The role of adiponectin in the production of IL-6, IL-8, VEGF and MMPs in human endothelial cells and osteoblasts: implications for arthritic joints

This study was performed to evaluate the contribution of adiponectin to the production of interleukin (IL)-6, IL-8, vascular endothelial growth factor (VEGF), matrix metalloproteinase (MMP)-1 and MMP-13 in human endothelial cells and osteoblasts in arthritic joints. Cultured human umbilical vascular endothelial cells (HUVECs) and osteoblasts were stimulated with adiponectin (1 or 10 μg ml⁻¹) or IL-1β (0.1 ng ml⁻¹) in the presence or absence of hypoxia for 24 h. The protein expression patterns were examined by analyzing culture supernatants using the enzyme-linked immunosorbent assay (ELISA). Adiponectin significantly stimulated the production of VEGF, MMP-1 and MMP-13 in osteoblasts but not in endothelial cells, whereas it significantly stimulated the production of IL-6 and IL-8 in both endothelial cells and osteoblasts. The increase in VEGF production induced by adiponectin was significantly greater than that induced by IL-1β. The production of IL-6 and IL-8 in adiponectin-stimulated endothelial cells was approximately 10-fold higher than that in IL-1β-stimulated endothelial cells; in osteoblasts, adiponectin-induced IL-6 and IL-8 secretion was approximately twofold higher than that induced by IL-1β. In addition, IL-8 production in endothelial cells was approximately sevenfold higher than in osteoblasts. However, IL-6 levels were similar between the two cell types, suggesting that adiponectin may be involved in the production of IL-8 in endothelial cells, which may have an important role in neutrophil recruitment to arthritic joints. Furthermore, the increases in protein expression induced by adiponectin were differentially regulated by hypoxia. In conclusion, adiponectin has a more important role than does IL-1β in the production of mediators that drive synovitis and joint destruction in endothelial cells and osteoblasts at physiological concentrations.     

兔主动脉冻结过程中未冻水份额的研究

利用差示扫描量热仪(DSC)技术中的分步扫描(Stepwise scanning)法,研究了不同浓度的低温保护剂对主动脉血管冻结过程中未冻水份额的影响。研究结果表明:分步扫描量热技术可以用于血管材料冻结过程中未冻水份额的定量研究,而且具有较高楠度;随着低温保护剂二甲亚砜(DMSO)浓度的增大,血管的初始冻结点温度呈线性降低,但其冻结过程的未冻水份额显著增大,这是由于高浓度DMSO具有很强水合能力所致。     

A segmentation procedure of the pervious area of the aorta artery from CT images without contrast medium

In this paper, we develop an algorithm for the segmentation of the pervious lumen of the aorta artery in computed tomography (CT) images without contrast medium, a challenging task due to the closeness gray levels of the different zones to segment. The novel approach of the proposed procedure mainly resides in enhancing the resolution of the image by the application of the algorithm deduced from the mathematical theory of sampling Kantorovich operators. After the application of suitable digital image processing techniques, the pervious zone of the artery can be distinguished from the occluded one. Numerical tests have been performed using 233 CT images, and suitable numerical errors have been computed and introduced ex novo to evaluate the performance of the proposed method. The above procedure is completely automatic in all its parts after the initial region of interest (ROI) selection. The main advantages of this approach relies in the potential possibility of performing diagnosis concerning vascular pathologies even for patients with severe kidney diseases or allergic problems, for which CT images with contrast medium cannot be achieved.     

Membrane Cholesterol and the Formation of Cholesterol Domains in the Pathogenesis of Cardiovascular Disease

At least three types of cholesterol-rich membrane domains have been described in biological membranes including cholesterol rafts, membrane caveolae and crystalline cholesterol domains,. While clear biological functions have been ascribed to both rafts and caveolae, little attention has been directed to the biological consequences of cholesterol enrichment of cell membranes and the formation of cholesterol domains. Elevated blood cholesterol levels have been shown to result in the enrichment of the cell plasma membrane with cholesterol in arterial smooth muscle cells (SMC), endothelial cells (EC) and cardiac myocytes. In the early period of cholesterol feeding (within days), the cell membrane enriches with cholesterol and membrane viscosity and membrane bilayer width increase. This latter effect severely alters membrane protein function, and recent data indicates that this induces the modulation of vascular cells (SMC and EC) to the atherosclerotic phenotype. In cardiac myocytes these membrane modifications appear to induce alterations in gene expression patterns that lead to the development of a heart failure phenotype. In addition, as the cholesterol content increases, phase separation of cholesterol occurs resulting in the formation of immiscible cholesterol domains within the membrane. These domains likely initiate nucleation of cholesterol crystals which would explain the origin of “cholesterol clefts” in atherosclerotic lesions. Taken together, these membrane alterations secondary to cholesterol enrichment constitute a “membrane lesion” which contribute to the very early pathogenic events underlying major human diseases including coronary artery disease, stroke and heart failure.     

Versican undergoes specific alterations in the fine molecular structure and organization in human aneurysmal abdominal aortas

Versican is the major matrix proteoglycan in aortic wall and participates in various biological functions of the tissue. In the present study the molecular characteristics of versican isolated from normal human aorta as well as those of versican expressed in aneurysmal aortic tissue were examined. Versican was isolated by combined anion-exchange and gel permeation chromatography and was further characterized by high-performance liquid chromatography, polyacrylamide gel electrophoresis and immunoblotting. In both tissues versican is exclusively substituted with chondroitin sulfate chains, in contrast to other human tissues where both chondroitin and dermatan sulfate chains are attached onto versican core proteins. Except for the significant decrease in the concentration of versican in the aneurysmal tissue, this PG undergoes specific alterations in the aneurysmal tissue. The molecular size of versican isolated from diseased tissue is decreased with a simultaneous increase in the ratio of glycosaminoglycan to protein in this tissue. The latter reflect the extensive fragmentation of versican in the diseased tissue and most probably the generation of shorter peptides enriched to glycosaminoglycan chains. Although the size of chondroitin sulfate chains is identical in both versican preparations, a significant increase in the percentage of 6-sulfated disaccharides is observed in chondroitin sulfate chains of versican in aneurysmal aortas, which is accompanied by decrease in 4-sulfated and non-sulfated units.     

Effects of size and location of distal tear on hemodynamics and wave propagation in type B aortic dissection

Applied Mathematics and Mechanics - The type B aortic dissection (TBAD) is a perilous disease with high morbidity and mortality rates. The hemodynamics of TBAD in different scenarios has been...     

Rapid biochemical profiling of endothelial dysfunction in diabetes,hypertension and cancer metastasis by hierarchical cluster analysis of Raman spectra

Raman spectroscopy is a label free, versatile, simple and fast method that is increasingly used to detect pathological changes in the cells and tissues that could be useful in medical diagnostics. In this work, we tested the hypothesis that Raman spectroscopy may serve to detect endothelial dysfunction in murine models of lifestyle diseases associated with endothelial dysfunction. For that purpose, we analysed spectra from ex vivo vessels taken from mice with diabetes, hypertension and cancer metastasis. We extracted 50–70 random, single spectra, recorded in 0.2 s, from endothelium of mice with diseases and respective control animals and subjected them to hierarchical cluster analysis. Independently on the sample preparation protocol, very good discrimination was obtained for three‐tested murine models, i.e. diabetes, hypertension and cancer metastasis. Obtained sensitivity and specificity parameters were between 93% and 96% (with the exception of sensitivity in the diabetes model equalled to 88%). Our results show that single, random spectra of endothelium, recorded in less than a second, contains enough information on biochemical content of the endothelium to detect endothelial dysfunction. Furthermore, we demonstrated that biochemical profile of the endothelial dysfunction in diabetes, hypertension or cancer metastasis differs with a very high specificity and sensitivity. This conclusion can be a good starting point for the development of in vivo fast diagnostic methodology of endothelium in the future. Copyright © 2016 John Wiley & Sons, Ltd.     

生物力学进展和趋向(续)

三、运动关节力学运动关节(diarthrodial joint)的功能在于使动物能灵巧地运动肢体。译成力学术语就是:传递载荷,吸收冲击、振动,承受相当高的应力,且运动时摩擦系数很小。L.L.Malcom曾精细地测量过牛肱关节的摩擦系数,在正应力1—20kg/cm~2的范围内,动摩擦系数为0.0025—0.0040,而最好的工程材料的摩擦系数为0.01—0.05,整整差一个量级。      

Novel Oxime Synthesized from a Natural Product of Senecio nutans SCh. Bip. (Asteraceae) Enhances Vascular Relaxation in Rats by an Endothelium-Independent Mechanism

Senecio nutans Sch. Bip. and its constituents are reported to have antihypertensive effects. We isolated metabolite–1, a natural compound from S. nutans (4-hydroxy-3-(isopenten-2-yl)-acetophenone), and synthesized novel oxime – 1 (4-hydroxy-3-(isopenten-2-yl)-acetophenoxime) to evaluate their effect on vascular reactivity. Compounds were purified (metabolite–1) or synthetized (oxime–1) and characterized using IR and NMR spectroscopy and Heteronuclear Multiple Quantum Coherence (HMQC). Using pharmacological agents such as phenylephrine (PE) and KCl (enhancing contraction), acetylcholine (ACh), L-NAME (nitric oxide (NO) and endothelial function), Bay K8644-induced Ca_V1.2 channel (calcium channel modulator), and isolated aortic rings in an organ bath setup, the possible mechanisms of vascular action were determined. Pre-incubation of aortic rings with 10⁻⁵ M oxime–1 significantly (p < 0.001) decreased the contractile response to 30 mM KCl. EC₅₀ to KCl significantly (p < 0.01) increased in the presence of oxime–1 (37.72 ± 2.10 mM) compared to that obtained under control conditions (22.37 ± 1.40 mM). Oxime–1 significantly reduced (p < 0.001) the contractile response to different concentrations of PE (10⁻⁷ to 10⁻⁵ M) by a mechanism that decreases Cav1.2-mediated Ca²⁺ influx from the extracellular space and reduces Ca²⁺ release from intracellular stores. At a submaximal concentration (10⁻⁵ M), oxime–1 caused a significant relaxation in rat aorta even without vascular endothelium or after pre-incubate the tissue with L-NAME. Oxime–1 decreases the contractile response to PE by blunting the release of Ca²⁺ from intracellular stores and blocking of Ca²⁺ influx by channels. Metabolite–1 reduces the contractile response to KCl, apparently by reducing the plasma membrane depolarization and Ca²⁺ influx from the extracellular space. These acetophenone derivates from S. nutans (metabolite–1 and oxime–1) cause vasorelaxation through pathways involving an increase of the endothelial NO generation or a higher bioavailability, further highlighting that structural modification of naturally occurring metabolites can enhance their intended pharmacological functions.