| 1. |
- Kalla, R., et al.
(författare)
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Whole blood profiling of T-cell derived miRNA allows the development of prognostic models in inflammatory bowel disease
- 2020
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Ingår i: Journal of Crohn's & Colitis. - : Elsevier. - 1873-9946 .- 1876-4479. ; 14:12, s. 1724-1733
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: MicroRNAs (miRNAs) are cell-specific small non-coding RNAs that can regulate gene expression and have been implicated in Inflammatory Bowel Disease (IBD) pathogenesis. In our study, we define the cell-specific miRNA profiles and investigate its biomarker potential in IBD.METHODS: In a 2-stage prospective multi-centre case control study, Next Generation sequencing was performed on a discovery cohort of immunomagnetically separated leucocytes from 32 patients (9 CD, 14 UC, 8 healthy controls) and differentially expressed signals were validated in whole blood in 294 patients (97 UC, 98 CD, 98 non-IBD) using quantitative PCR. Correlations were analysed with phenotype, including need for early treatment escalation as a marker of progressive disease using Cox proportional hazards.RESULTS: In stage 1, each leucocyte subset (CD4+ and CD8+ T-cells and CD14+ monocytes) was analysed in IBD and controls. Three specific miRNAs differentiated IBD from controls in CD4+ T-cells, including miR-1307-3p (p=0.01), miR-3615 (p=0.02) and miR-4792 (p=0.01). In the extension cohort, in stage 2, miR-1307-3p was able to predict disease progression in IBD (HR 1.98, IQR:1.20-3.27;logrank p=1.80×10-3), in particular CD (HR 2.81; IQR: 1.11-3.53, p=6.50×10-4). Using blood-based multimarker miRNA models, the estimated chance of escalation in CD was 83% if 2 or more criteria were met and 90% for UC if 3 or more criteria are met.INTERPRETATION: We have identified and validated unique CD4+ T-cell miRNAs that are differentially regulated in IBD. These miRNAs may be able to predict treatment escalation and have the potential for clinical translation; further prospective evaluation is now indicated.
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| 2. |
- Henry, Barbara J., et al.
(författare)
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A critical review of the application of polymer of low concern and regulatory criteria to fluoropolymers
- 2018
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Ingår i: Integrated Environmental Assessment and Management. - : Society of Environmental Toxicology and Chemistry (SETAC). - 1551-3777 .- 1551-3793. ; 14:3, s. 316-334
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Forskningsöversikt (refereegranskat)abstract
- Per- and poly-fluoroalkyl substances (PFAS) are a group of fluorinated substances that are in the focus of researchers and regulators due to widespread presence in the environment and biota, including humans, of perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA). Fluoropolymers, high molecular weight polymers within the PFAS group, have unique properties that constitute a distinct class within the PFAS group. Fluoropolymers have thermal, chemical, photochemical, hydrolytic, oxidative and biological stability. They have negligible residual monomer and oligomer content and low to no leachables. Fluoropolymers are practically insoluble in water and not subject to long-range transport. With a molecular weight well over 100,000 Da, fluoropolymers cannot cross the cell membrane. Fluoropolymers are not bioavailable or bioaccumulative, as evidenced by toxicology studies on PTFE: acute and subchronic systemic toxicity, irritation, sensitization, local toxicity on implantation, cytotoxicity, in vitro and in vivo genotoxicity, hemolysis, complement activation, and thrombogenicity. Clinical studies of patients receiving permanently implanted PTFE cardiovascular medical devices demonstrate no chronic toxicity or carcinogenicity, reproductive or developmental or endocrine toxicity. This paper brings together fluoropolymer toxicity data, human clinical data, and physical-chemical-thermal-biological data for review and assessment to show that fluoropolymers satisfy widely accepted assessment criteria to be considered as "Polymers of Low Concern". This review concludes that fluoropolymers are distinctly different from other polymeric and non-polymeric per- and poly-fluoroalkyl substances and should be separated from them for hazard assessment or regulatory purposes. Grouping fluoropolymers with all classes of PFAS for "read across" or structure activity relationship assessment is not scientifically appropriate.
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