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1.
Appl Opt ; 59(16): 4790-4795, 2020 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-32543471

RESUMO

In this paper, the self-absorption of InGaN quantum wells at high photon density is studied based on a rectangular ridge structure. The ridge structure was fabricated based on a standard GaN-based blue LED wafer grown on (0001) patterned sapphire substrate. The high-density photons were obtained by a high-power femtosecond laser with high excitation of 42kW/cm2 at room temperature. Based on the analysis of the photoluminescence intensities of the InGaN quantum wells, we found that the absorption coefficient of the InGaN quantum wells varies with the background photon density. The results revealed that the final absorption coefficient of the InGaN quantum well decreases with the increase of photon density, which can be 48.7% lower than its normal value under our experimental conditions.

2.
J Exp Clin Cancer Res ; 39(1): 17, 2020 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-31952546

RESUMO

BACKGROUND: STAT5 plays an important role in the transformation of hematopoietic cells by BCR-ABL. However, the downstream target genes activated by STAT5 in chronic myeloid leukemia (CML) cells remain largely unclear. Here, we investigated the mechanistic functional relationship between STAT5A-regulated microRNA and CML cell apoptosis. METHODS: The expression of USP15, Caspase-6, STAT5A-regulated miR-202-5p and STAT5A was detected by qRT-PCR and Western blotting in CML cell lines and PBMCs of CML patients. Cell apoptosis was evaluated by flow cytometry. Both gain- and loss-of-function experiments were used to investigate the roles of USP15, miR-202-5p and STAT5A in CML. Luciferase reporter assay detected the effect of miR-202-5p on USP15 expression. Xenograft animal model was used to test the effect of anti-miR-202-5p and pimozide on K562 cell xenograft growth. RESULTS: USP15 expression was significantly downregulated in CML cell lines and PBMCs of CML patients. Depletion of USP15 increased, whereas overexpression of USP15 reduced the resistance of CML cells to Imatinib. Further, decreased deubiquitinating activity of USP15 by USP15 downregulation led to reduced caspase-6 level, thus attenuating CML cell apoptosis. Mechanistically, miR-202-5p was upregulated in K562G cells and negatively regulated USP15 expression by directly targeting USP15 3'-UTR. Correspondingly, upregulation of miR-202-5p enhanced the resistance of CML cells to Imatinib by inhibiting cell apoptosis. Importantly, STAT5A was upregulated in CML cells and directly activated miR-202-5p transcription by binding to the pre-miR-202 promoter. Pimozide induced CML cell apoptosis and significantly reduced K562 cell xenograft growth in vivo by blocking STAT5A/miR-202-5p/USP15/Caspase-6 regulatory axis. CONCLUSIONS: we provide the first evidence that de-regulated STAT5A/miR-202-5p/USP15/Caspase-6 regulatory axis suppresses the apoptosis of CML cells, targeting this pathway might be a promising therapeutic approach for the treatment of CML.


Assuntos
Caspase 6/metabolismo , Mesilato de Imatinib/farmacologia , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Leucemia Mielogênica Crônica BCR-ABL Positiva/metabolismo , MicroRNAs/metabolismo , Fator de Transcrição STAT5/metabolismo , Proteínas Supressoras de Tumor/metabolismo , Proteases Específicas de Ubiquitina/metabolismo , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Estudos de Casos e Controles , Regulação para Baixo , Resistencia a Medicamentos Antineoplásicos , Humanos , Células K562 , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Leucemia Mielogênica Crônica BCR-ABL Positiva/patologia , Transdução de Sinais , Proteases Específicas de Ubiquitina/biossíntese
3.
Biosci Rep ; 39(4)2019 04 30.
Artigo em Inglês | MEDLINE | ID: mdl-30962263

RESUMO

microRNAs (miRNA), as tumor suppressors or oncogenes, are involved in modulating cancer cell behavior, including cell proliferation and apoptosis. The miR-140-5p acts as a tumor suppressor in several tumors, but the role of miR-140-5p in chronic myeloid leukemia (CML) remains unclear. Here, we investigated the suppression of miR-140-5p in CML patients and CML cell lines using quantitative PCR (qPCR) and fluorescence in situ hybridization (FISH). Overexpression miR-140-5p in CML cells significantly inhibited cell proliferation as revealed by the CCK-8 assay and promoted cell apoptosis as revealed by flow cytometry. Moreover, the sine oculis homeobox 1 (SIX1) gene had been confirmed as a direct target of miR-140-5p using bioinformatics analysis and luciferase reporter assays. Overexpression of miR-140-5p decreased the SIX1 protein level in CML cells. SIX1 mRNA and protein levels were significantly up-regulated in CML patients and CML cell lines. Knockdown of SIX1 expression significantly inhibited CML cell proliferation and promoted cell apoptosis. Furthermore, SIX1 as a transcriptional factor positively regulated pyruvate kinase isozyme type M2 (PKM2) expression and played an important role in the Warburg effect. In addition, these findings indicated that miR-140-5p functions as a tumor suppressor and plays a critical role in CML cell apoptosis and metabolism by targeting SIX1. Moreover, the miR-140-5p/SIX1 axis may be a potential therapeutic target in CML.


Assuntos
Proteínas de Homeodomínio/genética , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Leucemia Mielogênica Crônica BCR-ABL Positiva/patologia , MicroRNAs/genética , Adulto , Idoso , Apoptose/genética , Proteínas de Transporte/genética , Proteínas de Transporte/metabolismo , Linhagem Celular Tumoral , Feminino , Regulação Leucêmica da Expressão Gênica , Humanos , Células K562 , Leucócitos Mononucleares/patologia , Leucócitos Mononucleares/fisiologia , Masculino , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , MicroRNAs/metabolismo , Pessoa de Meia-Idade , Hormônios Tireóideos/genética , Hormônios Tireóideos/metabolismo
4.
Fitoterapia ; 129: 179-184, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29981396

RESUMO

The fruits of Swietenia macrophylla (skyfruits) are commercially used as healthcare products to improve blood circulation. An investigation of active ingredients of skyfruits led to the isolation of four new limonoids, swietemacrolides A-D (1-4), together with ten known limonoids (5-14) and one proto-limonoid (15). Their structures were elucidated on the basis of MS and NMR data analysis. Swietemacrolide C (3) at the concentration of 10 µM showed significant protective effect on H2O2-induced apoptosis in human umbilical vascular endothelial cells (HUVECs), while swieteliacate D (5) displayed moderate anti-apoptotic activity.


Assuntos
Apoptose/efeitos dos fármacos , Frutas/química , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Limoninas/farmacologia , Meliaceae/química , Humanos , Peróxido de Hidrogênio , Limoninas/isolamento & purificação , Melanesia , Estrutura Molecular
5.
Front Physiol ; 9: 1817, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30618827

RESUMO

In smokers with chronic obstructive pulmonary disease, more severe lung inflammation is associated with menthol cigarette smoking compared to non-menthol cigarette smoking. However, the mechanisms remain unclear. Menthol is an activator of transient receptor potential melastatin-8 (TRPM8), which is also sensitive to reactive oxygen species (ROS). Our recent in vitro study demonstrated that the extracts of menthol cigarette smoke (M-CS) can induce greater ROS-sensitive, TRPM8-mediated, mitogen-activated protein kinase (MAPK)-dependent inflammatory responses in lung epithelial cells than the extracts of non-menthol cigarette smoke (Non-M-CS) can. In this study, we tested the hypothesis that M-CS can induce more severe lung inflammation than Non-M-CS can via the additional action of menthol in M-CS on epithelial and lung TRPM8 in mice. Compared with Non-M-CS exposure, subchronic M-CS exposure for 7 days up-regulated the epithelial and lung expression of TRPM8, induced more vigorous activation of epithelial and lung MAPKs, and caused more severe lung inflammation. The MAPK activation was evidenced by the increased expression of phosphor-extracellular signal-regulated and phosphor-c-Jun N-terminal kinases. The lung inflammation was evidenced by pathohistological findings and increases in several inflammatory indices. Moreover, treatment with a TRPM8 antagonist (N-(3-aminopropyl)-2-{[(3-methylphenyl)methyl]oxy}-N-(2-thienylmethyl)benzamide; AMTB) greatly suppressed the MAPK activation and lung inflammation induced by Non-M-CS and M-CS, and the residual responses to these two types of CS did not differ. Conversely, the levels of biomarkers of acute CS exposure (20 min), including carboxyhemoglobin and cotinine (a nicotine metabolite) in blood plasma, and superoxide and hydrogen peroxide (two major types of ROS) in bronchoalveolar lavage fluid, did not show significant differences in the mice with Non-M-CS and M-CS exposure. We concluded that M-CS could induce greater TRPM8-mediated activation of MAPKs and lung inflammation than Non-M-CS could in mice with subchronic exposure. The augmented inflammatory effects of M-CS are unlikely due to a larger total amount of CS inhaled, but may be caused by an additional stimulation of epithelial and lung TRPM8 by menthol in M-CS. A common stimulant (presumably ROS) generated by both CS types may also stimulate TRPM8, activate MAPKs, and induce lung inflammation because treatment with AMTB could reduce these responses to Non-M-CS.

6.
Front Physiol ; 8: 263, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28496415

RESUMO

Clinical studies suggest that smokers with chronic obstructive pulmonary disease who use menthol cigarettes may display more severe lung inflammation than those who smoke non-menthol cigarette. However, the mechanisms for this difference remain unclear. Menthol is a ligand of transient receptor potential melastatin-8 (TRPM8), a Ca2+-permeant channel sensitive to reactive oxygen species (ROS). We previously reported that exposure of human bronchial epithelial cells (HBECs) to non-menthol cigarette smoke extract (Non-M-CSE) triggers a cascade of inflammatory signaling leading to IL-8 induction. In this study, we used this in vitro model to compare the inflammatory effects of menthol cigarette smoke extract (M-CSE) and Non-M-CSE and delineate the mechanisms underlying the differences in their impacts. Compared with Non-M-CSE, M-CSE initially increased a similar level of extracellular ROS, suggesting the equivalent oxidant potency. However, M-CSE subsequently produced more remarkable elevations in intracellular Ca2+, activation of the mitogen-activated protein kinases (MAPKs)/nuclear factor-κB (NF-κB) signaling, and IL-8 induction. The extracellular ROS responses to both CSE types were totally inhibited by N-acetyl-cysteine (NAC; a ROS scavenger). The intracellular Ca2+ responses to both CSE types were also totally prevented by NAC, AMTB (a TRPM8 antagonist), or EGTA (an extracellular Ca2+ chelator). The activation of the MAPK/NF-κB signaling and induction of IL-8 to both CSE types were suppressed to similar levels by NAC, AMTB, or EGTA. These results suggest that, in addition to ROS generated by both CSE types, the menthol in M-CSE may act as another stimulus to further activate TRPM8 and induce the observed responses. We also found that menthol combined with Non-M-CSE induced greater responses of intracellular Ca2+ and IL-8 compared with Non-M-CSE alone. Moreover, we confirmed the essential role of TRPM8 in these responses to Non-M-CSE or M-CSE and the difference in these responses between the both CSE types using HBECs with TRPM8 knockdown and TRPM8 knockout, and using HEK293 cells transfected with hTRPM8. Thus, compared with exposure to Non-M-CSE, exposure to M-CSE induced greater TRPM8-mediated inflammatory responses in HBECs. These augmented effects may be due to a double-hit on lung epithelial TRPM8 by ROS generated from CSE and the menthol in M-CSE.

7.
Front Physiol ; 8: 193, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28408888

RESUMO

Pulmonary fibrosis is a severe and progressive disease that is characterized by an abnormal deposition of extracellular matrix, such as collagens. The pathogenesis of this disease may be initiated by oxidative damage of lung epithelial cells by fibrogenic stimuli, leading to lung inflammation, which in turn promotes various lung fibrotic responses. The profibrogenic effect of transforming growth factor-ß1 (TGF-ß1) on lung fibroblasts is crucial for the pathogenesis of this disease. Paeonol, the main phenolic compound present in the Chinese herb Paeonia suffruticosa, has antioxidant and anti-inflammatory properties. However, whether paeonol has therapeutic effects against pulmonary fibrosis remains unclear. Using a murine model, we showed that 21 days after the insult, intratracheal bleomycin caused pulmonary inflammation and fibrosis, as evidenced by lung histopathological manifestations and increase in various indices. The inflammatory indices included an increase in total cell count, differential cell count, and total protein concentration in bronchoalveolar lavage fluid. The fibrotic indices included an increase in lung levels of TGF-ß1, total collagen, type 1α1 collagen (COL1A1), and α-smooth muscle actin (α-SMA; a marker of myofibroblasts). Bleomycin also was found to cause an increase in oxidative stress as reflected by increased levels of malondialdehyde and 4-hydroxynonenal in the lungs. Importantly, all these pathophysiological events were suppressed by daily treatment with paeonol. Using human lung fibroblasts, we further demonstrated that exposure of human lung fibroblasts to TGF-ß1 increased productions of α-SMA and COL1A1, both of which were inhibited by inhibitors of Jun N-terminal kinase (JNK), p38, and Smad3. JNK and p38 are two subfamily members of mitogen-activated protein kinases (MAPKs), whereas Smad3 is a transcription factor. TGF-ß1 exposure also increased the phosphorylation of JNK, p38, and Smad3 prior to the induction of α-SMA and COL1A1. Notably, all these TGF-ß1-induced cellular events were suppressed by paeonol treatment. Our findings suggest that paeonol has antioxidant, anti-inflammatory, and anti-fibrotic functions against bleomycin-induced pulmonary fibrosis in mice. The beneficial effect of paeonol may be, at least in part, mediated through the inhibition of the MAPKs/Smad3 signaling.

8.
Sci Rep ; 7: 39720, 2017 01 03.
Artigo em Inglês | MEDLINE | ID: mdl-28045089

RESUMO

We study theoretically the bio-sensing capabilities of metal nanowire surface plasmons. As a specific example, we couple the nanowire to specific sites (bacteriochlorophyll) of the Fenna-Matthews-Olson (FMO) photosynthetic pigment protein complex. In this hybrid system, we find that when certain sites of the FMO complex are subject to either the suppression of inter-site transitions or are entirely disconnected from the complex, the resulting variations in the excitation transfer rates through the complex can be monitored through the corresponding changes in the scattering spectra of the incident nanowire surface plasmons. We also find that these changes can be further enhanced by changing the ratio of plasmon-site couplings. The change of the Fano lineshape in the scattering spectra further reveals that "site 5" in the FMO complex plays a distinct role from other sites. Our results provide a feasible way, using single photons, to detect mutation-induced, or bleaching-induced, local defects or modifications of the FMO complex, and allows access to both the local and global properties of the excitation transfer in such systems.


Assuntos
Proteínas de Bactérias/química , Técnicas Biossensoriais/métodos , Complexos de Proteínas Captadores de Luz/química , Ressonância de Plasmônio de Superfície/métodos , Proteínas de Bactérias/genética , Transferência de Energia , Complexos de Proteínas Captadores de Luz/genética , Metais/química , Modelos Teóricos , Nanoestruturas/química
9.
Mediators Inflamm ; 2015: 148367, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26504357

RESUMO

The mechanism underlying the inflammatory role of TRPA1 in lung epithelial cells (LECs) remains unclear. Here, we show that cigarette smoke extract (CSE) sequentially induced several events in LECs. The Ca(2+) influx was prevented by decreasing extracellular reactive oxygen species (ROS) with the scavenger N-acetyl-cysteine, removing extracellular Ca(2+) with the chelator EGTA, or treating with the TRPA1 antagonist HC030031. NADPH oxidase activation was abolished by its inhibitor apocynin, EGTA, or HC030031. The increased intracellular ROS was halted by apocynin, N-acetyl-cysteine, or HC030031. The activation of the MAPKs/NF-κB signaling was suppressed by EGTA, N-acetyl-cysteine, or HC030031. IL-8 induction was inhibited by HC030031 or TRPA1 siRNA. Additionally, chronic cigarette smoke (CS) exposure in wild-type mice induced TRPA1 expression in LECs and lung tissues. In CS-exposure trpa1 (-/-) mice, the increased BALF level of ROS was similar to that of CS-exposure wild-type mice; yet lung inflammation was lessened. Thus, in LECs, CSE may initially increase extracellular ROS, which activate TRPA1 leading to an increase in Ca(2+) influx. The increased intracellular Ca(2+) contributes to activation of NADPH oxidase, resulting in increased intracellular ROS, which activate the MAPKs/NF-κB signaling leading to IL-8 induction. This mechanism may possibly be at work in mice chronically exposed to CS.


Assuntos
Canais de Cálcio/metabolismo , Cálcio/metabolismo , Pulmão/patologia , Proteínas do Tecido Nervoso/metabolismo , Fumaça/efeitos adversos , Canais de Receptores Transientes de Potencial/metabolismo , Acetanilidas/química , Acetofenonas/química , Animais , Biomarcadores/metabolismo , Líquido da Lavagem Broncoalveolar , Canais de Cálcio/genética , Quelantes/química , Quimiocina CXCL2/metabolismo , Ácido Egtázico/química , Ativação Enzimática , Regulação Neoplásica da Expressão Gênica , Humanos , Inflamação , Interleucina-8/metabolismo , Sistema de Sinalização das MAP Quinases , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , NADPH Oxidases/metabolismo , Proteínas do Tecido Nervoso/genética , Estresse Oxidativo , Purinas/química , RNA Interferente Pequeno/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Canal de Cátion TRPA1 , Canais de Receptores Transientes de Potencial/genética
10.
Appl Biochem Biotechnol ; 176(5): 1335-50, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26041055

RESUMO

Due to its systemic arginine degradation, arginine deiminase (ADI) has attracted attentions as an anti-tumor drug. Its low activity at physiological conditions among other limitations has necessitated its engineering for improved properties. The present study describes the hydrophobic mutagenesis and semi-rational engineering of ADI from Pseudomonas plecoglossicida (PpADI). Using an improved ADI variant M13 (D38H/A128T/E296K/H404R/I410L) as parent, site saturation mutagenesis at position 162 resulted in an over 20 % increase in protein solubility. Compared with M13 (15.23 U/mg), mutants M13-2 (M13+S245D) and M13-5 (M13+R243L) exhibited enhanced specific activity of 21.19 and 31.20 U/mg at physiological conditions. M13-5 displayed enhanced substrate specificity with a dramatic reduction in its K m value (from 0.52 to 0.16 mM). It is speculated that the improvements in M13-5 could mainly be attributed to the enhanced structural stability due to an R243L substitution. The hydrophobic contribution of Leu 243 was supported by mutant M13-9 (M13+A276W) generated based on the hydrophobic mutagenesis concept. M13-9 showed a specific activity of 18.68 U/mg, as well as remarkable thermal and pH stability. It retained over 90 % activity over pH range from 4.5 to 8.5. At 60 °C, the half-life of M13-9 was enhanced from 4 to 17.5 min in comparison with M13, and its specific activity at 62 °C (93.0 U/mg) was approximately fivefold of that determined at 37 °C. Our results suggest that the increased hydrophobicity around the active regions of PpADI might be crucial in improving its structural stability and ultimately catalytic efficiency.


Assuntos
Biocatálise , Hidrolases/metabolismo , Interações Hidrofóbicas e Hidrofílicas , Mutagênese , Engenharia de Proteínas/métodos , Rotação , Sequência de Aminoácidos , Eletroforese em Gel de Poliacrilamida , Estabilidade Enzimática , Ligação de Hidrogênio , Concentração de Íons de Hidrogênio , Hidrolases/química , Cinética , Modelos Moleculares , Dados de Sequência Molecular , Proteínas Mutantes/química , Proteínas Mutantes/metabolismo , Pseudomonas/enzimologia , Alinhamento de Sequência , Solubilidade , Temperatura
11.
J Cell Physiol ; 230(8): 1781-93, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25503516

RESUMO

Inhaled cigarette smoke (CS) causes persistent lung inflammation in smokers. Interleukin 8 (IL-8) released from macrophages is a key chemokine during initiation and progression of CS-induced lung inflammation, yet its regulation is largely unknown. AMP-activated protein kinase (AMPK), a crucial energy homeostasis regulator, may modulate inflammation. Here we report that CS extract (CSE) increased the level of intracellular reactive oxygen species (ROS), activating AMPK, mitogen-activated protein kinases (MAPKs), and NF-κB, as well as inducing IL-8, in human macrophages. N-acetyl-cysteine (ROS scavenger) or hexamethonium [nicotinic acetylcholine receptor (nAChR) antagonist] attenuated the CSE-induced increase in intracellular ROS, activation of AMPK and NF-κB, as well as IL-8 induction, which suggests that nAChRs and ROS are important. Prevention of AMPK activation by compound C or AMPK siRNA reduced CSE-induced IL-8 production, confirming the role of AMPK. Compound C or AMPK siRNA also inhibited the activation of MAPKs and NF-κB by CSE, which suggests that these molecules are downstream of AMPK. Additionally, exposure of human macrophages to nicotine activated AMPK and induced IL-8 and that these effects were lessened by hexamethonium or compound C, implying that nicotine in CS may be causative. Furthermore, chronic CS exposure in mice promoted AMPK phosphorylation and expression of MIP-2 (an IL-8 homolog) in infiltrated macrophages and in lung tissues, as well as induced lung inflammation, all of which were reduced by compound C treatment. Thus, we identified a novel nAChRs-dependent, ROS-sensitive, AMPK/MAPKs/NF-κB signaling pathway, which seems to be important to CS-induced macrophage IL-8 production and possibly to lung inflammation.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Interleucina-8/biossíntese , Macrófagos/metabolismo , Transdução de Sinais/efeitos dos fármacos , Fumaça/efeitos adversos , Produtos do Tabaco/efeitos adversos , Animais , Western Blotting , Linhagem Celular , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Humanos , Imuno-Histoquímica , Camundongos , NF-kappa B/metabolismo , Pneumonia/metabolismo , RNA Interferente Pequeno , Espécies Reativas de Oxigênio/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transfecção
12.
Front Physiol ; 5: 440, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25452730

RESUMO

Cigarette smoking causes chronic lung inflammation that is mainly regulated by redox-sensitive pathways. Our previous studies have demonstrated that cigarette smoke (CS) activates reactive oxygen species (ROS)-sensitive mitogen-activated protein kinases (MAPKs)/nuclear factor-κB (NF-κB) signaling resulting in induction of lung inflammation. Eicosapentaenoic acid (EPA), a major type of omega-3 polyunsaturated fatty acid, is present in significant amounts in marine-based fish and fish oil. EPA has been shown to possess antioxidant and anti-inflammatory properties in vitro and in vivo. However, whether EPA has similar beneficial effects against CS-induced lung inflammation remains unclear. Using a murine model, we show that subchronic CS exposure for 4 weeks caused pulmonary inflammatory infiltration (total cell count in bronchoalveolar lavage fluid (BALF), 11.0-fold increase), increased lung vascular permeability (protein level in BALF, 3.1-fold increase), elevated levels of chemokines (11.4-38.2-fold increase) and malondialdehyde (an oxidative stress biomarker; 2.0-fold increase) in the lungs, as well as lung inflammation; all of these CS-induced events were suppressed by daily supplementation with EPA. Using human bronchial epithelial cells, we further show that CS extract (CSE) sequentially activated NADPH oxidase (NADPH oxidase activity, 1.9-fold increase), increased intracellular levels of ROS (3.0-fold increase), activated both MAPKs and NF-κB, and induced interleukin-8 (IL-8; 8.2-fold increase); all these CSE-induced events were inhibited by pretreatment with EPA. Our findings suggest a novel role for EPA in alleviating the oxidative stress and lung inflammation induced by subchronic CS exposure in vivo and in suppressing the CSE-induced IL-8 in vitro via its antioxidant function and by inhibiting MAPKs/NF-κB signaling.

13.
Mediators Inflamm ; 2014: 651890, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25165413

RESUMO

Cigarette smoking causes persistent lung inflammation that is mainly regulated by redox-sensitive pathways. We have previously reported that cigarette smoke (CS) activates reactive oxygen species- (ROS-) sensitive mitogen-activated protein kinases (MAPKs)/nuclear factor-κB (NF-κB) signaling leading to induction of lung inflammation. Paeonol, the main phenolic compound present in the Chinese herb Paeonia suffruticosa, has antioxidant and anti-inflammatory properties. However, whether paeonol has similar beneficial effects against CS-induced lung inflammation remains unclear. Using a murine model, we showed that chronic CS exposure for 4 weeks caused pulmonary inflammatory infiltration, increased lung vascular permeability, elevated lung levels of chemokines, cytokines, and 4-hydroxynonenal (an oxidative stress biomarker), and induced lung inflammation; all of these CS-induced events were suppressed by chronic treatment with paeonol. Using human bronchial epithelial cells (HBECs), we demonstrated that cigarette smoke extract (CSE) sequentially increased extracellular and intracellular levels of ROS, activated the MAPKs/NF-κB signaling, and induced interleukin-8 (IL-8); all these CSE-induced events were inhibited by paeonol pretreatment. Our findings suggest a novel role for paeonol in alleviating the oxidative stress and lung inflammation induced by chronic CS exposure in vivo and in suppressing CSE-induced IL-8 in vitro via its antioxidant function and an inhibition of the MAPKs/NF-κB signaling.


Assuntos
Acetofenonas/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Pneumonia/induzido quimicamente , Pneumonia/tratamento farmacológico , Espécies Reativas de Oxigênio/metabolismo , Fumar/efeitos adversos , Animais , Western Blotting , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Transdução de Sinais/efeitos dos fármacos
14.
Free Radic Biol Med ; 69: 208-18, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24486342

RESUMO

Cigarette smoking causes persistent lung inflammation that is mainly regulated by redox-sensitive pathways. We have reported that cigarette smoke (CS) activates a NADPH oxidase-dependent reactive oxygen species (ROS)-sensitive AMP-activated protein kinase (AMPK) signaling pathway leading to induction of lung inflammation. Glucosamine, a dietary supplement used to treat osteoarthritis, has antioxidant and anti-inflammatory properties. However, whether glucosamine has similar beneficial effects against CS-induced lung inflammation remains unclear. Using a murine model we show that chronic CS exposure for 4 weeks increased lung levels of 4-hydroxynonenal (an oxidative stress biomarker), phospho-AMPK, and macrophage inflammatory protein 2 and induced lung inflammation; all of these CS-induced events were suppressed by chronic treatment with glucosamine. Using human bronchial epithelial cells, we demonstrate that cigarette smoke extract (CSE) sequentially activated NADPH oxidase; increased intracellular levels of ROS; activated AMPK, mitogen-activated protein kinases (MAPKs), nuclear factor-κB (NF-κB), and signal transducer and activator of transcription proteins 3 (STAT3); and induced interleukin-8 (IL-8). Additionally, using a ROS scavenger, a siRNA that targets AMPK, and various pharmacological inhibitors, we identified the signaling cascade that leads to induction of IL-8 by CSE. All these CSE-induced events were inhibited by glucosamine pretreatment. Our findings suggest a novel role for glucosamine in alleviating the oxidative stress and lung inflammation induced by chronic CS exposure in vivo and in suppressing the CSE-induced IL-8 in vitro by inhibiting both the ROS-sensitive NADPH oxidase/AMPK/MAPK signaling pathway and the downstream transcriptional factors NF-κB and STAT3.


Assuntos
Anti-Inflamatórios/administração & dosagem , Glucosamina/administração & dosagem , Pneumonia/tratamento farmacológico , Fumar/efeitos adversos , Proteínas Quinases Ativadas por AMP/biossíntese , Animais , Células Cultivadas , Humanos , Camundongos , Estresse Oxidativo/efeitos dos fármacos , Pneumonia/induzido quimicamente , Pneumonia/patologia , Espécies Reativas de Oxigênio/antagonistas & inibidores , Fator de Transcrição STAT3/biossíntese , Transdução de Sinais/efeitos dos fármacos
15.
Opt Express ; 18(9): 8759-66, 2010 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-20588719

RESUMO

Five cell parameters of a twisted nematic liquid crystal device (TNLCD), namely, cell gap, pretilt angle, twisted angle, rubbing angle, and phase retardation are precisely measured by the developed amplitude-sensitive heterodyne polarimeter (ASHP) simultaneously integrated with Yeh and Gu's transfer matrix and Lien's transfer matrix. This proposed method can characterize the five cell parameters under the arrangement of a single wavelength at normal incidence. In contrast to the conventional methods on cell parameter detection either by adopting a multiple wavelength laser beam at normal incidence or by using a single wavelength laser beam under oblique incident to TNLCD, this method presents the advantage of not only having a simple setup but also the possibility to measure simultaneously five cell parameters on the characterization of TNLCD at high speed.

16.
Appl Opt ; 48(9): 1628-34, 2009 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-19305458

RESUMO

To be compared with the wavelength modulation technique for measuring two-dimensional (2D) cell parameters of a twisted nematic liquid crystal (TN-LC), we propose an amplitude-sensitive heterodyne ellipsometer (ASHE) of a single wavelength that is able to characterize TN-LC in 2D quantitatively. A quarter-wave plate (QWP) is rotated continuously in this setup to modulate the polarization state of the incident laser beam to obtain the amplitude ratio of the S and P waves versus the rotation angle of the QWP. Thus the cell parameters, including the twisted angle Phi, untwisted phase retardation Gamma, rubbing direction angle alpha, and cell gap d, of a TN-LC cell are obtained simultaneously by best fitting the detected amplitude ratio with a prediction based on the transfer matrix of TN-LC cell. 2D distributions of (Phi,Gamma,alpha,d) are then obtained either by scanning the TN-LC cell or by using a CCD camera for high-speed measurement. In this experiment, the stability of the amplitude-ratio measurement of the proposed ASHE was 0.5%. The goal is to integrate the rotating elliptical wave plate with the TN-LC cell in a heterodyne ellipsometer to obtain cell parameters at amplitude sensitivity. This increases not only the sensitivity of the measurement but also the possibility of extending the 2D distribution of cell parameters in real time.


Assuntos
Interferometria/instrumentação , Cristais Líquidos , Desenho de Equipamento , Modelos Teóricos
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