A serum-stable branched dimeric anti-VEGF peptide blocks tumor growth via anti-angiogenic activity

Angiogenesis is critical and indispensable for tumor progression. Since VEGF is known to play a central role in angiogenesis, the disruption of VEGF-VEGF receptor system is a promising target for anti-cancer therapy. Previously, we reported that a hexapeptide (RRKRRR, RK6) blocked the growth and metastasis of tumor by inhibiting VEGF binding to its receptors. In addition, dRK6, the D-form derivative of RK6, retained its biological activity with improved serum stability. In the present study, we developed a serum-stable branched dimeric peptide (MAP2-dRK6) with enhanced anti-VEGF and anti-tumor activity. MAP2-dRK6 is more effective than dRK6 in many respects: inhibition of VEGF binding to its receptors, VEGF- and tumor conditioned medium-induced proliferation and ERK signaling of endothelial cells, and VEGF-induced migration and tube formation of endothelial cells. Moreover, MAP2-dRK6 blocks in vivo growth of VEGF-secreting colorectal cancer cells by the suppression of angiogenesis and the subsequent induction of tumor cell apoptosis. Our observations suggest that MAP2-dRK6 can be a prospective therapeutic molecule or lead compound for the development of drugs for various VEGF-related angiogenic diseases.     

1H NMR assignment of oligomeric grafts of maleic anhydride‐grafted polyolefin

The ¹ H NMR assignment of oligomeric grafts of maleic anhydride (MA)‐grafted polyolefin (PO), MA‐g‐PO hereafter, was experimentally demonstrated for the first time using NMR spectroscopy. ¹³ C DEPT, ¹ H‐¹ H DQF‐COSY, and ¹ H T₂‐edited spectroscopy of MA‐g‐PO proved that peaks of the intermediate methine protons of succinic anhydride oligomeric grafts, which are nearly tetrameric, are observed at 2.5–3.5 ppm and show broadening. Copyright © 2012 John Wiley & Sons, Ltd.     

Hydrophobic guar gum derivatives prepared by controlled grafting processes–Part II: rheological and degradation properties toward fracturing fluids applications

Introduction of polyalkoxyalkyleneamide grafts to guar gum produces new water soluble guar derivatives as described in an earlier publication. 10 In this paper, the rhelogical behavior of these products was explored in more detail at 25 and 65°C. In addition, the viscosity was measured at high temperatures (90 and 120°C) and pressure (150 psi) to partially simulate the down hole conditions of oil wells. Upon treatment with zirconium lactate, the cross‐linked hydrophobically‐modified CMG derivatives exhibited better high‐temperature stability and higher gel viscosities than the corresponding CMHPG derivatives. The cross‐linked gel viscosities indicate that gels will be capable of supporting a high proppant carrying capacity. To facilitate removal of the gels from the formation, the hydrophobically modified derivatives were treated with an enzyme breaker system which produced fragments capable of producing stable emulsions when extracted with toluene. Thus, the clean up process will be enhanced by emulsification of the gel fragments produced by the gel hydrolysis. The low viscosities of the linear derivatives, the rapid formation of high viscosity gels upon cross‐linking and generation of emulsifiers during the gel removal suggest that these new derivatives are good candidates for fracturing fluid applications. Copyright © 2007 John Wiley & Sons, Ltd.     

Degradable,microporous vascular prosthesis from segmented polyurethane

Small caliber (1.5 mm I. D.) vascular prostheses have been prepared from fractionated segmented polyurethane.The microporous and compliant prosthesis when implanted in the abdominal aorta of the rat, induced the growth of a neo-conduit, with a cellular structure similar to that of the natural artery. The process of growth of the neo-artery was accompanied by a progressive degradation of the prosthesis.Presented in part at the 11th Annual Meeting of the European Society of Artificial Organs, Alpbach-Innsbruck, September 1984.     

Synthesis of Tetrahydropyridinyltriazolothiadiazines as Possible Muscarinic Agonists

4-Amino-5-(pyridin-3-yl)-4H-l,2,4-triazole-3-thiol 1 were condensed with 2-bromo-l-(substituted phenyl)ethanone to give pyridinyltriazolothiadiazines 2a-c, which were quaternarized with methyl iodide and oxidized with 30 % hydrogen peroxide to afford the corresponding methyl pyridinium salts 3a-c and pyridine- 1 -oxides 4a-c, respectively. The redtiction of compounds 3 and 4 with NaBH4 in methanol produced the target compounds 1-methyl- 1.2.5.6-tetrahydropyridin-3-yl)-6-aryl-s-triazolothiadiazines 5a-c and 3-( l-hydroxyl- 1, 2, 5, 6-tetrahydropyridin -3-yl)-6-aryl-s-triazolothiadiazines 6a-c, respectively. The endothelium vascular relaxing activity of the target compounds was screened.     

Recent advancement and development of chitin and chitosan-based nanocomposite for drug delivery: Critical approach to clinical research

This review depicts the exposure of chitin and chitosan base multifunctional nanomaterial composites for promising applications in field of biomedical science structure, synthesis as well as potential application from a colossal angle. We elaborated critically each of the chitin and chitosan base nanomaterial with its potential application toward biomedical science. For different biomedical applications it use in form of hydrogels, microsphere, nanoparticles, aerogels, microsphere and in form of scaffold. Due to this it had been blended with different polymer such as starch, cellulose, alginate, lipid, hyaluronic acid, polyvinyl alcohol and caboxymethyl cellulose. In this review article, a comprehensive overview of combination of chitin and chitosan base nanomaterial with natural as well as synthetic polymers and their biomedical applications in biomedical field involving drug delivery system all the technical scientific issues have been addressed; highlighting the recent advancements.     

浙江维管植物分布新记录

报道了浙江维管植物分布新记录10种,分别为：睫毛蕨科Pleurosoriopsidaceae的睫毛蕨Pleurosoriopsis makinoi （Maxim.ex Makino） Fomin;榆科Ulmaceae的山黄麻Trema tomentosa （Roxb.） Hara;樟科Lauraceae的华南木姜子Litsea greenmaniana Allen和黄枝润楠Machilus versicolora S.K.Lee & F.N.Wei;景天科Crassulaceae的东至景天Sedum dongzhiense D.Q.Wang & Y.L.Shi和高岭景天Sedum tricarpum Makino;紫金牛科Myrsinaceae的少年红Ardisia alyxiaefolia Tsiang ex C.Chen;禾本科Poaceae的广州鼠尾粟Sporobolus hancei Rendle、远东芨芨草Achnatherum extremiorientale （Hara） Keng ex P.C.Kuo和南荻Miscanthus lutarioriparius L.Liu ex Renvoize & S.L.Chen.其中,睫毛蕨科为浙江新记录科.凭证标本保存于浙江农林大学植物标本室（ZJFC）.     

共价键合多层肝素薄膜修饰涂有硅橡胶的人工血管

报道一种采用医用硅橡胶涂层作软支撑共价键合多层肝素薄膜修饰人工血管等生物医学装置使其表面具有抗凝血性能的方法. 该项技术首先在人工血管的表面上涂上医用硅橡胶作为软支撑, 再在硅橡胶涂层的表面上涂上全氟磺酸(Nafion), 为接下来的层层静电组装提供活性基团. 然后将带正电荷的二苯胺重氮树脂(PA)和带负电荷的肝素分子(Hep)通过静电吸引作用交替沉积到全氟磺酸涂层的表面上. 紫外可见吸收光谱和傅立叶红外光谱数据表明, 在紫外光照射下, 重氮树脂的重氮基团与肝素的硫酸基团之间发生光化学反应, 生成硫酸酯, 使膜内层间离子键转变成共价键, 从而使肝素多层膜的稳定性大大提高. 研究表明经层层自组装和光化学反应后肝素分子呈现良好的抗凝血性能. 人工血管肝素化表面中的肝素分子以壁面结合的方式存在, 在人工血管表面固化肝素和抗凝血酶-III (AT-III)形成的络合物显示出较好的抗凝血性. 硅橡胶涂层使肝素分子与人工血管表面有一定距离, 有利于提高抗凝血性能. 在四个双层之内, 肝素对凝血酶失活的影响随着PA/Hep双层数目增加而增加, 说明了只有最外层的肝素才对凝血酶失活有直接影响. 该方法操作工艺简单, 重复性好, 可较广泛地适用于在多种生物医用装置和多孔组织工程支架材料的表面制备稳定的抗凝血涂层, 具有良好的应用前景.     

Quinazoline Based HDAC Dual Inhibitors as Potential Anti-Cancer Agents

Cancer is the most devastating disease and second leading cause of death around the world. Despite scientific advancements in the diagnosis and treatment of cancer which can include targeted therapy, chemotherapy, endocrine therapy, immunotherapy, radiotherapy and surgery in some cases, cancer cells appear to outsmart and evade almost any method of treatment by developing drug resistance. Quinazolines are the most versatile, ubiquitous and privileged nitrogen bearing heterocyclic compounds with a wide array of biological and pharmacological applications. Most of the anti-cancer agents featuring quinazoline pharmacophore have shown promising therapeutic activity. Therefore, extensive research is underway to explore the potential of these privileged scaffolds. In this context, a molecular hybridization approach to develop hybrid drugs has become a popular tool in the field of drug discovery, especially after witnessing the successful results during the past decade. Histone deacetylases (HDACs) have emerged as an important anti-cancer target in the recent years given its role in cellular growth, gene regulation, and metabolism. Dual inhibitors, especially based on HDAC in particular, have become the center stage of current cancer drug development. Given the growing significance of dual HDAC inhibitors, in this review, we intend to compile the development of quinazoline based HDAC dual inhibitors as anti-cancer agents.     

Cationic grafting of olefins from PVC: The effect of reaction conditions

The cationic grafting of isobutylene, styrene, α-methylstyrene, and β-pinene from a poly(vinyl chloride) (PVC) backbone was investigated. Grafting-from was induced by Et₂AlCl in 1,2-dichloroethane and methylene dichloride solutions from 20 to −70 °C. The effects of temperature and proton trap [2,6-di-tert-butylpyridine (DtBP)] on grafting-from efficiency (G_eff), extent of grafting, branch length (molecular weight), and number of branches per PVC molecule were determined. Reducing the temperature invariably increased the G_eff and the molecular weight of polyisobutylene, polystyrene, poly(α-methylstyrene), and poly(β-pinene) branches attached to PVC. The magnitude of the effects was different with the various olefins and depended on the reaction conditions. The effect of DtBP was examined in the 5 × 10⁻⁴–4 × 10⁻³ mol/L range. By increasing the DtBP concentration the G_eff increased; however, the number-average molecular weight of the grafted branches decreased. The lengths of the grafted branches can be controlled, and G_eff's close to 100% were obtained. The fact that the proton trap reduced the molecular weights of grafted branches suggests that besides proton scavenging, DtBP may also abstract protons from the growing carbenium ion site. © 2001 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 39: 1675–1680, 2001