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1.
ACS Cent Sci ; 10(2): 358-366, 2024 Feb 28.
Artículo en Inglés | MEDLINE | ID: mdl-38435533

RESUMEN

Encapsulating enzymes within metal-organic frameworks has enhanced their structural stability and interface tunability for catalysis. However, the small apertures of the frameworks restrict their effectiveness to small organic molecules. Herein, we present a green strategy directed by visible linker micelles for the aqueous synthesis of MAF-6 that enables enzymes for the catalytic asymmetric synthesis of chiral molecules. Due to the large pore aperture (7.6 Å), double the aperture size of benchmark ZIF-8 (3.4 Å), MAF-6 allows encapsulated enzyme BCL to access larger substrates and do so faster. Through the optimization of surfactants' effect during synthesis, BCL@MAF-6-SDS (SDS = sodium dodecyl sulfate) displayed a catalytic efficiency (Kcat/Km) that was 420 times greater than that of BCL@ZIF-8. This biocomposite efficiently catalyzed the synthesis of drug precursor molecules with 94-99% enantioselectivity and nearly quantitative yields. These findings represent a deeper understanding of de novo synthetic encapsulation of enzyme in MOFs, thereby unfolding the great potential of enzyme@MAF catalysts for asymmetric synthesis of organics and pharmaceuticals.

2.
Inorg Chem ; 63(5): 2647-2654, 2024 Feb 05.
Artículo en Inglés | MEDLINE | ID: mdl-38262040

RESUMEN

The increasing demands in optoelectronic applications have driven the advancement of organic-inorganic hybrid metal halides (OIMHs), owing to their exceptional optical and scintillation properties. Among them, zero-dimensional (0D) low-toxic manganese-based scintillators have garnered significant interest due to their exceptional optical transparency and elevated photoluminescence quantum yields (PLQYs), making them promising for colorful light-emitting diodes and X-ray imaging applications. In this study, two OIMH single crystals of (Br-PrTPP)2MnBr4 (Br-PrTPP = (3-bromopropyl) triphenylphosphonium) and (Br-BuTPP)2MnBr4 (Br-BuTPP = (4-bromobutyl) triphenylphosphonium) were prepared via a facile saturated crystallization method. Benefiting from the tetrahedrally coordinated [MnBr4]2- polyhedron, both of them exhibited strong green emissions peaked at 517 nm owing to the d-d electron transition of Mn2+ with near-unity PLQYs of 99.33 and 86.85%, respectively. Moreover, benefiting from the high optical transparencies and remarkable luminescence properties, these manganese halides also exhibit excellent radioluminescent performance with the highest light yield of up to 68,000 photons MeV-1, negligible afterglow (0.4 ms), and linear response to X-ray dose rate with the lowest detection limit of 45 nGyair s-1. In X-ray imaging, the flexible film made by the composite of (Br-PrTPP)2MnBr4 and PDMS shows an ultrahigh spatial resolution of 12.78 lp mm-1, which provides a potential visualization tool for X-ray radiography.

3.
J Inflamm Res ; 14: 3697-3706, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34377007

RESUMEN

PURPOSE: Inflammation has a significant impact on CYP3A activity. We hypothesized that this effect might be age dependent. Our objective was to conduct a population pharmacokinetic study of midazolam in mice at different developmental stages with varying degrees of inflammation to verify our hypothesis. METHODS: Different doses (2 and 5 mg/kg) of lipopolysaccharide (LPS) were used to induce different degrees of systemic inflammation in Swiss mice (postnatal age 9-42 days, n = 220). The CYP3A substrate midazolam was selected as the pharmacological probe to study CYP3A activity. Postnatal age, current body weight, serum amyloid A protein 1 (SAA1) levels and LPS doses were collected as covariates to perform a population pharmacokinetic analysis using NONMEM 7.2. RESULTS: A population pharmacokinetic model of midazolam in juvenile and adult mice was established. Postnatal age and current body weight were the most significant and positive covariates for clearance and volume of distribution. LPS dosage was the most significant and negative covariate for clearance. LPS dosage can significantly reduce the clearance of midazolam by 21.8% and 38.7% with 2 mg/kg and 5 mg/kg, respectively. Moreover, the magnitude of the reduction was higher in mice with advancing postnatal age. CONCLUSION: Both inflammation and ontogeny have an essential role in CYP3A activity in mice. The effect of LPS-induced systemic inflammation on midazolam clearance in mice is dependent on postnatal age.

4.
Huan Jing Ke Xue ; 42(9): 4406-4413, 2021 Sep 08.
Artículo en Chino | MEDLINE | ID: mdl-34414740

RESUMEN

In this study, domestic sewage was used to inoculate mature short-cut nitrification denitrifying phosphorus removal particles, which were cultivated and matured under artificial water. The operation of the short-cut nitrification denitrifying phosphorus removal system was optimized using different aerobic/anoxic durations combined with zoned sludge discharge. The results showed that regulating the aerobic/anoxic duration, in combination with zoned sludge discharge, can realize the stable operation of the system. In the later stable period, the effluent COD concentration was below 50 mg·L-1, the effluent TN concentration was below 15 mg·L-1, the TN removal rate reached about 83% and remained stable, the effluent P concentration was below 0.5 mg·L-1, and the average P removal rate was 93.72%. At the same time, zoned sludge discharge (70% top sludge and 30% bottom sludge) can be used to screen out microorganisms, maintain good nitrosation and phosphorus removal performance, limit the particle size distribution, and ensure the growth advantages of AOB and DPAOs. Increases in the anoxic duration improved the growth rate of anoxic heterotrophic bacteria, causing them to secrete more EPS and ensuring granular sludge improvements and continued stability.


Asunto(s)
Fósforo , Aguas del Alcantarillado , Reactores Biológicos , Nitrificación , Nitrógeno , Eliminación de Residuos Líquidos
5.
Front Pharmacol ; 12: 657287, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34295246

RESUMEN

Objective: The elucidation of CYP2D6 developmental pharmacogenetics in children has improved, however, these findings have been largely limited to studies of Caucasian children. Given the clear differences in CYP2D6 pharmacogenetic profiles in people of different ancestries, there remains an unmet need to better understand the developmental pharmacogenetics in populations of different ancestries. We sought to use loratadine as a substrate drug to evaluate the effects of ontogeny and pharmacogenetics on the developmental pattern of CYP2D6 in Chinese pediatric patients. Methods: Chinese children receiving loratadine treatment were enrolled in the present study. The metabolite-to-parent ratio (M/P ratio), defined as the molar ratio of desloratadine to loratadine of trough concentrations samples at steady-state condition, was used as a surrogate of CYP2D6 activity. Loratadine and desloratadine were determined by LC/MS/MS method. Variants of CYP2D6 were genotyped by polymerase chain reaction for CYP2D6 *4, *10, *41 and long polymerase chain reaction for CYP2D6 *5. Results: A total of 40 patients were available for final analysis. The mean age was 4.50 (range 0.50-9.00) years and the mean weight was 19.64 (range 7.00-42.00) kg. The M/P ratio was significantly lower in intermediate metabolizers (IMs) compared to normal metabolizers (NMs) (10.18 ± 7.97 vs. 18.80 ± 15.83, p = 0.03). Weight was also found to be significantly associated with M/P ratio (p = 0.03). Conclusion: The developmental pharmacogenetics of CYP2D6 in Chinese children was evaluated using loratadine as a substrate drug. This study emphasizes the importance of evaluating the developmental pharmacogenetics in populations of different ancestries.

6.
Huan Jing Ke Xue ; 42(8): 3858-3865, 2021 Aug 08.
Artículo en Chino | MEDLINE | ID: mdl-34309272

RESUMEN

To explore the effects of nitrite generation on the system of short-cut nitrification denitrifying phosphorus removal granules, nitrite was produced continuously and intermittently, under continuous and intermittent aeration, in two groups of SBR reactors of the same size. The effects of nitrogen and phosphorus removal, physical characteristics of the sludge, and microbial community structure were investigated. Nitrite was consumed immediately after intermittent production, with better and more stable nitrogen and phosphorus removal performance. In particular, the average rate of TN removal was 92.07% after 72 days. The utilization efficiency of the carbon source (by P/COD) was concentrated at 0.21-0.22 mg ·mg-1, to ensure full utilization of the carbon source and to further promote denitrification and phosphorus removal. Particle sizes were uniform and showed concentrated distribution, with particles exhibiting regular shapes and clear boundaries. Microbial community analysis showed that the abundance and diversity of microbial communities were higher in the intermittent nitrite system and more enriched in DPAOs genera (Dechloromonas and Pseudomonas). The combination of DPAOs genera and Nitrosomonas resulted in a dynamic balance and stable operation of the short-cut nitrification and denitrifying phosphorus removal system.


Asunto(s)
Nitrificación , Fósforo , Reactores Biológicos , Desnitrificación , Nitritos , Nitrógeno , Aguas del Alcantarillado , Eliminación de Residuos Líquidos
7.
Clin Pharmacokinet ; 60(11): 1435-1448, 2021 11.
Artículo en Inglés | MEDLINE | ID: mdl-34041714

RESUMEN

BACKGROUND: Population pharmacokinetic evaluations have been widely used in neonatal pharmacokinetic studies, while machine learning has become a popular approach to solving complex problems in the current era of big data. OBJECTIVE: The aim of this proof-of-concept study was to evaluate whether combining population pharmacokinetic and machine learning approaches could provide a more accurate prediction of the clearance of renally eliminated drugs in individual neonates. METHODS: Six drugs that are primarily eliminated by the kidneys were selected (vancomycin, latamoxef, cefepime, azlocillin, ceftazidime, and amoxicillin) as 'proof of concept' compounds. Individual estimates of clearance obtained from population pharmacokinetic models were used as reference clearances, and diverse machine learning methods and nested cross-validation were adopted and evaluated against these reference clearances. The predictive performance of these combined methods was compared with the performance of two other predictive methods: a covariate-based maturation model and a postmenstrual age and body weight scaling model. Relative error was used to evaluate the different methods. RESULTS: The extra tree regressor was selected as the best-fit machine learning method. Using the combined method, more than 95% of predictions for all six drugs had a relative error of < 50% and the mean relative error was reduced by an average of 44.3% and 71.3% compared with the other two predictive methods. CONCLUSION: A combined population pharmacokinetic and machine learning approach provided improved predictions of individual clearances of renally cleared drugs in neonates. For a new patient treated in clinical practice, individual clearance can be predicted a priori using our model code combined with demographic data.


Asunto(s)
Vías de Eliminación de Fármacos , Modelos Biológicos , Humanos , Recién Nacido , Aprendizaje Automático , Tasa de Depuración Metabólica , Vancomicina
8.
Huan Jing Ke Xue ; 42(6): 2946-2956, 2021 Jun 08.
Artículo en Chino | MEDLINE | ID: mdl-34032094

RESUMEN

In this experiment, three replicated SBR reactors were operated using asynchronous acclimation of the phased method (A/O-A/O/A), simultaneous domestication of continuous aeration by A/O/A, and simultaneous domestication of intermittent aeration by A/O/A. Using artificial water distribution as the influent substrate, flocculent sludge was inoculated and granulated by hydraulic selection. The domestication and nitrogen and phosphorus removal characteristics of shortcut nitrification denitrifying phosphorus removal granules under different operation modes were assessed. The results show that simultaneous domestication of intermittent aeration by A/O/A has the most efficient under the combination of short aeration time (140 min) and low aeration strength[3.5 L·(h·L)-1]. The average removal rates of carbon, nitrogen, and phosphorus were 90.74%, 91.15%, and 95.66%, respectively, which could achieve synchronous removal during later stable operation. The particle size was 895 µm, and the particles were small but uniformly dense in microscope observations. The f value (MLVSS/MLSS) was kept stable at 0.8-0.85 and sludge had a high biomass due to the alternate aerobic/anoxic operation with intermittent aeration. This supported anoxic heterotrophic bacteria at the core of the particles, which was conducive to the stability of the granular sludge structure. Batch experiments showed that the specific ammonia-oxidation rate of the simultaneous domestication of intermittent aeration by A/O/A system was 3.38 mg·(g·h)-1, and denitrifying phosphate accumulating organisms (DPAOs) able to utilize nitrite as electron acceptor accounted for 65.46%. This was more conducive to the simultaneous domestication and enrichment of ammonia-oxidizing bacteria (AOB) and NO2--type DPAOs, ensuring a stable treatment effect.

9.
J Antimicrob Chemother ; 76(3): 699-709, 2021 02 11.
Artículo en Inglés | MEDLINE | ID: mdl-33188385

RESUMEN

OBJECTIVES: Nowadays, real-world data can be used to improve currently available dosing guidelines and to support regulatory approval of drugs for use in neonates by overcoming practical and ethical hurdles. This proof-of-concept study aimed to assess the population pharmacokinetics of azlocillin in neonates using real-world data, to make subsequent dose recommendations and to test these in neonates with early-onset sepsis (EOS). METHODS: This prospective, open-label, investigator-initiated study of azlocillin in neonates with EOS was conducted using an adaptive two-step design. First, a maturational pharmacokinetic-pharmacodynamic model of azlocillin was developed, using an empirical dosing regimen combined with opportunistic samples resulting from waste material. Second, a Phase II clinical trial (ClinicalTrials.gov: NCT03932123) of this newly developed model-based dosing regimen of azlocillin was conducted to assure optimized target attainment [free drug concentration above MIC during 70% of the dosing interval ('70% fT>MIC')] and to investigate the tolerance and safety in neonates. RESULTS: A one-compartment model with first-order elimination, using 167 azlocillin concentrations from 95 neonates (31.7-41.6 weeks postmenstrual age), incorporating current weight and renal maturation, fitted the data best. For the second step, 45 neonates (30.3-41.3 weeks postmenstrual age) were subsequently included to investigate target attainment, tolerance and safety of the pharmacokinetic-pharmacodynamic model-based dose regimen (100 mg/kg q8h). Forty-three (95.6%) neonates reached their pharmacokinetic target and only two neonates experienced adverse events (feeding intolerance and abnormal liver function), possibly related to azlocillin. CONCLUSIONS: Target attainment, tolerance and safety of azlocillin was shown in neonates with EOS using a pharmacokinetic-pharmacodynamic model developed with real-world data.


Asunto(s)
Azlocilina , Sepsis , Antibacterianos/uso terapéutico , Humanos , Recién Nacido , Pruebas de Sensibilidad Microbiana , Estudios Prospectivos , Sepsis/tratamiento farmacológico
10.
Huan Jing Ke Xue ; 41(2): 867-875, 2020 Feb 08.
Artículo en Chino | MEDLINE | ID: mdl-32608748

RESUMEN

This paper investigated domestic sewage with a low C/N ratio. Mature phosphorus removal granules were inoculated to cultivate granules with a simultaneous short-cut nitrification and denitrification function. The characteristics of nitrogen and phosphorus removal of this process were analyzed. Results show that AOB can be enriched by prolonging the sludge age for 30 days with an aeration intensity of 5 L·(h·L)-1 and shorter aeration time (140 min), whereas the simultaneous nitrification and denitrification ability could not be improved. The nitrogen loss increased at the aerobic time when aeration intensity was reduced by 3.5 L·(h·L)-1 and aeration time was prolonged by 200 min. The aeration time was further optimized to restrain the transformation of NO2- to NO3-, and finally the effluent of TP < 0.5 mg·L-1 and TN < 15 mg·L-1. During the process of the system function transformation from phosphorus removal to nitrogen and phosphorus removal, the phosphorus release decreased, however PAOs still played a dominant role (60%) in the process of internal carbon storage. Batch experiments showed that DPAOs that can utilize nitrite as an electron acceptor accounts for 52.43% in the total PAOS, which alleviated the pressure of the carbon source and improved the simultaneous nitrogen and phosphorus removal.

11.
Xenobiotica ; 50(11): 1275-1284, 2020 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-32400275

RESUMEN

First dose prediction is challenging in neonates. Our objective in this proof-of-concept study was to perform a pharmacokinetic (PK) bridging study from juvenile mice to neonates for drugs metabolized by CYP3A. We selected midazolam and clindamycin as model drugs. We developed juvenile mice population PK models using NONMEM. The PK parameters of these two drugs in juvenile mice were used to bridge PK parameters in neonates using different correction methods. The bridging results were evaluated by the fold-error of 0.5- to 1.5-fold. Simple allometry with and without a correction factor for maximum lifespan potential could be used for a bridging of clearance (CL) and volume of distribution (Vd), respectively, from juvenile mice to neonates. Simulation results demonstrated that for midazolam, 100% of clinical studies for which both the predictive CL and Vd were within 0.5- to 1.5-fold of the observed. For clindamycin, 75% and 100% of clinical studies for which the predictive CL and Vd were within 0.5- to 1.5-fold of the observed. A PK bridging of drugs metabolized by CYP3A is feasible from juvenile mice to neonates. It could be a complement to the ADE and PBPK models to support the first dose in neonates.


Asunto(s)
Simulación por Computador , Citocromo P-450 CYP3A/metabolismo , Animales , Clindamicina/farmacocinética , Ratones , Midazolam/farmacocinética , Modelos Biológicos
12.
Artículo en Inglés | MEDLINE | ID: mdl-32247185

RESUMEN

Antimicrobial activity of cefoperazone, a high protein bound cephalosporin, depends on its unbound concentration. However, the protein binding data of cefoperazone in children is limited, making it challenging to optimize antimicrobial therapy in pediatric clinical practice. Furthermore, a validated method to measure the free part in children is unavailable with the small volume of samples that can be obtained. Therefore, in the present study, we developed and validated an LC-MS/MS method for the determination of free cefoperazone in children. In this study, 70 µL of plasma was used to prepare the ultrafiltrate (only containing the free drug). Chromatographic separation of the analyte was achieved on a C18 column using gradient elution with a mobile phase of acetonitrile and water (0.1% formic acid). Negative electrospray ionisation in the multiple reaction monitoring mode was applied for the detection of cefoperazone and ceftiofur (internal standard). The calibration curve was prepared in the range of 5-5000 ng/mL with excellent linearity. For each level of quality control samples, the intra- and inter-day precision (CV) was below 9.0%, and the accuracy ranged from 91.5% to 105.0%. The matrix effect was less than 11.7%, and the recovery was between 92.9% and 95.9% of cefoperazone. The validated method has been successfully applied to the determination of free plasma concentration of cefoperazone in pediatric patients. The results of the unbound fraction showed considerable individual variability (range: 8.1-48.0%). The correlation analysis showed that age and albumin had significant effects on the protein binding of cefoperazone.


Asunto(s)
Cefoperazona/sangre , Factores de Edad , Técnicas Biosensibles/métodos , Niño , Preescolar , Cromatografía Líquida de Alta Presión , Femenino , Humanos , Lactante , Recién Nacido , Límite de Detección , Masculino , Unión Proteica , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Espectrometría de Masas en Tándem
13.
Huan Jing Ke Xue ; 40(11): 5048-5056, 2019 Nov 08.
Artículo en Chino | MEDLINE | ID: mdl-31854573

RESUMEN

In this paper, the low C/N ratio of domestic sewage was studied, and mature phosphorus removal granules were inoculated to investigate the effect of solid retention time(SRT)on phosphorus removal and nitrification granular sludge at middle-low temperatures (14-21℃). The test showed that at room temperature (20℃±1℃), the enrichment of AOB in the phosphorus removal granules can be achieved with 30 d SRT and 5 L·(h·L)-1 aeration intensity, while the NAR was over 90%. When the temperature was lowered to 15℃ and the SRT was 40 d, the phosphorus removal performance deteriorated, and the granule structure became loose with the formation of filamentous bacteria. Relatively sufficient oxygen destabilized nitrosation and the NAR dropped by 22.4%. NOB does not have the ability to quickly adapt to environmental changes. The 12 d anaerobic starvation and sludge removal strategy weakened the relative activity of NOB and quickly restored the performance of phosphorus removal and nitrosation. Batch experiments showed that the temperature dropped from 20℃ to 15℃, and the PAOs still maintained a high oxygen utilization rate, but the SOUR of the AOB decreased by 18%. At this time, the temperature, not the dissolved oxygen concentration, restricted the ammonia oxidation ability. Controlling the sludge age to 30 d, while reducing the aeration intensity to 4 L·(h·L)-1, achieved stable operation of phosphorus removal and nitrosation at a low temperature (15℃±1℃).

14.
Cell Mol Neurobiol ; 37(2): 361-369, 2017 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-27193103

RESUMEN

Retinal ganglion cell (RGC) injury is one of the important pathological features of diabetes-induced retinal neurodegeneration. Increasing attention has been paid to find strategies for protecting against RGC injury. Long noncoding RNAs (lncRNAs) have emerged as the key regulators of many cell functions. Here, we show that Sox2OT expression is significantly down-regulated in the retinas of STZ-induced diabetic mice and in the RGCs upon high glucose or oxidative stress. SOX2OT knockdown protects RGCs against high glucose-induced injury in vitro. Moreover, Sox2OT knockdown plays a neuroprotective role in diabetes-related retinal neurodegeneration in vivo. Sox2OT knockdown could regulate oxidative stress response in RGCs and diabetic mouse retinas. Sox2OT knockdown plays an anti-oxidative role via regulating NRF2/HO-1 signaling activity. Taken together, Sox2OT knockdown may be a therapeutic strategy for the prevention and treatment of diabetes-induced retinal neurodegeneration.


Asunto(s)
Diabetes Mellitus Experimental/genética , Diabetes Mellitus Experimental/metabolismo , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Células Ganglionares de la Retina/metabolismo , Animales , Supervivencia Celular/efectos de los fármacos , Supervivencia Celular/fisiología , Diabetes Mellitus Experimental/patología , Retinopatía Diabética/genética , Retinopatía Diabética/metabolismo , Retinopatía Diabética/patología , Técnicas de Silenciamiento del Gen , Glucosa/toxicidad , Masculino , Ratones , Ratones Endogámicos C57BL , Células Ganglionares de la Retina/patología
15.
Cell Physiol Biochem ; 39(5): 2044-2054, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-27825165

RESUMEN

BACKGROUND/AIMS: Advanced glycation end products (AGEs) could elicit oxidative stress, trigger and aggravate endothelium damage in several ischemic retinopathies including diabetic retinopathy (DR). The leaves of Eucommia ulmoides O., also referred to as Tu-chung or Du-zhong, have been used for the treatment of hypertension and diabetes, showing great antioxidant activity and anti-glycation activity. Lignans is one of the main bioactive components of Eucommia ulmoides. This study mainly investigated the effect of lignans treatment on AGEs-induced endothelium damage. METHODS: MTT assay, Hoechst staining, and calcein-AM/ propidium iodide (PI) staining was conducted to determine the effect of lignans treatment on endothelial cell function in vitro. Retinal trypsin digestion, Evans blue assay, isolectin staining, and western blots were conducted to determine the effect of lignans treatment on retinal microvascular function in vivo. Western blot, protein immunoprecipitation (IP), MTT assays, and enzyme activity assay was conducted to detect the effect of ligans treatment on oxidative stress response. RESULTS: Lignans protected retinal endothelial cell against AGEs-induced injury in vitro and diabetes-induced vascular dysfunction in vivo. Lignans treatment could regulate oxidative stress response in retinal endothelial cell line, retina, and liver. Moreover, we showed that NRF2/HO-1 signaling was critical for lignans-mediated oxidative stress regulation. CONCLUSION: Lignans treatment could protect against endothelial dysfunction in vivo and in vitro via regulating Nrf2/HO-1 signaling. Lignans might be developed as a promising drug for the treatment of diabetes-induced microvascular dysfunction.


Asunto(s)
Diabetes Mellitus Experimental/tratamiento farmacológico , Retinopatía Diabética/tratamiento farmacológico , Eucommiaceae/química , Productos Finales de Glicación Avanzada/farmacología , Hiperglucemia/tratamiento farmacológico , Lignanos/farmacología , Animales , Barrera Hematorretinal/efectos de los fármacos , Barrera Hematorretinal/metabolismo , Línea Celular , Supervivencia Celular/efectos de los fármacos , Diabetes Mellitus Experimental/inducido químicamente , Diabetes Mellitus Experimental/genética , Diabetes Mellitus Experimental/patología , Retinopatía Diabética/inducido químicamente , Retinopatía Diabética/genética , Retinopatía Diabética/patología , Células Endoteliales/efectos de los fármacos , Células Endoteliales/metabolismo , Células Endoteliales/patología , Azul de Evans/metabolismo , Regulación de la Expresión Génica , Hemo-Oxigenasa 1/genética , Hemo-Oxigenasa 1/metabolismo , Hiperglucemia/inducido químicamente , Hiperglucemia/genética , Hiperglucemia/patología , Lignanos/aislamiento & purificación , Masculino , Proteínas de la Membrana/genética , Proteínas de la Membrana/metabolismo , Ratones , Ratones Endogámicos C57BL , Factor 2 Relacionado con NF-E2/genética , Factor 2 Relacionado con NF-E2/metabolismo , Extractos Vegetales/química , Hojas de la Planta/química , Especies Reactivas de Oxígeno/antagonistas & inhibidores , Especies Reactivas de Oxígeno/metabolismo , Retina/efectos de los fármacos , Retina/metabolismo , Retina/patología , Transducción de Señal , Estreptozocina
16.
Chin J Nat Med ; 14(9): 653-660, 2016 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-27667510

RESUMEN

The present study aimed to establish a pharmacodynamic method using the pySolo software to explore the influence of freeze-dried powders of Shuangxia Decoction (SXD) on the sleep of normal Drosophila melanogaster and the Drosophila melanogaster whose sleep was divested by light. The dose-effect and the time-effect relationships of SXD on sleep were examined. The effect-onset concentration of SXD was 0.25%, the plateau appeared at the concentration of 2.5% and the total sleep time showed a downtrend when the concentration was greater than 2.5%. The sleep time was the longest on the fourth day after SXD was given. The fruit fly sleep deprivation model was repeated by light stimulation at night. The middle dosage group (2.5%) had the best insomnia-curing effect. In conclusion, using the pySolo software, an approach for the pharmacodynamics study was established with Drosophila melanogaster as a model organism to determine the insomnia-curing effects of the traditional Chinese medicine (TCM). Our results demonstrated the reliability of this method. The freeze-dried powders of SXD could effectively improve the sleep quality of Drosophila melanogaster.


Asunto(s)
Medicamentos Herbarios Chinos/administración & dosificación , Trastornos del Inicio y del Mantenimiento del Sueño/tratamiento farmacológico , Animales , Modelos Animales de Enfermedad , Drosophila melanogaster , Femenino , Humanos , Masculino , Sueño , Trastornos del Inicio y del Mantenimiento del Sueño/fisiopatología
17.
Ann Hepatol ; 12(5): 824-9, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-24018503

RESUMEN

Hepatocellular carcinoma (HCC) typically originates from HBV or HCV associated liver cirrhosis. Primary Sjögren's syndrome (pSS) is a kind of autoimmune disease. A sixty-two year old female patient with mild liver damage was diagnosed with pSS after excluding viral, alcoholic and drug-induced hepatitis according to serum immunological detection and liver biopsy. But when she was hospitalized for a second time two years later, a CT scan revealed liver neoplasm. Surgery confirmed HCC and liver cirrhosis by pathology. The elevated level of AFP recovered to normal after tumorectomy. In conclusion, HCC might be a candidate outcome in patients with pSS; it is the doctors' responsibility to keep this kind of patient under surveillance.


Asunto(s)
Carcinoma Hepatocelular/etiología , Neoplasias Hepáticas/etiología , Síndrome de Sjögren/complicaciones , Biopsia , Carcinoma Hepatocelular/sangre , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/cirugía , Quimioterapia Adyuvante , Femenino , Hepatectomía , Humanos , Cirrosis Hepática/etiología , Neoplasias Hepáticas/sangre , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/cirugía , Persona de Mediana Edad , Síndrome de Sjögren/diagnóstico , Tomografía Computarizada por Rayos X , Resultado del Tratamiento , alfa-Fetoproteínas/metabolismo
19.
Sheng Wu Gong Cheng Xue Bao ; 23(4): 724-9, 2007 Jul.
Artículo en Chino | MEDLINE | ID: mdl-17822052

RESUMEN

DNA recombinase FLP gene exists on the 2 micro plasmid of Saccharomyces cerevisiae. Recombinase FLP could recognize an FRT site composed of 34bp and function the sequences for exchange, recombination, deletion and reversion between the two orientated FRT sites. These functions are highly recognized by molecular biologists and biotechnology engineers for theoretic and applicable technology studies. This work constructed a prokaryotic over-expressed vector harboring FLP gene nominated as pQE30-flpe and established its over-expression culture system in which recombinase FLP could be efficiently expressed in E. coli strain M15. Purification procedures for high purity and active FLP are established through combination of ammonium sulfate precipitation with a 0.5-1.0 mL micro-column technique of Ni affinity chromatography with gradient elution. To verify the recombinase activity of purified FLP, substrate vectors, sequence donor vector (pUC18-FRT-gfp-FRT) and sequence accepting vector (pET30a-FRT) are constructed with various number, orientation of FRTs harboring the GFP gene for the expression of visible assay of the functions of recombination, exchange and deletion. Results showed that the system not only over expressed recombinase FLP in prokaryotic E. coli, but also efficiently purified the enzyme with a higher activity of the function of recombination, exchange and deletion. The system and the method are easily implemented and feasibly manipulated for theoretic study and biotechnology application.


Asunto(s)
ADN Nucleotidiltransferasas/biosíntesis , ADN Nucleotidiltransferasas/metabolismo , Proteínas Recombinantes de Fusión/aislamiento & purificación , Saccharomyces cerevisiae/enzimología , Secuencia de Bases , ADN/genética , ADN Nucleotidiltransferasas/genética , Escherichia coli/genética , Escherichia coli/metabolismo , Proteínas Fúngicas/metabolismo , Datos de Secuencia Molecular , Proteínas Recombinantes de Fusión/biosíntesis , Proteínas Recombinantes de Fusión/genética , Recombinación Genética
20.
Hepatol Res ; 35(2): 111-7, 2006 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-16650799

RESUMEN

BACKGROUND: It has been reported that serum soluble E-selectin (sE-selectin) may be increased in some inflammatory liver diseases. The purpose of our study was to investigate changes of sE-selectin, T lymphocyte subsets, natural killer (NK) cells, and HBV load in patients with chronic hepatitis B (CHB), analyze the relationship between them, and discuss their significances. METHODS: Fifty-four patients with chronic hepatitis B and fourteen controls were studied. Serum sE-selectin, T lymphocyte subsets, NK cells, and hepatitis B virus (HBV) load were detected by enzyme-linked immunosorbent assay (ELISA), flow cytometry (FCM), and fluorescence quantitative polymerase chain reaction (FQ-PCR), respectively. RESULTS: sE-selectin level in patients with CHB increased significantly than that in controls (p<0.01). The percentages of CD4 positive cells and NK cells decreased while the percentage of CD8 positive cells increased significantly in CHB patients than in controls (p<0.01, respectively). sE-selectin level significantly related to levels of T lymphocyte subsets, NK cells, serum alanine aminotransferase (sALT) and aspartate aminotransferase (sAST) (p<0.01, respectively), but had no relationship with HBV level. CONCLUSION: The sE-selectin levels in patients with chronic hepatitis B increase significantly and correlate to liver inflammation, suggesting that sE-selectin can be considered as an additional useful marker of CHB inflammatory activity, and E-selectin may play part of role in pathogenesis of chronic hepatitis B.

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