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21.
Boys ML Schretzman LA Chandrakumar NS Tollefson MB Mohler SB Downs VL Penning TD Russell MA Wendt JA Chen BB Stenmark HG Wu H Spangler DP Clare M Desai BN Khanna IK Nguyen MN Duffin T Engleman VW Finn MB Freeman SK Hanneke ML Keene JL Klover JA Nickols GA Nickols MA Steininger CN Westlin M Westlin W Yu YX Wang Y Dalton CR Norring SA 《Bioorganic & medicinal chemistry letters》2006,16(4):839-844
We describe a series of 1,2,4-oxadiazoles, which are potent antagonists of the integrin alpha(v)beta3 and, in addition, show selectivity relative to the other beta3 integrin alpha(IIb)beta3. In whole cells, the majority of these analogs also demonstrated modest selectivity against other alpha(v) integrins such as alpha(v)beta1 and alpha(v)beta6. 相似文献
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Mijia Lu Yuexiu Zhang Piyush Dravid Anzhong Li Cong Zeng Mahesh KC Sheetal Trivedi Himanshu Sharma Supranee Chaiwatpongsakorn Ashley Zani Adam Kenney Chuanxi Cai Chengjin Ye Xueya Liang Jianming Qiu Luis Martinez-Sobrido Jacob S. Yount Prosper N. Boyaka Shan-Lu Liu Mark E. Peeples Amit Kapoor Jianrong Li 《Journal of virology》2021,95(20)
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We report a high-sensitivity cell secretome detection method using competitive immuno-aggregation and a micro-Coulter counter. A target cell secretome protein competes with anti-biotin-coated microparticles (MPs) to bind with a biotinylated antibody (Ab), causing decreased aggregation of the functionalized MPs and formation of a mixture of MPs and aggregates. In comparison, without the target cell secretome protein, more microparticles are functionalized, and more aggregates are formed. Thus, a decrease in the average volume of functionalized microparticles/aggregates indicates an increase in cell secretome concentration. This volume change is measured by the micro-Coulter counter, which is used to quantitatively estimate the cell secretome concentration. Vascular endothelial growth factor (VEGF), one of the key cell secretome proteins that regulate angiogenesis and vascular permeabilization, was used as the target protein to demonstrate the sensing principle. A standard calibration curve was generated by testing samples with various VEGF concentrations. A detection range from 0.01 ng/mL to 100.00 ng/mL was achieved. We further demonstrated the quantification of VEGF concentration in exogenous samples collected from the secretome of human mesenchymal stem cells (hMSCs) at different incubation times. The results from the assay agree well with the results of a parallel enzyme-linked immunoabsorbent assay (ELISA) test, indicating the specificity and reliability of the competitive immuno-aggregation assay. With its simple structure and easy sample preparation, this assay not only enables high sensitivity detection of VEGF but also can be readily extended to other types of cell secretome analysis as long as the specific Ab is known. 相似文献
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Breathing increases abruptly at the start of passive exercise, stimulated by afferent feedback from the moving limbs, and declines toward a steady-state hyperpnea as exercise continues. This decline has been attributed to decreased arterial CO2 levels and adaptation in afferent feedback; however, the relative importance of these two mechanisms is unknown. To address this issue, we compared ventilatory responses to 5 min of passive leg extension exercise performed on 10 awake human subjects (6 men and 4 women) in isocapnic and poikilocapnic conditions. End-tidal Pco2 decreased significantly during poikilocapnic (Delta = -1.5 +/- 0.5 Torr, P < 0.001), but not isocapnic, passive exercise. Despite this difference, the ventilatory responses to passive exercise were not different between the two conditions. Using the fast changes in ventilation at the start (5.46 +/- 0.40 l/min, P < 0.001) and end (3.72 +/- 0.33 l/min, P < 0.001) of passive exercise as measures of the drive to breathe from afferent feedback, we found a decline of 68%. We conclude that the decline in ventilation during passive exercise is due to an adaptation in the afferent feedback from the moving limbs, not a decline in CO2 levels. 相似文献
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Phillipson E. A.; Bowes G.; Townsend E. R.; Duffin J.; Cooper J. D. 《Journal of applied physiology》1981,51(6):1398-1403
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Buehrer BM Duffin DJ Lea-Currie YR Ribnicky D Raskin I Stephens JM Cefalu WT Gimble JM 《The Journal of nutritional biochemistry》2012,23(6):519-525
Plant extracts continue to represent an untapped source of renewable therapeutic compounds for the treatment and prevention of illnesses including chronic metabolic disorders. With the increase in worldwide obesity and its related morbidities, the need for identifying safe and effective treatments is also rising. As such, use of primary human adipose-derived stem cells represents a physiologically relevant cell system to screen for bioactive agents in the prevention and treatment of obesity and its related complications. By using these cells in a primary screen, the risk and cost of identifying artifacts due to interspecies variation and immortalized cell lines is eliminated. We demonstrate that these cells can be formatted into 384-well high throughput screens to rapidly identify botanical extracts that affect lipogenesis and lipolysis. Additionally, counterscreening with human primary stem cells from distinct adipose depots can be routinely performed to identify tissue specific responses. In our study, over 500 botanical extracts were screened and 16 (2.7%) were found to affect lipogenesis and 4 (0.7%) affected lipolysis. 相似文献