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排序方式: 共有271条查询结果,搜索用时 406 毫秒
161.
Mulhbacher J Ispas-Szabo P Ouellet M Alex S Mateescu MA 《International journal of biological macromolecules》2006,40(1):9-14
Acetate (Ac-), aminoethyl (AE-) and carboxymethyl (CM-)derivatives of cross-linked high amylose starch (HASCL-6) were previously shown to control, over more than 20h, the release of drugs from highly loaded (up to 60% drug) monolithic tablets. It was now of interest to evaluate their mucoadhesive characteristics in view of further utilization in buccal or vaginal transmucosal delivery. The present study shows that ionic AE-HASCL-6 and CM-HASCL-6 derivatives exhibit higher mucoadhesive properties than neutral HASCL-6 and Ac-HASCL-6, suggesting that the ionic groups introduced on cross-linked starch chains play a role in the bioadhesion process. The adhesiveness seemed related to capillary attraction forces. Surface adhesion parameters were calculated for slabs based on the mentioned polymers and corroborated with their swelling behavior at various pH changes. The positively charged AE-derivatives presented a higher adhesion at acidic pH, being thus recommended for vaginal delivery, whereas the negatively charged derivatives (CM-HASCL-6) exhibited a better adhesion at neutral pH, being thus more appropriate for buccal delivery. 相似文献
162.
Pylypenko O Rak A Durek T Kushnir S Dursina BE Thomae NH Constantinescu AT Brunsveld L Watzke A Waldmann H Goody RS Alexandrov K 《The EMBO journal》2006,25(1):13-23
In eukaryotic cells Rab/Ypt GTPases represent a family of key membrane traffic controllers that associate with their targeted membranes via C-terminally conjugated geranylgeranyl groups. GDP dissociation inhibitor (GDI) is a general and essential regulator of Rab recycling that extracts prenylated Rab proteins from membranes at the end of their cycle of activity and facilitates their delivery to the donor membranes. Here, we present the structure of a complex between GDI and a doubly prenylated Rab protein. We show that one geranylgeranyl residue is deeply buried in a hydrophobic pocket formed by domain II of GDI, whereas the other lipid is more exposed to solvent and is skewed across several atoms of the first moiety. Based on structural information and biophysical measurements, we propose mechanistic and thermodynamic models for GDI and Rab escort protein-mediated interaction of RabGTPase with intracellular membranes. 相似文献
163.
Modification of actin at Cys (374) with tetramethylrhodamine maleimide (TMR-actin) has been used for visualization of actin filaments and to produce high-resolution crystal structures of actin. We show that TMR-actin exhibits a 21% decrease in absorbance at 557 nm upon thermal unfolding, likely due to the movement of TMR to a more hydrophobic environment upon rapid unfolding and protein aggregation. We took advantage of this property to test models of actin protein unfolding. A transition temperature ( T m) of 60.2 +/- 0.2 degrees C for Ca (2+).ATP.TMR-actin was determined using A 557 and agreed with our own determinations employing different techniques and previous work with unlabeled actin. Our data show that the dependence of TMR-actin thermal stability on the bound nucleotide and cations follows a trend of Ca (2+).ATP > Mg (2+).ATP > Ca (2+).ADP > Mg (2+).ADP. The activation energies and frequency factors for the thermal unfolding of TMR-actin determined with two methods were in good agreement with those previously determined for unlabeled actin. We observed a biphasic trend in the T m of TMR-actin with increasing nucleotide concentrations, supporting a two-pathway model for actin protein unfolding where one pathway dominates at different concentrations of nucleotide. Additionally, TMR-actin bound by DNase I or gelsolin segment-1 exhibited elevated transition temperatures. 相似文献
164.
转铁蛋白导向脂质体核磁造影剂纳米粒子(TfNTR-LipNBD-Magnevist)——一种肿瘤靶向磁共振造影剂 总被引:1,自引:0,他引:1
造影剂辅助的核磁共振成像是目前肿瘤诊断的最好方法之一.但是由于核磁共振成像内在的低灵敏性以及造影剂的非特异性,导致肿瘤早期诊断较为困难.文章将一种新的肿瘤靶向核磁造影剂纳米粒子应用于早期肿瘤的影像诊断.这种新的肿瘤靶向核磁造影剂纳米粒子由配体转铁蛋白(Tf)、纳米水平的正电脂质体(Lip)载体和临床常用的造影剂Magnevist(TfNIR-LipNBD-Magnevist)三部分构成.另外转铁蛋白和脂质体粒子上,亦标记了荧光物质用于确定转铁蛋白-脂质体-造影剂纳米粒子的靶向性,以及肿瘤的光学影像诊断.在体外实验中,利用激光共聚焦显微镜和光学影像证明了靶向纳米粒子介导的细胞内吞和特异性结合.在裸鼠肿瘤模型中,造影剂纳米粒子TfNIR-LipNBD-Magnevist经尾静脉注入后,显著增强了肿瘤内信号与周围组织的对比度.由造影剂纳米粒子介导的肿瘤内信号显著强于单独Magnevist辅助的肿瘤内信号.同时,利用光学影像方法,在肿瘤内检测到特异的荧光信号.其结果进一步支持了转铁蛋白-脂质体-造影剂(TfNIR-LipNBD-Magnevist)纳米粒子的靶向性和肿瘤影像诊断的有效性. 相似文献
165.
166.
Plesca D Mazumder S Gama V Matsuyama S Almasan A 《The Journal of biological chemistry》2008,283(45):30796-30803
We have previously shown that caspase-mediated cleavage of Cyclin E generates p18-Cyclin E in hematopoietic tumor cells. Its expression can induce apoptosis or sensitize to apoptotic stimuli in many cell types. However, p18-cyclin E has a much shorter half-life than Cyclin E, being more effectively ubiquitinated and degraded by the 26 S proteasome. A two-step process has emerged that regulates accelerated degradation of Cyclin E, with a caspase-mediated cleavage followed by enhanced proteasome-mediated degradation. We show that recognition of p18-Cyclin E by the Skp1-Cul1-Fbw7 (SCF) complex and its interaction with the Fbw7 protein isoforms can take place independently of phosphorylation of p18-Cyclin E at a C-terminal phosphodegron. In addition to the SCF(Fbw7) pathway, Ku70 binding that facilitates Hdm2 recruitment may also be implicated in p18-Cyclin E ubiquitination. Blocking p18-Cyclin E degradation with proteasome inhibitors increases levels of p18-Cyclin E and enhances its association with Ku70, thus leading to Bax release, its activation, and apoptosis. Moreover, cells expressing p18-Cyclin E are more sensitive to treatment with proteasome inhibitors, such as Bortezomib. By preventing its proteasomal degradation, p18-Cyclin E, but not Cyclin E, may become an effective therapeutic target for Bortezomib and apoptotic effectors in hematopoietic malignancies. 相似文献
167.
Mihail Lucian Pascu Balazs Danko Ana Martins Nikoletta Jedlinszki Tatiana Alexandru Viorel Nastasa Mihai Boni Andra Militaru Ionut Relu Andrei Angela Staicu Attila Hunyadi Seamus Fanning Leonard Amaral 《PloS one》2013,8(2)
Introduction
Phenothiazines when exposed to white light or to UV radiation undergo a variety of reactions that result in degradation of parental compound and formation of new species. This process is slow and may be sped up with exposure to high energy light such as that produced by a laser.Methods
Varying concentrations of Chlorpromazine Hydrochloride (CPZ) (2–20 mg/mL in distilled water) were exposed to 266 nm laser beam (time intervals: 1–24 hrs). At distinct intervals the irradiation products were evaluated by spectrophotometry between 200–1500 nm, Thin Layer Chromatography, High Pressure Liquid Chromatography (HPLC) - Diode Array Detection, HPLC tandem mass spectrometry, and for activity against the CPZ sensitive test organism Staphylococcus aureus ATCC 25923.Results
CPZ exposure to 266 nm laser beam of given energy levels yielded species, whose number increased with duration of exposure. Although the major species produced were Promazine (PZ), hydroxypromazine or PZ sulfoxide, and CPZ sulfoxide, over 200 compounds were generated with exposure of 20 mg/mL of CPZ for 24 hrs. Evaluation of the irradiation products indicated that the bioactivity against the test organism increased despite the total disappearance of CPZ, that is due, most probably, to one or more new species that remain yet unidentified.Conclusions
Exposure of CPZ to a high energy (6.5 mJ) 266 nm laser beam yields rapidly a large number of new and stable species. For biological grade phenothiazines (in other words knowing the impurities in the samples: solvent and solute) this process may be reproducible because one can control within reasonably low experimental errors: the concentration of the parent compound, the laser beam wavelength and average energy, as well as the duration of the exposure time. Because the process is “clean” and rapid, it may offer advantages over the pyrogenically based methods for the production of derivatives. 相似文献168.
169.
Alexandru F. Cri?an Cristian Oancea Bogdan Timar Ovidiu Fira-Mladinescu Alexandru Cri?an Voicu Tudorache 《PloS one》2014,9(7)
Background/Purpose
Chronic obstructive pulmonary disease (COPD), especially in severe forms, is commonly associated with multiple cognitive problems. Montreal Cognitive Assessment test (MoCA) is used to detect cognitive impairment evaluating several areas: visuospatial, memory, attention and fluency. Our study aim was to evaluate the impact of stable COPD and exacerbation (AECOPD) phases on cognitive status using MoCA questionnaire.Methods
We enrolled 39 patients (pts), smokers with COPD group D (30 stable and 9 in AECOPD) and 13 healthy subjects (control group), having similar level of education and no significant differences regarding the anthropometric measurements. We analyzed the differences in MoCA score between these three groups and also the correlation between this score and inflammatory markers.Results
Patients with AECOPD had a significant (p<0.001) decreased MoCA score (14.6±3.4) compared to stable COPD (20.2±2.4) and controls (24.2±5.8). The differences between groups were more accentuated for the language abstraction and attention (p<0.001) and delayed recall and orientation (p<0.001) sub-topics. No significant variance of score was observed between groups regarding visuospatial and naming score (p = 0.095). The MoCA score was significantly correlated with forced expiratory volume (r = 0.28) and reverse correlated with C-reactive protein (CRP) (r = −0.57), fibrinogen (r = −0.58), erythrocyte sedimentation rate (ESR) (r = −0.55) and with the partial pressure of CO2 (r = −0.47).Conclusions
According to this study, COPD significantly decreases the cognitive status in advanced and acute stages of the disease. 相似文献170.
Weixian Zeng Wenhua Xiang Bo Zhou Shuai Ouyang Yelin Zeng Liang Chen Grégoire T. Freschet Oscar J. Valverde-Barrantes Alexandru Milcu 《Oikos》2021,130(1):1-14
The importance of species richness to ecosystem functioning and services is a central tenet of biological conservation. However, most of our theory and mechanistic understanding is based on diversity found aboveground. Our study sought to better understand the relationship between diversity and belowground function by studying root biomass across a plant diversity gradient. We collected soil cores from 91 plots with between 1 and 12 aboveground tree species in three natural secondary forests to measure fine root (≤ 2 mm in diameter) biomass. Molecular methods were used to identify the tree species of fine roots and to estimate fine root biomass for each species. This study tested whether the spatial root partitioning (species differ by belowground territory) and symmetric growth (the capacity to colonize nutrient-rich hotspots) underpin the relationship between aboveground species richness and fine root biomass. All species preferred to grow in nutrient-rich areas and symmetric growth could explain the positive relationship between aboveground species richness and fine root biomass. However, symmetric growth only appeared in the nutrient-rich upper soil layer (0–10 cm). Structural equation modelling indicated that aboveground species richness and stand density significantly affected fine root biomass. Specifically, fine root biomass depended on the interaction between aboveground species richness and stand density, with fine root biomass increasing with species richness at lower stand density, but not at higher stand density. Overall, evidence for spatial (i.e. vertical) root partitioning was inconsistent; assumingly any roots growing into deeper unexplored soil layers were not sufficient contributors to the positive diversity–function relationship. Alternatively, density-dependent biotic interactions affecting tree recruitment are an important driver affecting productivity in diverse subtropical forests but the usual root distribution patterns in line with the spatial root partitioning hypothesis are unrealistic in contexts where soil nutrients are heterogeneously distributed. 相似文献