| 1. |
- Dudka, Ilona, et al.
(författare)
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Metabolomic profiling reveals plasma GlycA and GlycB as a potential biomarkers for treatment efficiency in rheumatoid arthritis
- 2021
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Ingår i: Journal of Pharmaceutical and Biomedical Analysis. - : Elsevier. - 0731-7085 .- 1873-264X. ; 197
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Tidskriftsartikel (refereegranskat)abstract
- In this pilot study, we carried out metabolic profiling of patients with rheumatoid arthritis (RA) starting therapy with biological disease-modifying antirheumatic drugs (bDMARDs). The main aim of the study was to assess the occurring metabolic changes associated with therapy success and metabolic pathways involved. In particular, the potential of the metabolomics profiles was evaluated as therapeutically valuable prognostic indicators of the effectiveness of bDMARD treatment to identify responders versus non-responders prior to implementing treatment.Plasma metabolomic profiles of twenty-five patients with RA prior bDMARD treatment and after three months of therapy were obtained by 1H NMR, liquid chromatography - mass spectrometry, and gas chromatography - mass spectrometry and evaluated by statistical and multivariate analyses.In the group of responders, significant differences in their metabolic patterns were seen after three months of the bDMARD therapy compared with profiles prior to treatment. We identified 24 metabolites that differed significantly between these two-time points mainly belonging to amino acid metabolism, peptides, lipids, cofactors, and vitamins and xenobiotics. Eleven metabolites differentiated responders versus non-responders before treatment. Additionally, N-acetylglucosamine and N-acetylgalactosamine (GlycA) and N-acetylneuraminic acid (GlycB) persisted significant in comparison responders to non-responders after three months of therapy. Moreover, those two metabolites indicated prediction of response potential by results of receiver-operating characteristic (ROC) curve analysis.The applied analysis provides novel insights into the metabolic pathways involved in RA patient’s response to bDMARD and therapy effectiveness. GlycA and GlycB are promising biomarkers to identify responding patients prior onset of bDMARD therapy.
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| 2. |
- Szuba, Agata, et al.
(författare)
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Membrane binding controls ordered self-assembly of animal septins
- 2021
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Ingår i: eLIFE. - : eLife Sciences Publications Ltd. - 2050-084X. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- Septins are conserved cytoskeletal proteins that regulate cell cortex mechanics. The mechanisms of their interactions with the plasma membrane remain poorly understood. Here, we show by cell-free reconstitution that binding to flat lipid membranes requires electrostatic interactions of septins with anionic lipids and promotes the ordered self-assembly of fly septins into filamentous meshworks. Transmission electron microscopy reveals that both fly and mammalian septin hexamers form arrays of single and paired filaments. Atomic force microscopy and quartz crystal microbalance demonstrate that the fly filaments form mechanically rigid, 12- to 18-nm thick, double layers of septins. By contrast, C-terminally truncated septin mutants form 4-nm thin monolayers, indicating that stacking requires the C-terminal coiled coils on DSep2 and Pnut subunits. Our work shows that membrane binding is required for fly septins to form ordered arrays of single and paired filaments and provides new insights into the mechanisms by which septins may regulate cell surface mechanics.
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