RESUMO
Objective: To explore the effects of hinokiol on the cell cyle and apoptosis of CNE1 nasopharyngeal carcinoma cells and the relevant molecular mechanism. Methods: The CNE1 cells were cultured in vitro and incubated with different concentrations of honokiol, and the cells were divided into blank control group, 10 µmol/L, 20 µmol/L and 40 µmol/L hinokiol treatment groups, and 10 µg/ml cisplatin group. Cell viability was determined by methylthiazolyldiphenyl- tetrazolium bromide (MTT) method, the cell cycle distribution was detected by flow cytometry, mitochondrial membrane potential was detected by mitochondrial membrane potential test kit, apoptosis was detected by terminal deoxynucleotidyl transferase mediated dUTP nick end labeling (TUNEL) method, and the proteins expression of proliferating cell nuclear antigen (PCNA) and G1/S specific cyclin D1 (cyclin D1) were detected by immunoblotting. RNA-Seq was conducted in the hinokiol-treated cells. The mRNA expression of yes-associated protein delta (YAP) was detected by quantitative reverse transcription polymerase chain reaction (RT-qPCR). The proteins expression of phosphor-YAP (p-YAP) and nuclear YAP were detected by immunoblotting, the nuclear distribution of YAP protein was detected by immunofluorescence in the cells with or without treated with the mammalian STE20-like kinase 1/2 (MST1/2) inhibitor (XMU-MP-1), hinokiol, and XMU-MP-1+hinokiol. Statistical analysis of the data was conducted using GraphPad Prism 8.0 software. Resluts Compared with the control group, the cell viablity of CNE1 cells, the levels of mitochondrial membrane potential, the proteins expression of PCNA and cyclin D1 in hinokiol treatment groups were markedly decreased (all P values<0.05), while the proportion of G0/G1 phase cells and the ratio of TUNEL-positive cells were significantly increased (both P values<0.05). Transcriptome analysis showed that differential genes were mainly enriched in Wnt signaling pathway, tumor necrosis factor pathway, and Hippo signaling pathway. The mRNA level of YAP and the protein expression of YAP in the nucleus were decreased and the level of p-YAP protein was increased in cells treated with hinokiol, which were significantly different from control group (all P values<0.05). Compared with the hinokiol group, XMU-MP-1+hinokiol groups showed the decrease of p-YAP protein expression (1.157±0.076 vs 0.479±0.038, t=37.120, P<0.05), the increase of YAP protein expression in the nucleus (0.143±0.012 vs 0.425±0.031, t=29.181, P<0.05), the reduced proportion of cells in G0/G1 phase [(72.494±3.309)% vs (58.747±2.865)%, t=17.265, P<0.05], and the decrease of apoptosis ratio [(53.158±3.376)% vs (29.621±2.713)%, t=28.584, P<0.05]. Conclusion: Hinokiol can arrest the cell cycle and induce the cell apoptosis of CNE1 cells via Hippo/YAP signaling pathway.
Assuntos
Apoptose , Compostos de Bifenilo , Ciclo Celular , Via de Sinalização Hippo , Lignanas , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Transdução de Sinais , Humanos , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Carcinoma Nasofaríngeo/metabolismo , Ciclo Celular/efeitos dos fármacos , Neoplasias Nasofaríngeas/metabolismo , Neoplasias Nasofaríngeas/patologia , Lignanas/farmacologia , Compostos de Bifenilo/farmacologia , Fatores de Transcrição/metabolismo , Proteínas de Sinalização YAP , Proteínas Serina-Treonina Quinases/metabolismo , Proliferação de Células/efeitos dos fármacos , Ciclina D1/metabolismo , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Antígeno Nuclear de Célula em Proliferação/metabolismoRESUMO
Objective: To investigate the interventional effect of bicyclol on isoniazid-induced liver injury in rats and the expression of endoplasmic reticulum stress (ERS) protein, glucose regulatory protein 78 (GRP78), and growth arrest and DNA-damage-inducible gene 153(CHOP). Methods: Eighty Wistar rats were randomly divided into control group (8 rats) and model group (72 rats). After 10 days of intragastric administration of isoniazid, the model group rats were randomly divided into treatment group (A), natural recovery group (B), etiological persistence group (C) and etiological persistence plus treatment group (D). Sixteen rats from each group were sacrificed after 1 and 2 weeks of intervention with different methods. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were detected. Liver pathological morphology was observed. Apoptotic cells were detected by TUNEL assay. ERS protein expression was detected by Western blot. A t-test or randomized block analysis of variance, K-S test and Levene's test were used to analyze the normality and homogeneity of variance. Kruskal-Wallis rank sum test was used for data that did not suit the conditions of t-test and variance analysis. Results: ALT and AST were elevated in the model group, and liver pathological examination showed liver tissue damage. Apoptotic index was higher than control group (7.13% ± 1.55% vs. 0.75% ± 0.71%, Z = -3.411, P < 0.01), and the expression value of ERS protein in model group was significantly higher than control group (GRP78: 1.16 ± 0.30 vs. 0.23 ± 0.05, t = -6.008, P < 0.01; CHOP: 0.98±0.23 vs. 0.20 ± 0.10, t = -6.378, P < 0.01). Serum enzymes, apoptotic index and ERS protein expressions of rats were decreased after treatment with bicyclol, and the pathological damage was eased. Rats in natural recovery group recovered less than the treatment group. Conclusion: Isoniazid-induced liver injury is associated to ERS-related excessive apoptosis and the therapeutic effect of bicyclol on drug-induced liver injury may minimize ERS-induced apoptosis.
Assuntos
Estresse do Retículo Endoplasmático , Proteínas de Choque Térmico HSP70/metabolismo , Proteínas de Choque Térmico/metabolismo , Isoniazida/efeitos adversos , Fígado , Proteínas de Membrana/metabolismo , Animais , Apoptose , Compostos de Bifenilo , Doença Hepática Induzida por Substâncias e Drogas , DNA , Fígado/efeitos dos fármacos , Fígado/metabolismo , Ratos , Ratos Sprague-Dawley , Ratos WistarRESUMO
Objective: The quick sequential organ failure assessment (qSOFA) score has been proposed as part of diagnostic criteria for sepsis, but there might be an underestimation of the incidence of qSOFA-negative sepsis according to a few recent studies. The purpose of this study was to evaluate the value of Oxford acute severity of illness score (OASIS) in identifying qSOFA-negative (qSOFA<2) patients with sepsis. Methods: Sepsis patients with negative qSOFA scores were selected from the Medical Information Mart for Intensive Care â ¢(MIMIC-â ¢), a database comprising de-identified health-related data from patients staying in the critical care units of Beth Israel Deaconess Medical Center between 2001 and 2012. Non-infectious patients with both qSOFA and SOFA scores less than 2 were enrolled as controls. Propensity score matching (PSM) analysis was used to reduce the effects of selection bias. Receiver operating characteristic (ROC) curve analysis was performed to assess the value of OASIS in discriminating qSOFA-negative patients with sepsis and to determine its optimal cut-off. Associations of OASIS with 28-day mortality after intensive care unit (ICU) admission, ICU mortality, and hospital mortality were further examined using multivariate Cox regression and multivariate logistic regression analysis. Results: 2 273 qSOFA-negative patients with sepsis and 3 342 non-sepsis controls were included finally with a PSM cohort consisted of 1 677 sepsis patients and 1 677 controls. Results of ROC analysis showed that the area under ROC curve was 0.753 [95% confidence interval (CI) 0.741-0.765] and the optimal OASIS threshold according to the Youden index was 26.5 and yielded a 67.2% sensitivity and 70.8% specificity. Multivariate regression analysis indicated that OASIS>26 was an independent risk factor for 28-day mortality (hazard ratio 2.80, 95% CI 2.15-3.65, P<0.01), ICU mortality (odds ratio 4.69, 95% CI 2.60-8.49, P<0.01), and hospital mortality (odds ratio 4.48, 95% CI 3.13-6.42, P<0.01). Analysis of the PSM cohort presented consistent results. Conclusions: OASIS had a good discriminative value to differentiate qSOFA-negative patients with sepsis from those without sepsis.
Assuntos
Escores de Disfunção Orgânica , Sepse , Mortalidade Hospitalar , Humanos , Prognóstico , Curva ROC , Estudos Retrospectivos , Índice de Gravidade de DoençaRESUMO
The objective of this study was to investigate the effects of blueberry treatment on histone acetylation modification of carbon tetrachloride (CCl4)-induced liver disease in rats. Laboratory rats were randomly divided into control, hepatic fibrosis, blueberry treatment, blueberry intervention, and natural recovery groups. Rats in the model groups were treated with CCl4 administered subcutaneously at 4- and 8-week intervals, and then executed. Both the 4- and 8-week treatment groups were treated with blueberry juice for 8 weeks, and then executed after 12 and 16 weeks, respectively. Following the experiment, four liver function and hepatic fibrosis indices were measured. Liver index was calculated, hematoxylin-eosin staining was conducted, and H3K9, H3K14, and H3K18 expressions were evaluated among the nuclear proteins of the liver tissues. No differences in alanine transaminase were noted between the control and intervention groups, but significant differences were detected among the model, treatment, and natural recovery groups (P < 0.01). Significant differences were also observed in aspartate transaminase, hyaluronic acid, and collagen IV among the model, treatment, intervention, and natural recovery groups (P < 0.01, P < 0.01, P < 0.01). Liver index, and H3K9 and H3K14 expression were significantly different among the model groups (P < 0.05 and P < 0.01), whereas H3K18 expression was dramatically different among model, treatment, intervention, and natural recovery groups (P < 0.01). Following blueberry treatment, rat liver function and hepatic fibrosis improved, potentially indicating that blueberry components could regulate histone acetylation and improve liver pathologic changes in rats with CCl4-induced disease.
Assuntos
Mirtilos Azuis (Planta)/química , Tetracloreto de Carbono/toxicidade , Histonas/metabolismo , Cirrose Hepática/tratamento farmacológico , Extratos Vegetais/administração & dosagem , Acetilação/efeitos dos fármacos , Animais , Aspartato Aminotransferases/metabolismo , Modelos Animais de Doenças , Cirrose Hepática/induzido quimicamente , Cirrose Hepática/patologia , Testes de Função Hepática , Masculino , Extratos Vegetais/farmacologia , Distribuição Aleatória , Ratos , Ratos Sprague-DawleyRESUMO
Successful treatment of the secondary effluent ensures its safe disposal and water reclamation for water reuse. To understand the effect of ultraviolet (UV) irradiation in combination with hydrogen peroxide (H(2)O(2)) on secondary effluent under field conditions, an advanced oxidation system, UV+H(2)O(2), was installed and fed with the effluent at 1.0, 1.5 and 2.0 m(3) h(- 1) over a period of 6 months. The electrical energy density for the UV reactor was varied between 0.5 and 5.2 kWh m(-3) and H(2)O(2) added at concentrations of 0, 13 or 26 mg L(-1). The feed and product water samples were taken periodically and analyzed for biological (heterotrophic plate count-HPC, total and fecal coliform-TC and FC) and chemical (NH(4)(+)-N, NO(3)(-)-N, NO(2)(-)-N and total organic carbon-TOC) parameters. For the treatment of UV+26 mg L(- 1) H(2)O(2), flow rates of 1.0, 1.5 and 2.0 m(3) h(- 1) resulted in > 4-log removal of HPC with a maximum survivor of 20 CFU mL(-1) and > 4 log reduction of FC with a survivor of 8 CFU (100 mL)(- 1). The electrical energy density of 1.5 kWh m(-3) was optimum for the inactivation. The NO(2)(-)-N concentrations of the product water were 0.09-0.42 mg L(- 1) compared with 0.04-0.09 mg L(- 1)in the feed. With or without H(2)O(2) addition, NO(2)(-)-N concentration increased with increases in UV electrical energy density. The highest increase in NO(2)(-)-N was associated with the maximum energy density of 5.2 kWh m(-3). Increase in H(2)O(2) dose reduced NO(3)(-)-N concentration by 2.0 to 5.7%. The overall results showed that the advanced oxidation technology prepared the effluent for safe disposal and/or for water reclamation for reuse.
Assuntos
Água Doce/química , Água Doce/microbiologia , Poluentes Químicos da Água/metabolismo , Poluentes Químicos da Água/efeitos da radiação , Purificação da Água/métodos , Carbono/análise , Enterobacteriaceae/isolamento & purificação , Peróxido de Hidrogênio/metabolismo , Nitratos/análise , Nitritos/análise , Nitrogênio/análise , Compostos Orgânicos/análise , Compostos de Amônio Quaternário/análise , Raios UltravioletaRESUMO
A pilot plant was constructed with eight elements of an Asahi microfiltration (MF) membrane-a total filtration surface area of 56 m2. Performance of the plant was examined in preparation of a secondary sewage effluent without coagulant for reverse osmosis membrane treatment. Production at different permeate flux was tested for evaluation of the changes in transmembrane pressure (TMP) and specific permeate flux (SPF) with time. Clean-in-place (CIP) was conducted when TMP reached a value about 2 atm after each test. For permeate flux of 48, 55, 61 and 66 L m-2 h-1, the ceiling TMP was reached after filtration for approximately 420, 200, 225, and 195 h, respectively. The corresponding cumulative permeate volumes were 1130, 620, 765, 720 m3 before a CIP was necessary. The SPF decreased quickly with increases in permeate flux and the corresponding half-SPF times were 147, 89, 75 and 39 h for the respective flux studied. The membrane fouling tolerance was greater at a lower than at a higher flux. Analysis of the performance data suggests that run of the MF plant at higher permeate flux with more frequent and quick CIP might produce more water. The optimal filtration durations were found to be 12, 8, 7 and 3 days for permeate flux of 48, 55, 61 and 66 L m-2 h-1, respectively. Prolonged filtration after the optimal interval without CIP may not maximise the economical benefit.
Assuntos
Filtração/métodos , Purificação da Água/métodos , Filtração/instrumentação , Membranas Artificiais , Projetos Piloto , Purificação da Água/economiaRESUMO
This work studied the destruction of various M-EDTA complexes and trace organic pollutants in treated reusable wastewater under advanced oxidation using UV irradiation and ozonation. Effect of dosage of hydrogen peroxide and acidity of reaction matrices on oxidation efficiencies were investigated. The rate constant of mineralization presents a decreasing trend as Fe(III)-EDTA > Fe(II)-EDTA > Al(III)-EDTA > Pb(II)-EDTA > Na(I)-EDTA > Zn(II)-EDTA > Cu(II)-EDTA. The mineralization efficiencies using ozone alone are 15%, 40% and 15% for the water samples after reverse osmosis (RO), microfiltration (MF) and superfiltration (SF) processes, respectively. The presence of hydrogen peroxide in photochemical reaction matrixes can effectively enhance the mineralization of organic carbon species. When 150 mg l(-1) of H2O2 was added in the effluents, the mineralization markedly increased to 80%, 92% and 89%, respectively.
Assuntos
Ácido Edético/química , Ozônio/química , Fotoquímica/métodos , Raios Ultravioleta , Eliminação de Resíduos Líquidos/métodos , Poluentes Químicos da Água , Peróxido de Hidrogênio/química , Cinética , Oxirredução , Eliminação de Resíduos Líquidos/instrumentaçãoRESUMO
This contribution reports on luminescence properties of divalent ytterbium in alpha-SiAlON at room temperature. Ytterbium-doped alpha-SiAlON powders, with the compositions of (M(1-2x/v)Yb(x))(m/v)Si(12-m-n)Al(m+n)O(n)N(16-n) (M = Ca, Li, Mg, and Y, v is the valency of M, 0.002 < or = x < or = 0.10, 0.5 < or = m = 2n < or = 3.5), were synthesized by sintering at 1700 degrees C for 2 h under 0.5 MPa N2. A single, intense, broad emission band, centered at 549 nm, is observed due to the electronic transitions from the excited state 4f(13)5d to the ground state 4f14 of Yb2+. The luminescence of Yb2+ in alpha-SiAlON occurs at relatively low energy, which is attributable to the large crystal field splitting and nephelauxetic effect due to the nitrogen-rich coordination of Yb2+. The dependence of luminescence properties on the Yb2+ concentration, chemical composition, and annealing is discussed. It is suggested that this novel green phosphor could be applied in white light-emitting diodes (LEDs) when combined with a red phosphor and a blue LED.
RESUMO
The experimental results showed that ozone (O3) oxidation is an effective means to destroy phenolic organic pollutants present in water. High removal efficiencies can be readily achieved for most of the model compounds fortified in aqueous matrices within a reasonable time frame. This study also included the oxidation of phenolic compounds using ozone in combination with ultraviolet (UV) irradiation. The extent of mineralization measured in terms of the losses in total organic carbon is promoted by the joint action of ozone and UV in comparison with using ozone alone.