Thyroid autoregulation. Inhibitory effects of iodinated derivatives of arachidonic acid on iodine metabolism

Thyroid autoregulation has been linked to an organified iodocompound. Since several iodolipids are produced by the gland their possible role in thyroid autoregulation was examined. The following pure synthetic compounds were prepared: 1) 14-iodo-15-hydroxy-5,8,11-eicosatrienoic acid (I-OH-A); 2) its omega lactone (IL-omega); 3) 5-hydroxy-6-iodo-8,11,14-eicosatrienoic acid delta lactone (IL-delta). Their action on iodine metabolism was studied. Iodine uptake was measured in calf thyroid slices. At 10(-4)M I-OH-A caused a 64% decrease in the T/M ratio, while IL-omega inhibited it by 36% and IL-delta was without effect. At 10(-5)M the inhibition was 44% for I-OH-A and 19% for IL-omega, while T3 was without action. A possible isotopic dilution effect was excluded, and no change in iodine efflux was observed. The inhibition by I-OH-A of iodide uptake was observed after only 15 min preincubation. This compound also decreased 125I accumulation in rats. In calf thyroid slices, I-OH-A at 10(-4)M, inhibited PB125I formation by 80%, IL-omega by 62% and IL-delta by 37%. T3 and arachidonic acid were without action. I-OH-A also caused a dose-dependent inhibition of TSH-stimulated iodide organification. The present results demonstrate, for the first time, that iodinated derivatives of arachidonic acid inhibit thyroid function and mimic the effect of iodide on thyroid autoregulation.     

Thyroid autoregulation. Inhibitory effects of iodinated derivatives of arachidonic acid on iodine metabolism

Thyroid autoregulation has been linked to an organified iodocompound. Since several iodolipids are produced by the gland their possible role in thyroid autoregulation was examined. The following pure synthetic compounds were prepared: 1) 14-iodo-15-hydroxy-5,8,11-eicosatrienoic acid (I-OH-A); 2) its omega lactone (IL-ω);3)5-hydroxy-6-iodo-8,11,14-eicosatrienoic acid delta lactone (IL-δ). Their action on iodine metabolism was studied. Iodine uptake was measured in calf thyroid slices. At 10-⁴M I-OH-A caused a 64% decrease in the T/M ratio while IL-ω inhibited it by 36% and IL-δ was without effect. At 10⁻⁵M the inhibition was 44% for I-OH-A and 19% for IL-ω, while T₃ was without action. A possible isotopic dilution effect was excluded, and no change in iodine efflux was observed. The inhibition by I-OH-A of iodine uptake was observed after only 15 min preincubation. This compound alse decreased ¹²⁵I accumulation in rats.In calf thyroid slice, I-OH-A at 10⁻⁴M, inhibited PB¹²⁵I formation by 80%, IL-ω 62% and IL-ω by 37% and arachidonic acid were without action. I-OH-A also caused a dose-dependent inhibition of TSH-stimulated iodide organification.The present results demonstrate, for the first time, that iodinated derivatives of arachidonic acid inhibition thyroid function and mimic the effect of iodine on thyroid autoregulation.     

MSI2通过下调circRNA_001214促进急性髓系白血病细胞HL60生长

Musashi-2（MSI2）是一种RNA结合蛋白质,对维持造血干细胞功能具有重要作用。研究表明,MSI2高表达能促进急性髓系白血病（acute myelocytic leukemia, AML）进展,但其作用机制尚不明确。本研究稳定沉默HL60细胞MSI2后,第1、2、3、4 d对照组的相对细胞生长率分别为1.931 ± 0.027、3.070 ± 0.073、4.017 ± 0.092和4.215 ± 0.246;敲减组分别为1.927 ± 0.035、2.564 ± 0.090、2.825 ± 0.097和3.223 ± 0.182,两组相比具有统计学差异,P<0.001;细胞凋亡明显增加(7.967% ± 0.698% vs 3.400% ± 0.322%., P<0.01);G₀/G₁期细胞比例明显增高（67.430% ± 4.390% vs. 50.360% ± 2.160%, P<0.01）;NUMB蛋白明显上调,LEF1明显下降。环状RNA（circular RNA, circRNA）芯片筛选和荧光定量PCR验证显示,MSI2沉默组circRNA_001214表达水平是对照组3.48倍。这一结果也在NALM6细胞得到证实。进一步用生物信息学分析,显示circRNA_001214最可能与miR-1273a、miR-1273e和miR 5095结合,进而影响参与细胞凋亡相关基因（CYCS、AKT1、BAX、TNFRSF10A、TNFRSF10D）、Wnt信号基因（WNT4、WNT2B、WNT7B、 DKK2、SFRP1、CSNKE1和LEF1）以及参与细胞代谢相关基因（RPE, PGAM4, PGAM1, TAT, CBS、RPE、SUCLG2、PGAM4、PGAM1和 IDNK）。总而言之,MSI2可能通过干扰circRNA_001214生成,减少靶miRNA对凋亡、Wnt信号及细胞代谢相关基因表达的影响,促进细胞生长。     

Optimization of the conditions of the fermentation of beet molasses to lactic acid by Lactobacillus delbrueckii

Optimization studies were carried out for the production of L-lactic acid from the fermentation of beet molasses by Lactobacillus delbrueckii. A Central Composite Design was used to determine the optimum values of the process variables (temperature, pH, inoculum concentration, and initial sucrose concentration) for obtaining the maximum yield and the maximum volumetric productivity of lactic acid. Among the variables selected for study, it was found that all of them apart from the temperature significantly affected the responses (yield and volumetric productivity of lactic acid). The Central Composite Design also permitted formulating two second-order polynomial empirical models relating to the responses and the significant variables. From these models it was possible to determine the value of the variables giving the maximum yield of lactic acid production (87.8%) and the maximum volumetric rate of lactic acid biosynthesis (2.7 g/l · h). Finally, the dependence of the lactic acid yield and productivity on the model variables was investigated. All conclusions are restricted to the experimental range studied.     

城市生态系统的模拟方法：灵敏度模型及其改进

评估城市生态系统的持续发展能力,探讨其持续发展对策是一个复杂的动态问题,需要运用动态的模拟方法进行。由德国著名生态控制论专家Ｆ．Ｖｅｓｔｅｒ和Ａ．Ｖ．Ｈｅｓｌｅｒ教授提出的“灵敏度模型”方法,将系统科学思想、生态控制论方法及城市规划融为一体,解释、模拟、评价和规划城市复杂的系统关系,是模拟城市生态系统很好的方法。本文对该方法进行了改进。改进后的“灵敏度模型”为评价城市持续发展能力、探讨其持续发展对策提供了新的思路。     

慢性心功能不全大鼠心脏和血淋巴细胞β-肾上腺素受体的改变

在主动脉与肾动脉缩窄造成的慢性心功能不全大鼠,血浆儿茶酚胺浓度增高;心脏β-肾上腺素受体(β-AR)数量增加,其中β_1-AR及其mRNA增加,而β_2-AR及其mRNA不变;左心房异丙基肾上腺素(ISO)浓度-收缩效应曲线右移;而心肌ISO浓度-cAMP蓄积曲线无显著改变;血淋巴细胞β-AR数量显著减少.结果提示心功能不全时心脏β_1-AR数量增多,但其介导的正性变力效应反而降低,在cAMP生成以后的信号转导过程或心肌收缩成分功能存在障碍,而血淋巴细胞β-AR的改变与心脏β-AR的功能改变平行.     

Synthesis and biological evaluation of novel NK-1 tachykinin receptor antagonists: The use of cycloalkyl amino acids as a template

In the course of a program aimed at synthesizing novel, potent NK-1 tachykinin receptor antagonists, we developed upon a bioactive model by comparing the low energy structures of a series of peptide and nonpeptide Substance P antagonists. The comparison was based on the super imposition of the aromatic rings, assuming that the rest of the molecule behaves predominantly as a template to arrange the key aromatic groups in the right spatial position. A series of 2-aminocyclohexane carboxylic acid analogues were then selected as the best templates for reproducing the postulated bioactive structure, leading to several pseudo-peptides with interesting biological activity. According to the molecular modeling, these compounds exhibit a neat parallel facing of the indolyl and naphthyl groups at about 3 Å distance. Ultraviolet absorption and steady state fluorescence measurements support this conclusion, showing a linear correlation between the spectral properties and the binding affinity of these analogues. Stacking of the indole ring with naphthalene gives rise to a complex characterized by a well-defined molar extinction coefficient. Consistently, steady state and lifetime fluorescence measurements suggest that the quenching process is ascribable to ground-state interactions between the chromophores. Implications of the π stacking propensity of aromatic groups in the biological activity of the compounds examined are briefly discussed. © 1995 John Wiley & Sons, Inc.     

Oviposition and development of Drosophila modified by magnetic fields

Drosophila flies placed in a habitat with two lateral boxes demonstrated sensitivity to magnetic fields: Oviposition decreased by exposure to pulsated extremely low frequency (ELF) (100)Hz, 1.76 miliTesla (mT) and sinusosidal fields (50 Hz, 1 mT), while there was no initial effect of exposure to a static magnetic field (4.5 mT). Drosophila eggs treated for 48 h with the above described fields showed that (1) mortality of eggs was lower in controls than in eggs exposed to all tested magnetic fields; (2) mortality of larvae increased when a permanent magnet was used; (3) mortality of pupae was highest when a permanent magnet was used; and (4) general adult viability was highest in controls (67%) and diminished progressively when eggs were exposed to pulsated (55%), sinusoidal (45%), and static (35%) magnetic fields.     

FXR在胃粘膜肠化生及胃癌中的表达及其意义研究

目的:研究FXR在胃炎,胃粘膜肠化生及胃癌组织中的表达,分析其在胃癌发生中的意义。方法:采用免疫组化方法检测FXR在55例胃炎组织,61例胃黏膜肠化生组织及61例胃癌组织中的表达,利用统计学方法 SPSS17.0软件分析其在三种组织中的表达变化,结合文献回顾,分析FXR在胃癌发生中的意义。结果:FXR在胃黏膜肠化生中的表达明显高于胃炎组织(P0.05),而在胃癌组织中,FXR的表达显著低于胃粘膜肠化生组织(P0.05)。结论:FXR是一个潜在的胃癌发生生物标记物,其具体机制有待于进一步探索。     

外泌体在病毒感染诊断和治疗中的作用研究 *

外泌体是多泡体与细胞质膜融合后释放的细胞外囊泡.它们携带有源自分泌细胞的功能性蛋白质,脂质和核酸,能够介导细胞间通信,并在生物体的致病过程中发挥重要作用.当前,对外泌体在病毒感染中的作用机制研究,以及外泌体作为病毒感染诊断和治疗的潜在标志物研究仍处于初级阶段.首先阐述了外泌体的组成和生物学发生机制;然后重点阐述了外泌体在病毒感染中的作用机制,尤其是其在免疫调节中的作用;最后探讨了外泌体作为病毒感染诊断和治疗的潜在标志物的可能性及其应用前景.