| 1. |
- Assarsson, Malin, et al.
(författare)
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Narrowband UVB treatment induces expression of WNT7B, WNT10B and TCF7L2 in psoriasis skin
- 2019
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Ingår i: Archives of Dermatological Research. - : SPRINGER. - 0340-3696 .- 1432-069X. ; 311:7, s. 535-544
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Tidskriftsartikel (refereegranskat)abstract
- WNT/beta-catenin signaling pathways play a pivotal role in the human immune defense against infections and in chronic inflammatory conditions as psoriasis. Wnt gene alterations are linked to known comorbidities of psoriasis as obesity, diabetes and Crohns disease. The objective of this study was to investigate WNT7B, WNT10B, WNT16 and TCF7L2 gene and protein expression in lesional and non-lesional skin and in the peripheral blood of patients with chronic plaque psoriasis compared with healthy individuals. To investigate the effect of narrowband UVB radiation, expression of these genes were analyzed before and after narrowband UVB treatment. Associations between single nucleotide polymorphisms for WNT7B, WNT10B, WNT16 and TCF7L2 genes and psoriasis were tested. Our results show significantly decreased WNT7B, WNT10B and TCF7L2 gene expression in lesional skin compared with non-lesional skin and healthy controls. Narrowband UVB treatment significantly increased expression of these genes in lesional skin. Immunohistochemistry shows increased WNT16 expression in lesional skin. No significant differences in allele or genotype frequencies for Wnt or TCF7L2 gene polymorphisms were found between patient and control group. This study shows for the first time significant UVB induced upregulation of WNT7B, WNT10B and TCF7L2 in patients with psoriasis and suggests a potential role of these genes in psoriasis pathogenesis.
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| 2. |
- Assarsson, Malin, et al.
(författare)
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Significant Changes in the Skin Microbiome in Patients with Chronic Plaque Psoriasis after Treatment with Narrowband Ultraviolet B
- 2018
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Ingår i: Acta Dermato-Venereologica. - : ACTA DERMATO-VENEREOLOGICA. - 0001-5555 .- 1651-2057. ; 98:4, s. 428-436
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Tidskriftsartikel (refereegranskat)abstract
- Changes in the skin microbiome have been shown to promote cutaneous inflammation. The skin microbiome of patients with chronic plaque type psoriasis was analysed before and after treatment with narrowband ultraviolet B (UVB). Swab samples of the microbiome were taken from lesional and non-lesional skin of 26 patients. Microbiotas were characterized by sequencing 16S rRNA bacterial genes on the Illumina MiSeq platform. Lesional skin microbiome diversity correlated with psoriasis severity (measured with the Psoriasis Area and Severity Index; PASI). There was a significantly lower abundance of the phylum Firmicutes and the genus Staphylococcus in lesional skin compared with non-lesional skin before UVB treatment. Responders (amp;gt; 75% target Psoriasis Severity Index (PSI) improvement) had significantly lower abundance of the phyla Firmicutes in lesional and non-lesional skin and lower abundance of the genera Staphylococcus, Finegoldia, Anaerococcus, Peptoniphilus, Gardnerella, Prevotella and Clostridium in lesional skin after UVB treatment. Pseudomonas significantly decreased in lesional and non-lesional skin of treatment responders. These results suggest that skin microbiome alterations after UVB treatment could be related to treatment and treatment response.
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| 3. |
- Assarsson, Malin, et al.
(författare)
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Significant Differences in the Bacterial Microbiome of the Pharynx and Skin in Patients with Psoriasis Compared with Healthy Controls
- 2020
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Ingår i: Acta Dermato-Venereologica. - : ACTA DERMATO-VENEREOLOGICA. - 0001-5555 .- 1651-2057. ; 100
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Tidskriftsartikel (refereegranskat)abstract
- Studies have shown differences in the skin and gut bacterial microbiomes in patients with psoriasis, but the pharyngeal microbiome has not been studied previously. The aim of this study was to investigate differences in the bacterial microbiome of the pharynx and skin of patients with psoriasis compared with healthy controls. Swabs were taken from the pharynx and el-bow skin of 39 patients with psoriasis and 70 controls. Microbiomes were characterized by sequencing 16S rRNA genes on the Illumina MiSeq platform. Significant differences were found in alpha and beta diversity in the skin, but not in the pharynx. Significant differences were also found between several phyla and genera in both skin and pharynx. The severity of psoriasis did not correlate with any genera in the pharynx, but with Capnocytophaga, Leptotrichia, Abiotrophia and Tannerella in the skin. The composition of the pharyngeal and skin microbiome may be of importance in the pathogenesis of psoriasis.
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| 4. |
- Berggrund, Malin, et al.
(författare)
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Identification of candidate plasma protein biomarkers for cervical cancer using the multiplex proximity extension assay
- 2019
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Ingår i: Molecular & Cellular Proteomics. - 1535-9476 .- 1535-9484. ; 18:4, s. 735-743
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Tidskriftsartikel (refereegranskat)abstract
- Human papillomavirus (HPV) is recommended as the primary test in cervical cancer screening, with co-testing by cytology for HPV-positive women to identify cervical lesions. Cytology has low sensitivity and there is a need to identify biomarkers that could identify dysplasia that are likely to progress to cancer. We searched for plasma proteins that could identify women with cervical cancer using the multiplex proximity extension assay (PEA). The abundance of 100 proteins were measured in plasma collected at the time of diagnosis of patients with invasive cervical cancer and in population controls using the Olink Multiplex panels CVD II, INF I, and ONC II. Eighty proteins showed increased levels in cases compared to controls. We identified a signature of 11 proteins (PTX3, ITGB1BP2, AXIN1, STAMPB, SRC, SIRT2, 4E-BP1, PAPPA, HB-EGF, NEMO and IL27) that distinguished cases and controls with a sensitivity of 0.96 at a specificity of 1.0. This signature was evaluated in a prospective replication cohort with samples collected before, at or after diagnosis and achieved a sensitivity of 0.78 and a specificity 0.56 separating samples collected at the time of diagnosis of invasive cancer from samples collected prior to diagnosis. No difference in abundance was seen between samples collected prior to diagnosis or after treatment as compared to population controls, indicating that this protein signature is mainly informative close to time of diagnosis. Further studies are needed to determine the optimal window in time prior to diagnosis for these biomarker candidates.
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| 5. |
- Byman, Elin, et al.
(författare)
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Alpha-amylase 1A copy number variants and the association with memory performance and Alzheimer's dementia
- 2020
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Ingår i: Alzheimers Research & Therapy. - : Springer Science and Business Media LLC. - 1758-9193. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- Background Previous studies have shown that copy number variation (CNV) in the alpha (alpha)-amylase gene (AMY1A) is associated with body mass index, insulin resistance, and blood glucose levels, factors also shown to increase the risk of Alzheimer's dementia (AD). We have previously demonstrated the presence of alpha-amylase in healthy neuronal dendritic spines and a reduction of the same in AD patients. In the current study, we investigate the relationship between AMY1A copy number and AD, memory performance, and brain alpha-amylase activity. Methods and materials The association between AMY1A copy number and development of AD was analyzed in 5422 individuals (mean age at baseline 57.5 +/- 5.9, females 58.2%) from the Malmo diet and cancer study genotyped for AMY1A copy number, whereof 247 where diagnosed with AD during a mean follow-up of 20 years. Associations between AMY1A copy number and cognitive performance where analyzed in 791 individuals (mean age at baseline 54.7 +/- 6.3, females 63%), who performed Montreal Cognitive Assessment (MoCA) test. Correlation analysis between alpha-amylase activity or alpha-amylase gene expression and AMY1A copy number in post-mortem hippocampal tissue from on demented controls (n = 8) and AD patients (n = 10) was also performed. Results Individuals with very high ( >= 10) AMY1A copy number had a significantly lower hazard ratio of AD (HR = 0.62, 95% CI 0.41-0.94) and performed significantly better on MoCA delayed word recall test, compared to the reference group with AMY1A copy number 6. A trend to lower hazard ratio of AD was also found among individuals with low AMY1A copy number (1-5) (HR = 0.74, 95% CI 0.53-1.02). A tendency towards a positive correlation between brain alpha-amylase activity and AMY1A copy number was found, and females showed higher brain alpha-amylase activity compared to males. Conclusion Our study suggests that the degree of alpha-amylase activity in the brain is affected by AMY1A copy number and gender, in addition to AD pathology. The study further suggests that very high AMY1A copy number is associated with a decreased hazard ratio of AD and we speculate that this effect is mediated via a beneficial impact of AMY1A copy number on episodic memory performance.
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| 6. |
- Duvetorp, Albert, et al.
(författare)
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Narrowband-UVB treatment reduces levels of mediators of the Th17 pathway and chemotaxis in psoriatic skin without any concurring effect on mediator levels in serum
- 2022
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Ingår i: EJD. European journal of dermatology. - : JOHN LIBBEY EUROTEXT LTD. - 1167-1122 .- 1952-4013. ; 32:2, s. 250-259
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Tidskriftsartikel (refereegranskat)abstract
- Background: Narrowband-UVB (NB-UVB) is a common and effective psoriasis treatment. It exerts its effect locally and is therefore a better model for exploring dynamics of serum biomarkers reflecting psoriasis skin disease activity compared to other treatments with systemic uptake. Objectives: To perform an exploratory study to assess potential roles of multiple disease mediators as biomarkers for psoriasis disease activity, and increase understanding of NB-UVB treatment effects in psoriatic skin. Materials & Methods: Patients with plaque psoriasis were sampled (lesional, non-lesional skin, serum) before and after full NB-UVB treatment. Samples were assessed for 78 different mediators using Luminex assays. Correlation networks were analysed to explore interactions between lesional skin mediators before and after NB-UVB treatment. Results: None of the studied serum mediators were significantly affected by NB-UVB treatment after correction for multiple testing. Thirty mediators revealed a significant difference in lesional skin compared to non-lesional skin before treatment including interleukin 23 (IL-23) and C-C motif chemokine ligand 20 (CCL20), but also novel mediators such as angiopoietin-like 4 (ANGPTL4) and pentraxin 3 (PTX3). The levels of 25 mediators in skin decreased significantly, and network analysis revealed markedly reduced cluster formations and correlations after NB-UVB. Conclusion: NB-UVB treatment reduced the concentration of mediators of the Th17 inflammatory pathway and chemotaxis in psoriatic lesional skin, but also affected less studied and novel mediators. Although the treatment affected the levels of a majority of mediators in skin, no corresponding effect was observed in serum, thus challenging the possibility of a serum biomarker reflecting skin disease activity.
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| 7. |
- Duvetorp, Albert, et al.
(författare)
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Observational study on Swedish plaque psoriasis patients receiving narrowband-UVB treatment show decreased S100A8/A9 protein and gene expression levels in lesional psoriasis skin but no effect on S100A8/A9 protein levels in serum
- 2019
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Ingår i: PLOS ONE. - : PUBLIC LIBRARY SCIENCE. - 1932-6203. ; 14:3
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Tidskriftsartikel (refereegranskat)abstract
- S100A8 and S100A9 proteins are highly upregulated in patients with psoriasis and have been proposed as potential biomarkers for psoriasis. The present study was designed to analyze the effect of narrowband ultraviolet B therapy on these proteins. S100A8, S100A9 gene expression and S100A8/A9 heterocomplex protein levels were analyzed in lesional and non-lesional skin before and after narrowband-UVB treatment in patients with chronic plaque type psoriasis. In addition, disease severity was measured by psoriasis area and severity index (PASI) and serum protein levels of S100A8/A9 were repeatedly analyzed. Narrowband-UVB treatment significantly reduced S100A8, S100A9 gene expression and S100A8/A9 protein levels in lesional skin while serum levels showed no significant change. No correlation between PASI and serum S100A8/A9 protein levels was found. These results implicate a role of S100A8/A9 in the anti-inflammatory effect of narrowband-UVB. Serum S100A8/A9 levels do not respond to treatment suggesting that serum S100A8/A9 does not originate from psoriasis skin keratinocytes. Serum S100A8/A9 levels do not correlate with PASI questioning serum S100A8/A9 as a biomarker for psoriasis skin activity.
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| 8. |
- Enroth, Stefan, 1976-, et al.
(författare)
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A two-step strategy for identification of plasma protein biomarkers for endometrial and ovarian cancer
- 2018
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Ingår i: Clinical Proteomics. - : Springer Science and Business Media LLC. - 1542-6416 .- 1559-0275. ; 15
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundOver 500,000 women worldwide are diagnosed with ovarian or endometrial cancer each year. We have used a two-step strategy to identify plasma proteins that could be used to improve the diagnosis of women with an indication of gynecologic tumor and in population screening.MethodsIn the discovery step we screened 441 proteins in plasma using the proximity extension assay (PEA) and five Olink Multiplex assays (CVD II, CVD III, INF I, ONC II, NEU I) in women with ovarian cancer (n=106), endometrial cancer (n=74), benign ovarian tumors (n=150) and healthy population controls (n=399). Based on the discovery analyses a set of 27 proteins were selected and two focused multiplex PEA assays were developed. In a replication step the focused assays were used to study an independent set of cases with ovarian cancer (n=280), endometrial cancer (n=228), women with benign ovarian tumors (n=76) and healthy controls (n=57).ResultsIn the discovery step, 27 proteins that showed an association to cancer status were identified. In the replication analyses, the focused assays distinguished benign tumors from ovarian cancer stage III-IV with a sensitivity of 0.88 and specificity of 0.92 (AUC=0.92). The assays had a significantly higher AUC for distinguishing benign tumors from late stage ovarian cancer than using CA125 and HE4 (p=9.56e-22). Also, population controls could be distinguished from ovarian cancer stage III-IV with a sensitivity of 0.85 and a specificity of 0.92 (AUC=0.89).ConclusionThe PEA assays represent useful tools for identification of new biomarkers for gynecologic cancers. The selected protein assays could be used to distinguish benign tumors from ovarian and endometrial cancer in women diagnosed with an unknown suspicious pelvic mass. The panels could also be used in population screening, for identification of women in need of specialized gynecologic transvaginal ultrasound examination.FundingThe Swedish Cancer Foundation, Vinnova (SWELIFE), The Foundation for Strategic Research (SSF), Assar Gabrielsson Foundation.
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| 9. |
- Enroth, Stefan, 1976-, et al.
(författare)
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High throughput proteomics identifies a high-accuracy 11 plasma protein biomarker signature for ovarian cancer
- 2019
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Ingår i: Communications Biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 2
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Tidskriftsartikel (refereegranskat)abstract
- Ovarian cancer is usually detected at a late stage and the overall 5-year survival is only 30-40%. Additional means for early detection and improved diagnosis are acutely needed. To search for novel biomarkers, we compared circulating plasma levels of 593 proteins in three cohorts of patients with ovarian cancer and benign tumors, using the proximity extension assay (PEA). A combinatorial strategy was developed for identification of different multivariate biomarker signatures. A final model consisting of 11 biomarkers plus age was developed into a multiplex PEA test reporting in absolute concentrations. The final model was evaluated in a fourth independent cohort and has an AUC = 0.94, PPV = 0.92, sensitivity = 0.85 and specificity = 0.93 for detection of ovarian cancer stages I-IV. The novel plasma protein signature could be used to improve the diagnosis of women with adnexal ovarian mass or in screening to identify women that should be referred to specialized examination.
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| 10. |
- Gren, Louise, et al.
(författare)
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Underground emissions and miners' personal exposure to diesel and renewable diesel exhaust in a Swedish iron ore mine
- 2022
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Ingår i: International Archives of Occupational and Environmental Health. - : Springer Science and Business Media LLC. - 1432-1246 .- 0340-0131.
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: Underground diesel exhaust exposure is an occupational health risk. It is not known how recent intensified emission legislation and use of renewable fuels have reduced or altered occupational exposures. We characterized these effects on multipollutant personal exposure to diesel exhaust and underground ambient air concentrations in an underground iron ore mine.METHODS: Full-shift personal sampling (12 workers) of elemental carbon (EC), nitrogen dioxide (NO2), polycyclic aromatic hydrocarbons (PAHs), and equivalent black carbon (eBC) was performed. The study used and validated eBC as an online proxy for occupational exposure to EC. Ambient air sampling of these pollutants and particle number size distribution and concentration were performed in the vicinity of the workers. Urine samples (27 workers) were collected after 8 h exposure and analyzed for PAH metabolites and effect biomarkers (8-oxodG for DNA oxidative damage, 4-HNE-MA for lipid peroxidation, 3-HPMA for acrolein).RESULTS: The personal exposures (geometric mean; GM) of the participating miners were 7 µg EC m-3 and 153 µg NO2 m-3, which are below the EU occupational exposure limits. However, exposures up to 94 µg EC m-3 and 1200 µg NO2 m-3 were observed. There was a tendency that the operators of vehicles complying with sharpened emission legislation had lower exposure of EC. eBC and NO2 correlated with EC, R = 0.94 and R = 0.66, respectively. No correlation was found between EC and the sum of 16 priority PAHs (GM 1790 ng m-3). Ratios between personal exposures and ambient concentrations were similar and close to 1 for EC and NO2, but significantly higher for PAHs. Semi-volatile PAHs may not be effectively reduced by the aftertreatment systems, and ambient area sampling did not predict the personal airborne PAHs exposure well, neither did the slightly elevated concentration of urinary PAH metabolites correlate with airborne PAH exposure.CONCLUSION: Miners' exposures to EC and NO2 were lower than those in older studies indicating the effect of sharpened emission legislation and new technologies. Using modern vehicles with diesel particulate filter (DPF) may have contributed to the lower ambient underground PM concentration and exposures. The semi-volatile behavior of the PAHs might have led to inefficient removal in the engines aftertreatment systems and delayed removal by the workplace ventilation system due to partitioning to indoor surfaces. The results indicate that secondary emissions can be an important source of gaseous PAH exposure in the mine.
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