RESUMEN
High-fat (HF) diets and low-grade chronic inflammation contribute to the development of insulin resistance and type 2 diabetes (T2D), whereas n-3 polyunsaturated fatty acids (PUFAs), due to their anti-inflammatory effects, protect against insulin resistance. Interleukin (IL)-1ß is implicated in insulin resistance, yet how n-3 PUFAs modulate IL-1ß secretion and attenuate HF diet-induced insulin resistance remains elusive. In this study, a HF diet activated NLRP3 inflammasome via inducing reactive oxygen species (ROS) generation and promoted IL-1ß production primarily from adipose tissue preadipocytes, but not from adipocytes and induced insulin resistance in wild type (WT) mice. Interestingly, endogenous synthesized n-3 polyunsaturated fatty acids (PUFAs) reversed this process in HF diet-fed fat-1 transgenic mice although the HF diet induced higher weight gain in fat-1 mice, compared with the control diet. Mechanistically, palmitic acid (PA), the main saturated fatty acid in an HF diet inactivated AMPK and led to decreased GSK-3ß phosphorylation, at least partially through reducing Akt activity, which ultimately blocked the Nrf2/Trx1 antioxidant pathway and induced TXNIP cytoplasm translocation and NLRP3 inflammasome activation, whereas docosahexaenoic acid (DHA), the most abundant n-3 PUFA in fat-1 adipose tissue, reversed this process via inducing Akt activation. Our GSK-3ß shRNA knockdown study further revealed that GSK-3ß played a pivot role between the upstream AMPK/Akt pathway and downstream Nrf2/Trx1/TXNIP pathway. Given that NLRP3 inflammasome is implicated in the development of most inflammatory diseases, our results suggest the potential of n-3 PUFAs in the prevention or adjuvant treatment of NLRP3 inflammasome-driven diseases.
Asunto(s)
Diabetes Mellitus Tipo 2 , Ácidos Grasos Omega-3 , Resistencia a la Insulina , Proteínas Quinasas Activadas por AMP/metabolismo , Animales , Antiinflamatorios/farmacología , Antioxidantes/farmacología , Proteínas Portadoras , Dieta Alta en Grasa/efectos adversos , Ácidos Docosahexaenoicos/farmacología , Ácidos Grasos/farmacología , Ácidos Grasos Omega-3/farmacología , Glucógeno Sintasa Quinasa 3 beta , Inflamasomas/metabolismo , Resistencia a la Insulina/fisiología , Ratones , Ratones Endogámicos C57BL , Factor 2 Relacionado con NF-E2/genética , Proteína con Dominio Pirina 3 de la Familia NLR/genética , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Ácido Palmítico/farmacología , Proteínas Proto-Oncogénicas c-akt , ARN Interferente Pequeño , Especies Reactivas de Oxígeno , TiorredoxinasRESUMEN
The concentrations of trace elements in wines and health risk assessment via wine consumption were investigated in 315 wines. Samples were collected from eight major wine-producing regions in China. The concentrations of twelve trace elements were determined by inductively coupled plasma mass spectrometry (ICP-MS) and Duncan's multiple range test was applied to analyze significant variations (p < 0.05) of trace elements in different regions. Based on a 60 kg adult drinker consuming 200 mL of wine per day, the estimated daily intake (EDI) of each element from wines was far below the provisional tolerable daily intake (PTDI). Health risk assessment indicated the ingestion influence of individual elements and combined elements through this Chinese wine daily intake did not constitute a health hazard to people. However, Cr and Mn were the potential contaminants of higher health risk in Chinese wines. The cumulative impact of wine consumption on trace elements intake in the daily diet of drinkers should not be ignored due to the presence of other intake pathways.
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Medición de Riesgo , Análisis Espectral , Oligoelementos/análisis , Vino/análisis , China , Humanos , Espectrometría de Masas , Control de CalidadRESUMEN
Aquatic animals are frequently suffered from starvation due to restricted food availability or deprivation. It is currently known that gut microbiota assists host in nutrient acquisition. Thus, exploring the gut microbiota responses would improve our understanding on physiological adaptation to starvation. To achieve this, we investigated how the gut microbiota and shrimp digestion and immune activities were affected under starvation stress. The results showed that the measured digestion activities in starved shrimp were significantly lower than in normal cohorts; while the measured immune activities exhibited an opposite trend. A structural equation modeling (SEM) revealed that changes in the gut bacterial community were directly related to digestive and immune enzyme activities, which in turn markedly affected shrimp growth traits. Notably, several gut bacterial indicators that characterized the shrimp nutrient status were identified, with more abundant opportunistic pathogens in starved shrimp, although there were no statistical differences in the overall diversity and the structures of gut bacterial communities between starved and normal shrimp. Starved shrimp exhibited less connected and cooperative interspecies interaction as compared with normal cohorts. Additionally, the functional pathways involved in carbohydrate and protein digestion, glycan biosynthesis, lipid and enzyme metabolism remarkably decreased in starved shrimp. These attenuations could increase the susceptibility of starved shrimp to pathogens infection. In summary, this study provides novel insights into the interplay among shrimp digestion, immune activities and gut microbiota in response to starvation stress.
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Digestión , Microbioma Gastrointestinal , Penaeidae , Inanición , Estrés Fisiológico , Fosfatasa Ácida/metabolismo , Amilasas/metabolismo , Animales , Bacterias/genética , Digestión/inmunología , Digestión/fisiología , Hepatopáncreas/enzimología , Lipasa/metabolismo , Muramidasa/metabolismo , Penaeidae/inmunología , Penaeidae/microbiología , Penaeidae/fisiología , Pepsina A/metabolismo , ARN Ribosómico 16S/genética , Inanición/inmunología , Inanición/microbiología , Estómago/enzimología , Estrés Fisiológico/inmunología , Estrés Fisiológico/fisiología , Superóxido Dismutasa/metabolismoRESUMEN
AIM: 2-(4,6-Dimethoxy-1,3-dioxoisoindolin-2-yl) ethyl 2-chloroacetate (QSN-10c) is one of isoindolone derivatives with antiproliferative activity against human umbilical vein endothelial cells (HUVECs). The aim of this study was to investigate its antitumor activity in vitro and anti-angiogenic effects in vitro and in vivo. METHODS: K562 leukemic cells and HUVECs were used for in vitro studies. Cell viability was examined using MTT assay. Cell apoptosis and mitochondrial transmembrane potential (Δψm) were detected with flow cytometry. Tube formation and migration of HUVECs were studied using two-dimensional Matrigel assay and wound-healing migration assay, respectively. VEGF levels were analyzed with RT-PCR and Western blotting. A zebrafish embryo model was used for in vivo anti-angiogenic studies. The molecular mechanisms for apoptosis in K562 cells and antiangiogenesis were measured with Western blotting. RESULTS: In antitumor activity studies, QSN-10c suppressed the viability of K562 cells and induced apoptosis in dose- and time-dependent manners. Furthermore, QSN-10c dose-dependently decreased the Δψm in K562 cells, increased the release of cytochrome c and the level of Bax, and decreased the level of Bcl-2, suggesting that QSN-10c-induced apoptosis of K562 cells was mediated via the mitochondrial apoptotic pathway. In anti-angiogenic activity studies, QSN-10c suppressed the viability of HUVECs and induced apoptosis in dose dependent manners. QSN-10c treatment did not alter the Δψm in HUVECs, but dose-dependently inhibited the expression of VEGF, inhibited the tube formation and cell migration in vitro, and significantly suppressed the number of ISVs in zebrafish embryos in vivo. Furthermore, QSN-10c dose-dependently suppressed the phosphorylation of AKT and GSK3ß in both HUVECs and K562 cells. CONCLUSION: QSN-10c is a novel antitumor compound that exerts both antitumor and anti-angiogenic effects via inhibiting the PI3K/AKT/GSK3ß signaling pathway.
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Apoptosis/efectos de los fármacos , Isoindoles/farmacología , Neovascularización Patológica/tratamiento farmacológico , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Transducción de Señal/efectos de los fármacos , Inhibidores de la Angiogénesis/farmacología , Animales , Antineoplásicos/farmacología , Línea Celular , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Citocromos c/metabolismo , Células Endoteliales de la Vena Umbilical Humana , Humanos , Células K562 , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Neovascularización Patológica/metabolismo , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Factor A de Crecimiento Endotelial Vascular/metabolismo , Pez Cebra/metabolismo , Proteína X Asociada a bcl-2/metabolismoRESUMEN
Stress induced by ultraviolet-B (UV-B) irradiation stimulates the accumulation of various secondary metabolites in plants. Nitric oxide (NO) serves as an important secondary messenger in UV-B stress-induced signal transduction pathways. NO can be synthesized in plants by either enzymatic catalysis or an inorganic nitrogen pathway. The effects of UV-B irradiation on the production of baicalin and the associated molecular pathways in plant cells are poorly understood. In this study, nitric oxide synthase (NOS) activity, NO release and the generation of baicalin were investigated in cell suspension cultures of Scutellaria baicalensis exposed to UV-B irradiation. UV-B irradiation significantly increased NOS activity, NO release and baicalin biosynthesis in S. baicalensis cells. Additionally, exogenous NO supplied by the NO donor, sodium nitroprusside (SNP), led to a similar increase in the baicalin content as the UV-B treatment. The NOS inhibitor, Nω-nitro-l-arginine (LNNA), and NO scavenger, 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (cPTIO) partially inhibited UV-B-induced NO release and baicalin accumulation. These results suggest that NO is generated by NOS or NOS-like enzymes and plays an important role in baicalin biosynthesis as part of the defense response of S. baicalensis cells to UV-B irradiation.
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Flavonoides/metabolismo , Óxido Nítrico/metabolismo , Transducción de Señal/efectos de la radiación , Rayos Ultravioleta , Benzoatos/farmacología , Células Cultivadas , Inhibidores Enzimáticos/farmacología , Flavonoides/química , Imidazoles/farmacología , Estructura Molecular , Donantes de Óxido Nítrico/farmacología , Óxido Nítrico Sintasa/antagonistas & inhibidores , Óxido Nítrico Sintasa/metabolismo , Nitroarginina/farmacología , Nitroprusiato/farmacología , Células Vegetales/efectos de los fármacos , Células Vegetales/metabolismo , Células Vegetales/efectos de la radiación , Scutellaria baicalensis/citología , Transducción de Señal/efectos de los fármacos , Factores de TiempoRESUMEN
Epidemiologic and preclinical studieshave shown that marine n-3 polyunsaturated fatty acids (n-3 PUFAs) elicit promising chemoprevention against breast cancer. Docosahexaenoic acid monoglyceride (MAG-DHA), a docosahexaenoic acid sn-1-monoacylglycerol does not required pancreatic lipase to be absorbed, eliciting a better bioavailability when compared with other formulations such as DHA-free fatty acid, DHA-triglycerol, or DHA-ethyl ester. However, the anticancer actions and underlying mechanisms of MAG-DHA on breast cancer remain to be assessed. In this study, MAG-DHA induced significant growth inhibition in MCF-7 and MDA-MB-231 breast cancer cells in a dose-dependent manner. MAG-DHA treatment (80 µM) led to 83.8 and 94.3% growth inhibition between MCF-7 and MDA-MB-231 cells, respectively. MAG-DHA-induced growth inhibition was tightly associated with apoptosis, as evidenced by increased active forms of caspase-3, poly (ADP-ribose) polymerase (PARP) and caspase-12. In particular, MAG-DHA-induced apoptosis was triggered by oxidative stress-mediated endoplasmic reticulum (ER) stress, as evidenced by activation of the PERK-eIF2α pathway in ER. MAG-DHA treatment also strongly suppressed the growth of E0771 murine breast cancer xenografts, significant differences of tumor volume were found between MAG-DHA group (0.271 cm3 ) and control group (0.875 cm3 ) after 15 daily MAG-DHA treatments. The in vitro antibreast cancer mechanism of MAG-DHA was supported by the in vivo xenograft model. In addition, MAG-DHA-induced ER stress concomitantly triggered autophagy in these cancer cells, and the induction of autophagy suppressed its ability to induce apoptotic cell death. Our data suggested that MAG-DHA as dietary supplement, in combination with autophagy inhibitors may be a useful therapeutic strategy in treating breast cancer.
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Apoptosis , Autofagia , Neoplasias de la Mama , Estrés del Retículo Endoplásmico , Monoglicéridos , Animales , Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Autofagia/efectos de los fármacos , Neoplasias de la Mama/tratamiento farmacológico , Línea Celular Tumoral , Estrés del Retículo Endoplásmico/efectos de los fármacos , Femenino , Xenoinjertos , Humanos , Peroxidación de Lípido , Células MCF-7 , Ratones , Monoglicéridos/farmacologíaRESUMEN
ABSTRACT: Wines from different regions have different qualities due to the impact of geographical location and climate. The sale of inferior wines seriously violates the fair-trade rights of consumers. This article provides an elemental analysis classification method for verifying the geographical origin of wines in the People's Republic of China. Inductively coupled plasma mass spectrometry, liquid chromatography isotope ratio mass spectrometry, and an isotope ratio mass spectrometer were used to analyze 142 wine samples collected from Helan Mountain, Xinjiang, Yunchuanzang, the Yanhuai Valley, and the Hexi Corridor regions. The data included elemental profiles, carbon isotope ratios (δ13C), and oxygen isotope ratios (δ18O). The results of multivariate analysis revealed that the geographical origin of wine is closely related to variations in elemental profiles and isotope ratios. Introducing δ18O and the elements Li, Mn, Ag, In, Th, Ta, and Re into the discriminant model yielded correct classification rates of the linear discriminant model of 90.8% for the training set and 87.3% for the test set.
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Oligoelementos , Vino , Carbono , China , Humanos , Isótopos , Isótopos de Oxígeno/análisis , Oligoelementos/análisis , Vino/análisisRESUMEN
Oxidative stress (OS) is a crucial factor influencing the development of Parkinson's disease (PD). Here we first reported that Lindleyin (Lin), one of the major components of rhubarb, possessed neuroprotective effects against H2O2-induced SH-SY5Y cell injury and MPTP-induced PD of C57BL/6 mice. The results showed that Lin can decrease cell death and apoptotic rate induced by H2O2 through inhibiting mitochondrial apoptotic pathway and increasing the activities of SOD, GSH-Px, and CAT as well as decreasing the level of MDA. In addition, in vivo studies showed that oral administration of Lin (5 or 20 mg/kg) showed significant change in motor function deficits, antioxidant enzyme activities, apoptotic pathway, and tyrosine hydroxylase expression. Our results reveal that Lin might be a promising anti-PD agent by reducing OS and apoptosis.
RESUMEN
The paper reports the study of gel permeation chromatography (GPC), gas chromatography/mass spectrometry (GS/MS), and column chromatography tandem MS (LC/MS/MS) for 839 pesticides and chemical contaminants, through which a GPC data bank has been established for 744 pesticides, a GC/MS data bank for 541 pesticides, and an LC/MS/MS data bank for 464 pesticides. On the basis of this study, a new method for quantitative determination of 587 pesticide residues in animal muscles such as beef, mutton, pork, chicken, and rabbit has been established using GPC cleanup followed by GC/MS and LC/MS/MS. In the method, 10 g animal samples were mixed with 20 g sodium sulfate and extracted twice with 35 mL cyclohexane-ethyl acetate (1 + 1) by blender homogenization followed by centrifugation, filtration, and concentration. An equivalent of 5 g sample was injected into a 400 x 25 mm S-X3 GPC column, with cyclohexane-ethyl acetate (1 + 1) as the mobile phase at a flow rate of 5 mL/min. The 22-40 min fraction was collected for subsequent analysis. For the 478 pesticides determined by GC/MS, the portions collected from GPC were concentrated to 0.5 mL and exchanged twice with 5 mL hexane. For the 379 pesticides determined by LC/MS/MS, the portions collected from GPC were dissolved with acetonitrile-water (60 + 40) after taking the extract to dryness with nitrogen gas. At the limit of quantification (LOQ) and 10 LOQ fortification levels of 0.1-16 000 microg/kg, recoveries were within 40-130%, among which 563 pesticide recoveries were between 60 and 130%, accounting for 96% of the compounds; 24 analytes were recovered between 40 and 60%, accounting for 4% of the compounds. The relative standard deviation was below 30% for all 587 pesticides. The limits of detection for the method were 0.1-1600 microg/kg. In comparison with GC/MS, LC/MS/MS increased the detection sensitivity 2-1000 times for 236 pesticides.
Asunto(s)
Cromatografía en Gel/métodos , Cromatografía Liquida/métodos , Cromatografía de Gases y Espectrometría de Masas/métodos , Músculos/química , Residuos de Plaguicidas/análisis , Espectrometría de Masas en Tándem/métodos , AnimalesRESUMEN
BACKGROUND: Vascular endothelial growth factor receptor-tyrosine kinase inhibitors (VEGFR-TKIs) have been developed for targeted therapies in non-small-cell lung cancer (NSCLC); moreover, some drug-related toxic reactions among cancer patients have been reported. A meta-analysis of randomized controlled trials (RCTs) to definite the incidence and the risk of grade ≥3 adverse events (AEs), serious and fatal AEs (SAEs and FAEs), with VEGFR-TKIs in advanced/metastatic NSCLC patients was performed. METHODS: A comprehensive literature search was conducted for the clinical trials published up to December 2017. Qualified studies allotted patients with advanced/metastatic NSCLC to receive either chemotherapy alone or in combination with VEGFR-TKIs. Data were extracted by 2 authors. RESULTS: Eighteen RCTs of VEGFR-TKIs plus chemotherapy, involving 8461 advanced NSCLC patients were included. The proportion of patients with grade ≥3 AEs was increased with the addition of VEGFR-TKIs (relative risk, 1.35; 95% confidence interval [CI] 1.19-1.52; incidence, 68.1% vs 50.1%; Pâ<â.001). The most common grade ≥3 AEs was neutropenia (24.9% vs 15.4%, Pâ<â.001). Addition of VEGFR-TKIs was also related to the increased risk of SAEs (relative risk, 1.34; 95% CI 1.14-1.56; incidence, 37.8% vs 27.9%; Pâ<â.001) and FAEs (relative risk, 2.16, 95% CI 1.47-3.19; incidence, 3.4% vs 1.8%). Subgroup analysis suggested there was no difference in the rates of SAEs and FAEs in the second-line settings. No evidence of bias was found between the literatures. The study was registered with PROSPERO (CRD42018099654). CONCLUSIONS: In comparison with chemotherapy alone, the addition of VEGFR-TKIs in advanced NSCLC patients was related to the increased risk of grades ≥3 AEs, SAEs, and FAEs, especially in the first-line settings. Physicians should be aware of some specific grade ≥3 adverse effect, especially haematologic adverse events, and it is also necessary to monitor cancer patients receiving VEGFR-TKIs.
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Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Neoplasias Pulmonares/tratamiento farmacológico , Inhibidores de Proteínas Quinasas/uso terapéutico , Proteínas Tirosina Quinasas/antagonistas & inhibidores , Receptores de Factores de Crecimiento Endotelial Vascular/antagonistas & inhibidores , Adulto , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Resultado del TratamientoRESUMEN
Melanoma is a malignant tumor that arises from epidermal melanocytes with high morbidity and mortality, and currently, there are no effective conventional genotoxic treatments or systematic treatment. Increasing evidence shows that n-3 polyunsaturated fatty acids (PUFAs) exhibit anti-melanoma activity, but their anti-melanoma mechanism remains elusive. Here, C57BL/6 mice were injected with B16F10 melanoma cells via a tail vein to establish a lung metastasis model. n-3 PUFAs were significantly increased in lung metastatic tissues from mice treated with algal oil, especially rich in docosahexaenoic acid (DHA). Algal oil treatment significantly suppressed pulmonary metastases and outgrowth of melanoma cells, which was associated with autophagy induction, as evidenced by an increase in LC3-II levels. In addition, algae oil-triggered autophagy was mediated by inactivation of the mammalian target of rapamycin (mTOR) and p38 mitogen-activated protein (MAP) kinase, and activation of c-Jun N-terminal kinases (JNKs), which led to a decrease in p62 accumulation and decreased secretion of proinflammatory cytokine interleukin-1ß (IL-1ß). These results suggest that algal oil exerts its antitumourigenic activities via autophagy-mediated p62 elimination and anti-inflammatory properties.
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Autofagia/efectos de los fármacos , Chlorophyta/química , Ácidos Grasos Omega-3/administración & dosificación , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/fisiopatología , Melanoma/patología , Aceites de Plantas/administración & dosificación , Animales , Línea Celular Tumoral , Ácidos Grasos Omega-3/análisis , Humanos , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/secundario , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Masculino , Ratones , Ratones Endogámicos C57BL , Metástasis de la Neoplasia/tratamiento farmacológico , Aceites de Plantas/análisis , Serina-Treonina Quinasas TOR/genética , Serina-Treonina Quinasas TOR/metabolismoRESUMEN
A new method using gel permeation chromatography (GPC) cleanup followed by gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-tandem mass spectrometry (LC-MS-MS) has been established for quantitative determination of 437 pesticide residues in animal tissues such as beef, mutton, pork, chicken, and rabbit. Based on an appraisal of the characteristics of both GC-MS and LC-MS-MS, validation experiments were conducted for 660 pesticides. In the method, 10 g animal samples were mixed with 20 g sodium sulfate and extracted with 35 mL of cyclohexane+ethyl acetate (1+1) twice by blender homogenization, centrifugation, and filtration. Evaporation was conducted and an equivalent of 5 g sample was injected into a 400 mm x 25 mm S-X3 GPC column, with cyclohexane+ethyl acetate (1+1) as the mobile phase at a flow rate of 5 mL/min. The 22-40 min fraction was collected for subsequent analysis. For the 368 pesticides determined by GC-MS, the portions collected from GPC were concentrated to 0.5 mL and exchanged with 5 mL hexane twice. For the 69 pesticides by LC-MS-MS, the portions collected from GPC were dissolved with acetonitrile+water (60+40) after taking the extract to dryness with nitrogen gas. In the linear range of each pesticide, the correlation coefficient was r > or = 0.98, exceptions being dinobuton, linuron, and fenamiphos sulfoxide. At the low, medium and high three fortification levels of 0.2-4800 microg/kg, recoveries fell within 40-120%, among which 417 pesticides recoveries between 60% and 120%, accounting for 95%, 20 analytes between 40% and 60%, accounting for 5%. The relative standard deviation was below 28% for all 437 pesticides. The limits of detection for the method were 0.2-600 microg/kg, depending on each pesticide.
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Cromatografía en Gel/métodos , Cromatografía Liquida/métodos , Cromatografía de Gases y Espectrometría de Masas/métodos , Espectrometría de Masas/métodos , Residuos de Plaguicidas/análisis , Animales , Residuos de Plaguicidas/aislamiento & purificación , Reproducibilidad de los ResultadosRESUMEN
A method was developed for determination of residues of 446 pesticides in fruits and vegetables through the use of cleanup by a 3-cartridge solid-phase extraction-gas chromatography/ mass spectrometry (GC/MS) and liquid chromatography/tandem mass spectrometry (LC/MS/MS). Fruit and vegetable samples (20 g) were extracted with 40 mL acetonitrile, salted out, and centrifuged. Half of the supernatant was passed into an Envi-18 cartridge, eluted with acetonitrile, and cleaned up with Envi-Carb and aminopropyl Sep-Pak cartridges in series after concentration of the eluates. Pesticides were eluted with acetonitrile-toluene (3 + 1, v/v), and eluates were concentrated to 0.5 mL and then added into internal standards after solvent exchange with 2 mL hexane and used for determination of 383 pesticides by GC/MS. The other half of the supernatant was concentrated to 1 mL and cleaned up with Envi-Carb and aminopropyl Sep-Pak cartridges in series. Pesticides were eluted with acetonitrile-toluene (3 + 1, v/v), and the eluates were concentrated to 0.5 mL, dried with nitrogen gas, diluted to 1.0 mL with acetonitrile-water (3 + 2, v/v), and used for determination of 63 pesticides by LC/MS/MS. The limit of detection for the method was 0.2-600 ng/g depending on the individual pesticide. In the method, fortification recovery tests at high, medium, and low levels were conducted on 6 varieties of fruits and vegetables, i.e., apples, oranges, grapes, cabbage, tomatoes, and celery, with average recoveries falling within the range of 55.0-133.8% for 446 pesticides, among which average recoveries between 60.0-120.0% accounted for 99% of the results. The relative standard deviation was between 2.1-39.1%, of which a relative standard deviation of 2.1-25.0% made up 96% of the results. Experiments proved that the method was applicable for determination of residues of 446 pesticides in fruit and vegetables.
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Técnicas de Química Analítica/métodos , Cromatografía Liquida/métodos , Frutas/metabolismo , Cromatografía de Gases y Espectrometría de Masas/métodos , Espectrometría de Masas/métodos , Residuos de Plaguicidas/análisis , Plaguicidas/análisis , Verduras/metabolismo , Acetonitrilos/farmacología , Contaminación de Alimentos , Hexanos/análisis , Nitrógeno , Plaguicidas/aislamiento & purificación , Estándares de Referencia , Reproducibilidad de los Resultados , Solventes , Tolueno/análisis , Tolueno/químicaRESUMEN
BACKGROUND: Thalidomide is an immunomodulatory and anti-angiogenic drug that has shown promise in patients with myeloma. Trials comparing efficacy of standard melphalan and prednisone (MP) therapy with MP plus thalidomide (MPT) in transplant-ineligible or elderly patients with multiple myeloma (MM) have provided conflicting evidence. This meta-analysis aimed to determine the efficacy and toxicity of thalidomide in previously untreated elderly patients with myeloma. METHODS: Medline, the Cochrane Controlled Trials register, conference proceedings of the American Society of Hematology (1995-2014), the American Society of Clinical Oncology (1995-2014), and CBM, VIP, and CNKI databases were searched for randomized control trials with the use of the medical subject headings "MM " and "thalidomide ". Trials were assessed by two reviewers for eligibility. Meta-analysis was conducted using a fixed effects model. Sensitivity analysis was performed to test the robustness of the findings. RESULTS: Overall, seven trials were identified, covering a total of 1821 subjects. The summary hazard ratio (thalidomide vs. control) was 0.82 (95% confidence interval [CI]: 0.72-0.94) for overall survival (OS), and 0.65 (95% CI: 0.58-0.73) for progression-free survival, in favor of thalidomide treated group. The risk ratio of complete response with induction thalidomide was 3.48 (95% CI: 2.24-5.41). A higher rate of III/IV adverse events were observed in MPT arm compared with the MP arm. However, analysis of sub-groups administering anticoagulation as venous thromboembolism prophylaxis suggested no difference in relative risk of thrombotic events between two arms (RR = 1.47, 95% CI: 0.43-5.07, P = 0.54). Further analysis of trials on the treatment effects of MPT versus MP on adverse events-related mortality showed no statistical difference between two arms (RR = 1.24, 95% CI: [0.95-1.63], P = 0.120). CONCLUSION: Thalidomide appears to improve the OS of elderly and/or transplant-ineligible patients with MM when it is added to standard MP therapy.
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Inmunosupresores/uso terapéutico , Mieloma Múltiple/tratamiento farmacológico , Talidomida/uso terapéutico , Supervivencia sin Enfermedad , Humanos , Melfalán/uso terapéutico , Mieloma Múltiple/mortalidad , Prednisona/uso terapéuticoRESUMEN
Malignant melanoma is the most lethal form of skin cancer. Although preclinical studies have shown that n-3 polyunsaturated fatty acids (PUFAs) are beneficial for prevention of melanoma, the molecular mechanisms underlying the protective effects of n3 PUFAs on melanoma remain largely unknown. In the present study, endogenously increased levels of n-3 PUFAs in the tumor tissues of omega3 fatty acid desaturase (fat1) transgenic mice was associated with a reduction in the growth rate of melanoma xenografts. This reduction in tumor growth in fat1 mice compared with wildtype controls may have been associated, in part, to the: i) Increased expression of Ecadherin and the reduced expression of its transcriptional repressors, the zinc finger Ebox binding homeobox 1 and snail family transcriptional repressor 1; ii) significant repression of the epidermal growth factor receptor/Akt/ßcatenin signaling pathway; and iii) formation of significant levels of n3 PUFAderived lipid mediators, particularly resolvin D2 and E1, maresin 1 and 15hydroxyeicosapentaenoic acid. In addition, vitamin E administration counteracted n3 PUFAinduced lipid peroxidation and enhanced the antitumor effect of n3 PUFAs, which suggests that the protective role of n3 PUFAs against melanoma is not mediated by n3 PUFAsinduced lipid peroxidation. These results highlight a potential role of n3 PUFAs supplementation for the chemoprevention of melanoma in highrisk individuals, and as a putative adjuvant agent in the treatment of malignant melanoma.
Asunto(s)
Cadherinas/metabolismo , Proteínas de Caenorhabditis elegans/genética , Ácido Graso Desaturasas/genética , Ácidos Grasos Omega-3/metabolismo , Melanoma/metabolismo , Neoplasias Cutáneas/metabolismo , beta Catenina/metabolismo , Animales , Caenorhabditis elegans/genética , Línea Celular Tumoral , Femenino , Masculino , Melanoma/patología , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Transducción de Señal , Piel/metabolismo , Piel/patología , Neoplasias Cutáneas/patologíaRESUMEN
A method is described for the determination of 16 sulfonamides in honey. Samples are dissolved in phosphoric acid solution (pH2), cleaned up with 2 solid-phase extraction (SPE) cartridges, an aromatic sulfonic cation-exchange cartridge and an Oasis HLB SPE cartridge, and analyzed both qualitatively and quantitatively by liquid chromatography/tandem mass spectrometry (LC/MS/MS) under the selected conditions. Without exception, calibration curves were linear (r = > 0.995), when sulfamethizole was between 1.0 and 25.0 microg/kg; sulfacetamide, sulfapyridine, sulfadiazine, sulfachloropyridazine, sulfamethoxazole, sulfamerazine, sulfisoxazole, sulfamonomethoxine, and sulfadoxine were between 2.0 and 50.0 microg/kg; sulfamethoxypyridazine, sulfadimethoxine, and sulfathiazole were between 4.0 and 100.0 microg/kg; sulfamethazine and sulfameter were between 8.0 and 200.0 microg/kg; and sulfaphenazole was between 12.0 and 300.0 microg/kg. Average recoveries at 4 fortification levels in the range of 1.0-300 microg/kg in honey were 70.9-102.5%, and relative standard deviations were 2.02-11.52%. The limits of quantitation for the 16 sulfonamides were between 1.0 and 12.0 microg/kg, with the LC/MS/MS method.
Asunto(s)
Cromatografía Liquida/métodos , Análisis de los Alimentos/métodos , Miel/análisis , Espectrometría de Masas/métodos , Sulfonamidas/análisis , Sulfonamidas/clasificación , Tampones (Química) , Calibración , Fluorescencia , Concentración de Iones de Hidrógeno , Reproducibilidad de los Resultados , Sensibilidad y EspecificidadRESUMEN
Eighteen laboratories participated in a collaborative study on the determination of clopidol residues in chicken muscle tissues by liquid chromatography. Of these, results from 16 laboratories which rigorously followed the method were subjected to statistical analysis. The method performance was assessed by all participants using 14 samples of chicken muscle fortified at concentrations ranging from 0.1 to 5.0 mg/kg. In addition, 9 participants each reported results for 6 clopidol-incurred samples in chicken muscle. Test portions were extracted with acetonitrile, and the extracts were purified with alumina and anion exchange resin solid-phase extraction cartridges in sequence. Clopidol was separated by reversed-phase liquid chromatography and quantified at 270 nm. Average recoveries ranged from 81.8 to 85.4%, reproducibility relative standard deviation (RSDR) ranged from 11.9 to 22.6%, and repeatability relative standard deviation (RSDr) ranged from 9.9 to 15.1%. For clopidol-incurred samples at concentrations of 0.100-0.687 mg/kg, the mean determination value range was 0.099-0.659 mg/kg; RSDR was 12.6-19.8%, RSDr was 3.1-8.5%; and HORRAT values were 0.7-1.1. The accuracy and precision of the method are in conformity with the requirements specified by AOAC INTERNATIONAL. The method was adopted Official First Action in April 2003.
Asunto(s)
Pollos , Cromatografía Liquida/métodos , Clopidol/análisis , Coccidiostáticos/análisis , Residuos de Medicamentos/análisis , Músculo Esquelético/química , Animales , Laboratorios , Carne/análisis , Control de Calidad , Reproducibilidad de los Resultados , Sensibilidad y EspecificidadRESUMEN
This study demonstrated that streptomycin in honey is quite stable, and the results showed no obvious differences for 3 samples containing incurred analyte during continuous testing for 4 months. Fifteen laboratories evaluated method performance at 4 fortification levels ranging from 0.010 to 0.100 mg/kg; the recoveries ranged from 73.7 to 78.5%, the reproducibility relative standard deviations ranged from 5.76 to 15.85%, and the repeatability relative standard deviations ranged from 1.64 to 3.80%. In 1999-2002, the method was used to determine streptomycin residues in 5106 lots of honey samples from >20 provinces all over China. All of the honey samples were found to be in conformity with the requirements of customs clearance for exports to Europe, the United States, and Japan. The continuous 4-year quality analysis also found that C18 solid-phase extraction cartridges should be standardized to ensure that the analytical results are accurate when different lots of cartridges are used.
Asunto(s)
Antibacterianos/análisis , Residuos de Medicamentos/análisis , Miel/análisis , Estreptomicina/análisis , Tampones (Química) , Resinas de Intercambio de Catión , Cromatografía Liquida , Indicadores y Reactivos , Control de Calidad , Estándares de Referencia , Reproducibilidad de los Resultados , SolventesRESUMEN
α-eleostearic acid (α-ESA) has been shown to possess antitumor activity in cancer cells. However, the underlying mechanism(s) remain largely unknown. The present study was designed to investigate the antitumor effect of α-ESA in breast cancer cells showing different expression levels of the human epidermal growth factor receptor 2 (HER2). α-ESA inhibited cell growth and induced apoptosis in the SKBR3 and T47D breast cancer cell lines. The mechanism by which cell growth was inhibited involved G0/G1 and G2/M cell cycle phase arrest. The MTT assay showed that SKBR3 cells are more sensitive to α-ESA compared to T47D cells. Western blot analysis revealed that α-ESA treatment not only reduced HER2/HER3 protein expression, but also increased the level of phosphorylated phosphatase and tensin homolog protein (PTEN), which led to decreased levels of phosphorylated Akt. Inactive Akt further reduced phosphorylation of glycogen synthase kinase-3ß (GSK-3ß) and B-cell lymphoma 2 (Bcl-2)associated death promoter (BAD) proteins. Furthermore, the level of the anti-apoptotic protein Bcl-2 was found to be reduced following α-ESA treatment. Notably, nuclear factor κB (NF-κB) was activated by α-ESA treatment. Data of the present study showed that the antitumor activity of α-ESA is at least partly mediated by reduction of the HER2/HER3 heterodimer protein level, activation of the Akt/BAD/Bcl-2 apoptotic pathway and inhibition of the Akt/GSK-3ß survival pathway in the two breast cancer cell lines investigated in this study. Therefore, α-ESA may be considered a beneficial dietary factor for the prevention and treatment of invasive breast cancer in cells overexpressing HER2.
Asunto(s)
Apoptosis/efectos de los fármacos , Neoplasias de la Mama/fisiopatología , Ácidos Linolénicos/farmacología , Receptor ErbB-2/metabolismo , Receptor ErbB-3/metabolismo , Transducción de Señal/efectos de los fármacos , Antineoplásicos/farmacología , Neoplasias de la Mama/metabolismo , Puntos de Control del Ciclo Celular/efectos de los fármacos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Femenino , Glucógeno Sintasa Quinasa 3/metabolismo , Glucógeno Sintasa Quinasa 3 beta , Humanos , Fosfohidrolasa PTEN/metabolismo , Fosforilación , Proteínas Proto-Oncogénicas c-akt/metabolismo , Proteína Letal Asociada a bcl/metabolismoRESUMEN
Three cooking methods, namely boiling, steaming, and stir-frying for 5 to 10 min, were used to evaluate the effect on nutrient components, free amino acids, L-ascorbic acid, total phenolic contents, and antioxidant capacities of bamboo shoots (Phyllostachys praecox). Results showed that boiling and stir-frying had a great effect on the nutrient components and they decreased the contents of protein, soluble sugar, and ash, and caused a great loss in the total free amino acids (decreased by 38.35% and 34.86%, respectively). Significant differences (P<0.05) in free amino acids were observed in the samples cooked by different methods. Stir-fried bamboo shoots had a high fat content which increased by 528.57% because of the addition of edible oil. After boiling, the L-ascorbic acid and total phenolic contents were significantly reduced, while steaming increased total phenolic content by 3.98% and stir-frying well-preserved L-ascorbic acid (78.87% of its previous content). Results of the antioxidative property study showed that stir-frying could increase antioxidant capacities of bamboo shoots. It is concluded that stir-frying is more suitable for bamboo shoots because it could obtain the maximum retention of antioxidant capacities.