Modulation of protein biophysical properties by chemical glycosylation: biochemical insights and biomedical implications

Glycosylation constitutes one of the most important posttranslational modifications employed by biological systems to modulate protein biophysical properties. Due to the direct biochemical and biomedical implications of achieving control over protein stability and function by chemical means, there has been great interest in recent years towards the development of chemical strategies for protein glycosylation. Since current knowledge about glycoprotein biophysics has been mainly derived from the study of naturally glycosylated proteins, chemical glycosylation provides novel insights into its mechanistic understanding by affording control over glycosylation parameters. This review presents a survey of the effects that natural and chemical glycosylation have on the fundamental biophysical properties of proteins (structure, dynamics, stability, and function). This is complemented by a mechanistic discussion of how glycans achieve such effects and discussion of the implications of employing chemical glycosylation as a tool to exert control over protein biophysical properties within biochemical and biomedical applications. Received 15 December 2006; received after revision 28 March 2007; accepted 25 April 2007     

Biological and Potential Therapeutic Roles of Sirtuin Deacetylases

Sirtuins comprise a unique class of nicotinamide adenine dinucleotide (NAD⁺)-dependent deacetylases that target multiple protein substrates to execute diverse biological functions. These enzymes are key regulators of clinically important cellular and organismal processes, including metabolism, cell division and aging. The desire to understand the important determinants of human health and lifespan has resulted in a firestorm of work on the seven mammalian sirtuins in less than a decade. The implication of sirtuins in medically important areas such as diabetes, cancer, cardiovascular dysfunction and neurodegenerative disease has further catapulted them to a prominent status as potential targets for nutritional and therapeutic development. Here, we present a review of published results on sirtuin biology and its relevance to human disease. Received 25 June 2008; received after revision 20 August 2008; accepted 29 August 2008     

Integrin antagonists

Integrins are a family of cell surface glycoproteins that mediate numerous cell-cell and cell-matrix interactions and are involved in biological processes such as tissue morphogenesis, leukocyte recirculation and migration, wound healing, blood clotting and immune response. Aberrant cell adhesion has been implicated in the pathogenesis of several diseases, including a number of inflammatory disorders such as rheumatoid arthritis, inflammatory bowel disease and asthma, as well as cancer and coronary heart disease. As such integrins are seen as excellent targets for the development of therapeutic agents. This report begins with an examination of the structure of integrin molecules and their ligands and then goes on to review the current state of development of antiintegrin antagonists. Received 13 April 1999; received after revision 28 May 1999; accepted 28 May 1999     

Protein N-terminal methionine excision

N-terminal methionine excision (NME) is the major proteolytic pathway responsible for the diversity of N-terminal amino acids in proteins. Dedicated NME components have been identified in all organisms, in all compartments in which protein synthesis occurs: cytoplasm, plastids and mitochondria. Recent studies have revealed that NME is regulated at various levels and plays an important role in controlling protein turnover. NME is essential in Eubacteria and lower eukaryotes and is the target of many natural and synthetic inhibitors. Such inhibitors have considerable potential for use in the treatment of various human diseases, from cancer to bacterial and parasitic infections.Received 19 December 2003; received after revision 21 January 2004; accepted 4 February 2004     

TACE治疗对肝纤维化4项及肿瘤坏死因子-α影响的研究

探讨PHC经多次TACE术后肝纤维化的变化趋势及临床意义.选取30例PHC初诊病人进行3次TACE治疗,间隔6周,测定术前与术后血清中HA(透明质酸)、HPC-Ⅲ(人三型前胶原)I、V-C(四型前胶原)、LN(层粘蛋白)及TNF-α(肿瘤坏死因子-α)的含量.测量结果经统计学检验发现PHC病人在TACE治疗后HA、HPC-Ⅲ、IV-C、LN、TNF-α较术前明显升高,尤其在第3次TACE术后,可见上述指标含量升高明显(P0.01).4项肝纤维化指标中,以HA升高显著.重复进行TACE治疗PHC将加重肝纤维化,也使TNF-α含量增加,促使及加重肝纤维化的发生.提出在TACE治疗时应严格掌握适应症及提高操作水平,术后加强保肝及抗肝纤维化治疗.     

经单鼻孔蝶窦入路显微手术治疗垂体腺瘤

目的：总结我院采用经单鼻孔蝶窦入路显微手术治疗垂体腺瘤的疗效,讨论垂体腺瘤的手术治疗及并发症。方法：对2010年1月至2011年10月我科收住的垂体腺瘤病人及相关文献资料进行分析。结果：8例病人恢复良好,头痛缓解,视力恢复,溢乳消失。结论：经单鼻孔蝶窦入路显微手术治疗垂体腺瘤安全可靠,疗效好,出血较少,脑组织损伤最小,手术时间短,并发症少,反应轻,恢复快。     

Heparan sulfate-protein interactions: therapeutic potential through structure-function insights

Heparin and the related glycosaminoglycan, heparan sulfate, bind a myriad of proteins. The structural diversity of heparin and heparan sulfates is enormous, but differences in the conformational flexibility of the monosaccharide constituents add extra complexity and may influence protein binding. Silencing genes for heparin/ heparan sulfate biosynthetic enzymes profoundly affects mammalian development. Thus, altering the structure of heparan sulfate chains can alter protein binding and embryo development. Different heparan sulfate structures are located in particular tissue sites, and these structures are recognised by different sets of proteins. Regulation of certain heparan sulfate-protein interactions by pH or cations is described. Heparin/heparan sulfate structures are viewed as potential therapeutics for a variety of diseases. An understanding at the molecular and functional levels of the specificity and affinity of heparan sulfate-protein interactions is crucial for designing heparin-inspired drugs. How the development of synthesis techniques is facilitating structure-function analyses and drug development is discussed.Received 6 July 2004; received after revision 16 September 2004; accepted 28 September 2004     

空管糊剂与干髓剂治疗乳磨牙牙髓炎和根尖周围炎的临床观察

采用空管糊剂与干髓剂对394颗乳磨牙牙髓炎和根尖周炎进行治疗观察,并经过半年至2年的随访.结果表明:空管糊剂疗法治疗乳磨牙牙髓炎和根尖周炎,有效率为97.12%,干髓剂治疗有效率为86.42%.经统计学处理两组疗效有显著性差异,P<0.05.