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Sarah Gilgunn Keefe Murphy Henning Stckmann Paul J. Conroy T. Brendan Murphy R. William Watson Richard J. OKennedy Pauline M. Rudd Radka Saldova 《International journal of molecular sciences》2020,21(23)
The diagnosis and treatment of prostate cancer (PCa) is a major health-care concern worldwide. This cancer can manifest itself in many distinct forms and the transition from clinically indolent PCa to the more invasive aggressive form remains poorly understood. It is now universally accepted that glycan expression patterns change with the cellular modifications that accompany the onset of tumorigenesis. The aim of this study was to investigate if differential glycosylation patterns could distinguish between indolent, significant, and aggressive PCa. Whole serum N-glycan profiling was carried out on 117 prostate cancer patients’ serum using our automated, high-throughput analysis platform for glycan-profiling which utilizes ultra-performance liquid chromatography (UPLC) to obtain high resolution separation of N-linked glycans released from the serum glycoproteins. We observed increases in hybrid, oligomannose, and biantennary digalactosylated monosialylated glycans (M5A1G1S1, M8, and A2G2S1), bisecting glycans (A2B, A2(6)BG1) and monoantennary glycans (A1), and decreases in triantennary trigalactosylated trisialylated glycans with and without core fucose (A3G3S3 and FA3G3S3) with PCa progression from indolent through significant and aggressive disease. These changes give us an insight into the disease pathogenesis and identify potential biomarkers for monitoring the PCa progression, however these need further confirmation studies. 相似文献
129.
Lissy Z. F. Gross Mariana Sacerdoti Prof. Albrecht Piiper Prof. Stefan Zeuzem Dr. Alejandro E. Leroux Dr. Ricardo M. Biondi 《ChemMedChem》2020,15(18):1682-1690
Angiotensin converting enzyme 2 (ACE2) is the human receptor that interacts with the spike protein of coronaviruses, including the one that produced the 2020 coronavirus pandemic (COVID-19). Thus, ACE2 is a potential target for drugs that disrupt the interaction of human cells with SARS-CoV-2 to abolish infection. There is also interest in drugs that inhibit or activate ACE2, that is, for cardiovascular disorders or colitis. Compounds binding at alternative sites could allosterically affect the interaction with the spike protein. Herein, we review biochemical, chemical biology, and structural information on ACE2, including the recent cryoEM structures of full-length ACE2. We conclude that ACE2 is very dynamic and that allosteric drugs could be developed to target ACE2. At the time of the 2020 pandemic, we suggest that available ACE2 inhibitors or activators in advanced development should be tested for their ability to allosterically displace the interaction between ACE2 and the spike protein. 相似文献
130.
N. P. Shapkin A. A. Kapustina N. V. Dombai V. V. Libanov I. G. Khalchenko S. V. Gardionov V. V. Gribova 《Polymer Bulletin》2020,77(3):1177-1190
Interaction of molybdenyl(VI) bis(acetylacetonate) with polyphenylsiloxane in xylene and under mechanochemical activation conditions has been investigated. The interaction in solution proceeds with splitting of the siloxane bond and formation of polymolybdenum(VI) phenylsiloxane with different silicon/metal ratios. The fractions with the silicon/metal ratio < 2 are characterized with high degree of crystallinity and low solubility, whereas those with the ratio > 2 are amorphous. The interaction of the above reagents under mechanical activation conditions proceeds with the formation of soluble polymers similar to those obtained in a solution with the silicon/molybdenum ratio equal to 2.6. The crystal chemistry parameters of the fraction obtained in solution with the ratio Si/Mo equals to 1:2 have been calculated on the basis of the X-ray diffraction analysis data using the Debye–Shearer equation. It has been demonstrated that the chain cross section found using the Miller–Boyer method coincides with that calculated geometrically on the basis of literature data on bond lengths and angles. It is shown that the interaction of molybdenyl(VI) bis(acetylacetonate) with polyphenylsiloxane takes place in solution more deeply than under the conditions of mechanochemical activation and is accompanied by the process of separation siloxanes connection. This leads to the formation of a fraction with smaller ratio of substances than the initial ratio. 相似文献