Synthesis and Bio‐Evaluation of New 18F‐Labeled Pyridaben Analogs with Improved Stability for Myocardial Perfusion Imaging in Mice

To improve the stability of ¹⁸F‐labeled pyridaben analogs for myocardial perfusion imaging, three new analogs of pyridaben ([¹⁸F]FPTP2, [¹⁸F]FPTP‐P2, and [¹⁸F]FPTP‐P3) were synthesized with ‘side chain’ modifications. The radiolabeled tracers and corresponding non‐radioactive compounds were obtained by substituting tosyl group with ^18/19F. The effect of structure modification on myocardial targeting and physicochemical properties of new tracers were evaluated in vitro and in vivo. The total radiosynthesis time of these tracers was approximately 70–90 min with high decay‐corrected radiochemical yields (36–65%) and good radiochemical purity (> 98%). These lipophilic tracers exhibited obvious improved stability in water. Studies of their biodistribution in normal Kunming mice demonstrated that [¹⁸F]FPTP2 exhibited very high initial heart uptake (39.70 ± 2.81 %ID/g at 2 min after injection) and low background in the liver, blood, and soft tissues. The heart‐to‐liver, heart‐to‐lung, and heart‐to‐blood ratios were 3.59, 19.34, and 67.34 at 15 min postinjection, respectively. Favorable myocardial targeting property and remarkable improvement of stability of [¹⁸F]FPTP2 suggest that the substitution of the phenyl ‘sidechain’ with other non‐phenyl rings has no effect on the myocardial targeting property of ¹⁸F‐labeled pyridaben analogs.     

平贝碱乙的分离和鉴定

本文报道了自东北平贝母(Fritillaria ussuriensis Maxim)中分得一种新的甾体生物碱,经光谱(IR,MS,¹HNMR及¹³CNMR)解析和衍生物制备,推定其结构为5α,17β,22α-cevanine-3 β,6α,12α,14α,16β,20β-hexol,定名为平贝碱乙。     

天蚕素A截短肽在大肠埃希菌中的高效表达及活性分析

将构建好的含抗菌肽天蚕素A(cecropin A,CA)截短肽CA19(36、210)1～5倍串连体的pET-31b(+)载体进行诱导表达,其表达量比单体表达明显提高.将融合蛋白用亲和层析法将其纯化,其纯度达到90%以上.纯化融合蛋白免疫BALB/c小鼠,制备了其特异的多克隆抗体.纯化串连融合蛋白用溴化氰切割成单体检测其活性,发现均具有抑菌活性.本研究为抗菌肽的基因工程制备提供了新途径.     

樱桃叶水煎液的抗氧化及降糖作用研究

目的:观察樱桃叶水煎液对环磷酰胺所致免疫低下小鼠抗氧化能力的影响,以及对正常大鼠糖耐量及α-葡萄糖苷酶活性的抑制作用。方法:腹腔注射环磷酰胺建立小鼠免疫低下模型,测定血清中过氧化物歧化酶(SOD)、过氧化氢酶(CAT)活性及丙二醛(MDA)含量;观察樱桃叶体外对α-葡萄糖苷酶活性的抑制作用及对正常大鼠糖耐量的影响。结果:免疫低下小鼠给予樱桃叶水煎液后,血清中SOD、CAT活性明显升高,MDA含量显著降低;樱桃叶水煎液可显著抑制正常大鼠给予蔗糖后的血糖升高,体外实验中对α-葡萄糖苷酶活性具有明显抑制作用。结论:樱桃叶可增强免疫低下小鼠抗氧化能力,并且通过抑制α-葡萄糖苷酶活性而抑制餐后血糖升高。     

红芪化学成分及其抗氧化活性研究

目的对红芪化学成分及其抗氧化活性进行研究。方法采用色谱技术对红芪化学成分进行分离,利用理化性质和现代波谱技术确定化合物的结构,并应用过氧化氢损伤的SH-SY5Y细胞与野生型DJ-1基因转染的SH-SY5Y细胞模型对得到的代表性化合物进行抗氧化应激活性研究。结果从红芪中分离鉴定了6个化合物,其结构分别为大豆皂苷II甲酯（1）,大豆皂苷I（2）,芒柄花苷（3）,柚皮苷（4）,下箴桐碱（5）和色氨酸（6）。抗氧化活性实验结果表明化合物3具有较好的抗氧化作用。结论化合物4和6为首次从该属植物中分离得到,化合物3具有抗氧化应激作用。     

Curcumin: a calixarene derivative micelle potentiates anti-breast cancer stem cells effects in xenografted,triple-negative breast cancer mouse models

Triple-negative breast cancer (TNBC) is a heterogeneous and clinically aggressive disease with no approved targeted therapy. Curcumin has shown therapeutic potential against TNBC, but it shows low bioavailability and low efficacy when administered as a free drug. Here we describe a novel vehicle for in vivo delivery of curcumin based on the phosphorylated calixarene POCA4C6. Curcumin-loaded POCA4C6 micelles (CPM) were prepared using the thin-film method and they showed a unilamellar structure with an average particle size of 3.86?nm. The micelles showed high curcumin encapsulation efficiency and loading was based on liquid chromatography-tandem mass spectrometry. Studies with cell cultures suggest that CPM can sustainably release curcumin in a pH-dependent manner. The micelles efficiently inhibited proliferation, invasion, migration and tumor spheroid formation by BT-549 human breast cancer cells. These effects involved increased apoptosis and reduced levels of nuclear β-catenin and androgen receptor. After injection into tumor xenografts, CPM persisted in the tumor tissue and efficiently inhibited tumor growth without causing obvious systemic toxicity. CPM also significantly reduced levels of CD44⁺/CD133⁺ breast cancer stem cells. Our results highlight the potential of CPM as an effective therapy against TNBC.     

反义IGF—1抑制脑胶质瘤体内外增殖的实验研究

目的：明确IGF－1在肿瘤发生发展中的作用,为基因治疗优选靶的。方法：（1）转染含反义IGF－1cDNA的表达型质粒至鼠C6胶质瘤细胞,对比转染前后细胞IGF－1的表达、增殖活性等变化。（2）对Wistar大鼠－C6胶质瘤动物模型实施反义IGF－1基因治疗,对比治疗与否肿瘤大小、IGF－1表达、淋巴细胞浸润等的差别。结果：（1）含反义质粒的C6细胞系IGF－1表达减低,增殖活性下降约35％。（2）反义IGF－1治疗后的肿瘤8周内完全消失,而对照组持续增大,治疗组肿瘤的凋亡细胞、淋巴细胞浸润增加,IGF－1表达、细胞增殖活性下降,结论：反义IGF－1基因转染能有效抑制C6胶质瘤的体内外增殖,增殖活性下降和免疫系统攻击可能是双重原因。     

胆囊胆固醇沉积症患者血清瘦素、瘦素受体与血脂的相关性研究

目的 探讨胆囊胆固醇沉积症患者血清瘦素(Leptin,Lep)、可溶性瘦素受体(soluble leptin receptor,sLR)及血脂的变化及其相互关系.方法 胆囊胆固醇沉积症患者49例,对照组91例,测定其空腹血清瘦素、可溶性瘦素受体、胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白(LDL)、高密度脂蛋白(HDL),分析胆囊胆固醇沉积症患者血清Lep、sLR水平与血脂的关系.结果 胆囊胆固醇沉积症组患者血清TC、LDL和Lep值均显著高于对照组,sLR显著低于对照组,差异有统计学意义(P<0.05),单相关分析显示Lep与TC、TG呈正相关.结论 胆囊胆固醇沉积症患者血清瘦素水平与血脂异常有相关性.     

GJB2相关非综合征性感音神经性聋人工耳蜗植入后的疗效观察

目的：评价携带GJB2基因突变的儿童人工耳蜗植入后的疗效。方法：对40例携带GJB2基因突变的人工耳蜗植入患儿进行疗效评估,测试内容包括：声场助听听阈测试、（婴幼儿）有意义听觉整合量表、听觉行为分级标准评分、言语可懂度分级标准评分及普通话早期言语感知测试。以80例未检出已知热点突变者为对照组。结果：携带GJB2基因突变的患儿术后声场助听听阈优于对照组,其余测试与对照组比较差异无统计学意义（P〉0．05）。结论：携带GJB2基因突变的非综合征性感音神经性聋患儿适于行人工耳蜗植人手术,术后效果满意。     

K252a对腺样囊性癌培养中许旺细胞生长的阻断作用

目的观察并探讨K252a在体外坐骨神经长出的许旺细胞对腺样囊性癌细胞趋化生长中的影响。方法采用细胞培养技术,将经神经营养素的高亲和受体Trk特异性阻断剂K252a预处理的小鼠坐骨神经与腺样囊性癌细胞共培养（设24组）,以正常小鼠坐骨神经与腺样囊性癌细胞共培养为对照组（设24组）;结果与对照组相比,经K252a预处理的坐骨神经与腺样囊性癌细胞共培养长出的许旺细胞增生组数及趋化性生长组数X^2值分别为14．03、26．32,P值均小于0．025,说明两组之间的差异非常显著,许旺细胞丧失趋化性及细胞增生未被促进。结论K252a在许旺细胞对腺样囊性癌细胞趋化生长中的阻断作用间接地表明神经营养素可促进许旺细胞增生及向腺样囊性癌细胞趋化迁移,这可能是腺样囊性癌嗜神经性重要机制之一。