Antiviral Activity of a Cyclic Pro-Pro-β3-HoPhe-Phe Tetrapeptide against HSV-1 and HAdV-5

The core of Cyclolinopeptide A (CLA, cyclo(LIILVPPFF)), responsible for its high immunosuppressive activity, contains a Pro-Pro-Phe-Phe sequence. A newly synthesized cyclic tetrapeptide, cyclo(Pro-Pro-β³-HoPhe-Phe) (denoted as 4B8M) bearing the active sequence of CLA, was recently shown to exhibit a wide array of anti-inflammatory properties in mouse models. In this investigation, we demonstrate that the peptide significantly inhibits the replication of human adenovirus C serotype 5 (HAdV-5) and Herpes simplex virus type-1 (HSV-1) in epithelial lung cell line A-549, applying Cidofovir and Acyclovir as reference drugs. Based on a previously established mechanism of its action, we propose that the peptide may inhibit virus replication by the induction of PGE2 acting via EP2/EP4 receptors in epithelial cells. In summary, we reveal a new, antiviral property of this anti-inflammatory peptide.     

H2SO4-H2O中硝酸铜对脱硫石膏晶须生长的影响

以处理后的脱硫石膏为原料,在H₂SO₄-H₂O体系中以Cu(NO₃)₂为晶形控制剂采用水热法制备脱硫石膏晶须,探讨了Cu(NO₃)₂对脱硫石膏晶须生长的影响机理。结果表明:Cu(NO₃)₂对脱硫石膏有明显促溶作用,其中Cu²⁺可减小溶液中各离子的活度系数,使溶液中的Ca²⁺浓度增大。NO^-₃通过静电作用在Ca²⁺周围聚集并对SO^2-₄产生屏蔽作用,导致脱硫石膏继续溶解并使Ca²⁺和SO^2-₄的浓度处于相对稳定状态,有利于半水脱硫石膏晶体的形核与生长。此外,Cu²⁺还可在晶须的生长过程中选择性吸附在晶须表面,生成CuSO₄,促进了脱硫石膏的结晶生长,最终在Cu(NO₃)₂用量为2.0%(质量分数)时制备的脱硫石膏晶须长径比约为73。     

纳米氧化镱对熔融石英析晶动力学机制的影响

本文研究引入纳米氧化镱对熔融石英析晶机制及动力学过程的影响.通过X射线衍射仪(XRD)测试结果分析了纳米氧化镱的引入对熔融石英陶瓷析晶率的影响,采用动力学方法分析了纳米氧化镱的引入对熔融石英陶瓷析晶机制的影响,同时探讨了其等温析晶动力学过程.研究表明,熔融石英陶瓷的晶粒向二维兼有一维及三维的方式生长,引入纳米氧化镱的熔...     

Fe掺杂α-Bi2O3光电性质的第一性原理研究

采用第一性原理杂化泛函HSE06方法对Fe掺杂α-Bi2 O3的电子结构和光学性质进行了计算研究.结果表明,Fe掺杂α-Bi2 O3体系有较小的结构变形,本征α-Bi2 O3的禁带宽度为2.69 eV,Fe掺杂使α-Bi2 O3的禁带宽度减小(约为2.34 eV).对其光学性质研究得出Fe掺杂扩展了α-Bi2 O3对可...     

Euphorbiasteroid Abrogates EGFR and Wnt/β-Catenin Signaling in Non-Small-Cell Lung Cancer Cells to Impart Anticancer Activity

EGFR and Wnt/β-catenin signaling pathways play a prominent role in tumor progression in various human cancers including non-small-cell lung carcinoma (NSCLC). Transactivation and crosstalk between the EGFR and Wnt/β-catenin pathways may contribute to the aggressiveness of cancers. Targeting these oncogenic pathways with small molecules is an attractive approach to counteract various types of cancers. In this study, we demonstrate the effect of euphorbiasteroid (EPBS) on the EGFR and Wnt/β-catenin pathways in NSCLC cells. EPBS induced preferential cytotoxicity toward A549 (wildtype EGFR-expressing) cells over PC-9 (mutant EGFR-expressing) cells. EPBS suppressed the expression of EGFR, Wnt3a, β-catenin, and FZD-1, and the reduction in β-catenin levels was found to be mediated through the activation of GSK-3β. EPBS reduced the phosphorylation of GSK-3β^S9 with a parallel increase in β-TrCP and phosphorylation of GSK-3β^Y216. Lithium chloride treatment increased the phosphorylation of GSK-3β^S9 and nuclear localization of β-catenin, whereas EPBS reverted these effects. Forced expression or depletion of EGFR in NSCLC cells increased or decreased the levels of Wnt3a, β-catenin, and FZD-1, respectively. Overall, EPBS abrogates EGFR and Wnt/β-catenin pathways to impart its anticancer activity in NSCLC cells.     

Drugs Targeting the A3 Adenosine Receptor: Human Clinical Study Data

The A3 adenosine receptor (A3AR) is overexpressed in pathological human cells. Piclidenoson and namodenoson are A3AR agonists with high affinity and selectivity to A3AR. Both induce apoptosis of cancer and inflammatory cells via a molecular mechanism entailing deregulation of the Wnt and the NF-κB signaling pathways. Our company conducted phase I studies showing the safety of these 2 molecules. In the phase II studies in psoriasis patients, piclidenoson was safe and demonstrated efficacy manifested in significant improvements in skin lesions. Namodenoson is currently being developed to treat liver cancer, where prolonged overall survival was observed in patients with advanced liver disease and a Child–Pugh B score of 7. A pivotal phase III study in this patient population has been approved by the FDA and the EMA and is currently underway. Namodenoson is also being developed to treat non-alcoholic steatohepatitis (NASH). A Phase IIa study has been successfully concluded and showed that namodenoson has anti-inflammatory, anti-fibrosis, and anti-steatosis effects. A phase IIb study in NASH is currently enrolling patients. In conclusion, A3AR agonists are promising drug candidates in advanced stages of clinical development and demonstrate safety and efficacy in their targeted indications.     

Synthesis and Anti-Neuroinflammatory Activity of 1,7-diphenyl-1,4-heptadien-3-ones in LPS-Stimulated BV2 Microglia Via Inhibiting NF-κB/MAPK Signaling Pathways

A series of 1,7-diphenyl-1,4-heptadien-3-ones with various substituents (HO-, CH₃O-, CH₃-, Cl-) on the phenyl rings were synthesized and evaluated for anti-neuroinflammatory effects in LPS-stimulated BV2 microglia. The pharmacological results showed that the target compounds bearing methoxy groups greatly inhibited LPS-induced NO release, and that the active compounds CU-19 and CU-21 reduced the level of NO, TNF-α, IL-6 and PGE-2, downregulated the expression of COX-2 and iNOS in LPS-stimulated BV2 cells. A study of the mechanism of action revealed that CU-19 and CU-21 inhibited the nuclear translocation of NF-κB and phosphorylation of MAPKs (ERK, JNK, and p38). A preliminary pharmacokinetic study in rats revealed that the pharmacokinetic properties of CU-19 and CU-21 were dramatically ameliorated in comparison with the pharmacokinetic properties of curcumin.     

Cu3N薄膜及其研究现状

Cu3N薄膜是近10年来研究的热点材料之一.Cu3N是立方反ReO3结构,理想立方反ReO3结构的一个晶胞中Cu原子占据立方边的中心位置而N原子占据立方晶胞的八个顶点,此结构的体心位置有一较大间隙,Cu原子以及其他原子如Pd、碱金属原子等很有可能进入此位置导致Cu3N的电学性能、光学性能等发生很大的变化,这使得该材料具有很大的潜在应用价值.Cu3N的晶格常数为0.3815nm,密度5.84g/cm3,分子量204.63,颜色呈黑绿色或红褐色,空间点群Pm3m.Cu3N薄膜在室温下相当稳定并且热分解温度较低(300℃左右),热分解前后薄膜的光学反射率有较大差别,这可使Cu3N薄膜用作一次性光记录材料.此外,Cu3N薄膜还可用作在Si片上沉积金属Cu线的缓冲层、低磁阻隧道结的阻挡层、自组装材料的模板等.     

CTAB与SDBS对碳酸锶粒子生长形态调控及机理研究

以表面活性剂CTAB和SDBS为化学添加剂,采用化学共沉淀法对碳酸锶晶体的生长形态进行调控,成功地制备出了实心的树枝状和花瓣为空心的花状碳酸锶粉体,并用X射线衍射(XRD)、扫描电子显微镜(SEM)和傅里叶变换红外光谱(FT-IR)等分析手段对样品进行了表征;最后重点对化学添加剂可能产生的影响机理进行了初步的探讨.结果表明,CTAB和SDBS在晶体生长的过程中能起到显著的影响作用,两者对粒子分散性能的作用效果相反,而且后者对晶体(013)和(213)晶面表面能降低的贡献明显大于前者.     

Fe3+对KDP晶体光学质量的影响

金属离子Fe3+对KDP晶体的生长和光学性质有明显影响.本文在前期研究的基础上[1]系统考察了该杂质离子对KDP晶体光学质量的影响.实验结果表明,三价金属离子Fe3+会降低KDP晶体的透光率,同时对晶体均匀性和光损伤阈值也有明显影响.光损伤阈值降低的主要原因在于杂质诱发缺陷导致的电子崩电离、多光子电离(尤其是双光子电离)等过程的发生.