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81.
Alexander L. Ruchelman Hon-Wah Man Weihong Zhang Roger Chen Lori Capone Jian Kang Anastasia Parton Laura Corral Peter H. Schafer Darius Babusis Mehran F. Moghaddam Yang Tang Michael A. Shirley George W. Muller 《Bioorganic & medicinal chemistry letters》2013,23(1):360-365
A series of analogs of the immunomodulary drugs lenalidomide (1) and pomalidomide (2), in which the amino group is replaced with various isosteres, was prepared and assayed for immunomodulatory activity and activity against cancer cell lines. The 4-methyl and 4-chloro analogs 4 and 15, respectively, displayed potent inhibition of tumor necrosis factor-α (TNF-α) in LPS-stimulated hPBMC, potent stimulation of IL-2 in a human T cell co-stimulation assay, and anti-proliferative activity against the Namalwa lymphoma cell line. Both of these analogs displayed oral bioavailability in rat. 相似文献
82.
Chuangxing Guo Angelica Linton Mehran Jalaie Susan Kephart Martha Ornelas Mason Pairish Samantha Greasley Paul Richardson Karen Maegley Michael Hickey John Li Xin Wu Xiaodong Ji Zhi Xie 《Bioorganic & medicinal chemistry letters》2013,23(11):3358-3363
The M2 isoform of pyruvate kinase is an emerging target for antitumor therapy. In this letter, we describe the discovery of 2-((1H-benzo[d]imidazol-1-yl)methyl)-4H-pyrido[1,2-a]pyrimidin-4-ones as potent and selective PKM2 activators which were found to have a novel binding mode. The original lead identified from high throughput screening was optimized into an efficient series via computer-aided structure-based drug design. Both a representative compound from this series and an activator described in the literature were used as molecular tools to probe the biological effects of PKM2 activation on cancer cells. Our results suggested that PKM2 activation alone is not sufficient to alter cancer cell metabolism. 相似文献
83.
Ghasemlou M Khodaiyan F Oromiehie A 《International journal of biological macromolecules》2011,49(4):814-821
The rheological properties of kefiran film-forming solutions, as well as the structural characterisation of the resulting films, were investigated as a function of various plasticizer types. The behaviours of the storage (G′) and loss (G″) moduli as a function of frequency were typical of gel-like material, with the G′ higher than the G″. Kefiran-based films, which may find application as edible films, were prepared by a casting and solvent-evaporation method. Possible interaction between the adjacent chains in the kefiran polymer and various plasticizers was proven by Fourier-transform infrared spectroscopy (FT-IR). The crystallinity of plasticized kefiran film was also analysed using X-ray diffraction (XRD); this revealed an amorphous-crystalline structure. These results were explained by the film's microstructure, which was analysed by atomic force microscopy (AFM) and scanning electron microscopy (SEM). The present study has helped determine possible interactions of kefiran, plasticizer and water molecules in determining film properties. 相似文献
84.
A two-phase and three-phase predictive fluidization model based on the characteristics of a system such as media type and size, flow rates, and reactor cross sectional area was proposed to calculate bed expansion, solid, liquid and gas hold up and specific surface area (SSA) of the biofilm particles. The model was subsequently linked to 1d AQUIFAS APP software (Aquaregen) to model biological nutrient removal in two phase (anoxic) and three phase (aerobic) fluidized bed bioreactors. The credibility of the proposed model for biological nutrient removal was investigated using the experimental data from a Twin Circulating Fluidized Bed Bioreactors (TCFBBR) treating synthetic and municipal wastewater.The SSA of bio-particles and volume of the expanded bed were simulated as a function of operational parameters. Two-sided t-tests demonstrated that simulated SCOD, NH4-N, NO3-N, TN, VSS and biomass yields agreed with the experimental values at the 95% confidence level. 相似文献
85.
Solouk A Cousins BG Mirzadeh H Solati-Hashtjin M Najarian S Seifalian AM 《Biotechnology and applied biochemistry》2011,58(3):147-161
In this study, central composite design (CCD) was used to develop predictive models to optimize operating conditions of plasma surface modification. It was concluded that out of the two process variables, power and duration of plasma exposure, the latter was significantly affecting the surface energy (γ(s) ), chemistry, and topography of polyhedral oligomeric silsesquioxane-poly(carbonate-urea)urethane (POSS-PCU) films. On the basis of experimental data, CCD was used to model the γ(s) using a quadratic modeling of the process variables to achieve optimum surface energy to improve the interaction between endothelial cells (ECs). It was found that optimal water θ for EC adhesion and retention, which was reported 55° from supporting literature (equivalent to γ(s) = 51 mN/m), was easily achievable using the following experimental conditions: (1) power output at 30 W for 75 Sec, (2) 90 W for 40 Sec, and (3) 90 W for 55 Sec in oxygen. In vitro cell culture and metabolic activity studies on optimized films [as in (1)] demonstrate increased adhesion, coverage, and growth of human umbilical vein endothelial cells that were confluent over a shorter time period (<24 H) than controls. Such materials enhanced the EC response and promoted endothelialization on optimized films, thus demonstrating their use as bypass graft materials. 相似文献
86.
Willcocks MM Locker N Gomwalk Z Royall E Bakhshesh M Belsham GJ Idamakanti N Burroughs KD Reddy PS Hallenbeck PL Roberts LO 《Journal of virology》2011,85(9):4452-4461
The RNA genome of Seneca Valley virus (SVV), a recently identified picornavirus, contains an internal ribosome entry site (IRES) element which has structural and functional similarity to that from classical swine fever virus (CSFV) and hepatitis C virus, members of the Flaviviridae. The SVV IRES has an absolute requirement for the presence of a short region of virus-coding sequence to allow it to function either in cells or in rabbit reticulocyte lysate. The IRES activity does not require the translation initiation factor eIF4A or intact eIF4G. The predicted secondary structure indicates that the SVV IRES is more closely related to the CSFV IRES, including the presence of a bipartite IIId domain. Mutagenesis of the SVV IRES, coupled to functional assays, support the core elements of the IRES structure model, but surprisingly, deletion of the conserved IIId(2) domain had no effect on IRES activity, including 40S and eIF3 binding. This is the first example of a picornavirus IRES that is most closely related to the CSFV IRES and suggests the possibility of multiple, independent recombination events between the genomes of the Picornaviridae and Flaviviridae to give rise to similar IRES elements. 相似文献
87.
Proteomics reveals new salt responsive proteins associated with rice plasma membrane 总被引:7,自引:0,他引:7
Nohzadeh Malakshah S Habibi Rezaei M Heidari M Salekdeh GH 《Bioscience, biotechnology, and biochemistry》2007,71(9):2144-2154
The signaling processes in plants that initiate cellular responses to biotic and abiotic factors are believed to be located in the plasma membrane (PM). A better understanding of the PM proteome response to environmental stresses might lead to new strategies for improving stress-tolerant crops. A sub-cellular proteomics approach was applied to monitor changes in abundance of PM-associated protein in response to salinity, a key abiotic stress affecting rice productivity worldwide. Proteome was extracted from a root plasma-membrane-rich fraction of a rice salt tolerant variety, IR651, grown under saline and normal conditions. Comparative two-dimensional electrophoresis revealed that 24 proteins were differentially expressed in response to salt stress. From these, eight proteins were identified by mass spectrometry analysis. Most of the proteins identified are likely to be PM-associated and are known to be involved in several important mechanisms of plant adaptation to salt stress. These include regulation of PM pumps and channels, membrane structure, oxidative stress defense, signal transduction, protein folding, and the methyl cycle. To investigate the correlation between mRNA and protein level in response to salinity, we performed quantitative Real-Time PCR analysis of three genes that were salt responsive at the protein level, including 1,4-Benzoquinone reductase, a putative remorin and a hypersensitive induced response protein. No concordance was detected between the changes in levels of gene and protein expression. Our results indicate that the proteomics approach is suitable for expression analysis of membrane associated proteins under salt stress. 相似文献
88.
89.
Shahin Aghamiri Ali Jafarpour Farshid Zandsalimi Mehran Aghemiri Mohsen Shoja 《Journal of cellular biochemistry》2019,120(9):15671-15677
The aim of this study was to assess the efficacy of resveratrol (Res) on radiosensitivity of 5-fluorouracil (5-FU) in the spheroid culture of MCF-7 breast cancer cell line using colony formation examination. Spheroids on day 9 with 300 µm diameters were treated with 20 µM resveratrol and/or 1 µM 5-FU for one volume doubling time (VDT) (42 hours) and then irradiated with 2 Gy gamma radiation (60Co) in various groups. Then the viability of the cells and clonogenic ability were acquired by blue dye exclusion and colony formation assay, respectively. The population doubling time in the monolayer culture and the VDT of spheroid culture was 22.48 0.23 hours and 42 0.63 hours respectively. None of the drugs and combination of them had any effect on the viability of cells. The combination treatment of 5-FU+Res+ radiation significantly reduced the colony formation ability of spheroid cells in comparison with each treatment alone. Our results indicated that resveratrol can significantly decrease colony number of breast cancer spheroid cells treated with 5-FU in combination with gamma-rays. Thus, resveratrol as a hypoxia-inducible factor-1-alpha inhibitor increased the radiosensitization of breast cancer spheroid cells. 相似文献
90.