safe and dose-dependent manner. Chronic cough is associated with an increased sensitivity to inhaled capsaicin in patients with asthma. The aim of this study was to evaluate clinical impact of capsaicin provocation test for chronic cough, and to find relationship between capsaicin concentration producing coughs and clinical variables in patients with asthma. Methods: 385 patients with chronic cough [capsaicin provocation test (+, n = 152)] vs. [capsaicin provocation test (-, n = 233)] who has done with capsaicin provocation test recruited and evaluated by asthma diagnosis and clinical variables. Asthma diagnoses were based on the Global Initiative for Asthma guidelines. Results: Capsaicin positivity was more prevalent in patient with asthma diagnosis than in patients without asthma diagnosis (129/304 vs. 24/81, p = 0.037). Capsaicin positivity was more prevalent in female patients than in male patients (123/271 = 45.4% vs. 30/114 = 26.3%, p = 0.001). Capsaicin concentration producing coughs correlated with smoke amount (r = 0.126, p = 0.014). Capsaicin positivity was more prevalent in nonsmoker patients than in smoker patients (133/295 = 45.1% vs. 20/90 = 22.2%, p = 0.001). Capsaicin concentration producing coughs negatively correlated with methacholine PC20 (4 mg mL-1, p = 0.037), (16 mg mL-1, p = 0.069) and (20 mg mL-1, p = 0.045). Capsaicin concentration producing coughs correlated with BMI (r = 0.120, p = 0.019). Capsaicin concentration producing coughs negatively correlated with FEV1/FVC % pred. (r = -0.137, p = 0.007). There was no relationship between capsaicin concentration producing coughs and age, IgE, and atopy. Conclusions: Capsaicin test for asthma diagnosis should be considered for variable clinical factors. Key message Cough in asthmatic patients is not only common and troublesome but also predicts disease severity and poor prognosis. The capsaicin cough challenge test is a simple and reproducible provocation method for assessing cough susceptibility in patients with cough. Capsaicin test for asthma diagnosis should be considered for variable clinical factors.


Asunto(s)
Asma , Capsaicina , Administración por Inhalación , Asma/tratamiento farmacológico , Pruebas de Provocación Bronquial , Capsaicina/uso terapéutico , Tos/inducido químicamente , Tos/tratamiento farmacológico , Femenino , Humanos , Masculino , Cloruro de Metacolina
2.
Mar Drugs ; 19(8)2021 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-34436282

RESUMEN

One of the well-known causes of hearing loss is noise. Approximately 31.1% of Americans between the ages of 20 and 69 years (61.1 million people) have high-frequency hearing loss associated with noise exposure. In addition, recurrent noise exposure can accelerate age-related hearing loss. Phlorofucofuroeckol A (PFF-A) and dieckol, polyphenols extracted from the brown alga Ecklonia cava, are potent antioxidant agents. In this study, we investigated the effect of PFF-A and dieckol on the consequences of noise exposure in mice. In 1,1-diphenyl-2-picrylhydrazyl assay, dieckol and PFF-A both showed significant radical-scavenging activity. The mice were exposed to 115 dB SPL of noise one single time for 2 h. Auditory brainstem response(ABR) threshold shifts 4 h after 4 kHz noise exposure in mice that received dieckol were significantly lower than those in the saline with noise group. The high-PFF-A group showed a lower threshold shift at click and 16 kHz 1 day after noise exposure than the control group. The high-PFF-A group also showed higher hair cell survival than in the control at 3 days after exposure in the apical turn. These results suggest that noise-induced hair cell damage in cochlear and the ABR threshold shift can be alleviated by dieckol and PFF-A in the mouse. Derivatives of these compounds may be applied to individuals who are inevitably exposed to noise, contributing to the prevention of noise-induced hearing loss with a low probability of adverse effects.


Asunto(s)
Antioxidantes/uso terapéutico , Benzofuranos/uso terapéutico , Dioxinas/uso terapéutico , Pérdida Auditiva Provocada por Ruido/tratamiento farmacológico , Kelp , Extractos Vegetales/uso terapéutico , Animales , Antioxidantes/farmacología , Organismos Acuáticos , Benzofuranos/farmacología , Cóclea/efectos de los fármacos , Dioxinas/farmacología , Modelos Animales de Enfermedad , Potenciales Evocados Auditivos del Tronco Encefálico/efectos de los fármacos , Células Ciliadas Auditivas/efectos de los fármacos , Masculino , Ratones , Ratones Endogámicos C57BL , Fitoterapia , Extractos Vegetales/farmacología
3.
Opt Express ; 28(26): 40075-40087, 2020 Dec 21.
Artículo en Inglés | MEDLINE | ID: mdl-33379541

RESUMEN

We propose an alternating current (AC) field operation scheme by using an asymmetric voltage waveform to improve the electroluminescence property of AC field-induced electroluminescence (AC-FIEL) devices. Hole injection and transport can be improved by carbon nanotubes (CNT) doping into the emission layer of an AC-FIEL structure operated by a single electrode for AC-responsive alternating carrier injections. However, under an AC operation, highly unbalanced charge transports are inevitably present in CNT-doped AC-FIEL devices due to faster carrier paths through CNTs. Compared with symmetric waveform, asymmetric waveform can be adjusted to allow longer relative duty time for faster carriers in which the luminance level of CNT-doped AC-FIEL devices can be improved by 1.4 times at the same device structure and operation frequency condition.

4.
Int J Mol Sci ; 21(22)2020 Nov 20.
Artículo en Inglés | MEDLINE | ID: mdl-33233709

RESUMEN

Noise-induced hearing loss (NIHL) can lead to secondary changes that induce neural plasticity in the central auditory pathway. These changes include decreases in the number of synapses, the degeneration of auditory nerve fibers, and reorganization of the cochlear nucleus (CN) and inferior colliculus (IC) in the brain. This study investigated the role of microRNAs (miRNAs) in the neural plasticity of the central auditory pathway after acute NIHL. Male Sprague-Dawley rats were exposed to white band noise at 115 dB for 2 h, and the auditory brainstem response (ABR) and morphology of the organ of Corti were evaluated on days 1 and 3. Following noise exposure, the ABR threshold shift was significantly smaller in the day 3 group, while wave II amplitudes were significantly larger in the day 3 group compared to the day 1 group. The organ of Corti on the basal turn showed evidence of damage and the number of surviving outer hair cells was significantly lower in the basal and middle turn areas of the hearing loss groups relative to controls. Five and three candidate miRNAs for each CN and IC were selected based on microarray analysis and quantitative reverse transcription PCR (RT-qPCR). The data confirmed that even short-term acoustic stimulation can lead to changes in neuroplasticity. Further studies are needed to validate the role of these candidate miRNAs. Such miRNAs may be used in the early diagnosis and treatment of neural plasticity of the central auditory pathway after acute NIHL.


Asunto(s)
Núcleo Coclear , Pérdida Auditiva Provocada por Ruido/metabolismo , Colículos Inferiores , MicroARNs/metabolismo , Plasticidad Neuronal , Animales , Núcleo Coclear/metabolismo , Núcleo Coclear/patología , Potenciales Evocados Auditivos del Tronco Encefálico , Colículos Inferiores/metabolismo , Colículos Inferiores/patología , Masculino , Órgano Espiral/patología , Ratas , Ratas Sprague-Dawley
5.
Chem Res Toxicol ; 32(1): 139-145, 2019 01 22.
Artículo en Inglés | MEDLINE | ID: mdl-30608172

RESUMEN

Acrolein, an α/ß-unsaturated aldehyde, is volatile at room temperature. It is a respiratory irritant found in environmental tobacco smoke, which can be generated during cooking or endogenously at sites of injury. An acute high concentration of uncontrolled irritant exposure can lead to an asthma-like syndrome known as reactive airways dysfunction syndrome (RADS). However, whether acrolein can induce RADS remains poorly understood. The aim of study is to develop a RADS model of acrolein inhalation in mice and to clarify the mechanism of RADS. Mice were treated with ovalbumin (OVA) and exposed to acrolein (5 ppm/10 min). Airway hyper-responsiveness (AHR) was measured on days 24 and 56, and samples were collected on days 25 and 57. Tight junction protein, antioxidant-associated protein, and vascular endothelial growth factor (VEGF) levels were estimated by Western blotting and immunohistochemical staining. Reactive oxygen species (ROS) was calculated using enzyme linked immunosorbent assays. Acrolein or OVA groups exhibited an increase in airway inflammatory cells and AHR compared to a sham group. These effects were further increased in mice in the OVA + acrolein exposure group than in the OVA exposure group and persisted in the acrolein exposure group for 8 weeks. CLDNs, carbonyls, VEGF, Nrf2, and Keap1 were observed in the lungs. Our data demonstrate that acrolein induces RADS and that ROS, angiogenesis, and tight junction proteins are involved in RADS in a mouse model.


Asunto(s)
Acroleína/efectos adversos , Alérgenos/efectos adversos , Asma Ocupacional/inducido químicamente , Exposición a Riesgos Ambientales/efectos adversos , Ovalbúmina/efectos adversos , Hipersensibilidad Respiratoria/inducido químicamente , Acroleína/administración & dosificación , Administración por Inhalación , Alérgenos/administración & dosificación , Animales , Asma Ocupacional/diagnóstico , Claudinas/análisis , Claudinas/metabolismo , Femenino , Proteína 1 Asociada A ECH Tipo Kelch/análisis , Proteína 1 Asociada A ECH Tipo Kelch/metabolismo , Ratones , Ratones Endogámicos BALB C , Factor 2 Relacionado con NF-E2/análisis , Factor 2 Relacionado con NF-E2/metabolismo , Ovalbúmina/administración & dosificación , Hipersensibilidad Respiratoria/diagnóstico , Factor A de Crecimiento Endotelial Vascular/análisis , Factor A de Crecimiento Endotelial Vascular/metabolismo
6.
Proteome Sci ; 16: 2, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-29375273

RESUMEN

BACKGROUND: Acrolein (allyl Aldehyde) as one of smoke irritant exacerbates chronic airway diseases and increased in sputum of patients with asthma and chronic obstructive lung disease. But underlying mechanism remains unresolved. The aim of study was to identify protein expression in human lung microvascular endothelial cells (HMVEC-L) exposed to acrolein. METHODS: A proteomic approach was used to determine the different expression of proteins at 8 h and 24 h after treatment of acrolein 30 nM and 300 nM to HMVEC-L. Treatment of HMVEC-L with acrolein 30 nM and 300 nM altered 21 protein spots on the two-dimensional gel, and these were then analyzed by MALDI-TOF MS. RESULTS: These proteins included antioxidant, signal transduction, cytoskeleton, protein transduction, catalytic reduction. The proteins were classified into four groups according to the time course of their expression patterns such as continually increasing, transient increasing, transient decreasing, and continually decreasing. For validation immunohistochemical staining and Western blotting was performed on lung tissues from acrolein exposed mice. Moesin was expressed in endothelium, epithelium, and inflammatory cells and increased in lung tissues of acrolein exposed mice compared with sham treated mice. CONCLUSIONS: These results indicate that some of proteins may be an important role for airway disease exacerbation caused by acrolein exposure.

7.
Phys Chem Chem Phys ; 20(29): 19294-19306, 2018 Jul 25.
Artículo en Inglés | MEDLINE | ID: mdl-29856453

RESUMEN

We derived a new analytic physical model for describing the temperature-dependent dielectric permittivities εe(T) and εo(T) in anisotropic mesophase molecules of nematic liquid crystals (NLCs). These temperature-dependent dielectric properties of NLCs could be explained by a six-parameter dielectric permittivity model, where the analytic dielectric permittivity curves of εe(T), εo(T), and Δε(T) from the model using the six parameters ε*, Aε, Bε, (Δε)o, λε, and T* showed excellent agreement with experimental data. The six-parameter dielectric permittivity model was compared to the conventional four-parameter refractive index model. To systematically investigate the temperature-dependent properties of the refractive indices (ne(T) and no(T)) and dielectric permittivities according to the molecular structure of the NLCs, four similar types of fluorinated phenyl bicyclohexane NLCs were selected. Using the presented models, the temperature-dependent behaviour of these four fluorinated NLCs was discussed, according to the molecular length of the alkyl chains and the positions of the fluorine substituents. In particular, two fitting equations for the temperature-dependent properties of threshold voltage and splay elastic LC constant could also be developed using the physical coefficients extracted from the six-parameter dielectric permittivity model, and these equations coincided well with experimental results.

8.
Appl Opt ; 57(2): 119-129, 2018 Jan 10.
Artículo en Inglés | MEDLINE | ID: mdl-29328155

RESUMEN

We proposed and analyzed an optically isotropic nano-droplet liquid crystal (LC) doped with high k nanoparticles (NPs), exhibiting enhanced Kerr effects, which could be operated with reduced driving voltages. For enhancing the contrast ratio together with the light efficiencies, the LC droplet sizes were adjusted to be shorter than the wavelength of visible light to reduce depolarization effects by optical scattering of the LC droplets. Based on the optical analysis of the depolarization effects, the influence of the relationship between the LC droplet size and the NP doping ratio on the Kerr effect change was investigated.

9.
Lung ; 196(6): 681-689, 2018 12.
Artículo en Inglés | MEDLINE | ID: mdl-30182154

RESUMEN

PURPOSE: Annexin A5 (ANXA5) has a potential role in cellular signal transduction, inflammation, and fibrosis. However, the exact role of ANXA5 in asthma remains to be clarified. The aims of the present study were to investigate ANXA5 protein expression in a mouse model of asthma and pollutant exposure and to elucidate the relationships between clinical variables and plasma ANXA5 levels in patients with asthma. METHODS: A murine model of asthma induced by ovalbumin (OVA) and titanium dioxide (TiO2) nanoparticles has been established using BALB/c mice, and we examined ANXA5 expression and lung fibrosis using this model. Moreover, we also compared ANXA5 plasma levels in patients with controlled vs. exacerbated asthma. RESULTS: ANXA5 protein levels were lower in lung tissue from OVA + OVA mice than in control mice. Lung ANXA5, connective tissue growth factor (CTGF), and transforming growth factor ß1 (TGF-ß1) protein levels were higher in OVA + TiO2-exposed mice than in control or OVA + OVA mice. Although Dermatophagoides pteronyssinus (Derp1) treatment increased lung ANXA5 protein levels in MRC-5 cells and A549 epithelial cells, it decreased lung ANXA5 levels in NHBE cells. Treatment with TiO2 nanoparticles increased lung ANXA5, CTGF, and TGF-ß1 protein levels in MRC-5 cells, A549 epithelial cells, and NHBE cells. Plasma ANXA5 levels were lower in asthmatic patients than in healthy controls, and they were significantly enriched in patients with exacerbated asthma compared with those with controlled asthma (P < 0.05). ANXA5 levels were correlated with pulmonary function as assessed by spirometry. CONCLUSION: Our results imply that ANXA5 plays a potential role in asthma pathogenesis and may be a promising marker for exacerbated bronchial asthma and exposure to air pollutants.


Asunto(s)
Anexina A5/metabolismo , Antígenos Dermatofagoides/farmacología , Asma/diagnóstico , Asma/fisiopatología , Células A549/metabolismo , Anciano , Contaminantes Atmosféricos/efectos adversos , Animales , Asma/etiología , Asma/patología , Biomarcadores/sangre , Factor de Crecimiento del Tejido Conjuntivo/metabolismo , Dermatophagoides pteronyssinus , Modelos Animales de Enfermedad , Progresión de la Enfermedad , Femenino , Volumen Espiratorio Forzado , Humanos , Masculino , Ratones , Ratones Endogámicos BALB C , Persona de Mediana Edad , Nanopartículas/efectos adversos , Ovalbúmina , Fibrosis Pulmonar/patología , Titanio/efectos adversos , Factor de Crecimiento Transformador beta1/metabolismo , Capacidad Vital
10.
BMC Pulm Med ; 18(1): 1, 2018 Jan 04.
Artículo en Inglés | MEDLINE | ID: mdl-29301525

RESUMEN

BACKGROUND: Annexin-A1 (ANXA1) is a glucocorticoid-induced protein with multiple actions in the regulation of inflammatory cell activation. The anti-inflammatory protein ANXA1 and its N-formyl peptide receptor 2 (FPR2) have protective effects on organ fibrosis. However, the exact role of ANXA1 in asthma remains to be determined. The aim of this study was to identify the role of ANXA1 in bronchial asthma. METHODS: In mice sensitized and challenged with ovalbumin (OVA-OVA mice) and mice sensitized with saline and challenged with air (control mice), we investigated the potential links between ANXA1 levels and bronchial asthma using ELISA, immunoblotting, and immunohistochemical staining. Moreover, we also determined ANXA1 levels in blood from 50 asthmatic patients (stable and exacerbated states). RESULTS: ANXA1 protein levels in lung tissue and bronchoalveolar lavage fluid were significantly higher in OVA-OVA mice compared with control mice. FPR2 protein levels in lung tissue were significantly higher in OVA-OVA mice compared with control mice. Plasma ANXA1 levels were increased in asthmatic patients compared with healthy controls. Plasma ANXA1 levels were significantly lower in exacerbated patients compared with stable patients with bronchial asthma (p < 0.05). The plasma ANXA1 levels in controlled asthmatic patients were correlated with forced expiratory volume in 1 s (FEV1) (r = - 0.191, p = 0.033) and FEV1/forced vital capacity (FVC) (r = -0.202, p = 0.024). CONCLUSION: These results suggest that ANXA1 may be a potential marker and therapeutic target for asthma.


Asunto(s)
Anexina A1/sangre , Asma/sangre , Pulmón/fisiopatología , Adulto , Anciano , Animales , Anexina A1/análisis , Asma/inducido químicamente , Asma/fisiopatología , Líquido del Lavado Bronquioalveolar/química , Líquido del Lavado Bronquioalveolar/citología , Estudios de Casos y Controles , Femenino , Volumen Espiratorio Forzado , Humanos , Pulmón/metabolismo , Masculino , Ratones , Ratones Endogámicos BALB C , Persona de Mediana Edad , Ovalbúmina , Brote de los Síntomas , Capacidad Vital
11.
Environ Toxicol ; 33(7): 798-806, 2018 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-29673049

RESUMEN

Claudins (CLDNs) are a major transmembrane protein component of tight junctions (TJs) in endothelia and epithelia. CLDNs are not only essential for sustaining the role of TJs in cell permeability but are also vital for cell signaling through protein-protein interactions. Ozone induces oxidative stress and lung inflammation in humans and experimental models, but the impact of ozone on claudins remains poorly understood. This study was to determine the expression of TJ proteins, such as claudin 3, 4, 5, and 14 following ozone exposure. Mice were exposed to 0.1, 1, or 2 ppm of ozone or ambient air for 6 h for 3 days. The impact of ozone on CLDNs, Nrf2, Keap1, and reactive oxygen species (ROS) were estimated using immunoblotting, immunohistochemical staining, confocal imaging, and ELISA analysis in mice and bronchial epithelial cells. Mice exposed to ozone experienced increased airway inflammatory cell infiltration and bronchial hyper-responsiveness compared to control mice. Additionally, CLDN3, CLDN4, ROS, Nrf2, and Keap1 protein expression increased, and lung CLDN14 protein expression decreased, in mice exposed to ozone compared with control mice. These results indicate that CLDNs are involved in airway inflammation following ozone exposure, suggesting that ozone affects TJ proteins through oxidative mechanisms.


Asunto(s)
Claudinas/metabolismo , Pulmón/efectos de los fármacos , Ozono/toxicidad , Uniones Estrechas/metabolismo , Animales , Líquido del Lavado Bronquioalveolar/química , Líquido del Lavado Bronquioalveolar/citología , Células Cultivadas , Citocinas/metabolismo , Células Epiteliales/citología , Células Epiteliales/efectos de los fármacos , Células Epiteliales/metabolismo , Femenino , Humanos , Inflamación/metabolismo , Inflamación/patología , Pulmón/metabolismo , Pulmón/patología , Ratones , Ratones Endogámicos BALB C , Especies Reactivas de Oxígeno/metabolismo , Transducción de Señal/efectos de los fármacos
12.
Ann Allergy Asthma Immunol ; 116(4): 339-43, 2016 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-26776887

RESUMEN

BACKGROUND: Angiopoietin (Ang)-1 and -2 are involved in the pathogenesis of asthma and have been identified as markers of asthma severity. OBJECTIVE: To determine the relation between circulating angiopoietins and clinical variables of patients with asthma. METHODS: Fifty patients with bronchial asthma and 25 healthy controls were enrolled. Ang1 and Ang2 plasma levels were analyzed in patients with stable and exacerbated asthma. RESULTS: Plasma Ang1 levels were 28.4 ± 4.01 pg/mg in patients with bronchial asthma and 21.2 ± 5.21 pg/mg in healthy controls. Plasma Ang2 levels were 23.96 ± 1.38 pg/mg in patients with bronchial asthma compared with 36.8 ± 4.46 pg/mg in healthy controls (P = .010). The ratio of Ang2 to Ang1 was lower in patients with asthma than in control subjects. Plasma Ang1 concentrations were correlated with the ratio of forced expiratory volume in 1 second (FEV1) to forced vital capacity (FVC), and plasma Ang2 levels were correlated with FEV1 percentage of predicted, FEV1/FVC, and total immunoglobulin E values. The ratio of Ang2 to Ang1 was correlated with FEV1 percentage of predicted and FEV1/FVC. Although plasma Ang1 levels tended to be lower in the exacerbated state than in the stable state in patients with asthma, Ang2 levels were higher in the exacerbated state than in the stable state in patients with asthma (P = .001). Plasma Ang2 levels were correlated with initial eosinophil proportions and initial neutrophil proportions. Plasma Ang2 levels and the ratio of Ang2 to Ang1 were correlated with blood eosinophil proportions in the exacerbated state. CONCLUSION: These results indicate that circulating angiopoietins could be a useful marker of asthma exacerbation.


Asunto(s)
Angiopoyetina 2/sangre , Asma/diagnóstico , Biomarcadores/sangre , Eosinófilos/inmunología , Neutrófilos/inmunología , Adulto , Anciano , Angiopoyetina 1/sangre , Progresión de la Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Inmunoglobulina E/sangre , Masculino , Persona de Mediana Edad , Pruebas de Función Respiratoria , Pruebas Cutáneas
13.
Sensors (Basel) ; 16(11)2016 Oct 27.
Artículo en Inglés | MEDLINE | ID: mdl-27801812

RESUMEN

We propose a liquid crystal (LC)-based 3D optical surface profilometer that can utilize multiple fringe patterns to extract an enhanced 3D surface depth profile. To avoid the optical phase ambiguity and enhance the 3D depth extraction, 16 interference patterns were generated by the LC-based dynamic fringe pattern generator (DFPG) using four-step phase shifting and four-step spatial frequency varying schemes. The DFPG had one common slit with an electrically controllable birefringence (ECB) LC mode and four switching slits with a twisted nematic LC mode. The spatial frequency of the projected fringe pattern could be controlled by selecting one of the switching slits. In addition, moving fringe patterns were obtainable by applying voltages to the ECB LC layer, which varied the phase difference between the common and the selected switching slits. Notably, the DFPG switching time required to project 16 fringe patterns was minimized by utilizing the dual-frequency modulation of the driving waveform to switch the LC layers. We calculated the phase modulation of the DFPG and reconstructed the depth profile of 3D objects using a discrete Fourier transform method and geometric optical parameters.

14.
Toxics ; 11(10)2023 Oct 13.
Artículo en Inglés | MEDLINE | ID: mdl-37888708

RESUMEN

Air pollutants are associated with exacerbations of asthma, chronic bronchitis, and airway inflammation. Diesel exhaust particles (DEPs) can induce and worsen lung diseases. However, there are insufficient data to guide polymerase chain reaction (PCR) array proteomics studies regarding the impacts of DEPs on respiratory diseases. This study was performed to identify genes and proteins expressed in normal human bronchial epithelial (NHBE) cells. MicroRNAs (miRNAs) and proteins expressed in NHBE cells exposed to DEPs at 1 µg/cm2 for 8 h and 24 h were identified using PCR array analysis and 2D PAGE/LC-MS/MS, respectively. YWHAZ gene expression was estimated using PCR, immunoblotting, and immunohistochemical analyses. Genes discovered through an overlap analysis were validated in DEP-exposed mice. Proteomics approaches showed that exposing NHBE cells to DEPs led to changes in 32 protein spots. A transcriptomics PCR array analysis showed that 6 of 84 miRNAs were downregulated in the DEP exposure groups compared to controls. The mRNA and protein expression levels of YWHAZ, ß-catenin, vimentin, and TGF-ß were increased in DEP-treated NHBE cells and DEP-exposed mice. Lung fibrosis was increased in mice exposed to DEPs. Our combined PCR array-omics analysis demonstrated that DEPs can induce airway inflammation and lead to lung fibrosis through changes in the expression levels of YWHAZ, ß-catenin, vimentin, and TGF-ß. These findings suggest that dual approaches can help to identify biomarkers and therapeutic targets involved in pollutant-related respiratory diseases.

15.
Front Cell Infect Microbiol ; 12: 824575, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35646744

RESUMEN

Lymphangiogenesis and angiogenesis might have significant involvement in the pathogenesis of otitis media with effusion. This study investigated the effect of diesel exhaust particles (DEP) on inflammation and lymphangiogenesis in a mouse model of acute otitis media (AOM). BALB/c mice were injected with LPS and exposed to 100 µg/m3 DEP. The mice were divided into four groups: control (no stimulation), AOM, AOM + DEP, and DEP + AOM. The effects of DEP inhalation pre- and post-DEP induction were estimated based on measurements of the auditory brainstem response, mRNA levels of lymphangiogenesis-related genes and cytokines, and histology of the middle ear. Cell viability of human middle ear epithelial cells decreased in a dose-response manner at 24 and 48 hours post-DEP exposure. DEP alone did not induce AOM. AOM-induced mice with pre- or post-DEP exposure showed thickened middle ear mucosa and increased expression of TNF-α and IL1-ß mRNA levels compared to the control group, but increased serum IL-1ß levels were not found in the AOM + Post DEP. The mRNA expression of TLR4, VEGFA, VEGFAC, and VEGFR3 was increased by pre-AOM DEP exposure. The expression of VEFGA protein was stronger in the AOM + Post DEP group than in any other group. The expression of CD31 and CD45 markers in the mouse middle ear tissue was higher in the Pre DEP + AOM group than in the AOM group. This result implies that pre-exposure to DEP more strongly increases inflammation and lymphangiogenesis in a mouse model of acute otitis media.


Asunto(s)
Otitis Media , Emisiones de Vehículos , Animales , Modelos Animales de Enfermedad , Inflamación , Lipopolisacáridos/toxicidad , Linfangiogénesis , Ratones , Ratones Endogámicos BALB C , Otitis Media/inducido químicamente , Otitis Media/metabolismo , ARN Mensajero/metabolismo , Emisiones de Vehículos/toxicidad
16.
J Allergy Clin Immunol ; 136(6): 1694-1696.e5, 2015 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-26409663
17.
Sci Rep ; 11(1): 16997, 2021 08 20.
Artículo en Inglés | MEDLINE | ID: mdl-34417533

RESUMEN

Nanoparticulate matter activates the aryl hydrocarbon receptor (AhR) pathway in the respiratory system in a process involving the AhR nuclear translocator (ARNT) and cytochrome P450 family 1, member A1 (CYP1A1). We examined changes in AhR-related pathways following intranasal instillation of nanoparticulate matter in the olfactory bulb and cerebral cortex. Twice a day for 5 days per week for 1 week or 2 weeks, 8-week-old Sprague-Dawley rats were intranasally instilled with 10 µL nanoparticulate matter (nano group; n = 36). An equal volume of saline was intranasally instilled in control rats (n = 36). One week after intranasal instillation, olfactory function and Y-maze tests were performed. The expression levels of AhR in the olfactory bulb and temporal cortex were analyzed using western blotting and immunofluorescence assays. The expression levels of AhR, CYP1A1, inducible nitric oxide synthase (iNOS), and five genes encoding cation transporters (ARNT, ATP7B, ATPB1, OCT1, and OCT2) in the olfactory bulb were analyzed using quantitative reverse transcription. The olfactory discrimination capability was reduced in the nano group compared with the control group. Proportional changes in the Y-maze test were not significantly different between the nano and control groups. AhR mRNA and protein expression in the olfactory bulb increased 1.71-fold (P < 0.001) and 1.60-fold (P = 0.008), respectively. However, no significant changes were observed in the temporal cortex. In the olfactory bulb, the expression of ARNT, ATP7B, ATPB1, and OCT2 was downregulated. CYP1A1 and iNOS expression in the olfactory bulb was upregulated compared with that in the temporal cortex. The intranasal instillation of nanoparticulate matter decreased the olfactory discrimination ability, which was accompanied by upregulation of AhR expression and downregulation of cation transporters in the olfactory bulb.


Asunto(s)
Nanopartículas/administración & dosificación , Bulbo Olfatorio/fisiología , Administración Intranasal , Animales , Citocromo P-450 CYP1A1/genética , Citocromo P-450 CYP1A1/metabolismo , Regulación de la Expresión Génica , Metales Pesados/análisis , Nanopartículas/ultraestructura , Óxido Nítrico Sintasa de Tipo II/genética , Óxido Nítrico Sintasa de Tipo II/metabolismo , Bulbo Olfatorio/ultraestructura , ARN Mensajero/genética , ARN Mensajero/metabolismo , Ratas Sprague-Dawley , Receptores de Hidrocarburo de Aril/genética , Receptores de Hidrocarburo de Aril/metabolismo , Olfato
18.
Ann Otol Rhinol Laryngol ; 129(3): 245-255, 2020 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-31646875

RESUMEN

OBJECTIVES: Diesel exhaust particles (DEP)s are notorious ambient pollutants composed of a complex mixture of a carbon core and diverse chemical irritants. Several studies have demonstrated significant relationships between DEP exposure and serious nasal inflammatory response in vitro, but available information regarding underlying networks in terms of gene expression changes has not sufficiently explained potential mechanisms of DEP-induced nasal damage, especially in vivo. METHODS: In the present study, we identified DEP-induced gene expression profiles under short-term and long-term exposure, and identified signaling pathways based on microarray data for understanding effects of DEP exposure in the mouse nasal cavity. RESULTS: Alteration in gene expression due to DEP exposure provokes an imbalance of the immune system via dysregulated inflammatory markers, predicted to disrupt protective responses against harmful exogenous substances in the body. Several candidate markers were identified after validation using qRT-PCR, including S100A9, CAMP, IL20, and S100A8. CONCLUSIONS: Although further mechanistic studies are required for verifying the utility of the potential biomarkers suggested by the present study, our in vivo results may provide meaningful suggestions for understanding the complex cellular signaling pathways involved in DEP-induced nasal damages.


Asunto(s)
Expresión Génica , Rinitis/inducido químicamente , Emisiones de Vehículos/toxicidad , Animales , Péptidos Catiónicos Antimicrobianos/genética , Péptidos Catiónicos Antimicrobianos/metabolismo , Antígeno B7-1/genética , Antígeno B7-1/metabolismo , Biomarcadores/metabolismo , Calgranulina A/genética , Calgranulina A/metabolismo , Calgranulina B/genética , Calgranulina B/metabolismo , Interleucinas/genética , Interleucinas/metabolismo , Ratones Endogámicos BALB C , Modelos Animales , Pruebas de Provocación Nasal , Análisis de Secuencia por Matrices de Oligonucleótidos , ARN/metabolismo , Reacción en Cadena en Tiempo Real de la Polimerasa , Rinitis/metabolismo , Transducción de Señal , Miembro 9 de la Superfamilia de Receptores de Factores de Necrosis Tumoral/genética , Miembro 9 de la Superfamilia de Receptores de Factores de Necrosis Tumoral/metabolismo , Catelicidinas
19.
Respir Physiol Neurobiol ; 271: 103292, 2020 01.
Artículo en Inglés | MEDLINE | ID: mdl-31542455

RESUMEN

The interaction between chronic inflammation and neural dysfunction points to a link between the nervous and immune systems in the airways. In particular, environmental exposure to nanoparticles (NPs), defined as particulate matter having one dimension <100 nm, is associated with an enhanced risk of childhood and adult asthma. However, the impact of NPs on the neural response in asthma remains to be determined. This study determined the impact of NPs on neuroinflammation in a mouse model of allergic asthma. Ovalbumin (OVA) sensitized mice were treated with saline (Sham), OVA challenged and exposed to 200 µg/m3 NPs 1 h a day for 3 days on days 21-23 in a closed-system chamber attached to a ultrasonic nebulizer. The effect of NPs on the levels of neuropeptides, transient receptor potential vanilloid 1 (TRPV1), TRPV4, P2 × 4, and P2 × 7 was assessed by enzyme-linked immunosorbent assays, immunoblotting, and immunohistochemistry. NP exposure increased airway inflammation and responsiveness in OVA mice, and these increases were augmented in OVA plus NP-exposed mice. The lung tissue levels of TRPV1, TRPV4, P2 × 4, and P2 × 7 were increased in OVA mice, and these increases were augmented in OVA plus NP-exposed mice. The substance P, adenosine triphosphate (ATP), and calcitonin gene-related peptide (CGRP) levels in bronchoalveolar lavage fluid were increased in OVA mice, and these increases were augmented in OVA plus NP-exposed mice. Bradykinin, ATP, and CGRP were dose dependently increased in NP-exposed normal human bronchial epithelial (NHBE) cells. The calcium concentration was increased in NHBE cells exposed to NPs for 8 h. These results indicate that neuroinflammation can be involved in the pathogenesis of bronchial asthma and that NPs can exacerbate asthma via neuromediator release.


Asunto(s)
Asma/inducido químicamente , Asma/metabolismo , Modelos Animales de Enfermedad , Mediadores de Inflamación/metabolismo , Nanopartículas/toxicidad , Animales , Células Cultivadas , Femenino , Humanos , Exposición por Inhalación/efectos adversos , Ratones , Ratones Endogámicos BALB C , Material Particulado/efectos adversos , Titanio/toxicidad
20.
Sci Rep ; 9(1): 19421, 2019 12 19.
Artículo en Inglés | MEDLINE | ID: mdl-31857661

RESUMEN

The inhalation of particulate matter (PM) increases the perineuronal nets (PNNs) in the cerebral cortex; however, little is known about the related molecular changes. We explored how PM exposure impacted cognitive function and the levels of PNN-related genes. BALB/c mice (6-week-old females, n = 32) were exposed to 1-5-µm diesel-extracted particles (DEPs) (100 µg/m3, 5 hours per day, 5 days per week) and categorized into the following four groups: 1) 4-week DEP exposure (n = 8); 2) 4-week control (n = 8); 3) 8-week DEP exposure (n = 8); and 4) 8-week control (n = 8). The Y-maze test and olfactory function test were conducted after 4 and 8 weeks of DEP exposure. The prefrontal cortex, olfactory bulb and temporal cortex were harvested from the animals in each group. The expression of genes related to PNNs (Tenascin C, matrix metalloproteinase [MMP]14, MMP9) and synaptic vesicular transporters of vesicular glutamergic transporter 1 (VGLUT1), VGLUT2, vesicular GABAergic transporter (VGAT) were measured. The temporal cortex was immunostained for neurocan, VGLUT1, and VGAT. The 4-week DEP group had lower total arm entry in the Y-maze test and olfactory sensitivity. These impaired behavioral functions recovered in the 8-week DEP group. Expression of tenascin C and MMP9 were increased in the cerebral cortex in the 8-week DEP group compared with the control group. The levels of VGLUT1, VGLUT2, and VGAT were elevated in the cerebral cortex of the 8-week DEP group compared with the control group. In immunostaining of the temporal cortex, the expression of neurocan, VGLUT1, and GAD67 were increased in the 8-week DEP group compared with the control group. The 4-week DEP inhalation impaired spatial activities and olfactory sensitivities. After 8 weeks of DEP exposure, the PNN components and their proteolytic enzymes and the vesicular transporters increased in the cerebral cortex.


Asunto(s)
Corteza Cerebral/patología , Exposición por Inhalación , Neuronas/patología , Material Particulado/efectos adversos , Animales , Peso Corporal , Metaloproteinasa 9 de la Matriz/genética , Metaloproteinasa 9 de la Matriz/metabolismo , Aprendizaje por Laberinto/efectos de la radiación , Memoria a Corto Plazo/efectos de los fármacos , Ratones Endogámicos BALB C , Neurocano/genética , Neurocano/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismo , Olfato/efectos de los fármacos , Tenascina/genética , Tenascina/metabolismo , Emisiones de Vehículos , Proteínas de Transporte Vesicular/metabolismo
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