骨桥蛋白与肝脏发育、肝再生及肝脏疾病

骨桥蛋白(osteopontin,OPN)是一种分泌型磷酸化糖蛋白,结构上与多种胞外基质蛋白相似,功能上具有细胞因子的特点,在多种生理、病理过程中发挥重要作用。在肝中,它可能参与肝脏发育和肝再生,并与急性肝炎、脂肪性肝炎、肝纤维化及肝癌等疾病的发生、发展密切相关。本文综述了OPN在肝脏发育、肝再生和肝脏疾病等中的作用研究进展,为开展OPN在促进肝再生及肝脏疾病诊断、治疗方面的应用提供重要理论基础。     

骨桥蛋白表达和翻译后修饰与肿瘤生物学行为的关系

骨桥蛋白(osteopontin,OPN)是一种分泌型磷酸化糖蛋白。研究表明OPN在肿瘤中高表达,并通过与CD44突变体CD44v6及整联蛋白αvβ3作用参与肿瘤的发生发展。近年来发现OPN存在磷酸化、糖基化、硫酸化、唾液酸化等多种翻译后修饰,在肿瘤发生发展过程中,这些修饰状态的改变和生物学意义已成为研究关注的热点之一。     

骨桥蛋白在高血压及其靶器官损害中的研究进展

高血压是以动脉压升高为特征的一种常见的慢性病,可伴有心脏、血管、脑和肾脏等器官功能性或器质性改变的全身性疾病。骨桥蛋白(osteopontin,OPN)是一种具有趋化作用的分泌性糖基化磷蛋白。大量实验研究证明,OPN在骨形成、免疫调节、炎症、肿瘤转移等方面起重要作用。最新的研究发现OPN参与了高血压及其靶器官损害的发生发展。本文对近年来OPN在高血压及高血压动脉粥样硬化、高血压心脏病、高血压肾病、高血压脑血管病等靶器官损害中研究作一综述。     

骨桥蛋白与肿瘤治疗

骨桥蛋白(osteopontin,OPN)是一种分泌型磷酸化糖蛋白,由多种组织细胞合成与分泌,参与调节细胞的黏附、增殖、趋化、转移、浸润和凋亡过程。OPN在多种肿瘤中高表达,与肿瘤的发生和发展密切相关,组织和血液中的OPN表达量也是肿瘤诊断和预后的指标。近年来,越来越多的研究通过抑制OPN、OPN的受体以及OPN的下游信号通路的方法抑制了肿瘤的发展。本文将从多方面阐述OPN与肿瘤的关系以及与肿瘤治疗的研究进展。     

骨桥蛋白与糖尿病肾病关系的研究进展

骨桥蛋白(OPN)是一种具有细胞粘附和迁移功能的分泌型磷酸化糖蛋白。在肾脏中有广泛分布,研究发现其参与糖尿病肾病(DN)蛋白尿形成、DN的炎症反应及肾脏纤维化过程,抑制OPN可改善糖尿病肾脏病变。     

骨桥蛋白与糖尿病肾病关系的研究进展

骨桥蛋白（OPN）是一种具有细胞粘附和迁移功能的分泌型磷酸化糖蛋白。在肾脏中有广泛分布,研究发现其参与糖尿病肾病（DN）蛋白尿形成、DN的炎症反应及肾脏纤维化过程,抑制OPN可改善糖尿病肾脏病变。     

骨桥蛋白对细胞生存的多重作用

骨桥蛋白(osteopontin, OPN)作为一种分泌性蛋白质广泛存在于多种组织细胞中,不仅调控肿瘤细胞的转移、侵袭和增殖,也在炎症反应、血管再生等生理过程中发挥作用。OPN通过与受体结合直接或间接地激活细胞内信号途径,介导细胞与细胞、细胞与细胞外基质之间的相互作用,从而参与调控细胞的生存。大量实验证实,OPN能够促进细胞的增殖,抑制细胞凋亡,尤其是对于肿瘤细胞。但在有些细胞中,OPN对细胞命运的影响却恰恰相反。本文综述了OPN在不同条件下对细胞存活、活化和增殖,细胞自噬和细胞凋亡的多重作用及其作用途径,为进一步研究OPN对不同细胞作用的受体及其信号网络机制提供重要理论基础。     

综述与专论: 运动调节骨源性因子改善阿尔茨海默病的机制

阿尔茨海默病 （Alzheimer’s disease， AD） 作为一种神经退行性疾病会引起中枢神经病变。骨骼和大脑的紧密联系揭示出骨骼和AD之间的内在关联。骨骼作为骨内分泌器官逐渐受到重视。骨骼可分泌骨源性因子（SOST、OCN、OPN）、生成小胶质样细胞以及骨髓干细胞，这些骨源性因子和来源于骨骼的细胞通过血脑屏障调节大脑的生理特性，改善AD的代谢过程。运动刺激骨骼内分泌功能，调节骨源性因子分泌和表达水平，最终延缓AD病理变化并改善AD认知功能水平。本文侧重于阐述骨源性因子对AD的改善作用，以及运动刺激骨骼内分泌改善AD过程的新方法和新视角，为脑骨交互研究提供新思路。     

PI3K/AKT信号通路在常见神经退行性疾病中的机制研究进展

神经退行性疾病是一类以大脑和脊髓中特定的神经元损伤或丢失为主要病理特征的疾病。常见的神经退行性疾病包括阿尔兹海默症(AD)、帕金森症(PD)、肌萎缩侧索硬化(ALS)、亨廷顿病(HD)和多发性硬化(MS),给患者及其家庭带来了很大的困扰,也造成了很大的社会经济负担,已成为全球性的健康问题。近年来,PI3K/AKT信号路径作为一种参与多种细胞功能的信号通路,在多种神经退行性疾病中的作用被广泛研究。本文总结了PI3K/AKT信号通路在常见神经退行性疾病中的作用机制,并对其在不同神经退行性疾病及癌症中的作用异同进行了讨论,进而展望未来相应领域的理论研究及在药物开发中的应用趋势。     

星形胶质细胞在阿尔茨海默病中的作用及其分子机制

阿尔茨海默病(Alzheimer’s disease,AD)是一种多因素导致的神经退行性疾病。随着社会的老龄化,阿尔茨海默病的发病率呈逐渐上升的趋势,给患者以及社会带来极大的生理痛苦和经济负担。星形胶质细胞在中枢神经系统中数量最多、分布最广,对神经元有营养支持作用,并且还能够调控神经元的活性。在AD的病理情况下,星形胶质细胞能参与Aβ代谢影响老年斑的形成,分泌多种炎症因子和趋化因子参与AD的病理进程,并且还能通过影响突触谷氨酸循环来调节神经元的活性。近年来,星形胶质细胞在AD的病理生理机制中的作用受到越来越多的关注。现就星形胶质细胞在AD发病机制中的作用进行综述。     

EAHFE – TROPICA2 study. Prognostic value of troponin in patients with acute heart failure treated in Spanish hospital emergency departments

Objective: Evaluate the use of different cardiac troponin (cTn) immunoassays and the prognostic value of increased cTn values in patients diagnosed with acute heart failure (AHF) in the emergency department (ED).

Method: The epidemiology acute heart failure emergency-TROPonin in acute heart failure2 (EAHFE-TROPICA2) is a retrospective study including patients with AHF admitted in 34 Spanish EDs with cTn values determined in the ED. We studied the prevalence of elevated troponin (value above the established reference limit) for the different types of troponin. We also assessed crude and adjusted primary (1-year all-cause death) and secondary (30 d ED revisit due to AHF) outcomes for every type of cTn and different magnitudes of troponin elevation.

Results: We analysed 4705 episodes of AHF. Troponin was elevated in 48.4% of the cases (25.3% in cTnI, 37.9% in cTnT and 82.2% in hs-cTnT). Mortality at one year was higher in patients with elevated troponin (adjusted HR 1.61; CI 95% 1.38–1.88) regardless of the type of cTn determined. Elevated troponin was not related to ED revisit within 30 d after discharge (1.01; 0.87–1.19).

Conclusions: The use of conventional troponin in the ED is useful to predict one-year mortality in patients with AHF. Highly sensitive cTnT (hs-cTnT) elevations less than double the reference value have no impact on patient outcome.     

我国疾病靶点研究最新进展

主要通过对中国学者2013—2014 年间在国内外发表的相关论文进行查阅和整理,分类综述我国在神经退行性疾病、抑郁症、 心脑血管疾病、代谢性疾病、感染性疾病、肿瘤、自身免疫性疾病等各种重大疾病靶点研究方面的最新进展。     

药物作用靶点研究最新进展

通过对我国学者近2年在国内外发表的相关论文进行检索和整理,分类综述针对神经退行性疾病（如阿尔茨海默病、帕金森病等）、心血管疾病（如高血压、心律失常、心衰、冠心病、心肌梗死、动脉粥样硬化等）、脑血管疾病、代谢类疾病（如肥胖症、血脂异常、脂肪肝、糖尿病等）、感染性疾病（如艾滋病、流感、结核病等）、恶性肿瘤、自身免疫性疾病等多种疾病的药物作用靶点研究最新进展。     

基于疾病本体的疾病相似性计算方法

疾病相似性研究对于复杂疾病发病机制的理解、诊断、预测和药物研发具有重要意义.最近,研究人员通过集成多种疾病术语库,构建了描述疾病关系的疾病本体(disease ontology,DO),这为从DO角度研究疾病相似性打下了基础.本文综述了基于DO及其注释信息的疾病相似性计算方法,探讨了疾病相似性计算存在的问题和挑战,为疾病相似性进一步的研究提供有益参考.     

Mitochondria, calcium and cell death: A deadly triad in neurodegeneration

Mitochondrial Ca²⁺ accumulation is a tightly controlled process, in turn regulating functions as diverse as aerobic metabolism and induction of cell death. The link between Ca²⁺ (dys)regulation, mitochondria and cellular derangement is particularly evident in neurodegenerative disorders, in which genetic models and environmental factors allowed to identify common traits in the pathogenic routes. We will here summarize: i) the current view of mechanisms and functions of mitochondrial Ca²⁺ homeostasis, ii) the basic principles of organelle Ca²⁺ transport, iii) the role of Ca²⁺ in neuronal cell death, and iv) the new information on the pathogenesis of Alzheimer's, Huntington's and Parkinson's diseases, highlighting the role of Ca²⁺ and mitochondria.     

Clinical and Molecular Characteristics of Japanese Gaucher Disease

Clinical signs and symptoms of Gaucher disease are more severe in Japanese than in Jewish and other non-Japanese patients. A higher percentage of bone crises and splenectomy was demonstrated by Japanese patients, and there were five fatalities among patients with type 1 Gaucher disease. Additionally, neonatal Gaucher disease, clinically characterized by hydrops foetalis, was observed. Japanese patients with type 2 and type 3 disease also demonstrate clinical heterogeneity. About 100 alleles of patients with Japanese Gaucher disease were examined for genotype determination with the PCR and SSCP methods. About 18 different mutations, including several novel mutations in Japanese patients, were identified. The most common mutations in Japanese patients were 1448C(L444P), accounting for 41 (41%) of alleles. The second most prevalent mutation was 754A(F2131), accounting for 14 (14%) of alleles. Other alleles identified included the 1324C, IVS2 and other mutations. Unidentified alleles comprised 16% of the total number of alleles studied. To date, neither the 1226G (N370S) nor the 84GG mutation has been identified in the Japanese population, although these mutations account for about 70% and 10% of the mutations in Jewish and other non-Japanese populations, respectively. The phenotype-genotype correlation in Japanese patients is more complex compared with that of the Jewish population. In Japanese patients, the 1448C mutation, in either heteroallelic or homoallelic forms, exhibits both neurological and non-neurological phenotypes. Japanese patients with the 754A mutation also exhibit both neuronopathic and non-neuronopathic disease. On the other hand, patients with the D409H mutation show only type 3 neurological disease, and those with the 1447–1466 del 20 ins TG mutation have the severe, neonatal neurological form of Gaucher disease. The 1503T allele was present only in patients with type 1 non-neurological disease. However, since this correlation was observed only in young patients, we do not as yet know the final phenotypic outcome of this mutation. Probably, Japanese patients with Gaucher disease have few mutations that exhibit non-neurological signs and symptoms.     

Mitochondrial Dysfunction in Neurodegeneration

Numerous toxins are known to interfere with mitochondrial respiratory chain function. Use has been made of these in the development of pesticides and herbicides, and accidental use in man has led to the development of animal models for human disease. The propensity for mitochondrial toxins to induce neuronal cell death may well reflect not only their metabolic pathways but also the sensitivity of neurons to inhibition of oxidative phosphorylation. Thus, the accidental exposure of humans to l-methyl-4-phenyl-l,2,3,6-tetrahydropyridine and to 3-nitropropionic acid has led to primate models of Parkinson's disease and Huntington's disease, respectively. These models were made all the more remarkable when identical biochemical deficiencies were identified in relevant areas of humans suffering from the respective idiopathic diseases. The place of complex I deficiency in Parkinson's disease remains undetermined, but there is recent evidence to suggest that, in some cases at least, it may play a primary role. The complex II/III deficiency in Huntington's disease is likely to be secondary and induced by other pathogenetic factors. The potential to intervene in the cascade of reactions involving mitochondrial dysfunction and cell death offers prospects for the development of new treatment strategies either for neuroprotection in prophylaxis or rescue.     

Wildlife disease elimination and density dependence

Disease control by managers is a crucial response to emerging wildlife epidemics, yet the means of control may be limited by the method of disease transmission. In particular, it is widely held that population reduction, while effective for controlling diseases that are subject to density-dependent (DD) transmission, is ineffective for controlling diseases that are subject to frequency-dependent (FD) transmission. We investigate control for horizontally transmitted diseases with FD transmission where the control is via culling or harvest that is non-selective with respect to infection and the population can compensate through DD recruitment or survival. Using a mathematical model, we show that culling or harvesting can eradicate the disease, even when transmission dynamics are FD. Eradication can be achieved under FD transmission when DD birth or recruitment induces compensatory growth of new, healthy individuals, which has the net effect of reducing disease prevalence by dilution. We also show that if harvest is used simultaneously with vaccination, and there is high enough transmission coefficient, application of both controls may be less efficient than vaccination alone. We illustrate the effects of these control approaches on disease prevalence for chronic wasting disease in deer where the disease is transmitted directly among deer and through the environment.     

Soluble CD40 ligand in haemodialysis patients: survival impact and cardiovascular prognostic role

Context: Soluble CD40 ligand (sCD40l) can predict cardiovascular events (CVE) and mortality in haemodialysis (HD) patients (short-, medium-term follow-up studies).

Objective: To evaluate the relationship between sCD40l and survival, CVE and mortality in HD patients on long-term follow-up.

Methods: We registered 46?HD patients’ baseline characteristics, mortality and CVE for 108 months.

Results: SCD40l correlated positively with C-reactive protein, was higher in survivors, but had no impact on survival and was not predictive for CVE or CV mortality.

Conclusion: The levels of sCD40l have no influence on survival or CVE and mortality in HD patients in a long-term follow-up.     

More than metabolic: Considering the broader paleoepidemiological impact of vitamin D deficiency in bioarchaeology

Vitamin D deficiency has traditionally been viewed as a metabolic bone disease by bioarchaeologists and considered primarily in terms of the development of specific musculoskeletal changes used for diagnosis in paleopathological research. These skeletal manifestations are usually interpreted as representing general ill‐health. Clinical research shows that vitamin D is also integral to a number of extra‐skeletal physiological processes including immunoregulation, blood pressure homeostasis, cell division, and programmed cell death. Vitamin D deficiency and sub‐clinical insufficiency are thought to be risk factors for infectious and autoimmune diseases, as well as certain cancers and cardiovascular diseases. Epidemiological work indicates that the skeletal manifestations of vitamin D deficiency represent the extreme end of a spectrum of morbidity associated with negative health outcomes, including increased risk for secondary tuberculosis. This article provides a review of clinical research on the extra‐skeletal roles of vitamin D and the pathological consequences of poor vitamin D status. Additionally, it presents an interpretive model for bioarchaeological analyses of rickets and osteomalacia for consideration of the whole‐body impact of poor vitamin D nutriture and possible comorbidities that may have affected the wider population. Am J Phys Anthropol 160:183–196, 2016. © 2016 Wiley Periodicals, Inc.