| 1. |
- Abohalaka, Reshed, et al.
(författare)
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Endocannabinoid metabolism inhibition ameliorates ovalbumin-induced allergic airway inflammation and hyperreactivity in Guinea pigs.
- 2022
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Ingår i: Life sciences. - : Elsevier BV. - 1879-0631 .- 0024-3205. ; 306
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Tidskriftsartikel (refereegranskat)abstract
- Endocannabinoids are biologically active cannabinoid-related substances endogenously synthesized in many mammalian tissues. Mainly two enzymes carry out their degradation; Fatty Acid Amide Hydrolase (FAAH) and Monoacylglycerol Lipase (MAGL). Endocannabinoids are shown to affect the modulation of inflammatory processes and airway responsiveness. In the present study, we investigated the effects of FAAH and MAGL inhibitor treatments in experimental allergic airway inflammation in guinea pigs.Guinea pigs were sensitized and challenged by ovalbumin to induce an allergic asthma model. Then, the effects of FAAH inhibitor URB597, MAGL inhibitor JZL184, and dual (FAAH/MAGL) inhibitor JZL195 on airway inflammation and hyperreactivity were evaluated.Ovalbumin challenge increased airway reactivity, IgE in serum, IL-4, and IL-13, and the percentage of eosinophils in bronchoalveolar lavage (BAL). In addition, inhibition of FAAH or MAGL enzymes leads to an increase in endocannabinoid levels. The selective inhibition of the FAAH enzyme prevented inflammation indicators such as cytokine production and inflammatory cell infiltration but had a negligible effect on airway hyperreactivity. However, the inhibition of the MAGL enzyme or dual inhibition of both FAAH and MAGL enzymes tent to moderate both pulmonary inflammation and airway hyperreactivity.We have previously demonstrated that modulation of endocannabinoid levels in the airways by FAAH or MAGL inhibition can be useful in preventing acute lung inflammation. The results of the present study further suggest that FAAH and MAGL inhibitor treatment can also be a promising strategy for bronchial hyperreactivity and airway inflammation in allergic asthma.
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| 2. |
- Abohalaka, Reshed, et al.
(författare)
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The effects of fatty acid amide hydrolase and monoacylglycerol lipase inhibitor treatments on lipopolysaccharide-induced airway inflammation in mice.
- 2020
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Ingår i: Pulmonary pharmacology & therapeutics. - : Elsevier BV. - 1522-9629 .- 1094-5539. ; 62
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Tidskriftsartikel (refereegranskat)abstract
- Cannabinoids and the endocannabinoid system significantly contributes to the airway inflammation. Fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL) are two main enzymes responsible for the metabolism of the endocannabinoids anandamide (AEA) and 2-arachydonoyl glycerol (2-AG), respectively. In the present study, we aimed to investigate the effects of local and systemic FAAH and MAGL inhibitor treatments in experimental airway inflammation and tracheal hyperreactivity in mice. Airway inflammation was induced by intranasal (i.n.) lipopolysaccharide (LPS) application (60 μl; 0,1 mg/ml in PBS) to mice and the control group received PBS. Systemic (intraperitoneal (i.p.)) or local (i.n.) FAAH inhibitor URB597 and MAGL inhibitor JZL184 treatments were administered 1h before LPS/PBS application. Fourty 8 h after LPS/PBS application, tracheas were removed to assess airway reactivity, and the lungs and bronchoalveolar lavage (BAL) fluids were isolated for histopathological evaluation, cytokine and endocannabinoid measurements. LPS application lead to an increase in 5-hydroxytryptamine (5-HT) contractions in isolated tracheal rings while carbachol contractions remained unchanged. The increased 5-HT contractions were prevented by both systemic and local URB597 and JZL184 treatments. Systemic treatment with URB597 and JZL184, and local treatment with JZL184 reduced peribronchial and paranchymal inflammation in the LPS group while i.n. application of URB597 worsened the inflammation in the lungs. Systemic URB597 treatment increased lung AEA level whereas it had no effect on 2-AG level. However, JZL184 treatment increased 2-AG level by either systemic or local application, and also elevated AEA level. Inflammation-induced increase in neutrophil numbers was only prevented by systemic URB597 treatment. However, both URB597 and JZL184 treatments abolished the increased TNF-α level either they are administered systemically or locally. These results indicate that FAAH and MAGL inhibition may have a protective effect in airway inflammation and airway hyperreactivity, and therefore their therapeutic potential for airway diseases should be further investigated.
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| 3. |
- Abohalaka, Reshed, et al.
(författare)
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The effects of systemic and local fatty acid amide hydrolase and monoacylglycerol lipase inhibitor treatments on the metabolomic profile of lungs.
- 2022
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Ingår i: Biomedical chromatography : BMC. - : Wiley. - 1099-0801 .- 0269-3879. ; 36:1
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Tidskriftsartikel (refereegranskat)abstract
- The contribution of the endocannabinoid system to both physiology and pathological processes in the respiratory system makes it a promising target for inflammatory airway diseases. Previously, we have shown that increasing the tissue endocannabinoid levels by fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL) inhibitors can prevent airway inflammation and hyperreactivity. In this study, the changes in the levels of major metabolites of endocannabinoids by systemic and local FAAH or MAGL inhibitor treatments were evaluated. Mice were treated with either the FAAH inhibitor URB597 or the MAGL inhibitor JZL184 by local (intranasal) or systemic (intraperitoneal) application. Bronchoalveolar lavage (BAL) fluids and lungs were isolated afterward in order to perform histopathological and metabolomic analyses. There were no significant histopathological changes in the lungs and neutrophil, and macrophage and lymphocyte numbers in BAL fluid were not altered after local and systemic treatments. However, GC-MS-based metabolomics profile allowed us to identify 102 metabolites in lung samples, among which levels of 75 metabolites were significantly different from the control. The metabolites whose levels were changed by treatments were mostly related to the endocannabinoid system and energy metabolism. Therefore, these changes may contribute to the anti-inflammatory effects of URB597 and JZL184 treatments in mice.
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| 4. |
- Kfir, Ofer, et al.
(författare)
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Generation of bright phase-matched circularly-polarized extreme ultraviolet high harmonics
- 2015
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Ingår i: Nature Photonics. - 1749-4885 .- 1749-4893. ; 9:2, s. 99-105
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Tidskriftsartikel (refereegranskat)abstract
- Circularly-polarized extreme ultraviolet and X-ray radiation is useful for analysing the structural, electronic and magnetic properties of materials. To date, such radiation has only been available at large-scale X-ray facilities such as synchrotrons. Here, we demonstrate the first bright, phase-matched, extreme ultraviolet circularly-polarized high harmonics source. The harmonics are emitted when bi-chromatic counter-rotating circularly-polarized laser pulses field-ionize a gas in a hollow-core waveguide. We use this new light source for magnetic circular dichroism measurements at the M-shell absorption edges of Co. We show that phase-matching of circularly-polarized harmonics is unique and robust, producing a photon flux comparable to linearly polarized high harmonic sources. This work represents a critical advance towards the development of table-top systems for element-specific imaging and spectroscopy of multiple elements simultaneously in magnetic and other chiral media with very high spatial and temporal resolution.
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| 5. |
- Kfir, Ofer, et al.
(författare)
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Helicity-selective phase-matching and quasi-phase matching of circularly polarized high-order harmonics : towards chiral attosecond pulses
- 2016
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Ingår i: Journal of Physics B: Atomic, Molecular and Optical Physics. - : IOP Publishing. - 0953-4075 .- 1361-6455. ; 49:12
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Tidskriftsartikel (refereegranskat)abstract
- Phase matching of circularly polarized high-order harmonics driven by counter-rotating bi-chromatic lasers was recently predicted theoretically and demonstrated experimentally. In that work, phase matching was analyzed by assuming that the total energy, spin angular momentum and linear momentum of the photons participating in the process are conserved. Here we propose a new perspective on phase matching of circularly polarized high harmonics. We derive an extended phase matching condition by requiring a new propagation matching condition between the classical vectorial bi-chromatic laser pump and harmonics fields. This allows us to include the influence of the laser pulse envelopes on phase matching. We find that the helicity dependent phase matching facilitates generation of high harmonics beams with a high degree of chirality. Indeed, we present an experimentally measured chiral spectrum that can support a train of attosecond pulses with a high degree of circular polarization. Moreover, while the degree of circularity of the most intense pulse approaches unity, all other pulses exhibit reduced circularity. This feature suggests the possibility of using a train of attosecond pulses as an isolated attosecond probe for chiral-sensitive experiments.
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| 6. |
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| 7. |
- Rudolf, Dennis, et al.
(författare)
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Element Selective Investigation of Spin Dynamics in Magnetic Multilayers
- 2015
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Ingår i: Ultrafast Magnetism I. - Cham : Springer International Publishing. - 9783319077437 - 9783319077420 ; , s. 307-309
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Konferensbidrag (refereegranskat)abstract
- Our understanding of ultrafast switching processes in novel spin-based electronics depends on our detailed knowledge of interactions between spin, charge and phonons in magnetic structures. We present element-selective studies, using extreme ultraviolet (XUV) light, to gain insight into spin dynamics in exchange coupled magnetic multilayers on the femtosecond time scale.
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| 8. |
- Rudolf, Dennis, et al.
(författare)
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Ultrafast magnetization enhancement in metallic multilayers driven by superdiffusive spin current
- 2012
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 3, s. 1037-
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Tidskriftsartikel (refereegranskat)abstract
- Uncovering the physical mechanisms that govern ultrafast charge and spin dynamics is crucial for understanding correlated matter as well as the fundamental limits of ultrafast spin-based electronics. Spin dynamics in magnetic materials can be driven by ultrashort light pulses, resulting in a transient drop in magnetization within a few hundred femtoseconds. However, a full understanding of femtosecond spin dynamics remains elusive. Here we spatially separate the spin dynamics using Ni/Ru/Fe magnetic trilayers, where the Ni and Fe layers can be ferroor antiferromagnetically coupled. By exciting the layers with a laser pulse and probing the magnetization response simultaneously but separately in Ni and Fe, we surprisingly find that optically induced demagnetization of the Ni layer transiently enhances the magnetization of the Fe layer when the two layer magnetizations are initially aligned parallel. Our observations are explained by a laser-generated superdiffusive spin current between the layers.
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| 9. |
- Turgut, Emrah, et al.
(författare)
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Stoner versus Heisenberg : Ultrafast exchange reduction and magnon generation during laser-induced demagnetization
- 2016
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Ingår i: PHYSICAL REVIEW B. - 2469-9950. ; 94:22
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Tidskriftsartikel (refereegranskat)abstract
- Understanding how the electronic band structure of a ferromagnetic material is modified during laser-induced demagnetization on femtosecond time scales has been a long-standing question in condensed matter physics. Here, we use ultrafast high harmonics to measure time-, energy-, and angle-resolved M-edge magnetic asymmetry spectra for Co films after optical pumping to induce ultrafast demagnetization. This provides a complete data set that we can compare with advanced ab initio magneto-optical calculations. Our analysis identifies that the dominant mechanisms contributing to ultrafast demagnetization on time scales up to several picoseconds are a transient reduction in the exchange splitting and the excitation of ultrafast magnons. Surprisingly, we find that the magnon contribution to ultrafast demagnetization is already strong on subpicosecond time scales, while the reduction in exchange splitting persists to several picoseconds.
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| 10. |
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