卵巢肿瘤的蛋白质组学诊治研究进展

卵巢肿瘤早期诊断是改善预后的最有效方法。目前以CA125结合超声为主的诊断模式，缺乏足够的敏感性和特异性。以二维凝胶电泳和质谱为代表的蛋白质组学技术的应用，发现了多种除CA125外的差异表达蛋白，为潜在的肿瘤标志物。蛋白质组学研究还揭示了卵巢肿瘤患者体内信号传导通路的改变和蛋白质分子的翻译后修饰，这些改变介导了瘤变或耐药过程，为药物治疗提供了新的靶标，亦为患者个体化治疗提供了可能。     

脑蛋白质组学研究进展

人类和多个物种的基因组全序列测定即将完成，生命科学研究逐渐从结构基因组学转向功能基因组学；在了解基因功能的同时，对基因表达产物——蛋白质的研究愈发重要。蛋白质是整个生命活动的基础，目前至少有40％-60％的基因编码蛋白质功能是未知的。这是因为每个蛋白质不是一个基因的直接产物，其表达具有动态性、时空性和可调节性，存在转录后的剪接和翻译后的修饰作用；相比之下，基因组是相对稳定的。随着分析仪器和生物信息学的发展和改进，蛋白质组学的研究日益成熟；它既能独立于基因组研究，又能与基因组研究相互完善和补充，而其表达图谱比基因组表达图谱更能真实地反映生物体的功能机制。随着分子生物学和其他相关学科的进步，脑科学取得了飞速发展，蛋白质组学技术为了解脑功能提供了前所未有的机会和研究方法，并在脑科学研究方面已经取得了令人鼓舞的成绩。     

细菌的蛋白质组学研究进展

随着“人类基因组计划”的完成，包括双向电泳和质谱技术的蛋白质组学逐渐成为了医学研究的中心，细菌作为医学研究的对象和工具，其蛋白质组的研究是对其基因组的补充，对人类蛋白质组的前瞻。研究主要集中在新蛋白的发现，蛋白质间的修饰，蛋白质组的比较和蛋白质间的相互作用等方面，为新抗生素靶位的发现，新替代疫苗的研制，致病机制及耐药机制的研究提供了依据。本文就细菌蛋白质组研究进展作一简要的概述。     

心血管疾病的蛋白质组学研究进展

蛋白质组学是作为继基因组学后提出的新学科，其以组织或细胞的全部蛋白质为研究对象，以蛋白质表达的整体水平为研究特点，为生命科学的研究提供了新视角。心血管疾病的研究是蛋白质组学研究的重要领域，并且取得了不少阶段性成果。现对蛋白质组学在心血管疾病领域，包括比较蛋白质组、功能蛋白质组的研究进展作一综述。     

金黄色葡萄球菌的蛋白质组学研究进展

金黄色葡萄球菌是一种重要的人类致病菌，致病机制非常复杂，涉及多种蛋白。借助蛋白质组学，能在蛋白质水平上全面了解金黄色葡萄球菌各种生理生化及致病过程。本文概述了涉及金黄色葡萄球菌应激、致病性、耐药、治疗等方面的蛋白质组学研究进展。     

蛋白质组学对于胰腺癌诊断的研究进展

胰腺癌缺乏早期特异性症状,恶性程度极高,早期就有局部侵犯和转移。手术切除是根治胰腺癌的唯一方法。胰腺癌的早期诊断已经成为实施有效治疗,提高根治性手术切除率以及延长术后生存率的关键所在,也就成为国内外研究的热点和难点。肿瘤的早期诊断是蛋白质组学在肿瘤研究中应用较多的一个领域。利用SELDI-TOF-MS技术和芯片能发现胰腺癌患者血清中的特征蛋白,对胰腺癌的早期诊断具有重要意义。本文就蛋白质组学对于胰腺癌的早期诊断的研究进展进行简要阐述。     

抗血小板人源化抗体的研究进展

血小板在出血和血栓性疾病中发挥着重要作用.抗血小板人源化抗体在治疗特发性血小板减少性紫癜和防止血栓性疾病方面有极大的临床应用价值.本文就血小板在出血和血栓性疾病中的作用,人源化抗体的发展现状和抗血小板人源化抗体在出血性及血栓性疾病中的应用作一综述.     

蛋白质组学在输血医学中的研究进展

<正>2003年随着人类基因组计划(human genome plan,HGP)的完成,宣告了"后基因组时代"的到来,生命科学的研究重点也从对基因结构的研究转向对基因组功能及其产物蛋白质组的研究。目前,蛋白质组学(proteomics)研究已成为21     

蛋白质组学在消化系统肿瘤中的研究进展

蛋白质组学相关理论和技术的完善,为肿瘤研究带来新的思维方式和研究领域,不仅可以从蛋白质整体水平这一全新角度来研究肿瘤的发病机理,而且能寻找用于肿瘤诊断和防治的生物标志物。现就蛋白质组学的基本概念、研究技术和消化系统肿瘤蛋白质组学研究进展作一综述。     

Abnormal platelet function in C3-deficient mice

Summary.  Background and Objectives:  The complement system is a biochemical cascade composed of several plasma proteins that can interact with endothelial cells and blood cells, including platelets. In order to investigate the effect of the complement system on platelets, we studied platelet function in C3-deficient mice that lack complement activity. Method and Results:  Tail-cut bleeding time was prolonged and platelet aggregation in response to protease-activated receptor-4 (PAR4) peptide was decreased in C3-deficient mice as compared with wild-type littermates. Platelet aggregation in response to other agonists (ADP and collagen) was similar between C3-deficient mice and their normal littermates. Isolated platelets from wild-type mice aggregate less in C3-deficient plasma than in normal plasma, and, conversely, addition of plasma from wild-type mice or plasma-purified C3 improved aggregation of C3-deficient platelets. We also monitored the formation of murine arteriole or venule thrombi in an intravital microscopy thrombosis model. We found that C3-deficient mice had a significantly delayed thrombotic response in arterioles as compared with their wild-type littermates. Furthermore, thrombi in C3-deficient mice were less stable and embolized more frequently than those in wild-type mice. Conclusions:  Platelets of C3-deficient mice have subnormal function, resulting in a prolonged tail-cut bleeding time and delayed thrombosis after vessel wall injury.     

Negative regulators of platelet activation and adhesion

Summary

Platelets are small anucleated cells that constantly patrol the cardiovascular system to preserve its integrity and prevent excessive blood loss where the vessel lining is breached. Their key challenge is to form a hemostatic plug under conditions of high shear forces. To do so, platelets have evolved a molecular machinery that enables them to sense trace amounts of signals at the site of damage and to rapidly shift from a non‐adhesive to a pro‐adhesive state. However, this highly efficient molecular machinery can also lead to unintended platelet activation and cause clinical complications such as thrombocytopenia and thrombosis. Thus, several checkpoints are in place to tightly control platelet activation and adhesiveness in space and time. In this review, we will discuss select negative regulators of platelet activation, which are critical to maintain patrolling platelets in a quiescent, non‐adhesive state and/or to limit platelet adhesion to sites of injury.

     

川崎病患儿血小板α-颗粒膜蛋白及血小板参数变化的观察与探讨

目的探讨川崎病(Kawasaki Disease,KD)患儿急性期血小板α-颗粒膜蛋白(CD62P)、血小板参数的动态变化与本病发病机制及冠状动脉并发症之间的关系.方法应用荧光标记单克隆抗体和流式细胞仪以及自动血球记数仪分别对30例KD急性期患儿血清CD62P及50例KD急性期患儿血小板参数进行了检测,并与20例健康体检儿童进行对照.结果 KD组急性期血浆CD62P表达明显高于对照组(P<0.01),血小板计数(PLT)、血小板压积(PCT)、血小板分布宽度(PDW)水平也明显高于对照组(P<0.01).结论 KD急性期患儿血浆CD62P呈高表达,PLT、PCT、PDW水平明显增高,提示急性期KD患儿体内血小板代谢旺盛,释放因子较多,活化程度显著增高,表现为高聚集、高黏附,高凝固及低血浓度的血液流变特点;而此期也正是临床KD患儿动脉血栓及冠状动脉瘤形成的高峰期,提示活化的血小板参与或促发了冠状动脉血栓的形成;因此动态检测CD62P、血小板参数的变化,及时采取有效抗炎抗凝措施,对于减轻KD患儿血管炎症,防止血栓形成,预防冠状动脉并发症的发生具有重要的临床意义.     

Dynamics of platelet thrombus formation

Summary.  Platelet aggregation and thrombus formation at sites of atherosclerotic plaque rupture is a dynamic process that can lead to intermittent or permanent obstruction to blood flow, resulting in ischemic tissue injury and organ dysfunction. There is a growing body of evidence suggesting that the dynamics of platelet aggregation and initial thrombus development are regulated by two distinct, complementary processes, involving: (i) rheological (biomechanical) and (ii) soluble-agonist -dependent mechanisms. Rheological-dependent platelet aggregation occurs between discoid platelets and requires the biomechanical adhesive and signaling function (mechanotransduction) of the major platelet adhesion receptors, GPIb and integrin α_IIbβ₃. Soluble agonists further potentiate platelet activation, stimulating global platelet shape change and degranulation, and play a major role in stabilizing formed aggregates. Unraveling the dynamics of platelet aggregation and thrombus formation in vivo requires consideration of the cooperative interplay between rheological- and soluble agonist-dependent platelet aggregation mechanisms.     

PDPN/CLEC-2活化血小板与疾病相关性的研究进展

血小板表面C型凝集素样受体2(C-type lectin-like receptor-2,CLEC-2)与其内源性配体平足蛋白(podoplanin,PDPN)相互作用后,诱导血小板活化,在促进血栓形成、协助肿瘤细胞转移、调节炎症反应、调节肺部发育、参与人早孕期母-胎界面的表达与调控等方面起重要作用。     

Variable effect of P2Y12 inhibition on platelet thrombus volume in flowing blood

Summary. Background and objectives: Patients treated with percutaneous coronary intervention receive aspirin and P2Y12 ADP receptor inhibitors to reduce thrombotic complications. The choice of methodology for monitoring the effects of treatment and assessing its efficacy is still a topic of debate. We evaluated how decreased P2Y12 function influences platelet aggregate (thrombus) size measured ex vivo. Methods and results: We used confocal videomicroscopy to measure in real time the volume of platelet thrombi forming upon blood perfusion over fibrillar collagen type I at a wall shear rate of 1500 s^?1. The average volume was significantly smaller in 31 patients receiving aspirin and clopidogrel (19) or ticlopidine (12) than in 21 controls, but individual values were above the lower limit of the normal distribution, albeit mostly within the lower quartile, in 61.3% of cases. Disaggregation of platelet thrombi at later perfusion times occurred frequently in the patients. Vasodilator‐stimulated phosphoprotein phosphorylation, reflecting P2Y12 inhibition, was also decreased in the patient group, and only 22.6% of individual values were above the lower normal limit. We found no correlation between volume of thrombus formed on collagen fibrils and level of P2Y12 inhibition, suggesting that additional and individually variable factors can influence the inhibitory effect of treatment on platelet function. Conclusions: Measurements of platelet thrombus formation in flowing blood reflects the consequences of antiplatelet therapy in a manner that is not proportional to P2Y12 inhibition. Combining the results of the two assays may improve the assessment of thrombotic risk.     

Orbofiban: an orally active GPIIb/IIIa platelet receptor antagonist

A key role has been established for platelet activation and thrombus formation in the pathogenesis of acute coronary syndromes, and restenosis after percutaneous interventions. Antiplatelet agents that have a wider spectrum of activity than aspirin, and clopidogrel would be expected to provide improved antithrombotic protection. Preclinical studies were used to predict clinical efficacy of orally active GPIIb/IIIa antagonists such as xemilofiban, sibrafiban, lefradafiban, and orbofiban. While clinical trials have shown potent and sustained platelet inhibition, outcomes of trials with these first generation GPIIb/IIIa compounds have been disappointing. The active moiety of orbofiban is a potent and specific inhibitor of fibrinogen binding to GPIIb/IIIa, leading to inhibition of platelet aggregation to a wide variety of agonists. Studies comparing inhibition of aggregation and bleeding suggest that chronic inhibition of platelet aggregation can be achieved without major bleeding side effects. Thrombus formation is prevented in canine models of thrombosis. Orbofiban is approximately 28% bioavailable with a t(1/2) of 18 hr. The high bioavailability, long half-life, and potential safety suggest orbofiban would be suitable for chronic oral administration. Clinical data demonstrate that orally administered orbofiban has the desired pharmacodynamic effect of inhibiting platelet aggregation but does not demonstrate clinical benefit when examined in large-scale trials.     

Vitronectin stabilizes thrombi and vessel occlusion but plays a dual role in platelet aggregation.

The role of vitronectin (Vn) in thrombosis is currently controversial; both inhibitory and supportive roles have been reported. To monitor directly the function of Vn in thrombotic events at the site of vascular injury, we studied Vn-deficient (Vn-/-) and wild-type (WT) control mice with two real-time intravital microscopy thrombosis models. In the mesenteric arteriole model, vessel injury was induced by ferric chloride. We observed unstable thrombi and a significantly greater number of emboli in Vn-/- mice. Vessel occlusion was also delayed and frequent vessel re-opening occurred. In the cremaster muscle arteriole model, vessel injury was induced by a nitrogen dye laser. We observed significantly fewer platelets, lower fibrin content, and unstable fibrin within the thrombi of Vn-/- mice. To define further the role of Vn in thrombus growth, we studied platelet aggregation in vitro. Consistent with our in vivo data, the second wave of thrombin-induced aggregation of gel-filtered platelets was abolished at a low concentration of thrombin in Vn-/- platelets. Interestingly, adenosine diphosphate (ADP)-induced platelet aggregation was significantly increased in Vn-/- platelet-rich plasma (PRP) and this effect was attenuated by adding purified plasma Vn. We also observed increased platelet aggregation induced by shear stress in Vn-/- whole blood. These data demonstrate that Vn is a thrombus stabilizer. However, in contrast to released platelet granule Vn which enhances platelet aggregation, plasma Vn inhibits platelet aggregation.     

血小板抗体检测及配型对血小板输注无效的临床意义

目的 通过对比血小板配型前后血小板的输注效果,评估血小板抗体检测及配型对血小板输注无效的临床意义.方法 以出血症状改善情况、血小板计数增高指数(CCI)、血小板恢复百分率(PPR)为标准,对比配型前后血小板的输注效果.结果 25例血小板输注无效患者的血小板抗体筛查阳性9例; 9例血小板抗体阳性患者血小板交叉配型前后血小板输注有效率差异有统计学意义(P<0.01),配型后输注的 1 h和24 h CCI、PPR数值明显高于配型前输注的.结论 血小板抗体检测及血小板配型输注可以为患者选择适用的血小板,提高单采血小板的输注有效率,避免滥用血小板.