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- Emilsson, Louise, 1982-
(författare)
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Cardiac complications in celiac disease
- 2013
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: Celiac disease (CD) is an immune-mediated enteropathy induced by dietary gluten that affects about 1% of western populations. CD has been associated to an increased risk of cardiovascular mortality in some studies; however associations to cardiovascular diseases have not been broadly researched.Aim: The aim of this thesis was to examine the associations between CD and some cardiovascular diseases, namely; atrial fibrialltion, dilated cardiomyopathy and risk factors of ischemic heart disease.Methods: We used computerized data on all Swedish patients with biopsy-verified CD equal to villous atrophy from 1969 to 31st of December 2008. All CD patients were matched on age, sex, county and calendar year with up to five reference individuals. Altogether we had data on 29,096 CD patients and 144,522 reference individuals. Data were linked to different Swedish national registries and the Swedish quality and cardiac care registry SWEDEHEART. Main outcomes in the studies were: I: atrial fibrillation registered in the national patient registry or the cause of death registry, II: chart validated idiopathic dilated cardiomyopathy, III: different risk factors, clinical presentation and parameters in patients with first myocardial infarction (MI) registered in SWEDEHEART and IV: follow-up parameters, 6-10 weeks and one year after MI, registered in SWEDEHEART.Result: We showed a 34% increased risk of atrial fibrillation in CD and a 73% increased risk of dilated cardiomyopathy, the latter only of borderline significance, p=0.052. In the third study we showed that CD patients with MI had a more beneficial cardiovascular risk factor profile, better left ventricular ejection fraction and fewer stenoses on coronary angiography compared to reference individuals with MI. The fourth study showed that follow-up after MI does not differ from follow-up in reference individuals.Conclusion: This thesis supports an association of cardiovascular diseases in CD. Potential mechanisms include shared risk factors and chronic in-flammation.
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- Girardi, Benedetta, et al.
(författare)
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Selective Monovalent Galectin-8 Ligands Based on 3-Lactoylgalactoside
- 2022
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Ingår i: ChemMedChem. - : Wiley. - 1860-7179 .- 1860-7187. ; 17:3
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Tidskriftsartikel (refereegranskat)abstract
- Galectin-8 has gained attention as a potential new pharmacological target for the treatment of various diseases, including cancer, inflammation, and disorders associated with bone mass reduction. To that end, new molecular probes are needed in order to better understand its role and its functions. Herein we aimed to improve the affinity and target selectivity of a recently published galectin-8 ligand, 3-O-[1-carboxyethyl]-β-d-galactopyranoside, by introducing modifications at positions 1 and 3 of the galactose. Affinity data measured by fluorescence polarization show that the most potent compound reached a KD of 12 μM. Furthermore, reasonable selectivity versus other galectins was achieved, making the highlighted compound a promising lead for the development of new selective and potent ligands for galectin-8 as molecular probes to examine the protein's role in cell-based and in vivo studies.
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- hower, lee, et al.
(författare)
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investigating cell type changes in schizophrenia with spatially-resolved transcriptomics
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Annan publikation (populärvet., debatt m.m.)abstract
- Schizophrenia is a heritable and genetically complex disorder with poorly understood aetiology. Previous study from our lab has shown that this disorder could affect a limited number of cell types in the brain1. Here, we build on these findings and present the first spatially-resolved transcriptomics study of schizophrenia with a large number of samples (17 in total). By comparing spatial cell type distributions in diseased and healthy prefrontal cortices, we discover that certain non-neuronal cell types change their co-localization patterns
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- Huang, Xiaoli, et al.
(författare)
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The Molecular Basis for Inhibition of Stemlike Cancer Cells by Salinomycin
- 2018
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Ingår i: ACS Central Science. - : American Chemical Society (ACS). - 2374-7943 .- 2374-7951. ; 4:6, s. 760-767
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Tidskriftsartikel (refereegranskat)abstract
- Tumors are phenotypically heterogeneous and include subpopulations of cancer cells with stemlike properties. The natural product salinomycin, a K+-selective ionophore, was recently found to exert selectivity against such cancer stem cells. This selective effect is thought to be due to inhibition of the Wnt signaling pathway, but the mechanistic basis remains unclear. Here, we develop a functionally competent fluorescent conjugate of salinomycin to investigate the molecular mechanism of this compound. By subcellular imaging, we demonstrate a rapid cellular uptake of the conjugate and accumulation in the endoplasmic reticulum (ER). This localization is connected to induction of Ca2+ release from the ER into the cytosol. Depletion of Ca2+ from the ER induces the unfolded protein response as shown by global mRNA analysis and Western blot analysis of proteins in the pathway. In particular, salinomycin-induced ER Ca2+ depletion up-regulates C/EBP homologous protein (CHOP), which inhibits Wnt signaling by down-regulating β-catenin. The increased cytosolic Ca2+ also activates protein kinase C, which has been shown to inhibit Wnt signaling. These results reveal that salinomycin acts in the ER membrane of breast cancer cells to cause enhanced Ca2+ release into the cytosol, presumably by mediating a counter-flux of K+ ions. The clarified mechanistic picture highlights the importance of ion fluxes in the ER as an entry to inducing phenotypic effects and should facilitate rational development of cancer treatments.
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- Kumpiene, Jurate, et al.
(författare)
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Impact of water saturation level on arsenic and metal mobility in the Fe-amended soil
- 2009
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Ingår i: Chemosphere. - : Elsevier. - 0045-6535 .- 1879-1298. ; 74:2, s. 206-215
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Tidskriftsartikel (refereegranskat)abstract
- The impact of water saturation level (oxidizing-reducing environment) on As and metal solubility in chromium, copper, arsenic (CCA)-contaminated soil amended with Fe-containing materials was studied. The soil was mixed with 0.1 and 1 wt% of iron grit (Fe(0)) and 1, 7 and 15 wt% of oxygen scarfing granulate (OSG, a by-product of steel processing). Solubility of As and metals was evaluated by a batch leaching test and analysis of soil pore water. Soil saturation with water greatly increased As solubility in the untreated as well as in the Fe-amended soil. This was related to the reductive dissolution of Fe oxides and increased concentration of As(III) species. Fe amendments showed As reducing capacity under both oxic and anoxic conditions. The cytotoxicity of the soil pore water correlated with the concentration of As(III). The Fe-treatments as well as water saturation of soil were less significant for the solubility of Cu, Cr and Zn than for As. The batch leaching test used for waste characterization substantially underestimated As solubility that could occur under water-saturated (anaerobic) conditions. In the case of soil landfilling, other techniques than Fe-stabilization of As containing soil should be considered.
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- Leffler, Per, et al.
(författare)
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Toxicity and accumulation of trinitrotoluene (TNT) and its metabolites in atlantic salmon alevins exposed to an industrially polluted water
- 2014
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Ingår i: Journal of Toxicology and Environmental Health. - : Taylor & Francis Group. - 1528-7394 .- 1087-2620. ; 77:19, s. 1183-1191
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Tidskriftsartikel (refereegranskat)abstract
- A pond in an industrial area in Sweden was selected to study adverse effects on salmon alevins from 2,4,6-trinitrotoluene (TNT)-contaminated water. Chemical screening revealed heavy contamination of TNT and its degradation products, 2-amino-4,6-dinitrotoluene (2-ADNT) and 4-amino-2,6-dinitrotoluene (4-ADNT), ranging from 0.05 to 230 g/kg in the sediment (dry weight) within the water system. Pond water contained 3 mg/L TNT. A dilution series of pond water mixed with tap water revealed increased death frequency in alevins down to fivefold dilution (approximate 0.4 mg TNT/L). Uptake was concentration dependent, reaching 7, 9, and 22 μg/g tissue for TNT, 2-ADNT, and 4-ADNT at the highest test concentration. A time-dependent uptake of TNT and its degradation products was found at a water concentration of 0.08 mg TNT/L. Degradation products of TNT showed a more efficient uptake compared to native TNT, and accumulation of 4-ADNT was more pronounced during the late phase of the 40-d exposure study. Bioconcentration factors (BCF) (0.34, 52, and 134 ml/g for TNT, 2-ADNT, and 4-ADNT, respectively) demonstrated a significant uptake of the metabolite 4-ADNT in alevin tissue. Disturbed physiological conditions and delayed development in alevins were not studied, but may not be excluded even at 125-fold diluted pond water (0.016 mg TNT/L). BCF data indicated that bioaccumulation of TNT metabolites need to be considered in TNT chronic toxicity. Fish species and age differences in the accumulation of TNT metabolites need to be further studied.
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