人胎盘的生殖内分泌学研究——Ⅲ.妊娠早期人滋养层组织孕酮分泌的调节

在体外无血清培养条件下,低剂量的促黄体素释放激素(GnRH)(10~(10)—10~(-8)mol/L)可促进妊娠6—8周人胎盘绒毛的孕酮分泌,高剂量则抑制孕酮的分泌,抗hCG多克隆抗血清与单克隆IgG明显抑削孕酮的生成,而且抑制程度与抗体剂量及作用时间相关,然而不同浓度的TRH,PGE_2,PGF_(2a),睾酮、雌二醇等对胎盘绒毛的孕酮分泌则无显著影响,本研究结果表明,妊娠早期人胎盘绒毛的孕酮分泌是受GnRH与hCG调节的,这为证明胎盘中可能存在激素分泌的自我调节系统提供了重要的依据。     

石蒜内铵对小鼠肝癌细胞染色质结构和活性的影响

原位缺口平移法测得,体外5—50μg/ml石蒜内铵(LBT)对小鼠肝癌细胞不产生DNA单链断裂,但能程度不等地抑制染色质活性,其作用有浓度和时间依赖性.LBT对不同活性结构状态的基因作用不同,可使c-myc,N-ras癌基因和β_2微球蛋白基因对DNA酶Ⅰ的敏感性分别从75±6,66±4,70±8％降至28±8,25±5,28±7％。但对c-myb癌基因和β珠蛋白基因作用不明显。     

LHRH脉冲型式的变化对灌流的雄性大鼠垂体细胞LH分泌的影响

本实验应用体外分散垂体细胞动力学培养的方法,观察了LHRH脉冲幅度和频率以及LHRH连续刺激对雄性大鼠垂体前叶细胞LH分泌活动的影响。结果表明,LHRH在1×10~(-10)—1×10~(-6)mol/L范围内,与LH分泌的剂量-效应关系曲线呈线性。LHRH脉冲频率使LH分泌产生双相反应,随着刺激频率的增高,LH基础水平升高,LH/脉冲减少。当LHRH脉冲幅度在1×10~(-9)mol/L或以上,刺激频率在3脉冲/h或以上时,可观察到LH分泌达最高峰并随之逐渐下降至基础水平,即明显的自身激发作用和脱敏作用。增加LHRH的脉冲幅度可减少引起激发作用所需要的脉冲频率,增加高幅度LHRH脉冲的频率可使激发作用更快产生。另外,低浓度的LHRH(1×10~(-10)mol/L)连续刺激细胞也可产生自身激发作用,但需要较长时间的刺激。这些结果提示:垂体前叶LH细胞的分泌型式依赖于LHRH脉冲的幅度和频率,这有助于阐明体内的LH脉冲波动的动力学机理。     

水溶性铜卟啉配合物的合成、与DNA的相互作用及抗肿瘤活性

合成了3种水溶性铜卟啉配合物,分别为水溶性含溴铜卟啉(CuP-1)及其溴取代衍生物(CuP-2、CuP-3),并采用核磁氢谱、元素分析、质谱等手段进行了结构表征。利用紫外光谱法、EB-DNA荧光淬灭法、粘度法以及圆二色谱法等光谱法研究了CuP-1、CuP-2和CuP-3与小牛胸腺DNA(CT-DNA)的相互作用。采用噻唑兰(MTT)法,以体外培养的宫颈癌细胞(Hela)和乳腺癌细胞(MDA)为测试细胞株对CuP-1~CuP-3的抗肿瘤活性进行检测。人成纤维细胞(L929)作为正常细胞系。光谱法实验结果表明,CuP-1以插入的方式与CT-DNA相互作用,而CuP-2和CuP-3与CT-DNA以沟面结合的方式相互作用,且CuP-1与CT-DNA的结合能力优于CuP-2和CuP-3。体外抗癌活性实验结果表明,CuP-1~CuP-3对Hela和MDA均有体外抑制细胞增殖作用,呈时间、剂量依赖关系,并且CuP-1的体外抗肿瘤活性明显优于CuP-2、CuP-3。     

镱及其络合物对体外培养细胞作用的研究

本文报道镱及其四种络合物对体外培养细胞的作用。实验结果表明,5mM的YbCl_3对体外培养细胞具有明显的毒性作用;当其与配体形成络合物后,其毒性降低。四种络合物对人二倍体细胞生长、贴壁等均无破坏作用,但四种络合物对人癌细胞却产生不同形式的破坏作用:抑制人癌细胞贴壁,导致细胞死亡;配体I与Yb~(3+)的络合物破坏分裂期癌细胞,使之形成畸变分裂相;其余三种配体与Yb~(3+)的络合物则是对间期人癌细胞具有破坏作用,其作用与剂量相关。     

大鼠滤泡纤蛋白溶酶原激活因子及抑制因子的相互作用和调节

本文证明卵巢滤泡分泌两种纤蛋白溶酶原激活因子(即tPA和uPA)和一种抑制因子(PAI),并研究了这些因子的相互作用和调节。实验证明,只有tPA,而不是uPA受促性腺激素调节,并在排卵前达到高峰。PAI主要是由内膜-间质细胞分泌的,也受促性腺激素的调节。PA和PAI的相互结合可完全抑制和部分抑制卵巢细胞PA活性。上述资料提示,滤泡的PA以及PAI间的相互作用可能在排卵机制和维持卵巢的正常生理功能中起重要作用。     

肾上腺皮质球状带细胞上的苯二氮受体

本文研究结果表明,大鼠肾上腺皮质球状带细胞上存在外周型苯二氮草受体,后者与[~3H]PK 11195结合的表观平衡解离常数K_D为9.4±2.8 nmol/L,最大结合容量B_(max)为5.6±1.8 pmol/10~6个细胞。五种配体:PK11195,4’-氯安定、氟硝安定、安定和氯硝安定,可增强球状带细胞由血管紧张素Ⅱ和K~+浓度升高所致醛固酮分泌反应,其EC_(50)的对数与其受体结合抑制常数K_i的对数呈良好的正相关,提示上述醛固酮分泌的增强效应可能系由球状带细胞上的苯二氮(艹卓)受体所中解。     

硝酸镧对人神经胶质瘤SWO细胞的作用

采用体外培养技术,通过MTT比色法、光镜、扫描电镜和透射电镜等实验方法观察La(NO3)3对人神经胶质瘤SWO细胞的作用。结果表明浓度为0.1,0.5,1.0,1.5mmol·L-1的La(NO3)3均可抑制SWO细胞的增殖,并具有剂量依赖性,La(NO3)3作用后细胞收缩变圆,细胞膜上出现孔洞,核膜皱缩、异染色质凝集增多、细胞器破碎。La(NO3)3对SWO细胞具有抑制杀伤作用。     

稀土对人正常肝细胞株7701和人宫颈癌Hela细胞生长的影响及其诱导细胞凋亡的作用

采用MTT法考察了16种稀土元素在9×10-8~2×10-4mol.L-1浓度范围内对体外培养的人正常肝细胞株7701细胞和宫颈癌Hela细胞的生长的影响。结果表明,稀土对细胞生长的影响存在浓度依赖性;低浓度促进细胞增殖,高浓度抑制细胞生长;不同稀土离子对细胞作用强弱不同,稀土间存在轻重分组效应;不同细胞对稀土的响应不同,表现出稀土对正常细胞和癌细胞作用的某种选择性。Hoechst 33258标记细胞DNA,用激光共聚焦显微镜和流式细胞仪对稀土处理的肝细胞株7701进行形态学观察和DNA含量分析。结果表明,较高浓度的稀土作用后的肝细胞株7701出现了明显的凋亡特征,稀土表现出的细胞毒性作用,其本质是诱导细胞发生凋亡。     

基于Taylor弥散理论的纳米粒子与蛋白质相互作用研究

在微流控芯片中将Taylor弥散分析(TDA)与激光诱导荧光检测(LIF)结合,测定了荧光素钠标记狗血清蛋白(FITC-DSA)的水合半径为(6.12±1.21)nm,扩散系数为(4.11±0.78)×10-11m2/s;然后,初步研究了FITC-DSA与不同粒径金纳米粒子(AuNPs)的相互作用.研究结果表明,不同粒径的AuNPs与蛋白质的作用不同;50 nm的AuNPs与FITC-DSA作用会导致其荧光信号增强.本研究为高通量测定纳米粒子与蛋白质相互作用提供了一种新方法.本方法具有简单快速、耗样量极少等优点,有助于深入了解纳米材料的毒性,推动安全纳米药物的发展.     

二氧化碳和丙烯直接合成甲基丙烯酸的NiPMo/TiO2催化剂的研究

用溶胶-凝胶法以磷钼酸(MPA)的镍盐溶液水解钛酸四丁酯制备了NiPMo/TiO2催化剂.使用ICP、 XRD、 TG-DTA、 IR、 TPD-MS和微反应技术研究了催化剂的化学组成、热稳定性、化学吸附性质和催化反应性能.杂多钼酸盐与TiO2通过O2-在TiO2表面发生了键合.在623 K下,杂多阴离子仍保持原有的Keggin结构.CO2在Lewis酸位Ni(Ⅱ)和Lewis碱位Ni-O-Mo的桥氧协同作用下生成CO2卧式吸附态Ni(Ⅱ)←O-(CO)←(O--Ni).丙烯有多种吸附态在催化剂上吸附.在563 K、 1 MPa和空速1500 h-1的反应条件下,丙烯的摩尔转化率为3.2%,产物MAA选择性为95%.     

CoFe2O4自形成磁性液体场致结构化对磁化的影响

The Langevin paramagnetic theory can’t describe the relation between magnetization of ferrofluids and applied magnetic field. The structuralization of ferrofluids, which is considered the main influence factor of the magnetization, is regarded. The part of magnetization works is deposited when the structure is forming. This action influences the magnetization of ferrofluids directly or indirectly. On the base of the “compressing” model, the Langevin function that usually describes the magnetization of ferrofluid is modified, and a well-fitted curve is obtained. An equation of the relation between the equivalent volume fraction after being “compressed” and the intensity of magnetic field is discovered, which approximately describes the process of magnetization. The relation between the approximate initial susceptibility and the volume fraction can be obtained from modified formula.     

Highly regioselective Buchwald–Hartwig amination at C-2 of 2,4-dichloropyridine enabling a novel approach to 2,4-bisanilinopyridine (BAPyd) libraries

The highly regioselective Buchwald–Hartwig amination at C-2 of the cheap and readily accessible reagent, 2,4-dichloropyridine with a range of anilines and heterocyclic amines is described. This new methodology is robust and provides a facile access to 4-chloro-N-phenylpyridin-2-amines on 0.25 mol scale. These intermediates undergo a further Buchwald–Hartwig amination at higher temperature to enable rapid exploration of the chemical space at C-4 and to provide a library of 2,4-bisaminopyridines.     

Sulfur-directed metal-free and regiospecific methyl C(sp3)–H imidation of thioanisoles

Regiospecific and direct imidation of the methyl C(sp³)–H bond of thioanisoles is realized under mild and metal-free conditions with N-fluorobis(benzenesulfonyl)imide as an oxidant and nitrogen source. Proposed mechanism suggests that thionium ion intermediates and a Pummerer-type reaction are involved. The imidation has advantages such as high step-economy, excellent functionality tolerance, and regiospecificity, giving structurally diverse imidation products.     

Selective syntheses of 2H-1,3-oxazines and 1H-pyrrol-3(2H)-ones via temperature-dependent Rh(II)-carbenoid-mediated 2H-azirine-ring expansion

The Rh(II)-catalyzed reaction of 2-carbonyl-substituted 2H-azirines with ethyl 2-cyano-2-diazoacetate or 2-diazo-3,3,3-trifluoropropionate provides an easy access to 2H-1,3-oxazines and 1H-pyrrol-3(2H)-ones. These compounds can be selectively prepared from the same starting material using temperature as the only varied parameter. The 2-azabuta-1,3-diene intermediate, a common precursor for both heterocyclic products, isomerizes into 2H-1,3-oxazine under kinetic control, while 1H-pyrrol-3(2H)-one is the sole product of the reaction at elevated temperatures. According to DFT-calculations a one-atom oxazine ring contraction involving ring-opening to a 2-azabuta-1,3-diene intermediate, followed by a 1,5- and 1,2-prototropic shift leads to the consecutive formation of imidoylketene and azomethine ylide, which then further undergo cyclization to the pyrrole derivative.     

Copper catalyzed/mediated synthetic methodology for ebselen and related isoselenazolones

Scope of the copper catalyzed/mediated selenium-nitrogen coupling reaction has been studied for the synthesis of isoselenazolones. It is noticed that the 2-chloro, 2-bromo-, and 2-iodo-aryl amides substrates can be exploited in the selenium-nitrogen coupling reaction by employing 25-100 mol % of CuI/1,10-phenanthroline (L) and potassium carbonate as a base in DMF. Furthermore, electron rich 2-chloro-arylamides also underwent selenium-nitrogen coupling reaction to give biologically important selenium-nitrogen heterocycles. Also, copper-catalyzed selenium-nitrogen coupling reaction has been meticulously applied for the synthesis of diaryl diselenides having methoxy, amine, and amide functionality from respective aryl iodides in the presence of stoichiometric amount of succinimide as an external Se-N coupling partner.     

Knoevenagel condensation catalyzed by novel Nmm-based ionic liquids in water

A series of novel N-methyl morpholine (Nmm) based ionic liquids with 1,2-propanediol group were synthesized and used as catalysts for Knoevenagel condensation at room temperature in water. Under the effect of the catalyst, various aldehydes or aliphatic ketones could react with a wide range of activated methylene compounds well, including malononitrile, alkyl cyanoacetate, cyanoacetamide, β-diketone, barbituric acid, 2-arylacetonitrile and thiazolidinedione. Furthermore, most of the products could be separated just by filtrating and washing with water. Additionally, the catalyst is recyclable and applicable for the large-scale synthesis.     

Construction of polyheterocyclic spirotetrahydrothiophene derivatives via sulfa-Michael/aldol cascade reaction

A series of polyheterocyclic spirotetrahydrothiophene derivatives were obtained in moderate to excellent yields via a catalyst-free sulfa-Michael/aldol cascade reaction of chalcones 1 and commercially available 1,4-dithiane-2,5-diol 2 under mild conditions. We also present the first asymmetric sulfa-Michael/aldol cascade reaction of chalcones 1 and commercially available 1,4-dithiane-2,5-diol 2 with moderate to good enantioselectivities catalyzed by readily available chiral phase-transfer catalysts (PTCs).     

Suzuki-Miyaura reactions of the soluble guanylate cyclase inhibitor NS2028: a non-product specific route to C-8 substituted analogues

Both soluble guanylate cyclase (sGC) inhibitors ODQ 1 and NS2028 2 are synthesized via improved protocols. In the former case treating 3,4-dihydroquinoxalin-2(1H)-one oxime 8, which can be prepared in two steps from 1,2-benzenediamine, with 1,1′-carbonyldiimidazole (CDI) gives the dihydro-ODQ 10 that in the presence of KMnO₄ oxidises to give ODQ 1 in an overall yield of 46% starting from 1,2-benzenediamine. In the latter case, the synthesis affords NS2028 2 from 2-amino-4-bromophenol 3 in three steps with an overall yield of 85% and avoids the need for chromatography. Furthermore, Suzuki-Miyaura reaction conditions are described that enable the preparation of 8-aryl and 8-heteroaryl derivatives of NS2028 directly from NS2028 2. Finally, demethylation of the 8-(methoxyphenyl) substituted analogues afforded the 8-(hydroxyphenyl) derivatives 40-42. All new products are fully characterised.