| 1. |
- Mezheyeuski, Artur, et al.
(författare)
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An immune score reflecting pro- and anti-tumoural balance of tumour microenvironment has major prognostic impact and predicts immunotherapy response in solid cancers
- 2023
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Ingår i: EBioMedicine. - : Elsevier. - 2352-3964. ; 88
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Tidskriftsartikel (refereegranskat)abstract
- Background: Cancer immunity is based on the interaction of a multitude of cells in the spatial context of the tumour tissue. Clinically relevant immune signatures are therefore anticipated to fundamentally improve the accuracy in predicting disease progression.Methods: Through a multiplex in situ analysis we evaluated 15 immune cell classes in 1481 tumour samples. Single-cell and bulk RNAseq data sets were used for functional analysis and validation of prognostic and predictive associations.Findings: By combining the prognostic information of anti-tumoural CD8+ lymphocytes and tumour supportive CD68+CD163+ macrophages in colorectal cancer we generated a signature of immune activation (SIA). The prognostic impact of SIA was independent of conventional parameters and comparable with the state-of-art immune score. The SIA was also associated with patient survival in oesophageal adenocarcinoma, bladder cancer, lung adenocarcinoma and melanoma, but not in endometrial, ovarian and squamous cell lung carcinoma. We identified CD68+CD163+ macrophages as the major producers of complement C1q, which could serve as a surrogate marker of this macrophage subset. Consequently, the RNA-based version of SIA (ratio of CD8A to C1QA) was predictive for survival in independent RNAseq data sets from these six cancer types. Finally, the CD8A/C1QA mRNA ratio was also predictive for the response to checkpoint inhibitor therapy.Interpretation: Our findings extend current concepts to procure prognostic information from the tumour immune microenvironment and provide an immune activation signature with high clinical potential in common human cancer types.
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| 2. |
- Mezheyeuski, Artur, et al.
(författare)
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The ratio of CD8+ lymphocytes to CD68+CD163+ macrophages is prognostic in immunogenic tumors and predicts immunotherapy response
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Immune cells in the microenvironment shape tumor development and progression. Through in situ analyses we assessed 15 immune cell classes in 352 colorectal cancers and identified a simpleprognostic signature based on the ratio of anti-tumoral CD8+ lymphocytes to tumor-supportiveCD68+CD163+ macrophages in the tumor microenvironment. The prognostic ability of this signature was superior to the state-of-art immune score and was also demonstrated in four other tumor types. Single-cell analyses identified these CD68+CD163+ macrophages as the source of complement C1q, and the ratio of CD8A to C1QA gene expression levels in bulk RNA predicted survival in five tumor types. In single cell analyses, RNA-based versions of the signature also predicted response to checkpoint inhibitor therapy. This supports broad clinical applicability of immune scores considering CD68+CD163+ macrophages as prognostic and predictive biomarkers in common cancers.
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| 3. |
- Agebratt, Christian, et al.
(författare)
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A Randomized Study of the Effects of Additional Fruit and Nuts Consumption on Hepatic Fat Content, Cardiovascular Risk Factors and Basal Metabolic Rate
- 2016
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 11:1, s. e0147149-
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundFruit has since long been advocated as a healthy source of many nutrients, however, the high content of sugars in fruit might be a concern.ObjectivesTo study effects of an increased fruit intake compared with similar amount of extra calories from nuts in humans.MethodsThirty healthy non-obese participants were randomized to either supplement the diet with fruits or nuts, each at +7 kcal/kg bodyweight/day for two months. Major endpoints were change of hepatic fat content (HFC, by magnetic resonance imaging, MRI), basal metabolic rate (BMR, with indirect calorimetry) and cardiovascular risk markers.ResultsWeight gain was numerically similar in both groups although only statistically significant in the group randomized to nuts (fruit: from 22.15±1.61 kg/m2 to 22.30±1.7 kg/m2, p = 0.24 nuts: from 22.54±2.26 kg/m2 to 22.73±2.28 kg/m2, p = 0.045). On the other hand BMR increased in the nut group only (p = 0.028). Only the nut group reported a net increase of calories (from 2519±721 kcal/day to 2763±595 kcal/day, p = 0.035) according to 3-day food registrations. Despite an almost three-fold reported increased fructose-intake in the fruit group (from 9.1±6.0 gram/day to 25.6±9.6 gram/day, p<0.0001, nuts: from 12.4±5.7 gram/day to 6.5±5.3 gram/day, p = 0.007) there was no change of HFC. The numerical increase in fasting insulin was statistical significant only in the fruit group (from 7.73±3.1 pmol/l to 8.81±2.9 pmol/l, p = 0.018, nuts: from 7.29±2.9 pmol/l to 8.62±3.0 pmol/l, p = 0.14). Levels of vitamin C increased in both groups while α-tocopherol/cholesterol-ratio increased only in the fruit group.ConclusionsAlthough BMR increased in the nut-group only this was not linked with differences in weight gain between groups which potentially could be explained by the lack of reported net caloric increase in the fruit group. In healthy non-obese individuals an increased fruit intake seems safe from cardiovascular risk perspective, including measurement of HFC by MRI.
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| 4. |
- Arnqvist, Hans, et al.
(författare)
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Vitamin D status in longstanding type 1 diabetes and controls. Association with upper extremity impairments
- 2023
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Ingår i: Upsala Journal of Medical Sciences. - : UPSALA MED SOC. - 0300-9734 .- 2000-1967. ; 128:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Patients with type 1 diabetes have a high prevalence of upper extremity impairments (UEIs), such as frozen shoulder, carpal tunnel syndrome, and trigger finger. The UEIs are strongly associated with activity limitations and impaired quality of life. The etiology of the UEI is not clear. Vitamin D deficiency has been considered to play a role in the pathogenesis of type 1 diabetes and in the development of macro- and microvascular complications in diabetes. Aim: To characterize vitamin D status in a large population of patients with type 1 diabetes, if vitamin D deficiency is associated with metabolic factors and possible association with UEI. Material and methods: Patients who diagnosed before 35 years of age, whose diabetes duration >20 years, and who are not older than 65 years were invited to participate in this cross-sectional case-control, multicenter study. Controls matched for age and sex were obtained from the national population registry. Fasting blood samples were collected and stored at -80 degrees C until analyzed regarding 25-hydroxy-vitamin D (25(OH)D3) by a liquid chromatographic-mass spectrometric method (LC-MS/MS). Results: Vitamin D levels varied with season as expected in the northern hemisphere. The association between 25(OH)D3 and clinical variables was analyzed in a univariate general linear model, which indicated no difference in 25(OH)D3 in men with and without diabetes but higher values in women with diabetes. About 30% of both patients and controls had vitamin D deficiency (=50 nmol/L). Analyzed by binary logistic regression UEIs was not associated with 25(OH)D3 levels. In both patients and controls, 25(OH)D3 was correlated to apolipoprotein A1 (r = 0.153; 0.220, P < 0.001). Conclusion: In patients with type 1 diabetes and a duration of 20 years or more, vitamin D level is not lower than in nondiabetic controls and is not associated with UEIs.
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| 5. |
- Chung, Rosanna W S, et al.
(författare)
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Lutein exerts anti-inflammatory effects in patients with coronary artery disease.
- 2017
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Ingår i: Atherosclerosis. - : Elsevier. - 0021-9150 .- 1879-1484. ; 262, s. 87-93
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND AIMS: Many coronary artery disease (CAD) patients exhibit chronic low-grade inflammation. Carotenoids are anti-oxidants with potential anti-inflammatory properties. Here, we first assessed relationships between interleukin (IL)-6 and individual carotenoids in plasma from CAD patients. Based on the results, we proceeded to assess anti-inflammatory effects of one carotenoid, lutein, in peripheral blood mononuclear cells (PBMCs) from CAD patients.METHODS: Lutein + zeaxanthin (isomers with lutein being dominant), β-cryptoxanthin, lycopene, α- and β-carotene and IL-6 were measured in plasma from 134 patients with stable angina (SA) and 59 patients with acute coronary syndrome. In 42 patients, plasma measurements were also performed 3 months after coronary intervention. PBMCs from SA patients were pre-treated with lutein (1, 5 and 25 μM) for 24 h followed by 24 h incubation ± lipopolysaccharide (LPS). Cell pellets were collected for IL-6, IL-1β and TNF mRNA and intracellular lutein. Cytokine secretion was measured in cell media.RESULTS: Only lutein + zeaxanthin were inversely correlated with IL-6 in SA patients at baseline (r = -0.366, p < 0.001) and follow-up (r = -0.546, p < 0.001). Ex vivo, lutein was taken up by PBMCs from SA patients in a dose- and time-dependent manner. Pre-treatment with lutein dose-dependently lowered LPS-induced secretion of IL-6, IL-1β (p < 0.01) and TNF (p < 0.05), and also reduced IL-6, IL-1β and TNF mRNA expression (p < 0.05).CONCLUSIONS: Clinical findings highlighted the inverse association between lutein and IL-6 in CAD patients. Anti-inflammatory effects of lutein in PBMCs from CAD patients were consolidated in ex vivo experiments. Taken together, these results show that lutein has the potential to play a role in resolution of chronic inflammation in CAD patients.
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| 6. |
- Eriksson, Ida, et al.
(författare)
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Imidacloprid Induces Lysosomal Dysfunction and Cell Death in Human Astrocytes and Fibroblasts-Environmental Implication of a Clinical Case Report
- 2023
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Ingår i: Cells. - : MDPI. - 2073-4409. ; 12:24
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Tidskriftsartikel (refereegranskat)abstract
- Imidacloprid (IMI), a neonicotinoid insecticide, has potential cytotoxic and genotoxic effects on human and experimental models, respectively. While being an emerging environmental contaminant, occupational exposure and related cellular mechanisms are unknown. Herein, we were motivated by a specific patient case where occupational exposure to an IMI-containing plant protection product was associated with the diagnosis of Bell's palsy. The aim was to investigate the toxic effects and cellular mechanisms of IMI exposure on glial cells (D384 human astrocytes) and on human fibroblasts (AG01518). IMI-treated astrocytes showed a reduction in cell number and dose-dependent cytotoxicity at 24 h. Lower doses of IMI induced reactive oxygen species (ROS) and lysosomal membrane permeabilisation (LMP), causing apoptosis and autophagic dysfunction, while high doses caused significant necrotic cell death. Using normal fibroblasts, we found that IMI-induced autophagic dysfunction and lysosomal damage, activated lysophagy, and resulted in a compensatory increase in lysosomes. In conclusion, the observed IMI-induced effects on human glial cells and fibroblasts provide a possible link between IMI cytotoxicity and neurological complications observed clinically in the patient exposed to this neonicotinoid insecticide.
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| 7. |
- Ghafouri, Bijar, et al.
(författare)
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Interstitial concentration of serotonin is increased in myalgic human trapezius muscle during rest, repetitive work and mental stress - an in vivo microdialysis study
- 2010
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Ingår i: Scandinavian Journal of Clinical and Laboratory Investigation. - : Taylor and Francis. - 0036-5513 .- 1502-7686. ; 70:7, s. 478-486
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: The pathophysiology of trapezius myalgia is not fully elucidated. Serotonin (5-HT) is involved in modulation of nociception and hyperalgesia. Our aim was to compare the interstitial 5-HT levels of the trapezius muscle in women with chronic trapezius myalgia and in pain-free controls. MATERIALS AND METHODS: Microdialysate of the trapezius muscle collected every 20 minutes during rest, work (100 min) and stress (20 min) was used to study the dynamics of 5-HT in women with chronic trapezius myalgia (MYA; n=18) and in pain-free controls (CON; n=30). RESULTS: MYA had higher levels of 5-HT than CON at baseline, during repetitive work, during mental stress and during recovery. There were no significant time effects on 5-HT levels. CONCLUSION: 5-HT has the potential of a biomarker of chronic myalgia. Elevated levels of 5-HT may be involved in maintenance of habitual chronic pain and might contribute to increased pain during exercise by facilitating the effect of released algesic substances linked to such muscle demands.
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| 8. |
- Karlsson, Helen, et al.
(författare)
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Lipoproteomics I : Mapping of proteins in low-density lipoprotein using two-dimensional gel electrophoresis and mass spectrometry
- 2005
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Ingår i: Proteomics. - : Wiley. - 1615-9853 .- 1615-9861. ; 5:2, s. 551-565
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Tidskriftsartikel (refereegranskat)abstract
- The molecular mechanisms underlying the relationship between low-density lipoprotein (LDL) and the risk of atherosclerosis are not clear. Therefore, detailed information about the protein composition of LDL may contribute to reveal its role in atherogenesis and the mechanisms that lead to coronary disease in humans. Here, we sought to map the proteins in human LDL by a proteomic approach. LDL was isolated by two-step discontinuous density-gradient ultracentrifugation and the proteins were separated with two-dimensional gel electrophoresis and identified with peptide mass fingerprinting, using matrix assisted laser desorption/ionization-time of flight-mass spectrometry and with amino acid sequencing using electrospray ionization tandem mass spectrometry. These procedures identified apo B-100, apo C-II, apo C-III (three isoforms), apo E (four isoforms), apo A-I (two isoforms), apo A-IV, apo J and apo M (three isoforms not previously described). In addition, three proteins that have not previously been identified in LDL were found: serum amyloid A-IV (two isoforms), calgranulin A, and lysozyme C. The identities of apo M, calgranulin A, and lysozyme C were confirmed by sequence information obtained after collision-induced dissociation fragmentation of peptides characteristic for these proteins. Moreover, the presence of lysozyme C was further corroborated by demonstrating enriched hydrolytic activity in LDL against Micrococcus lysodeikticus. These results indicate that in addition to the dominating apo B-100, LDL contains a number of other apolipoproteins, many of which occur in different isoforms. The demonstration, for the first time, that LDL contains calgranulin A and lysozyme C raises the possibility that LDL proteins may play hitherto unknown role(s) in immune and inflammatory reactions of the arterial wall.
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| 9. |
- Karlsson, Helen, et al.
(författare)
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Lipoproteomics II : Mapping of proteins in high-density lipoprotein using two-dimensional gel electrophoresis and mass spectrometry
- 2005
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Ingår i: Proteomics. - : Wiley. - 1615-9853 .- 1615-9861. ; 5:5, s. 1431-1445
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Tidskriftsartikel (refereegranskat)abstract
- High-density lipoprotein (HDL) is the most abundant lipoprotein particle in the plasma and a negative risk factor of atherosclerosis. By using a proteomic approach it is possible to obtain detailed information about its protein content and protein modifications that may give new information about the physiological roles of HDL. In this study the two subfractions; HDL2 and HDL3, were isolated by two-step discontinuous density-gradient ultracentrifugation and the proteins were separated with two-dimensional gel electrophoresis and identified with peptide mass fingerprinting, using matrix-assisted laser desorption/ionisation time of flight mass spectrometry. Identified proteins in HDL were: the dominating apo A-I as six isoforms, four of them with a glycosylation pattern and one of them with retained propeptide, apolipoprotein (apo) A-II, apo A-IV, apo C-I, apo C-II, apo C-III (two isoforms), apo E (five isoforms), the recently discovered apo M (two isoforms), serum amyloid A (two isoforms) and serum amyloid A-IV (six isoforms). Furthermore, alpha-1-antitrypsin was identified in HDL for the first time. Additionally, salivary alpha-amylase was identified as two isoforms in HDL2, and apo L and a glycosylated apo A-II were identified in HDL3. Besides confirming the presence of different apolipoproteins, this study indicates new patterns of glycosylated apo A-I and apo A-II. Furthermore, the study reveals new proteins in HDL; alpha-1-antitrypsin and salivary alpha-amylase. Further investigations about these proteins may give new insight into the functional role of HDL in coronary artery diseases.
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| 10. |
- Kentson, Magnus, et al.
(författare)
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The influence of disease severity and lifestyle factors on the peak annual 25(OH)D value of COPD patients
- 2018
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Ingår i: The International Journal of Chronic Obstructive Pulmonary Disease. - : DOVE MEDICAL PRESS LTD. - 1176-9106 .- 1178-2005. ; 13, s. 1389-1398
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Tidskriftsartikel (refereegranskat)abstract
- Background: The prevalence of individuals deficient in vitamin D (defined as a serum level of the stable metabolite 25(OH)D amp;lt; 50 nmol/L) is increasing in countries with low annual ultraviolet (UV) radiation and among individuals unable to perform outdoor activities, for example, COPD patients. Objective: To assess the role of vitamin D deficiency, independently of seasonal variation, the peak annual value of 25(OH)D was measured in subjects with advanced COPD +/- long-term oxygen therapy (LTOT) and lung healthy control subjects. A method to grade the individual annual UV light exposure was designed and tested. Subjects and methods: Sixty-six Caucasians with advanced COPD (28 with LTOT) and 47 control subjects were included, and the levels of 25(OH)D were determined in late summer/ early fall when the annual peak was assumed. Questionnaires about COPD symptoms, general health, lifestyle, dietary habits and QoL were used to collect data. Lung function tests and blood sampling were performed. Results: The peak annual 25(OH)D of COPD subjects was significantly lower than in the control subjects, but there was no significant difference between COPD patients with and without LTOT. Ongoing vitamin D supplementation was the single most important intervention to maintain 25(OH)D levels amp;gt;= 50 nmol/L. Among vitamin D-deficient COPD subjects, 25(OH)D correlated positively with forced expiratory volume in 1 second as % predicted, Modified British Medical Research Council score, blood oxygenation, food portion size, Mediterranean Diet Score and Ultraviolet Score. Conclusion: Vitamin D deficiency was common among healthy individuals and COPD subjects. Peak annual 25(OH)D levels of COPD subjects correlated with clinically important outcomes. The present study emphasizes the need to routinely monitor vitamin D status among patients with advanced COPD and to consider to medicate those with vitamin D deficiency with vitamin D supplementation.
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| 11. |
- Leandersson, Per
(författare)
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Isocyanates and hydrogen cyanide in fumes from heated proteins and protein-rich foods
- 2019
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Ingår i: Indoor Air. - : WILEY. - 0905-6947 .- 1600-0668. ; 29:2, s. 291-298
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Tidskriftsartikel (refereegranskat)abstract
- Toxic compounds in cooking fumes could cause respiratory problems. In the present study, the formation of isocyanic acid (ICA), methyl isocyanate (MIC), and hydrogen cyanide (HCN) was studied during the heating of proteins or frying of protein-rich foods. Heating was performed in an experimental setup using a tube oven set at 200-500 degrees C and in a kitchen when foods with different protein content were fried at a temperature around 300 degrees C. ICA, MIC, and HCN were all generated when protein or meat was heated. Individual amino acids were also heated, and there was a significant positive correlation between their respective nitrogen content and the formation of the measured compounds. Gas from heated protein or meat also caused carbamylation in albumin. ICA, MIC, and HCN were also present in fumes generated when meat, egg, and halloumi were fried in a kitchen pan. The levels of ICA were here twice that of the Swedish occupational exposure limit. If ICA, MIC, and HCN in fumes from heated protein-rich foods could contribute to the risk of airway dysfunction among those exposed is not clear, but it is important to avoid inhaling frying and grilling fumes and to equip kitchens with good exhaust ventilation.
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| 12. |
- Leandersson, Per, 1958-
(författare)
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Mineral fibers, cigarette smoke, and oxidative DNA damage : An experimental study
- 1992
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This study concerns the ability of mineral fibers and cigarette smoke to generate reactive oxygen metabolites and to cause damage to DNA. The generation of hydroxyl radicals (OH") was demonstrated by using the DNA base, deoxyguanosine (dG) as a trapping agent for OH" and determining its hydroxylation to 8-hydroxydeoxyguanosine (80HdG), and oxidative DNA damage was assessed as formation of 80HdG in isolated DNA or in DNA of human lung cells in culture. Both asbestos (chrysotile) and manmade mineral fibers (~)were found to generate OH" and damage DNA in aqueous buffer solutions, andmore OH· was generated by the iron-containing rock and slag wools than by glass wool and ceramic fibers. The OH• generation by rock wool was decreased by treatment with heat, oxygen or desferrioxamine, indicating that chemical characteristics including iron on the fiber surface were important determinants of the OH" formation. A variety of natural mineral fibers (asbestos, erionite, and wollastonite) and MMMF (rock wool, glass wool, and ceramic fibers) were found to stimulate polymorphonuclear leukocytes (PMNL) togenerate OH" in the presence of exogenously added iron, and amosite, crocidolite, antophyllite, erionite, and wollastonite caused OH" formation also in the absence of exogenously added iron. Cigarette smoke potentiated the damaging action of rock wool onisolated DNA, suggesting that iron-containing fibers might catalyze O:H" formation from hydrogen peroxide generated in the smoke. Cigarette smoke-induced damage to isolated DNA was inhibited by tyrosinase and catalase, indicating that polyphenols in the smoke,e.g. hydroquinone and catechol, were important for the hydrogen peroxide generation. Cigarette smoke was also found to cause oxidative DNA damage and DNA strand break formation in cultured human lung cells by mechanisms involving OH" attack on the DNAmolecule and endonuclease activation. Moreover, cigarette tar was demonstrated to promote P:MNL-mediated DNA strand-break formation in human lung cells, and tar loaded with iron was more damaging than regular tar.These fmdings indicate that mineral fibers, by producing OH· themselves and by stimulating PMNL to generate OH· in the presence of iron, may cause oxidative DNA damage under experimental conditions. They also indicate that cigarette smoke may cause DNA base hydroxylation and DNA strand-break formation in human lung cells via mechanisms involving OH", and that iron is important for the OH•-formation. Altogether, the findings point to the possibility that mineral fibers may promote OH" generation by cigarette smoke and inflammatory cells and so increase the risk of DNA damage in human lung cells.
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| 13. |
- Lindroos, Anna-Karin, 1958, et al.
(författare)
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Use of a Web-Based Dietary Assessment Tool (RiksmatenFlex) in Swedish Adolescents: Comparison and Validation Study
- 2019
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Ingår i: Journal of Medical Internet Research. - : JMIR Publications Inc.. - 1438-8871. ; 21:10
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Tidskriftsartikel (refereegranskat)abstract
- Background: A Web-based dietary assessment tool-RiksmatenFlex-was developed for the national dietary survey of adolescents in Sweden. Objective: This study aimed to describe the Web based method RiksmatenFlex and to test the validity of the reported dietary intake by comparing dietary intake with 24-hour dietary recalls (recall interviews), estimated energy expenditure, and biomarkers. Methods: Adolescents aged 11-12, 14-15, and 17-18 years were recruited through schools. In total, 78 students had complete dietary information and were included in the study. Diet was reported a few weeks apart with either RiksmatenFlexDiet (the day before and a random later day) or recall interviews (face-to-face, a random day later by phone) in a cross-over, randomized design. At a school visit, weight and height were measured and blood samples were drawn for biomarker analyses. Students wore an accelerometer for 7 days for physical activity measurements. Dietary intake captured by both dietary methods was compared, and energy intake captured by both methods was compared with the accelerometer-estimated energy expenditure (EEest). Intake of whole grain wheat and rye and fruit and vegetables by both methods was compared with alkylresorcinol and carotenoid concentrations in plasma, respectively. Results: The mean of the reported energy intake was 8.92 (SD 2.77) MJ by RiksmatenFlexDiet and 8.04 (SD 2.67) MJ by the recall interviews (P=.01) Intake of fruit and vegetables was 224 (169) g and 227 (150) g, and whole grain wheat and rye intake was 12.4 (SD 13.2) g and 12.0 (SD 13.1) g, respectively; the intakes of fruit and vegetables as well as whole grain wheat and iye did not differ between methods. Intraclass correlation coefficients ranged from 0.57 for protein and carbohydrates to 0.23 for vegetables. Energy intake by RiksmatenFlexDiet was overreported by 8% (P=.03) but not by the recall interviews (P=.53) compared with EEest. The Spearman correlation coefficient between reported energy intake and EEest was 0.34 (P=.008) for RiksmatenFlexDiet and 0.16 (P=.21) for the recall interviews. Spearman correlation coefficient between whole grain wheat and rye and plasma total alkylresorcinol homologs was 0.36 (P=.002) for RiksmatenFlexDiet and 0.29 (P=.02) for the recall interviews. Spearman correlations between intake of fruit and vegetables and plasma carotenoids were weak for both dietary tools. The strongest correlations were observed between fruit and vegetable intake and lutein/zeaxanthin for RiksmatenFlexDiet (0.46; P<.001) and for recall interviews (0.28; P=.02). Conclusions: RiksmatenFlexDiet provides information on energy, fruit, vegetables, and whole grain wheat and rye intake, which is comparable with intake obtained from recall interviews in Swedish adolescents. The results are promising for cost-effective dietary data collection in upcoming national dietary surveys and other studies in Sweden. Future research should focus on how, and if, new technological solutions could reduce dietary reporting biases.
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| 14. |
- Ludvigsson, Johnny, 1943-, et al.
(författare)
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Combined vitamin D, ibuprofen and glutamic acid decarboxylase-alum treatment in recent onset Type I diabetes: lessons from the DIABGAD randomized pilot trial.
- 2020
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Ingår i: Future science OA. - London, United Kingdom : Future Science Ltd. - 2056-5623. ; 6:7
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Tidskriftsartikel (refereegranskat)abstract
- Double-blind placebo-controlled intervention using glutamic acid decarboxylase (GAD)-alum, vitamin D and Ibuprofen in recent onset Type I diabetes (T1D).64 patients (T1D since <4months, age 10-17.99, fasting sC-peptide ≥0.12nmol/l, GADA-positive) were randomized intoDay(D) 1-90 400mg/day Ibuprofen, D1-450 vitamin D 2000IU/day, D15, 45 sc. 20μg GAD-alum; as A but placebo instead of Ibuprofen; as B but 40μg GAD-alum D15, 45; placebo.Treatment was safe and tolerable. No C-peptide preservation was observed. We observed a linear correlation of baseline C-peptide, HbA1c and insulin/per kilogram/24h with change in C-peptide AUC at 15months (r=-0.776, p<0.0001).Ibuprofen, vitamin D + GAD-alum did not preserve C-peptide. Treatment efficacy was influenced by baseline clinical and immunological factors and vitamin D concentration. Clinical Trial Registration: NCT01785108 (ClinicalTrials.gov).
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| 15. |
- Mehmeti, Meliha, et al.
(författare)
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Wnt5a is a TLR2/4-ligand that induces tolerance in human myeloid cells
- 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
- Innate immune responses are rapid, dynamic and highly regulated to avoid overt reactions. This regulation is executed by innate immune tolerance mechanisms that remain obscure. Wnt5a is a signalling protein mainly involved in developmental processes and cancer. The effect of Wnt5a on inflammatory myeloid cells is controversial. Here, we combine primary cell cultures, in vitro binding studies, mass spectrometry and Drosophila protein modelling to show that Wnt5a is a direct ligand of toll-like receptor (TLR) 2 and 4. The binding promotes a MyD88-non-canonical nuclear factor of kappa B (NFκB) and AP-1 signalling cascade, with contradictory profiles in mouse (pro-inflammatory) and human (anti-inflammatory) myeloid immune cells. These data reveal that the true nature of Wnt5a in inflammatory cells, is to regulate TLR signals, and in human myeloid cells it acts as an endogenous, tolerance-associated molecular pattern (TAMP), inducing IL-10 and innate immune tolerance.
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| 16. |
- Mezheyeuski, Artur, et al.
(författare)
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The Immune Landscape of Colorectal Cancer
- 2021
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Ingår i: Cancers. - : MDPI. - 2072-6694. ; 13:21
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Tidskriftsartikel (refereegranskat)abstract
- We sought to provide a detailed overview of the immune landscape of colorectal cancer in the largest study to date in terms of patient numbers and analyzed immune cell types. We applied a multiplex in situ staining method in combination with an advanced scanning and image analysis pipeline akin to flow cytometry, and analyzed 5968 individual multi-layer images of tissue defining in a total of 39,078,450 cells. We considered the location of immune cells with respect to the stroma, and tumor cell compartment and tumor regions in the central part or the invasive margin. To the best of our knowledge, this study is the first comprehensive spatial description of the immune landscape in colorectal cancer using a large population-based cohort and a multiplex immune cell identification.While the clinical importance of CD8+ and CD3+ cells in colorectal cancer (CRC) is well established, the impact of other immune cell subsets is less well described. We sought to provide a detailed overview of the immune landscape of CRC in the largest study to date in terms of patient numbers and in situ analyzed immune cell types. Tissue microarrays from 536 patients were stained using multiplexed immunofluorescence panels, and fifteen immune cell subclasses, representing adaptive and innate immunity, were analyzed. Overall, therapy-naive CRC patients clustered into an 'inflamed' and a 'desert' group. Most T cell subsets and M2 macrophages were enriched in the right colon (p-values 0.046-0.004), while pDC cells were in the rectum (p = 0.008). Elderly patients had higher infiltration of M2 macrophages (p = 0.024). CD8+ cells were linked to improved survival in colon cancer stages I-III (q = 0.014), while CD4+ cells had the strongest impact on overall survival in metastatic CRC (q = 0.031). Finally, we demonstrated repopulation of the immune infiltrate in rectal tumors post radiation, following an initial radiation-induced depletion. This study provides a detailed analysis of the in situ immune landscape of CRC paving the way for better diagnostics and providing hints to better target the immune microenvironment.
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| 17. |
- Nosratabadi, Ali Reza, 1964-
(författare)
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Novel Methods for Sampling, Characterization and Analysis of Airborne Street Particles in a Health Perspective
- 2022
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Over the last decades, there has been much attention on air quality, especially in urban environments. A significant factor effecting the air quality in the urban environment is airborne particulate matter (PM). Long-term exposure to PM causes increased risk for heart disease, decreased lung function, exacerbation of asthma, and lung cancer. Therefore, many countries have implemented exposure limits to the concentration of ambient PM in the urban environments. The toxicity of PM is dependent on several factors such as chemical composition, shape, adsorbed materials, and particle sizes (usually divided in ultrafine, fine and coarse particles). However, the relationship between different PM properties and developing health hazards are not clear. Therefore, further studies to investigate different properties of PM may contribute to understanding the influence of PM on human health. In the present work, different novel methods to investigate sampled airborne PM and to investigate potential health effects have been used to increase the knowledge regarding street and wear particles. In study I, a sampling plan involving collecting one filter from Tapered Element Oscillating Microbalance (TEOM) monitoring stations used for Environmental monitoring each month for 20 months were developed. Particles on the filters were extracted into a suspension. TEOM particles were then studied with respect to constituents and variables that reflect their toxicity. The constituent and toxicity was found to be spatial and seasonal dependent. As a follow-up, in study II, TEOM filters from three geographical different cities were collected once a month for a year. The variation in particle mass measured with TEOM monitor, cadmium and lead contents, as well as endotoxin levels between locations and time points over the year was studied. The correlation between studied variables and biological effect was investigated. The results show that the concentration of metals and endotoxin in TEOM particles have no relationship to particle mass, while endotoxin levels coincided with pro-inflammatory response. These studies show that results from analyzing different variables on obtained particles from TEOM filters in combination with information about the ambient particle concentration, could be helpful in the evaluation of differences in the risk of breathing air at various locations. The dominant road traffic particle sources are wear particles from the road and tyre interface, and from vehicle brake pads. The particle concentrations are highest in cities with high traffic amounts and a high frequency of braking. There are a few cell studies that have investigated the toxicological and biological effect of these wear particles, but there is a lack of knowledge regarding their effect on tissue level. Furthermore, the knowledge about importance of rock materials in pavement is deficient. To mitigate these knowledge gaps, the effect of different wear particles from pavement and brake pad were tested using a model with isolated perfused rat lungs in study III. The wear particles from the pavement showed a significant decrease of tidal volume compared to unexposed controls. The largest effect were found with quartzite stone material. Wear particles from brakes instead showed a larger effect on released proinflammatory cytokines. The study shows that the toxic effect on lungs exposed to airborne particles can be investigated using repetitive measurements of tidal volume. Furthermore, the study shows that the choice of rock material in road pavements has the potential to affect the toxicity of road wear particles. This should be considered in environments where the concentrations and exposures are high. The brake particles showed a different effect than stone particles, indicating the need to differentiate wear particles from different sources in relation to health effects. In summary, the present work have investigated different aspects of airborne particles collected from streets as well as generated wear particles. These indicate different important aspects of the particles that may be of importance to better understand their health effects.
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- Sjögren, Elaine, 1955-, et al.
(författare)
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Psycholsocial factors and biological mechanisms in stress
- 2004
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Ingår i: The 26th World Congress of the International Federation of Biomedical Laboratory Science IFBLS,2004. - Stockholm : ABCD Swedish Association of health professionals. ; , s. 74-
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Konferensbidrag (refereegranskat)
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