| 1. |
- Kanai, M, et al.
(författare)
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- 2023
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swepub:Mat__t
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| 2. |
- Niemi, MEK, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 3. |
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| 4. |
- Zheng, TH, et al.
(författare)
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Genome-wide analysis of 944 133 individuals provides insights into the etiology of haemorrhoidal disease
- 2021
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Ingår i: Gut. - : BMJ. - 1468-3288 .- 0017-5749. ; 70:8, s. 1538-1549
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Tidskriftsartikel (refereegranskat)abstract
- Haemorrhoidal disease (HEM) affects a large and silently suffering fraction of the population but its aetiology, including suspected genetic predisposition, is poorly understood. We report the first genome-wide association study (GWAS) meta-analysis to identify genetic risk factors for HEM to date.DesignWe conducted a GWAS meta-analysis of 218 920 patients with HEM and 725 213 controls of European ancestry. Using GWAS summary statistics, we performed multiple genetic correlation analyses between HEM and other traits as well as calculated HEM polygenic risk scores (PRS) and evaluated their translational potential in independent datasets. Using functional annotation of GWAS results, we identified HEM candidate genes, which differential expression and coexpression in HEM tissues were evaluated employing RNA-seq analyses. The localisation of expressed proteins at selected loci was investigated by immunohistochemistry.ResultsWe demonstrate modest heritability and genetic correlation of HEM with several other diseases from the GI, neuroaffective and cardiovascular domains. HEM PRS validated in 180 435 individuals from independent datasets allowed the identification of those at risk and correlated with younger age of onset and recurrent surgery. We identified 102 independent HEM risk loci harbouring genes whose expression is enriched in blood vessels and GI tissues, and in pathways associated with smooth muscles, epithelial and endothelial development and morphogenesis. Network transcriptomic analyses highlighted HEM gene coexpression modules that are relevant to the development and integrity of the musculoskeletal and epidermal systems, and the organisation of the extracellular matrix.ConclusionHEM has a genetic component that predisposes to smooth muscle, epithelial and connective tissue dysfunction.
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| 5. |
- Juzenas, S., et al.
(författare)
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Sequencing-based hematopoietic miRNA landscape reveals common and distinct features of autoimmune inflammatory phenotypes
- 2019
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Ingår i: Journal of Crohn's & Colitis. - : Oxford University Press. - 1873-9946 .- 1876-4479. ; 13:Suppl. 1, s. S614-S614
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background: MiRNAs represent a class of small non-coding RNAs which are involved in regulation of protein-coding gene expression. Being implicated in various processes such as development and regu-latory circuits of cells, miRNAs also play an important role in the etiology of a variety of diseases. Imbalance of the regulatory pro-cesses within immune system development and response may lead to disturbed production of pro-inflammatory cytokines and over-reactivity of the immune cells, thus causing relapsing inflamma-tion, a characteristic feature of inflammatory bowel disease (IBD). Recent studies of colonic miRNAs employed NGS for the distinction between CD, UC and healthy controls, or among different CD sub-types. However, NGS-based profiles of blood-circulating miRNAs have thus far not been investigated in the context of IBD together with other immune-mediated diseases, including ankylosing spon-dylitis, psoriasis, systemic lupus erythematosus, rheumatoid arthritis and sarcoidosis, as well as non-immune hemolytic-uremic syndrome.Methods: Study participants were recruited in Germany and Sweden, where peripheral blood samples (PAXgene) as well as phenotypical and clinical information (such as treatment status, dis-ease activity and location) was collected. Small RNA transcriptomes of 680 individuals (Figure 1) were sequenced using Illumina NGS platform. Small RNA-seq data preprocessing and quantification were performed using cutadapt and miraligner (ref. miRBase v22), respectively. Differential expression analysis (DESeq2) and correla-tion (Spearman) analysis have been performed to identify disease activity-, trait- and treatment-specific miRNA signatures. These sig-natures were then utilized in a machine-learning approach to build classification models for IBD diagnostics.Results: The results of multiple pairwise differential expression anal-yses among different immune-mediated inflammatory conditions and healthy controls revealed inflammation-specific as well and dis-ease-specific deregulation of miRNAs. Correlation analysis identified miRNAs positively and negatively correlated with IBD activity. The preliminary results of machine learning classifiers based on miRNA profiles showed that median Matthews correlation coefficient for all model types showed remarkable predictive performance estimated as being 1.00 (median over main diagnoses), as well as ranging from 0.68 to 0.76 (median over CD location) and from 0.69 to 0.77 (median over UC extent).Conclusions: Immune-mediated inflammatory diseases share com-mon and distinct differentially expressed miRNAs, which have a potential to be used in the diagnostics of IBD, including the evalua-tion of the disease activity.
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| 6. |
- Coelho, S. C., et al.
(författare)
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Gold nanoparticle delivery-enhanced proteasome inhibitor effect in adenocarcinoma cells
- 2013
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Ingår i: Expert Opinion on Drug Delivery. - : Informa Healthcare. - 1742-5247 .- 1744-7593. ; 10:10, s. 1345-1352
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Tidskriftsartikel (refereegranskat)abstract
- Background: Proteasome inhibition is a current therapeutic strategy used in the treatment of multiple myeloma. Drugs controlling proteasome activity are ideally suited for unidirectional manipulation of cellular pathways such as apoptosis. The first proteasome inhibitor approved in clinics was bortezomib. This drug is currently used in combination with other anticancer agents. Objectives: In this study, the enhancement of bortezomib activity was evaluated using gold nanoparticles coated with poly(ethylene glycol). The uptake mechanism of the gold nanoparticles in pancreatic cell lines, S2-013 and hTERT-HPNE, was assessed by laser scanning confocal microscopy (LSCM). Results: Pancreatic cancer cells internalized the nanoparticles together with the drug in few minutes through the formation of endocytic vesicles. This rapid uptake leads to an increase in the concentration and diffusion of bortezomib in the cytoplasm yielding an increased toxicity on the cells when compared to the drug alone. Conclusion: Gold nanoparticles can be used as effective delivery systems to increasing the permeation and retention of drugs in cancer cells.
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| 7. |
- Coelho, S. C., et al.
(författare)
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Enhancing Proteasome-Inhibitor Effect by Functionalized Gold Nanoparticles
- 2014
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Ingår i: Journal of Biomedical Nanotechnology. - : American Scientific Publishers. - 1550-7033. ; 10:4, s. 717-723
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Tidskriftsartikel (refereegranskat)abstract
- Colloidal gold nanoparticles intensify the anticancer response of the drug bortezomib, a proteasome inhibitor. Polyethylene glycol-coated gold nanoparticles and the drug show a synergistic effect in reducing the cell viability of prostate cancer cell line Du145. It was observed a significant cell viability reduction with bortezomib concentrations as low as 4 nM. The proteasome inhibitor alone had to be present at concentrations in the ranger of 120 nM to induce identical cytotoxicity response. These findings demonstrate that gold nanoparticles enhancing the permeation and retention (EPR) effect in Du145 cells and open the possibility to decrease multi-drug resistance (MDR). The in vitro results of functionalized gold nanoparticles, internalized by cancer cells, pave the way for a more efficient proteasome inhibitor delivery and release in adenocarcinoma cells.
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| 8. |
- Kleinauskas, A., et al.
(författare)
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Carbon-core silver-shell nanodots as sensitizers for phototherapy and radiotherapy
- 2013
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Ingår i: Nanotechnology. - : IOP Publishing. - 1361-6528 .- 0957-4484. ; 24:32
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Tidskriftsartikel (refereegranskat)abstract
- Spherical carbon nanoparticles (carbon nanodots) with a silver shell were investigated as potential sensitizing agents. The cytotoxicity of the combination of ultraviolet radiation or x-rays with the nanodots was examined in cancer cells in vitro. The cell viability decreased following the exposure to the radiation. The carbon nanodots enhanced the radiation effects by significantly reducing the amount of surviving cells compared to that of the cells exposed only to the radiation. Carbon-core silver-shell nanodots can be proposed as a bimodal sensitization platform for biological and medicinal applications employing non-ionizing or ionizing radiation.
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