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1.
Heliyon ; 10(17): e36611, 2024 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-39281453

RESUMEN

Compressors are important production equipment in the petrochemical industry, and the accuracy of their fault diagnosis is critical. In order to detect and diagnose compressor equipment faults in a timely manner, this paper constructs a deep residual shrinkage visual network (DRS-ViT). The network comprises a modified residual network (ResNet) and a vision transformer (ViT). The obtained compressor vibration signals were transformed into gram angle sum field (GASF) plots using gram angle field (GAF). The resulting image is the passed through a modified ResNet network to extract initial features. The extracted feature images are subsequently input into the ViT model for fault classification. The experimental results demonstrate that the fault diagnosis accuracy achieved by the DRS-ViT model is 99.5 %. The visualization of the model indicates that it can effectively identify the fault points. The validity and robustness of the DRS-ViT model are confirmed through comparison and analysis with various models.

2.
Planta ; 257(2): 45, 2023 Jan 25.
Artículo en Inglés | MEDLINE | ID: mdl-36695892

RESUMEN

MAIN CONCLUSION: This study reported seven new plastomes from Impatiens and observed three highly variable regions for phylogeny and DNA barcoding, which resolved the relationships among sections of subgenus Impatiens. Impatiens L. (Balsaminaceae, Ericales) is one of the largest and most diverse genera of angiosperms, widely known for its taxonomic difficulty. In this study, we reevaluated the infrageneric relationships within the genus Impatiens, using complete plastome sequence data. Seven complete plastomes of Impatiens (representing 6 species) were newly sequenced and characterized along with 20 previously published plastomes of other Impatiens species, plus 2 plastomes of outgroups (Hydrocera triflora, Balsaminaceae; Marcgravia coriacea, Marcgraviaceae). The total size of these 29 plastomes ranged from 151,538 bp to 152,917 bp, except 2 samples of Impatiens morsei, which exhibited a shorter length and lost some genes encoding NADH dehydrogenase subunits. Moreover, the number of simple sequence repeats (SSRs) ranged from 51 to 113, and the number of long repeats from 17 to 26. In addition, three highly variable regions were identified (trnG-GCC (The previous one), ndhF-rpl32-trnL-UGA-ccsA, and ycf1). Our phylogenomic analysis based on 80 plastome-derived protein-coding genes strongly supported the monophyly of Impatiens and its two subgenera (Clavicarpa and Impatiens), and fully resolved relationships among the six (out of seven) sampled sections of subgenus Impatiens. Overall, the plastome DNA markers and phylogenetic results reported in this study will facilitate future identification, taxonomic and DNA barcoding studies in Impatiens as well as evolutionary studies in Balsaminaceae.


Asunto(s)
Balsaminaceae , Impatiens , Balsaminaceae/genética , Impatiens/genética , Filogenia , Secuencia de Bases , Evolución Molecular
3.
Sci Total Environ ; 851(Pt 1): 158053, 2022 Dec 10.
Artículo en Inglés | MEDLINE | ID: mdl-35985601

RESUMEN

In the present work, a delicate CFD research of a multi-street canyon model with varying thermal stratifications and non-uniformities of buildings was conducted to investigate the street ventilation and pollutant dispersion between the compact urban blocks. Non-isothermal turbulent wind flow, temperature field and pollutant dispersion in a two-dimensional computational domain were solved by the Renormalization Group (RNG) k-ε turbulence model along with the enhanced wall treatment. Present numerical results indicated that the variation of ground heating intensity has a significant influence on the airflow pattern in the step-down case, and the distribution of pollutants in the street canyons mainly depends on the variation of the upper clockwise vortex. The canyon ventilation performance became better as the unstable thermal stratification strengthened. Similarly, the increase of ground heating intensity could reduce ADF (atmospheric dispersion factor) in the step-down case and ADF became the lowest when Ri = -3.92 was maintained. Additionally, the increase of building unevenness further complicated the canyon airflow structure, which aggravated the pollution of the canyon. In the step-down configuration, as the standard deviation of adjacent building height gradually increases, canyon ventilation could be further enhanced. For the step-up configuration, the best ventilation performance was found at σH = 16.7 %. ADF of adjacent canyons also varied greatly. When σH = 33.3 % was maintained, the peak and bottom values of ADF were discovered in the step-up and step-down cases, respectively. Present research has provided a theoretical reference for guiding urban design and improve living environment in modern compact cities.


Asunto(s)
Contaminantes Atmosféricos , Contaminantes Ambientales , Contaminantes Atmosféricos/análisis , Ciudades , Modelos Teóricos , Emisiones de Vehículos/análisis , Viento
4.
Chin J Integr Med ; 28(3): 195-201, 2022 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-33423188

RESUMEN

OBJECTIVE: To explore the therapeutic effect of Bushen Yiqi Huoxue Decoction BYHD) in patients with diminished ovarian reserve (DOR). METHODS: A total of 180 patients with DOR diagnosed from December 2013 to December 2014 were equally assigned into progynova and duphaston (E+D) group, Zuogui Pill group and BYHD group with 60 cases in each by computerized randomization. Patients received E+D, Zuogui Pill or BYHD for 12 months, respectively. Follicle stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), anti-Müllerian hormone (AMH), antral follicle count (AFC), ovarian volume, endometrial thickness, and the resistance indices (RIs) of ovarian arteries and uterine arteries were observed before and after treatment. RESULTS: Nine women (4 from the E+D group, 3 from the Zuogui Pill group, and 2 from the BYHD group) withdrew from the study. After 6 months, Zuogui Pill and BYHD significantly decreased FSH and LH and increased endometrial thickness and AMH (all P<0.01). BYHD also resulted in E2 elevation (P<0.05), ovary enlargement (P<0.05), AFC increase (P<0.01), and RI of ovarian arteries decrease (P<0.05). After 12 months, further improvements were observed in the Zuogui Pill and BYHD groups (all P<0.01), but BYHD showed better outcomes, with lower FSH, larger ovaries and a thicker endometrium compared with the Zuogui Pill group (all P<0.01). However, E+D only significantly increased endometrial thickness (P<0.01) and no significant improvements were observed in the RI of uterine arteries in the three groups. CONCLUSIONS: BYHD had a favorable therapeutic effect in patients with DOR by rebalancing hormone levels, promoting ovulation, and repairing the thin endometrium. The combination of tonifying Shen (Kidney), benefiting qi and activating blood circulation may be a promising therapeutic strategy for DOR.


Asunto(s)
Reserva Ovárica , Hormona Antimülleriana/farmacología , Medicamentos Herbarios Chinos , Femenino , Hormona Folículo Estimulante , Humanos , Hormona Luteinizante
5.
BMC Gastroenterol ; 21(1): 459, 2021 Dec 07.
Artículo en Inglés | MEDLINE | ID: mdl-34876031

RESUMEN

BACKGROUND: Helicobacter pylori (Hp) is a class I carcinogen in gastric carcinogenesis, but its role in Barrett's esophagus (BE) is unknown. Therefore, we aimed to explore the possible relationship. METHODS: We reviewed observational studies published in English until October 2019. Summary odds ratios (ORs) and 95% confidence intervals (CIs) were calculated for included studies. RESULTS: 46 studies from 1505 potential citations were eligible for inclusion. A significant inverse relationship with considerable heterogeneity was found between Hp (OR = 0.70; 95% CI, 0.51-0.96; P = 0.03) and BE, especially the CagA-positive Hp strain (OR = 0.28; 95% CI, 0.15-0.54; P = 0.0002). However, Hp infection prevalence was not significantly different between patients with BE and the gastroesophageal reflux disease (GERD) control (OR = 0.99; 95% CI, 0.82-1.19; P = 0.92). Hp was negatively correlated with long-segment BE (OR = 0.47; 95% CI, 0.25-0.90; P = 0.02) and associated with a reduced risk of dysplasia. However, Hp had no correlated with short-segment BE (OR = 1.11; 95% CI, 0.78-1.56; P = 0.57). In the present infected subgroup, Hp infection prevalence in BE was significantly lower than that in controls (OR = 0.69; 95% CI, 0.54-0.89; P = 0.005); however, this disappeared in the infection history subgroup (OR = 0.88; 95% CI, 0.43-1.78; P = 0.73). CONCLUSIONS: Hp, especially the CagA-positive Hp strain, and BE are inversely related with considerable heterogeneity, which is likely mediated by a decrease in GERD prevalence, although this is not observed in the absence of current Hp infection.


Asunto(s)
Esófago de Barrett , Reflujo Gastroesofágico , Infecciones por Helicobacter , Helicobacter pylori , Esófago de Barrett/epidemiología , Reflujo Gastroesofágico/complicaciones , Reflujo Gastroesofágico/epidemiología , Infecciones por Helicobacter/complicaciones , Infecciones por Helicobacter/epidemiología , Humanos , Estudios Observacionales como Asunto
6.
Front Cell Infect Microbiol ; 11: 665406, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34350129

RESUMEN

Gut microbiota has been proved to be involved in the occurrence and development of many diseases, such as type 2 diabetes, obesity, coronary heart disease, etcetera. It provides a new idea for the pathogenesis of polycystic ovary syndrome (PCOS). Our study showed that the gut microbial community of PCOS with high low-density lipoprotein cholesterol (LDLC) has a noticeable imbalance. Gut microbiota of PCOS patients was significantly changed compared with CON, and these changes were closely related to LDLC. Gut microbiota may affect the metabolic level of PCOS patients through multiple metabolic pathways, and lipid metabolism disorder may further aggravate the imbalance of gut microbiota. Actinomycetaceae, Enterobacteriaceae and Streptococcaceae had high accuracy in the diagnosis of PCOS and the differentiation of subgroups, suggesting that they may play an important role in the diagnosis and treatment of PCOS in the future. Also, the model we built showed good specificity and sensitivity for distinguishing PCOS from CON (including L_CON and L_PCOS, H_CON and H_PCOS). In conclusion, this is the first report on the gut microbiota of PCOS with high LDLC, suggesting that in the drug development or treatment of PCOS patients, the difference of gut microbiota in PCOS patients with different LDLC levels should be fully considered.


Asunto(s)
Diabetes Mellitus Tipo 2 , Microbioma Gastrointestinal , Síndrome del Ovario Poliquístico , Colesterol , HDL-Colesterol , LDL-Colesterol , Femenino , Humanos
7.
Trials ; 21(1): 169, 2020 Feb 11.
Artículo en Inglés | MEDLINE | ID: mdl-32046752

RESUMEN

BACKGROUND: Polycystic ovary syndrome (PCOS) is a complex endocrine syndrome with poorly understood mechanisms. To provide patients with PCOS with individualized therapy, it is critical to precisely diagnose the phenotypes of the disease. However, the criteria for diagnosing the different phenotypes are mostly based on symptoms, physical examination and laboratory results. This study aims to compare the accuracy and efficacy of diagnosing PCOS by integrating metabolomic markers with common clinical characteristics. METHODS: This is a prospective, multicenter, analyst-blinded, randomized controlled trial. Participants will be grouped into (1) people without PCOS (healthy control group), (2) patients diagnosed with PCOS based on clinical indices (experimental group 1), and (3) patients diagnosed with PCOS based on metabolomic indices (experimental group 2). A total of 276 participants, including 60 healthy people and 216 patients with PCOS, will be recruited. The 216 patients with PCOS will be randomly assigned to the two experimental groups in a 1:1 ratio, and each group will receive a different 6-month treatment. The primary outcome for the experimental groups will be the effect of PCOS treatment. DISCUSSION: The results of this trial should help to determine whether using metabolomic indices is more accurate and effective than using clinical characteristics in diagnosing the phenotypes of PCOS. The results could provide a solid foundation for the accurate diagnosis of different PCOS subgroups and for future research on individualized PCOS therapy. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ID: ChiCTR-INR-1800016346. Registered 26 May 2018.


Asunto(s)
Metabolómica , Síndrome del Ovario Poliquístico/diagnóstico , Adolescente , Adulto , Biomarcadores/sangre , Biomarcadores/metabolismo , Femenino , Hormonas/metabolismo , Humanos , Metabolismo de los Lípidos , Persona de Mediana Edad , Estudios Multicéntricos como Asunto , Examen Físico , Síndrome del Ovario Poliquístico/sangre , Síndrome del Ovario Poliquístico/metabolismo , Síndrome del Ovario Poliquístico/terapia , Estudios Prospectivos , Ensayos Clínicos Controlados Aleatorios como Asunto , Adulto Joven
8.
Nanomaterials (Basel) ; 8(2)2018 Jan 25.
Artículo en Inglés | MEDLINE | ID: mdl-29370148

RESUMEN

Synthesizing phosphors with high performance is still a necessary work for phosphor-converted white light-emitting diodes (W-LEDs). In this paper, three series of CaAlSiN3:Eu2+ (denoted as CASN:Eu2+) phosphors using Eu2O3, EuN and EuB6 as raw materials respectively are fabricated by under the alloy precursor normal pressure nitridation synthesis condition. We demonstrate that CASN:Eu2+ using nano-EuB6 as raw material shows higher emission intensity than others, which is ascribed to the increment of Eu2+ ionic content entering into the crystal lattice. An improved thermal stability can also be obtained by using nano-EuB6 due to the structurally stable status, which is assigned to the partial substitution of Eu-O (Eu-N) bonds by more covalent Eu-B ones that leads to a higher structural rigidity. In addition, the W-LEDs lamp was fabricated to explore its possible application in W-LEDs based on blue LEDs. Our results indicate that using EuB6 as raw materials can provide an effective way of enhancing the red emission and improving the thermal stability of the CASN:Eu2+ red phosphor.

9.
PLoS One ; 9(8): e105573, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-25140872

RESUMEN

Mycorrhizal association is known to be important to orchid species, and a complete understanding of the fungi that form mycorrhizas is required for orchid ecology and conservation. Liparis japonica (Orchidaceae) is a widespread terrestrial photosynthetic orchid in Northeast China. Previously, we found the genetic diversity of this species has been reduced recent years due to habitat destruction and fragmentation, but little was known about the relationship between this orchid species and the mycorrhizal fungi. The Rhizoctonia-like fungi are the commonly accepted mycorrhizal fungi associated with orchids. In this study, the distribution, diversity and specificity of culturable Rhizoctonia-like fungi associated with L. japonica species were investigated from seven populations in Northeast China. Among the 201 endophytic fungal isolates obtained, 86 Rhizoctonia-like fungi were identified based on morphological characters and molecular methods, and the ITS sequences and phylogenetic analysis revealed that all these Rhizoctonia-like fungi fell in the same main clade and were closely related to those of Tulasnella calospora species group. These findings indicated the high mycorrhizal specificity existed in L. japonica species regardless of habitats at least in Northeast China. Our results also supported the wide distribution of this fungal partner, and implied that the decline of L. japonica in Northeast China did not result from high mycorrhizal specificity. Using culture-dependent technology, these mycorrhizal fungal isolates might be important sources for the further utilizing in orchids conservation.


Asunto(s)
Especificidad del Huésped , Orchidaceae/microbiología , Rhizoctonia/genética , China , ADN Intergénico , Micorrizas/genética , Micorrizas/aislamiento & purificación , Filogenia , Rhizoctonia/aislamiento & purificación , Rhizoctonia/patogenicidad
10.
J Biol Chem ; 289(23): 16006-15, 2014 Jun 06.
Artículo en Inglés | MEDLINE | ID: mdl-24755224

RESUMEN

There are multiple isoforms of p90 ribosomal S6 kinase (RSK), which regulate diverse cellular functions such as cell growth, proliferation, maturation, and motility. However, the relationship between the structures and functions of RSK isoforms remains undetermined. Artemia is a useful model in which to study cell cycle arrest because these animals undergo prolonged diapauses, a state of obligate dormancy. A novel RSK isoform was identified in Artemia, which was termed Ar-Rsk2. This isoform was compared with an RSK isoform that we previously identified in Artemia, termed Ar-Rsk1. Ar-Rsk2 has an ERK-docking motif, whereas Ar-Rsk1 does not. Western blot analysis revealed that Ar-Rsk1 was activated by phosphorylation, which blocked meiosis in oocytes. Knockdown of Ar-Rsk1 reduced the level of phosphorylated cdc2 and thereby suppressed cytostatic factor activity. This indicates that Ar-Rsk1 regulates the cytostatic factor in meiosis. Expression of Ar-Rsk2 was down-regulated in Artemia cysts in which mitosis was arrested. Knockdown of Ar-Rsk2 resulted in decreased levels of cyclin D3 and phosphorylated histone H3, and the production of pseudo-diapause cysts. This indicates that Ar-Rsk2 regulates mitotic arrest. PLK and ERK RNAi showed that Ar-Rsk2, but not Ar-Rsk1, could be activated by PLK-ERK in Artemia. This is the first study to report that RSK isoforms with and without an ERK-docking motif regulate mitosis and meiosis, respectively. This study provides insight into the relationship between the structures and functions of RSK isoforms.


Asunto(s)
Artemia/citología , Isoenzimas/metabolismo , Meiosis , Mitosis , Proteínas Quinasas S6 Ribosómicas 90-kDa/metabolismo , Secuencia de Aminoácidos , Animales , Artemia/embriología , Artemia/enzimología , Secuencia de Bases , ADN , Desarrollo Embrionario , Técnicas de Silenciamiento del Gen , Humanos , Datos de Secuencia Molecular , Filogenia , Reacción en Cadena de la Polimerasa , Proteínas Quinasas S6 Ribosómicas 90-kDa/genética , Homología de Secuencia de Aminoácido
11.
J Pharmacol Sci ; 124(4): 433-44, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-24739263

RESUMEN

Accumulating evidences have shown that diabetes upregulated the function and expression of CYP3A4, but the mechanism remained unclear. In this study, HepG2 cells were incubated with serum from diabetic rats induced by streptozotocin, and the activity of CYP3A4 was measured by substrate metabolism. Results showed that incubation with diabetic serum significantly induced CYP3A4 activity in HepG2 cells. To identify the specific factors contributing to the regulation, the abnormally altered components in diabetic serum, including glucose, insulin, cholesterol, and free fatty acids were screened. It was found that only fatty acids concentration-dependently up-regulated CYP3A4 activity, and the induction by fatty acids was further confirmed in Fa2N-4 cells. Data from western blotting and QT-PCR showed that induction of CYP3A4 activity was associated with up-regulation of CYP3A4 protein and mRNA levels. In addition, effects of pharmacological inhibitors on fatty acid-induced CYP3A4 activity were studied. The results indicated that the induction of CYP3A4 activity by oleic acid may be partly via AMPK-, PKC-, and NF-κB-dependent pathways, whereas that by palmitic acid was possibly associated with the PKC-dependent pathway. In conclusion, the increased levels of fatty acids may be one of the reasons leading to the elevated function and expression of CYP3A4 under diabetic conditions.


Asunto(s)
Citocromo P-450 CYP3A/genética , Citocromo P-450 CYP3A/metabolismo , Diabetes Mellitus Experimental/enzimología , Diabetes Mellitus Experimental/metabolismo , Ácidos Grasos/metabolismo , Hígado/enzimología , Hígado/metabolismo , Animales , Línea Celular , Diabetes Mellitus Experimental/sangre , Inducción Enzimática/efectos de los fármacos , Ácidos Grasos/sangre , Ácidos Grasos/farmacología , Ácidos Grasos/fisiología , Expresión Génica/efectos de los fármacos , Células Hep G2 , Hepatocitos , Humanos , ARN Mensajero/metabolismo , Ratas , Estreptozocina , Regulación hacia Arriba/efectos de los fármacos
12.
Artículo en Inglés | MEDLINE | ID: mdl-24657409

RESUMEN

A high-performance liquid chromatographic-tandem mass spectrometric (HPLC-MS/MS) method was developed and validated to determine sitafloxacin in human plasma with dextrorphan as internal standard. Chromatographic separation was performed on a ZORBAX SB-C18 column (3.5µm, 2.1mm×100mm) with the mobile phase of methanol/water (containing 0.1% formic acid) (46:54, v/v) at a flow rate of 0.2mL/min. Quantification was performed using multiple-reaction monitoring of the transitions at m/z 410.2 → 392.2 for sitafloxacin and m/z 258.1 → 157.1 for dextrorphan, respectively. The calibration curve was linear over the range of 5-2500ng/mL with the lower limit of quantification of 5ng/mL for sitafloxacin. The intra- and inter-day precisions were less than 8.3% and the deviations of assay accuracies were within ±4.1%. Sitafloxacin was sufficiently stable under all relevant analytical conditions. This method was successfully applied to the pharmacokinetic study of sitafloxacin in healthy Chinese volunteers.


Asunto(s)
Cromatografía Liquida/métodos , Fluoroquinolonas/sangre , Espectrometría de Masas en Tándem/métodos , Adulto , Estabilidad de Medicamentos , Femenino , Fluoroquinolonas/química , Fluoroquinolonas/farmacocinética , Humanos , Límite de Detección , Modelos Lineales , Masculino , Reproducibilidad de los Resultados , Adulto Joven
13.
Biomed Chromatogr ; 28(3): 446-52, 2014 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-24254834

RESUMEN

A sensitive and accurate HPLC-MS/MS method was developed for the simultaneous determination of dextromethorphan, dextrorphan and chlorphenamine in human plasma. Three analytes were extracted from plasma by liquid-liquid extraction using ethyl acetate and separated on a Kromasil 60-5CN column (3 µm, 2.1 × 150 mm) with mobile phase of acetonitrile-water (containing 0.1% formic acid; 50:50, v/v) at a flow rate of 0.2 mL/min. Quantification was performed on a triple quadrupole tandem mass spectrometer in multiple reaction monitoring mode using positive electrospray ionization. The calibration curve was linear over the range of 0.01-5 ng/mL for dextromethorphan, 0.02-5 ng/mL for dextrorphan and 0.025-20 ng/mL for chlorphenamine. The lower limits of quantification for dextromethorphan, dextrorphan and chlorphenamine were 0.01, 0.02 and 0.025 ng/mL, respectively. The intra- and inter-day precisions were within 11% and accuracies were in the range of 92.9-102.5%. All analytes were proved to be stable during sample storage, preparation and analytic procedures. This method was first applied to the pharmacokinetic study in healthy Chinese volunteers after a single oral dose of the formulation containing dextromethorphan hydrobromide (18 mg) and chlorpheniramine malaeate (8 mg).


Asunto(s)
Clorfeniramina/sangre , Cromatografía Líquida de Alta Presión/métodos , Dextrometorfano/sangre , Dextrorfano/sangre , Espectrometría de Masas en Tándem/métodos , Adulto , Clorfeniramina/química , Clorfeniramina/farmacocinética , Dextrometorfano/química , Dextrometorfano/farmacocinética , Dextrorfano/química , Dextrorfano/farmacocinética , Estabilidad de Medicamentos , Femenino , Humanos , Análisis de los Mínimos Cuadrados , Masculino , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Espectrometría de Masa por Ionización de Electrospray/métodos , Adulto Joven
14.
Biochem J ; 456(2): 185-94, 2013 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-24063546

RESUMEN

Trehalase, which specifically hydrolyses trehalose into glucose, plays an important role in the metabolism of trehalose. Large amounts of trehalose are stored in the diapause encysted embryos (cysts) of Artemia, which are not only vital to their extraordinary stress resistance, but also provide a source of energy for development after diapause is terminated. In the present study, a mechanism for the transcriptional regulation of trehalase was described in Artemia parthenogenetica. A trehalase-associated protein (ArTAP) was identified in Artemia-producing diapause cysts. ArTAP was found to be expressed only in diapause-destined embryos. Further analyses revealed that ArTAP can bind to a specific intronic segment of a trehalase gene. Knockdown of ArTAP by RNAi resulted in the release of cysts with coarse shells in which two chitin-binding proteins were missing. Western blotting showed that the level of trehalase was increased and apoptosis was induced in these ArTAP-knockdown cysts compared with controls. Taken together, these results show that ArTAP is a key regulator of trehalase expression which, in turn, plays an important role in trehalose metabolism during the formation of diapause cysts.


Asunto(s)
Apoptosis , Artemia/enzimología , Proteínas de Artrópodos/metabolismo , Embrión no Mamífero/enzimología , Trehalosa/metabolismo , Animales , Artemia/citología , Artemia/embriología , Proteínas de Artrópodos/genética , Secuencia de Bases , Clonación Molecular , Proteínas de Unión al ADN/fisiología , Embrión no Mamífero/citología , Regulación Enzimológica de la Expresión Génica , Intrones , Datos de Secuencia Molecular , Unión Proteica , Transporte de Proteínas , Análisis de Secuencia de ADN , Transcripción Genética , Trehalosa/genética
15.
Acta Pharmacol Sin ; 33(6): 767-74, 2012 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-22543702

RESUMEN

AIM: To investigate the effects of nitric oxide (NO) donors on the function and expression of P-glycoprotein (P-gp) in Caco-2 cells. METHODS: Caco-2 cells were exposed to NO donors for designated times. P-gp function and expression were assessed using Rhodamine123 uptake assay and Western blotting, respectively. Intracellular reactive oxygen species (iROS) and intracellular reactive nitrogen species (iRNS) levels were measured using ROS and RNS assay kits, respectively. RESULTS: Exposure of Caco-2 cells to 0.1 or 2 mmol/L of sodium nitroprusside (SNP) affected the function and expression of P-gp in concentration- and time-dependent manners. A short-term (4 h) exposure reduced P-gp function and expression accompanied with significantly increased levels of iROS and iRNS. In contrast, a long-term (24 h) exposure stimulated the P-gp function and expression. The stimulatory effects of 2 mmol/L SNP was less profound as compared to those caused by 0.1 mmol/L SNP. The other NO donors SIN-1 and SNAP showed similar effects. Neither the NO scavenger PTIO (2 mmol/L) nor soluble guanylate cyclase inhibitor ODQ (50 µmol/L) reversed the SNP-induced alteration of P-gp function. On the other hand, free radical scavengers ascorbate, glutathione and uric acid (2 mmol/L for each), PKC inhibitor chelerythrine (5 µmol/L), PI3K/Akt inhibitor wortmannin (1 µmol/L) and p38 MAPK inhibitor SB203580 (10 µmol/L) reversed the upregulation of P-gp function by the long-term exposure to SNP, but these agents had no effect on the impaired P-gp function following the short-term exposure to SNP. CONCLUSION: NO donors time-dependently regulate P-gp function and expression in Caco-2 cells: short-term exposure impairs P-gp function and expression, whereas long-term exposure stimulates P-gp function and expression. The regulation occurs via a NO-independent mechanism.


Asunto(s)
Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/genética , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/metabolismo , Regulación de la Expresión Génica/efectos de los fármacos , Donantes de Óxido Nítrico/farmacología , Nitroprusiato/farmacología , Células CACO-2 , Depuradores de Radicales Libres/farmacología , Humanos , Especies de Nitrógeno Reactivo/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Transducción de Señal/efectos de los fármacos
16.
Drug Metab Dispos ; 40(6): 1104-12, 2012 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-22393122

RESUMEN

The purpose of this study was to evaluate the contributions of impaired cytochrome P450 and breast cancer resistance protein (BCRP) activity and expression to drug pharmacokinetics under diabetic conditions. Diabetes was induced in rats with the intraperitoneal administration of streptozocin. Glibenclamide (GLB), a substrate of BCRP, served as a model drug. The pharmacokinetics of orally administered GLB (10 mg/kg) were studied. The results showed that diabetes mellitus significantly increased exposure (area under the curve and peak concentration) to GLB after oral administration. Data from hepatic microsomes suggested impairment of GLB metabolism in diabetic rats. GLB metabolism in hepatic microsomes was significantly inhibited by a selective inhibitor (sulfaphenazole) of CYP2C11 and an anti-CYP2C11 antibody. Western blotting further indicated the contribution of impaired CYP2C11 expression to the impairment of GLB metabolism. Excretion data showed that ∼72% of the orally administered dose was excreted in the feces of normal rats, which indicates an important role for intestinal BCRP. Diabetes significantly decreased the recovery from feces, which was only 40% of the orally administered dose. Results from in situ, single-pass, intestinal perfusion experiments revealed that diabetes significantly increased the apparent effective permeability and decreased the efflux of GLB through the intestine; this suggests impairment of intestinal BCRP function, which may play a role in the increased exposure to orally administered GLB in diabetic rats. Insulin treatment partly or completely reversed the changes in diabetic rats. All results yielded the conclusion that impaired hepatic CYP2C11 and intestinal BCRP expression and activity induced by diabetes contributed to the increased exposure of orally administered GLB.


Asunto(s)
Transportadoras de Casetes de Unión a ATP/biosíntesis , Hidrocarburo de Aril Hidroxilasas/metabolismo , Diabetes Mellitus Experimental/tratamiento farmacológico , Diabetes Mellitus Experimental/metabolismo , Regulación de la Expresión Génica , Gliburida/administración & dosificación , Esteroide 16-alfa-Hidroxilasa/metabolismo , Transportador de Casetes de Unión a ATP, Subfamilia G, Miembro 2 , Administración Oral , Animales , Hidrocarburo de Aril Hidroxilasas/fisiología , Familia 2 del Citocromo P450 , Activación Enzimática/fisiología , Gliburida/metabolismo , Masculino , Microsomas Hepáticos/efectos de los fármacos , Microsomas Hepáticos/metabolismo , Ratas , Ratas Sprague-Dawley , Esteroide 16-alfa-Hidroxilasa/fisiología
17.
Xenobiotica ; 42(8): 709-18, 2012 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-22324395

RESUMEN

Many studies have demonstrated that Mrp2 is highly regulated in some physiopathological situations. The aim of this study was to investigate effects of diabetes mellitus on function and expression of multidrug resistance-associated protein 2 (Mrp2) in rat liver, kidney and intestine. Diabetic rats were induced by an intraperitoneal administration of streptozotocin (65 mg/kg) and randomly divided into diabetic (DM) rats and insulin-treated diabetic rats. Sulfobromophthalein (BSP), a substrate of Mrp2, was used to evaluate Mrp2 function in vivo. Data from excretion experiments demonstrated that compared with normal rats, diabetes markedly enhanced BSP excretion via bile, urine and intestinal perfusate, which contributed to the elevated plasma clearance of BSP after intravenous administration of 45 µmol/kg BSP. Western blot results showed higher levels of hepatic, renal and intestinal Mrp2 protein in DM rats, although no difference was observed in renal Mrp2. Insulin treatment partly reversed these alterations. Induction of Mrp2 by diabetes was in parallel with the increase in bile flow, levels of biliary and plasma total bile acid (TBA), and plasma conjugated bilirubin in DM rats. Diabetes may enhance Mrp2 function and expression in liver, kidney and intestine, which might be due to insulin deficiency, increased TBA and conjugated bilirubin.


Asunto(s)
Diabetes Mellitus Experimental/metabolismo , Mucosa Intestinal/metabolismo , Riñón/metabolismo , Hígado/metabolismo , Proteínas Asociadas a Resistencia a Múltiples Medicamentos/metabolismo , Animales , Ácidos y Sales Biliares/sangre , Diabetes Mellitus Experimental/sangre , Diabetes Mellitus Experimental/tratamiento farmacológico , Glutatión/metabolismo , Glutatión Transferasa/metabolismo , Inyecciones Intravenosas , Insulina/uso terapéutico , Intestinos/enzimología , Riñón/enzimología , Hígado/enzimología , Masculino , Proteína 2 Asociada a Resistencia a Múltiples Medicamentos , Ratas , Ratas Sprague-Dawley , Sulfobromoftaleína/administración & dosificación , Sulfobromoftaleína/farmacocinética
18.
J Comput Assist Tomogr ; 36(1): 14-9, 2012.
Artículo en Inglés | MEDLINE | ID: mdl-22261765

RESUMEN

OBJECTIVE: The objective of the study was to determine the value of addition of hepatobiliary phase to dynamic gadobenate dimeglumine (Gd-BOPTA)-enhanced imaging for the detection of focal liver lesions (nodules with diameter ≤3.0 cm). METHODS: Routine nonenhanced magnetic resonance images were obtained in 25 patients with focal liver lesions suggested by ultrasonography and/or computed tomography.T1-weighted dynamic gradient-echo images were acquired immediately and 100 minutes after bolus injection of Gd-BOPTA. The number of the lesions detected by T1-weighted imaging, T2-weighted imaging, diffusion-weighted imaging, dynamic contrast-enhanced, and delayed hepatobiliary-phase imaging was counted, respectively. Contrast-to-noise ratios were measured for all the sequences including delayed hepatobiliary-phase imaging. The signal intensity and morphologic features of liver parenchyma and lesions were recorded and analyzed. RESULTS: There were 7 patients with hepatocellular carcinomas, 6 with hemangiomas, 7 with metastases, and 5 with cholangiocarcinomas. The delayed hepatobiliary-phase imaging showed a homogeneous enhancement of liver parenchyma and distinctive enhancement features of focal liver lesions. The delayed hepatobiliary-phase imaging was better than diffusion-weighted imaging for the detection of focal liver lesions (P < 0.05). CONCLUSION: The addition of hepatobiliary-phase imaging to Gd-BOPTA-enhanced dynamic imaging increased the sensitivity and accuracy for the detection of focal hepatic lesions.


Asunto(s)
Carcinoma Hepatocelular/diagnóstico , Colangiocarcinoma/diagnóstico , Medios de Contraste , Hemangioma/diagnóstico , Neoplasias Hepáticas/diagnóstico , Imagen por Resonancia Magnética/métodos , Meglumina/análogos & derivados , Compuestos Organometálicos , Adulto , Anciano , Carcinoma Hepatocelular/diagnóstico por imagen , Distribución de Chi-Cuadrado , Colangiocarcinoma/diagnóstico por imagen , Pancreatocolangiografía por Resonancia Magnética , Imagen de Difusión por Resonancia Magnética , Femenino , Hemangioma/diagnóstico por imagen , Humanos , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/secundario , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Sensibilidad y Especificidad , Tomografía Computarizada por Rayos X , Ultrasonografía
19.
Acta Pharmacol Sin ; 32(7): 956-66, 2011 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-21685928

RESUMEN

AIM: To investigate the changes of expression and function of P-glycoprotein (P-GP) in cerebral cortex, hippocampus, liver, intestinal mucosa and kidney of streptozocin-induced diabetic rats. METHODS: Diabetic rats were prepared via a single dose of streptozocin (65 mg/kg, ip). Abcb1/P-GP mRNA and protein expression levels in tissues were evaluated using quantitative real time polymerase chain reaction (QRT-PCR) analysis and Western blot, respectively. P-GP function was investigated via measuring tissue-to-plasma concentration ratios and body fluid excretion percentages of rhodamine 123. RESULTS: In 5- and 8-week diabetic rats, Abcb1a mRNA levels were significantly decreased in cerebral cortices and intestinal mucosa, but dramatically increased in hippocampus and kidney. In liver, the level was increased in 5-week diabetic rats, and decreased in 8-week diabetic rats. Abcb1b mRNA levels were increased in cerebral cortex, hippocampus and kidney, but reduced in liver and intestinal mucosa in the diabetic rats. Western blot results were in accordance with the alterations of Abcb1a mRNA levels in most tissues examined. P-GP activity was markedly decreased in most tissues of diabetic rats, except kidney tissues. CONCLUSION: Alterations in the expression and function of Abcb1/P-GP under diabetic conditions are tissue specific, Abcb1 specific and diabetic duration-dependent.


Asunto(s)
Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/genética , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/metabolismo , Diabetes Mellitus Experimental/genética , Expresión Génica , ARN Mensajero/genética , Animales , Corteza Cerebral/metabolismo , Diabetes Mellitus Experimental/metabolismo , Hipocampo/metabolismo , Mucosa Intestinal/metabolismo , Riñón/metabolismo , Hígado/metabolismo , Masculino , Ratas , Ratas Sprague-Dawley
20.
Chin J Cancer Res ; 23(4): 301-5, 2011 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-23357927

RESUMEN

OBJECTIVE: Based on liver cancer model built in SD rats, the contents of trace elements (Cu, Fe, Zn, Ca and Mg), AFP, CEA, SF, TH and IGF-II in serum were measured at different stages to explore the molecular changes during the rat liver cancer development. METHODS: The SD rat liver cancer model was built by using diethylnitrosamine (DENA) as the mutagen. During 16 weeks of DENA gavage, blood samples were taken in the 14th, 28th, 56th, 77th, 105th and 112th days respectively after the first day of gavage with DENA, then the contents of five trace elements (Cu, Fe, Zn, Ca and Mg), T3, T4, IGF-II, AFP, CEA and SF in serum were determined. RESULTS: During the development of the rat liver cancer, in the test group, the Cu content significantly increased in serum, while the contents of Fe, Zn and Ca significantly decreased. The content of Mg showed no significant change. AFP and CEA of the test group showed same expression level with the control group; while the content of SF was lower than that of the control group when cancerization appeared. T3 and T4 increased at the first stage and then went down, and the content of IGF-II was always high. CONCLUSION: Cu, Fe, Zn, Ca, T3, T4, SF and IGF-II are closely related to the development of liver cancer. The changes of their contents in the development of cancer could enlighten the researches on cancer pathogenesis and prevention.

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