Synthesis of 4'-hydroxy-3'-piperidinomethylchalcone derivatives and their cytotoxicity against PC-3 cell lines

A new series of mono Mannich bases of 4'-hydroxychalcones 2a-e carrying a variety of aryl groups was synthesized and the in vitro cytotoxic activities of the new compounds were screened against PC-3 cell lines. Bioactivities of 2a-e, which are reported for the first time in this study, were compared against their precursor 4'-hydroxychalcones 1a-e. Compound 2b was found to be the most potent (IC(50 )= 3.7 microM) among the compounds synthesized. In addition, the compounds 1a-c and 2d showed moderate cytotoxicity. Incorporation of the 3'-piperidinomethyl group in 1b and 1d raised the potency by 1.68 and 2.19 times respectively and, therefore, seemed to be a noteworthy molecular modification. Correlations were noted between cytotoxicity and one or more physiochemical constants of the aryl ring as well as log P values for the compounds 2a-e. The significant improvement of cytotoxicity of 2b, 2d, and 2e against PC-3 cell lines compared with their chalcone precursors suggests that the incorporation of a piperidinomethyl group is a useful molecular modification and further development of these compounds as candidate cytotoxic agents may be warranted.     

Cadmium and T cell differentiation: limited impact in vivo but significant toxicity in fetal thymus organ culture

DNA lesions, including oxydated bases, nucleotide damage and double strand breaks, are continuously produced in living cells and represent a threat for genetic stability. Highly conserved repair processes have evolved to maintain DNA integrity. Cadmium (Cd) is an environmental carcinogenic pollutant known to inactivate several proteins involved in DNA repair systems while at the same time creating an oxidative stress that can result in additional DNA lesions. Cd also has potent immunotoxic effects. DNA repair by non-homologous end joining (NHEJ) is absolutely required for T lymphocyte differentiation. In this study, we examined the impact of Cd on non-homologous end joining pathway by analyzing T cell development in the thymus of mice that received Cd-supplemented drinking water. In vivo, the absence of major alteration indicates that Cd does not affect NHEJ, despite its accumulation in the thymus. Cd contamination affects only a discrete population of developing thymocytes. However, these cells are functional as the cellular response observed in mice following gamma-radiation exposure is identical in treated and control mice. Furthermore, Cd diet did not perturb the redox status in thymocytes and more importantly did not generate significant DNA lesions in organs that accumulate the highest concentration of Cd. Our results show that in vivo, Cd does not affect NHEJ or base and nucleotide repair, and that Cd toxicity to T cells is rather linked to cell cycle perturbations.     

建立GMP教学基地培养应用人才

以药事管理学教学和教学实践为主线,以药品质量管理规范教学实习基地为活动场地,以研究性主题设计为活动内容,使学生认知社会,认知药事组织,认知自我,找准自我定位,培养社会需要的应用型人才。     

气相色谱高温液晶固定液的合成和性能研究——Ⅲ.双-(对烷氧基苄叉)-4,4''-二氨基二苯乙烷薛夫碱类液晶

合成了十种文题所述液晶,其通式为: (其中R为CH_3、C_2H_5……C_(10)H_(21)) 测定了它们的元素分析、红外光谱、液晶相态和温度范围。应用为高温液晶固定液,对蒽油的组分分析和蒽、菲的分离,已取得较好结果。     

含 2-取代-1,3-二硫杂环戊烷席夫碱大环化合物的合成及其抑菌活性研究

目的 开发新型抗菌药物。方法 以不同的β-二酮、二硫化碳、1,2-二溴乙烷等为原料合成含2-取代-1,3-二硫杂环戊烷大环席夫碱化合物,并进行初步抑菌活性研究。结果 合成得到的中间体(Ⅰa~Ⅰc)及目标席夫碱大环化合物(Ⅱa~Ⅱc)经元素分析、红外光谱、1H-NMR、MS等手段进行了结构表征。合成的席夫碱大环化合物抑菌能力优越。结论 本试验合成了含2-取代-1,3-二硫杂环戊烷大环席夫碱化合物,其具有更加优越的抑菌能力。     

Tailor-made release triggering from hot-melt extruded complexes of basic polyelectrolyte and poorly water-soluble drugs

The aim of the study was the formulation of polyelectrolyte complexes composed of poorly water-soluble acid drugs and basic polymethacrylates by hot-melt extrusion enabling a tailor-made release pattern by the addition of inorganic salts. The influence of different electrolytes was analyzed at varying conditions in order to control drug delivery from the complexes. Poorly water-soluble model drugs naproxen and furosemide were applied in their non-ionic form.After hot-melt extrusion of the naproxen-polymethacrylate powder blend, XRPD and DSC measurements indicated the formation of a single-phase amorphous system. Milled extrudates were stable under storage at long-term and intermediate conditions. Polyelectrolyte complex formation by an acid–base reaction during hot-melt extrusion could be proven by the lack of vibrations of dimethylamino and carboxylic groups by FT-IR and Raman spectroscopy. The complexes did not dissolve in demineralized water. Drug release could be immediately induced by addition of neutral electrolytes. Tailor-made dissolution profiles were realized by controlled electrolyte triggering. Maximal effects were achieved by concentrations of 0.05–0.15 M NaCl. Different anions of alkali halogenides revealed variant magnitudes of the effect depending on the anion radius. Polyelectrolyte complex formation and dissolution principles were also confirmed for furosemide.     

B淋巴瘤6号染色体微卫星不稳定性及杂合性缺失

目的:探讨6号染色体微卫星不稳定性(microsatelliteinstability,MSI)及杂合性缺失(lossofheterozygosity,LOH),碱基错配修复系统GTBP和hMLH1基因蛋白在B细胞淋巴瘤(Bcellnonhodgkin’slymphoma,BNHL)发生学上的意义。方法:选取6号染色体上7对多态微卫星标记,结合PCR及银染技术,采用凝胶成像图象分析系统,分别检测58例BNHL染色体微卫星MSI及LOH。对其中23例BNHL细胞进行EnVinsion法检测MMR的功能基因GTBP、hMLH1的表达情况。结果:弥漫性大B细胞淋巴瘤(diffuselargeBcelllymphoma,DLBCL)与滤泡性淋巴瘤(follicularlymphoma,FL)中GTBP和hMLH1蛋白表达差异无统计学意义,P值分别为0.98和1.30。原发生于淋巴结内与淋巴结外的GTBP、hMLH1蛋白表达差异无统计学意义,P值分别为0.54和0.67。GTBP蛋白在高、低度恶性表达之间差异无统计学意义,P=1.00;而hMLH1蛋白表达在低度恶性较高度恶性高,P=0.99。在位点D6S275MSI的发生率为7.5%(4/53),其中包括DLBCL2例,FL和BCLL/SLL各1例,LOH总的发生率达66.0%(35/53),其中包括DLBCL19例(19/21,90.5%),FL8例(8/13,61.5%),BCLL/SLL8例(8/19,42.1%),DLBCL的LOH率同BCLL/SLL和FL相比,差异有统计学意义,P=10.60。结论:hMLH1和GTBP错配修复基因蛋白表达与BNHL组织学类型、肿瘤的发生部位可能无关系。位点D6S275可能存在一个抑癌基因,该基因的缺失以及与错配修复基因hMLH1突变的关系对B细胞淋巴瘤的发生作用有待进一步研究。     

DNA Sequence Copy Number Aberrations Associated with Histological Subtypes and DNA Ploidy in Gastric Carcinoma

We have analyzed DNA sequence copy number aberrations (DSCNAs) and DNA ploidy by using comparative genomic hybridization and laser scanning cytometer in gastric carcinomas (GCs) to elucidate the genomic aberrations in relation to clinicopathological parameters. Thirty-two out of 33 cases showed one or more DSCNAs with a mean number of 11.7 per tumor. High-level gains were detected at 2p, 3q, 6p, 7p, 7q, 8q, 12p, 13q, 19q, and 20q. Frequency of gross genomic abnormalities and chromosome regions that have genomic aberrations were similar in both intestinal-and diffuse-type GCs, except aberrations at 8p, 9p, 12q, and 20q. The overall number of DSCNAs was significantly greater in DNA aneuploid tumors than that in DNA diploid tumors. We detected genomic aberrations characterized by histological subtype, tumor location, and DNA ploidy status: gain of 20q and losses of 8p and 9p in intestinal-type GCs, gains of 8p and 12q in diffuse-type GCs, gain of 20q in the lower third GCs, and loss of 5q, 9p, lOq, 16q, and 18q in DNA aneuploid GCs. Furthermore, 5q loss is associated with DNA aneuploidy ( P =0.0001) or the total number of losses ( P =0.001), gain+losses ( P =0.004), and high-level gains ( P =0.001) in GCs. Among these loci, chromosome 8p was unique. Gain of 8p was more common in diffuse-type GC, whereas loss of 8p was more frequently detected in intestinal-type GC. In conclusion, we describe chromosomal regions of 5q, 8p, and 20q, which are of interest for further investigation of GCs.     

Mutational Signature Analysis Reveals NTHL1 Deficiency to Cause a Multi-tumor Phenotype

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颅中窝底骨折并发面神经损伤15例分析

目的：分析面神经损伤的临床特点及受伤机制,探讨治疗方法。方法：对2006年1月～2010年1月收治的15例颅中窝底骨折并面神经损伤患者进行回顾性分析。结果：采用非手术综合性治疗,入院3周内完全恢复9例,3周～1个月完全恢复2例,不完全恢复3例,1例转院手术治疗。随访6个月,12例（80.0%）完全恢复,2例（13.3%）部分恢复,1例（6.7%）效果差。结论：在及时处理合并伤的基础上,尽早应用药物减轻局部水肿和创伤反应,改善神经代谢及血管供血,并结合针灸、理疗,是促进神经功能恢复的关键因素。