Simultaneous determination of rivanol and mifepristone in human plasma by a HPLC-UV method with solid-phase extraction

A HPLC method with UV detection was developed and validated for the simultaneous determination of rivanol and mifepristone in human plasma. Norethisterone was used as the internal standard. Separation was performed by a C18 reversed-phase column maintained at 20 degrees C. The mobile phase was a mixture of methanol-acetonitrile-0.05% sodium dodecylsulfonate in a 0.05 M phosphate buffer with the pH adjusted to 3.0 (30:30:40, v/v/v) at a flow rate of 0.8 ml/min. Dual wavelength mode was used, with mifepristone monitored at UV 302 nm, while rivanol and norethisterone at 272 nm. A reliable biological sample pre-treatment procedure by means of solid-phase extraction was used, which allowed to obtain good extraction efficiency (>93%) for both of the analytes and the internal standard. The calibration curves were both linear with the correlation coefficient r equal to 0.9999. For rivanol, the assay gave CV% values for precision always lower than 7.8% and mean accuracy values higher than 95.3%. As to mifepristone, precision was always lower than 10.1% and mean accuracy values were higher than 93.8%. The limit of detection for the assay of rivanol and mifepristone was 1.1 and 3 ng/ml, respectively. The method is simple, sensitive and accurate, and allow for simultaneous determination of nanogram levels of rivanol and mifepristone in human plasma. It could be applied to assess the plasma level of rivanol and mifepristone in women undergoing polypharmacy with the two drugs.     

Structural insights into microtubule doublet interactions in axonemes

Coordinated sliding of microtubule doublets, driven by dynein motors, produces periodic beating of eukaryotic cilia and flagella. Recent structural studies of the axoneme, which forms the core of cilia and flagella, have used cryo-electron tomography to reveal new details of the interactions between some of the multitude of proteins that form the axoneme and regulate its movement. Connections between the several types of dyneins, in particular, suggest ways in which their action might be coordinated. Study of the molecular architecture of isolated doublets has provided a structural basis for understanding mechanical properties related to the bending of the axoneme, and has also offered insight into the potential role of doublets in the mechanism of dynein activity regulation.     

The discovery of a potent orally efficacious indole androgen receptor antagonist through in vivo screening

A series of novel 2-(1H-indol-2-yl)-propan-2-ols have been designed, synthesized, and screened for their ability to inhibit testosterone-induced prostate weight increases in immature rats. Through the use of this paradigm, we were able to identify compounds that exhibited in vivo potency equal to that of the marketed antiandrogen Casodex when orally administered.     

Synthesis and identification of novel 11beta-aryl-4',5'-dihydrospiro[estra-4,9-diene-17beta,4'-oxazole] analogs with dissociated antiprogesterone activities

A series of novel 11beta-aryl-4',5'-dihydrospiro[estra-4,9-diene-17beta,4'-oxazole] analogs have been evaluated for their antagonist hormonal properties using the T47D cell-based alkaline phosphatase assay and the A549 cell-based functional assay. Some of the compounds showed highly potent, and more selective antiprogestational activity against antiglucocorticoid activity than mifepristone (RU 486).     

Discovery of novel phosphorus-containing steroids as selective glucocorticoid receptor antagonist

Mifepristone is a non-selective antagonist of 3-oxosteroid receptors with both abortifacient and anti-diabetic activities. For glucocorticoid receptor (GR) program, we sought an unexplored, synthetically accessible phosphorus-containing steroidal mimetic of mifepristone, suitable for parallel synthesis of analogues. One compound 4a, with high oral bioavailability (59%) in rat, exhibited functional antagonism of GR in oral glucose tolerance test (OGTT). Thus this series of compounds might be potentially useful for the treatment of type II diabetes.     

Response of T cells in vivo induced by repeated superantigen treatments at different time intervals

We have investigated the response of T cells to staphylococcal enterotoxin A （SEA） injections in vivo. We found that a single injection of SEA with an optimal dose of 10μg increased the expression of both CD4 and CD8 significantly. There was expansion of SEA-reactive T cells in vivo after SEA re-injection and the time interval between injections strongly influenced the responsiveness of CD4^＋ and CD8^＋ T cells. Anergy of T cells was observed after three SEA treatments. The time interval between injections mainly affected the unresponsiveness of CD4^＋ T cells, not CD8^＋ T cells. Marked deletion followed by anergy of CD4^＋ T cells was induced at short intervals, and anergy without obvious deletion of CD4^＋ T cells was induced at long intervals. We also found that the anergic state was reversible in vivo. Repeated SEA stimulation led to down-regulation of interleukin （IL）-2, and high levels of IL-10. This study showed that both CD4^＋ and CD8^＋ SEA-primed T cells were responsive to SEA rechallenge in vivo, and a third injection was needed to induce the anergy of T cells.     

Protein kinase A modulates PLC-dependent regulation and PIP2-sensitivity of K+ channels

Neurotransmitter and hormone regulation of cellular function can result from a concomitant stimulation of different signaling pathways. Signaling cascades are strongly regulated during disease and are often targeted by commonly used drugs. Crosstalk of different signaling pathways can have profound effects on the regulation of cell excitability. Members of all the three main structural families of potassium channels: inward-rectifiers, voltage-gated and 2-P domain, have been shown to be regulated by direct phosphorylation and Gq-coupled receptor activation. Here we test members of each of the three families, Kir3.1/Kir3.4, KCNQ1/KCNE1 and TREK-1 channels, all of which have been shown to be regulated directly by phosphatidylinositol bisphosphate (PIP2). The three channels are inhibited by activation of Gq-coupled receptors and are differentially regulated by protein kinase A (PKA). We show that Gq-coupled receptor regulation can be physiologically modulated directly through specific channel phosphorylation sites. Our results suggest that PKA phosphorylation of these channels affects Gq-coupled receptor inhibition through modulation of the channel sensitivity to PIP2.     

Traditional Uses,Chemical Constituents and Biological Activities of Plants from the Genus Thymus

The genus Thymus (Lamiaceae) comprises about 214 species throughout the world, mainly found in North Africa, Europe, and temperate Asia zone. They are traditionally used as food additives and folk medicines. This review comprehensively summarizes information about traditional uses, chemical constituents, and biological activities of this genus and provides recommendations for future investigations. All information was gathered from scientific databases including Google Scholar, Sci‐Finder, Web of Science, ScienceDirect, and CNKI. Volatile oils are the most concerned constituents of this genus. Flavonoids, phenylpropanoids, tannins, organic acids, terpenoids, and phytosterols were also summarized. This genus plants possessed a variety of activities including antimicrobial, antioxidant, anti‐inflammatory, cytotoxic, analgesic, and antidiabetic. In brief, this review will be helpful to provide valuable data for explorations and create more interests towards Thymus genus in the future.     

Effects of incident light intensity and light path length on cell growth and oil accumulation in Botryococcus braunii (Chlorophyta)

Botryococcus braunii was cultured in different light path length under different incident light intensity to investigate the effect of light on alga growth as well as hydrocarbon and fatty acid accumulation. Results indicated that longer light path length required higher incident light intensity in order to meet the light requirement of algal growth and hydrocarbon accumulation during the course of cultivation. However, hydrocarbon profile was only affected by the incident light intensity and not influenced by the light path length. High incident light intensity enhanced the accumulation of hydrocarbons with longer carbon chains. Besides, the fatty acid content and profiles were significantly influenced by both incident light intensity and light path. Higher fatty acid content and higher percentage of C18 and monounsaturated fatty acid components were achieved at the higher incident light intensity and lower light path length. Taken together, these results are benefit to improve its biomass and oil productivity through the optimization of light and photobioreactor design.     

小黑杨基因组的初步组装及SSR信息分析

小黑杨是人们以小叶杨和欧洲黑杨为亲本培育出的杂交种,兼具双亲生长速度快、抗性强的优点。本研究通过二代测序技术,对小黑杨进行全基因组测序,初步组装出小黑杨基因组,并以此为基础,识别分析其SSR序列,为小黑杨品种划分、表型性状关联等提供参考。结果表明,共组装得到了366 876条总计368.96 Mbp的contig序列;对其中不小于2 000 bp的21 788条的非冗余contig进行SSR分析,共识别出18 111条SSR序列,其中一、二、三核苷酸重复基序较多。对得到的SSR序列设计引物,共得到12 838对引物,供今后实验使用。