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排序方式: 共有300条查询结果,搜索用时 62 毫秒
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Piotr Wacinski Mariusz Gadzinowski Wojciech Dabrowski Justyna Szumilo Jakub Wacinski Nathalie Oru Eric Vicaut Stanislaw Czuczwar Janusz Kocki Teresa Basinska Stanislaw Slomkowski 《International journal of molecular sciences》2021,22(14)
Atherosclerosis involves an ongoing inflammatory response of the vascular endothelium and vessel wall of the aorta and vein. The pleiotropic effects of statins have been well described in many in vitro and in vivo studies, but these effects are difficult to achieve in clinical practice due to the low bioavailability of statins and their first-pass metabolism in the liver. The aim of this study was to test a vessel wall local drug delivery system (DDS) using PLA microstructures loaded with simvastatin. Wistar rats were fed high cholesterol chow as a model. The rat vessels were chemically injured by repeated injections of perivascular paclitaxel and 5-fluorouracil. The vessels were then cultured and treated by the injection of several concentrations of poly(L,L-lactide) microparticles loaded with the high local HMG-CoA inhibitor simvastatin (0.58 mg/kg) concentration (SVPLA). Histopathological examinations of the harvested vessels and vital organs after 24 h, 7 days and 4 weeks were performed. Microcirculation in mice as an additional test was performed to demonstrate the safety of this approach. A single dose of SVPLA microspheres with an average diameter of 6.4 μm and a drug concentration equal to 8.1% of particles limited the inflammatory reaction of the endothelium and vessel wall and had no influence on microcirculation in vivo or in vitro. A potent pleiotropic (anti-inflammatory) effect of simvastatin after local SVPLA administration was observed. Moreover, significant concentrations of free simvastatin were observed in the vessel wall (compared to the maximum serum level). In addition, it appeared that simvastatin, once locally administered as SVPLA particles, exerted potent pleiotropic effects on chemically injured vessels and presented anti-inflammatory action. Presumably, this effect was due to the high local concentrations of simvastatin. No local or systemic side effects were observed. This approach could be useful for local simvastatin DDSs when high, local drug concentrations are difficult to obtain, or systemic side effects are present. 相似文献
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Dominik Mierzwa Justyna Szadzińska Andrzej Pawłowski Reihaneh Pashminehazar Abdolreza Kharaghani 《Drying Technology》2019,37(8):988-1001
This study was conducted to investigate the drying characteristics and quality of raspberries dried in non-stationary conditions. Seven drying programs were carried out, including convective (CV) drying as a reference. The non-stationary-hybrid programs were based on continuous CV drying with intermittent microwave and ultrasound assistance. The Midilli–Kucuk model was used successfully to describe the drying kinetics of raspberry fruits. The comparison between moisture ratio, drying rate, diffusion coefficient, energy consumption, and quality analysis, showed that non-stationary-hybrid drying improves process kinetics and results in less color change, higher anthocyanin retention, and better texture profile analysis characteristics with optimal energy usage than other methods. In addition, the physical and microstructural changes occurred during different drying processes were discussed. 相似文献
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Olufunmilayo Olukemi Akapo Joanna M. Macnar Justyna D. Kry Puleng Rosinah Syed Khajamohiddin Syed Dominik Gront 《International journal of molecular sciences》2021,22(15)
Cytochrome P450 monooxygenase CYP51 (sterol 14α-demethylase) is a well-known target of the azole drug fluconazole for treating cryptococcosis, a life-threatening fungal infection in immune-compromised patients in poor countries. Studies indicate that mutations in CYP51 confer fluconazole resistance on cryptococcal species. Despite the importance of CYP51 in these species, few studies on the structural analysis of CYP51 and its interactions with different azole drugs have been reported. We therefore performed in silico structural analysis of 11 CYP51s from cryptococcal species and other Tremellomycetes. Interactions of 11 CYP51s with nine ligands (three substrates and six azoles) performed by Rosetta docking using 10,000 combinations for each of the CYP51-ligand complex (11 CYP51s × 9 ligands = 99 complexes) and hierarchical agglomerative clustering were used for selecting the complexes. A web application for visualization of CYP51s’ interactions with ligands was developed (http://bioshell.pl/azoledocking/). The study results indicated that Tremellomycetes CYP51s have a high preference for itraconazole, corroborating the in vitro effectiveness of itraconazole compared to fluconazole. Amino acids interacting with different ligands were found to be conserved across CYP51s, indicating that the procedure employed in this study is accurate and can be automated for studying P450-ligand interactions to cater for the growing number of P450s. 相似文献
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Evaluation of apple texture with contact acoustic emission detector: A study on performance of calibration models 总被引:1,自引:0,他引:1
Artur Zdunek Justyna CybulskaDorota Konopacka Krzysztof Rutkowski 《Journal of food engineering》2011,106(1):80-87
Performance of calibration models for evaluation of apples sensory texture with contact acoustic emission detector (CAED) was studied. For model evaluation and testing, 2500 apples of 19 cultivars were harvested over two seasons. Apples were stored at normal atmosphere (NA), controlled atmosphere (CA) for different periods or were treated with 1-methylcyclopropene (1-MCP) in order to obtain a high variability of texture and fruit maturity. Apples were tested simultaneously in two distinct laboratories. The models were created and validated on averaged values from 10 fruits using simple linear regression, multiple linear regression (MLR) and principal component regression (PCR). Performance statistics of the models were expressed in terms of determination coefficient (R2), root mean square errors of cross validation (RMSECV) or prediction (RMSEP) and ratio of prediction to deviation (RPD). Firmness and total acoustic emission counts were predictors of sensory texture in the models. MLR and PCR models show better performance for prediction of sensory data than simple linear regression models however PCR models show the best results among models tested in this study. Common PCR models for several cultivars allow for successful prediction of hardness (RPD > 2.0), crispness and overall texture (1.5 < RPD < 2.0). The single-cultivar PCR models, constructed on data sets containing 26-39 averaged values, reveal significantly better performance (RPD > 2.0 for most of the cases) than the common PCR models for many varieties. 相似文献
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Pawe Lenartowicz Mateusz Psurski Aleksandra Kotynia Aleksandra Pienina Monika Cuprych Klaudia Poniatowska Justyna Brasu Pawe Kafarski 《International journal of molecular sciences》2021,22(4)
Background: Dehydropeptides are analogs of peptides containing at least one conjugate double bond between α,β-carbon atoms. Its presence provides unique structural properties and reaction centre for chemical modification. In this study, the series of new class of dipeptides containing S-substituted dehydrocysteine with variety of heterocyclic moieties was prepared. The compounds were designed as the building blocks for the construction of artificial metalloenzymes (artzymes). Therefore, the complexing properties of representative compounds were also evaluated. Furthermore, the acknowledged biological activity of natural dehydropeptides was the reason to extend the study for antiproliferative action of against several cancer cell lines. Methods: The synthetic strategy involves glycyl and phenylalanyl-(Z)-β-bromodehydroalanine as a substrate in one pot addition/elimination reaction of thiols. After deprotection of N-terminal amino group the compounds with triazole ring were tested as complexones for copper(II) ions using potentiometric titration and spectroscopic techniques (UV-Vis, CD, EPR). Finally, the antiproliferative activity was evaluated by sulforhodamine B assay. Results and Conclusions: A simple and efficient procedure for preparation of dipeptides containing S-substituded dehydrocysteine was provided. The peptides containing triazole appeared to be strong complexones of copper(II) ions. Some of the peptides exhibited promising antiproliferative activities against number of cancer cell lines, including cell lines resistant to widely used anticancer agent. 相似文献
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Justyna Popi Agnieszka Gunia-Krzyak Karolina Soczyska Paulina Koczurkiewicz-Adamczyk Kamil Piska Katarzyna Wjcik-Pszczoa Dorota elaszczyk Anna Krupa Pawe mudzki Henryk Marona Elbieta Pkala 《International journal of molecular sciences》2021,22(1)
Excessive UV exposure contributes to several pathological conditions like skin burns, erythema, premature skin aging, photodermatoses, immunosuppression, and skin carcinogenesis. Effective protection from UV radiation may be achieved with the use of sunscreens containing UV filters. Currently used UV filters are characterized by some limitations including systemic absorption, endocrine disruption, skin allergy induction, and cytotoxicity. In the research centers all over the world new molecules are developed to improve the safety, photostability, solubility, and absorption profile of new derivatives. In our study, we designed and synthesized seventeen novel molecules by combining in the structures two chromophores: xanthone and (E)-cinnamoyl moiety. The ultraviolet spectroscopic properties of the tested compounds were confirmed in chloroform solutions. They acted as UVB or UVA/UVB absorbers. The most promising compound 9 (6-methoxy-9-oxo-9H-xanthen-2-yl)methyl (E)-3-(2,4-dimethoxyphenyl)acrylate) absorbed UV radiation in the range 290–369 nm. Its photoprotective activity and functional photostability were further evaluated after wet milling and incorporation in the cream base. This tested formulation with compound 9 possessed very beneficial UV protection parameters (SPFin vitro of 19.69 ± 0.46 and UVA PF of 12.64 ± 0.32) which were similar as broad-spectrum UV filter tris-biphenyl triazine. Additionally, compound 9 was characterized by high values of critical wavelength (381 nm) and UVA/UVB ratio (0.830) thus it was a good candidate for broad-spectrum UV filter and it might protect skin against UVA-induced photoaging. Compound 9 were also shown to be photostable, non-cytotoxic at concentrations up to 50 µM when tested on five cell lines, and non-mutagenic in Ames test. It also possessed no estrogenic activity, according to the results of MCF-7 breast cancer model. Additionally, its favorable lipophilicity (miLogP = 5.62) does not predispose it to penetrate across the skin after topical application. 相似文献