RESUMO
Probiotics can ferment nondigestible carbohydrates and produce short-chain fatty acids (SCFA; acetate, propionate, and butyrate) in the human colon. In this study, the levels of SCFA were determined in the following yogurts fermented with different combinations of probiotics: (1) cocultures of Streptococcus thermophilus and Lactobacillus bulgaricus (control, C); (2) S. thermophilus, L. bulgaricus, and Bifidobacterium bifidum (C-Bb); (3) S. thermophilus, L. bulgaricus, and Lactobacillus acidophilus (C-La); and (4) S. thermophilus, L. bulgaricus, and Lactobacillus gasseri (C-Lg). Results showed that the acetate levels were significantly higher in C-Bb, C-La, and C-Lg yogurts than in C yogurt. Fermentation and physicochemical characteristics of all yogurts were identical. Treatment of mucus-secreting colon epithelial cells (HT29-MTX) with C-Bb, C-La, and C-Lg yogurt supernatants resulted in an increase in the expression of MUC2 and CDX2 and the production of mucin proteins. The adhesion of probiotics onto HT29-MTX cells increased following treatment with C-Bb, C-La, and C-Lg yogurt supernatants. Our data suggest that a yogurt diet rich in acetate improves the protective function of the intestinal epithelium.
Assuntos
Probióticos , Iogurte , Animais , Colo , Células Epiteliais , Ácidos Graxos Voláteis , Fermentação , Humanos , Mucinas , Streptococcus thermophilusRESUMO
BACKGROUND: Patients with chronic granulomatous disease (CGD), whom inherit abnormal function of NADPH oxidase 2 (Nox2), suffer from hyperinflammatory responses in lung as well as bacterial and fungal infection. There have been studies to reveal the function of Nox2 in hyperinflammatory diseases, especially in asthma, but the exact role of Nox2 in asthma is still unclear and controversial. Therefore, we attempted to clarify the exact role of Nox2 in asthma, using various experimental asthma models. METHODS: Asthma phenotypes were analyzed in response to various allergen-induced experimental asthma using Nox2-deficient mice and recombinase gene-activating-1-deficient mice. To understand the underlying mechanisms of exaggerated Th2 effector functions, we investigated the degree of T-cell activation, levels of activation-induced cell death (AICD), and regulatory T (Treg)-cell differentiation in Nox2-deficient T cells. RESULTS: Asthma phenotypes were increased through enhanced Th2 differentiation and function in Nox2-null mice regardless of dose and route of various allergens. Nox2-deficient T cells also showed hyperactivation, reduced AICD, and diminished Treg-cell differentiation through increased AKT phosphorylation (T308/S473) and enhanced mitochondrial ROS production. CONCLUSION: Our findings indicate that Nox2 deficiency results in exaggerated experimental asthma, which is caused by enhanced Th2 effector function in a T-cell-intrinsic manner.
Assuntos
Diferenciação Celular/genética , Diferenciação Celular/imunologia , NADPH Oxidase 2/deficiência , Células Th2/citologia , Células Th2/fisiologia , Alérgenos/imunologia , Animais , Asma/diagnóstico , Asma/genética , Asma/imunologia , Asma/metabolismo , Citocinas/metabolismo , Modelos Animais de Doenças , Progressão da Doença , Doença Granulomatosa Crônica/diagnóstico , Doença Granulomatosa Crônica/genética , Doença Granulomatosa Crônica/imunologia , Doença Granulomatosa Crônica/metabolismo , Pulmão/imunologia , Pulmão/metabolismo , Pulmão/patologia , Ativação Linfocitária/genética , Ativação Linfocitária/imunologia , Camundongos , Camundongos Knockout , Fenótipo , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/metabolismoRESUMO
We investigated the temperature-dependent locomotion of Caenorhabditis elegans by using the mobile phone-based microscope. We developed the customized imaging system with mini incubator and smartphone to effectively control the thermal stimulation for precisely observing the temperature-dependent locomotory behaviours of C. elegans. Using the mobile phone-based microscope, we successfully followed the long-term progress of specimens of C. elegans in real time as they hatched and explored their temperature-dependent locomotory behaviour. We are convinced that the mobile phone-based microscope is a useful device for real time and long-term observations of biological samples during incubation, and can make it possible to carry out live observations via wireless communications regardless of location. In addition, this microscope has the potential for widespread use owing to its low cost and compact design.
Assuntos
Caenorhabditis elegans/fisiologia , Caenorhabditis elegans/efeitos da radiação , Telefone Celular , Locomoção , Imagem Óptica/métodos , Tecnologia de Sensoriamento Remoto/métodos , Animais , TemperaturaRESUMO
The (TMP-HT)2Ir(acac) was synthesized with 2-bromo-4-(trifluoromethyl)pyridine and 5-hexyl-2-thiopheneboronic acid pinacol ester for organic light-emitting diodes (OLEDs). This material was designed on the basis of Gaussian modeling program results. The ligands have both the electron donor and acceptor in a molecule. There are pyridyl group which decrease electron density and thiophene group which increase electron density. Therefore, it showed intramolecular charge transfer (ICT) property. For solution process, the ligand have a alkyl group which has hydrophobic property. The (TMP-HT)21r(acac) was synthesized by Suzuki coupling reaction and Nonoyama reaction. The (TMP-HT)21r(acac) emitted at approximately 600 nm. The device structures were ITO/PEDOT (500 Å)/TFB (170 Å)/PVK:PBD (40%): (TMPHT)21r(acac) (300 Å:10%)/BH:BD5% (150 Å)/L201(50 Å)/Liq(200 Å)/Al. Electroluminescent properties were observed with devices doped with various doping concentrations.
Assuntos
Irídio/química , Dimerização , Ligantes , Soluções , Espectrofotometria UltravioletaRESUMO
Poly(styrene-b-2-vinyl pyridine) (PS-b-P2VP) lamellar film which is hydrophobic block-hydrophilic polyelectrolyte block polymer of 52 kg/mol-b-57 kg/mol and PS-b-P2VP film with reactive monomer (RM257) were prepared for photonic gel films. The lamellar stacks, which is alternating layer of hydrophilic and hydrophobic moiety of PS-b-P2VP, were obtained by exposing the spin coated film under chloroform vapor. The lamellar films were quaternized with 5 wt% of iodomethane diluted by n-hexane. We reported about the influence of reactive monomer on those photonic gel films. Added reactive monomer photonic gel film had higher absorbance than pure photonic gel films. As a result the photonic gel film with RM had more clear color. The lamellar films were swollen by DI water, ethanol (aq) and calcium carbonate solution. The band gaps of the lamellar films were drastically shifted to longer wavelength swollen by calcium carbonate solution. And the lamellar films were shifted to shorter wave length swollen by ethanol. So each lamellar film showed different color.
Assuntos
Poliestirenos/química , Polivinil/química , Piridinas/química , Microscopia Eletrônica de Varredura , Espectrofotometria UltravioletaRESUMO
BACKGROUND: This phase 1 trial utilising a Bayesian continual reassessment method evaluated bortezomib and sunitinib to determine the maximum tolerated dose (MTD), dose-limiting toxicities (DLT), and recommended doses of the combination. METHODS: Patients with advanced solid organ malignancies were enrolled and received bortezomib weekly with sunitinib daily for 4 weeks, every 6 weeks. Initial doses were sunitinib 25 mg and bortezomib 1 mg m(-2). Cohort size and dose level estimation was performed utilising the Escalation with Overdose Control (EWOC) adaptive method. Seven dose levels were evaluated; initially, sunitinib was increased to a goal dose of 50 mg with fixed bortezomib, then bortezomib was increased. Efficacy assessment occurred after each cycle using RECIST criteria. RESULTS: Thirty patients were evaluable. During sunitinib escalation, DLTs of grade 4 thrombocytopenia (14%) and neutropenia (6%) at sunitinib 50 mg and bortezomib 1.3 mg m(-2) were seen. Subsequent experience showed tolerability and activity for sunitinib 37.5 mg and bortezomib 1.9 mg m(-2). Common grade 3/4 toxicities were neutropenia, thrombocytopenia, hypertension, and diarrhoea. The recommended doses for further study are bortezomib 1.9 mg m(-2) and sunitinib 37.5 mg. Four partial responses were seen. Stable disease >6 months was noted in an additional six patients. CONCLUSION: Bortezomib and sunitinib are well tolerated and have anticancer activity, particularly in thyroid cancer. A phase 2 study of this combination in thyroid cancer patients is planned.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Ácidos Borônicos/administração & dosagem , Indóis/administração & dosagem , Pirazinas/administração & dosagem , Pirróis/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Teorema de Bayes , Bortezomib , Esquema de Medicação , Feminino , Humanos , Masculino , Dose Máxima Tolerável , Pessoa de Meia-Idade , Neoplasias/tratamento farmacológico , Sunitinibe , Neoplasias da Glândula Tireoide/tratamento farmacológicoRESUMO
OBJECTIVE: Serum gamma-glutamyl transferase (GGT), an indicator of oxidative stress and/or a chronic inflammatory process, is associated with the levels of leukotrienes and other inflammatory mediators that play a critical role in the pathogenesis of asthma. This study aimed at investigating whether apparently healthy subjects with higher serum GGT levels at a national health check-up are at an increased risk of developing asthma in the near future. PATIENTS AND METHODS: We analyzed 564,213 Korean adults, aged 20-80 years who underwent a national general health examination, including measurement of baseline serum GGT between 2003 and 2015, using data from a large-scale representative cohort of the Korean population. Data were analyzed using a Cox proportional hazards regression analysis. RESULTS: In total, 516,956 participants were included in the final analysis. During the mean follow-up period of 8 years (standard deviation, 4.0), 7,439 incident asthma events occurred. We then classified the male and female participants according to quartiles of blood GGT levels (males: ≤ 20, 21-30, 31-51, and ≥ 52 IU/L; females: ≤ 12, 13-16, 17-22, and ≥ 23 IU/L, respectively). The adjusted hazard ratio (aHR) for incident asthma was significantly greater for subjects in the highest GGT quartile than for those in the lowest GGT quartile (aHR, 1.47; 95% confidence intervals, 1.36-1.59). Further, there was a significant linear trend across quartiles with regard to asthma (ptrend<0.001). We estimated the optimal cut-off values (using the minimum p-value approach) as 35 IU/L for the total population, 35 IU/L for males, and 36 IU/L for females, respectively. CONCLUSIONS: Clinicians should be aware of the risk of incident asthma in healthy subjects with elevated GGT levels. Our findings advance our understanding of asthma pathogenesis.
Assuntos
Asma , gama-Glutamiltransferase/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Povo Asiático , Asma/epidemiologia , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , República da Coreia/epidemiologia , Fatores de Risco , Adulto JovemRESUMO
A retroviral vector containing the wild-type p53 gene under control of a beta-actin promoter was produced to mediate transfer of wild-type p53 into human non-small cell lung cancers by direct injection. Nine patients whose conventional treatments failed were entered into the study. No clinically significant vector-related toxic effects were noted up to five months after treatment. In situ hybridization and DNA polymerase chain reaction showed vector-p53 sequences in posttreatment biopsies. Apoptosis (programmed cell death) was more frequent in posttreatment biopsies than in pretreatment biopsies. Tumor regression was noted in three patients, and tumor growth stabilized in three other patients.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/terapia , Técnicas de Transferência de Genes , Genes p53 , Terapia Genética , Neoplasias Pulmonares/terapia , Retroviridae/genética , Idoso , Sequência de Bases , Carcinoma Pulmonar de Células não Pequenas/patologia , Primers do DNA , Terapia Genética/efeitos adversos , Terapia Genética/métodos , Vetores Genéticos/efeitos adversos , Vetores Genéticos/genética , Humanos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Dados de Sequência MolecularRESUMO
White organic light-emitting diodes (WOLEDs) have drawn increasing attention due to their potential use in various applications such as solid-state lighting and backlight of liquid crystal displays and full-color OLEDs of red, green, and blue pixel. N,N'-dicabazolyl-3,5-benzene (mCP), the host material, was co-doped with Iridium (III) bis[(4,6-difluorophenyl)-pyridinato-N,C2']-picolinate (FIrpic), which functions not only as phosphorescent sensitizer but also blue emitter, and (2Z,2'Z)-3,3'-[4,4"-bis (dimethylamino)-1,1':4',1"-terphenyl-2',5'-diyl]bis (2-phenylacrylonitrile) (ABCV-P), which is a red fluorescent material. The fabricated device structures were as follows: (device A) Indium tin oxide (ITO)/N,N'-bis-(1-naphyl)-N,N'-diphenyl-1,1'-biphenyl-4,4'-diamine (NPB)/(mCP)/mCP:ABCV-P (1%)/4,7-diphenyl-1,10-phenanthroline (Bphen)/lithium quinolate (Liq)/aluminum (Al), (device B) ITO/NPB/mCP/mCP:FIrpic (8%)/Bphen/Liq/Al and (device C) ITO/NPB/mCP/mCP:FIrpic:ABCV-P (8%, 1%)/Bphen/Liq/Al, respectively. Phosphorescent FIrpic harvesting both singlet and triplet excitions not only emitted blue light but also transferred energy to fluorescent ABCV-P. The maximum luminance efficiency, external quantum efficiency, and luminance of white light device were measured to be 5.95 cd/A, 2.45% and 2500 cd/m2, respectively. The white device gave practically white light with the Commision Internationale de l'Eclairage (CIE(xy)) coordinate of (0.44, 0.49) which was close to warm white color (CIE(xy) = 0.45, 0.45).
RESUMO
Defects are one of the most important factors influencing the optical properties of groups III-V nitride semiconductor materials and thereby their applicability to light-emitting diodes. In this paper, we demonstrate that it is possible to estimate the presence of defects in InGaN laser diodes by performing pump-probe measurements and observing the induced absorptions. We have confirmed that the induced absorption originates from defects by performing experiments in which the pump intensity is varied. We believe that our method provides a powerful tool for evaluating the optical quality of InGaN materials before processing them into device fabrications.
Assuntos
Análise de Falha de Equipamento/métodos , Gálio/química , Índio/química , Lasers Semicondutores , Fotometria/métodos , PrótonsRESUMO
OBJECTIVE: To evaluate whether the degree of cervical length shortening is valuable in predicting the success of serial induction of labor on the second day in women in whom it failed on the first day, and to compare its performance with that of cervical length. METHODS: This was a prospective observational study. We enrolled 92 consecutive women with singleton gestations at > 34.0 weeks' gestation who failed labor induction on the first day of serial induction. Transvaginal sonographic measurement of cervical length and determination of the Bishop score were undertaken before performing each labor induction on the first and second days. RESULTS: The overall success rate of labor induction performed on the second day was 65% (60/92). Multiple logistic regression analysis demonstrated that the degree of cervical length shortening and cervical length were significantly associated with the successful induction of labor after adjustment for body mass index, parity, use of prostaglandin and Bishop score. There were no significant differences between areas under the ROC curves for degree of cervical length shortening and cervical length. CONCLUSIONS: The degree of cervical length shortening is valuable in predicting the success of induction of labor on the second day in women in whom induction failed on the first day. However, compared with sonographic cervical length it is no better at predicting the success of subsequent induction of labor.
Assuntos
Colo do Útero/diagnóstico por imagem , Trabalho de Parto Induzido , Adulto , Medida do Comprimento Cervical/métodos , Colo do Útero/anatomia & histologia , Feminino , Humanos , Trabalho de Parto Induzido/métodos , Valor Preditivo dos Testes , Gravidez , Estudos Prospectivos , Curva ROCRESUMO
OBJECTIVES: To identify the clinical and sonographic parameters at 37 weeks' gestation that predict the risk of Cesarean delivery in labor for nulliparas. METHODS: This prospective observational study recruited nulliparas with singleton pregnancies at 37 weeks' gestation. Determination of the Bishop score, ultrasound measurement of the cervical length, and fetal biometry were performed. The clinical parameters studied were maternal age, height and weight and Bishop score. The sonographic parameters included fetal biparietal diameter, femur length, abdominal circumference (AC), estimated fetal weight (EFW), amniotic fluid index and cervical length. RESULTS: Four hundred and fifty-three women were examined; 57 women (12.6%) underwent an emergency Cesarean delivery in labor. Logistic regression analysis identified maternal age and height and fetal AC and EFW, but not cervical length or Bishop score, as the best predictors of Cesarean delivery. Of these predictors, maternal age and height and fetal AC at 37 weeks were included in a final model for risk scoring. The model was shown to have an adequate goodness of fit (P = 0.473), and the area under the receiver-operating characteristics curve was 0.758, indicating reasonably good discrimination. CONCLUSIONS: Maternal age and height and fetal AC and EFW at 37 weeks' gestation are the most important parameters in predicting the risk of Cesarean delivery in nulliparas; sonographic measurement of the cervical length and the Bishop score were not predictive of Cesarean delivery. A predictive model using these parameters at 37 weeks provides useful information in the decision-making process regarding the mode of delivery.
Assuntos
Colo do Útero/diagnóstico por imagem , Cesárea/estatística & dados numéricos , Adulto , Maturidade Cervical/fisiologia , Colo do Útero/fisiopatologia , Feminino , Peso Fetal/fisiologia , Idade Gestacional , Humanos , Trabalho de Parto Induzido , Idade Materna , Valor Preditivo dos Testes , Gravidez , Estudos Prospectivos , Curva ROC , Ultrassonografia Pré-NatalRESUMO
BACKGROUND: Locally advanced laryngeal and hypopharyngeal cancers (LHC) represent a group of cancers for which surgery, laryngectomy-free survival (LFS), overall survival (OS), and progression-free survival (PFS) are clinically meaningful end points. PATIENTS AND METHODS: These outcomes were analyzed in the subgroup of assessable LHC patients enrolled in TAX 324, a phase III trial of sequential therapy comparing docetaxel plus cisplatin and fluorouracil (TPF) against cisplatin and fluorouracil (PF), followed by chemoradiotherapy. RESULTS: Among 501 patients enrolled in TAX 324, 166 had LHC (TPF, n = 90; PF, n = 76). Patient characteristics were similar between subgroups. Median OS for TPF was 59 months [95% confidence interval (CI): 31-not reached] versus 24 months (95% CI: 13-42) for PF [hazard ratio (HR) for death: 0.62; 95% CI: 0.41-0.94; P = 0.024]. Median PFS for TPF was 21 months (95% CI: 12-59) versus 11 months (95% CI: 8-14) for PF (HR: 0.66; 95% CI: 0.45-0.97; P = 0.032). Among operable patients (TPF, n = 67; PF, n = 56), LFS was significantly greater with TPF (HR: 0.59; 95% CI: 0.37-0.95; P = 0.030). Three-year LFS with TPF was 52% versus 32% for PF. Fewer TPF patients had surgery (22% versus 42%; P = 0.030). CONCLUSIONS: In locally advanced LHC, sequential therapy with induction TPF significantly improved survival and PFS versus PF. Among operable patients, TPF also significantly improved LFS and PFS. These results support the use of sequential TPF followed by carboplatin chemoradiotherapy as a treatment option for organ preservation or to improve survival in locally advanced LHC.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células Escamosas/terapia , Neoplasias Hipofaríngeas/terapia , Neoplasias Laríngeas/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/radioterapia , Quimioterapia Adjuvante , Cisplatino/administração & dosagem , Intervalo Livre de Doença , Docetaxel , Feminino , Fluoruracila/administração & dosagem , Humanos , Neoplasias Hipofaríngeas/tratamento farmacológico , Neoplasias Hipofaríngeas/mortalidade , Neoplasias Hipofaríngeas/patologia , Neoplasias Hipofaríngeas/radioterapia , Neoplasias Hipofaríngeas/cirurgia , Estimativa de Kaplan-Meier , Neoplasias Laríngeas/tratamento farmacológico , Neoplasias Laríngeas/mortalidade , Neoplasias Laríngeas/patologia , Neoplasias Laríngeas/radioterapia , Neoplasias Laríngeas/cirurgia , Laringectomia , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Radioterapia Adjuvante , Medição de Risco , Taxoides/administração & dosagem , Fatores de Tempo , Resultado do TratamentoRESUMO
Recent studies have suggested that virulent strains of Mycobacterium tuberculosis induce apoptosis in macrophages less often than do attenuated strains. K-strain, which belongs to the Beijing family, is the most frequently isolated clinical strain of M. tuberculosis in Korea. In this study, we investigated the differential induction of cell death in human monocytic THP-1 cells by K-strain and H37Rv, a virulent but laboratory-adapted strain of M. tuberculosis. Although no significant difference in growth rate was observed between the cells exposed to K-strain and those exposed to H37Rv, the levels of protective cytokines such as tumour necrosis factor (TNF)-alpha, interleukin (IL)-6 and IL-12p40 were lower in K-strain-infected cells than in H37Rv-infected cells. Cell viability assays showed that both K-strain and H37Rv, but not heat- or streptomycin-killed bacteria, induced THP-1 cell death in a TNF-independent manner. In contrast, double staining with fluorochrome-labelled inhibitors of caspase and propidium iodide and lactate dehydrogenase release assays revealed that K-strain induced significantly higher levels of necrotic cell death, rather than apoptosis, in THP-1 cells than did H37Rv. Anti-apoptotic Bcl-2, Mcl-1, Bfl-1 and Bcl-xL in the cells were significantly upregulated following infection with K-strain compared with H37Rv, whereas Bax was slightly upregulated in response to infection with both H37Rv and K-strain. These results suggest that the highly virulent K-strain keeps cellular apoptosis as a host defense mechanism to a minimum and induces necrosis in macrophages.
Assuntos
Apoptose/imunologia , Macrófagos/imunologia , Mycobacterium tuberculosis/patogenicidade , Tuberculose/imunologia , Linhagem Celular , Sobrevivência Celular , Citocinas/metabolismo , Humanos , Coreia (Geográfico) , Macrófagos/microbiologia , Antígenos de Histocompatibilidade Menor , Proteína de Sequência 1 de Leucemia de Células Mieloides , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Tuberculose/microbiologia , Regulação para Cima , Virulência , Proteína X Associada a bcl-2/metabolismo , Proteína bcl-X/metabolismoRESUMO
The localization of various Ca(2+) transport and signaling proteins in secretory cells is highly restricted, resulting in polarized agonist-stimulated Ca(2+) waves. In the present work, we examined the possible roles of the Sec6/8 complex or the exocyst in polarized Ca(2+) signaling in pancreatic acinar cells. Immunolocalization by confocal microscopy showed that the Sec6/8 complex is excluded from tight junctions and secretory granules in these cells. The Sec6/8 complex was found in at least two cellular compartments, part of the complex showed similar, but not identical, localization with the Golgi apparatus and part of the complex associated with Ca(2+) signaling proteins next to the plasma membrane at the apical pole. Accordingly, immunoprecipitation (IP) of Sec8 did not coimmunoprecipitate betaCOP, Golgi 58K protein, or mannosidase II, all Golgi-resident proteins. By contrast, IP of Sec8 coimmunoprecipitates Sec6, type 3 inositol 1,4,5-trisphosphate receptors (IP(3)R3), and the Gbetagamma subunit of G proteins from pancreatic acinar cell extracts. Furthermore, the anti-Sec8 antibodies coimmunoprecipitate actin, Sec6, the plasma membrane Ca(2+) pump, the G protein subunits Galphaq and Gbetagamma, the beta1 isoform of phospholipase C, and the ER resident IP(3)R1 from brain microsomal extracts. Antibodies against the various signaling and Ca(2+) transport proteins coimmunoprecipitate Sec8 and the other signaling proteins. Dissociation of actin filaments in the immunoprecipitate had no effect on the interaction between Sec6 and Sec8, but released the actin and dissociated the interaction between the Sec6/8 complex and Ca(2+) signaling proteins. Hence, the interaction between the Sec6/8 and Ca(2+) signaling complexes is likely mediated by the actin cytoskeleton. The anti-Sec6 and anti-Sec8 antibodies inhibited Ca(2+) signaling at a step upstream of Ca(2+) release by IP(3). Disruption of the actin cytoskeleton with latrunculin B in intact cells resulted in partial translocation of Sec6 and Sec8 from membranes to the cytosol and interfered with propagation of agonist-evoked Ca(2+) waves. Our results suggest that the Sec6/8 complex has multiple roles in secretory cells including governing the polarized expression of Ca(2+) signaling complexes and regulation of their activity.
Assuntos
Sinalização do Cálcio/fisiologia , Cálcio/metabolismo , Proteínas de Transporte/metabolismo , Pâncreas/citologia , Pâncreas/fisiologia , Actinas/fisiologia , Animais , Brefeldina A/farmacologia , Canais de Cálcio/isolamento & purificação , Canais de Cálcio/fisiologia , Sinalização do Cálcio/efeitos dos fármacos , Carbacol/farmacologia , Proteínas de Transporte/análise , Membrana Celular/fisiologia , Membrana Celular/ultraestrutura , Polaridade Celular , Células Cultivadas , Citoesqueleto/fisiologia , Citoesqueleto/ultraestrutura , Proteínas de Ligação ao GTP/isolamento & purificação , Proteínas de Ligação ao GTP/metabolismo , Complexo de Golgi/fisiologia , Complexo de Golgi/ultraestrutura , Receptores de Inositol 1,4,5-Trifosfato , Fosfatos de Inositol/farmacologia , Potenciais da Membrana/efeitos dos fármacos , Potenciais da Membrana/fisiologia , Proteínas de Membrana , Técnicas de Patch-Clamp , Ratos , Receptores Citoplasmáticos e Nucleares/isolamento & purificação , Receptores Citoplasmáticos e Nucleares/fisiologiaRESUMO
A red fluorescent material (2E,2'E)-3,3'-[4,4"-bis(dimethylamino)-1,1': 4',1 "-terphenyl-2',5'-diyl]bis[2-(2-thienyl)acrylonitrile] (ABCV-Th) was synthesized for use in organic light emitting diodes (OLEDs) as the host emissive material. It has been reported some green and blue host emissive materials used in OLEDs revealed high device performance but, owing to concentration quenching, comparable red light emitting materials are still rare in OLEDs application. Non-doped organic light emitting diodes, with the structure of ITO/NPB/ABCV-Th (30 nm and 50 nm)/BCP/Alq3/Liq/Al were fabricated using ABCV-Th as the host emitter. The peak wavelength and full width at half maximum (FWHM) of electroluminescence (EL) were 629.5 nm and 68.5 nm, respectively. The maximum brightness and turn on voltage of the device were measured to be 1330 cd/m2 at 14.6 V and 3.4 V, respectively. The device exhibited authentic red emission (Commission Internationale De L'Eclairage (CIE(xy)) = 0.65, 0.34) which is almost close to the standard red (CIE(xy) = 0.67, 0.33) demanded by the national television system committee (NTSC).
RESUMO
OBJECTIVES: We report the outcomes of patients with squamous cell carcinoma of the head and neck (HNSCC) whose circulating tumor cells (CTCs) were quantified using surface-enhanced Raman scattering (SERS) nanotechnology. METHODS: SERS tagged with EGF was used to directly measure targeted CTCs. Patient charts were retrospectively reviewed. An optimal cut point for CTCs in 7.5 ml of peripheral blood predictive of for distant metastasis-free survival (DMFS) was identified by maximizing the log-rank statistic. An ROC analysis was also performed. RESULTS: Of 82 patients, 13 experienced metastatic progression. The optimal cut point for DMFS was 675 CTCs (p = 0.047). For those with distant recurrence (n = 13) versus those without distant recurrence (n = 69), the CTC cut point which results in the largest combined sensitivity and specificity values is also 675 (sensitivity = 69%, specificity = 68%). CONCLUSION: Liquid biopsy techniques in HNSCC show promise as a means of identifying patients at greater risk of disease progression.
Assuntos
Biomarcadores Tumorais/sangue , Neoplasias de Cabeça e Pescoço/patologia , Células Neoplásicas Circulantes/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Adulto , Idoso , Área Sob a Curva , Intervalo Livre de Doença , Feminino , Neoplasias de Cabeça e Pescoço/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Curva ROC , Sensibilidade e Especificidade , Carcinoma de Células Escamosas de Cabeça e Pescoço/mortalidade , Adulto JovemRESUMO
Caveolin-1 (Cav-1) plays an important role in modulating cellular signalling, but its role in metastasis is not well defined. A significant reduction in Cav-1 levels was detected in lymph node metastases as compared with primary tumour of head and neck squamous cell carcinoma (HNSCC) specimens (P<0.0001), confirming the downregulation of Cav-1 observed in a highly metastatic M4 cell lines derived from our orthotopic xenograft model. To investigate the function of Cav-1 in metastasis of HNSCC, we compared stable clones of M4 cells carrying human cav-1 cDNA (CavS) with cells expressing an empty vector (EV) in vitro and in the orthotopic xenograft model. Overexpression of Cav-1 suppressed growth of the CavS tumours compared with the EV tumours. The incidence of lung metastases was significantly lower in animals carrying CavS tumours than those with EV tumours (P=0.03). In vitro, CavS cells displayed reduced cell growth, invasion, and increased anoikis compared with EV cells. In CavS cells, Cav-1 formed complex with integrin beta1 and Src. Further application of integrin beta1 neutralising antibody or Src inhibitor PP2 to EV cells illustrated similar phenotypes as CavS cells, suggesting that Cav-1 may play an inhibitory role in tumorigenesis and lung metastasis through regulating integrin beta1- and Src-mediated cell-cell and cell-matrix interactions.
Assuntos
Carcinoma de Células Escamosas/metabolismo , Caveolina 1/biossíntese , Neoplasias de Cabeça e Pescoço/metabolismo , Animais , Anoikis , Carcinoma de Células Escamosas/fisiopatologia , Linhagem Celular Tumoral , Proliferação de Células , Modelos Animais de Doenças , Regulação para Baixo , Feminino , Neoplasias de Cabeça e Pescoço/fisiopatologia , Humanos , Linfonodos/patologia , Metástase Linfática/fisiopatologia , Masculino , Camundongos , Camundongos Nus , Pessoa de Meia-Idade , Metástase Neoplásica , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
CC-chemokine ligand 20 (CCL20), a unique chemokine ligand of CC-chemokine receptor 6 (CCR6), play roles in various pathologic conditions. However, the characteristic expression profiles of CCL20 during human tuberculosis (TB) have been largely unknown. The present study analyzed the production and regulatory mechanisms of CCL20 in peripheral blood mononuclear cells (PBMC) and monocyte-derived macrophages (MDM) from active pulmonary TB patients and healthy controls (HC). The 30-kDa antigen (Ag) of Mycobacterium tuberculosis actively induced the production of CCL20 by human PBMC and MDM. A comparative analysis revealed that the expression of CCL20 protein was prominently up-regulated in PBMC, MDM, bronchoalveolar lavage fluids (not in sera) from TB patients compared with the corresponding cells or body fluids from HC. Blockade of either tumour necrosis factor-alpha or interferon-gamma, but not interleukin-10, significantly attenuated the CCL20 production. In addition, recombinant CCL20 induced CCR6 expression by CD45RO+ T lymphocytes in a dose-dependent manner. Furthermore, the expression of CCR6 was significantly increased in CD45RO+ T lymphocytes from TB patients, as compared with those from HC. Pharmacological inhibition studies showed that the 30-kDa Ag-induced CCL20 mRNA expression involves mitogen-activated protein kinases (MAPK; extracellular signal-regulated kinase 1/2 and p38)- and NF-kappaB-dependent signalling. Collectively, the present study demonstrated that TB patients show the up-regulated expression of CCL20, which is modulated by proinflammatory cytokines, and through MAPK/NF-kappaB-mediated transcriptional mechanisms. The findings suggest important implications of potential roles of CCL20-CCR6 in immunopathogenesis of TB.
Assuntos
Quimiocina CCL20/genética , Quimiocina CCL20/metabolismo , Regulação da Expressão Gênica/imunologia , Tuberculose Pulmonar/metabolismo , Adulto , Antígenos de Bactérias/imunologia , Quimiocina CCL20/biossíntese , Feminino , Humanos , Mediadores da Inflamação/fisiologia , Leucócitos Mononucleares/imunologia , Macrófagos/imunologia , Macrófagos/metabolismo , Masculino , Pessoa de Meia-Idade , Tuberculose Pulmonar/imunologia , Regulação para Cima/imunologiaRESUMO
Most organic light-emitting diodes (OLEDs) have a multilayer structure composed of organic layers such as a hole injection layer (HIL), a hole transport layer (HTL), an emission layer (EML), an electron transport layer (ETL) and an electron injection layer (EIL) sandwiched between two electrodes. The organic layers are thin solid films with a thickness from a few nano meters to a few tenths nano meter, respectively. Surface morphology of an organic thin solid film in OLEDs depends on the molecular structure of the organic material and has an affect on device performance. To analyze the effect of surface morphology of an organic thin solid film on fluorescence and electroluminescence (EL) properties, thin solid films of 4-(dicyanomethylene)-2-methyl-6-(julolidin-4-yl-vinyl)-4H-pyran (DCM2) and new red fluorophores, (2E,2'E)-3,3'-[4,4''-bis(dimethylamino)-1,1':4',1''-terphenyl-2',5'-diyl]bis[2-(2-thienyl)acrylonitrile] (ABCV-Th) and (2Z,2'Z)-3,3'-[4,4''-bis(dimethylamino)-1,1':4',1''-terphenyl-2',5'-diyl]bis(2-phenylacrylonitrile) (ABCV-P) were investigated by atomic force microscopy (AFM). The samples for EL and AFM measurement were fabricated by the high-vacuum thermal deposition (8 x 10(-7) Torr) of organic materials onto the surface of indium tin oxide (ITO)-coated glass substrate, in which the layer structures of samples for AFM measurement and those for EL measurement were ITO/NPB (40 nm)/red emitters (80 nm) and ITO/NPB (40 nm)/red emitters (80 nm)/BCP (30 nm)/Liq (2 nm)/Al (100 nm), respectively. The analysis based on AFM measurements well supported that the photoluminescence properties and the device performance were very much dependent upon surface morphology of an organic thin layer.