视黄酸合成酶基因Raldh2敲除鼠肢体发育起始的挽救

视黄酸合成酶基因Raldh2敲除鼠胚胎心脏膨大,没有肢体发育的起始.肌细胞增强子基因Mef2C敲除鼠胚胎心脏较小,但肢体的发育起始正常.Raldh2/Mef2C双基因敲除鼠与Raldh2敲除鼠形态相似.Tbx5在Raldh2/Mef2C基因敲除鼠第9天的胚胎表达表明,双基因敲除鼠胚胎没有肢体的发育.这一结果表明Mef2C敲除鼠没有挽救Raldh2敲除鼠肢体发育的起始.     

高效液相色谱法快速测定生物样品中的视黄酸

建立了快速测定生物样品中全反式(all-trans-),9-顺式(9-cis-),13-顺式(13-cis-).视黄酸(RA)的高效液相色谱分析方法.经2次液-液萃取提取生物样品中的视黄酸后.直接应用高效液相色谱法同时测定了3种视黄酸同分异构体的含量.采用Waters C18反相柱(3.9×150mm),V(乙腈):V(0.1%冰醋酸溶液)=86:14为流动相,流速1.0 mL/min,柱温为25℃,检测波长为350 nm.3种视黄酸同分异构体的线性范围均为5-500 ng/mL,r2均大于0.999;检出限均为1 ng/mL;提取回收率为92.7%-101.8%,方法回收率为102,4%-104.4%;日内精密度小于8.3%,日间精密度小于11%.本方法适用于不同生物样品中视黄酸的定量研究.     

大鼠去势后肾上腺与前列腺中Cyp17a1基因的表达

通过定量检测大鼠去势前后肾上腺和前列腺中Cyp17a1基因的表达, 试图从分子水平解释去势手术后大鼠机体内雄性激素水平的变化.     

Copper-catalyzed direct oxidation and N-arylation of benzylamines with diaryliodonium salts

<正>1 The study of reaction conditions Table S1 The optimization of the rate of copper slats and ligand a) Entry Anion Cu/ligand Yield b)(%) 1 2 3 OTf OTf OTf 10%:20% 10%:10% 5%:10% 91 65 45 a) Reaction conditions: 1a(0.60 mmol), 2a(0.20 mmol), Cu(OTf)2(x mol%), K2CO3(2.5 equiv.), 1,10-phenanthroline(y mol%), DMSO(2 mL), 150 °C, 24 h; b) isolated yields. Table S2 The optimization of the substrates' rate a) Entry 1a/2a(mmol) Yield b)(%) 1 2 3 4 5 6 0.2:0.2 0.2:0.24 0.2:0.4 0.6:0.2 0.4:0.2 1.0:0.2 54 60 58 91 73 83 a) Reaction conditions: 1a(x mmol), 2a(y mmol), Cu(OTf)2(10 mol%), K2CO3(2.5 equiv.), 1,10-phenanthroline(20 mol%), DMSO(2 mL), 150 °C, 24 h; b) isolated yields.     

Synthesis of Cholest-5-en-24-oxo-3b, 19-Diacetate

Two biologically active 19-hydroxylated sterols, 24-methylenecholesta-3b, 5a, 6b, 19- tetrol 1, 24-methylenecholesta-5-ene-3b, 7b, 19-triol 2, were isolated from the soft corals, Nephthea albida and Nepthea tiexieral verseveldt by L. M. Zeng1,2. 1 showed strong anti-inflamatory activity comparable with dexamethone and 2 showed potent anti-leukemic activity (IC50 0.01 mg/mL). We have designed a synthetic route for the synthesis of 1 and 2 as shown in Scheme 1. In this route, cholest-5-en-…     

猪去氧胆酸化学7.(24R)-24,25-双羟基,(24R,25S)-24,25,26-三羟基和(25R)-25,26-双羟基胆固醇的立体选择性和区域选择性合成

本文报道以猪去氧胆酸甲酯(2a)为原料, 立体选择和区域选择性地合成了维生素D~3代谢产物及类似物的关键中间体(24O)-24,25-双羟基胆固醇(3b),(24O,25, 26-三羟基胆固醇(3c)和(25O)-25,26-双羟基胆固醇(3d).,总收率分别为27,27和38%.     

新型龙胆酸衍生物的合成及其抑制酪氨酸酶活性研究

为发现新型的美白活性化合物,以龙胆酸甲酯、卤代烃和α-羟基酸乙酯为原料,合成了10个未见文献报道的2-羟基-5-烷(H)氧基苯甲酸酯类衍生物(3a,3b和6a～6h),其结构经1H NMR,IR,MS和HRMS确认.初步生物活性测试结果表明6a,6b,6e和6f具有较强的抑制酪氨酸酶活性,进一步药理实验表明经取代改造后的6a～6h,其毒性和光学毒性都相对龙胆酸甲酯和氢醌更低.     

Synthesis of Certain 3-Aminopyrazolo[5,4-b]pyridine and 3,4-Substituted Pyrido[2′,3′：3,4]pyrazolo[5,1-c][1,2,4]triazine Derivatives

2-Thioxo-1,2-dihydropyridine derivatives 2a, 2b were reacted with methyl iodide to give 2-methylthiopyridines 3a, 3b, which were reacted with hydrazine hydrate to produce 3-aminopyrazolo[5,4-b]pyridines 4a, 4b. Compounds 4a, 4b were diazotized to afford the corresponding diazonium salts 5a, 5b, which were reacted with some active methylene compounds 6a-6h to give the corresponding pyrido[2′,3′ ： 3,4]pyrazole[5,1-c][1,2,4]triazines 7-14.     

6-羟基-3-硫酸酯钠甾体化合物的合成及生理活性研究

甾醇硫酸酯钠化合物由于其独特的结构特征和特殊的生理活性正引起人们越来越多的关注.从天然存在的甾醇1a～1b出发,经过PCC氧化得到4-烯-3,6-二羰基甾体化合物2a～2b,然后在Ni2+存在的条件下用硼氢化钠还原2a～2b,得到3-羟基-6-酮甾体化合物3a～3b.利用三乙胺-三氧化硫复合物对3a～3b进行硫酸酯化得到4a～4b,然后通过阳离子(钠型)交换树脂对4a～4b进行Na+交换得到6-氧代-3β-硫酸酯钠盐5a～5b,5a～5b进一步通过NaBH4还原得到6-羟基-3β-硫酸酯钠(6a～6b).另外,采用类似的方法合成了6-羟基胆甾-4-烯-3β-硫酸酯钠(10a).并对化合物5a～5b和6a～6b进行抗肿瘤活性试验,结果表明6a在体外对卵巢癌(Hey-1B)细胞株具有较好的细胞毒性,IC50值为48 nmol/mL.     

α'-三氟甲基-含氟β-二酮镧系螯合物的合成及其用作位移试剂的研究

本文合成了α'-三氟甲基-含氟β-二酮镧系螯合物Ln{CF3CF2[CF2OCF(CF3)]nCOCHCOC(CH3)3}3[n=1; Ln=Eu(1a), Pr(1b), Nd(1c),Sm(1d), Gd(1e), Tb(1f), Dy(1g), Er(1h). n=2; Ln=Eu(2a), Pr(2b), Nd(2c),Sm(2d), Gd(2e), Tb(2f), Dy(2g), Er(2h)], 并研究了它们的位移性能. 1a、1b、2a和2b在用作位移试剂时, 不仅具备Ln(fod)3(Ln=Eu, Pr)的所有优点, 而且还有另外两个优点: (1)在底物存在时, 试剂自身的叔丁基峰明显向高场迁移, 特别是在醇类化合物存在下, δ-Bu^t接近于0ppm, 因此, 1a和2a的t-Bu峰总是处于底物ω-甲基的高场, 不干扰图谱的解析. (2)1b和2b虽为镨类螯合物, 但与1a与2a一样, 都能得到非常清晰的一级图谱. c、f和g均使谱峰向高场迁移, 而h却使谱峰向低场迁移. c的位移能力略低于b. f、g和h的位移能力极强.     

探讨维甲酸诱导小鼠肝癌细胞凋亡血清微量元素的变化

为探讨维甲酸诱导小鼠肝癌细胞凋亡的血清微量元素的变化,收集30例实验组BALBC小鼠血清标品,应用等离子体发射光谱仪测定了se、zn、cu、Fe、Ca、Mg含量。结果表明,血清微量元素含量测定,维甲酸组Zn、Mg含量低于对照组,se、cu、Fe、ca含量和对照组比差异无显著性（P〉0．05）。提示维甲酸诱导小鼠肝细胞凋亡,血清微量元素含量变化不大与肝癌发生、靠展无相关件．     

全反式维甲酸合钇(Ⅲ)配合物对DNA的切割和键合作用(英)

以紫外光谱、荧光光谱、粘度法和凝胶电泳方法研究了全反式维甲酸合钇(Ⅲ)配合物与DNA的作用。结果表明，该配合物能在生理条件下比配体和金属离子更有效地切割质粒DNA，体系离子强度和pH值的变化对配合物的切割活性有较大影响，自由基捕捉剂的加入不影响配合物的切割活性。该配合物对DNA的切割可能通过水解机理进行。该配合物可使DNA的粘度增加，使EB-DNA体系的荧光强度和DNA溶液的紫外吸收强度降低。据此推断，该配合物主要以嵌入方式与DNA作用。     

Computer‐aided design of a novel ligand for retinoic acid receptor in cancer chemotherapy

The isotypes of RAR and RXR are retinoic acid and retinoid X acid receptors, respectively, whose ligand‐binding domain contains the ligand‐dependent activation function, with distinct pharmacological targets for retinoids, involved in the treatment of various cancers and skin diseases. Due to the major challenge which cancer treatment and cure still imposes after many decades to the international scientific community, there is actually considerable interest in new ligands with increased bioactivity. We have focused on the retinoid acid receptor, which is considered an interesting target for drug design. In this work, we carried out density functional geometry optimizations and different docking procedures. We performed screening in a large database (hundreds of thousands of molecules which we optimized at the AM1 level) yielding a set of potential bioactive ligands. A new ligand was selected and optimized at the B3LYP/6‐31G* level. A flexible docking program was used to investigate the interactions between the receptor and the new ligand. The result of this work is compared with several crystallographic ligands of RAR. Our theoretically more bioactive new ligand indicates stronger and more hydrogen bonds as well as hydrophobic interactions with the receptor. © 2005 Wiley Periodicals, Inc. Int J Quantum Chem, 2005     

Nanoporous membrane-based cell chip for the study of anti-cancer drug effect of retinoic acid with impedance spectroscopy

This paper presents a novel microchip with nanoporous anodic alumina membrane for the study of anti-cancer drug effect of retinoic acid (RA) on human esophageal squamous epithelial KYSE30 cancer cells in vitro with impedance spectroscopy. The impedance experiments with 0.01 M retinoic acid (RA) were explored for the study of anti-cancer drug effects on KYSE30 cancer cells. The impedance was monitored in the time domain at 0.1 Hz. After addition of 0.01 M RA to the cell chip, the impedance magnitude decreased with time from the value with confluent cell layer and returned to the initial base line after around 12 h. The fluorescence experiments testified that this impedance decrease was due to the cell morphology change induced by RA.     

A STRATEGY FOR ISOLATING DIFFERENTIATIONINDUCING COMPLEMENTARY DNAs FROM HUMAN ESOPHAGEAL CANCER CELL LINE TREATED WITH RETINOIC ACID

Treatment of the human esophageal cancer cell line EC8712 with retinoic acid (RA) stopped the cell growth significantly and gave rise to terminal differentiation of the cells characterized by increased expression of involucrin gene. Two cDNA libraries were constructed from the parental and RA-treated cells respectively. Repeated subtractive hybridization of single-stranded plasmid DNA prepared from pooled colonies of cDNA library of the parental cells with cDNA probe generated from the RA-treated cells exhausted sequences common to both libraries of the cell. The unhybridized cDNA probe represented, therefore, the genes activated after RA-treatment. By using these enriched cDNAs as probe to screen the cDNA library constructed from the RA-treated cells thirty-nine positive colonies were obtained, of which two were specifically due to RA-induction. One of these two cDNA clones, designated as pRA538, has undergone further analysis and shown differentiation-inducing effect on parental cancer cells. A novel     

Synthesis and anti-tumor activity of all-trans retinoic acid derivatives

A series of retinoate and retinamide derivatives were designed,synthesized,and their anti-tumor activities were investigated in NB4 by MTT and flow cytometry assays(FCM).All compounds showed cytotoxicity,especially compounds 1a and 1d exhibited a higher cytotoxicity than other derivatives and all-trans retinoic acid(ATRA).Furthermore,compound 1d could induce NB4 cell lines differentiation efficiently.     

叶酸高分子纳米胶束在小鼠体内的靶向分布

合成了带有叶酸靶向和荧光染料的聚合物FA-PEG-PLA和mPEG-b-P（LA-co-MHC／NIR）,通过混合胶束的方法制备近红外染料胶束P（NIR）（含染料NIR6％）,叶酸胶束FA-P（NIR）1（含染料NIR5．4％,叶酸LFA0．5％）和叶酸胶束FA-P（NIR）2（含染料NIR4．8％,叶酸FA0．9％）;建立了H22肝癌小鼠模型,考察了高分子纳米胶束及叶酸靶向纳米胶束在H22肝癌小鼠体内分布．结果表明,高分子纳米胶束及叶酸靶向纳米胶束在小鼠体内分布都具有时间相关性,无叶酸配体的高分子纳米胶束在尾静脉注射24h后在肿瘤部位有少量聚集,大部分胶束在肝部聚集,30h内大部分已被排泄系统排出体外;含有叶酸配体的纳米胶束在尾静脉注射后6-30h内在肿瘤部位有明显的聚集,其中,FA-P（NIR）1胶束在肿瘤和肝部位的聚集相当,FA-P（NIR）2胶束在静脉注射24h后在肿瘤聚集明显高于肝部．带有叶酸配体的高分子纳米胶束相对于不带叶酸配体的纳米胶束在小鼠肿瘤部位具有明显的聚集,并且随着叶酸含量的增大,聚集效果更明显．     

THE EFFECT OF CHRONIC APPLICATIONS OF TRETINOIN(RETINOIC ACID) ON ACUTE RESPONSES OF MAMMALIAN SKIN TO UVB RADIATION IN VIVO

Abstract The effects of long—term applications of tretinoin(retinoic acid; RA) on acute responses to UVB radiation were examined in hairless mouse skin in vivo. The skin was examined histologically and the radioactive tracer [³H]-thymidine was used to study premitotic semiconservative DNA synthesis in the epidermal basal cells. Ten and 23 wk applications of a 0.05% RA solution (3 times a wk) induced epidermal acanthosis, hypertrophy of the individual cells and an increased number of [³H]-thymidine-labelled basal cells. At both time periods there was a distinct reduction in the expected inhibition of DNA synthesis at 4 h and the expected acceleration of DNA synthesis at 48 h after a single exposure to UVB radiation. In addition, the histologic morphology was unchanged at 48 h post irradiation. Thus, the repeated RA applications had a definitive influence on at least two aspects of the cutaneous response to UVB energy.