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1.
Nano Lett ; 23(11): 4785-4792, 2023 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-37220025

RESUMO

While the performance of metal halide perovskite light-emitting diodes (PeLEDs) has rapidly improved in recent years, their stability remains a bottleneck to commercial realization. Here, we show that the thermal stability of polymer hole-transport layers (HTLs) used in PeLEDs represents an important factor influencing the external quantum efficiency (EQE) roll-off and device lifetime. We demonstrate a reduced EQE roll-off, a higher breakdown current density of approximately 6 A cm-2, a maximum radiance of 760 W sr-1 m-2, and a longer device lifetime for PeLEDs using polymer HTLs with high glass-transition temperatures. Furthermore, for devices driven by nanosecond electrical pulses, a record high radiance of 1.23 MW sr-1 m-2 and an EQE of approximately 1.92% at 14.6 kA cm-2 are achieved. Thermally stable polymer HTLs enable stable operation of PeLEDs that can sustain more than 11.7 million electrical pulses at 1 kA cm-2 before device failure.

2.
J Am Chem Soc ; 145(21): 11846-11858, 2023 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-37202123

RESUMO

Metal halide perovskites are promising for optoelectronic device applications; however, their poor stability under solar illumination remains a primary concern. While the intrinsic photostability of isolated neat perovskite samples has been widely discussed, it is important to explore how charge transport layers─employed in most devices─impact photostability. Herein, we study the effect of organic hole transport layers (HTLs) on light-induced halide segregation and photoluminescence (PL) quenching at perovskite/organic HTL interfaces. By employing a series of organic HTLs, we demonstrate that the HTL's highest occupied molecular orbital energy dictates behavior; furthermore, we reveal the key role of halogen loss from the perovskite and subsequent permeation into organic HTLs, where it acts as a PL quencher at the interface and introduces additional mass transport pathways to facilitate halide phase separation. In doing so, we both reveal the microscopic mechanism of non-radiative recombination at perovskite/organic HTL interfaces and detail the chemical rationale for closely matching the perovskite/organic HTL energetics to maximize solar cell efficiency and stability.

3.
J Infect Dis ; 226(7): 1224-1230, 2022 09 28.
Artigo em Inglês | MEDLINE | ID: mdl-35299253

RESUMO

BACKGROUND: Humoral immunity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may wane rapidly in persons recovered from mild coronavirus disease 2019 (COVID-19), but little is known about the longevity. METHODS: Serum samples were obtained 8, 12, and 18 months after infection from 20 patients with mild COVID-19. The binding activities of serum antibodies (immunoglobulin [Ig]A, IgG, and IgM) against SARS-CoV-2 antigens of the Wuhan-1 reference strain (wild-type) and the B.1.1.7, P.1, B.1.167.2, and B.1.1.529 variants were measured by enzyme-linked immunosorbent assays. Neutralizing antibody titers were measured using a cytopathic effect-based live virus neutralization assay. RESULTS: Serum IgA and IgG antibodies against spike or receptor-binding domain (RBD) protein of wild-type SARS-CoV-2 were detected for up to 18 months, and neutralizing antibodies persisted for 8 to 18 months after infection. However, any significant antibody responses against RBD proteins of SARS-CoV-2 variants were not observed, and median neutralizing antibody titers against the Delta variant at 8, 12, and 18 months were 8- to 11-fold lower than against wild-type viruses (P<.001). CONCLUSIONS: Humoral immunity persisted for up to 18 months after SARS-CoV-2 infection in patients with mild COVID-19. However, humoral immune activity against more recently circulating variants was reduced in this population.


Assuntos
COVID-19 , SARS-CoV-2 , Anticorpos Neutralizantes , Anticorpos Antivirais , Formação de Anticorpos , Humanos , Imunoglobulina A , Imunoglobulina G , Imunoglobulina M , Glicoproteína da Espícula de Coronavírus
4.
BMC Med ; 20(1): 181, 2022 05 04.
Artigo em Inglês | MEDLINE | ID: mdl-35508998

RESUMO

BACKGROUND: Practical guidance is needed regarding the vaccination of coronavirus disease 2019 (COVID-19) convalescent individuals in resource-limited countries. It includes the number of vaccine doses that should be given to unvaccinated patients who experienced COVID-19 early in the pandemic. METHODS: We recruited COVID-19 convalescent individuals who received one or two doses of an mRNA vaccine within 6 or around 18 months after a diagnosis of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection. Their samples were assessed for IgG-binding or neutralizing activity and cell-mediated immune responses against SARS-CoV-2 wild-type and variants of concern. RESULTS: A total of 43 COVID-19 convalescent individuals were analyzed in the present study. The results showed that humoral and cellular immune responses against SARS-CoV-2 wild-type and variants of concern, including the Omicron variant, were comparable among patients vaccinated within 6 versus around 18 months. A second dose of vaccine did not significantly increase immune responses. CONCLUSION: One dose of mRNA vaccine should be considered sufficient to elicit a broad immune response even around 18 months after a COVID-19 diagnosis.


Assuntos
COVID-19 , SARS-CoV-2 , Anticorpos Antivirais , COVID-19/prevenção & controle , Teste para COVID-19 , Vacinas contra COVID-19 , Humanos , Imunidade Celular , RNA Mensageiro/genética , SARS-CoV-2/genética , Vacinação , Vacinas Sintéticas , Vacinas de mRNA
5.
Int J Mol Sci ; 23(9)2022 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-35563434

RESUMO

Hydrogels capable of stimuli-responsive deformation are widely explored as intelligent actuators for diverse applications. It is still a significant challenge, however, to "program" these hydrogels to undergo highly specific and extensive shape changes with precision, because the mechanical properties and deformation mechanism of the hydrogels are inherently coupled. Herein, two engineering strategies are simultaneously employed to develop thermoresponsive poly(N-isopropyl acrylamide) (PNIPAm)-based hydrogels capable of programmable actuation. First, PNIPAm is copolymerized with poly(ethylene glycol) diacrylate (PEGDA) with varying molecular weights and concentrations. In addition, graphene oxide (GO) or reduced graphene oxide (rGO) is incorporated to generate nanocomposite hydrogels. These strategies combine to allow the refined control of mechanical and diffusional properties of hydrogels over a broad range, which also directly influences variable thermoresponsive actuation. It is expected that this comprehensive design principle can be applied to a wide range of hydrogels for programmable actuation.


Assuntos
Hidrogéis , Peso Molecular , Nanogéis
6.
Exp Lung Res ; 47(1): 1-8, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33076710

RESUMO

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.


Assuntos
Asma , Capsaicina , Administração por Inalação , Asma/tratamento farmacológico , Testes de Provocação Brônquica , Capsaicina/uso terapêutico , Tosse/induzido quimicamente , Tosse/tratamento farmacológico , Feminino , Humanos , Masculino , Cloreto de Metacolina
7.
J Asthma ; 58(9): 1143-1154, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-32419535

RESUMO

BACKGROUND: Asthma characterized by airway hyperresponsiveness, inflammation, fibrosis, and angiogenesis. SRY-related HMG-box 18 (SOX18) is an important transcription factor involved in angiogenesis, tissue injury, wound-healing, and in embryonic cardiovascular and lymphatic vessels development. The role of angiogenic transcription factors, SOX18 and the related, prospero homeobox 1 (PROX1) and chicken ovalbumin upstream promoter transcription factor II (COUP-TFII), in asthma has had limited study. OBJECTIVE: In this study, we aimed to elucidate the role of SOX18 in the pathogenesis of bronchial asthma. METHODS: Plasma SOX18 protein was measured in control subjects, and subject with stable or exacerbated asthma. SOX18, PROX1, and COUP-TFII protein was measured by western blot, and immunohistochemistry in a murine model of ovalbumin-induced allergic asthma (OVA). SOX18, PROX1, and COUP-TFII protein was measured in lung human microvascular endothelial cells (HMVEC-L) and normal human bronchial epithelial (NHBE) cells treated with house dust mite (Der p1). RESULTS: Plasma SOX18 tended to be higher in subject with asthma compared to control subjects and increased more during exacerbation as compared to stable disease. In mice, OVA challenge lead to increased lung SOX18, PROX1, COUP-TFII, mucous gland hyperplasia and submucosal collagen. In NHBE cells, SOX18, PROX1 and COUP-TFII increased following Der p1 treatment. SOX18 protein increased in HMVEC-L following Der p1 treatment. CONCLUSION: These results suggest that SOX18 may be involved in asthma pathogenesis and be associated with asthma exacerbation.


Assuntos
Asma/sangue , Fatores de Transcrição SOXF/sangue , Adulto , Idoso , Alérgenos/imunologia , Animais , Antígenos de Dermatophagoides/imunologia , Proteínas de Artrópodes/imunologia , Asma/imunologia , Asma/patologia , Líquido da Lavagem Broncoalveolar/citologia , Líquido da Lavagem Broncoalveolar/imunologia , Fator II de Transcrição COUP/imunologia , Linhagem Celular , Cisteína Endopeptidases/imunologia , Progressão da Doença , Feminino , Fibrose , Proteínas de Homeodomínio/imunologia , Humanos , Interleucina-5/imunologia , Pulmão/imunologia , Pulmão/patologia , Masculino , Camundongos Endogâmicos BALB C , Pessoa de Meia-Idade , Neovascularização Fisiológica , Ovalbumina/imunologia , Proteínas Supressoras de Tumor/imunologia , Fator A de Crescimento do Endotélio Vascular/imunologia
8.
Int J Mol Sci ; 22(13)2021 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-34206616

RESUMO

The biophysical properties of therapeutic antibodies influence their manufacturability, efficacy, and safety. To develop an anti-cancer antibody, we previously generated a human monoclonal antibody (Ab417) that specifically binds to L1 cell adhesion molecule with a high affinity, and we validated its anti-tumor activity and mechanism of action in human cholangiocarcinoma xenograft models. In the present study, we aimed to improve the biophysical properties of Ab417. We designed 20 variants of Ab417 with reduced aggregation propensity, less potential post-translational modification (PTM) motifs, and the lowest predicted immunogenicity using computational methods. Next, we constructed these variants to analyze their expression levels and antigen-binding activities. One variant (Ab612)-which contains six substitutions for reduced surface hydrophobicity, removal of PTM, and change to the germline residue-exhibited an increased expression level and antigen-binding activity compared to Ab417. In further studies, compared to Ab417, Ab612 showed improved biophysical properties, including reduced aggregation propensity, increased stability, higher purification yield, lower pI, higher affinity, and greater in vivo anti-tumor efficacy. Additionally, we generated a highly productive and stable research cell bank (RCB) and scaled up the production process to 50 L, yielding 6.6 g/L of Ab612. The RCB will be used for preclinical development of Ab612.


Assuntos
Anticorpos Monoclonais/química , Modelos Moleculares , Molécula L1 de Adesão de Célula Nervosa/química , Engenharia de Proteínas , Animais , Anticorpos Monoclonais/genética , Anticorpos Monoclonais/farmacologia , Afinidade de Anticorpos , Células CHO , Fenômenos Químicos , Cricetulus , Desenho de Fármacos , Avaliação Pré-Clínica de Medicamentos , Humanos , Molécula L1 de Adesão de Célula Nervosa/antagonistas & inibidores , Engenharia de Proteínas/métodos , Estabilidade Proteica , Termodinâmica
9.
J Korean Med Sci ; 35(43): e362, 2020 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-33169556

RESUMO

BACKGROUND: Calprotectin is the major cytosolic protein in neutrophil granulocytes. Although asthma is known to cause eosinophilic inflammation, some patients with asthma have non-eosinophilic inflammation, which is characterized by local neutrophilic inflammation. The aim of this study was to assess calprotectin expression levels in a mouse model of asthma, and to observe the relationship of serum calprotectin level and clinical variables in patients with asthma. METHODS: Mice were sensitized and challenged with 10 µg and 20 µg of Aspergillus fumigatus, respectively; mice treated with saline were used as a control. The levels of calprotectin were determined using enzyme-linked immunosorbent assay, immunoblotting, and immunohistochemical analysis. The serum levels of calprotectin were also assessed in patients with asthma. The relationship between calprotectin and clinicopathological characteristics was determined. RESULTS: Calprotectin, S100A8, and S100A9 expression was elevated in the mouse lungs, calprotectin levels were higher in the serum of patients with asthma (n = 33) compared with those of healthy individuals (n = 28). Calprotectin levels correlated with forced expiratory volume in one second/forced vital capacity (r = -0.215, P = 0.043), smoke amount (r = 0.413, P = 0.017), body mass index (r = -0.445, P = 0.000), and blood neutrophil percentage (r = 0.300, P = 0.004) in patients with asthma. CONCLUSION: Our data suggest that calprotectin could potentially be used as a biomarker for asthma.


Assuntos
Asma/sangue , Inflamação/sangue , Complexo Antígeno L1 Leucocitário/sangue , Sistema Respiratório/metabolismo , Animais , Asma/tratamento farmacológico , Biomarcadores/sangue , Biomarcadores/metabolismo , Calgranulina A/sangue , Calgranulina B/sangue , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Immunoblotting , Imuno-Histoquímica , Pulmão , Camundongos , Capacidade Vital
10.
Chemistry ; 25(2): 649-656, 2019 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-30395365

RESUMO

The effects of the molecular structure of thiazole-based polymers on the active layer morphologies and performances of electronic and photovoltaic devices were studied. Thus, thiazole-based conjugated polymers with a novel thiazole-vinylene-thiazole (TzVTz) structure were designed and synthesized. The TzVTz structure was introduced to extend the π conjugation and coplanarity of the polymer chains. By combining alkylthienyl-substituted benzo[1,2-b:4,5-b']dithiophene (BDT) or dithieno[2,3-d:2',3'-d']benzo[1,2-b:4,5-b']dithiophene (DTBDT) electron-donating units and a TzVTz electron-accepting unit, enhanced intermolecular interactions and charge transport were obtained in the novel polymers BDT-TzVTz and DTBDT-TzVTz. With a view to using the polymers in transistor and photovoltaic applications, the molecular self-assembly in and their nanoscale morphologies of the active layers were controlled by thermal annealing to enhance the molecular packing and by introducing a diphenyl ether solvent additive to improve the miscibility between polymer donors and [6,6]phenyl-C71-butyric acid methyl ester (PC71 BM) acceptors, respectively. The morphological characterization of the photoactive layers showed that a higher degree of π-electron delocalization and more favorable molecular packing in DTBDT-TzVTz compared with in BDT-TzVTz leads to distinctly higher performances in transistor and photovoltaic devices. The superior performance of a photovoltaic device incorporating DTBDT-TzVTz was achieved through the superior miscibility of DTBDT-TzVTz with PC71 BM and the improved crystallinity of DTBDT-TzVTz in the nanofibrillar structure.

11.
Chemistry ; 25(53): 12316-12324, 2019 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-31184399

RESUMO

A series of acene-modified small molecules have been designed and synthesized, and their photovoltaic characteristics were studied by using the small molecules in organic photovoltaics (OPVs). Different cores were introduced to modulate the conjugation lengths of the small molecules and the bulk heterojunction (BHJ) morphologies. Three small-molecule donors were prepared, namely Ph-TTR, Na-TTR, and An-TTR, which have phenyl, naphthalene, and anthracene moieties, respectively, as conjugated cores. These donors were synthesized in a few steps and exhibited favorable BHJ morphologies, thereby giving promising power conversion efficiencies (PCEs). The donors showed excellent miscibility with the acceptor PC71 BM, and the use of the additive 1,8-diiodooctane (DIO) led to a remarkable increase in crystallinity, thereby increasing the PCEs of their OPVs. Of the three donors, Na-TTR showed the most efficient charge carrier generation and favorable molecular packing structures; hence, of the three types of devices tested, the Na-TTR:PC71 BM devices exhibited the highest PCE, specifically 6.27 %, without pre- or post-treatments. The promising PCEs achieved from these easily synthesized acene-modified small molecules suggested that acene-modified small molecules can be useful materials in OPVs.

12.
Chem Res Toxicol ; 32(1): 139-145, 2019 01 22.
Artigo em Inglês | MEDLINE | ID: mdl-30608172

RESUMO

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.


Assuntos
Acroleína/efeitos adversos , Alérgenos/efeitos adversos , Asma Ocupacional/induzido quimicamente , Exposição Ambiental/efeitos adversos , Ovalbumina/efeitos adversos , Hipersensibilidade Respiratória/induzido quimicamente , Acroleína/administração & dosagem , Administração por Inalação , Alérgenos/administração & dosagem , Animais , Asma Ocupacional/diagnóstico , Claudinas/análise , Claudinas/metabolismo , Feminino , Proteína 1 Associada a ECH Semelhante a Kelch/análise , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Fator 2 Relacionado a NF-E2/análise , Fator 2 Relacionado a NF-E2/metabolismo , Ovalbumina/administração & dosagem , Hipersensibilidade Respiratória/diagnóstico , Fator A de Crescimento do Endotélio Vascular/análise , Fator A de Crescimento do Endotélio Vascular/metabolismo
13.
Lung ; 196(6): 681-689, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30182154

RESUMO

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.


Assuntos
Anexina A5/metabolismo , Antígenos de Dermatophagoides/farmacologia , Asma/diagnóstico , Asma/fisiopatologia , Células A549/metabolismo , Idoso , Poluentes Atmosféricos/efeitos adversos , Animais , Asma/etiologia , Asma/patologia , Biomarcadores/sangue , Fator de Crescimento do Tecido Conjuntivo/metabolismo , Dermatophagoides pteronyssinus , Modelos Animais de Doenças , Progressão da Doença , Feminino , Volume Expiratório Forçado , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Pessoa de Meia-Idade , Nanopartículas/efeitos adversos , Ovalbumina , Fibrose Pulmonar/patologia , Titânio/efeitos adversos , Fator de Crescimento Transformador beta1/metabolismo , Capacidade Vital
14.
Exp Mol Med ; 56(2): 478-490, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38413821

RESUMO

Idiopathic pulmonary fibrosis (IPF) is characterized by aberrant lung remodeling and the excessive accumulation of extracellular matrix (ECM) proteins. In a previous study, we found that the levels of ornithine aminotransferase (OAT), a principal enzyme in the proline metabolism pathway, were increased in the lungs of patients with IPF. However, the precise role played by OAT in the pathogenesis of IPF is not yet clear. The mechanism by which OAT affects fibrogenesis was assessed in vitro using OAT-overexpressing and OAT-knockdown lung fibroblasts. The therapeutic effects of OAT inhibition were assessed in the lungs of bleomycin-treated mice. OAT expression was increased in fibrotic areas, principally in interstitial fibroblasts, of lungs affected by IPF. OAT levels in the bronchoalveolar lavage fluid of IPF patients were inversely correlated with lung function. The survival rate was significantly lower in the group with an OAT level >75.659 ng/mL than in the group with an OAT level ≤75.659 ng/mL (HR, 29.53; p = 0.0008). OAT overexpression and knockdown increased and decreased ECM component production by lung fibroblasts, respectively. OAT knockdown also inhibited transforming growth factor-ß1 (TGF)-ß1 activity and TGF-ß1 pathway signaling. OAT overexpression increased the generation of mitochondrial reactive oxygen species (ROS) by activating proline dehydrogenase. The OAT inhibitor L-canaline significantly attenuated bleomycin-induced lung injury and fibrosis. In conclusion, increased OAT levels in lungs affected by IPF contribute to the progression of fibrosis by promoting excessive mitochondrial ROS production, which in turn activates TGF-ß1 signaling. OAT may be a useful target for treating patients with fibrotic lung diseases, including IPF.


Assuntos
Fibrose Pulmonar Idiopática , Fator de Crescimento Transformador beta1 , Animais , Humanos , Camundongos , Bleomicina , Proteínas da Matriz Extracelular , Fibrose , Pulmão/enzimologia , Ornitina-Oxo-Ácido Transaminase , Espécies Reativas de Oxigênio
15.
Toxics ; 11(10)2023 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-37888708

RESUMO

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.

16.
ACS Appl Mater Interfaces ; 15(27): 32610-32620, 2023 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-37376772

RESUMO

Fluorinated amorphous polymeric gate-insulating materials for organic thin-film transistors (OTFTs) not only form hydrophobic surfaces but also significantly reduce traps at the interface between the organic semiconductor and gate insulator. Therefore, these polymeric materials can enhance the OTFT's operation stability. In this study, we synthesized a new polymeric insulating material series composed of acrylate and fluorinated functional groups (with different ratios) named MBHCa-F and used them as gate insulators for OTFTs and in other applications. The insulating features of the MBHCa-F polymers, including surface energy, surface atomic content properties, dielectric constant, and leakage current, were clearly analyzed with respect to the content of the fluorinated functional groups. At higher fluorine-based functional group content, the polymeric series exhibited higher fluorine-based contents at the surface and superior electrical properties, such as field-effect mobility and driving stability, at OTFTs. Therefore, we believe that this study provides a substantial method for synthesizing polymeric insulating materials to enhance the operational stability and electrical performance of OTFTs.

17.
Sci Rep ; 13(1): 9044, 2023 06 03.
Artigo em Inglês | MEDLINE | ID: mdl-37270622

RESUMO

Proper lipid metabolism is crucial to maintain alveolar epithelial cell (AEC) function, and excessive AEC death plays a role in the pathogenesis of idiopathic pulmonary fibrosis (IPF). The mRNA expression of fatty acid synthase (FASN), a key enzyme in the production of palmitate and other fatty acids, is downregulated in the lungs of IPF patients. However, the precise role of FASN in IPF and its mechanism of action remain unclear. In this study, we showed that FASN expression is significantly reduced in the lungs of IPF patients and bleomycin (BLM)-treated mice. Overexpression of FASN significantly inhibited BLM-induced AEC death, which was significantly potentiated by FASN knockdown. Moreover, FASN overexpression reduced BLM-induced loss of mitochondrial membrane potential and the production of mitochondrial reactive oxygen species (ROS). Oleic acid, a fatty acid component increased by FASN overexpression, inhibited BLM-induced cell death in primary murine AECs and rescue BLM induced mouse lung injury/fibrosis. FASN transgenic mice exposed to BLM exhibited attenuated lung inflammation and collagen deposition compared to controls. Our findings suggest that defects in FASN production may be associated with the pathogenesis of IPF, especially mitochondrial dysfunction, and augmentation of FASN in the lung may have therapeutic potential in preventing lung fibrosis.


Assuntos
Bleomicina , Ácido Graxo Sintase Tipo I , Fibrose Pulmonar Idiopática , Animais , Camundongos , Bleomicina/toxicidade , Bleomicina/metabolismo , Fibrose Pulmonar Idiopática/induzido quimicamente , Fibrose Pulmonar Idiopática/genética , Fibrose Pulmonar Idiopática/tratamento farmacológico , Pulmão/patologia , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Mitocôndrias/metabolismo , Humanos , Ácido Graxo Sintase Tipo I/genética , Ácido Graxo Sintase Tipo I/metabolismo
18.
Exp Mol Med ; 54(5): 662-672, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35624153

RESUMO

Excessive oxidative stress causes lysosomal membrane permeabilization (LMP), which leads to cell death. Vacuolar ATPase (V-ATPase) is the enzyme responsible for pumping H+ into the cytosol and thus maintaining intracellular pH. Previously, we reported that V-ATPase B2 subunit expression is upregulated in the TiO2-exposed lung epithelium. We investigated the role of the lysosomal V-ATPase B2 subunit in oxidative stress-induced alveolar epithelial cell death and in an experimental lung injury/fibrosis model. Overexpression of V-ATPase B2 increased lysosomal pH and lysosomal activities in the cells. In the presence of H2O2, overexpression of V-ATPase B2 increased survival, and silencing of V-ATPase B2 dramatically increased cell death. Overexpression of V-ATPase B2 diminished H2O2-triggered LMP, as evidenced by a reduction in acridine orange staining and leakage of cathepsin D from the lysosome to the cytoplasm. In addition, V-ATPase B2-overexpressing macrophages exhibited significantly enhanced uptake and degradation of collagen. V-ATPase B2-overexpressing transgenic mice showed significant inhibition of the bleomycin-induced increases in lung inflammation and fibrosis. We conclude that V-ATPase B2 is critical for maintaining lysosomal activities against excessive oxidative stress by stabilizing LMP. Our findings reveal a previously unknown role of this V-ATPase subunit in a lung injury and fibrosis model.


Assuntos
Lesão Pulmonar , Fibrose Pulmonar , ATPases Vacuolares Próton-Translocadoras/metabolismo , Animais , Colágeno/metabolismo , Fibrose , Peróxido de Hidrogênio/metabolismo , Lesão Pulmonar/genética , Lesão Pulmonar/metabolismo , Lisossomos/metabolismo , Camundongos , Fibrose Pulmonar/genética , Fibrose Pulmonar/metabolismo , ATPases Vacuolares Próton-Translocadoras/genética
19.
Artigo em Inglês | MEDLINE | ID: mdl-35544719

RESUMO

Solution-based printing has contributed to the facile deposition of various types of materials, including the building blocks of printed electronics. In particular, solution-processable organic semiconductors (OSCs) are regarded as one of the most fascinating candidates for the fabrication of printed electronics. Herein, we report electrohydrodynamic (EHD) jet-printed p- and n-type OSCs, namely 6,13-bis(triisopropylsilylethynyl)pentacene (TIPS-PEN) and 6,13-bis((triisopropylsilyl)ethynyl)-5,7,12,14-tetraazapentacene (TIPS-TAP), and their use as single-OSC layers and as OSC mixed p-n layers to fabricate solution-processed p-, n-, and ambipolar-type organic field-effect transistors (OFETs). Use of the dragging mode of EHD jet printing, a process driven under a low electrostatic field with a short nozzle-to-substrate distance, was found to provide favorable conditions for growth of TIPS-PEN and TIPS-TAP crystals. In this way, the similar molecular structures of TIPS-PEN and TIPS-TAP yielded a homogeneous solid solution and showed ambipolar transport properties in OFETs. Therefore, the combination of single- and mixed-OSC layers enabled the preparation of various charge-transported devices from unit to integrated devices (NOT, NAND, NOR, and multivalued logic). Therefore, this fabrication technology can be useful for assisting in the production of OSC layers for practical applications in the near future.

20.
ACS Appl Mater Interfaces ; 14(5): 7073-7081, 2022 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-35080374

RESUMO

A π-conjugated polymer semiconductor, PBDTTTffPI, was synthesized for use as an organic semiconductor suitable for electrohydrodynamic (EHD) jet printing technology. Bulky alkylation of the polymer gave PBDTTTffPI good solubility in several organic solvents. EHD jet printing using PBDTTTffPI ink produced direct patterns of polymer semiconductors while maintaining smooth surface morphologies and crystal structures similar to those of spin-coated PBDTTTffPI films. EHD-jet-printed PBDTTTffPI was appropriate for use as a semiconductor layer in organic field-effect transistors (OFETs) and logic gates. OFETs that used EHD-jet-printed PBDTTTffPI had better electrical characteristics than devices that used spin-coated semiconductor films. When a dielectric material (Al2O3) with a high dielectric constant was introduced, the jet-printed PBDTTTffPI operated well at low voltages. Integrated devices such as inverters, NAND gates, and NOR gates were fabricated by printing PBDTTTffPI patterns and showed good switching behaviors. Therefore, the use of printable PBDTTTffPI provides an advance toward fabrication of practical integrated arrays in next-generation devices.

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