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191.
Laïos I Journe F Laurent G Nonclercq D Toillon RA Seo HS Leclercq G 《The Journal of steroid biochemistry and molecular biology》2003,87(2-3):207-221
This study aimed at a better understanding of estrogen receptor alpha (ER) up regulation induced by partial estrogen antagonists. Effect of treatment with hydroxytamoxifen (OH-Tam) on ER level in MCF-7 cells was investigated by an approach combining ER measurement (enzyme immunoassay) and morphological demonstration (immunofluorescence). Furthermore, the influence of drug exposure on the rates of ER synthesis and degradation was assessed by determining [35S]methionine incorporated into the receptor in different experimental conditions (measurement of synthesis or pulse-chase experiments). ER up regulation was already induced by a 1-h pulse treatment with OH-Tam, thus a continuous exposure was not required. This process appeared reversible (i.e. ER accumulation due to OH-Tam rapidly vanished upon subsequent exposure to 17beta-estradiol (E2) or the pure antiestrogen RU 58668). While OH-Tam did not affect the rate of [35S]methionine incorporation into ER, it clearly caused an impairment of ER degradation (pulse-chase experiments) indicating that up regulation results from a stabilization of the receptor associated with the maintenance of its synthesis. Various tamoxifen derivatives, as well as a few related partial antiestrogens, were compared on the basis of binding ability and propensity to induce ER up regulation. A close relationship was found between both properties. Structure-activity analysis revealed that the capacity of these compounds to induce ER up regulation is associated with characteristics of their aminoalkyle side-chain, similar to those required for antiestrogenicity. 相似文献
192.
Anna Marchiani Stefano Mammi Giuliano Siligardi Rohanah Hussain Isabella Tessari Luigi Bubacco Giovanna Delogu Davide Fabbri Maria A. Dettori Daniele Sanna Sonia Dedola Pier A. Serra Paolo Ruzza 《Amino acids》2013,45(2):327-338
Curcumin, a dietary polyphenol, has shown a potential to act on the symptoms of neurodegenerative disorders, including Alzheimer’s and Parkinson’s diseases, as a consequence of its antioxidant, anti-inflammatory and anti-protein aggregation properties. Unfortunately, curcumin undergoes rapid degradation at physiological pH into ferulic acid, vanillin and dehydrozingerone, making it an unlikely drug candidate. Here, we evaluated the ability of some curcumin by-products: dehydrozingerone (1), its O-methyl derivative (2), zingerone (3), and their biphenyl analogues (4–6) to interact with α-synuclein (AS), using CD and fluorescence spectroscopy. In addition, the antioxidant properties and the cytoprotective effects in rat pheochromocytoma (PC12) cells prior to intoxication with H2O2, MPP+ and MnCl2 were examined while the Congo red assay was used to evaluate the ability of these compounds to prevent aggregation of AS. We found that the biphenyl zingerone analogue (6) interacts with high affinity with AS and also displays the best antioxidant properties while the biphenyl analogues of dehydrozingerone (4) and of O-methyl-dehydrozingerone (5) are able to partially inhibit the aggregation process of AS, suggesting the potential role of a hydroxylated biphenyl scaffold in the design of AS aggregation inhibitors. 相似文献
193.
Multiple nanosecond duration molecular dynamics simulations on the pore-lining M2 helix of the nicotinic acetylcholine receptor reveal how its structure and dynamics change as a function of environment. In water, the M2 helix partially unfolds to form a molecular hinge in the vicinity of a central Leu residue that has been implicated in the mechanism of ion channel gating. In a phospholipid bilayer, either as a single transmembrane helix, or as part of a pentameric helix bundle, the M2 helix shows less flexibility, but still exhibits a kink in the vicinity of the central Leu. The single M2 helix tilts relative to the bilayer normal by 12 degrees, in agreement with recent solid state NMR data (Opella et al., Nat Struct Biol 6:374-379, 1999). The pentameric helix bundle, a model for the pore domain of the nicotinic receptor and for channels formed by M2 peptides in a bilayer, is remarkably stable over a 2-ns MD simulation in a bilayer, provided one adjusts the pK(A)s of ionizable residues to their calculated values (when taking their environment into account) before starting the simulation. The resultant transbilayer pore shows fluctuations at either mouth which transiently close the channel. Proteins 2000;39:47-55. 相似文献
194.
Andrew C. Steer Adam W. J. Jenney Joseph Kado Michael R. Batzloff Sophie La Vincente Lepani Waqatakirewa E. Kim Mulholland Jonathan R. Carapetis 《PLoS neglected tropical diseases》2009,3(6)
Background
Impetigo and scabies are endemic diseases in many tropical countries; however the epidemiology of these diseases is poorly understood in many areas, particularly in the Pacific.Methodology/Principal Findings
We conducted three epidemiological studies in 2006 and 2007 to determine the burden of disease due to impetigo and scabies in children in Fiji using simple and easily reproducible methodology. Two studies were performed in primary school children (one study was a cross-sectional study and the other a prospective cohort study over ten months) and one study was performed in infants (cross-sectional). The prevalence of active impetigo was 25.6% (95% CI 24.1–27.1) in primary school children and 12.2% (95% CI 9.3–15.6) in infants. The prevalence of scabies was 18.5% (95% CI 17.2–19.8) in primary school children and 14.0% (95% CI 10.8–17.2) in infants. The incidence density of active impetigo, group A streptococcal (GAS) impetigo, Staphylococcus aureus impetigo and scabies was 122, 80, 64 and 51 cases per 100 child-years respectively. Impetigo was strongly associated with scabies infestation (odds ratio, OR, 2.4, 95% CI 1.6–3.7) and was more common in Indigenous Fijian children when compared with children of other ethnicities (OR 3.6, 95% CI 2.7–4.7). The majority of cases of active impetigo in the children in our study were caused by GAS. S. aureus was also a common cause (57.4% in school aged children and 69% in infants).Conclusions/Significance
These data suggest that the impetigo and scabies disease burden in children in Fiji has been underestimated, and possibly other tropical developing countries in the Pacific. These diseases are more than benign nuisance diseases and consideration needs to be given to expanded public health initiatives to improve their control. 相似文献195.
196.
Quarta D Ferré S Solinas M You ZB Hockemeyer J Popoli P Goldberg SR 《Journal of neurochemistry》2004,88(5):1151-1158
Previous studies have demonstrated opposing roles for adenosine A1 and A2A receptors in the modulation of extracellular levels of glutamate and dopamine in the striatum. In the present study, acute systemic administration of motor-activating doses of the A2A receptor antagonist MSX-3 significantly decreased extracellular levels of dopamine and glutamate in the shell of the rat nucleus accumbens (NAc) and counteracted both dopamine and glutamate release induced by systemic administration of motor-activating doses of either the A1 receptor antagonist CPT or caffeine. Furthermore, exposure to caffeine in the drinking water (1 mg/mL, 14 days) resulted in tolerance to the effects of systemic injection of CPT or caffeine, but not MSX-3, on extracellular levels of dopamine and glutamate in the NAc shell. The present results show: first, the existence of opposite tonic effects of adenosine on extracellular levels of dopamine and glutamate in the shell of the NAc mediated by A1 and A2A receptors; second, that complete tolerance to caffeine's dopamine- and glutamate-releasing effects which develops after chronic caffeine exposure is attributable to an A1 receptor-mediated mechanism. Development of tolerance to the dopamine-releasing effects of caffeine in the shell of the NAc may explain its weak addictive properties and atypical psychostimulant profile. 相似文献
197.
Wild Sicilian Rosemary: Phytochemical and Morphological Screening and Antioxidant Activity Evaluation of Extracts and Essential Oils 下载免费PDF全文
Edoardo M. Napoli Laura Siracusa Antonella Saija Antonio Speciale Domenico Trombetta Teresa Tuttolomondo Salvatore La Bella Mario Licata Giuseppe Virga Raffaele Leone Claudio Leto Laura Rubino Giuseppe Ruberto 《化学与生物多样性》2015,12(7):1075-1094
To identify the best biotypes, an extensive survey of Sicilian wild rosemary was carried out by collecting 57 samples from various sites, followed by taxonomic characterization from an agronomic perspective. All the biotypes collected were classified as Rosmarinus officinalis L. A cluster analysis based on the morphological characteristics of the plants allowed the division of the biotypes into seven main groups, although the characteristics examined were found to be highly similar and not area‐dependent. Moreover, all samples were analyzed for their phytochemical content, applying an extraction protocol to obtain the nonvolatile components and hydrodistillation to collect the essential oils for the volatile components. The extracts were characterized by LC‐UV‐DAD/ESI‐MS, and the essential oils by GC‐FID and GC/MS analyses. In the nonvolatile fractions, 18 components were identified, namely, 13 flavones, two organic acids, and three diterpenes. In the volatile fractions, a total of 82 components were found, with as predominant components α‐pinene and camphene among the monoterpene hydrocarbons and 1,8‐cineole, camphor, borneol, and verbenone among the oxygenated monoterpenes. Cluster analyses were carried out on both phytochemical profiles, allowing the separation of the rosemary samples into different chemical groups. Finally, the total phenol content and the antioxidant activity of the essential oils and extracts were determined with the Folin–Ciocalteu (FC) colorimetric assay, the UV radiation‐induced peroxidation in liposomal membranes (UV‐IP test), and the scavenging activity of the superoxide radical (O$\rm{{_{2}^{{^\cdot} -}}}$ ). The present study confirmed that the essential oils and organic extracts of the Sicilian rosemary samples analyzed showed a considerable antioxidant/free radical‐scavenging activity. 相似文献
198.
Simon N. Haydar Chiara Ghiron Laura Bettinetti Hendrick Bothmann Thomas A. Comery John Dunlop Salvatore La Rosa Iolanda Micco Martina Pollastrini Joanna Quinn Renza Roncarati Carla Scali Michela Valacchi Maurizio Varrone Riccardo Zanaletti 《Bioorganic & medicinal chemistry》2009,17(14):5247-5258
Alpha 7 nicotinic acetylcholine receptor (α7 nAChR) agonists are promising therapeutic candidates for the treatment of cognitive impairment associated with a variety of disorders including Alzheimer’s disease and schizophrenia. Alpha 7 nAChRs are expressed in brain regions associated with cognitive function, regulate cholinergic neurotransmission and have been shown to be down regulated in both schizophrenia and Alzheimer’s disease. Herein we report a novel, potent small molecule agonist of the alpha 7 nAChR, SEN12333/WAY-317538. This compound is a selective agonist of the α7 nAChR with excellent in vitro and in vivo profiles, excellent brain penetration and oral bioavailability, and demonstrates in vivo efficacy in multiple behavioural cognition models. The SAR and biological evaluation of this series of compounds are discussed. 相似文献
199.
Giudici AM Regente MC Villalaín J Pfüller K Pfüller U De La Canal L 《Physiologia plantarum》2004,121(1):2-7
Viscotoxins (Vts) are basic peptides expressed in mistletoe leaves, seeds and stems which have been shown to be cytotoxic to mammalian cells. The aim of this study was to analyse whether Vts were able to control and/or inhibit the growth of phytopathogenic fungi to obtain a clue to their biological function. Incubation of two Vt isoforms, VtA3 and VtB, at a final concentration of 10 µ M resulted in a complete blockage of the germination of spores from three different pathogenic fungi. It was also shown that lower concentrations than 10 µ M of VtA3 and VtB inhibit their mycelial growth in a dose-dependent manner. The protein dose required to inhibit the growth of Fusarium solani and Sclerotinia sclerotiorum to a 50% was between 1.5 and 3.75 µ M , which represents a potent activity. No significant differences in the antifungal potency for each Vt isoform, either VtA3 and VtB, were observed, although they have been shown to exert differential cytotoxicity on mammalian cells. It was also demonstrated that Vts act as fungicidal compounds. To explore the basis of the antifungal activity the ability of VtA3 to induce changes in membrane permeability and on the oxidative status of F. solani spores was analysed. By using a specific fluorescent probe on intact spores, it was demonstrated that VtA3 produces rapid changes in fungal membrane permeability. It also induces H2 O2 production verified by a histochemical staining. The data presented in this study support a direct role of Vts in the plant defence determined by their lethal effect on fungal pathogens. 相似文献
200.
Sancho R Macho A de La Vega L Calzado MA Fiebich BL Appendino G Muñoz E 《Journal of immunology (Baltimore, Md. : 1950)》2004,172(4):2341-2351