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排序方式: 共有257条查询结果,搜索用时 15 毫秒
31.
Turk S Verlaine O Gerards T Zivec M Humljan J Sosič I Amoroso A Zervosen A Luxen A Joris B Gobec S 《PloS one》2011,6(5):e19418
Background
Penicillin-binding proteins (PBPs) are well known and validated targets for antibacterial therapy. The most important clinically used inhibitors of PBPs β-lactams inhibit transpeptidase activity of PBPs by forming a covalent penicilloyl-enzyme complex that blocks the normal transpeptidation reaction; this finally results in bacterial death. In some resistant bacteria the resistance is acquired by active-site distortion of PBPs, which lowers their acylation efficiency for β-lactams. To address this problem we focused our attention to discovery of novel noncovalent inhibitors of PBPs.Methodology/Principal Findings
Our in-house bank of compounds was screened for inhibition of three PBPs from resistant bacteria: PBP2a from Methicillin-resistant Staphylococcus aureus (MRSA), PBP2x from Streptococcus pneumoniae strain 5204, and PBP5fm from Enterococcus faecium strain D63r. Initial hit inhibitor obtained by screening was then used as a starting point for computational similarity searching for structurally related compounds and several new noncovalent inhibitors were discovered. Two compounds had promising inhibitory activities of both PBP2a and PBP2x 5204, and good in-vitro antibacterial activities against a panel of Gram-positive bacterial strains.Conclusions
We found new noncovalent inhibitors of PBPs which represent important starting points for development of more potent inhibitors of PBPs that can target penicillin-resistant bacteria. 相似文献32.
Background
Liquid chromatography coupled to mass spectrometry (LC/MS) has been widely used in proteomics and metabolomics research. In this context, the technology has been increasingly used for differential profiling, i.e. broad screening of biomolecular components across multiple samples in order to elucidate the observed phenotypes and discover biomarkers. One of the major challenges in this domain remains development of better solutions for processing of LC/MS data. 相似文献33.
Ablation of PGC-1beta results in defective mitochondrial activity, thermogenesis, hepatic function, and cardiac performance 下载免费PDF全文
Lelliott CJ Medina-Gomez G Petrovic N Kis A Feldmann HM Bjursell M Parker N Curtis K Campbell M Hu P Zhang D Litwin SE Zaha VG Fountain KT Boudina S Jimenez-Linan M Blount M Lopez M Meirhaeghe A Bohlooly-Y M Storlien L Strömstedt M Snaith M Oresic M Abel ED Cannon B Vidal-Puig A 《PLoS biology》2006,4(11):e369
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36.
I Ottestad S Hassani GI Borge A Kohler G Vogt T Hyötyläinen M Orešič KW Brønner KB Holven SM Ulven MC Myhrstad 《PloS one》2012,7(8):e42550
Background
While beneficial health effects of fish and fish oil consumption are well documented, the incorporation of n-3 polyunsaturated fatty acids in plasma lipid classes is not completely understood. The aim of this study was to investigate the effect of fish oil supplementation on the plasma lipidomic profile in healthy subjects.Methodology/Principal Findings
In a double-blinded randomized controlled parallel-group study, healthy subjects received capsules containing either 8 g/d of fish oil (FO) (1.6 g/d EPA+DHA) (n = 16) or 8 g/d of high oleic sunflower oil (HOSO) (n = 17) for seven weeks. During the first three weeks of intervention, the subjects completed a fully controlled diet period. BMI and total serum triglycerides, total-, LDL- and HDL-cholesterol were unchanged during the intervention period. Lipidomic analyses were performed using Ultra Performance Liquid Chromatography (UPLC) coupled to electrospray ionization quadrupole time-of-flight mass spectrometry (QTOFMS), where 568 lipids were detected and 260 identified. Both t-tests and Multi-Block Partial Least Square Regression (MBPLSR) analysis were performed for analysing differences between the intervention groups. The intervention groups were well separated by the lipidomic data after three weeks of intervention. Several lipid classes such as phosphatidylcholine, phosphatidylethanolamine, lysophosphatidylcholine, sphingomyelin, phosphatidylserine, phosphatidylglycerol, and triglycerides contributed strongly to this separation. Twenty-three lipids were significantly decreased (FDR<0.05) in the FO group after three weeks compared with the HOSO group, whereas fifty-one were increased including selected phospholipids and triglycerides of long-chain polyunsaturated fatty acids. After seven weeks of intervention the two intervention groups showed similar grouping.Conclusions/Significance
In healthy subjects, fish oil supplementation alters lipid metabolism and increases the proportion of phospholipids and triglycerides containing long-chain polyunsaturated fatty acids. Whether the beneficial effects of fish oil supplementation may be explained by a remodeling of the plasma lipids into phospholipids and triglycerides of long-chain polyunsaturated fatty acids needs to be further investigated.Trial Registration
ClinicalTrials.gov NCT01034423相似文献37.
Progression to type 1 diabetes is characterized by complex interactions of environmental, metabolic and immune system factors, involving both degenerative pathways leading to loss of pancreatic β-cells as well as protective pathways. The interplay between the degenerative and protective pathways may hold the key to disease outcomes, but no models have so far captured the two together. Here we propose a mathematical framework, an ordinary differential equation (ODE) model, which integrates metabolism and the immune system in early stages of disease process. We hypothesize that depending on the degree of regulation, autoimmunity may also play a protective role in the initial response to stressors. We assume that β-cell destruction follows two paths of loss: degenerative and autoimmune-induced loss. The two paths are mutually competing, leading to termination of the degenerative loss and further to elimination of the stress signal and the autoimmune response, and ultimately stopping the β-cell loss. The model describes well our observations from clinical and non-clinical studies and allows exploration of how the rate of β-cell loss depends on the amplitude and duration of autoimmune response. 相似文献
38.
Schwab U Seppänen-Laakso T Yetukuri L Agren J Kolehmainen M Laaksonen DE Ruskeepää AL Gylling H Uusitupa M Oresic M;GENOBIN Study Group 《PloS one》2008,3(7):e2630
Background
The effect of weight loss on different plasma lipid subclasses at the molecular level is unknown. The aim of this study was to examine whether a diet-induced weight reduction result in changes in the extended plasma lipid profiles (lipidome) in subjects with features of metabolic syndrome in a 33-week intervention.Methodology/Principal Findings
Plasma samples of 9 subjects in the weight reduction group and 10 subjects in the control group were analyzed using mass spectrometry based lipidomic and fatty acid analyses. Body weight decreased in the weight reduction group by 7.8±2.9% (p<0.01). Most of the serum triacylglycerols and phosphatidylcholines were reduced. The decrease in triacylglycerols affected predominantly the saturated short chain fatty acids. This decrease of saturated short chain fatty acid containing triacylglycerols correlated with the increase of insulin sensitivity. However, levels of several longer chain fatty acids, including arachidonic and docosahexanoic acid, were not affected by weight loss. Levels of other lipids known to be associated with obesity such as sphingolipids and lysophosphatidylcholines were not altered by weight reduction.Conclusions/Significance
Diet-induced weight loss caused significant changes in global lipid profiles in subjects with abnormal glucose metabolism. The observed changes may affect insulin sensitivity and glucose metabolism in these subjects.Trial Registration
ClinicalTrials.gov NCT00621205相似文献39.
Lipidomics: a new window to biomedical frontiers 总被引:1,自引:0,他引:1
Lipids are a highly diverse class of molecules with crucial roles in cellular energy storage, structure and signaling. Lipid homeostasis is fundamental to maintain health, and lipid defects are central to the pathogenesis of important and devastating diseases. Newly emerging advances have facilitated the development of so-called lipidomics technologies and offer an opportunity to elucidate the mechanisms leading to disease. Furthermore, these advances also provide the tools to unravel the complexity of the 'allostatic forces' that allow maintenance of normal cellular/tissue phenotypes through the application of bioenergetically inefficient adaptive mechanisms. An alternative strategy is to focus on tissues with limited allostatic capacity, such as the eye, that could be used as readouts of metabolic stress over time. Identification of these allostatic mechanisms and pathological 'scares' might provide a window to unknown pathogenic mechanisms, as well as facilitate identification of early biomarkers of disease. 相似文献
40.
Cvek Jakub Vondráček Vladimir Dvořák Jan Argalacsová Sona Navrátil Matej Buřil Jan 《Reports of Practical Oncology and Radiotherapy》2012,17(2):79-84
AimTo evaluate the outcome of prostate cancer patients with initial PSA value >40 ng/ml.BackgroundThe outcome of prostate cancer patients with very high initial PSA value is not known and patients are frequently treated with palliative intent. We analyzed the outcome of radical combined hormonal treatment and radiotherapy in prostate cancer patients with initial PSA value >40 ng/ml.MethodsBetween January 2003 and December 2007 we treated, with curative intent, 56 patients with non-metastatic prostate cancer and initial PSA value >40 ng/ml. The treatment consisted of two months of neoadjuvant hormonal treatment (LHRH analog), radical radiotherapy (68–78 Gy, conformal technique) and an optional two-year adjuvant hormonal treatment.ResultsThe median time of follow up was 61 months. 5-Year overall survival was 90%. 5-Year biochemical disease free survival was 62%. T stage, Gleason score, PSA value, and radiotherapy dose did not significantly influence the outcome. Late genitourinal and gastrointestinal toxicity was acceptable.ConclusionRadical treatment in combination with hormonal treatment and radiotherapy can be recommended for this subgroup of prostate cancer patients with good performance status and life expectancy. 相似文献