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- Alijagic, Andi, 1992-, et al.
(författare)
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A Novel Nanosafety Approach Using Cell Painting, Metabolomics, and Lipidomics Captures the Cellular and Molecular Phenotypes Induced by the Unintentionally Formed Metal-Based (Nano)Particles
- 2023
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Ingår i: Cells. - : MDPI. - 2073-4409. ; 12:2
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Tidskriftsartikel (refereegranskat)abstract
- Additive manufacturing (AM) or industrial 3D printing uses cutting-edge technologies and materials to produce a variety of complex products. However, the effects of the unintentionally emitted AM (nano)particles (AMPs) on human cells following inhalation, require further investigations. The physicochemical characterization of the AMPs, extracted from the filter of a Laser Powder Bed Fusion (L-PBF) 3D printer of iron-based materials, disclosed their complexity, in terms of size, shape, and chemistry. Cell Painting, a high-content screening (HCS) assay, was used to detect the subtle morphological changes elicited by the AMPs at the single cell resolution. The profiling of the cell morphological phenotypes, disclosed prominent concentration-dependent effects on the cytoskeleton, mitochondria, and the membranous structures of the cell. Furthermore, lipidomics confirmed that the AMPs induced the extensive membrane remodeling in the lung epithelial and macrophage co-culture cell model. To further elucidate the biological mechanisms of action, the targeted metabolomics unveiled several inflammation-related metabolites regulating the cell response to the AMP exposure. Overall, the AMP exposure led to the internalization, oxidative stress, cytoskeleton disruption, mitochondrial activation, membrane remodeling, and metabolic reprogramming of the lung epithelial cells and macrophages. We propose the approach of integrating Cell Painting with metabolomics and lipidomics, as an advanced nanosafety methodology, increasing the ability to capture the cellular and molecular phenotypes and the relevant biological mechanisms to the (nano)particle exposure.
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| 2. |
- Andersson, Linda, 1973, et al.
(författare)
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Glucosylceramide synthase deficiency in the heart compromises β1-adrenergic receptor trafficking
- 2021
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Ingår i: European Heart Journal. - : Oxford University Press. - 0195-668X .- 1522-9645. ; 42:43, s. 4481-4492
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: Cardiac injury and remodelling are associated with the rearrangement of cardiac lipids. Glycosphingolipids are membrane lipids that are important for cellular structure and function, and cardiac dysfunction is a characteristic of rare monogenic diseases with defects in glycosphingolipid synthesis and turnover. However, it is not known how cardiac glycosphingolipids regulate cellular processes in the heart. The aim of this study is to determine the role of cardiac glycosphingolipids in heart function.METHODS AND RESULTS: Using human myocardial biopsies, we showed that the glycosphingolipids glucosylceramide and lactosylceramide are present at very low levels in non-ischaemic human heart with normal function and are elevated during remodelling. Similar results were observed in mouse models of cardiac remodelling. We also generated mice with cardiomyocyte-specific deficiency in Ugcg, the gene encoding glucosylceramide synthase (hUgcg-/- mice). In 9- to 10-week-old hUgcg-/- mice, contractile capacity in response to dobutamine stress was reduced. Older hUgcg-/- mice developed severe heart failure and left ventricular dilatation even under baseline conditions and died prematurely. Using RNA-seq and cell culture models, we showed defective endolysosomal retrograde trafficking and autophagy in Ugcg-deficient cardiomyocytes. We also showed that responsiveness to β-adrenergic stimulation was reduced in cardiomyocytes from hUgcg-/- mice and that Ugcg knockdown suppressed the internalization and trafficking of β1-adrenergic receptors.CONCLUSIONS: Our findings suggest that cardiac glycosphingolipids are required to maintain β-adrenergic signalling and contractile capacity in cardiomyocytes and to preserve normal heart function.
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| 5. |
- Blanc, Mélanie, 1993-, et al.
(författare)
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Multi- and transgenerational effects following early-life exposure of zebrafish to permethrin and coumarin 47 : Impact on growth, fertility, behavior and lipid metabolism
- 2020
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Ingår i: Ecotoxicology and Environmental Safety. - : Academic Press. - 0147-6513 .- 1090-2414. ; 205
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Tidskriftsartikel (refereegranskat)abstract
- Transgenerational effects induced by environmental stressors are a threat to ecosystems and human health. However, there is still limited observation and understanding of the potential of chemicals to influence life outcomes over several generations. In the present study, we investigated the effects of two environmental contaminants, coumarin 47 and permethrin, on exposed zebrafish (FO) and their progeny (F1-F3). Coumarin 47 is commonly found in personal care products and dyes, whereas permethrin is used as a domestic and agricultural pyrethroid insecticide/insect repellent. Zebrafish (F0) were exposed during early development until 28 days post-fertilization and their progeny (F1-F3) were bred unexposed. On one hand, the effects induced by coumarin 47 suggest no multigenerational toxicity. On the other hand, we found that behavior of zebrafish larvae was significantly affected by exposure to permethrin in F1 to F3 generations with some differences depending on the concentration. This suggests persistent alteration of the neural or neuromuscular function. In addition, lipidomic analyses showed that permethrin treatment was partially correlated with lysophosphatidylcholine levels in zebrafish, an important lipid for neurodevelopment. Overall, these results stress out one of the most widely used pyrethroids can trigger long-term, multi- and possibly transgenerational changes in the nervous system of zebrafish. These neurobehavioral changes echo the effects observed under direct exposure to high concentrations of permethrin and therefore call for more research on mechanisms underlying effect inheritance.
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| 6. |
- Djekic, Demir, 1989-, et al.
(författare)
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Effects of a Lacto-Ovo-Vegetarian Diet on the Plasma Lipidome and Its Association with Atherosclerotic Burden in Patients with Coronary Artery Disease-A Randomized, Open-Label, Cross-over Study
- 2020
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Ingår i: Nutrients. - : MDPI. - 2072-6643. ; 12:11
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Tidskriftsartikel (refereegranskat)abstract
- A vegetarian diet has been associated with a lower risk of coronary artery disease (CAD). Plasma triacylglycerols, ceramides, and phosphatidylcholines may improve prediction of recurrent coronary events. We sought to investigate effects of a lacto-ovo-vegetarian diet (VD) on plasma lipidome in CAD patients and simultaneously assess associations of plasma lipids with the extent of coronary atherosclerotic burden. We analyzed 214 plasma lipids within glycerolipid, sphingolipid, and sterol lipid classes using lipidomics from a randomized controlled, crossover trial comprising 31 CAD patients on standard medical therapy. Subjects completed a four-week intervention with VD and isocaloric meat diet (MD), separated by a four-week washout period. The VD increased levels of 11 triacylglycerols and lowered 7 triacylglycerols, 21 glycerophospholipids, cholesteryl ester (18:0), and ceramide (d18:1/16:0) compared with MD. VD increased triacylglycerols with long-chain polyunsaturated fatty acyls while decreased triacylglycerols with saturated fatty acyls, phosphatidylcholines, and sphingomyelins than MD. The Sullivan extent score (SES) exhibited on coronary angiograms were inversely associated with triacylglycerols with long-chain unsaturated fatty acyls. Phosphatidylcholines that were lower with VD were positively associated with SES and the total number of stenotic lesions. The VD favorably changed levels of several lipotoxic lipids that have previously been associated with increased risk of coronary events in CAD patients.
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| 7. |
- Djekic, Demir, 1989-, et al.
(författare)
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Serum untargeted lipidomic profiling reveals dysfunction of phospholipid metabolism in subclinical coronary artery disease
- 2019
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Ingår i: Vascular Health and Risk Management. - : DOVE Medical Press Ltd.. - 1176-6344 .- 1178-2048. ; 15, s. 123-135
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Disturbed metabolism of cholesterol and triacylglycerols (TGs) carries increased risk for coronary artery calcification (CAC). However, the exact relationship between individual lipid species and CAC remains unclear. The aim of this study was to identify disturbances in lipid profiles involved in the calcification process, in an attempt to propose potential biomarker candidates.Patients and methods: We studied 70 patients at intermediate risk for coronary artery disease who had undergone coronary calcification assessment using computed tomography and Agatston coronary artery calcium score (CACS). Patients were divided into three groups: with no coronary calcification (NCC; CACS: 0; n=26), mild coronary calcification (MCC; CACS: 1-250; n=27), or severe coronary calcification (SCC; CACS: >250; n=17). Patients' serum samples were analyzed using liquid chromatography-mass spectrometry in an untargeted lipidomics approach.Results: We identified 103 lipids within the glycerolipid, glycerophospholipid, sphingolipid, and sterol lipid classes. After false discovery rate correction, phosphatidylcholine (PC)(16:0/20:4) in higher levels and PC(18:2/18:2), PC(36:3), and phosphatidylethanolamine(20:0/18:2) in lower levels were identified as correlates with SCC compared to NCC. There were no significant differences in the levels of individual TGs between the three groups; however, clustering the lipid profiles showed a trend for higher levels of saturated and monounsaturated TGs in SCC compared to NCC. There was also a trend for lower TG (49:2), TG(51:1), TG(54:5), and TG(56:8) levels in SCC compared to MCC.Conclusion: In this study we investigated the lipidome of patients with coronary calcification. Our results suggest that the calcification process may be associated with dysfunction in autophagy. The lipidomic biomarkers revealed in this study may aid in better assessment of patients with subclinical coronary artery disease.
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| 9. |
- Holster, S., et al.
(författare)
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Correlations between microbiota and metabolites after faecal microbiota transfer in irritable bowel syndrome
- 2021
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Ingår i: Beneficial Microbes. - : Wageningen Academic Publishers. - 1876-2883 .- 1876-2891. ; 12:1, s. 17-30
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Tidskriftsartikel (refereegranskat)abstract
- Faecal microbiota transfer (FMT) consists of the infusion of donor faecal material into the intestine of a patient with the aim to restore a disturbed gut microbiota. In this study, it was investigated whether FMT has an effect on faecal microbial composition, its functional capacity, faecal metabolite profiles and their interactions in 16 irritable bowel syndrome (IBS) patients. Faecal samples from eight different time points before and until six months after allogenic FMT (faecal material from a healthy donor) as well as autologous FMT (own faecal material) were analysed by 16S RNA gene amplicon sequencing and gas chromatography coupled to mass spectrometry (GS-MS). The results showed that the allogenic FMT resulted in alterations in the microbial composition that were detectable up to six months, whereas after autologous FMT this was not the case. Similar results were found for the functional profiles, which were predicted from the phylogenetic sequencing data. While both allogenic FMT as well as autologous FMT did not have an effect on the faecal metabolites measured in this study, correlations between the microbial composition and the metabolites showed that the microbe-metabolite interactions seemed to be disrupted after allogenic FMT compared to autologous FMT. This shows that FMT can lead to altered interactions between the gut microbiota and its metabolites in IBS patients. Further research should investigate if and how this affects efficacy of FMT treatments.
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