磷光成像技术及其在肿瘤和视血管疾病诊断中的应用

本文简述了磷光成像技术的基本原理及其在肿瘤和其它与体内氧浓度变化有关的疾病的早期诊断中潜在的应用价值。并指出该技术尚存在的问题及今后研究的课题。     

5,2′-Dibromo-2,4′,5′-trihydroxydiphenylmethanone Inhibits LPS-Induced Vascular Inflammation by Targeting the Cav1 Protein

Vascular inflammation is directly responsible for atherosclerosis. 5,2′-Dibromo-2,4′,5′-trihydroxydiphenylmethanone (TDD), a synthetic bromophenol derivative, exhibits anti-atherosclerosis and anti-inflammatory effects. However, the underlying pathways are not yet clear. In this study, we first examined the effects of TDD on toll-like receptor-4 (TLR4) activity, the signaling receptor for lipopolysaccharide (LPS), and found that TDD does not inhibit LPS-induced TLR4 expression in EA.hy926 cells and the vascular wall in vivo. Next, we investigated the global protein alterations and the mechanisms underlying the action of TDD in LPS-treated EA.hy926 cells using an isobaric tag for the relative and absolute quantification technique. Western blot analysis revealed that TDD inhibited NF-κB activation by regulating the phosphorylation and subsequent degradation IκBα. Among the differentially expressed proteins, TDD concentration-dependently inhibited Caveolin 1(Cav1) expression. The interaction between Cav1 and TDD was determined by using biolayer interference assay, UV-vis absorption spectra, fluorescence spectrum, and molecular docking. We found that TDD can directly bind to Cav1 through hydrogen bonds and van der Waals forces. In conclusion, our results showed that TDD inhibited LPS-induced vascular inflammation and the NF-κB signaling pathway by specifically targeting the Cav1 protein. TDD may be a novel anti-inflammatory compound, especially for the treatment of atherosclerosis.     

Design,Preparation, and Performance of a Novel Bilayer Tissue‐Engineered Small‐Diameter Vascular Graft

In clinical practice, the need for small‐diameter vascular grafts continues to increase. Decellularized xenografts are commonly used for vascular reconstructive procedures. Here, porcine coronary arteries are decellularized, which destroys the extracellular matrix structure, leading to the decrease of vascular strength and the increase of vascular permeability. A bilayer tissue‐engineered vascular graft (BTEV) is fabricated by electrospinning poly(l ‐lactide‐co‐carprolactone)/gelatin outside of the decellularized vessels and functionalized by immobilizing heparin, which increases the biomechanical strength and anticoagulant activity of decellularized vessels. The biosafety and efficacy of the heparin‐modified BTEVs (HBTEVs) are verified by implanting in rat models. HBTEVs remain patent and display no expansion or aneurism. After 4 weeks of implantation, a cell monolayer in the internal surface and a dense middle layer have formed, and the mechanical properties of regenerated vessels are similar to those of rat abdominal aorta. Therefore, HBTEVs can be used for rapid remodeling of small‐diameter blood vessels.     

Role of vitamin D-binding protein in isocyanate-induced occupational asthma

The development of a serological marker for early diagnosis of isocyanate-induced occupational asthma (isocyanate-OA) may improve clinical outcome. Our previous proteomic study found that expression of vitamin D-binding protein (VDBP) was upregulated in the patients with isocyanate-OA. In the present study, we evaluated the clinical relevance of VDBP as a serological marker in screening for isocyanate-OA among exposed workers and its role in the pathogenesis of isocyanate-OA. Three study groups including 61 patients with isocyanate-OA (group I), 180 asymptomatic exposed controls (AECs, group II), 58 unexposed healthy controls (NCs, group III) were enrolled in this study. The baseline serum VDBP level was significantly higher in group I compared with groups II and III. The sensitivity and specificity for predicting the phenotype of isocyanate-OA with VDBP were 69% and 81%, respectively. The group I subjects with high VDBP (≥311 μg/ml) had significantly lower PC(20) methacholine levels than did subjects with low VDBP. The in vitro studies showed that TDI suppressed the uptake of VDBP into RLE-6TN cells, which was mediated by the downregulation of megalin, an endocytic receptor of the 25-hydroxycholecalciferol-VDBP complex. Furthermore, toluene diisocyanate (TDI) increased VEGF production and secretion from this epithelial cells by suppression of 1,25-dihydroxycholecalciferol [1,25(OH)(2)D(3)] production. The findings of this study suggest that the serum VDBP level may be used as a serological marker for the detection of isocyanate-OA among workers exposed to isocyanate. The TDI-induced VEGF production/ secretion was reversed by 1,25(OH)(2)D(3) treatment, which may provide a potential therapeutic strategy for patients with isocyanate-OA.     

Effect of swirling flow on platelet concentration distribution in small-caliber artificial grafts and end-to-end anastomoses

Platelet concentration near the blood vessel wall is one of the major factors in the adhesion of platelets to the wall.In our previous studies,it was found that swirling flows could suppress platelet adhesion in small-caliber artificial grafts and end-to-end anastomoses.In order to better understand the beneficial effect of the swirling flow,we numerically analyzed the near-wall concentration distribution of platelets in a straight tube and a sudden tubular expansion tube under both swirling flow and normal flow conditions.The numerical models were created based on our previous experimental studies.The simulation results revealed that when compared with the normal flow,the swirling flow could significantly reduce the near-wall concentration of platelets in both the straight tube and the expansion tube.The present numerical study therefore indicates that the reduction in platelet adhesion under swirling flow conditions in small-caliber arterial grafts,or in end-to-end anastomoses as observed in our previous experimental study,was possibly through a mechanism of platelet transport,in which the swirling flow reduced the near-wall concentration of platelets.     

Mechanical investigation of bilayer vascular grafts electrospun from aliphatic polyesters

Electrospun biodegradable vascular grafts provide a wide range of design components from the selection of materials to the modification of fiber structure. In this study, both single layer and bilayer tubular scaffolds with inner diameter of 6 mm were electrospun from polycaprolactone with different molecular weights and poly(l ‐lactide) caprolactone polymers. Bilayer scaffolds were designed by using different combinations of the polymer types in each layer and obtaining fiber orientation in outer layers. Scaffolds were analyzed morphologically and mechanically. Obtained results of mechanical performance were discussed according to the used polymer‐type composition, fiber orientation, and composite effect of both layer in the final graft. Smooth muscle cells were seeded on the scaffolds to test biocompatibility of presented scaffolds. Results indicate that the use of different biodegradable polymers in different combinations in each layer causes notable differences in fiber morphology and mechanical performance of the scaffolds. Moreover, fiber orientation in outer layer improves tensile strength and burst pressures in radial directions while creating a suitable fibrous layer for smooth muscle cells by mimicking the extracellular matrix of tunica media in native vessels. Copyright © 2016 John Wiley & Sons, Ltd.     

Development of a Dual‐Functional Hydrogel Using RGD and Anti‐VEGF Aptamer

Synthetic molecular libraries hold great potential to advance the biomaterial development. However, little effort is made to integrate molecules with molecular recognition abilities selected from different libraries into a single biomolecular material. The purpose of this work is to incorporate peptides and nucleic acid aptamers into a porous hydrogel to develop a dual‐functional biomaterial. The data show that an anti‐integrin peptide can promote the attachment and growth of endothelial cells in a 3D porous poly(ethylene glycol) hydrogel and an antivascular endothelial growth factor aptamer can sequester and release VEGF of high bioactivity. Importantly, the dual‐functional porous hydrogel enhances the growth and survival of endothelial cells. This work demonstrates that molecules selected from different synthetic libraries can be integrated into one system for the development of novel biomaterials.     

Stromal Vascular Fraction Loaded Silk Fibroin Mats Effectively Support the Survival of Diabetic Mice after Pancreatic Islet Transplantation

The aim of this study is to assess whether stromal vascular fraction (SVF)‐soaked silk fibroin nonwoven mats (silk‐SVF) can preserve the functionality of encapsulated pancreatic endocrine cells (alginate‐PECs) after transplantation in the subcutaneous tissue of diabetic mice. Silk scaffolds are selected to create an effective 3D microenvironment for SVF delivery in the subcutaneous tissue before diabetes induction: silk‐SVF is subcutaneously implanted in the dorsal area of five healthy animals; after 15 d, mice are treated with streptozotocin to induce diabetes and then alginate‐PECs are implanted on the silk‐SVF. All animals appear in good health, increasing weight during time, and among them, one presents euglycemia until the end of experiments. On the contrary, when PECs are simultaneously implanted with SVF after diabetes induction, mice are euthanized due to suffering. This work clearly demonstrates that silk‐SVF creates a functional niche in subcutaneous tissue and preserves endocrine cell survival and engraftment.     

Molecular Modeling Studies of Vascular Endothelial Growth Factor Receptor Tyrosine Kinase Inhibitors Combining Molecular Docking and 3D-QSAR Methods

The vascular endothelial growth factor (VEGF) and its receptor tyrosine kinases VEGFR-2 or kinase insertdomain receptor (KDR) have emerged as attractive targets for the design of novel anticancer agents. In the present work, molecular docking method combined with three dimensional quantitative structure-activity relationships (comparative molecular field analysis (CoMFA) and comparative molecular similarity indice analysis (CoMSIA)) to analyze the possible interactions between KDR and those derivatives which acted as selective inhibitors. The CoMFA and CoMSIA models gave a cross-validated coefficient Q2 of 0.713 and 0.549, non-cross-validated R2 values of 0.974 and 0.878, and predicted R2 values of 0.966 and 0.823, respectively. The 3D contour maps generated by the CoMFA and CoMSIA models were used to identify the key structural requirements responsible for the biological activity. The information obtained from 3D-QSAR and docking studies were very helpful to design novel selective inhibitors of KDR with desired activity and good chemical property.     

短穗柽柳幼苗形态解剖结构观察

柽柳（ＴａｍａｒｉｘＳｐｐ．）在荒漠的非河岸区自然侵移现象已被发现，本文试图通过对短穗柽柳（ＴａｍａｒｉｘＬａｘａ）幼苗在生长发育过程中形态解剖结构变化规律的研究，探讨柽柳在沙漠非河岸区自然侵移定居成功的内部形态的适应特征，幼苗自５月萌发至９月，叶面积由２．９１ｍｍ＾２减小到０．８０ｍｍ＾２，栅栏组织细胞排列由疏松到紧密，栅栏组织厚度由５４．５μｍ，增至８６．０μｍ，维管束／茎半径的比值由２５．３