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791.
Magdalena M. Scharf Dr. Mirjam Zimmermann Florian Wilhelm Raimond Stroe Dr. Maria Waldhoer Prof. Dr. Peter Kolb 《ChemMedChem》2020,15(10):882-890
The binding pockets of aminergic G protein-coupled receptors are often targeted by drugs and virtual screening campaigns. In order to find ligands with unprecedented scaffolds for one of the best-investigated receptors of this subfamily, the β2-adrenergic receptor, we conducted a docking-based screen insisting that molecules would address previously untargeted residues in extracellular loop 2. We here report the discovery of ligands with a previously undescribed coumaran-based scaffold. Furthermore, we provide an analysis of the added value that X-ray structures in different conformations deliver for such docking screens. 相似文献
792.
Giulia Gagno Federico Ferro Alessandra Lucia Fluca Milijana Janjusevic Maddalena Rossi Gianfranco Sinagra Antonio Paolo Beltrami Rita Moretti Aneta Aleksova 《International journal of molecular sciences》2020,21(24)
Ischemic heart disease (IHD) is among the leading causes of death in developed countries. Its pathological origin is traced back to coronary atherosclerosis, a lipid-driven immuno-inflammatory disease of the arteries that leads to multifocal plaque development. The primary clinical manifestation of IHD is acute myocardial infarction (AMI),) whose prognosis is ameliorated with optimal timing of revascularization. Paradoxically, myocardium re-perfusion can be detrimental because of ischemia-reperfusion injury (IRI), an oxidative-driven process that damages other organs. Amyloid-β (Aβ) plays a physiological role in the central nervous system (CNS). Alterations in its synthesis, concentration and clearance have been connected to several pathologies, such as Alzheimer’s disease (AD) and cerebral amyloid angiopathy (CAA). Aβ has been suggested to play a role in the pathogenesis of IHD and cerebral IRI. The purpose of this review is to summarize what is known about the pathological role of Aβ in the CNS; starting from this evidence, we will illustrate the role played by Aβ in the development of coronary atherosclerosis and its possible implications in the pathophysiology of IHD and myocardial IRI. Better elucidation of Aβ’s contribution to the molecular pathways underlying IHD and IRI could be of great help in developing new therapeutic strategies. 相似文献
793.
Ioannis Tsialtas Achilleas Georgantopoulos Maria E. Karipidou Foteini D. Kalousi Aikaterini G. Karra Demetrios D. Leonidas Anna-Maria G. Psarra 《International journal of molecular sciences》2021,22(14)
Estrogens are steroid hormones that play a crucial role in the regulation of the reproductive and non-reproductive system physiology. Among non-reproductive systems, the nervous system is mainly affected by estrogens due to their antioxidant, anti-apoptotic, and anti-inflammatory activities, which are mediated by membranous and nuclear estrogen receptors, and also by non-estrogen receptor-associated estrogen actions. Neuronal viability and functionality are also associated with the maintenance of mitochondrial functions. Recently, the localization of estrogen receptors, especially estrogen receptor beta, in the mitochondria of many types of neuronal cells is documented, indicating the direct involvement of the mitochondrial estrogen receptor beta (mtERβ) in the maintenance of neuronal physiology. In this study, cell lines of N2A cells stably overexpressing a mitochondrial-targeted estrogen receptor beta were generated and further analyzed to study the direct involvement of mtERβ in estrogen neuroprotective antioxidant and anti-apoptotic actions. Results from this study revealed that the presence of estrogen receptor beta in mitochondria render N2A cells more resistant to staurosporine- and H2O2-induced apoptotic stimuli, as indicated by the reduced activation of caspase-9 and -3, the increased cell viability, the increased ATP production, and the increased resistance to mitochondrial impairment in the presence or absence of 17-β estradiol (E2). Thus, the direct involvement of mtERβ in antioxidant and anti-apoptotic activities is documented, rendering mtERβ a promising therapeutic target for mitochondrial dysfunction-associated degenerative diseases. 相似文献
794.
Yasuhiro Unno Toshiya Sasami Masayuki Hagiwara Shinichi Sasaki Akira Yunoki 《Journal of Nuclear Science and Technology》2013,50(3):376-384
We proposed a method to measure the radioactivity of Sr/Y-90 in the mixture of Cs-134 and Cs-137 without chemical pretreatment. It was realized by subtracting the electrons produced in Cs-134 and Cs-137 from entire electron emission rate that can be determined by the efficiency tracer technique in the 4πβ–γ coincidence counting method. The radioactivity of Cs-134 and Cs-137 can be determined by gamma ray spectrometry. The measurements were conducted using plastic and NaI(Tl) scintillation detector with a large solid angle. The validity of the measurement method was shown by agreement of the results with the known radioactivities. 相似文献
795.
《Journal of Nuclear Science and Technology》2013,50(4):237-240
Americium-241 was recovered by coprecipitation from an aqueous solution discarded after the purification of 50 g of plutonium. Incidental plutonium which had leaked out from the purification processes was also recovered. The aqueous waste solution (30l) was made alkaline by adding an excess of calcium hydroxide. Plutonium and 241 Am were carried with a fresh precipitate of calcium hydroxide and separated from each other by ion exchange technique. Approximately 30 mg of 241Am and 2g of plutonium were recovered. The yields were about 80% for both 241Am and plutonium. The salt solution after the recovery was converted to solid waste and discarded. 相似文献
796.
利用接枝共聚的方法制备了β-环糊精交联磁性壳聚糖,并将其用于吸附水溶液中的U(Ⅵ),考察了溶液初始pH、吸附时间、温度等因素对U(Ⅵ)去除率的影响。吸附实验结果表明:β-环糊精交联磁性壳聚糖对U(Ⅵ)的吸附平衡时间为60 min;温度越低,吸附剂投加量越大;溶液初始pH在3.0~6.0的弱酸性范围内有利于β-环糊精交联磁性壳聚糖对U(Ⅵ)的吸附。解吸实验结果表明,β-环糊精交联磁性壳聚糖经5次解吸后对U(Ⅵ)的吸附去除率仅下降7.41%。SEM表明,β-环糊精交联磁性壳聚糖表面粗糙。IR分析显示,β-环糊精交联磁性壳聚糖表面的-OH、-NH2是U(Ⅵ)结合的主要位点,吸附U(Ⅵ)后并未明显改变原有结构。 相似文献
797.
798.
Protective effects of s-ethyl cysteine (SEC) and s-methyl cysteine (SMC) in kidney of diabetic mice were examined. SEC and SMC at 0.5, 1, 1.5, 2 g/L were added to the drinking water for 6 wk. Results showed that the intake of SEC or SMC alleviated body weight loss and urine output, as well as markedly decreased plasma blood urea nitrogen (BUN) and creatinine clearance (CCr) in diabetic mice (P < 0.05). The intake of SEC caused significantly dose-dependent increase in insulin and decrease in blood glucose, urinary albumin and type IV collagen (P < 0.05). SEC and SMC intake significantly and dose-dependently decreased malondialdehyde level and increased glutathione content in kidney (P < 0.05). The intake of these agents also increased renal GPx activity (P < 0.05), but there was no dose-dependent effect. SEC treatments dose-dependently decreased IL-6 and TNF-alpha levels, increased IL-4 and IL-10 levels, as well as upregulated IL-10 mRNA expression (P < 0.05). SMC treatments significantly suppressed renal IL-6 and TNF-alpha levels (P < 0.05), but did not affect IL-4 and IL-10 levels (P < 0.05). SEC or SMC intake significantly suppressed renal TGF-beta1 level and renal PKC activity (P < 0.05); however, only SEC treatments showed dose-dependent effect. SEC and SMC treatments significantly down-regulated mRNA expression of renal TGF-beta1 (P < 0.05), only SEC treatments had dose-dependent effects. Based on the observed antioxidative, antiinflammatory, and antifibrogenic effects, the supplement of SEC or SMC might be helpful for the prevention or treatment of diabetic kidney diseases. 相似文献
799.
Worapon Kiatkittipong Suwimol WongsakulphasatchNattapon Tintan Navadol LaosiripojanaPiyasan Praserthdam Suttichai Assabumrungrat 《Fuel Processing Technology》2011,92(10):1999-2004
This research studied the modification of beta-zeolite for self-etherification process of fluidized catalytic cracking (FCC) gasoline and ethanol. The catalytic activity of reducing olefins in FCC gasoline accompanied with higher ethanol substitution was evaluated; moreover, the influences of Si/Al ratio in beta zeolite and the addition of copper (Cu) or magnesium (Mg) in the beta zeolite on the reaction performance were also investigated. It was found that the beta zeolite with Si/Al ratio of 27 (beta27) can enhance higher ethanol conversion than those of 42 and 77. In addition, the modification of beta27 by Cu (Cu-beta27) can further improve the ethanol conversion from 38.2% (beta27) to 55.1%, and the olefin content reduction from 46.2% (beta27) to 62.4%. The improvement of the catalytic activity also enhances the obtained gasoline properties i.e. lower blending Reid vapor pressure (bRvp) and higher research octane number (RON). 相似文献
800.
Ladiwala AR Mora-Pale M Lin JC Bale SS Fishman ZS Dordick JS Tessier PM 《Chembiochem : a European journal of chemical biology》2011,12(11):1749-1758
Substantial evidence suggests that soluble prefibrillar oligomers of the Aβ42 peptide associated with Alzheimer's disease are the most cytotoxic aggregated Aβ isoform. Limited previous work has revealed that aromatic compounds capable of remodeling Aβ oligomers into nontoxic conformers typically do so by converting them into off-pathway aggregates instead of dissociating them into monomers. Towards identifying small-molecule antagonists capable of selectively dissociating toxic Aβ oligomers into soluble peptide at substoichiometric concentrations, we have investigated the pathways used by polyphenol aglycones and their glycosides to remodel Aβ soluble oligomers. We find that eleven polyphenol aglycones of variable size and structure utilize the same remodeling pathway whereby Aβ oligomers are rapidly converted into large, off-pathway aggregates. Strikingly, we find that glycosides of these polyphenols all utilize a distinct remodeling pathway in which Aβ oligomers are rapidly dissociated into soluble, disaggregated peptide. This disaggregation activity is a synergistic combination of the aglycone and glycone moieties because combinations of polyphenols and sugars fail to disaggregate Aβ oligomers. We also find that polyphenolic glycosides and aglycones use the same opposing pathways to remodel Aβ fibrils. Importantly, both classes of polyphenols fail to remodel nontoxic Aβ oligomers (which are indistinguishable in size and morphology to Aβ soluble oligomers) or promote aggregation of freshly disaggregated Aβ peptide; thus revealing that they are specific for remodeling toxic Aβ conformers. We expect that these and related small molecules will be powerful chemical probes for investigating the conformational and cellular underpinnings of Aβ-mediated toxicity. 相似文献