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Sökning: FÖRF:(Per Jansson)

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1.
  • Fryk, Emanuel, et al. (författare)
  • Galectin-1 correlates with inflammatory markers and T regulatory cells in children with type 1 diabetes and/or celiac disease
  • 2024
  • Ingår i: Clinical and Experimental Immunology. - : Oxford University Press. - 1365-2249 .- 0009-9104. ; 215:3, s. 240-250
  • Tidskriftsartikel (refereegranskat)abstract
    • Type 1 diabetes (T1D) and celiac disease (CeD) are common autoimmune diseases in children where the pathophysiology is not fully characterized. The autoimmune process involves a complex scenario of both inflammatory and regulatory features. Galectin-1 (GAL-1) has a wide range of biological activities e.g. interaction with immune cells. We examined the relationship between GAL-1 and soluble immune markers and T-cell subsets in a cohort of children with T1D and/or CeD relative to healthy children. GAL-1, together with several soluble immune markers [e.g. interleukins (IL)], tumor necrosis factor (TNF), acute phase proteins, and matrix metalloproteinases (MMP) were measured in sera from children with T1D and/or CeD by fluorochrome (Luminex) technique using children without these diseases as a reference. Subgroups of T cells, including T-regulatory (Treg) cells, were analysed by flow cytometry. Association between GAL-1, pro-inflammatory markers, and Treg cells differed depending on which illness combination was present. In children with both T1D and CeD, GAL-1 correlated positively with pro-inflammatory markers (IL-1 beta, IL-6, and TNF-alpha). Composite scores increased the strength of correlation between GAL-1 and pro-inflammatory markers, Th1-associated interferon (IFN)-gamma, and T1D-associated visfatin. Contrary, in children diagnosed with exclusively T1D, GAL-1 was positively correlated to CD25hi and CD25hiCD101+ Treg cells. For children with only CeD, no association between GAL-1 and other immune markers was observed. In conclusion, the association observed between GAL-1, soluble immune markers, and Treg cells may indicate a role for GAL-1 in the pathophysiology of T1D and, to some extent, also in CeD. Type 1 diabetes (T1D) and celiac disease (CeD) are common autoimmune diseases in children where pathophysiology is not fully characterized. The autoimmune process involves a complex scenario of both inflammatory and regulatory features. Galectin-1 (GAL-1) has a wide range of biological activities e.g. interaction with immune cells and the association observed between GAL-1, soluble immune markers, and T regulatory (Treg) cells may indicate a role for GAL-1 in the pathophysiology of children with T1D and, to some extent, also in children with CeD. Graphical Abstract
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2.
  • Fryk, Emanuel, et al. (författare)
  • Feasibility of high-dose tadalafil and effects on insulin resistance in well-controlled patients with type 2 diabetes (MAKROTAD): a single-centre, double-blind, randomised, placebo-controlled, cross-over phase 2 trial
  • 2023
  • Ingår i: Eclinicalmedicine. ; 59
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Phosphodiesterase-5 inhibitors exert positive vascular and metabolic effects in type 2 diabetes (T2D), but the effect on insulin resistance in T2D is unclear. Methods This randomised, double blind, placebo-controlled, two-period crossover trial was conducted at Sahlgrenska University Hospital (Gothenburg, Sweden). Men without apparent erectile dysfunction (age 40-70 years) and women (age 55-70 years, post-menopause) diagnosed with T2D between 3 months and 10 years, haemoglobin A1c (HbA1c) < 60 mmol/mol and a body mass index (BMI) 27-40 kg/m2 were enrolled. Participants were randomly assigned to one period of oral tadalafil 20 mg once a day and one period of placebo for 6 weeks, separated by an 8-week wash-out period. Placebo and tadalafil tablets were made visually indistinguishable and delivered randomized in two separate boxes for each participant. Both treatment periods ended with a glucose clamp, and measurements of body composition and metabolic markers in blood, subcutaneous and muscular interstitial fluid. The primary aim was to assess difference in whole-body insulin resistance after 6-weeks of treatment, determined after completion of the two study arms, and secondary aims were to study effects of tadalafil on pathophysiology of T2D as well as tolerability of high-dose tadalafil in T2D. Primary analysis was performed in participants with full analysis set (FAS) and safety analysis in all participants who received at least one dose of study medication. This trial is registered with ClinicalTrials.gov (NCT02601989), and EudraCT (2015-000573). Findings Between January 22nd, 2016, and January 31st, 2019, 23 participants with T2D were enrolled, of whom 18 were included in the full analysis set. The effect of tadalafil on insulin resistance was neutral compared with placebo. However, tadalafil decreased glycaemia measured as HbA1c (mean difference -2.50 mmol/mol, 95% confidence interval (CI), -4.20; -0.78, p = 0.005), and, further, we observed amelioration of endothelial function and markers of liver steatosis and glycolysis, whereas no statistically significant differences of other clinical phenotyping were shown. Muscle pain, dyspepsia, and headache were more frequent in participants on high-dose tadalafil compared with placebo (p < 0.05) but no difference between treatments appeared for serious adverse events. Interpretation High-dose tadalafil does not decrease whole-body insulin resistance, but increases microcirculation, induces positive effects in the liver and in intermediate metabolites, in parallel with an improved metabolic control measured as HbA1c. High-dose tadalafil is moderately well tolerated, warranting larger trials to define the optimal treatment regimen in T2D.
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3.
  • Hägg, Daniel, 1974, et al. (författare)
  • Osteoblast-lineage cells regulate metabolism and fat mass
  • 2023
  • Ingår i: Current Opinion in Endocrine and Metabolic Research. - 2451-9650. ; 31
  • Forskningsöversikt (refereegranskat)abstract
    • As energy depots in many circumstances have been limited during evolution, it is necessary to prioritize how to manage energy resources. In this review we summarize data from the last 15 years indicating that osteoblast-lineage cells are regulators of whole-body energy metabolism and fat mass. We focus mainly on three factors, osteocalcin, lipocalin-2 and sclerostin, that are released by osteoblast-lineage cells and proposed to exert endocrine effects on metabolism. In addition, we present a hypothesis on why osteoblast-lineage cells during evolution have developed a function to regulate metabolism and fat mass. We propose that osteoblast-lineage cells through the osteocyte network in bone are sensors of gravitational forces induced by body mass and gravity on land-living species. By sensing the body weight, the osteoblastlineage cells may then feed-back this information on the whole-body nutritional status via osteoblast-derived endocrine factors or via the nervous system to regulate energy metabolism and fat mass.
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4.
  • Jansson, John-Olov, 1954, et al. (författare)
  • The dual hypothesis of homeostatic body weight regulation, including gravity-dependent and leptin-dependent actions.
  • 2023
  • Ingår i: Philosophical transactions of the Royal Society of London. Series B, Biological sciences. - 1471-2970. ; 378:1888
  • Forskningsöversikt (refereegranskat)abstract
    • Body weight is tightly regulated when outside the normal range. It has been proposed that there are individual-specific lower and upper intervention points for when the homeostatic regulation of body weight is initiated. The nature of the homeostatic mechanisms regulating body weight at the lower and upper ends of the body weight spectrum might differ. Previous studies demonstrate that leptin is the main regulator of body weight at the lower end of the body weight spectrum. We have proposed that land-living animals use gravity to regulate their body weight. We named this homeostatic system the gravitostat and proposed that there are two components of the gravitostat. First, an obvious mechanism involves increased energy consumption in relation to body weight when working against gravity on land. In addition, we propose that there exists a component, involving sensing of the body weight by osteocytes in the weight-bearing bones, resulting in a feedback regulation of energy metabolism and body weight. The gravity-dependent homeostatic regulation is mainly active in obese mice. We, herein, propose the dual hypothesis of body weight regulation, including gravity-dependent actions (= gravitostat) at the upper end and leptin-dependent actions at the lower end of the body weight spectrum. This article is part of a discussion meeting issue 'Causes of obesity: theories, conjectures and evidence (Part II)'.
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5.
  • Li, Ziyu, et al. (författare)
  • Enhancing Rheocasting Process Control with AI-based Systems
  • 2023
  • Konferensbidrag (refereegranskat)abstract
    • Semisolid casting has emerged as an attractivealternative to conventional casting methods due to its potentialto yield superior mechanical properties, reduce environmentalpollution, and decrease production costs. However, optimizingprocess parameters and controlling the casting process remainschallenging. Process control largely relies on human expertise,associated with significant time and cost expenditures. Inresponse, this study presents a third-circle research project toinvestigate the correlation between the casting process and thesolidification process. The study proposes leveraging AI technologyto digitize the entire process control, thereby increasing thereliability and stability of cast products’ quality. The researchwill focus on understanding the key factors influencing thecasting process and developing an AI-based decision supportsystem to aid in process parameter selection and optimization.The outcomes of this study are expected to contribute to thedevelopment of more reliable and efficient semisolid castingprocesses.
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6.
  • Wallach, Daniel, et al. (författare)
  • Proposal and extensive test of a calibration protocol for crop phenology models
  • 2023
  • Ingår i: Agronomy for Sustainable Development. - : Springer Nature. - 1774-0746 .- 1773-0155. ; 43:4
  • Tidskriftsartikel (refereegranskat)abstract
    • A major effect of environment on crops is through crop phenology, and therefore, the capacity to predict phenology for new environments is important. Mechanistic crop models are a major tool for such predictions, but calibration of crop phenology models is difficult and there is no consensus on the best approach. We propose an original, detailed approach for calibration of such models, which we refer to as a calibration protocol. The protocol covers all the steps in the calibration workflow, namely choice of default parameter values, choice of objective function, choice of parameters to estimate from the data, calculation of optimal parameter values, and diagnostics. The major innovation is in the choice of which parameters to estimate from the data, which combines expert knowledge and data-based model selection. First, almost additive parameters are identified and estimated. This should make bias (average difference between observed and simulated values) nearly zero. These are "obligatory" parameters, that will definitely be estimated. Then candidate parameters are identified, which are parameters likely to explain the remaining discrepancies between simulated and observed values. A candidate is only added to the list of parameters to estimate if it leads to a reduction in BIC (Bayesian Information Criterion), which is a model selection criterion. A second original aspect of the protocol is the specification of documentation for each stage of the protocol. The protocol was applied by 19 modeling teams to three data sets for wheat phenology. All teams first calibrated their model using their "usual" calibration approach, so it was possible to compare usual and protocol calibration. Evaluation of prediction error was based on data from sites and years not represented in the training data. Compared to usual calibration, calibration following the new protocol reduced the variability between modeling teams by 22% and reduced prediction error by 11%.
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7.
  • Drake, Isabel, et al. (författare)
  • The role of circulating galectin-1 in type 2 diabetes and chronic kidney disease: evidence from cross-sectional, longitudinal and Mendelian randomisation analyses
  • 2022
  • Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 0012-186X .- 1432-0428. ; 65, s. 128-139
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims/hypothesis Galectin-1 modulates inflammation and angiogenesis, and cross-sectional studies indicate that galectin-1 may be a uniting factor between obesity, type 2 diabetes and kidney function. We examined whether circulating galectin-1 can predict incidence of chronic kidney disease (CKD) and type 2 diabetes in a middle-aged population, and if Mendelian randomisation (MR) can provide evidence for causal direction of effects. Methods Participants (n = 4022; 58.6% women) in the Malmo Diet and Cancer Study-Cardiovascular Cohort enrolled between 1991 and 1994 (mean age 57.6 years) were examined. eGFR was calculated at baseline and after a mean follow-up of 16.6 +/- 1.5 years. Diabetes status was ascertained through registry linkage (mean follow-up of 18.4 +/- 6.1 years). The associations of baseline galectin-1 with incident CKD and type 2 diabetes were assessed with Cox regression, adjusting for established risk factors. In addition, a genome-wide association study on galectin-1 was performed to identify genetic instruments for two-sample MR analyses utilising the genetic associations obtained from the Chronic Kidney Disease Genetics (CKDGen) Consortium (41,395 cases and 439,303 controls) and the DIAbetes Genetics Replication And Meta-analysis (DIAGRAM) consortium (74,124 cases and 824,006 controls). One genome-wide significant locus in the galectin-1 gene region was identified (sentinel SNP rs7285699; p = 2.4 x 10(-11)). The association between galectin-1 and eGFR was also examined in individuals with newly diagnosed diabetes from the All New Diabetics In Scania (ANDIS) cohort. Results Galectin-1 was strongly associated with lower eGFR at baseline (p = 2.3 x 10(-89)) but not with incident CKD. However, galectin-1 was associated with increased risk of type 2 diabetes (per SD increase, HR 1.12; 95% CI 1.02, 1.24). Two-sample MR analyses could not ascertain a causal effect of galectin-1 on CKD (OR 0.92; 95% CI 0.82, 1.02) or type 2 diabetes (OR 1.05; 95% CI 0.98, 1.14) in a general population. However, in individuals with type 2 diabetes from ANDIS who belonged to the severe insulin-resistant diabetes subgroup and were at high risk of diabetic nephropathy, genetically elevated galectin-1 was significantly associated with higher eGFR (p = 5.7 x 10(-3)). Conclusions/interpretation Galectin-1 is strongly associated with lower kidney function in cross-sectional analyses, and two-sample MR analyses suggest a causal protective effect on kidney function among individuals with type 2 diabetes at high risk of diabetic nephropathy. Future studies are needed to explore the mechanisms by which galectin-1 affects kidney function and whether it could be a useful target among individuals with type 2 diabetes for renal improvement.
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8.
  • Fryk, Emanuel, et al. (författare)
  • Galectin-1 in Obesity and Type 2 Diabetes
  • 2022
  • Ingår i: Metabolites. - : MDPI AG. - 2218-1989. ; 12:10
  • Tidskriftsartikel (refereegranskat)abstract
    • Galectin-1 is a carbohydrate-binding protein expressed in many tissues. In recent years, increasing evidence has emerged for the role of galectin-1 in obesity, insulin resistance and type 2 diabetes. Galectin-1 has been highly conserved through evolution and is involved in key cellular functions such as tissue maturation and homeostasis. It has been shown that galectin-1 increases in obesity, both in the circulation and in the adipose tissue of human and animal models. Several proteomic studies have independently identified an increased galectin-1 expression in the adipose tissue in obesity and in insulin resistance. Large population-based cohorts have demonstrated associations for circulating galectin-1 and markers of insulin resistance and incident type 2 diabetes. Furthermore, galectin-1 is associated with key metabolic pathways including glucose and lipid metabolism, as well as insulin signalling and inflammation. Intervention studies in animal models alter animal weight and metabolic profile. Several studies have also linked galectin-1 to the progression of complications in diabetes, including kidney disease and retinopathy. Here, we review the current knowledge on the clinical potential of galectin-1 in obesity and type 2 diabetes.
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9.
  • Jarfors, Anders E.W. 1963-, et al. (författare)
  • In-Production Rheometry of Semi-Solid Metal Slurries
  • 2022
  • Ingår i: Metals. - : MDPI. - 2075-4701. ; 12:7
  • Tidskriftsartikel (refereegranskat)abstract
    • Semi-solid aluminium alloy processing (SSM) has advanced into a more mature process with many applications. The current paper aims to investigate the in-process behaviour of a production slurry using an engineering approach to estimate the properties. A method to assess the rheological properties of a semi-solid metal slurry was tested and found capable of producing meaningful measurements. The foundations of this were to use a Rushton turbine setup for the assessment through a model to optimize the factors included in the slurry rheology. In the analysis of the static and dynamic part of the viscosity, it was concluded that the slurry turns increasingly into a solid with increasing solid fractions where the static shear strength dominates the rheology more and more compared to the dynamic components. The static yield strength was also found significantly more dominant with increasing solid fraction, suggesting that the industrial-scale analysis using models based on Ostwald-de Waale and Carreau modelling is far from sufficient for a process, such as the RheoMetal process, with a very rapid slurry generation.
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10.
  • Jarfors, Anders E.W. 1963-, et al. (författare)
  • Selecting Cast Alloy Alloying Elements Suitable for a Circular Society
  • 2022
  • Ingår i: Sustainability. - : MDPI. - 2071-1050. ; 14:11
  • Tidskriftsartikel (refereegranskat)abstract
    • Resource efficiency, energy usage, and carbon footprint drive the need to use aluminium alloys to manufacture lightweight components. The current paper targets the effects of alloy composition on the heat associated with remelting from a material circularity perspective. Si as an alloying element increases the required heat in the recycling cycle. Limiting the Si content in cast materials can reduce the energy needed in the recycling process by 20%, leading to significant gains in energy usage and CO2 emissions from gas heated furnaces and fossil fuel-generated electricity.
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