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- Andelid, Kristina, 1953, et al.
(author)
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Lung macrophages drive mucus production and steroid-resistant inflammation in chronic bronchitis
- 2021
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In: Respiratory research. - : Springer Science and Business Media LLC. - 1465-993X. ; 22:1
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Journal article (peer-reviewed)abstract
- Background: Patients with chronic obstructive pulmonary disease (COPD) frequently suffer from chronic bronchitis (CB) and display steroid-resistant inflammation with increased sputum neutrophils and macrophages. Recently, a causal link between mucus hyper-concentration and disease progression of CB has been suggested. Methods: In this study, we have evaluated the steroid sensitivity of purified, patient-derived sputum and alveolar macrophages and used a novel mechanistic cross-talk assay to examine how macrophages and bronchial epithelial cells cross-talk to regulate MUC5B production. Results: We demonstrate that sputum plug macrophages isolated from COPD patients with chronic bronchitis (COPD/CB) are chronically activated and only partially respond to ex vivo corticosteroid treatment compared to alveolar macrophages isolated from lung resections. Further, we show that pseudo-stratified bronchial epithelial cells grown in air-liquid-interface are inert to direct bacterial lipopolysaccharide stimulation and that macrophages are able to relay this signal and activate the CREB/AP-1 transcription factor complex and subsequent MUC5B expression in epithelial cells through a soluble mediator. Using recombinant protein and neutralizing antibodies, we identified a key role for TNF alpha in this cross-talk. Conclusions: For the first time, we describe ex vivo pharmacology in purified human sputum macrophages isolated from chronic bronchitis COPD patients and identify a possible basis for the steroid resistance frequently seen in this population. Our data pinpoint a critical role for chronically activated sputum macrophages in perpetuating TNF alpha-dependent signals driving mucus hyper-production. Targeting the chronically activated mucus plug macrophage phenotype and interfering with aberrant macrophage-epithelial cross-talk may provide a novel strategy to resolve chronic inflammatory lung disease.
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- Berg, H, et al.
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Electronic structure and stability of the LixMn2O4 (0 < x < 2) system
- 1999
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In: JOURNAL OF MATERIALS CHEMISTRY. - : ROYAL SOC CHEMISTRY. - 0959-9428. ; 9:11, s. 2813-2820
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Journal article (other academic/artistic)abstract
- LMTO-ASA self-consistent band structure calculations have been performed for the cubic spinel LiMn2O4 and its delithiated and lithiated phases: lambda-MnO2 and Li2Mn2O4. It has been shown that the Jahn-Teller distortion plays a vital role le in the stabil
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- GORANSSON, K, et al.
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STRUCTURE REFINEMENTS FOR SOME PLATINUM METAL MONOSILICIDES
- 1991
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In: J. Magn. Magn. Mater.. ; 98, s. 37-46
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Journal article (peer-reviewed)abstract
- The crystal structures of platinum metal monosilicides were refined from powder diffraction data using the Rietveld method. The compounds studied were the FeSi-type structure RuSi, OsSi and RhSi, and the MnP-type structure RhSi, IrSi, PdSi and PtSi. The
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- Lauvsnes, M. B., et al.
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Neurofilament light in plasma is a potential biomarker of central nervous system involvement in systemic lupus erythematosus
- 2022
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In: Journal of Neurology. - : Springer Science and Business Media LLC. - 0340-5354 .- 1432-1459. ; 269, s. 3064-3074
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Journal article (peer-reviewed)abstract
- Background Neuropsychiatric manifestations (NP) are common in systemic lupus erythematosus (SLE). However, the pathophysiological mechanisms are not completely understood. Neurofilament light protein (NfL) is part of the neuronal cytoskeleton. Increased NfL concentrations, reflecting neurodegeneration, is observed in cerebrospinal fluid (CSF) in several neurodegenerative and neuroinflammatory conditions. We aimed to explore if plasma NfL could serve as a biomarker for central nervous system (CNS) involvement in SLE. Methods Sixty-seven patients with SLE underwent neurological examination; 52 underwent lumbar puncture, while 62 underwent cerebral magnetic resonance imaging (MRI). We measured selected auto-antibodies and other laboratory variables postulated to have roles in NP pathophysiology in the blood and/or CSF. We used SPM12 software for MRI voxel-based morphometry. Results Age-adjusted linear regression analyses revealed increased plasma NfL concentrations with increasing creatinine (beta = 0.01, p < 0.001) and Q-albumin (beta = 0.07, p = 0.008). We observed higher plasma NfL concentrations in patients with a history of seizures (beta = 0.57, p = 0.014), impaired motor function (beta = 0.36, p = 0.008), increasing disease activity (beta = 0.04, p = 0.008), and organ damage (beta = 0.10, p = 0.002). Voxel-based morphometry suggested an association between increasing plasma NfL concentrations and the loss of cerebral white matter in the corpus callosum and hippocampal gray matter. Conclusion Increased plasma NfL concentrations were associated with some abnormal neurological, cognitive, and neuroimaging findings. However, plasma NfL was also influenced by other factors, such as damage accrual, creatinine, and Q-albumin, thereby obscuring the interpretation of how plasma NfL reflects CNS involvement. Taken together, NfL in CSF seems a better marker of neuronal injury than plasma NfL in patients with SLE.
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- Wang, Conan K L, et al.
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Anti-HIV cyclotides from the Chinese medicinal herb Viola yedoensis
- 2008
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In: Journal of natural products (Print). - : American Chemical Society (ACS). - 0163-3864 .- 1520-6025. ; 71:1, s. 47-52
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Journal article (peer-reviewed)abstract
- Cyclotides are macrocyclic plant peptides characterized by a knotted arrangement of three disulfide bonds. They display a range of interesting bioactivities, including anti-HIV and insecticidal activities. More than 100 different cyclotides have been isolated from two phylogenetically distant plant families, the Rubiaceae and Violaceae. In this study we have characterized the cyclotides from Viola yedoensis, an important Chinese herb from the Violaceae family that has been reported to contain potential anti-HIV agents. From V. yedoensis five new and three known cyclotides were identified and shown to have anti-HIV activity. The most active of these is cycloviolacin Y5, which is one of the most potent of all cyclotides tested so far using in vitro XTT-based anti-HIV assays. Cycloviolacin Y5 is the most hydrophobic of the cyclotides from V. yedoensis. We show that there is a positive correlation between the hydrophobicity and the anti-HIV activity of the new cyclotides and that this trend tracks with their ability to disrupt membranes, as judged from hemolytic assays on human erythrocytes.
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