| 1. |
- Iglesia, I., et al.
(författare)
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Folate and vitamin B-12 concentrations are associated with plasma DHA and EPA fatty acids in European adolescents : the Healthy Lifestyle in Europe by Nutrition in Adolescence (HELENA) study
- 2017
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Ingår i: British Journal of Nutrition. - : CAMBRIDGE UNIV PRESS. - 0007-1145 .- 1475-2662. ; 117:1, s. 124-133
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Tidskriftsartikel (refereegranskat)abstract
- This study aimed to examine the association between vitamin B-6, folate and vitamin B-12 biomarkers and plasma fatty acids in European adolescents. A subsample from the Healthy Lifestyle in Europe by Nutrition in Adolescence study with valid data on B-vitamins and fatty acid blood parameters, and all the other covariates used in the analyses such as BMI, Diet Quality Index, education of the mother and physical activity assessed by a questionnaire, was selected resulting in 674 cases (43% males). B-vitamin biomarkers were measured by chromatography and immunoassay and fatty acids by enzymatic analyses. Linear mixed models elucidated the association between B-vitamins and fatty acid blood parameters (changes in fatty acid profiles according to change in 10 units of vitamin B biomarkers). DHA, EPA) and n-3 fatty acids showed positive associations with B-vitamin biomarkers, mainly with those corresponding to folate and vitamin B12. Contrarily, negative associations were found with n-6: n-3 ratio, trans-fatty acids and oleic: stearic ratio. With total homocysteine (tHcy), all the associations found with these parameters were opposite (for instance, an increase of 10 nmol/l in red blood cell folate or holotranscobalamin in females produces an increase of 15.85 mu mol/l of EPA (P value < 0.01), whereas an increase of 10 nmol/l of tHcy in males produces a decrease of 2.06 mu mol/l of DHA (P value < 0.05). Positive associations between B-vitamins and specific fatty acids might suggest underlying mechanisms between B-vitamins and CVD and it is worth the attention of public health policies.
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| 2. |
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| 3. |
- Åberg, Anna, et al.
(författare)
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Helicobacter pylori adapts to chronic infection and gastric disease via ph-responsive baba-mediated adherence
- 2017
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Ingår i: Cell Host and Microbe. - : Elsevier BV. - 1931-3128 .- 1934-6069. ; 21:3, s. 376-389
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Tidskriftsartikel (refereegranskat)abstract
- The BabA adhesin mediates high-affinity binding of Helicobacter pylori to the ABO blood group antigen-glycosylated gastric mucosa. Here we show that BabA is acid responsive-binding is reduced at low pH and restored by acid neutralization. Acid responsiveness differs among strains; often correlates with different intragastric regions and evolves during chronic infection and disease progression; and depends on pH sensor sequences in BabA and on pH reversible formation of high-affinity binding BabA multimers. We propose that BabA's extraordinary reversible acid responsiveness enables tight mucosal bacterial adherence while also allowing an effective escape from epithelial cells and mucus that are shed into the acidic bactericidal lumen and that bio-selection and changes in BabA binding properties through mutation and recombination with babA-related genes are selected by differences among individuals and by changes in gastric acidity over time. These processes generate diverse H. pylori subpopulations, in which BabA's adaptive evolution contributes to H. pylori persistence and overt gastric disease.
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| 4. |
- Dongiovanni, P., et al.
(författare)
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Transmembrane 6 Superfamily Member 2 Gene Variant Disentangles Nonalcoholic Steatohepatitis From Cardiovascular Disease
- 2015
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Ingår i: Hepatology. - : Ovid Technologies (Wolters Kluwer Health). - 0270-9139 .- 1527-3350. ; 61:2, s. 506-514
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Tidskriftsartikel (refereegranskat)abstract
- Excess hepatic storage of triglycerides is considered a benign condition, but nonalcoholic steatohepatitis (NASH) may progress to fibrosis and promote atherosclerosis. Carriers of the TM6SF2 E167K variant have fatty liver as a result of reduced secretion of very-low-density lipoproteins (VLDLs). As a result, they have lower circulating lipids and reduced risk of myocardial infarction. In this study, we aimed to assess whether TM6SF2 E167K affects liver damage and cardiovascular outcomes in subjects at risk of NASH. Liver damage was evaluated in 1,201 patients who underwent liver biopsy for suspected NASH; 427 were evaluated for carotid atherosclerosis. Cardiovascular outcomes were assessed in 1,819 controls from the Swedish Obese Subjects (SOS) cohort. Presence of the inherited TM6SF2 E167K variant was determined by TaqMan assays. In the liver biopsy cohort, 188 subjects (13%) were carriers of the E167K variant. They had lower serum lipid levels than noncarriers (P<0.05), had more-severe steatosis, necroinflammation, ballooning, and fibrosis (P<0.05), and were more likely to have NASH (odds ratio [OR]: 1.84; 95% confidence interval [CI]: 1.23-2.79) and advanced fibrosis (OR, 2.08; 95% CI: 1.20-3.55), after adjustment for age, sex, body mass index, fasting hyperglycemia, and the I148M PNPLA3 risk variant. However, E167K carriers had lower risk of developing carotid plaques (OR, 0.49; 95% CI: 0.25-0.94). In the SOS cohort, E167K carriers had higher alanine aminotransferase ALT and lower lipid levels (P<0.05), as well as a lower incidence of cardiovascular events (hazard ratio: 0.61; 95% CI: 0.39-0.95). Conclusions: Carriers of the TM6SF2 E167K variant are more susceptible to progressive NASH, but are protected against cardiovascular disease. Our findings suggest that reduced ability to export VLDLs is deleterious for the liver. (Hepatology 2015;61:506-514)
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| 5. |
- Glad, Camilla A M, 1981, et al.
(författare)
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The GH receptor exon 3 deleted/full-length polymorphism is associated with central adiposity in the general population.
- 2015
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Ingår i: European journal of endocrinology / European Federation of Endocrine Societies. - 1479-683X .- 0804-4643. ; 172:2, s. 123-128
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To test the hypothesis that the growth hormone (GH) receptor (GHR) d3/fl polymorphism influences anthropometry and body composition in the general population. Design and Setting: The Swedish Obese Subjects (SOS) reference study is a cross-sectional population-based study, randomly selected from a population registry. A sub-group of the population-based Malmö Diet and Cancer Study (MDC-CC) was used as a replication cohort. Methods: The SOS reference study comprises 1135 subjects (46.2% men), with an average age of 49.5 yrs. The MDC-CC includes 5451 successfully genotyped subjects (41.5% men), with an average age of 57.5 yrs. GHR d3/fl genotypes were determined using tagSNP rs6873545. Linear regression analyses were used to test for genotype - phenotype associations. Results: In the SOS reference study, subjects homozygous for the d3-GHR weighed approximately four kilos more (p=0.011), had larger waist-to-hip ratio (WHR, p=0.036), waist circumference (p=0.016) and more fat free mass estimated from total body potassium (TBK, p=0.026) than grouped fl/d3 and fl/fl subjects (d3-recessive genetic model). The association with WHR was replicated in the MDC-CC (p=0.002), but not those with other anthropometric traits. Conclusions: In this population-based study the GHR d3/fl polymorphism was found to be of functional relevance and associated with central adiposity, such that subjects homozygous for the d3-GHR showed an increased abdominal obesity.
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| 6. |
- Labbé, David P., et al.
(författare)
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TOP2A and EZH2 provide early detection of an aggressive prostate cancer subgroup
- 2017
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Ingår i: Clinical Cancer Research. - 1078-0432. ; 23:22, s. 7072-7083
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Current clinical parameters do not stratify indolent from aggressive prostate cancer. Aggressive prostate cancer, defined by the progression from localized disease to metastasis, is responsible for the majority of prostate cancer–associated mortality. Recent gene expression profiling has proven successful in predicting the outcome of prostate cancer patients; however, they have yet to provide targeted therapy approaches that could inhibit a patient's progression to metastatic disease. Experimental Design: We have interrogated a total of seven primary prostate cancer cohorts (n = 1,900), two metastatic castration-resistant prostate cancer datasets (n = 293), and one prospective cohort (n = 1,385) to assess the impact of TOP2A and EZH2 expression on prostate cancer cellular program and patient outcomes. We also performed IHC staining for TOP2A and EZH2 in a cohort of primary prostate cancer patients (n = 89) with known outcome. Finally, we explored the therapeutic potential of a combination therapy targeting both TOP2A and EZH2 using novel prostate cancer–derived murine cell lines. Results: We demonstrate by genome-wide analysis of independent primary and metastatic prostate cancer datasets that concurrent TOP2A and EZH2 mRNA and protein upregulation selected for a subgroup of primary and metastatic patients with more aggressive disease and notable overlap of genes involved in mitotic regulation. Importantly, TOP2A and EZH2 in prostate cancer cells act as key driving oncogenes, a fact highlighted by sensitivity to combination-targeted therapy. Conclusions: Overall, our data support further assessment of TOP2A and EZH2 as biomarkers for early identification of patients with increased metastatic potential that may benefit from adjuvant or neoadjuvant targeted therapy approaches.
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| 7. |
- Pankov, Dmitry, et al.
(författare)
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In vivo immuno-targeting of an extracellular epitope of membrane bound preferentially expressed antigen in melanoma (PRAME)
- 2017
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Ingår i: Oncotarget. - : Impact Journals, LLC. - 1949-2553. ; 8:39, s. 65917-65931
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Tidskriftsartikel (refereegranskat)abstract
- Preferentially Expressed Antigen in Melanoma (PRAME) is a cancer/testis antigen that is overexpressed in a broad range of malignancies, while absent in most healthy human tissues, making it an attractive diagnostic cancer biomarker and therapeutic target. Although commonly viewed as an intracellular protein, we have demonstrated that PRAME has a membrane bound form with an external epitope targetable with conventional antibodies. We generated a polyclonal antibody (Membrane associated PRAME Antibody 1, MPA1) against an extracellular peptide sequence of PRAME. Binding of MPA1 to recombinant PRAME was evaluated by Enzyme-Linked Immunosorbent Assay (ELISA). Flow cytometry and confocal immunofluorescence microscopy of MPA1 was performed on multiple tumor cell lines. Reverse Transcription Polymerase Chain Reaction (RTPCR) for PRAME was conducted to compare protein and transcriptional expression levels. We demonstrated a robust proof-of-concept for PRAME targeting in vivo by radiolabeling MPA1 with zirconium-89 (89Zr-DFO-MPA1) and demonstrating high specific uptake in PRAME expressing tumors. To our knowledge, this is the first time a cancer testis antigen has been targeted using conventional antibody technologies. Thus, PRAME can be exploited for multiple clinical applications, including targeted therapy, diagnostic imaging and treatment guidance in a widerange of malignancies, with minimal off-target toxicity.
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| 8. |
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| 9. |
- Strandberg, Bo, 1960, et al.
(författare)
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Evaluation of polyurethane foam passive air sampler (PUF) as a tool for occupational PAH measurements
- 2018
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Ingår i: Chemosphere. - : Elsevier BV. - 0045-6535 .- 1879-1298. ; 190, s. 35-42
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Tidskriftsartikel (refereegranskat)abstract
- Routine monitoring of workplace exposure to polycyclic aromatic hydrocarbons (PAHs) is performed mainly via active sampling. However, active samplers have several drawbacks and, in some cases, may even be unusable. Polyurethane foam (PUF) as personal passive air samplers constitute good alternatives for PAH monitoring in occupational air (8 h). However, PUFs must be further tested to reliably yield detectable levels of PAHs in short exposure times (1–3 h) and under extreme occupational conditions. Therefore, we compared the personal exposure monitoring performance of a passive PUF sampler with that of an active air sampler and determined the corresponding uptake rates (Rs). These rates were then used to estimate the occupational exposure of firefighters and police forensic specialists to 32 PAHs. The work environments studied were heavily contaminated by PAHs with (for example) benzo(a)pyrene ranging from 0.2 to 56 ng m−3, as measured via active sampling. We show that, even after short exposure times, PUF can reliably accumulate both gaseous and particle-bound PAHs. The Rs-values are almost independent of variables such as the concentration and the wind speed. Therefore, by using the Rs-values (2.0–20 m3 day−1), the air concentrations can be estimated within a factor of two for gaseous PAHs and a factor of 10 for particulate PAHs. With very short sampling times (1 h), our method can serve as a (i) simple and user-friendly semi-quantitative screening tool for estimating and tracking point sources of PAH in micro-environments and (ii) complement to the traditional active pumping methods. © 2017 The Authors
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| 10. |
- Wallas, A., et al.
(författare)
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Traffic noise exposure in relation to adverse birth outcomes and body mass between birth and adolescence
- 2019
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Ingår i: Environmental Research. - : Elsevier BV. - 0013-9351 .- 1096-0953. ; 169, s. 362-367
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Tidskriftsartikel (refereegranskat)abstract
- Background: There is growing evidence that traffic noise exposure is associated with adiposity among adults but data in children are limited. Objective: This longitudinal study examined whether pre- and postnatal noise exposure is associated with body mass index (BMI) between birth and adolescence or with adverse birth outcomes. Methods: The study was conducted using data from the BAMSE birth cohort, which included 4089 children born in Stockholm County, Sweden. Data on BMI from birth to adolescence were collected via questionnaires, clinical examinations and health care records. A national register provided information on birth outcomes. Road traffic noise levels at the most exposed façade were estimated for all residences of the children during follow-up, as well as of their mothers during pregnancy, and time-weighted average exposure was calculated for different time windows. Maternal occupational noise exposure was obtained from a job-exposure-matrix. Logistic- and quantile regression models were used to estimate associations between noise exposure and health outcomes. Results: We found residential road traffic noise exposure to be associated with increases in BMI from school age to adolescence, but not at earlier ages. In the age groups 8–11 years and 12–16 years the BMI increments were 0.11 kg/m2 per 10 dB Lden (95% CI 0.08–0.13) and 0.20 kg/m2 per 10 dB Lden (95% CI 0.17–0.22), respectively. Maternal noise exposure during pregnancy was generally unrelated to adverse birth outcomes and BMI from birth to adolescence in the children, however, traffic noise exposure was associated with a decreased risk of preterm birth Conclusion: Residential road traffic noise exposure was associated with BMI increases from school age to adolescence, but not at earlier ages. Maternal occupational noise exposure or exposure from road traffic during pregnancy were not consistently related to birth outcomes or BMI from birth to adolescence. © 2018 The Authors
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