| 1. |
- Ahrentorp, Fredrik, et al.
(författare)
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Sensitive magnetic biodetection using magnetic multi-core nanoparticles and RCA coils
- 2017
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Ingår i: Journal of Magnetism and Magnetic Materials. - : Elsevier BV. - 0304-8853 .- 1873-4766. ; 427, s. 14-18
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Tidskriftsartikel (refereegranskat)abstract
- We use functionalized iron oxide magnetic multi-core particles of 100 nm in size (hydrodynamic particle diameter) and AC susceptometry (ACS) methods to measure the binding reactions between the magnetic nanoparticles (MNPs) and bio-analyte products produced from DNA segments using the rolling circle amplification (RCA) method. We use sensitive induction detection techniques in order to measure the ACS response. The DNA is amplified via RCA to generate RCA coils with a specific size that is dependent on the amplification time. After about 75 min of amplification we obtain an average RCA coil diameter of about 1 mu m. We determine a theoretical limit of detection (LOD) in the range of 11 attomole (corresponding to an analyte concentration of 55 fM for a sample volume of 200 mu L) from the ACS dynamic response after the MNPs have bound to the RCA coils and the measured ACS readout noise. We also discuss further possible improvements of the LOD.
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| 2. |
- Andõn, F. T., et al.
(författare)
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Biodegradation of Single-Walled Carbon Nanotubes by Eosinophil Peroxidase
- 2013
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Ingår i: Small. - : Wiley-VCH Verlagsgesellschaft. - 1613-6810 .- 1613-6829. ; 9:16, s. 2721-2729
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Tidskriftsartikel (refereegranskat)abstract
- Eosinophil peroxidase (EPO) is one of the major oxidant-producing enzymes during inflammatory states in the human lung. The degradation of single-walled carbon nanotubes (SWCNTs) upon incubation with human EPO and H2O 2 is reported. Biodegradation of SWCNTs is higher in the presence of NaBr, but neither EPO alone nor H2O2 alone caused the degradation of nanotubes. Molecular modeling reveals two binding sites for SWCNTs on EPO, one located at the proximal side (same side as the catalytic site) and the other on the distal side of EPO. The oxidized groups on SWCNTs in both cases are stabilized by electrostatic interactions with positively charged residues. Biodegradation of SWCNTs can also be executed in an ex vivo culture system using primary murine eosinophils stimulated to undergo degranulation. Biodegradation is proven by a range of methods including transmission electron microscopy, UV-visible-NIR spectroscopy, Raman spectroscopy, and confocal Raman imaging. Thus, human EPO (in vitro) and ex vivo activated eosinophils mediate biodegradation of SWCNTs: an observation that is relevant to pulmonary responses to these materials. Human eosinophil peroxidase (EPO) is able to degrade SWCNTs in vitro in the presence of H2O2. EPO is one of the major oxidant-generating enzymes present in human lungs during inflammatory states. The biodegradation of SWCNTs is evidenced also in an ex vivo culture system using primary murine eosinophils stimulated to undergo degranulation. These results are relevant to potential respiratory exposure to carbon nanotubes.
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| 3. |
- Artiach, Gonzalo, et al.
(författare)
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Omega-3 Polyunsaturated Fatty Acids Decrease Aortic Valve Disease through the Resolvin E1 and ChemR23 Axis.
- 2020
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Ingår i: Circulation. - 0009-7322 .- 1524-4539. ; 142, s. 776-789
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Tidskriftsartikel (refereegranskat)abstract
- Background: Aortic valve stenosis (AVS), which is the most common valvular heart disease, causes a progressive narrowing of the aortic valve as a consequence of thickening and calcification of the aortic valve leaflets. The beneficial effects of omega-3 polyunsaturated fatty acids (n-3 PUFA) in cardiovascular prevention have been recently demonstrated in a large randomized controlled trial. In addition, n-3 PUFA serve as the substrate for the synthesis of specialized pro-resolving mediators (SPMs), which are known by their potent beneficial anti-inflammatory, pro-resolving and tissue-modifying properties in cardiovascular disease. However, the effects of n-3 PUFA and SPMs on AVS have not yet been determined. The aim of this study was to identify the role of n-3 PUFA-derived SPMs in relation to the development of AVS. Methods: Lipidomic and transcriptomic analyses were performed in human tricuspid aortic valves. Apoe-/- mice and wire injury in C57BL/6J mice were used as models for mechanistic studies. Results: We found that n-3 PUFA incorporation into human stenotic aortic valves was higher in non-calcified regions compared with calcified regions. LC-MS-MS based lipid mediator lipidomics identified that the n-3 PUFA-derived SPM resolvin E1 (RvE1) was dysregulated in calcified regions and acted as a calcification inhibitor. Apoe-/- mice expressing the Caenorhabditis elegans Fat-1 transgene (Fat-1tgxApoe-/-), which enables the endogenous synthesis of n-3 PUFA, increased valvular n-3 PUFA content, exhibited reduced valve calcification, lower aortic valve leaflet area, increased M2 macrophage polarization and improved echocardiographic parameters. Finally, abrogation of the RvE1 receptor ChemR23 enhanced disease progression, and the beneficial effects of Fat-1tg were abolished in the absence of ChemR23. Conclusions: n-3 PUFA-derived RvE1 and its receptor ChemR23 emerge as a key axis in the inhibition of AVS progression, and may represent a novel potential therapeutic opportunity to be evaluated in patients with AVS.
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| 4. |
- Aurell, Erik, et al.
(författare)
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The inner structure of Zeldovich pancakes
- 2003
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Ingår i: Physica D. - : Elsevier BV. - 0167-2789 .- 1872-8022. ; 186:04-mar, s. 171-184
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Tidskriftsartikel (refereegranskat)abstract
- The evolution of a planar perturbation in a Einstein-de Sitter Universe is studied using a previously introduced Lagrangian scheme. An approximate discrete dynamical system is derived, which describes the mass agglomeration process. Quantitative predictions for the late-time mean density profile are obtained therefrom, and validated by numerical simulations. A simple but important result is that the characteristic scale of a mass agglomeration is an increasing function of cosmological time t. For one kind of initial conditions we further find a scaling regime for the density profile of a collapsing object. These results are compared with analogous investigations for the adhesion model (Burgers equation with positive viscosity). We further study the mutual motion of two mass agglomerations, and show that they oscillate around each other for long times, like two heavy particles. Individual particles in the two agglomerations do not mix effectively on the time scale of the inter-agglomeration motion.
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| 5. |
- Benser, Jasmin, et al.
(författare)
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Impact of physical activity and cardiovascular fitness on total homocysteine concentrations in European adolescents : The HELENA study
- 2015
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Ingår i: Journal of Nutritional Science and Vitaminology. - : Center for Academic Publications Japan. - 0301-4800 .- 1881-7742. ; 61:1, s. 45-54
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Tidskriftsartikel (refereegranskat)abstract
- We examined the association of physical activity (PA), cardiovascular fitness (CVF) and fatness with total homocysteine (tHcy) concentrations in European adolescents. The present study comprised 713 European adolescents aged 14.8±1.2 y (females 55.3%) from the multicenter HELENA cross-sectional study. PA was assessed through accelerometry, CVF by the 20-m shuttle run test, and body fat by skinfold thicknesses with the Slaughter equation. Plasma folate, cobalamin, and tHcy concentrations were measured. To examine the association of tHcy with PA, CVF, and fatness after controlling for a set of confounders including age, maturity, folate, cobalamin, creatinine, smoking, supplement use, and methylenetetrahydrofolate reductase 677 genotype (CC 47%, CT 43%, TT 10%), bivariate correlations followed by multiple regression models were performed. In the bivariate correlation analysis, tHcy concentrations were slightly negatively correlated (p<0.0 5) with CVF in females (measured both by stages: r=-0.118 and by VO 2 max: r=-0.10 2) and positively with body mass index (r=0.10 0). However, daily time spent with moderate and vigorous PA showed a weak positive association with tHcy in females (p<0.0 5). tHcy concentrations showed a tendency to decrease with increasing CVF and increase with increasing BMI in female European adolescents. However, tHcy concentrations were positively associated with moderate and vigorous PA in female European adolescents.
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| 6. |
- Berg, Robert, et al.
(författare)
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Synthesis of thieno[2,3-b]indole-2,3-diones and their ring expansions induced by diazomethane
- 2017
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Ingår i: Tetrahedron. - : Elsevier BV. - 0040-4020 .- 1464-5416. ; 73:38, s. 5654-5658
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Tidskriftsartikel (refereegranskat)abstract
- Indole-2-thione 3 reacted quickly with oxalyl chloride to yield thieno[2,3-b]indole-2,3-dione 4 together with the isomer thiazolo[3,2-a]indole-2,3-dione 5. These thieno[2,3-b]indole-2,3diones underwent ring expansions when treated with diazomethane and e.g. thieno[2,3-b]indole-2,3-dione 4 gave the thiopyrano derivative 16, after two insertions.
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| 7. |
- Berglund, U. W., et al.
(författare)
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Validation and development of MTH1 inhibitors for treatment of cancer
- 2016
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Ingår i: Annals of Oncology. - : Elsevier BV. - 0923-7534 .- 1569-8041. ; 27:12, s. 2275-2283
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Tidskriftsartikel (refereegranskat)abstract
- Background: Previously, we showed cancer cells rely on the MTH1 protein to prevent incorporation of otherwise deadly oxidised nucleotides into DNA and we developed MTH1 inhibitors which selectively kill cancer cells. Recently, several new and potent inhibitors of MTH1 were demonstrated to be non-toxic to cancer cells, challenging the utility of MTH1 inhibition as a target for cancer treatment. Material and methods: Human cancer cell lines were exposed in vitro to MTH1 inhibitors or depleted of MTH1 by siRNA or shRNA. 8-oxodG was measured by immunostaining and modified comet assay. Thermal Proteome profiling, proteomics, cellular thermal shift assays, kinase and CEREP panel were used for target engagement, mode of action and selectivity investigations of MTH1 inhibitors. Effect of MTH1 inhibition on tumour growth was explored in BRAF V600E-mutated malignant melanoma patient derived xenograft and human colon cancer SW480 and HCT116 xenograft models. Results: Here, we demonstrate that recently described MTH1 inhibitors, which fail to kill cancer cells, also fail to introduce the toxic oxidized nucleotides into DNA. We also describe a new MTH1 inhibitor TH1579, (Karonudib), an analogue of TH588, which is a potent, selective MTH1 inhibitor with good oral availability and demonstrates excellent pharmacokinetic and anti-cancer properties in vivo. Conclusion: We demonstrate that in order to kill cancer cells MTH1 inhibitors must also introduce oxidized nucleotides into DNA. Furthermore, we describe TH1579 as a best-in-class MTH1 inhibitor, which we expect to be useful in order to further validate the MTH1 inhibitor concept.
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| 8. |
- Bergman, Jan, et al.
(författare)
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Oxidative Ring Expansion of Spirocyclic Oxindole Derivatives
- 2014
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Ingår i: Journal of Organic Chemistry. - : American Chemical Society (ACS). - 0022-3263 .- 1520-6904. ; 79:19, s. 9065-9073
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Tidskriftsartikel (refereegranskat)abstract
- Oxidation of the spirocyclic oxindole derivative, isamic acid 1, led to decarboxylation and ring expansion to quinazolino[4,5-b]quinazoline-6,8-dione 7 rather than, as previously believed, its isomer 6. The structure of 7 was confirmed by X-ray crystallography. Condensation of isatin (indole-2,3-dione) and 2-aminobenzamide led to the spirocyclic molecule, spiro[3H-indole-3,2'(1H)quinazoline]-2,4'(1H,3H)dione 8, which was also identified as an intermediate in the oxidation of isamic acid. Mild hydrolysis of 7 gave the 10-membered molecule 22. Isamic acid could easily be converted to N-nitrosoisamic acid, which when heated in ethanol underwent a ring expansion to a hydroximino derivative, 38, of compound 6. The structure of 38 was confirmed by X-ray crystallography.
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| 9. |
- Bergman, Åke, et al.
(författare)
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Science and policy on endocrine disrupters must not be mixed : a reply to a "common sense" intervention by toxicology journal editors
- 2013
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Ingår i: Environmental Health. - : BioMed Central (BMC). - 1476-069X. ; 12
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Tidskriftsartikel (refereegranskat)abstract
- The "common sense" intervention by toxicology journal editors regarding proposed European Union endocrine disrupter regulations ignores scientific evidence and well-established principles of chemical risk assessment. In this commentary, endocrine disrupter experts express their concerns about a recently published, and is in our considered opinion inaccurate and factually incorrect, editorial that has appeared in several journals in toxicology. Some of the shortcomings of the editorial are discussed in detail. We call for a better founded scientific debate which may help to overcome a polarisation of views detrimental to reaching a consensus about scientific foundations for endocrine disrupter regulation in the EU.
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| 10. |
- Bhattacharya, Kunal, et al.
(författare)
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Enzymatic 'stripping' and degradation of PEGylated carbon nanotubes
- 2014
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Ingår i: Nanoscale. - : Royal Society of Chemistry (RSC). - 2040-3364 .- 2040-3372. ; 6:24, s. 14686-14690
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Tidskriftsartikel (refereegranskat)abstract
- Single-walled carbon nanotubes (SWCNTs) coated or functionalized with PEG chains of different molecular weight were assessed for their propensity to undergo biodegradation under in vitro conditions using recombinant myeloperoxidase (MPO) or ex vivo using freshly isolated primary human neutrophils. Our findings suggest that under natural conditions, a combined process of 'stripping' (i.e., defunctionalization) and biodegradation of PEG-SWCNTs might occur and that PEG-SWCNTs are a promising-and degradable-nanomedicine vector.
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