RESUMO
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 = -â0.191, 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.
Assuntos
Anexina A1/sangue , Asma/sangue , Pulmão/fisiopatologia , Adulto , Idoso , Animais , Anexina A1/análise , Asma/induzido quimicamente , Asma/fisiopatologia , Líquido da Lavagem Broncoalveolar/química , Líquido da Lavagem Broncoalveolar/citologia , Estudos de Casos e Controles , Feminino , Volume Expiratório Forçado , Humanos , Pulmão/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Pessoa de Meia-Idade , Ovalbumina , Exacerbação dos Sintomas , Capacidade VitalRESUMO
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.
Assuntos
Angiopoietina-2/sangue , Asma/diagnóstico , Biomarcadores/sangue , Eosinófilos/imunologia , Neutrófilos/imunologia , Adulto , Idoso , Angiopoietina-1/sangue , Progressão da Doença , Feminino , Seguimentos , Humanos , Imunoglobulina E/sangue , Masculino , Pessoa de Meia-Idade , Testes de Função Respiratória , Testes CutâneosRESUMO
Aluminum is one of the most widely used nonferrous metals and an important industrial material, especially for automotive coatings. However, potential toxicity caused by aluminum in humans limits the used of this metal. α-alumina is the most stable form of aluminum in various phases. Although the results of studies evaluating the dermal toxicity of α-alumina remained unclear, this compound can still be used as a pigment in cosmetics for humans. In the current study, we further evaluated the dermal cytotoxic effects of α-alumina on human skin cells and an in vivo mouse model. We also measured the in vitro penetration profile of flake-like α-alumina in porcine skin and assessed the degree of cellular metabolic disorders. Our findings demonstrated that treatment with flake-like α-alumina did not significantly affect cell viability up to 24 h. This compound was found to have a non-penetration profile based on a Franz modified diffusion cell assay. In addition, flake-like α-alumina was not found to induce dermal inflammation as assessed by histology of epidermal architecture, hyperplasia, and the expression of Interleukin-1ß and Cyclooxygenase-2. Results of the cellular metabolic disorder assay indicated that flake-like α-alumina does not exert a direct effect on human skin cells. Taken together, our findings provided not only evidence that flake-like α-alumina may serve as a pearlescent pigment in cosmetics but also experimental basis utilizing α-alumina for human application. Our results also obviously provide new insight of the further toxicity study to aluminum based nanoparticles for skin.
Assuntos
Óxido de Alumínio/toxicidade , Corantes/toxicidade , Dermatite de Contato/etiologia , Dermatite de Contato/imunologia , Pele/efeitos dos fármacos , Pele/imunologia , Óxido de Alumínio/química , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Dermatite de Contato/patologia , Relação Dose-Resposta a Droga , Fibroblastos/efeitos dos fármacos , Humanos , Teste de Materiais , Pele/patologiaRESUMO
The polyhedra unit structure (MOx) in an amorphous metal oxide network has more freedom and flexibility than the same unit structure in a crystalline phase. Consequently, a mild external stimulus (e.g., instant photonic and acoustic energy) could affect and change this network parameter, thereby enhancing and modulating the electrical properties. However, it is difficult to tune these atomic parameters solely while maintaining the metal oxide's initial global amorphous phase and thereby preventing mechanical instability at the film-substrate interface (i.e., cracking or distortion). Here, we report local disordering in an amorphous network of a solution-processable indium tin oxide (ITO) film, where the disordering is triggered by mild-light irradiation (<0.1 mJ/cm2). Through a combination of systematic characterizations of the global structural and chemical compositional changes in conjunction with extended X-ray absorption fine structure analyses, we revealed the distortion of the atomic structure in the amorphous network of the ITO film led to the formation of additional structural oxygen vacancies. Our findings enabled us to fabricate mechanical-instability-free, perfect amorphous-phase ITO thin films on plastic substrates, where the sheet resistance substantially decreased to â¼ 2 × 103 Ω/â¡. Furthermore, this sheet resistance did not vary when the film and substrate were bent to a radius of 2 mm and could operate at low temperatures. This work can pave the novel way to fabricate high-quality flexible transparent electrodes suitable for rapid, cost-effective, and patternable processing on plastic substrates, and the domain can be extended to flexible electronics.
RESUMO
Cranial irradiation is the main therapeutic strategy for treating primary and metastatic brain tumors. However, radiation is well-known to induce several unexpected side effects including emotional disorders. Although radiation-induced depression may cause decreased quality of life after radiotherapy, investigations of its molecular mechanism and therapeutic strategies are still insufficient. In this study, we found that behavioral symptoms of depression on mice models with the decrease of BrdU/NeuN- and Dcx-positive populations and MAP-2 expression in hippocampus were induced by cranial irradiation, and transthyretin (TTR) was highly expressed in hippocampus after irradiation. It was shown that overexpression of TTR resulted in the inhibition of retinol-mediated neuritogenesis. PAK1 phosphorylation and MAP-2 expression were significantly reduced by TTR overexpression following irradiation. Moreover, we observed that treatment of allantoin and neferine, the active components of Nelumbo nucifera, interrupted irradiation-induced TTR overexpression, consequently leading to the increase of PAK1 phosphorylation, neurite extension, BrdU/NeuN- and Dcx-positive populations, and MAP-2 expression. Behavioral symptoms of depression following cranial irradiation were also relieved by treatment of allantoin and neferine. These findings demonstrate that TTR plays a critical role in neurogenesis after irradiation, and allantoin and neferine could be potential drug candidates for recovering the effects of radiation on neurogenesis and depression.
Assuntos
Regulação da Expressão Gênica/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos da radiação , Hipocampo/citologia , Neurogênese/efeitos dos fármacos , Neurogênese/efeitos da radiação , Pré-Albumina/metabolismo , Vitamina A/farmacologia , Alantoína/farmacologia , Animais , Benzilisoquinolinas/farmacologia , Linhagem Celular Tumoral , Depressão/etiologia , Depressão/metabolismo , Depressão/patologia , Depressão/psicologia , Proteína Duplacortina , Emoções/efeitos da radiação , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Hipocampo/efeitos da radiação , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Crescimento Neuronal/efeitos da radiação , Lesões Experimentais por Radiação/metabolismo , Lesões Experimentais por Radiação/patologia , Lesões Experimentais por Radiação/psicologia , Receptores do Ácido Retinoico/metabolismo , Transdução de Sinais/efeitos da radiação , Vitamina A/metabolismo , Quinases Ativadas por p21/metabolismo , Proteínas rac1 de Ligação ao GTP/metabolismoRESUMO
Increased survival of cancer cells mediated by high levels of ionizing radiation (IR) reduces the effectiveness of radiation therapy for non-small cell lung cancer (NSCLC). In the present study, danshensu which is a selected component of traditional oriental medicine (TOM) compound was found to reduce the radioresistance of NSCLC by inhibiting the nuclear factor-κB (NF-κB) pathway. Of the various TOM compounds reported to inhibit the IR activation of NF-κB, danshensu was chosen as a final candidate based on the results of structural comparisons with human metabolites and monoamine oxidase B (MAOB) was identified as the putative target enzyme. Danshensu decreased the activation of NF-κB by inhibiting MAOB activity in A549 and NCI-H1299 NSCLC cells. Moreover, it suppressed IR-induced epithelial-to-mesenchymal transition, expressions of NF-κB-regulated prosurvival and proinflammatory genes, and in vivo radioresistance of mouse xenograft models. Taken together, this study shows that danshensu significantly reduces MAOB activity and attenuates NF-κB signaling to elicit the radiosensitization of NSCLC.
Assuntos
Antineoplásicos Fitogênicos/farmacologia , Carcinoma Pulmonar de Células não Pequenas/terapia , Lactatos/farmacologia , Neoplasias Pulmonares/terapia , Inibidores da Monoaminoxidase/farmacologia , Monoaminoxidase/genética , Tolerância a Radiação/efeitos dos fármacos , Animais , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular Tumoral , Medicamentos de Ervas Chinesas , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Transição Epitelial-Mesenquimal/efeitos da radiação , Raios gama/uso terapêutico , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Medicina Tradicional do Leste Asiático , Camundongos , Camundongos Nus , Monoaminoxidase/metabolismo , NF-kappa B/genética , NF-kappa B/metabolismo , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
BACKGROUND/AIMS: We sought to increase our understanding of the rhinitis-asthma relationship and improve strategies for the treatment of patients with these diseases. The aim of this study was to identify a connection between upper airway inflammation and lower airway responsiveness. METHODS: We counted eosinophils on nasal smears, and performed spirometry, allergic skin tests, and methacholine challenge tests in 308 schoolchildren plus a questionnaire on respiratory symptoms. The methacholine concentration causing a 20% fall in forced expiratory volume in 1 second (PC20 < 25 mg/mL) was used as the threshold of bronchial hyperresponsiveness (BHR). RESULTS: In total, 26% of subjects had positive nasal eosinophils on a smear, and 46.2% of subjects had BHR at < 25 mg/mL methacholine PC20. Nasal symptoms were higher in subjects with than without nasal eosinophils (p = 0.012). Asthma symptoms did not differ between subjects with and without nasal eosinophils. Nasal eosinophils were higher in subjects with atopy than those without (p = 0.006), and there was no difference in PC20 methacholine according to atopy (15.5 ± 1.07 vs. 17.5 ± 0.62; p > 0.05). No difference in BHR was detected when comparing subjects with and without nasal eosinophils. There were significant differences in the PC20 between subjects with greater than 50% nasal eosinophils and without nasal eosinophils (11.01 ± 2.92 mg/mL vs. 17.38 ± 0.61 mg/mL; p < 0.001). CONCLUSIONS: These findings demonstrated that nasal eosinophilic inflammation might contribute to lower airway responsiveness in schoolchildren, based on an epidemiological survey.
Assuntos
Asma/epidemiologia , Hiper-Reatividade Brônquica/enzimologia , Eosinofilia/epidemiologia , Pulmão/fisiopatologia , Mucosa Nasal/imunologia , Rinite/epidemiologia , Adolescente , Distribuição por Idade , Fatores Etários , Asma/diagnóstico , Asma/fisiopatologia , Hiper-Reatividade Brônquica/diagnóstico , Hiper-Reatividade Brônquica/fisiopatologia , Testes de Provocação Brônquica , Criança , Eosinofilia/diagnóstico , Eosinofilia/imunologia , Eosinófilos/imunologia , Feminino , Inquéritos Epidemiológicos , Humanos , Testes Intradérmicos , Contagem de Leucócitos , Masculino , República da Coreia/epidemiologia , Rinite/diagnóstico , Rinite/imunologia , Espirometria , Inquéritos e QuestionáriosRESUMO
Cancer is a complex disease resulting from alterations of multiple signaling networks. Cancer networks have been identified as scale-free networks and may contain a functionally important key player called a hub that is linked to a large number of interactors. Since a hub can serve as a biological marker in a given network, targeting the hub could be an effective strategy for enhancing the efficacy of cancer treatment. Chemotherapies and radiotherapies are generally used to treat tumors not amenable to resection, and target single or multiple molecules associated with hubs. However, these therapies may unexpectedly induce the resistance of cancer cells to drugs and radiation. Cancer cells can overcome therapy-induced damage via the activation of back-up signaling pathways and flexible modulation of affected networks. These activities are considered to be the main reasons for chemoresistance and radioresistance, and subsequent failure of cancer therapies. Much effort is required to identify the key molecules that control the modulation of signaling networks in response to drugs and radiation. Network-based therapy that affects network flexibility, including rewired network structures and hub molecules in these networks, could minimize the occurrence of side-effects and be a promising strategy for enhancing the therapeutic efficacy of cancer treatments. This review is intended to offer an overview of current research efforts including ones focused on cancer-associated complex networks, their modulation in response to cancer therapy, and further strategies targeting networks that may improve cancer treatment efficacy.