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101.
102.
Pavlik R Wypior G Hecht S Papadopoulos P Kupka M Thaler C Wiest I Pestka A Friese K Jeschke U 《Histochemistry and cell biology》2011,136(3):289-299
Estradiol and progesterone mediate their actions by binding to classical nuclear receptors, estrogen receptor α (ERα) and
estrogen receptor β (ERβ) and progesterone receptor A and B (PR-A and PR-B) and the non-classical G protein-coupled estrogen
receptor (GPER). Several animal knock-out models have shown the importance of the receptors for growth of the oocyte and ovulation.
The aim of our study was to identify GPER in human granulosa cells (GC) for the first time. Moreover, the effect of different
doses of gonadotropins on estrogen and progesterone receptors in the human ovary should be investigated as follicle stimulating
hormone (FSH) and luteinizing hormone (LH) are also responsible for numerous mechanisms in the ovary like induction of the
steroid biosynthesis. Human GC were cultured in vitro and stimulated with different doses of recombinant human FSH or LH.
Receptor expression was analyzed by immunocytochemistry and quantitative real-time RT-PCR. GPER could be identified for the
first time in human GC. It could be shown that high concentrations of LH increase GPER protein expression. Furthermore FSH
and LH increased ERβ, PR-A and PR-B significantly on protein level. These findings were verified for high doses of FSH and
LH on mRNA level. ERα was not affected with FSH or LH. We assume that gonadotropins induce GPER, ERβ and PR in luteinized
granulosa cells. 相似文献
103.
Ratcliffe P Adam JM Baker J Bursi R Campbell R Clark JK Cottney JE Deehan M Easson AM Ecker D Edwards D Epemolu O Evans L Fields R Francis S Harradine P Jeremiah F Kiyoi T McArthur D Morrison A Passier P Pick J Schnabel PG Schulz J Steinbrede H Walker G Westwood P Wishart G de Haes JU 《Bioorganic & medicinal chemistry letters》2011,21(8):2541-2546
We report an expansion of the structure-activity relationship (SAR) of a novel series of indole-3-heterocyclic CB1 receptor agonists. Starting from the potent but poorly soluble lead, 1, a rational approach was taken in order to balance solubility, hERG activity and potency while retaining the desired long duration of action within the mouse tail flick test. This led to the discovery of compound 38 which successfully progressed into clinical development. 相似文献
104.
105.
106.
Trapani A Denora N Iacobellis G Sitterberg J Bakowsky U Kissel T 《AAPS PharmSciTech》2011,12(4):1302-1311
Brain tumor treatment employing methotrexate (MTX) is limited by the efflux mechanism of Pg-p on the blood–brain barrier.
We aimed to investigate MTX-loaded chitosan or glycol chitosan (GCS) nanoparticles (NPs) in the presence and in the absence
of a coating layer of Tween 80 for brain delivery of MTX. The effect of a low Tween 80 concentration was evaluated. MTX NPs
were formulated following the ionic gelation technique and size and zeta potential measurements were acquired. Transport across
MDCKII-MDR1 monolayer and cytotoxicity studies against C6 glioma cell line were also performed. Cell/particles interaction
was visualized by confocal microscopy. The particles were shown to be cytotoxic against C6 cells line and able to overcome
MDCKII-MDR1 cell barrier. GCS-based NPs were the most cytotoxic NPs. Confocal observations highlighted the internalization
of Tween 80-coated fluorescent NPs more than Tween 80-uncoated NPs. The results suggest that even a low concentration of Tween
80 is sufficient for enhancing the transport of MTX from the NPs across MDCKII-MDR1 cells. The nanocarriers represent a promising
strategy for the administration of MTX to brain tumors which merits further investigations under in vivo conditions. 相似文献
107.
Kempf T Zarbock A Widera C Butz S Stadtmann A Rossaint J Bolomini-Vittori M Korf-Klingebiel M Napp LC Hansen B Kanwischer A Bavendiek U Beutel G Hapke M Sauer MG Laudanna C Hogg N Vestweber D Wollert KC 《Nature medicine》2011,17(5):581-588
Inflammatory cell recruitment after myocardial infarction needs to be tightly controlled to permit infarct healing while avoiding fatal complications such as cardiac rupture. Growth differentiation factor-15 (GDF-15), a transforming growth factor-β (TGF-β)-related cytokine, is induced in the infarcted heart of mice and humans. We show that coronary artery ligation in Gdf15-deficient mice led to enhanced recruitment of polymorphonuclear leukocytes (PMNs) into the infarcted myocardium and an increased incidence of cardiac rupture. Conversely, infusion of recombinant GDF-15 repressed PMN recruitment after myocardial infarction. In vitro, GDF-15 inhibited PMN adhesion, arrest under flow and transendothelial migration. Mechanistically, GDF-15 counteracted chemokine-triggered conformational activation and clustering of β(2) integrins on PMNs by activating the small GTPase Cdc42 and inhibiting activation of the small GTPase Rap1. Intravital microscopy in vivo in Gdf15-deficient mice showed that Gdf-15 is required to prevent excessive chemokine-activated leukocyte arrest on the endothelium. Genetic ablation of β(2) integrins in myeloid cells rescued the mortality of Gdf15-deficient mice after myocardial infarction. To our knowledge, GDF-15 is the first cytokine identified as an inhibitor of PMN recruitment by direct interference with chemokine signaling and integrin activation. Loss of this anti-inflammatory mechanism leads to fatal cardiac rupture after myocardial infarction. 相似文献
108.
Lutz A Nackenhorst U von Lewinski G Windhagen H Floerkemeier T 《Biomechanics and modeling in mechanobiology》2011,10(5):627-640
Numerical investigations with regard to the subtrochanteric fracture risk induced by three alternative methods for the treatment
of femoral head necrosis are outlined in this presentation. The traditional core decompression technique will be compared
with minimal invasive multiple low diameter drillings and the implantation of an innovative tantalum implant. With emphasis
to the newly introduced computational strategies and modeling approaches, the modeling of critical loading conditions as well
as mesh convergence is outlined in detail. In addition to the immediate postoperative fracture risk, the long-term stability
of the different approaches for treating femoral head necrosis is predicted by performing well-established bone remodeling
simulation techniques. The computed results are augmented for results obtained from clinical experience. 相似文献
109.
Plant-based material, protein and biodegradable plastic 总被引:3,自引:0,他引:3
Fibrous proteins from spiders, proteins with synthetic multiple repeats and mammalian structural proteins such as collagen have been produced in transgenic plants. Recent advances in the production of biodegradable plastic in plants also show the potential of molecular farming for research into and production of materials. Selection of a growing variety of such products, optimization of expression, and the development of effective purification strategies will further promote this growing field of biotechnology. 相似文献
110.
A new series of N-linked 5-triazolylmethyl oxazolidinones with varying substitution at the piperazine nitrogen 4-position were synthesized and tested against a panel of Gram-positive and Gram-negative bacteria including clinical isolates. Most of the compounds showed excellent antibacterial activity against susceptible and resistant Gram-positive organisms. One of the compounds showed enhanced antibacterial activity against Moraxella catarrhalis. 相似文献