Tobacco Smoke Hemoglobin Adducts in Maternal and Fetal Blood

The maternal-fetal exchange of the potent tobacco related human carcinogen, 4-aminobiphenyl, was studied in women smokers during pregnancy. Maternal and fetal blood samples were classified as coming from nonsmokers (n=74), individuals smoking less than 1 pack of cigarettes per day (n=16), individuals smoking 1 pack of cigarettes per day (n=19), individuals smoking 1–2 packs of cigarettes per day (n=19), and individuals smoking greater than 2 packs of cigarettes per day (n=20). 4-Aminobiphenyl was extracted from both maternal and fetal blood samples using organic extractions and the released amine was qualitatively and quantitatively characterized by analysis of the samples by gas chromatographic and mass spectrometric analysis. Increasing levels of 4-aminobiphenyl - hemoglobin adducts were found as the smoking status of the women increased ranging from 144 ± 22.2 (<1 pack per day) to 633 ± 87.9 (>2 packs per day). A corresponding increase in the presence of fetal 4-aminobiphenyl hemoglobin adducts was also detected (74.3 ± 17.8; <1 pack/day to 319 ± 50.5; >2 packs/day).     

促红素对人血小板活动度与血红蛋白水平的影响

目的 观察促红素(EPO)对人血小板活动度和血红蛋白水平的影响。方法 采用随机、对照、双盲法将30名健康男性志愿者分为3组;静脉注射EPO100U/kg、静脉注射EPO500U/kg和静脉注射安慰剂组。每周注射2次,共注射3周。分另在第8天和第15天对志愿者采静脉血200ml,检测血小板活动度和血红蛋白水平。结果在注射促红素期间,接受EPO的志愿者血红蛋白水平均有不同程度升高,血小板上P-选择素含量和CD63阳性血小板增加 2～3倍。同时血浆中循环的P-选择素增加 50％,也反映出血小板活动度明显增高。血浆中循环的E-选择素显示出剂量依赖性增加100％,表明内皮细胞具有潜在活性。在用药第5天接受EPO的志愿者血小板计数增加在10％～20％之间。安慰剂组中仅在第1次采血几天后血小板计数略有增长。结论 促红素在提升人血红蛋白水平的同时可以明显增加血小板的活动度和内皮细胞的活性,从而使出凝血时间缩短。     

Synthesis and Properties of Azo Compounds Based on Nitroaniline Derivatives of 2,4,6-Trinitrotoluene and 1,3,5-Trinitrobenzene

Theoretical Foundations of Chemical Engineering - New research results, as well as those published earlier by the authors, on the synthesis of azo compounds based on nitroanilines obtained by the...     

Hemoglobin Adducts of Benzo[a]Pyrene in Tobacco Smokers : Characterization of Benzo[a]Pyrene Adducts in Maternal and Fetal Blood Samples

The formation of hemoglobin - carcinogen adducts has been detected in carcinogen treated animals and in human populations. Although polynuclear aromatic hydrocarbons are ubiquitous in the human environment and DNA - aromatic hydrocarbon adducts have been detected in human tissue, the occurrence of hemoglobin - polynuclear aromatic hydrocarbon adducts in humans has not been thoroughly described. In this study we examined the effects of reaction condition on the extent of in vitro reaction of human hemoglobin and (+) [³H]benzo[a]pyrene-7,8-diol-9,10-epoxide (anti)(BPDE), a metabolite thought to be largely responsible for the carcinogenic effect of benzo[a]pyrene. The chromatographic properties of the resulting hemoglobin - BPDE adducts were examined by conventional DEAE-cellulose ion exchange liquid chromatography and by reversed phase high performance liquid chromatography. Several adducts were formed which were chromatographically resolved from hemoglobin and from the individual globins. We applied these techniques to the qualitative and quantitative assessment of benzo(a)pyrene hemoglobin adducts in smokers, correlating both maternal and fetal adducts with smoking status.     

阿魏酸修饰的血红蛋白自氧化的研究(加急)

为研究FA-Hb的自氧化,以阿魏酸酯（FA-NBA）与血红蛋白（Hb）为原料,制备了阿魏酸血红蛋白（FA-Hb）。通过紫外光谱扫描、血氧分析仪等检测手段,分析了修饰前后血红蛋白的特征吸收峰的变化情况和氧饱和曲线的差别;研究了有无叠氮钠、黄嘌呤-黄嘌呤氧化酶介导下,血红蛋白和阿魏酸修饰的血红蛋白的自氧化速率的改变。实验结果表明,阿魏酸修饰血红蛋白,保持了血红蛋白的功能结构,仍具备血红蛋白的载氧活性,有效降低了自氧化速率。     

Hemoglobin immobilized on whisker-like carbon composites and its direct electrochemistry

We developed a novel mesoporous carbon/whisker-like carbon (MCWC) composite which can promote the direct electron transfer of hemoglobin (Hb) immobilized on its surface. The cyclic voltammetric results showed that Hb immobilized on the surface of the MCWC composite could undergo a direct quasi-reversible electrochemical reaction. Its formal redox potential, E^0′ is −0.313 V in the phosphate buffer solution (pH 6.9) at a scan rate of 200 mV/s and is almost independent of the scan rate in the range of 100-600 mV/s. The dependence of E^0′ on the pH of phosphate buffer solution indicated that the redox reaction of Hb includes a one-electron-transfer reaction process coupled with one-proton-transfer. The experiment obtained larger value of electron transfer rate constant, k_s, than that of Hb immobilized on other carriers reported previously due to its special structure of loosely packed nanometer-scale carbon whiskers and thus formed “V-type” nano-pores. Furthermore, Hb immobilized on the surface of the MCWC composite can retain the stable bioelectrocatalytic activity for the reduction of H₂O₂.     

1,3,5-三硝基-六氢化-1,3,5-三嗪-2-酮的合成与表征

以尿素、甲醛和叔丁胺为原料,通过Mannich缩合反应制备出5-叔丁基-1,3,5-三嗪-2-酮(TBT),再经硝酸-乙酸酐硝化合成出1,3,5-三硝基-六氢化-1,3,5-三嗪-2-酮(Keto-RDX),用核磁、红外光谱、质谱、元素分析等对TBT和Keto-RDX的结构进行了表征.探讨了TBT环化反应历程,确定了制...     

Ozone Degradation of Biological Macromolecules: Proteins,Hemoglobin, RNA,and DNA

The reactions of ozone with a series of biological macromolecules are reviewed. With proteins, ozone causes the oxidation or the ozonolysis of certain amino acid residues, for instance, tryptophan, tyrosine and cysteine. As a result of this attack the protein molecules undergo changes in their usual folding and binding ability and are denaturated as shown by polarimetric or chirooptical measurements and by the inhibition of their biological activity. In any case viscosimetric measurements show that the amide bond of proteins is resistant to the ozone attack and no chain scission phenomena occur as in the case of radiolysis of proteins. A special protein is hemoglobin which is characterized by a complex tetrameric structure where each of the 4 polypeptide chains binds a prosthetic haeme group having a porphyn structure. It is shown by a series of systematic studies on model molecules, on the isolated prosthetic groups, on isolated hemoglobin (methemoglobin) and on whole blood that the action of ozone is specifically directed toward the prosthetic haeme groups of this protein causing their fission into oxidized degradation products. Therefore, ozone is selectively bound by haeme groups of hemoglobin. RNA and DNA are very reactive with ozone in comparison to proteins. The ozone attack is directed mainly toward the nucleic acids. The stoichiometric ratio between ozone and RNA monomeric unit has been determined both polarimetrically and iodometrically. The complete collapse of RNA supramolecular structure occurs at a RNA/O₃ molar ratio between 2.0 and 1.5. Also DNA appears to be highly reactive with ozone, reactivity which is similar to RNA in all aspects.     

血红蛋白在碳纳米管-聚苯胺修饰电极上的直接电化学行为研究

利用滴涂法将血红蛋白(Hb)和多壁碳纳米管(MWNT)-聚苯胺纳米纤维(PANnano)复合纳米粒子修饰到碳糊电极(CPE)表面,并对其电化学行为进行研究。实验结果表明,血红蛋白在PANnano/MWNT膜内保持了其天然构象和较好的直接电化学行为。     

Butyl pyrene containing poly(arylene ethynylene)s for highly sensitive and selective sensing of TNT

A series of poly(arylene ethynylene)s (PAEs) containing ^tbutyl pyrene in the main chain were synthesized for nitroaromatic sensors. As control, similar polymers containing unsubstituted pyrene were also synthesized. The sensory properties of the polymers were studied towards various nitroaromatic compounds like trinitrotoluene (TNT), dinitrotoluene (DNT), nitrotoluene (NT), nitrobenzene (NB) and picric acid (PA) in solution as well as vapor state. Interestingly, all the ^tbutyl substituted pyrene containing polymers showed higher sensitivity than the corresponding unsubstituted pyrene containing polymers. Moreover, the polymers showed high sensitivity towards TNT as compared to the other nitroaromatic compounds. The sensitivity of one of the polymer PB was found several folds higher than that of the similar reported polymer containing unsubstituted pyrene ring. In addition, ^tbutyl pyrene containing polymers were found to have improved molecular weight, thermal stability, fluorescence quantum yield, film forming properties and solubility in common organic solvents as compared to the control polymers.     

1,3,5-三羟乙基三嗪酮的富能化合成与表征

以1,3,5-三羟乙基三嗪酮为原料,经过硝化、叠氮化过程合成了1,3,5-三硝氧乙基三嗪酮(TNEIC)和1,3,5-三叠氮乙基三嗪酮(TAEIC);通过实验确定最佳硝化条件为:发烟硝酸与浓硫酸体积比1∶1,反应温度25℃,时间0.25 h,收率92.0%.采用元素分析、红外光谱、核磁共振光谱等鉴定了目标产物结构,并借助DSC等分析方法测定了产物的热性能.结果表明,TAEIC性能优良,熔点较低,有望用于熔铸炸药配方.     

新型1,3-茚满二酮类螺环化合物的合成与表征

以1,3-茚满二酮和取代苯甲醛为原料,通过Knoevenagel缩合反应生成2-芳基亚甲基-1,3-茚满二酮,然后2-芳基亚甲基-1,3-茚满二酮与4-氯代乙酰乙酸乙酯在催化剂作用下发生Michael/γ-Alkylation串联反应,获得了6个新型1,3-茚满二酮类螺环化合物。并且进行了催化剂、溶剂和温度的筛选,发现三乙胺为最优的催化剂,在室温下,以氯仿为溶剂,反应获得了最好的收率(98%)和非对映选择性(98∶2 dr)。产物的结构经1HNMR、13CNMR、HRMS确证。     

GSTM1/T1 Genotypes and Benzo(A)Pyrene Hemoglobin Adducts in Maternal and Fetal Blood

Both genetic and environmental factors are involved in the development of cancer. The capacity to metabolize certain drugs and carcinogens is known to be variable in humans and appears to be of critical importance in determining the risk an individual has of developing cancer when exposed to carcinogens. For many phase I and phase II enzyme systems involved in foreign compound metabolism it is now understood that germ-line genetic variation within the genes encoding these enzymes leads to altered phenotypic expression impacting the metabolic capacity of the individual. This genetic variation is referred to as genetic polymorphism and the study of the association between genetic polymorphism and the resulting phenotypic changes in drug or foreign compound metaboism is referred to as pharmacogenetics. This variation in metabolic capacity is linked to environment–gene interactions on carcinogenesis and has been well demonstrated by enzymes that are involved in the metabolism of carcinogens including several human cytochrome P450 enzymes as well as certain glutathione S-transferases and N-acetyltransferases. The genetic lesion may involve a single but critical base pair change or complete gene deletion. Screening assays based on PCR amplification coupled to restriction fragment length polymorphism (RFLP) analysis or allele specific PCR have been developed to correlate genetic polymorphism with phenotypic expression and susceptibility to genotoxicity or carcinogenesis. The phase II enzymes, including GSTs, N-acetyltransferases, as well as epoxide hydrolase, are all involved in the detoxification of activated metabolites of carcinogens, including those carcinogens found in tobacco smoke. The substrates of GSTs include benzo(a)pyrene as well as other carcinogens. In the present study, we investigated the relationship between polymorphism of glutathione S-transferase in maternal and fetal cord blood samples obtained at delivery and correlated genotype with presence of hemoglobin adducts to the tobacco carcinogen benzo(a)pyrene.     

Effect of film thickness, blending and undercoating on optical detection of nitroaromatics using fluorescent polymer films

In this work, using a fluorescent poly(phenylene ethynylene) containing the rigid pentiptycene and large cholesteryl ester pendent groups, the fluorescence quenching properties of the polymer thin films in response to vapor of 2,4-dinitrotulene (DNT) have been investigated by varying the film thickness, applying an undercoating and blending with another polar polymer. A significant change in fluorescence intensity (51% in 60 s) in response to DNT vapor exposure at ambient temperature was achieved when the polymer film coated on glass plate was about 2 nm in thickness. In comparison with the film of polymer alone, the film undercoated with (3-aminopropyl)triethoxysilane and the film of polymer blend containing a non-fluorescent polymer showed additional 18.5% (in 20-s exposure) and 18.7% (in 5-min exposure) decrease in fluorescence intensity, respectively. The use of polymer or polymer blend coated on optic-fiber tip for detection of DNT vapor has also been demonstrated.     

Targeted Protein Degradation as a Promising Tool for Epigenetic Upregulation of Fetal Hemoglobin

The level of fetal hemoglobin (HbF) is an important disease modifier for β-thalassemia and sickle cell disease patients. Indeed, genetic tinkering with the HbF repression machinery has demonstrated great potential for disease mitigation. Such genetic treatments are costly and the high incidence of β-hemoglobinopathies in low-income countries, therefore, calls for the development of affordable, off-the-shelf, oral treatments. The use of PROTAC ( PR oteolysis TA rgeting C himeras) technology to influence the epigenetic mechanisms involved in HbF suppression may provide a solution. In this minireview, we briefly explain the HbF repression network highlighting the epigenetic factors that could be targeted for degradation by PROTACs. We hope that this review will inspire clinicians, molecular and chemical biologists to collaborate and contribute to this fascinating field, which should ultimately deliver drugs that reactivate HbF expression with high specificity and low toxicity.     

一种含三嗪环的四臂引发核的合成与表征

以三聚氯氰(CNC)和乙二胺(EDA)为原料,通过亲核取代反应合成了含1,3,5-三嗪环的四臂引发核:N,N′-二-(4,6-二氯-[1,3,5]-三嗪基)-乙二胺。考察了反应物投料摩尔比,碱的种类和用量,加料速率和反应时间对产物收率的影响。结果表明:n(CNC)∶n(EDA)=2∶1,碱用NaOH,且n(NaOH)∶n(EDA)=2∶1,以V(二氯甲烷)∶V(水)=1∶1为溶剂,乙二胺的NaOH水溶液的滴加速率为1 mL/m in,0~5℃反应2 h,收率达95.5%。通过元素分析、质谱、核磁共振、红外光谱对目标产物的结构进行了分析表征。     

Evaluation of the electron transport chain inhibition and uncoupling of mitochondrial bioelectrocatalysis with antibiotics and nitro-based compounds

Mitochondrial bioelectrocatalysis can be useful for sensing applications due to the unique metabolic pathways than can be selectively inhibited and uncoupled in mitochondria. This paper details the comparison of different inhibitors and nitro-containing explosive uncouplers in a mitochondria-catalyzed biofuel cell for self-powered explosive sensing. Previous research has reported inhibition of pyruvate oxidation at a mitochondria-modified electrode followed by nitroaromatic uncoupling of current and power. We have previously used oligomycin as the antibiotic and nitrobenzene as the uncoupler of the membrane in the mitochondria-catalyzed biofuel cell, but no comprehensive comparison of various mitochondria inhibitors or explosives has been performed. Results are discussed here for inhibitors targeting complex I, complex III, ATP synthases, adenine nucleotide transport and monocarboxylic acid transport. Reactivation with nitrobenzene was possible in the presence of these inhibitors: oligomycin, 3,3′-diindolylmethane, atractyloside, rotenone, α-cyano-4-hydroxy cinnamic acid and antimycin A. All eleven explosives studied, including: 2,4,6-trinitrotoluene (TNT) and 1,3,5-trinitroperhydro-1,3,5-triazine (RDX), caused uncoupling of the mitochondria function and could be detected by the biosensor.     

Synthesis and Photodiode Characterization of Novel Twisted Carbazole Derivatives with 1,3,5-Benzene Core

In this study, considering the information given in the literature the Ullman and Suzuki-Miyaura coupling reactions were carried out using carbazole, 1,3,5 tribromo benzene and aryl boronic acid. The synthesized novel carbazole derivative (CPF4) were characterized by 1H NMR and 13C NMR. The photophysical and thermal properties of the synthesized novel carbazole derivatives CPF4 were investigated Graphene oxide (GO) doped CPF4/p-Si photodiodes were fabricated. The electrical properties of these photodiodes were characterized by current–voltage (I?V) and capacitance–voltage (C?V) measurements. The photocurrent properties of the diode were studied under various illumination intensities. The photoresponse properties of the diodes increased with GO content. The results indicate that CPF4:GO/p-Si heterojunctions can be used as a photodetector for optoelectronic applications.     

聚（癸二酸-1,3-丙二醇）酯低聚物的合成与表征

在无催化剂、相对较低温度下合成了聚(癸二酸-1,3-丙二醇)酯低聚物。GPC色谱显示,过量1,3-丙二醇常使粗产物呈现多组分,但随其用量减少,粗产物逐渐变均一。FTIR光谱表明,低聚物主链为酯键结构,且羟基含量随单体摩尔比降低及第二阶段反应进行而趋于减小。1H NMR分析发现,低聚物实际摩尔组成远低于初始单体摩尔比;低聚物摩尔质量为967.14～3970.49g/mol,1,3-丙二醇封端度为38%～66%。该低聚物期望在口香糖制备中用作无毒、环境友好、可生物降解型增塑剂。     

1，3，5-三（甲基三氟丙基）环三硅氧烷／六甲基环三硅氧烷共聚物的合成与表征

由1,3，5-三（甲基三氟丙基）环三硅氧烷和六甲基环三硅氧烷的阴离子本体开环共聚制备了不同组成的共聚氟硅生胶，并结合硅氧烷的开环机理分析了聚合过程中特性粘数变化趋势。发现聚合过程中特性粘数变化趋势为先快速增长，然后下降并趋于稳定。不同共聚组成的硫化共聚氟硅胶均具有优良的热稳定性。