Increased circulating Wnt5a protein in patients with rheumatoid arthritis-associated interstitial pneumonia (RA-ILD)

An early diagnosis of interstitial lung disease (ILD) is important for guiding treatments of rheumatoid arthritis (RA)-associated ILD (RA-ILD) in clinical settings. The non-canonical Wnt signaling representative ligand Wnt5a was recently found to involve in idiopathic pulmonary fibrosis (IPF) and pathogenesis of RA. The goal of this study was to examine the clinical relevance of Wnt5a in RA-ILD. In this report, the clinical relevance of plasma Wnt5a protein was evaluated in 40 RA-ILD patients and 41 non-ILD RA cohorts. The results showed an elevated Wnt5a protein in plasmas of RA-ILD patients compared with non-ILD RA patients (p < 0.01), which was positively correlated with the plasma level of rheumatoid factor (RF). Of note, more abundant Wnt5a was also found in patients with usual interstitial pneumonia (UIP) than those with nonspecific interstitial pneumonia (NSIP) and other ILD patterns. More importantly, the disease severity was correlated with the circulating Wnt5a as ascertained by high-resolution computed tomography (HRCT)-UIP scores. The multiple-factor non-conditional logistic regression analysis further revealed that the age, RA duration, smoking and plasma Wnt5a were risk factors with clinical significance for RA-ILD. Interestingly, more Wnt5a-positive patients were identified in RA-ILD smokers relative to RA-ILD never-smokers, and longer smoking duration was strongly correlated with Wnt5a in RA-ILD patients. In consistence, ROC curve also suggested that the Wnt5a was a potential candidate biomarker for identifying patients with RA-UIP. These results demonstrate that the circulating Wnt5a may be a risk factor and potential biomarker for identifying UIP and accessing the severity and progression of ILD in RA patients.     

Inflammatory mediators mediate airway smooth muscle contraction through a G protein-coupled receptor–transmembrane protein 16A–voltage-dependent Ca2+ channel axis and contribute to bronchial hyperresponsiveness in asthma

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肱骨三维有限元分析及其记忆生物力学意义

目的:分析肱骨不同载荷加载下应力分布,探讨其相关的记忆生物力学意义。方法:选择湿肱骨标本行CT成像,大型有限元分析软件ANSYS5.6建立肱骨三维模型以及天鹅记忆加压接骨器(shapememoryconector,SMC)固定模型,同时进行相应力学分析。结果:当纵向加压的压力P=300N时,Z方向的正应力为-4.0～-4.5MPa,断面区域的压应力为0～0.2MPa。结论:SMC固定肱骨后三维有限元的分析,可以为肱骨骨折后内固定的力学研究提供新思路。     

Biomarkers in TAA—The Holy Grail

Thoracic aortic aneurysm (TAA) is a silent disease, often discovered at a time point that dramatic complications, as rupture and dissection, occur. For the detection of asymptomatic TAA and prevention of such complications, it is essential to have an adequate screening tool. Until now, routine laboratory blood tests have played only a minor role in the screening, diagnosis, tracking and prediction of the natural history of TAAs. However, the knowledge about biomarkers is rapidly expanding in the cardiovascular field, and there are several potential biomarkers that might be implemented into TAA clinical practice in the near future. The most important and promising markers for TAA will be discussed in this overview.     

RAD50, an SMC family member with multiple roles in DNA break repair: how does ATP affect function?

The protein complex including Mre11, Rad50, and Nbs1 (MRN) functions in DNA double-strand break repair to recognize and process DNA ends as well as signal for cell cycle arrest. Amino acid sequence similarity and overall architecture make Rad50 a member of the structural maintenance of chromosome (SMC) protein family. Like SMC proteins, Rad50 function depends on ATP binding and hydrolysis. All current evidence indicates that ATP binding and hydrolysis cause architectural rearrangements in SMC protein complexes that are important for their functions in organizing DNA. In the case of the MRN complex, the functional significance of ATP binding and hydrolysis are not yet defined. Here we review the data on the ATP-dependent activities of MRN and their possible mechanistic significance. We present some speculation on the role of ATP for function of the MRN complex based on the similarities and differences in the molecular architecture of the Rad50-containing complexes and the SMC complexes condensin and cohesin.     

Vascular endothelial growth factors: biology and current status of clinical applications in cardiovascular medicine

Members of the vascular endothelial growth factor (VEGF) family are among the most powerful modulators of vascular biology. They regulate vasculogenesis, angiogenesis, and vascular maintenance during embryogenesis and in adults. Because of their profound effects on blood vessels, VEGFs have received much attention regarding their potential therapeutic use in cardiovascular medicine, especially for therapeutic vascular growth in myocardial and peripheral ischemia. However, completed randomized controlled VEGF trials have not provided convincing evidence of clinical efficacy. On the other hand, recent preclinical proangiogenic VEGF studies have given insight, and anti-VEGF studies have shown that the disturbance of vascular homeostasis by blocking VEGF-A may lead to endothelial dysfunction and adverse vascular effects. Excess VEGF-A may contribute to neovascularization of atherosclerotic lesions but, currently, there is no evidence that transient overexpression by gene transfer could lead to plaque destabilization. Here, we review the biology and effects of VEGFs as well as the current status of clinical applications and future perspectives of the therapeutic use of VEGFs in cardiovascular medicine.