Polymeric micelles with glycolipid-like structure and multiple hydrophobic domains for mediating molecular target delivery of paclitaxel

Herein, polymeric micelles with glycolipid-like structure and about 40 nm diameter are prepared by self-aggregation from stearate-grafted chitosan oligosaccharides in aqueous medium. The micelles, with high degree of substitution (DS), present specific spatial structure with multiple hydrophobic "minor cores", and thus obtain excellent internalization into cancer cells and accumulation in cytoplasm. Furthermore, the micelles showed pH-sensitive properties, thus favoring intracellular delivery of encapsulated drug via endocytosis. The cell cytotoxicity of paclitaxel encapsulated in micelles was improved sharply and contributed to the increased intracellular delivery of the drug. The present micelles are a promising carrier candidate for targeting therapy of antitumor drugs with a cytoplasmic molecule target.     

Reconstruction of lignin and hemicelluloses by aqueous ethanol anti‐solvents to improve the ionic liquid‐acid pretreatment performance of Arundo donax Linn

Ionic liquid (IL)‐acid pretreatment is known to not only enhance the enzymatic hydrolysis efficiency of lignocellulose but also to generate deposits on the surface of fiber by conventional water regeneration, which retard the increment. In this study, ethanol aqueous solution regeneration was developed as a new method to change the substrates characteristics for IL‐acid pretreatment and their effects on the enzymatic hydrolysis were evaluated. Following the IL‐acid reaction, the biomass slurry was subjected to ethanol aqueous solution at various concentration. Results indicated that anti‐solvent choice significantly influenced the reconstruction of both hemicelluloses and lignin as a result of the competition between water and ethanol. The partial removal of hemicelluloses and suitable lignin re‐localization contributed to a more porous structure. Consequently, the cellulose digestibility of aqueous ethanol regenerated samples was dramatically enhanced to ～100% and approximately 11‐ and 2‐fold higher than that of untreated and conventional water regenerated pretreated samples, respectively. A giant leap in the initial rate of enzymatic hydrolysis was also detected in 50% ethanol aqueous solution regenerated samples and only about 10 hr was needed to convert 80% of cellulose to glucose due to the appearance of cellulose II hydrate‐like and more porous structure.     

新型染料木素磺酸酯的前药判定与大鼠体内生物利用度

为寻找染料木素(GE)新的前药,采用建立的生物样品中药物浓度测定的液相色谱法对新型大豆异黄酮染料木素磺酸酯(GB)进行前药判定以及大鼠体内药物动力学研究,以考察前药中染料木素的口服生物利用度是否改善.在大鼠体内药物代谢实验中,灌胃给予GB的大鼠血浆中能检测到明显的GE.在临床前药物动力学实验中,该前体静注给药和以40 mg/kg灌胃药后,GE在大鼠体内的动力学过程均符合一室模型.GB中GE的相对口服生物利用度为原药的110.9％.研究表明,相对于原药GE,前药中GE的相对口服生物利用度达到预期的改善,该前药有进一步研究意义.     

Polymorphisms of 5,10-methylenetetralydrofolate reductase (MTHFR), fruit and vegetable intake, and the risk of stomach cancer

Stomach cancer is a serious public health problem in China. 5,10-Methylenetetralydrofolate reductase (MTHFR) may be involved in both DNA methylation and DNA synthesis. Folate deficiency is associated with cancer risk that may be modulated by a genetic variation in the MTHFR gene in folate metabolism. The main goal of this study was to evaluate the association between polymorphisms of the MTHFR gene and the risk of stomach cancer. This study also explored the modification effects of fruit and vegetable intake (one of the main constituents is folate) on the risk of this disease. A population-based case-control study was conducted in Taixing, China, consisting of 206 newly diagnosed cases with primary stomach cancer and 415 healthy population controls. Polymorphisms of MTHFR C677T and A1298C were assayed by polymerase chain reaction-restricted fragment length polymorphism (PCR-RFLP) techniques. The data were analysed using the logistic regression model. No obvious association between the MTHFR A1298C polymorphism and the risk of stomach cancer was observed in this study. The frequencies of 677 C/C, C/T, and T/T were 34.5, 50.9, and 14.6%, respectively, in controls. The frequency of the MTHFR 677 wild homozygotic genotype was 25.8% in cases, which was lower than that in controls (34.5%). The adjusted odds ratio (OR) for the MTHFR 677 any T genotype was 2.05 (95% confidence interval (CI), 1.26-3.34) when compared with the C/C genotype. In the low fruit and vegetable intake group an increasing trend was observed with the T allele exposure, p=0.0056. The adjusted ORs were 1.68 (95% CI = 0.86-3.29) for the C/T genotype and 3.58 (95% CI = 1.46-8.75) for the T/T genotype, respectively. The MTHFR 677 any T genotype was associated with an increased risk of primary stomach cancer among the Chinese population. Folate deficiency might modify the MTHFR gene polymorphism and influence the risk of stomach cancer.     

元谋干热河谷生态恢复区昆虫多样性研究

以元谋退化生态系统初始生态恢复中人工构建植被为研究对象,在样地调查的基础上,对比分析了退化生态系统和恢复生态系统昆虫群落多样性组成与结构的恢复状况及其对人工群落类型的生态响应。结果表明,植物群落组成是影响昆虫群落多样性的关键因子。与天然植被相比,混交林促进了昆虫在退化地的扩散和定居,物种多样性明显增加。主成分分析排序将6种生境分为两大类:第Ⅰ类为赤桉纯林,代表物种单一、林下空旷、环境干燥为特点的植被;第Ⅱ类为扭黄茅草坡、车桑子灌丛及赤桉 银合欢、赤桉 相思、相思 银合欢3种混交林,代表物种相对复杂,生境偏向湿润的植被。不同生境的特有昆虫和优势昆虫种类和数量分析表明,在3种混交林中,相思 合欢恢复的效果较赤桉 相思与赤桉 合欢显著,是最好的先锋群落植物混交模式,能够较快改良生境,提高其物种多样性。但由于造林面积较小,植被恢复时间短,受人为干扰较大,昆虫多样性恢复的效果还不明显。     

Effect of TLR4/MyD88/NF‐kB axis in paraventricular nucleus on ventricular arrhythmias induced by sympathetic hyperexcitation in post‐myocardial infarction rats

Sympathetic activation after myocardial infarction (MI) leads to ventricular arrhythmias (VAs), which can result in sudden cardiac death (SCD). The toll‐like receptor 4 (TLR4)/myeloid differentiation primary response 88 (MyD88)/nuclear factor‐kappa B (NF‐kB) axis within the hypothalamic paraventricular nucleus (PVN), a cardiac‐neural sympathetic nerve centre, plays an important role in causing VAs. An MI rat model and a PVN‐TLR4 knockdown model were constructed. The levels of protein were detected by Western blotting and immunofluorescence, and localizations were visualized by multiple immunofluorescence staining. Central and peripheral sympathetic activation was visualized by immunohistochemistry for c‐fos protein, renal sympathetic nerve activity (RSNA) measurement, heart rate variability (HRV) analysis and norepinephrine (NE) level detection in serum and myocardial tissue measured by ELISA. The arrhythmia scores were measured by programmed electrical stimulation (PES), and cardiac function was detected by the pressure–volume loop (P‐V loop). The levels of TLR4 and MyD88 and the nuclear translocation of NF‐kB within the PVN were increased after MI, while sympathetic activation and arrhythmia scores were increased and cardiac function was decreased. However, inhibition of TLR4 significantly reversed these conditions. PVN‐mediated sympathetic activation via the TLR4/MyD88/NF‐kB axis ultimately leads to the development of VAs after MI.     

Identification,Design and Bio-Evaluation of Novel Hsp90 Inhibitors by Ligand-Based Virtual Screening

Heat shock protein 90 (Hsp90), whose inhibitors have shown promising activity in clinical trials, is an attractive anticancer target. In this work, we first explored the significant pharmacophore features needed for Hsp90 inhibitors by generating a 3D-QSAR pharmacophore model. It was then used to virtually screen the SPECS databases, identifying 17 hits. Compound S1 and S13 exhibited the most potent inhibitory activity against Hsp90, with IC₅₀ value 1.61±0.28 μM and 2.83±0.67 μM, respectively. Binding patterns analysis of the two compounds with Hsp90 revealed reasonable interaction modes. Further evaluation showed that the compounds exhibited good anti-proliferative effects against a series of cancer cell lines with high expression level of Hsp90. Meanwhile, S13 induced cell apoptosis in a dose-dependent manner in different cell lines. Based on the consideration of binding affinities, physicochemical properties and toxicities, 24 derivatives of S13 were designed, leading to the more promising compound S40, which deserves further optimization.     

Cardiac telocytes exist in the adult Xenopus tropicalis heart

Recent research has revealed that cardiac telocytes (CTs) play an important role in cardiac physiopathology and the regeneration of injured myocardium. Recently, we reported that the adult Xenopus tropicalis heart can regenerate perfectly in a nearly scar‐free manner after injury via apical resection. However, whether telocytes exist in the X tropicalis heart and are affected in the regeneration of injured X tropicalis myocardium is still unknown. The present ultrastructural and immunofluorescent double staining results clearly showed that CTs exist in the X tropicalis myocardium. CTs in the X tropicalis myocardium were mainly twined around the surface of cardiomyocyte trabeculae and linked via nanocontacts between the ends of the telopodes, forming a three‐dimensional network. CTs might play a role in the regeneration of injured myocardium.