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51.
Abdallah E. Abdallah Reda R. Mabrouk Maged Mohammed Saleh Al Ward Sally I. Eissa Eslam B. Elkaeed Ahmed B. M. Mehany Mariam A. Abo-Saif Ola A. El-Feky Mohamed S. Alesawy Mohamed Ayman El-Zahabi 《Journal of enzyme inhibition and medicinal chemistry》2022,37(1):573
Based on quinazoline, quinoxaline, and nitrobenzene scaffolds and on pharmacophoric features of VEGFR-2 inhibitors, 17 novel compounds were designed and synthesised. VEGFR-2 IC50 values ranged from 60.00 to 123.85 nM for the new derivatives compared to 54.00 nM for sorafenib. Compounds 15a, 15b, and 15d showed IC50 from 17.39 to 47.10 µM against human cancer cell lines; hepatocellular carcinoma (HepG2), prostate cancer (PC3), and breast cancer (MCF-7). Meanwhile, the first in terms of VEGFR-2 inhibition was compound 15d which came second with regard to antitumor assay with IC50 = 24.10, 40.90, and 33.40 µM against aforementioned cell lines, respectively. Furthermore, Compound 15d increased apoptosis rate of HepG2 from 1.20 to 12.46% as it significantly increased levels of Caspase-3, BAX, and P53 from 49.6274, 40.62, and 42.84 to 561.427, 395.04, and 415.027 pg/mL, respectively. Moreover, 15d showed IC50 of 253 and 381 nM against HER2 and FGFR, respectively. 相似文献
52.
Antiviral susceptibility testing of cytomegalovirus: criteria for detecting resistance to antivirals
Testing cytomegaloviruses for antiviral susceptibility is increasing especially since the reports of 'resistance' to ganciclovir and foscarnet (Erice et al., 1989; Knox et al., 1991). There is however no standardized method for susceptibility testing nor are there criteria for designating an isolate as sensitive or resistant. In a previous paper we utilized a plaque reduction assay and suggested that a resistant strain be defined as one requiring > 12 microM ganciclovir for inhibition of 50% of viral plaques. (Drew et al., 1991) This concentration was chosen because it was at least four-fold greater than the mean concentration required to inhibit pretherapy isolates. In this paper we present the results of testing a large number of isolates prior to and during therapy with either ganciclovir or foscarnet. By analyzing the results of these assays we propose revised criteria for susceptibility of cytomegalovirus = 5 microM for ganciclovir and <400 microM for foscarnet. 相似文献
53.
R.N. Haddadin S.A. Saleh R.A. Mahmoud A.A. Shehabi 《Letters in applied microbiology》2010,51(1):48-53
Aims: To investigate the presence of a relationship between the strength of attachment of Pseudomonas aeruginosa to stainless steel surfaces and their observed multiple drug resistance. Methods and Results: Multiple drug resistance of clinical and environmental isolates of Ps. aeruginosa was evaluated using disc diffusion method. The blot succession technique was used to quantify the strength of attachment of Ps. aeruginosa isolates. Different multiple drug–resistant Ps. aeruginosa isolates exhibited variable attachment strength. Although the highest multiple drug–resistant clinical isolate was shown to have the least attachment strength among clinical isolates, a weak correlation was found between attachment strength and multiple resistance among our investigated Ps. aeruginosa isolates. Conclusions: There is a weak correlation between multiple drug resistance and strength of attachment to stainless steel surfaces. Significance and Impact of the Study: Even low‐resistant Ps. aeruginosa could have the potential of attaching firmly to surfaces and forming biofilm. 相似文献
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55.
Anti-inflammatory effects of the products from Wilbrandia ebracteata on carrageenan-induced pleurisy in mice. 总被引:2,自引:0,他引:2
R R Peters T F Saleh M Lora C Patry A J de Brum-Fernandes M R Farias R M Ribeiro-do-Valle 《Life sciences》1999,64(26):2429-2437
Wilbrandia ebracteata Cogn. (Cucurbitaceae) is commonly known in Brazil as "Taiuia". The roots are employed in folk medicine for the treatment of several diseases, such as rheumatic disease. This study has evaluated the anti-inflammatory action of dicloromethane fraction (F-DCM), purified fraction (PFIII) and Cucurbitacin B extracted from crude extract of W. ebracteata in experimental models in vivo. The F-DCM (0.3 to 10 mg.kg(-1), i.p. or 3 to 30 mg.kg(-1) p.o.) produced significant but not dose-dependent inhibition of the carrageenan-induced cell influx and exsudate leakage in the pleural cavity of mice. The F-DCM 0.01 to 10 mg.kg(-1), i.p. or 0.1 to 10 mg.kg(-1) p.o.) decreased the levels of PGE2 in the exsudate leakage induced by carrageenan in the pleural cavity after 4 h with a calculated ID50 of 0.01 (0.002-0.09, i.p.) and 0.29 (0.05-1.45, p.o.) mg.kg(-1). The PFIII (3 mg.kg(-1), i.p.) inhibited 80% of cell migration (1.50 +/- 0.09 x 10(6) cells/cavity) and exsudate leakage by about 50% (3.09 +/- 0.71 microg/ml) in relation to the control group. Cucurbitacin B (0.1 mg.kg(-1), i.p.), the main compound of PFIII, reduced significantly the levels of PGE2 in the exsudate leakage by 40.7% (10.41 +/- 2.67 ng.ml(-1)). These data show that the active principle(s) present in the F-DCM of W. ebracteata elicited pronounced anti-inflammatory effects when assessed by i.p. or p.o. routes, as well as PFIII. The F-DCM was also able to prevent PGE2 formation in exsudate leakage induced by carrageenan, as well as Cucurbitacin B, its active principle. These results indicate that the anti-inflammatory activity of Wilbrandia ebracteata can be related with the inhibition of the production of PGE2. 相似文献
56.
BACKGROUND: Myelolipoma is a benign tumor composed of mature adipose tissue and hematopoietic cells. Although they are commonly found in adrenal glands, extraadrenal myelolipomas (EMLs) are rare but well documented. They have been found in various sites, including mediastinum, liver, stomach, lungs, pelvis, spleen, retroperitoneum, presacral region and mesentery. EMLs must be distinguished from extramedullary hematopoieses, which are also composed of hematopoietic elements but may lack adipose tissue and are associated with anemia and marked bone marrow hyperplasia. CASE: We describe a case of a pleura-based, extraadrenal myelolipoma in a 53-year-old female with unremarkable bone marrow findings that were initially encountered on fluoroscopy-guided fine needle aspiration (FNA). One year later the mass was removed via open thoracotomy. It showed typical EML features histologically. CONCLUSION: EML manifests on aspiration cytology as a cellular specimen with numerous trilineage hematopoietic cells and a variable proportion of mature adipose cells. To our knowledge, FNA cytology of EML has not been found in this location before. Aspiration biopsy offers a simple and reliable method for the diagnosis of EML in the presence of appropriate clinical settings. 相似文献
57.
58.
Enzymes, especially proteases, have become an important and indispensable part of the processes used by the modern food and feed industry to produce a large and diversified range of products for human and animal consumption. A cysteine protease, used extensively in the food industry, was purified from germinated wheat Triticum aestivum (cv. Giza 164) grains through a simple reproducible method consisting of extraction, ion exchange chromatography and gel filtration. The molecular weight of the enzyme was estimated to be 61000+/-1200-62000+/-1500 by SDS-PAGE and gel filtration. The cysteine protease had an isoelectric point and pH optimum at 4.4 and 4.0, respectively. The enzyme exhibited more activity toward azocasein than the other examined substrates with K(m) 2.8+/-0.15 mg azocasein/ml. In addition, it had a temperature optimum of 50 degrees C and based on a heat stability study 55% of its initial activity remained after preincubation of the enzyme at 50 degrees C for 30 min prior to substrate addition. All the examined metal cations inhibited the enzyme except Co(2+), Mg(2+), Mn(2+) and Li(+). The proteolytic activity of the enzyme was inhibited by thiol-specific inhibitors, whereas iodoacetate and p-hydroxymercuribenzoate caused a competitive inhibition with Ki values 6+/-0.3 mM and 21+/-1.2 microM, respectively. Soybean trypsin inhibitor had no effect on the enzyme. The enzyme activity remained almost constant for 150 days of storage at -20 degrees C. The properties of this enzyme, temperature and pH optima, substrate specificity, stability and sensitivity to inhibitors or activators, meet the prerequisites needed for food industries. 相似文献
59.
Möller S Koczan D Serrano-Fernandez P Zettl UK Thiesen HJ Ibrahim SM 《In silico biology》2004,4(4):417-427
Common complex polygenic diseases as autoimmune diseases have not been completely understood on a molecular level. While many genes are known to be involved in the pathways responsible for the phenotype, explicit causes for the susceptibility of the disease remain to be elucidated. The susceptibility to disease is thought to be the result of genetic epistatic interactions between common polymorphic genes. This polymorphism is mostly caused by single nucleotide polymorphisms (SNPs). Human subpopulations are known to differ in the susceptibility to the diseases and generally in the distribution of single nucleotide polymorphisms. The here presented approach retrieves SNPs with the most divergent frequencies for selected human subpopulations to help defining properties for the experimental verification of SNPs within defined regions. A web-accessible program implementing this approach was evaluated for multiple sclerosis (MS), a common human polygenic disease. A link to a summary of data from "The SNP Consortium" (TSC) with sex-dependencies of SNPs is available. Associations of SNPs to genes, genetic markers and chromosomal loci are retrieved from the Ensembl project. This tool is recommended to be used in conjunction with microarray analyses or marker association studies that link genes or chromosomal loci to particular diseases. 相似文献
60.
Rheumatoid arthritis (RA) is a common human disease with a prevalence of about 1% in most parts of the world. At the time
of symptom onset it is difficult to predict the severity of subsequent disease course. After 2 years joint erosions are seen
in most patients, and most patients become clinically disabled within 20 years. A recent meeting at the Kennedy Institute
of Rheumatology (Imperial College, London) brought together representatives from several European centres of excellence, to
discuss research funded by the EU Framework 5 Quality of Life Programme. This research network combines gene and protein expression
profiling with different animal models of RA to identify cells, genes and pathways contributing to arthritis initiation, progression
and chronicity. The studies discussed highlight the reality that collaboration between different research groups is the basis
of groundbreaking research and, it is hoped, eventual new therapies for RA. 相似文献