Preparation and bio-distribution of bone tumor therapeutic radiopharmaceutical ~(153)Sm-TTHMP

TTHMP (triethylenetetraaminehexamethylenephosphonic acid) was labeled with 153Sm. The labeling condition, stability, mole ratio of 153Sm to TTHMP, rabbit bone imaging and bio-distribution of 153Sm-TTHMP in mice were investigated. The results showed that weak basie media and high concentration ligands were favorable to form 153Sm-TTHMP; labeling compounds were stable at pH 7 in 7 days. The results also indicated that the chemical mole ratio of 153Sm-TTHMP is n(153Sm) : n(TTHMP) = 1 : 1 and skeleton uptake of 153Sm-TTHMP is high((13.96±3.51)%/g at 1h post injection and (13.54±2.98)%/g at 48h post injection), while the non-target tissue uptake is relatively low, so 153Sm-TTHMP is a promising bone tumor therapeutic agent.     

Design,Synthesis and Evaluation of Novel Derivatives of Curcuminoids with Cytotoxicity

Curcumin and curcuminoids have been discussed frequently due to their promising functional groups (such as scaffolds of α,β-unsaturated β-diketone, α,β-unsaturated ketone and β′-hydroxy-α,β-unsaturated ketone connected with aromatic rings on both sides) that play an important role in various bioactivities, including antioxidant, anti-inflammatory, anti-proliferation and anticancer activity. A series of novel curcuminoid derivatives (a total of 55 new compounds) and three reference compounds were synthesized with good yields using three-step organic synthesis. The anti-proliferative activities of curcumin derivatives were examined for six human cancer cell lines: HeLaS3, KBvin, MCF-7, HepG2, NCI-H460 and NCI-H460/MX20. Compared to the IC₅₀ values of all the synthesized derivatives, most α,β-unsaturated ketones displayed potent anti-proliferative effects against all six human cancer cell lines, whereas β′-hydroxy-α,β-unsaturated ketones and α,β-unsaturated β-diketones presented moderate anti-proliferative effects. Two potent curcuminoid derivatives were found among all the novel derivatives and reference compounds: (E)-5-hydroxy-7-phenyl-1-(3,4,5-trimethoxyphenyl)hept-1-en-3-one (compound 3) and (1E,4E)-1,7-bis(3,4,5-trimethoxyphenyl)hepta-1,4-dien-3-one (compound MD12a). These were selected for further analysis after the evaluation of their anti-proliferative effects against all human cancer cell lines. The results of apoptosis assays revealed that the number of dead cells was increased in early apoptosis and late apoptosis, while cell proliferation was also decreased after applying various concentrations of (E)-5-hydroxy-7-phenyl-1-(3,4,5-trimethoxyphenyl)hept-1-en-3-one (compound 3) and (1E,4E)-1,7-bis(3,4,5-trimethoxyphenyl)hepta-1,4-dien-3-one (compound MD12a) to MCF-7 and HpeG2 cancer cells. Analysis of the gene expression arrays showed that three genes (GADD45B, SESN2 and BBC3) were correlated with the p53 pathway. From the quantitative PCR analysis, it was seen that (1E,4E)-1,7-bis(3,4,5-trimethoxyphenyl)hepta-1,4-dien-3-one (compound MD12a) effectively induced the up-regulated expression of GADD45B, leading to the suppression of MCF-7 cancer cell formation and cell death. Molecular docking analysis was used to predict and sketch the interactions of the GADD45B-α,β-unsaturated ketone complex for help in drug design.     

基于ARM的线阵CCD测量系统应用分析

介绍了一种基于LPC2106的线阵CCD测量系统,其中应用了ARM微处理器,系统主要包括：线阵CCD传感器、模数转换器、ARM微处理器、显示模块及控制电路等几部分．阐述了线阵CCD的光采集工作原理和驱动脉冲的产生原理,以及ARM芯片LPC2106的软硬件设计和系统其他模块的具体操作．     

153Sm-EDTMP与云克联合治疗转移性骨肿瘤疼痛的临床价值

为探讨^153Sm-EDTMP（^153钐－乙二胺四亚甲基膦酸）与云克（^99Tc-MDP，即^99锝－亚甲基二膦酸盐）联合治疗转移性骨肿瘤疼痛的临床价值。对210例癌骨转移患者分别为^153Sm-EDTMP单独治疗或与云克联合治疗，观察其疗效。结果显示，^153Sm-EDTMP单独治疗组，止痛有效率为83．7％，转移灶消失或缩小的总有效率为21．6％；^153Sm-EDTMP与云克静脉滴注联合治疗组，止痛有效率为94．7％，转移灶消失或缩小的总有效率为35．1％。后者明显高于单独治疗组。表明^153Sm-EDTMP联合云克静脉滴注对恶性肿瘤多发性骨转移所致疼痛有明显疗效，且安全无副作用。联合治疗组疗效优于单独治疗组。     

^60Coγ射线照射淋巴细胞诱导PIG3和GADD45基因mRNA变化

用60Coγ射线照射正常人外周血永生化淋巴细胞系后,初步分析受照细胞中PIG3和GADD45基因mRNA表达水平的改变状况,并探讨上述基因作为辐射生物剂量计的可能性及意义.用60Coγ射线照射淋巴细胞,采用不同剂量(0～10Gy)照射和照射后不同时间点(0～72h)收集细胞,抽提mRNA,用Real-time PCR检测细胞中PIG3和GADD45基因mRNA表达水平的变化.结果表明,正常人外周血永生化淋巴细胞系中PIG3和GADD45基因mRNA表达水平随照射剂量的增高而增加,并呈现出剂量效应关系.5Gy剂量60Coγ射线照射后,淋巴细胞中PIG3和GADD45基因mRNA表达水平随时间的推移不断增高,在8h时均达到最高,随后开始降低.PIG3和GADD45基因对辐射均较敏感,其表达具有良好的剂量效应和时间效应关系,但相比而言,PIG3的表达随照射剂量和照射后时间的变化更加显著,更有潜力作为生物剂量计以满足实际需要.     

Three years of monitoring of PCDD/F,DL-PCB and NDL-PCB residues in bovine milk from Lombardy and Emilia Romagna regions (Italy): Contamination levels and human exposure assessment

In the three-years period 2012–2014, 160 cow milk samples from farms located in Lombardy and Emilia Romagna regions (Italy) were analyzed during the implementation of the Italian National Residues Monitoring Plan to assess the presence of PCDD/F, DL-PCB and NDL-PCB residues. The obtained contamination data were combined with cow milk consumption data from the Italian national dietary survey to estimate PCDD/F, DL-PCB and NDL-PCB human dietary exposure through the consumption of whole, semi skimmed and skimmed bovine milk. The exposure assessment was carried out separately for children, teenagers, adults and elderly. Average contamination levels of the analyzed samples were found to be 1.26 pg WHO-TEQ/g fat for the sum of PCDD/Fs and DL-PCBs and 9.30 ng/g fat for the sum of the 6 NDL-PCB indicators. PCB 126 was found to be the main contributor to the total WHO-TEQ. Using the upper bound approach, the estimated mean dietary intakes ranged from 0.07 pg WHO-TEQ/kg bw per day to 0.39 pg WHO-TEQ/kg bw per day for the sum of PCDD/Fs and DL-PCBs and considering exposure from whole milk. NDL-PCB mean dietary intakes resulted between 0.52 ng/kg bw per day and 2.86 ng/kg bw per day for consumption of whole milk. Children and teenagers were found to be the most exposed groups. This is the first time that Italian consumers exposure to NDL-PCBs is assessed using contamination data of cow milk produced in Italy.     

天然靶制备 ~(153)Sm 照射条件研究

在重水研究堆和轻水游泳池反应堆中，对不同靶型天然丰度的１５２Ｓｍ靶照射条件进行了研究。实验结果表明：在游泳池反应堆宜于采用液体靶照射，１５３Ｓｍ的比活度比在重水研究堆中采用固体靶提高了２倍；天然钐靶照射后１５３Ｓｍ的核纯度大于９９％，满足临床治疗使用要求。     

骨肿瘤治疗药物的研究 Ⅰ.~(153)Sm及~(153)Sm-EDTMP的制备

作者用天然丰度的钐氧化物(Sm_2O_3,~(152)Sm丰度为26.7％)作靶料,在中子注量率为4×10~(13)n/cm~2·s的条件下,照射时间大于110h,可得核纯很高。比度不低于5.18GBq(140mCi)/mg Sm_2O_3的~(153)Sm。~(153)Sm与EDTMP(乙二胺四甲撑膦酸)络合条件的研究表明:在pH为8-10的范围内,沸水浴中反应30min,~(153)Sm-EDTMP产率大于98％。采用~(153)Sm示踪法测定了Sm(~(153)Sm)-EDTMP的组成,结果证明,Sm(~(153)Sm)与EDTMP络合组成为1:1。~(153)Sm-EDTMP稳定性实验结果表明:在络合物形成后的一个星期内,产率基本不变。     

配体量对~(153)Sm-HEDTMP生化性能的影响

研究了配体羟乙基乙二胺三甲撑膦酸（HEDTMP）的量对配合物^153Sm-HEDTMP的脂水分配系数、配合物与牛血清白蛋白（BSA）结合性以及配合物在羟基磷灰石（HA）上吸附性能的影响。结果表明，随着配体量的增大，配合物在正辛醇－水中的分配系数减小；与牛血清白蛋白的结合率下降；在HA上的吸附率有降低的趋势，但不明显。根据三项生化性能对^153Sm-HEDTMP在体内代谢的影响，实际应用时配体应适当过量。     

Semirational Protein Engineering of CYP153AM.aq.‐CPRBM3 for Efficient Terminal Hydroxylation of Short‐ to Long‐Chain Fatty Acids

The regioselective terminal hydroxylation of alkanes and fatty acids is of great interest in a variety of industrial applications, such as in cosmetics, in fine chemicals, and in the fragrance industry. The chemically challenging activation and oxidation of non‐activated C?H bonds can be achieved with cytochrome P450 enzymes. CYP153A_M.aq.‐CPR_BM3 is an artificial fusion construct consisting of the heme domain from Marinobacter aquaeolei and the reductase domain of CYP102A1 from Bacillus megaterium. It has the ability to hydroxylate medium‐ and long‐chain fatty acids selectively at their terminal positions. However, the activity of this interesting P450 construct needs to be improved for applications in industrial processes. For this purpose, the design of mutant libraries including two consecutive steps of mutagenesis is demonstrated. Targeted positions and residues chosen for substitution were based on semi‐rational protein design after creation of a homology model of the heme domain of CYP153A_M.aq., sequence alignments, and docking studies. Site‐directed mutagenesis was the preferred method employed to address positions within the binding pocket, whereas diversity was created with the aid of a degenerate codon for amino acids located at the substrate entrance channel. Combining the successful variants led to the identification of a double variant—G307A/S233G—that showed alterations of one position within the binding pocket and one position located in the substrate access channel. This double variant showed twofold increased activity relative to the wild type for the terminal hydroxylation of medium‐chain‐length fatty acids. This variant furthermore showed improved activity towards short‐ and long‐chain fatty acids and enhanced stability in the presence of higher concentrations of fatty acids.