Design,synthesis and antithrombotic evaluation of novel dabigatran prodrugs containing methyl ferulate

A novel series of prodrugs containing dabigatran and methyl (E)-3-(4-hydroxy-2-methoxyphenyl)propenoate (methyl ferulate) were synthesized. All of them reveal the effect of thrombin-induced anti-platelet aggregation in vitro. In addition, in vivo experiment shows that one of the target compounds, X-2 (ED₅₀ = 3.7 ± 1.0 μmol/kg) possesses a more potent activity for inhibiting venous thrombosis than that of dabigatran etexilate (ED₅₀ = 7.8 ± 1.5 μmol/kg).     

Discovery of natural estrogen receptor modulators with structure-based virtual screening

Eleven compounds were identified as estrogen receptor modulators from an in-house natural product database (NPD) by structure-based virtual screening for ERα and ERβ. Among them, 3 compounds were confirmed as ER agonists and 8 compounds were confirmed as ER antagonists by yeast two-hybrid (Y2H) assay, with EC₅₀ values ranging from several micromolar to 100 micromolar. In this study, a novel series of cycloartane triterpenoids isolated from Schisandra glaucescens Diels was found to have ER antagonistic effect, the most potent antagonist of which exhibited activity with EC₅₀ value of 2.55 and 4.68 μM for ERα and ERβ, respectively. Moreover, the types of modulation and subtype selectivity were also investigated through molecular docking simulation.     

山东省大学生生物化学实验技能大赛选题分析

通过分析山东省大学生生物化学实验技能大赛两届获奖课题的特点,找出目前大学生在该项竞赛选题中展现出来的不足,对大学生今后在此类实验技能比赛中的选题方向及方法提出了建议。     

A retrospective analysis of 140 patients with giant cell tumor in the extremity: A multicenter study based on four hospitals in South China

Background: Update reports are rarely available regarding the bone giant cell tumors (GCTs) in the extremity in Chinese people. The aim of this study was to review the epidemiological characteristics of bone GCT in the extremity based on the clinical data from four hospitals in South China. Methods: We searched medical electronic records from January 2001 to December 2011 in four hospitals in South China to identify patients with definite diagnosis of extremity GCT. Epidemiological data including gender, tumor site, age at the time of first diagnosis, local recurrence and pulmonary metastasis were collected and analyzed statistically. Differences between-genders were particularly analyzed regarding first diagnosis age, tumor site, local recurrence and pulmonary metastasis. T-test and Chi-square test were used for continuous and dichotomous variables, respectively. Results: A total of 140 GCT patients (87 males and 53 females) were identified. The gender ratio was 1.64 for a male predominance. GCTs were mostly located around the knee (67 cases). 92 patients were in their 20s to 40s upon first diagnosis. The average age at the time of first diagnosis for all was 30.49 years, 30.76 years for males and 30.06 years for females (P = 0.757). GCT recurred locally in 50 patients (26 males and 24 females) with no gender difference (P = 0.065). The average interval from first surgery to local recurrence was 21.42 months. Pulmonary metastasis was found in 11 patients (8 males and 3 females) also with no gender difference (P = 0.667). The average interval from first diagnosis to metastasis was 36.45 months. Conclusions: Extremity GCT may have a male predominance in Chinese population and mostly occur at 20–40 years of age and around the knee. Follow-ups for GCT patients should be carried on for at least 3 years after primary surgery according to the average intervals for possible local recurrence and pulmonary metastasis.     

CD138免疫磁珠细胞分选的FISH技术在多发性骨髓瘤诊断中的应用

为了分析CD138免疫磁珠细胞分选的染色体荧光原位杂交(FISH)技术在提高多发性骨髓瘤(MM)细胞遗传学异常检测敏感性的作用。本研究选取我院收治的30例确诊MM的患者为研究对象,分离骨髓单个核细胞,应用探针组合,同时采用2种方法进行细胞遗传学检测:实验组采用CD138免疫磁珠分选浆细胞后行荧光原位杂交技术(MACS-FISH)检测;对照组直接荧光原位杂交技术(D-FISH)检测。结果:30例MM患者,实验组采用CD138 MACS-FISH检出率为83.3%,对照组D-FISH法细胞遗传异常检出率为46.7%,两组差异具有统计学意义(p<0.05)。研究结果表明:分析不同类型的细胞遗传异常,MACS-FISH法1q21检出率为46.7%,RB1检出率为50.0%,Ig H检出率为70.0%,P53检出率为20.0%;D-FISH法检出率分别为23.3%,30.0%、36.7%、10.0%。通过细胞核型分析,30例MM患者中,发现5例患者为异常核型,仅为16.7%,其中1例患者为单一结构异常,复杂异常核型患者为4例。我们的研究结论表明:进行CD138免疫磁珠分选浆细胞的FISH技术在多发性骨髓瘤诊断应用中可显著提高细胞遗传学异常检测敏感性,具有临床推广应用的价值。     

Visualization and Characterization of High-Order Chromatin Fibers under Light Microscope during Interphase and Mitotic Stages in Plants

Using genomic in situ hybridization with genomic DNA, high-order chromatin fibers were successfully exhibited under a light microscope through the cell cycle in barley, rice, maize and field bean. From the interphase to prophase and metaphase of mitosis, the fibers were basically similar. Each was estimated to be around 200 nm in diameter, but the strength of signals was not the same along the fiber length. Through the cell cycle a series of dynamic distribution changes occurred in the fibers. In the interphase, they were unraveled. At the early prophase they were arranged with parallel and mirror symmetry. During late-prophase and metaphase, the fibers were bundled and became different visible chromosomes. The parallel coiling and mirror symmetry structures were visible clearly until the metaphase. In anaphase they disappeared. During telophase, in peripheral regions of congregated chromosome group, borderlines of the chromosomes disappeared and the fibers were unraveled. This demonstrated that mitotic chromosomes are assembled and organized by parallel and adjacent coiling of the fibers and the fibers should be the highest order structure for DNA coiling.