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排序方式: 共有330条查询结果,搜索用时 750 毫秒
61.
Saad M. Alshahrani Abdullah S. Alshetaili Ahmed Alalaiwe Bader B. Alsulays Md. Khalid Anwer Ramadan Al-Shdefat Faisal Imam Faiyaz Shakeel 《AAPS PharmSciTech》2018,19(1):123-133
Sunitinib malate (SM) is reported as a weakly soluble drug in water due to its poor dissolution rate and oral bioavailability. Hence, in the current study, various “self-nanoemulsifying drug delivery systems (SNEDDS)” of SM were prepared, characterized and evaluated for the enhancement of its in vitro dissolution rate and anticancer efficacy. On the basis of solubilization potential of SM in various excipients, “Lauroglycol-90 (oil), Triton-X100 (surfactant) and Transcutol-P (cosurfactant)” were selected for the preparation of SM SNEDDS. SM-loaded SNEDDS were developed by spontaneous emulsification method, characterized and evaluated for “thermodynamic stability, self-nanoemulsification efficiency, droplet size, polydispersity index (PDI), zeta potential (ZP), surface morphology, refractive index (RI), the percent of transmittance (% T) and drug release profile.” In vitro dissolution rate of SM was significantly enhanced from an optimized SNEDDS in comparison with SM suspension. The optimized SNEDDS of SM with droplet size of 42.3 nm, PDI value of 0.174, ZP value of ?36.4 mV, RI value of 1.339, % T value of 97.3%, and drug release profile of 95.4% (after 24 h via dialysis membrane) was selected for in vitro anticancer efficacy in human colon cancer cells (HT-29) by MTT assay. MTT assay indicated significant anticancer efficacy of optimized SM SNEDDS against HT-29 cells in comparison with free SM. The results of this study showed the great potential of SNEDDS in the enhancement of in vitro dissolution rate and anticancer efficacy of poorly soluble drug such as SM. 相似文献
62.
In the present study laccase production potential of a photosynthetic, non nitrogen fixing cyanobacteria Arthrospira maxima (SAE-25780) was investigated for their probable use in synthetic dye decolorization which poses environmental pollution problem in aquatic bodies. A. maxima (SAE-25780) showed a constitutive production of laccase which increased up to 80% in the presence of inducer guaiacol. The optimal condition for laccase was 30 °C, 10 mM sucrose as a carbon source, 10 mM sodium nitrate as a nitrogen source, and 2 mM copper as metal activator. The partially purified laccase showed 84% and 49% decolorization potential for the two anthroquinonic dyes-Reactive Blue 4 and Remazol Brilliant Blue R, respectively (RBBR) within 96 h without any mediator. Therefore the laccase extracted from A. maxima (SAE-25780) can be used efficiently in bioremediation of synthetic dyes from paper, pulp and textile industries. 相似文献
63.
Ayesha A. Rasheed Kristina Hambley Gabriel Chan Carlos A. de la Rosa Brenda Larison Daniel T. Blumstein 《Ethology : formerly Zeitschrift fur Tierpsychologie》2018,124(3):155-160
Island populations may provide unique insights into the evolution and persistence of antipredator behavior. If antipredator behavior is costly and islands have reduced predation risk, then we expect the reduction or loss of antipredator behavior on islands. However, if even a single predator remains, the multipredator hypothesis predicts that antipredator behaviors will be conserved. We compared the flight initiation distances (FID) of California quail (Callipepla californica) on Santa Catalina Island (a location with reduced predation pressure) with quail on the mainland. We found no differences in FID between mainland and island quail. However, despite employing consistent testing methods, the starting distance from which quail were approached was significantly reduced for quail studied on the island when compared with quail studied on the mainland. Our results are consistent with the multipredator hypothesis because, while the island population had substantially fewer predators, some predators remained and some antipredator behavior persisted. 相似文献
64.
Olga Zakharova Olga Luzina Alexandra Zakharenko Dmitry Sokolov Alexandr Filimonov Nadezhda Dyrkheeva Arina Chepanova Ekaterina Ilina Anna Ilyina Kristina Klabenkova Boris Chelobanov Dmitry Stetsenko Ayesha Zafar Chatchakorn Eurtivong Jóhannes Reynisson Konstantin Volcho Nariman Salakhutdinov Olga Lavrik 《Bioorganic & medicinal chemistry》2018,26(15):4470-4480
Tyrosyl-DNA phosphodiesterase 1 (Tdp1) is a repair enzyme for stalled DNA-topoisomerase 1 (Top 1) cleavage complexes and other 3′-end DNA lesions. Tdp1 is a promising target for anticancer therapy, since it can repair DNA lesions caused by Top1 inhibitors leading to drug resistance. Hence, Tdp1 inhibition should result in synergistic effect with Top1 inhibitors. Twenty nine derivatives of (+)-usnic acid were tested for in vitro Tdp1 inhibitory activity using a fluorescent-based assay. Excellent activity was obtained, with derivative 6m demonstrating the lowest IC50 value of 25?nM. The established efficacy was verified using a gel-based assay, which gave close results to that of the fluorescent assay. In addition, molecular modeling in the Tdp1 substrate binding pocket suggested plausible binding modes for the active analogues. The synergistic effect of the Tdp1 inhibitors with topotecan, a Top1 poison in clinical use, was tested in two human cell lines, A-549 and HEK-293. Compounds 6k and 6x gave very promising results. In particular, 6x has a low cytotoxicity and an IC50 value of 63?nM, making it a valuable lead compound for the development of potent Tdp1 inhibitors for clinical use. 相似文献
65.
Neelam Sultan Irfan Ali Shazia Anwer Bukhari Shahid Mahmood Baig Muhammad Asif Muhammad Qasim Muhammad Imran Naseer Mahmood Rasool 《Genes & genomics.》2018,40(5):553-559
Retinitis pigmentosa (RP) is the most frequent genetically and clinically heterogeneous inherited retinal degeneration. To date, more than 80 genes have been identified that cause autosomal dominant, autosomal recessive and X linked RP. However, locus and allelic heterogeneity of RP has not been fully captured yet. This heterogeneity and lack of an accurate genotype phenotype correlation makes molecular dissection of the disease more difficult. The present study was designed to characterize the underlying pathogenic variants of RP in Pakistan. For this purpose, a large consanguineous family with RP phenotype showing autosomal recessive mode of inheritance was selected after a complete ophthalmological examination. Next generation sequencing was used for the identification of molecular determinant followed by Sanger-sequencing for confirmation. After sequence analysis a novel homozygous missense mutation, (c.602 C?>?T) in exon 4 of the RDH5 gene (MIM: 601617) was identified. This mutation resulted in substitution of phenyl alanine for serine at amino acid 201 (p.Ser201Phe) of the RDH5 gene. The same mutation was not detected in the 200 ethnically-matched control samples by Sanger sequencing. The identified mutant allele segregated in homozygous fashion in all the affected individuals of pedigree. Identification of this mutation reveals the allelic heterogeneity of RDH5 in patients with RP phenotype. The findings of this study demonstrate the clinical significance of next generation sequencing to understand the molecular basis of diseases and would help to reveal new proteins and their function in visual cycle will pave the way for early diagnosis, genetic counseling and better therapeutic inventions. 相似文献
66.
67.
A Anwer A A El-Aaser S Hassanein M Hassanein 《Acta biologica Academiae Scientiarum Hungaricae》1975,26(1-2):105-110
A lead method for demonstrating alkaline phosphatase is described. The method is based on direct precipitation of lead as lead phosphatase at pH 9.5, the pH optimum of the enzyme. Stable incubation medium was achieved by using tartrate, instead of maleate, as chelating for lead. The method was found to be suitable for visualization of alkaline phosphatase in different types of tissues. 相似文献
68.
Matthew Webb Fernanda Alves Ayesha Tulloch Justine Shaw Sally Bryant Dejan Stojanovic Ross Crates Robert Heinsohn 《Austral ecology》2019,44(3):523-533
Refuges for threatened species are important to prevent species extinction. They provide protection from a range of environmental and biotic stressors, and ideally provide protection against all threatening processes. However, for some species it may not be clear why some areas are refuges and others are not. The forty‐spotted pardalote (Pardalotus quadragintus) is an endangered, sedentary, cryptic and specialised bird endemic to the island of Tasmania, Australia. Having undergone an extreme range contraction over the past century the species is now mostly confined to a few small offshore island refuges. Key threatening processes to the species include habitat loss, wildfire, competition and predation. The ways in which these processes have molded the species’ contemporary range have not been clearly evaluated. Furthermore, the security of the remnant population within refuges is uncertain. To overcome this uncertainty we assessed key threats and established the population status in known refuges by developing a robust survey protocol within an occupancy modelling framework. We discuss our results in the context of planning trial reintroductions of this endangered species in suitable habitat across its former range. We found very high occupancy rates (0.75–0.96) at two refuges and in suitable conditions, the species was highly detectable (p, 0.43–0.77). At a third location our surveys indicated a local extinction, likely due to recent wildfire. We demonstrate that all refuges are at high risk of one or more threatening processes and the current distribution across island refuges is unlikely to secure the species from extinction. We identified large areas of potential habitat across the species’ former mainland range, but these are likely too distant from source populations for natural recolonisation. We propose that establishing new populations of forty‐spotted pardalotes via reintroduction is essential to secure the species and that this is best achieved while robust source populations still exist. 相似文献
69.
Diana Castaeda Mohanad Gabani Soo‐Kyoung Choi Quynh My Nguyen Cheng Chen Ayesha Mapara Adam Kassan Alexis A. Gonzalez Karima Ait‐Aissa Modar Kassan 《Obesity (Silver Spring, Md.)》2019,27(7):1050-1058
Over the past three decades, the increasing rates of obesity have led to an alarming obesity epidemic worldwide. Obesity is associated with an increased risk of cardiovascular diseases; thus, it is essential to define the molecular mechanisms by which obesity affects heart function. Individuals with obesity and overweight have shown changes in cardiac structure and function, leading to cardiomyopathy, hypertrophy, atrial fibrillation, and arrhythmia. Autophagy is a highly conserved recycling mechanism that delivers proteins and damaged organelles to lysosomes for degradation. In the hearts of patients and mouse models with obesity, this process is impaired. Furthermore, it has been shown that autophagy flux restoration in obesity models improves cardiac function. Therefore, autophagy may play an important role in mitigating the adverse effects of obesity on the heart. Throughout this review, we will discuss the benefits of autophagy on the heart in obesity and how regulating autophagy might be a therapeutic tool to reduce the risk of obesity‐associated cardiovascular diseases. 相似文献
70.
Neuropeptide Y (NPY) Y4 receptor (Y4R) in rat brainstem has been implicated in the signaling of satiety. In this study, we investigated the effects of leptin, and refeeding-induced satiety on Y4R mRNA expression in rat brainstem. Y4R receptor-specific primers were used to amplify the mRNA obtained from hypothalamus and brainstem utilizing conventional RT-PCR and quantitative real-time RT-PCR. No PCR product for Y4R was obtained from entire hypothalamic mRNA. Real-time RT-PCR showed a significant two-fold increase in the relative quantity of Y4R mRNA in brainstem of refed rats in comparison to food deprived or ad lib fed rats. Consistently, plasma leptin level was elevated in refed rats in comparison to food deprived rats. Similarly, leptin-treated rats exhibited a significant increase in Y4R mRNA in brainstem as compared to saline-injected rats. Plasma leptin was significantly elevated in leptin-treated rats. These results suggest that refeeding stimulates the expression of Y4R gene in the brainstem and that leptin may be one of the peripheral factors involved in this anorectic signaling mechanism. 相似文献