RESUMEN
To investigate the mechanism of apoptosis in myocardial cells of aging rats induced by D-galactose and to study the effect of the Polysaccharide isolated from the seeds of Cuscuta chinensis Lam (PCCL) on apoptosis of cardiomyocytes and its corresponding machinasim in aging rat model. Fifty male SD rats were randomly divided into 5 groups. Normal control group (NC). D-galactose (100 mg · kg(-1)d(-1) for 56 day) indued aging group (MC), D-galactose plus 100 mg kg(-1) d(-1) PCCL group (ML), D-galactose plus 200 mg kg(-1) d(-1) PCCL group (MM), and D-galactose plus 400 mg kg(-1) d(-1) PCCL group (MH). Same volume of solution (water, or PCCL aqueous solution) was given by gavage for 56 days. Then the hearts were collected and apoptosis parameters were evaluated. Caspase-3 and Cyt c were determined by fluorescence spectrometer, the apoptosis rate was assessed by AnnexinV-FITC method by Flow-Cytometry, [Ca(2+)]i and [Ca(2+)]i overloaded by KCL were observed by laser scanning confocal microscopy (LSCM); Bcl-2 and Bax were examined by immunohistochemistry. The content of Cyt C, [Ca(2+)]i of cardiomyocytes, the activity of Caspase-3, Bax expression level in D-galactose induced aging group were higher than NC (p < 0.05). The ratio of Bcl-2/Bax was decreased in D-galactose induced aging group compared to NC. On the other hand, the content of Cyt C, [Ca(2+)]i of cardiomyocytes, the activity of Caspase-3 and apoptosis rate, as well as Bax expression level in all three PCCL groups were decreased compared to galactose induced group (p < 0.05). Bcl-2/Bax ratio was increased in all PCCL groups compared to galactose induced aging group. PCCL could decrease the apoptosis of cardiomyocytes by the mitochondria apoptosis pathway.
Asunto(s)
Envejecimiento , Apoptosis/efectos de los fármacos , Cuscuta/química , Miocitos Cardíacos/efectos de los fármacos , Polisacáridos/farmacología , Semillas/química , Animales , Calcio/metabolismo , Caspasa 3/genética , Caspasa 3/metabolismo , Citocromos c/genética , Citocromos c/metabolismo , Galactosa/administración & dosificación , Galactosa/efectos adversos , Masculino , Microscopía Confocal , Miocitos Cardíacos/metabolismo , Extractos Vegetales/farmacología , Cloruro de Potasio/metabolismo , Ratas , Ratas Sprague-Dawley , Proteína X Asociada a bcl-2/genética , Proteína X Asociada a bcl-2/metabolismoRESUMEN
The synergistic effects of tamoxifen on the sensitivity of MCF-7 cells to daunorubicin have been reported. Whether the effects of daunorubicin on MCF-7/adr cells can be improved by tamoxifen in liposomes and how tamoxifen changes daunorubicin's behavior in vivo remains unclear. The aim of this study was to investigate the effects of tamoxifen on the uptake and biodistribution of daunorubicin liposomes by breast-cancer-resistant MCF-7/adr cells in vitro and in vivo. The uptake of liposomes by MCF-7/adr cells in vitro studies was measured using flow cytometry and laser confocal microscopy. The biodistributions of carriers and free drugs were evaluated by DiR dye using in vivo imaging. Tamoxifen obviously enhanced the cellular uptake of liposomes by MCF-7/adr cells in time-dependent manners. According to the results from in vivo imaging analysis, the mean fluorescence intensity of DiR liposomes with tamoxifen in the tumor regions of MCF-7/adr tumor-bearing nude mice was much stronger than that of DiR liposomes alone (16,450 ± 1,331 versus 3,666 ± 321; n = 3). Pegylated liposomes elongated the existence of daunorubicin in the circulatory system and the enhanced permeability and retention effect enhanced its concentration in local tumor tissues, which may provide the precondition for tamoxifen further promoting the uptake by MCF-7/Adr cells in vivo. Using daunorubicin liposomes and tamoxifen together generates better biodistribution profiles in tumor tissue than using daunorubicin liposomes only, which contributes to improving the therapeutic effect of breast cancer treatment.
Asunto(s)
Daunorrubicina/administración & dosificación , Daunorrubicina/farmacocinética , Portadores de Fármacos/farmacocinética , Liposomas/química , Liposomas/farmacocinética , Tamoxifeno/administración & dosificación , Tamoxifeno/farmacología , Animales , Antineoplásicos/administración & dosificación , Antineoplásicos/química , Antineoplásicos/farmacología , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Daunorrubicina/química , Daunorrubicina/farmacología , Relación Dosis-Respuesta a Droga , Portadores de Fármacos/administración & dosificación , Portadores de Fármacos/química , Ensayos de Selección de Medicamentos Antitumorales , Estabilidad de Medicamentos , Femenino , Citometría de Flujo , Humanos , Liposomas/administración & dosificación , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Microscopía Confocal , Relación Estructura-Actividad , Tamoxifeno/farmacocinética , Distribución Tisular/efectos de los fármacosRESUMEN
The process of swine manure and wheat straw aerobic composting was examined, with exogenous microbial agents being added in treatment group. The physicochemical properties were measured by conventional methods, and bacterial community characteristics were investigated by high throughput sequencing analysis. Exogenous microbial agents increased high-temperature duration, reduced pH value at the end of fermentation stage, augmented total nitrogen content, reduced C/N ratio. Results from principal component analysis showed that microbial agents affected the stability of bacterial community during composting. At the phylum level, the relative abundance of Firmicutes, Proteobacteria, and Chloroflexi was higher in the treatment group. At the class level, the relative abundance of Clostridia, Alphaproteobacteria, and Gammaproteobacteria in the treatment group were higher at the mesophilic and thermophilic phases. At the family level, Peptostreptococcaceae, Clostridiaceae_1, and Halanaerobiaceae of the Clostridia and Micromonosporaceae in the treatment group were higher at the mesophilic and thermophilic phases. Halocella was significantly positively correlated with exogenous microbial agents, while Ammoniibacillus was significantly negatively correlated with it. It suggested that microbial agents significantly changed the physicochemical properties and bacterial community structure during swine composting.
Asunto(s)
Compostaje , Animales , Bacterias , Calor , Estiércol , Nitrógeno , Suelo , PorcinosRESUMEN
The aim of this study was to stabilize all-trans-retinol (RE) by complexification with chitosan derivatives through H-bonding. Succinated chitosan (CHI-succ) with three different degrees (5, 10, 20 mol%) of succinylation were synthesized to form complexes with RE. Various weight ratios (w/w) of CHI-succ/RE complexes were prepared and characterized to produce stable complexes in nanometer size. The CHI-succ(0.20)/RE complex with approximate 250 nm in diameter was obtained using a CHI-succ(0.20) concentration of 0.005% (w/v) in double deionized water with various contents of RE. From fine-tuning the degree of succinylation and the weight ratio of the CHI-succ and RE, the formation of supramolecular complexes simultaneously improved water solubility and stability of RE. The cell viability of CHI-succ polymers and their RE complexes in 3T3 cells were all>85% relative to the control. The antioxidant ability of the CHI-succ(0.20)/RE complexes was significantly greater than that of pure RE using a 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay (p<0.01).
Asunto(s)
Quitosano/química , Nanopartículas/química , Ácido Succínico/química , Vitamina A/química , Vitamina A/farmacología , Agua/química , Células 3T3 , Animales , Compuestos de Bifenilo/química , Cápsulas , Supervivencia Celular/efectos de los fármacos , Depuradores de Radicales Libres/química , Depuradores de Radicales Libres/farmacología , Depuradores de Radicales Libres/toxicidad , Enlace de Hidrógeno , Ratones , Picratos/química , Solubilidad , Vitamina A/toxicidadRESUMEN
It is well known that puerarin attenuates ischemia-reperfusion injury and promotes function recovery of ischemic region. However, due to its reverse physiochemical properties, puerarin does not easily cross the blood-brain barrier. The aim of the present study is to create puerarin nanoparticles which increase and prolong the puerarin concentration in the brain. Using emulsion solvent evaporation techniques, we designed puerarin-loaded poly(D,L-lactic-co-glycolic acid) nanoparticles. Hydroxypropyl beta cyclodextrin (HP-ß-CD) was used to increase the solubility of puerarin and gelatin to enhance viscosity of inner water phase, which improved puerarin entrapment. The drug release kinetics and nanoparticle degradation in phosphate buffered saline (PBS) were analyzed by electronic microscopy and high-performance liquid chromatography. Computerized tomography scans were used to detect the infarction volume and electroencephalogram (EEG) was recorded to estimate the recovery of brain function. The results showed that the combined HP-ß-CD and gelatin significantly improved the entrapment efficiency. The infarction volume was significantly decreased on days 3 and 7 after the administration of puerarin nanoparticles compared with that of control and pure puerarin. EEG was also significantly improved. Puerarin nanoparticles are potentially applicable for the brain injury induced by ischemic-reperfusion.