嵌段共聚物聚乙二醇-聚苹果酸苄基酯载药胶束的制备及性质研究

目的：为构建聚合物胶束药物运载体系,制备嵌段共聚物聚乙二醇-聚苹果酸苄基酯载药胶束并测定其性质。方法：以L-天冬氨酸为原料,重氮化、环化后经开环聚合得到聚苹果酸苄基酯。氨基聚乙二醇通过酰胺键连接到β-聚苹果酸苄基酯上形成两亲性嵌段共聚物,喜树碱做药物模型制备载药胶束。动态光散射法测定胶束粒径、评价胶束稳定性,高效液相法测定喜树碱载药率和包封率,芘荧光法与动态光散射法测定临界胶束浓度。结果：喜树碱包封率72%,载药率6%,临界胶束浓度为40μg.mL-1。随着聚苹果酸苄基酯分子量减小,胶束稳定性增强。结论：聚乙二醇-聚苹果酸苄基酯在疏水链/亲水链分子量比值为2-4时在水中可自组装形成纳米胶束,可作为性能优良的聚合物药物载体。     

A study on early tolerance of Mactra chinensis philippi to salinity

In order to evaluate the early tolerance of Mactra chinensis to salinity, the treatments of salinity gradients and salinity gradual changes were set in this study, and the post growth and development of juveniles were analyzed in recovery experiment, respectively. The result showed that the optimum hatching of zygotes was found at a salinity from 24 to 32, which is narrower than that of larvae (20–32); a slight of low salinity (16–32) will benefit the early growth and development of M. chinensis; at planktonic and creeping stages, low salinity stress (20) was conducive to promoting the growth of juvenile M. chinensis philippi; 4, 48 was the ultimate salinity of M. chinensis; The range of early tolerance of larvae M. chinensis philippi to salinity can be widened through a short period of salinity acclimation.     

Ring A rearranged limonoids from the fruits of Aphanamixis grandifolia and their cytotoxicity evaluation

Two new limonoids aphanamolides C (1) and D (2), together with two known limonoids aphanamolide A (3) and aphapolynin A (4), were isolated from the fruits of Aphanamixis grandifolia. Their structures were assigned on the basis of spectroscopic data, with the absolute configurations of 1 and 2 being established by electronic circular dichroism (ECD) spectroscopic analyses. Those limonoids varied in the ring A: aphanamolide C featured two oxygenated bridges, and aphanamolide D was the second example containing β-hydroxy-α,β:γ,δ-dienoate moiety. The cytotoxic activities were also evaluated in vitro against four human cancer cell lines (MCF-7, A549, SMMC-7721, and HL-60).     

Cyanine 5.5 Conjugated Nanobubbles as a Tumor Selective Contrast Agent for Dual Ultrasound-Fluorescence Imaging in a Mouse Model

Nanobubbles and microbubbles are non-invasive ultrasound imaging contrast agents that may potentially enhance diagnosis of tumors. However, to date, both nanobubbles and microbubbles display poor in vivo tumor-selectivity over non-targeted organs such as liver. We report here cyanine 5.5 conjugated nanobubbles (cy5.5-nanobubbles) of a biocompatible chitosan–vitamin C lipid system as a dual ultrasound-fluorescence contrast agent that achieved tumor-selective imaging in a mouse tumor model. Cy5.5-nanobubble suspension contained single bubble spheres and clusters of bubble spheres with the size ranging between 400–800 nm. In the in vivo mouse study, enhancement of ultrasound signals at tumor site was found to persist over 2 h while tumor-selective fluorescence emission was persistently observed over 24 h with intravenous injection of cy5.5-nanobubbles. In vitro cell study indicated that cy5.5-flurescence dye was able to accumulate in cancer cells due to the unique conjugated nanobubble structure. Further in vivo fluorescence study suggested that cy5.5-nanobubbles were mainly located at tumor site and in the bladder of mice. Subsequent analysis confirmed that accumulation of high fluorescence was present at the intact subcutaneous tumor site and in isolated tumor tissue but not in liver tissue post intravenous injection of cy5.5-nanobubbles. All these results led to the conclusion that cy5.5-nanobubbles with unique crosslinked chitosan–vitamin C lipid system have achieved tumor-selective imaging in vivo.     

Tyrosylprotein Sulfotransferase-1 and Tyrosine Sulfation of Chemokine Receptor 4 Are Induced by Epstein-Barr Virus Encoded Latent Membrane Protein 1 and Associated with the Metastatic Potential of Human Nasopharyngeal Carcinoma

The latent membrane protein 1 (LMP1), which is encoded by the Epstein-Barr virus (EBV), is an important oncogenic protein that is closely related to carcinogenesis and metastasis of nasopharyngeal carcinoma (NPC), a prevalent cancer in China. We previously reported that the expression of the functional chemokine receptor CXCR4 is associated with human NPC metastasis. In this study, we show that LMP1 induces tyrosine sulfation of CXCR4 through tyrosylprotein sulfotransferase-1 (TPST-1), an enzyme that is responsible for catalysis of tyrosine sulfation in vivo, which is likely to contribute to the highly metastatic character of NPC. LMP1 could induce tyrosine sulfation of CXCR4 and its associated cell motility and invasiveness in a NPC cell culture model. In contrast, the expression of TPST-1 small interfering RNA reversed LMP1-induced tyrosine sulfation of CXCR4. LMP1 conveys signals through the epidermal growth factor receptor (EGFR) pathway, and EGFR-targeted siRNA inhibited the induction of TPST-1 by LMP1. We used a ChIP assay to show that EGFR could bind to the TPST-1 promoter in vivo under the control of LMP1. A reporter gene assay indicated that the activity of the TPST-1 promoter could be suppressed by deleting the binding site between EGFR and TPST-1. Finally, in human NPC tissues, the expression of TPST-1 and LMP1 was directly correlated and clinically, the expression of TPST-1 was associated with metastasis. These results suggest the up-regulation of TPST-1 and tyrosine sulfation of CXCR4 by LMP1 might be a potential mechanism contributing to NPC metastasis.     

A New Molecular Phylogeny and a New Genus,Pendulorchis, of the Aerides–Vanda Alliance (Orchidaceae: Epidendroideae)

Background

The Aerides–Vanda alliance is a complex group in the subtribe Aeridinae (subfamily Epidendroideae, Orchidaceae). Some phylogenetic systems of this alliance have been previously proposed based on molecular and morphological analyses. However, several taxonomic problems within this alliance as well as between it and its allies remain unsolved.

Methodology/Principal Findings

We utilized ITS and five plastid DNA regions in this phylogenetic analysis. Consensus trees strongly indicate that the Aerides–Vanda alliance is monophyletic, and the 14 genera of this alliance can be grouped into the following clades with 14 subclades: 1. Aerides, comprising two subclades: Rhynchostylis and Aerides; 2. Ascocentropsis; 3. Papilionanthe; 4. Vanda, comprising five subclades: Neofinetia, Christensonia, Seidenfadenia, Ascocentrum, and Vanda–Trudelia, in which Vanda and Trudelia form a subclade; 5. Tsiorchis, comprising three subclades: Chenorchis, Tsiorchis, and two species of Ascocentrum; 6. Paraholcoglossum; and 7. Holcoglossum. Among the 14 genera, only Ascocentrum is triphyletic: two species of the Ascocentrum subclade, an independent subclade Ascocentrum subclade in the Tsiorchis clade; the Ascocentrum subclade in the Vanda clade; and one species in the Holcoglossum clade. The Vanda and Trudelia species belong to the same subclade. The molecular conclusion is consistent with their morphological characteristics.

Conclusions

We elucidate the relationship among the 14 genera of the Aerides–Vanda alliance. Our phylogenetic results reveal that the Aerides–Vanda alliance is monophyletic, but it can be divided into 14 genera. The data prove that Ascocentrum is triphyletic. Plants with elongate-terete leaves and small flowers should be treated as a new genus, Pendulorchis. Saccolabium himalaicum (Ascocentrum himalaicum) should be transferred to Pendulorchis. Ascocentrum pumilum, endemic to Taiwan, should be transferred to Holcoglossum. A new combination, Holcoglossum pumilum, was also established. Trudelia should not be recognized as an independent genus. Two new species, Pendulorchis gaoligongensis and Holcoglossum singchianum, were described as well.     

Artemether Combined with shRNA Interference of Vascular Cell Adhesion Molecule-1 Significantly Inhibited the Malignant Biological Behavior of Human Glioma Cells

Artemether is the derivative extracted from Chinese traditional herb and originally used for malaria. Artemether also has potential therapeutic effects against tumors. Vascular cell adhesion molecule-1 (VCAM-1) is an important cell surface adhesion molecule associated with malignancy of gliomas. In this work, we investigated the role and mechanism of artemether combined with shRNA interference of VCAM-1 (shRNA-VCAM-1) on the migration, invasion and apoptosis of glioma cells. U87 human glioma cells were treated with artemether at various concentrations and shRNA interfering technology was employed to silence the expression of VCAM-1. Cell viability, migration, invasiveness and apoptosis were assessed with MTT, wound healing, Transwell and Annexin V-FITC/PI staining. The expression of matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9) and phosphorylated Akt (p-Akt) was checked by Western blot assay. Results showed that artemether and shRNA-VCAM-1 not only significantly inhibited the migration, invasiveness and expression of MMP-2/9 and p-Akt, but also promoted the apoptosis of U87 cells. Combined treatment of both displayed the maximum inhibitory effects on the malignant biological behavior of glioma cells. Our work revealed the potential therapeutic effects of artemether and antiVCAM-1 in the treatments of gliomas.