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Tb-doped magneto-optical (MO) glass is widely used in fiber optics, optical isolators, and modulators. However, only the paramagnetic Tb3+ ions exhibit significant MO effects, whereas the diamagnetism Tb4+ ions suppress the MO effects. Therefore, the valence state control of Tb ions is very critical to optimize MO performance. Here, a reduction strategy was introduced to adjust the Tb valence in glass to achieve the high MO effect. The TiO, which has low valence Ti2+ ions and good reducibility, was used to suppress the oxidation of Tb3+ to Tb4+ ions. In the TiO-B2O3-Al2O3-Na2O glass, 10 mol% TiO can increase the Verdet constant at 650 nm by 19%. With the further increase in Tb2O3 concentration, the Verdet constant reaches a high value of 117 rad/(T·m) at 650 nm, which is close to the Verdet constant of TGG crystal (121 rad/(T·m)). This work provides a new approach to increase the Verdet constant of MO glass.
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Laser lighting devices, comprising an ultraviolet (UV) laser chip and a phosphor material, have emerged as a highly efficient approach for generating high-brightness light sources. However, the high power density of laser excitation may exacerbate thermal quenching in conventional polycrystalline or amorphous phosphors, leading to luminous saturation and the eventual failure of the device. Here, for the first time, we raise a single-crystal (SCs) material for laser lighting considering the absence of grain boundaries that scatter electrons and phonons, achieving high thermal conductivity (0.81 W m-1 K-1) and heat-resistance (575 °C). The SCs products exhibit a high photoluminescence quantum yield (89%) as well as excellent stability toward high-power lasers (>12.41 kW/cm2), superior to all previously reported amorphous or polycrystalline matrices. Finally, the laser lighting device was fabricated by assembling the SC with a UV laser chip (50 mW), and the device can maintain its performance even after continuous operation for 4 h. Double perovskite single crystals doped with Yb3+/Er3+ demonstrated multimodal luminescence with the irradiation of 355 and 980 nm lasers, respectively. This characteristic holds significant promise for applications in spectrally tunable laser lighting and multimodal anticounterfeiting.
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2D <100>-oriented Dion-Jacobson or Ruddlesden-Popper perovskites are widely recognized as promising candidates for optoelectronic applications. However, the large interlayer spacing significantly hinders the carrier transport. <110>-oriented 2D perovskites naturally exhibit reduced interlayer spacings, but the tilting of metal halide octahedra is typically serious and leads to poor charge transport. Herein, a <110>-oriented 2D perovskite EPZPbBr4 (EPZ = 1-ethylpiperazine) with minimized tilting is designed through A-site stereo-hindrance engineering. The piperazine functional group enters the space enclosed by the three [PbBr6]4- octahedra, pushing PbâBrâPb closer to a straight line (maximum PbâBrâPb angle ≈180°), suppressing the tilting as well as electron-phonon coupling. Meanwhile, the ethyl group is located between layers and contributes an extremely reduced effective interlayer distance (2.22 Å), further facilitating the carrier transport. As a result, EPZPbBr4 simultaneously demonstrates high µτ product (1.8 × 10-3 cm2 V-1) and large resistivity (2.17 × 1010 Ω cm). The assembled X-ray detector achieves low dark current of 1.02 × 10-10 A cm-2 and high sensitivity of 1240 µC Gy-1 cm-2 under the same bias voltage. The realized specific detectivity (ratio of sensitivity to noise current density, 1.23 × 108 µC Gy-1 cm-1 A-1/2) is the highest among all reported perovskite X-ray detectors.
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Infrared evanescent wave sensing based on chalcogenide fiber is an emerging technology for qualitative and quantitative analysis of most organic compounds. Here, a tapered fiber sensor made from Ge10As30Se40Te20 glass fiber was reported. The fundamental modes and intensity of evanescent waves in fibers with different diameters were simulated with COMSOL. The 30 mm length tapered fiber sensors with different waist diameters, 110, 63, and 31 µm, were fabricated for ethanol detection. The sensor with a waist diameter of 31 µm has the highest sensitivity of 0.73 a.u./% and a limit of detection (LoD) of 0.195 vol.% for ethanol. Finally, this sensor has been used to analyze alcohols, including Chinese baijiu (Chinese distilled spirits), red wine, Shaoxing wine (Chinese rice wine), Rio cocktail, and Tsingtao beer. It is shown that the ethanol concentration is consistent with the nominal alcoholicity. Moreover, other components such as CO2 and maltose can be detected in Tsingtao beer, demonstrating the feasibility of its application in detecting food additives.
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Metal halide perovskite (MHP) single crystals (SCs) have been demonstrated to have significant potential in photodetectors and photovoltaic devices due to their exceptional optoelectronic properties. The most promising approach for large-scale fabrication of high-quality MHP SCs is the synthesis of MHP SCs in solution. To explain the mechanism and guide the crystal growth process, the classical nucleation-growth theory was established. However, it mainly focuses on zone melting systems and does not account for the interaction between perovskite and solvent. In this review, we specifically focus on the difference in the growth mechanism between MHP SCs in solution and traditional SCs synthesized by the melting method, which includes a discussion of the dissolution, nucleation, and growth processes. We then summarize recent advances in the preparation of MHP SCs based on the special growth mechanism of the perovskite system. The purpose of this review is to provide comprehensive information to offer targeted theoretical guidance as well as unified understanding for the preparation of high-quality MHP SCs in solution.
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Compostos de Cálcio , Metais , Óxidos , CristalizaçãoRESUMO
Perovskite materials have demonstrated great potential for ultrafast scintillators with high light yield. However, the decay time of perovskite still cannot be further minimized into sub-nanosecond region, while sub-nanosecond scintillators are highly demanded in various radiation detection, including high speed X-ray imaging, time-of-flight based tomography or particle discrimination, and timing resolution measurement in synchrotron radiation facilities, etc. Here, a rational design strategy is showed to shorten the scintillation decay time, by maximizing the dielectric difference between organic amines and Pb-Br octahedral emitters in 2D organic-inorganic hybrid perovskites (OIHP). Benzimidazole (BM) with low dielectric constant inserted between [PbBr6 ]2- layers, resulting in a surprisingly large exciton binding energy (360.3 ± 4.8 meV) of 2D OIHP BM2 PbBr4 . The emitting decay time is shortened as 0.97 ns, which is smallest among all the perovskite materials. Moreover, the light yield is 3190 photons MeV-1 , which is greatly higher than conventional ultrafast scintillator BaF2 (1500 photons MeV-1 ). The rare combination of ultrafast decay time and considerable light yield renders BM2 PbBr4 excellent performance in γ-ray, neutron, α-particle detection, and the best theoretical coincidence time resolution of 65.1 ps, which is only half of the reference sample LYSO (141.3 ps).
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Due to the high transparency, high Verdet constant, as well as easy processing properties, rare-earth ion-doped glasses have demonstrated great potential in magneto-optical (MO) applications. However, the variation in the valence state of rare-earth ions (Tb3+ to Tb4+) resulted in the decreased effective concentration of the paramagnetic ions and thus degraded MO performance. Here, a strategy was proposed to inhibit the oxidation of Tb3+ into Tb4+ as well as improve the thermal stability by tuning the optical basicity of glass networks. Moreover, the depolymerization of the glass network was modulated to accommodate more Tb ions. Thus, a record high effective concentration (14.19 × 1021/cm3) of Tb ions in glass was achieved, generating a high Verdet constant of 113 rad/(T·m) at 650 nm. Lastly, the first application of MO glass for magnetic field sensors was demonstrated, achieving a sensitivity of 0.139 rad/T. We hope our work provides guidance for the fabrication of MO glass with high performance and thermal stability and could push MO glass one step further for magnetic sensing applications.
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Fenpropathrin has been a commonly used insecticide to control agricultural and household insects over a few decades. Up to now, fenpropathrin residue in soil and water has been often determined due to its widespread use, which poses serious threat to environment and aquatic organisms. The potential of fenpropathrin to affect aquatic lives is still poorly understood. In this study, we used zebrafish (Danio rerio) embryo as an experimental model system to evaluate the toxicity of fenpropathrin to the development of zebrafish nervous system. Zebrafish embryos were separately exposed to fenpropathrin at the dose of 0.016 mg/L, 0.032 mg/L, 0.064 mg/L, starting at 6 h post-fertilizationhpf (hpf) up to 96 hpf. The results showed that fenpropathrin exposure gives rise to physiological, behavioral, and neurodevelopmental impairments in zebrafish embryos, including enhanced acetylcholinesterase (AChE) activity, abnormal swimming behavior, karyopyknosis in brain cells, increased intercellular space, and uneven migration of neuron in brain area. In addition, the expressions of genes concerning neurodevelopment and neurotransmitter system were inhibited following fenpropathrin exposure. We also found that fenpropathrin exposure distinctly induced oxidative stress by increasing reactive oxygen species (ROS) generation and inhibiting the production of antioxidant enzymes catalase (CAT) and superoxide dismutase (SOD). Expectedly, some apoptosis-associated genes were induced and the apoptosis appeared in the brain and heart cells of zebrafish embryos. Moreover, fenpropathrin exposure also inhibited the expressions of genes in Nrf2 signaling pathway, such as heme oxygenase-1 (HO-1) and SOD. In summary, the results of this study indicate that oxidative stress-triggered apoptosis may be an underlying fundamental of fenpropathrin-induced neurotoxicity in zebrafish embryos.
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Poluentes Químicos da Água , Peixe-Zebra , Animais , Peixe-Zebra/metabolismo , Acetilcolinesterase/metabolismo , Estresse Oxidativo/genética , Superóxido Dismutase/metabolismo , Embrião não Mamífero/metabolismo , Poluentes Químicos da Água/toxicidadeRESUMO
BACKGROUND: Asthma is one of the most common chronic diseases that affects more than 300 million people worldwide. Though most asthma can be well controlled, individuals with severe asthma experience recurrent exacerbations and impose a substantial economic burden on healthcare system. Neutrophil inflammation often occurs in patients with severe asthma who have poor response to glucocorticoids, increasing the difficulty of clinical treatment. METHODS: We established several neutrophil-dominated allergic asthma mouse models, and analyzed the airway hyperresponsiveness, airway inflammation and lung pathological changes. Neutrophil extracellular traps (NETs) formation was analyzed using confocal microscopy and western blot. RESULTS: We found that the ovalbumin (OVA)/complete Freund's adjuvant (CFA)/low-dose lipopolysaccharide (LPS)-induced mouse model best recapitulated the complex alterations in the airways of human severe asthmatic patients. We also observed OVA/CFA/LPS-exposed mice produced large quantities of neutrophil extracellular traps (NETs) in lung tissue and bone marrow neutrophils. Furthermore, we found that reducing the production of NETs or increasing the degradation of NETs can reduce airway inflammation and airway hyperresponsiveness. CONCLUSION: Our findings identify a novel mouse model of neutrophilic asthma. We have also identified NETs play a significant role in neutrophilic asthma models and contribute to neutrophilic asthma pathogenesis. NETs may serve as a promising therapeutic target for neutrophilic asthma.
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Asma , Hipersensibilidade Respiratória , Camundongos , Humanos , Animais , Ovalbumina , Lipopolissacarídeos/toxicidade , Ativação de Neutrófilo , Adjuvante de Freund/efeitos adversos , Modelos Animais de Doenças , Glucocorticoides/efeitos adversos , Asma/metabolismo , Inflamação/induzido quimicamente , Inflamação/patologia , Hipersensibilidade Respiratória/induzido quimicamenteRESUMO
BACKGROUND: Tyrosine kinase inhibitors (TKI) have been the standard first-line therapy for advanced non-small cell lung cancer (NSCLC) of epidermal growth factor receptor (EGFR) sensitive mutations. Uncommon EGFR mutations are increasingly reported with the development of next-generation sequencing. However, their sensitivity to TKIs is variable with limited clinical evidence. CASE SUMMARY: Here, we report a patient with the rare delE709_T710insD mutation, who showed the favorable efficacy of dacomitinib and achieved a partial response with a progression-free survival of 7.0 mo. CONCLUSION: To our knowledge, this is the first report displaying the clinical efficacy of dacomitinib for patients with delE709_T710insD, which may help to provide alternatives in non-classical variant NSCLC patients. Further studies are warranted to make the optimal choice of EGFR-TKI for rare mutations.
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Lead-free double perovskites (DPs) have outstanding luminescent properties, which make them excellent candidates for wide use in optoelectronics. Herein, a solvent-free melting-crystallization technique, which can produce kilogram-scale DP microcrystals (DP-MCs) in one batch, is invented to synthesize the Cs2NaxAg1-xInCl6: Bi (x = 0, 0.2, 0.4, 0.6, 0.8, and 1) DP-MCs. The structure and composition analysis confirmed the products are pure Cs2NaxAg1-xInCl6 DP-MCs. Affected by Jahn-Teller distortion of AgCl6 octahedra, self-trapped excitons appear in the excited state, resulting in the broadband emission (400-850 nm) of Cs2Ag1-xNaxInCl6: Bi DP-MCs. The enhancement of the photoluminescence quantum yield can be realized by introducing Na+ to break the parity-forbidden transition in the Cs2AgInCl6 DP. Optimized Cs2Na0.4Ag0.6InCl6: Bi DP-MC phosphors combined with commercial blue and green phosphors were coated on ultraviolet chips (365 nm) to fabricate white light-emitting diodes (WLEDs) from warm white (2930 K) to cold white (6957 K). An ultrahigh color rendering index of 97.1 and a CCT of 5548 K as well as Commission Internationale de l'Eclairage color coordinates of (0.331, 0.339) have been demonstrated. This kilogram-scale synthesis technique could stimulate the industrial development of WLEDs for general lighting based on DP-MC phosphors.
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Halide double perovskites have attracted substantial attention for optoelectronic applications owing to their low toxicity and high stability. However, double perovskites have strict requirements in terms of the halide type, thus rendering many of their properties unchangeable, including the band gap, atomic number, and carrier transport. By introducing long-chain organic amines, the chloride site of double perovskites can be completely replaced by bromide. Using this strategy, two dimensions silver-indium-bromide double perovskites (PEA)4AgInBr8 and (i-BA)4AgInBr8 were successfully synthesized [(PEA)+ = C6H5(CH2)2NH3+, (i-BA)+ = CH(CH3)2CH2NH3+]. Density functional theory calculations and spectroscopy characterizations were performed to unveil the semiconducting behaviors and photoluminescence properties of the title compounds. Electrical characterization confirms their good carrier-transport property (µτ product: 2.0 × 10-3 cm2 V-1) and low dark current. Moreover, the presence of heavy atoms, together with the ultrastable baseline contributes to a high X-ray detection sensitivity (185 µC Gyair-1 cm-2), greater than that of most previous double-perovskite detectors. Our work lays the foundation for broadening the family of potential double perovskites, creating a new path for the realization of long-sought perovskites with low toxicity and high stability that retain good optoelectronic performance.
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BACKGROUND: Lung cancer is the primary cause of cancer-related mortality worldwide. The anticancer effect of stilbene has been noted in various tumor types. GMQ3, which has a stilbene-mimicking skeleton, is a novel small-molecule compound with promising antitumor activity. Our results revealed that GMQ3 not only suppressed cell proliferation and cell migration of lung cancer cells but also led to G1 phase cell cycle arrest and triggered caspase-dependent apoptosis. Furthermore, investigation of the molecular mechanism showed that GMQ3 could inhibited proliferation and induced apoptosis via the p38-MAPK/SIRT1 pathway both in vitro and in vivo. Xenograft tumor mouse models showed that GMQ3 significantly inhibited tumor growth in vivo without affecting body weight. Our findings indicated that GMQ3 exerts a strong anticancer action by suppressing cell proliferation, inhibiting cell migration and inducing cell apoptosis. Moreover, the efficacy of GMQ3 was enhanced in the presence of CDK4/6 inhibitor Abemaciclib. We conclude that GMQ3 is a promising agent with potential for lung cancer.
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Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Sirtuína 1/metabolismo , Estilbenos/farmacologia , Aminopiridinas/farmacologia , Aminopiridinas/uso terapêutico , Animais , Antineoplásicos/química , Antineoplásicos/uso terapêutico , Benzimidazóis/farmacologia , Benzimidazóis/uso terapêutico , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Quimioterapia Combinada , Feminino , Humanos , Camundongos , Camundongos Nus , Sirtuína 1/genética , Estilbenos/química , Estilbenos/uso terapêutico , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Lead halide perovskites have exhibited excellent performance in solar cells, LEDs and detectors. Thermal properties of perovskites, such as heat capacity and thermal conductivity, have rarely been studied and corresponding devices have barely been explored. Considering the high absorption coefficient (104~105 cm-1), low specific heat capacity (296-326 J kg-1 K-1) and small thermal diffusion coefficient (0.145 mm2 s-1), herein we showcase the successful use of perovskite in optoacoustic transducers. The theoretically calculated phonon spectrum shows that the overlap of optical phonons and acoustic phonons leads to the up-conversion of acoustic phonons, and thus results in experimentally measured low thermal diffusion coefficient. The assembled device of PDMS/MAPbI3/PDMS simultaneously achieves broad bandwidths (-6 dB bandwidth: 40.8 MHz; central frequency: 29.2 MHz), and high conversion efficiency (2.97 × 10-2), while all these parameters are the record values for optoacoustic transducers. We also fabricate miniatured devices by assembling perovskite film onto fibers, and clearly resolve the fine structure of fisheyes, which demonstrates the strong competitiveness of perovskite based optoacoustic transducers for ultrasound imaging.
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BACKGROUND: Cigarette smoke is well known to worsen asthma symptoms in asthmatic patients and to make them refractory to treatment, but the underling molecular mechanism is unclear. We hypothesized that cigarette smoke can reduce the expression of HDAC2 in asthma and the process was achieved by activating the PI3K-δ/Akt signaling pathway. We further hypothesized that roxithromycin (RXM) can alleviate the impacts by cigarette smoke. METHODS: A murine model of asthma induced by ovalbumin (OVA) and cigarette smoke has been established. The infiltration of inflammatory cells and inflammatory factors was examined in this model. Finally, we evaluated the expression of HDAC2, Akt phosphorylation levels, and the effects of RXM treatment on the model described earlier. RESULTS: Cigarette smoke exposure reduced HDAC2 protein expression by enhancing the phosphorylation of Akt in PI3K-δ/Akt signaling pathway. Furthermore, RMX reduced the airway inflammation and improved the level of expression of HDAC2 in the cigarette smoke-exposed asthma mice. CONCLUSIONS: This study provides a novel insight into the mechanism of cigarette smoke exposure in asthma and the effects of RXM treatment on this condition. These results may be helpful for treating refractory asthma and emphasizing the need for a smoke-free environment for asthmatic patients.
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Antiasmáticos/uso terapêutico , Antibacterianos/uso terapêutico , Asma/tratamento farmacológico , Histona Desacetilase 2/metabolismo , Nicotiana , Roxitromicina/uso terapêutico , Fumaça/efeitos adversos , Alérgenos , Animais , Antiasmáticos/farmacologia , Antibacterianos/farmacologia , Asma/genética , Asma/metabolismo , Asma/patologia , Líquido da Lavagem Broncoalveolar/citologia , Líquido da Lavagem Broncoalveolar/imunologia , Modelos Animais de Doenças , Eosinófilos/imunologia , Feminino , Histona Desacetilase 2/genética , Pulmão/efeitos dos fármacos , Pulmão/imunologia , Pulmão/patologia , Camundongos Endogâmicos BALB C , Neutrófilos/imunologia , Ovalbumina , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Roxitromicina/farmacologiaRESUMO
CdSe quantum dots (QDs) doped glasses have been widely investigated for optical filters, LED color converter and other optical emitters. Unlike CdSe QDs in solution, it is difficult to passivate the surface defects of CdSe QDs in glass matrix, which strongly suppress its intrinsic emission. In this study, surface passivation of CdSe quantum dots (QDs) by Cd1-xZnxSe shell in silicate glass was reported. An increase in the Se/Cd ratio can lead to the partial passivation of the surface states and appearance of the intrinsic emission of CdSe QDs. Optimizing the heat-treatment condition promotes the incorporation of Zn into CdSe QDs and results in the quenching of the defect emission. Formation of CdSe/Cd1-xZnxSe core/graded shell QDs is evidenced by the experimental results of TEM and Raman spectroscopy. Realization of the surface passivation and intrinsic emission of II-VI QDs may facilitate the wide applications of QDs doped all inorganic amorphous materials.
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BACKGROUND AND AIM: Paraneoplastic syndrome is a disease or symptom that is the consequence of cancer in the body but, unlike mass effect, is not due to the local presence of cancer cells. An overlap of two paraneoplastic syndromes secondary to lung cancer in a patient is very rare. In order to improve the diagnosis of two paraneoplastic syndromes secondary to lung cancer, we reported an overlap of two paraneoplastic syndromes secondary to lung squamous carcinoma in a patient. METHODS: We reported a case of a 60-year-old male smoker who presented multiple erythematous lesions for 6 months with progressive proximal muscular weakness, and developed to dysphonia in 2 months. His chest computed tomography showed a spiculate pulmonary nodule near the hilar in the right upper lobe and mediastinal lymph nodes enlargement. Lung biopsy showed squamous cell carcinoma. The patient's blood test revealed elevated creatine kinase levels. Electromyography results were consistent with moderate myopathy accompanied with a pattern suggestive of Lambert-Eaton myasthenic syndrome. RESULTS: So we made the diagnosis of an overlap of two paraneoplastic syndromes (dermatomyositis and Lambert-Eaton myasthenic syndrome) secondary to lung squamous carcinoma. CONCLUSION: Recognition of paraneoplastic syndrome is crucial for early diagnosis of lung cancer because up to 80% of patients may present paraneoplastic syndromes before any other direct indication of malignancy. Early diagnosis and treatment of paraneoplastic syndrome is also important because delayed diagnosis may result in rapid disease progression and irreversible neurological damage.
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Carcinoma de Células Pequenas/diagnóstico , Dermatomiosite/diagnóstico , Síndrome Miastênica de Lambert-Eaton/diagnóstico , Neoplasias Pulmonares/diagnóstico , Carcinoma de Células Pequenas/patologia , Humanos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-IdadeRESUMO
OBJECTIVE: To explore the effects of smoking on airway inflammation through the expressions of hypoxia-inducible factor-1α (HIF-1α) and histone deacetylase-2 (HDAC2) in asthmatic mice. METHODS: A total of 30 female SPF BALB/c mice were divided randomly into 3 groups of control (C), asthma (A) and smoking asthma (S). The latter two groups were sensitized and challenged with ovalbumin (OVA) for asthmatic modeling. The mice of group S were placed into a self-made fumigating box for passive smoking. While group S was sensitized and challenged with normal saline instead of OVA. The pathological changes of different groups were observed. The different cell counts of bronchoalveolar fluid (BALF) were analyzed. The expressions of HIF-1α and HDAC2 were detected by immunohistochemistry. The level of interleukin (IL)-8 in BALF was detected by enzyme-linked immunosorbent assay (ELISA). And the levels of HIF-1α and HDAC2 in lung homogenate were measured by Western blot. RESULTS: The ratios of eosinophil (EOS) to total cell numbers of BALF in groups A and S were significantly higher than that in group C ((8.90 ± 1.60)%, (7.52 ± 0.63)% vs (0.60 ± 0.10)%, both P < 0.01), while the ratio of neutrophile (NEU) in group S was higher than that in group A ((18.24 ± 5.19)% vs (8.46 ± 1.58)%, P < 0.01). Western blot showed that HIF-1α expressions in lung homogenate of groups A and S were significantly elevated than that in groups C (0.144 ± 0.008, 0.238 ± 0.015 vs 0.081 ± 0.005, both P < 0.01). While the HIF-1α level of group S was higher than that of group A (P < 0.01). And the expressions of HDAC2 in groups A and S significantly decreased than that in group C (0.287 ± 0.008, 0.164 ± 0.015 vs 0.452 ± 0.041, both P < 0.01). While the HDAC2 level of group S was lower than that of group A (P < 0.01). The BALF level of IL-8 in group S was higher than those in groups A and C ((42.07 ± 4.54) vs (21.66 ± 2.78), (14.33 ± 3.73) pg/ml, both P < 0.01). There were significantly negative correlations between the expressions of HIF-1α and HDAC2 (r = -0.950, P < 0.01) in lung as well as HDAC2 in lung and IL-8 (r = -0.855, P < 0.01) in BALF. CONCLUSION: Cigarette smoking aggravates the airway inflammation through a down-regulated expression of HDAC2 by activating HIF-1α.
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Asma , Fumar , Animais , Ensaio de Imunoadsorção Enzimática , Eosinófilos , Feminino , Histona Desacetilase 2 , Subunidade alfa do Fator 1 Induzível por Hipóxia , Interleucina-8 , Pulmão , Camundongos , Camundongos Endogâmicos BALB CRESUMO
BACKGROUND: Roxithromycin (RXM) has been widely used in asthma treatment; however, the mechanism has not been fully understood. The aim of our study was to investigate the underlying mechanism of RXM treatment in mediating the effect of transforming growth factor (TGF)-ß1 on airway smooth muscle cells (ASMCs) proliferation and caveolinn-1 expression. METHODS: Firstly, the rat ovalbumin (OVA) model was built according to the previous papers. Rat ASMCs were prepared and cultured, and then TGF-ß1 production in ASMCs was measured by enzyme-linked immunosorbent assay (ELISA). Moreover, the proliferation of ASMCs was determined using cell counting kit (CCK-8) assay. Additionally, the expressions of caveolin-1, phosphorylated-ERK1/2 (p-ERK1/2) and phosphorylated-AKT (p-AKT) in ASMCs treated with or without PD98059 (an ERK1/2 inhibitor), wortannin (a PI3K inhibitor), ß-cyclodextrin (ß-CD) and RXM were measured by Western blot. Finally, data were evaluated using t-test or one-way ANOVA, and then a P value < 0.05 was set as a threshold. RESULTS: Compared with normal control, TGF-ß1 secretion was significantly increased in asthmatic ASMCs; meanwhile, TGF-ß1 promoted ASMCs proliferation (P < 0.05). However, ASMCs proliferation was remarkably inhibited by RXM, ß-CD, PD98059 and wortmannin (P < 0.05). Moreover, the expressions of p-ERK1/2 and p-AKT were increased and peaked at 20 min after TGF-ß1 stimulation, and then suppressed by RXM. Further, caveolin-1 level was down-regulated by TGF-ß1 and up-regulated by inhibitors and RXM. CONCLUSION: Our findings demonstrate that RXM treatment inhibits TGF-ß1-induced activation of ERK and AKT and down-regulation of caveolin-1, which may be the potential mechanism of RXM protection from chronic inflammatory diseases, including bronchial asthma.