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191.
DNA-dependent protein kinase (DNA-PK) is a key enzyme in non-homologous DNA end joining (NHEJ) repair pathway. The targeted inhibition of such enzyme would furnish a valuable option for cancer treatment. In this study we report the development of validation of enzyme homology model, and the subsequent use of this model to perform docking-based virtual screening against a database of FDA-approved drugs. The nominated highest ranking hits (Praziquantel and Dutasteride) were subjected to biological investigation. Additionally, molecular dynamic study was carried-out for binding mode exploration. Results of the biological evaluation revealed that both compounds inhibit the DNA-PK enzymatic activity at relatively high concentration levels with an IC50 of 17.3 μM for praziquantel and >20 μM for dutasteride. Furthermore, both agents enhanced the anti-proliferative effects of doxorubicin and cisplatin on breast cancer (MCF7) and lung cancer (A549) cell lines. This result indicates that these two hits are good candidate as DNA-PK inhibitors and worth further structural modifications to enhance their enzyme inhibitory effects. 相似文献
192.
193.
《International journal of food sciences and nutrition》2013,64(2):225-235
Seaweeds are rich in vitamins, minerals, dietary fibres, proteins, polysaccharides and various functional polyphenols. Many researchers have focused on brown algae as a potential source of bioactive materials in the past few decades. Ecklonia cava is a brown seaweed that is abundant in the subtidal regions of Jeju Island in the Republic of Korea. This seaweed attracted extensive interest due to its multiple biological activities. E. cava has been identified as a potential producer of wide spectrum of natural substances such as carotenoids, fucoidans and phlorotannins showing different biological activities in vital industrial applications including pharmaceutical, nutraceutical, cosmeceutical and functional food. This review focuses on biological activities of the brown seaweed E. cava based on latest research results, including antioxidant, anticoagulative, antimicrobial, antihuman immunodeficiency virus, anti-inflammatory, immunomodulatory, antimutagenic, antitumour and anticancer effects. The facts summarized here may provide novel insights into the functions of E. cava and its derivatives and potentially enable their use as functional ingredients in potential industrial applications. 相似文献
194.
Internal thoracic artery (ITA) and small saphenous vein (SSV) are two viable conduits for coronary artery bypass grafts. The aim of this study was to investigate the viscoelastic behavior of the small saphenous vein and internal thoracic artery under compressive and tensile loadings at body temperature. The dynamic mechanical analysis was used to measure the viscoelastic properties of the ITA and SSV at both the desired temperature and load frequency range. Storage modulus, loss modulus as well as phase angle of both the blood vessels were measured at the temperature of 37 ± 1 °C and under a sinusoidal load with the frequency range of 1–2 Hz. The mean storage and loss modulus of the SSV were both higher than that of the ITA. Furthermore, the SSV showed a higher stiffness and internal friction compared to those values under the tensile load. While ITA was stiffer under the tensile load, no considerable difference was observed among the compressive and tensile loss modulus. A more intense viscous behavior was observed under the radial direction. The results also revealed that the SSV has much higher stiffness whereas less viscous behavior compared to the ITA, especially in the radial direction. The results may have implications not only for understanding of the viscoelastic time-dependent mechanical behavior of the ITA and SSV but also for tissue engineering applications to make scaffolds according to the real time-dependent viscoelastic mechanical properties of these arteries and veins. 相似文献
195.
Edema factor (EF) is a calmodulin (CaM)-activated adenylyl cyclase (AC) toxin from Bacillus anthracis that contributes to anthrax pathogenesis. Anthrax is an important medical problem, but treatment of B. anthracis infections is still unsatisfying. Thus, selective EF inhibitors could be valuable drugs in the treatment of anthrax infection, most importantly shock. The catalytic site of EF, the EF/CaM interaction site and allosteric sites constitute potential drug targets. To this end, most efforts have been directed towards targeting the catalytic site. A major challenge in the field is to obtain compounds with high selectivity for AC toxins relative to mammalian membranous ACs (mACs). 3′-(N-methyl)anthraniloyl-2′-deoxyadenosine-5′-triphosphate is the most potent EF inhibitor known so far (Ki, 10 nM), but selectivity relative to mACs needs to be improved (currently ~5–50-fold, depending on the specific mAC isoform considered). AC toxin inhibitors can be identified in virtual screening studies based on available EF crystal structures and examined in cellular test systems or at the level of purified toxin using classic radioisotopic or non-radioactive fluorescence assays. Binding of certain MANT-nucleotides to AC toxins elicits large direct fluorescence- or fluorescence resonance energy transfer signals upon interaction with CaM, and these signals can be used to identify toxin inhibitors in competition binding studies. Collectively, potent EF inhibitors are available, but before they can be used clinically, selectivity against mACs must be improved. However, several methodological approaches, complementing each other, are now available to direct the development of potent, selective, orally applicable and clinically useful EF inhibitors. 相似文献
196.
《Seminars in diagnostic pathology》2017,34(1):15-21
Mycosis Fungoides (MF) and Sézary Syndrome (SS) are clonal proliferations of mature T-cells manifesting as lymphoproliferative disorders in which the neoplastic cells show a strong propensity for skin-homing. While the predominant site of presentation in MF is the skin, the peripheral blood carries a significant tumor burden in Sézary Syndrome such that it resembles a “leukemic” disease. While the genetic basis of these diseases has been studied using different approaches in the previous years, recent genome-wide studies employing massively parallel sequencing techniques now offer new insights into the molecular pathogenesis of these diseases. In this chapter, we discuss the recent findings elucidating the genomic landscape of MF and SS. The pathways targeted by mutational alterations are discussed and a model for understanding the pathogenesis of these diseases is proposed. It is anticipated that prognostic stratification and therapeutic targeting based on mutational signatures will be achieved in the near future based on the improved understanding of the molecular pathogenesis of these diseases. 相似文献
197.
PurposeTo evaluate the effects of electron-beam (E-beam) irradiation on the human cornea and the potential for E-beam sterilization of Boston keratoprosthesis (BK) devices when pre-assembled with a donor cornea prior to sterilization.MethodsHuman donor corneas and corneas pre-assembled in BK devices were immersed in recombinant human serum albumin (rHSA) media and E-beam irradiated at 25 kGy. Mechanical (tensile strength and modulus, and compression modulus), chemical, optical, structural, and degradation properties of the corneal tissue after irradiation and after 6 months of preservation were evaluated.ResultsThe mechanical evaluation showed that E-beam irradiation enhanced the tensile and compression moduli of human donor corneas, with no impact on their tensile strength. By chemical and mechanical analysis, E-beam irradiation caused a minor degree of crosslinking between collagen fibrils. No ultrastructural changes due to E-beam irradiation were observed. E-beam irradiation slightly increased the stability of the cornea against collagenase-induced degradation and had no impact on glucose diffusion. The optical evaluation showed transparency of the cornea was maintained. E-beam irradiated corneal tissues and BK-cornea pre-assembled devices were stable for 6 months after room-temperature preservation.ConclusionsE-beam irradiation generated no detrimental effects on the corneal tissues or BK-cornea pre-assembled devices and improved native properties of the corneal tissue, enabling prolonged preservation at room temperature. The pre-assembly of BK in a donor cornea, followed by E-beam irradiation, offers the potential for an off-the-shelf, ready to implant keratoprosthesis device. 相似文献
198.
To investigate the gradual failure of high-density polyethylene (HDPE) geomembrane as a result of long-term corrosion, four dynamic corrosion tests were conducted at different temperatures and durations. By combining tension and puncture tests, we systematically studied the variation law of tension and puncture properties of the HDPE geomembrane under different corrosion conditions. Results showed that tension and puncture failure of the HDPE geomembrane was progressive, and tensile strength in the longitudinal grain direction was evidently better than that in the transverse direction. Punctures appeared shortly after puncture force reached the puncture strength. The tensile strength of geomembrane was in inversely proportional to the corrosion time, and the impact of corrosion was more obvious in the longitudinal direction than transverse direction. As corrosion time increased, puncture strength decreased and corresponding deformation increased. As with corrosion time, the increase of corrosion temperature induced the decrease of geomembrane tensile strength. Tensile and puncture strength were extremely sensitive to temperature. Overall, residual strength had a negative correlation with corrosion time or temperature. Elongation variation increased initially and then decreased with the increase in temperature. However, it did not show significant law with corrosion time. The reduction in puncture strength and the increase in puncture deformation had positive correlations with corrosion time or temperature. The geomembrane softened under corrosion condition. The conclusion may be applicable to the proper designing of the HDPE geomembrane in landfill barrier system. 相似文献
199.
Thibaud Pintiaux David Viet Virginie Vandenbossche Luc Rigal Antoine Rouilly 《Materials》2013,6(6):2240-2261
Commercial α-cellulose was compression-molded to produce 1A dog-bone specimens under various operating conditions without any additive. The resulting agromaterials exhibited a smooth, plastic-like surface, and constituted a suitable target as replacement for plastic materials. Tensile and three-points bending tests were conducted according to ISO standards related to the evaluation of plastic materials. The specimens had strengths comparable to classical petroleum-based thermoplastics. They also exhibited high moduli, which is characteristic of brittle materials. A higher temperature and higher pressure rate produced specimens with higher mechanical properties while low moisture content produced weaker specimens. Generally, the strong specimen had higher specific gravity and lower moisture content. However, some parameters did not follow the general trend e.g., thinner specimen showed much higher Young’s Modulus, although their specific gravity and moisture content remained similar to control, revealing a marked skin-effect which was confirmed by SEM observations. 相似文献
200.
Carbon fiber (CF)-reinforced high-temperature thermoplastics such as poly(phenylene sulphide) (PPS) are widely used in structural composites for aerospace and automotive applications. The porosity of CF-reinforced polymers is a very important topic for practical applications since there is a direct correlation between void content and mechanical properties. In this study, inorganic fullerene-like tungsten disulphide (IF-WS2) lubricant nanoparticles were used to manufacture PPS/IF-WS2/CF laminates via melt-blending and hot-press processing, and the effect of IF-WS2 loading on the quality, thermal and mechanical behaviour of the hybrid composites was investigated. The addition of IF-WS2 improved fiber impregnation, resulting in lower degree of porosity and increased delamination resistance, compression and flexural properties; their reinforcement effect was greater at temperatures above the glass transition (Tg). IF-WS2 contents higher than 0.5 wt % increased Tg and the heat deflection temperature while reduced the coefficient of thermal expansion. The multiscale laminates exhibited higher ignition point and notably reduced peak heat release rate compared to PPS/CF. The coexistence of micro- and nano-scale fillers resulted in synergistic effects that enhanced the stiffness, strength, thermal conductivity and flame retardancy of the matrix. The results presented herein demonstrate that the IF-WS2 are very promising nanofillers to improve the thermomechanical properties of conventional thermoplastic/CF composites. 相似文献