A5051892061- Atherosclerosis and Cardiovascular Diseases
- Immune Response and Inflammation
- Hormonal Regulation and Hypertension
- Monoclonal and Polyclonal Antibodies Research
- Vitamin D Research Studies
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Oral microbiology and periodontitis research
- Pharmacogenetics and Drug Metabolism
- Adipokines, Inflammation, and Metabolic Diseases
- Inflammasome and immune disorders
- Cell Adhesion Molecules Research
- Drug Transport and Resistance Mechanisms
- Electrolyte and hormonal disorders
- Liver Disease Diagnosis and Treatment
- Cholesterol and Lipid Metabolism
- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Burkholderia infections and melioidosis
- Genomics, phytochemicals, and oxidative stress
- Complement system in diseases
- Adrenal Hormones and Disorders
- Protein purification and stability
- Advanced Glycation End Products research
- Macrophage Migration Inhibitory Factor
- Radiopharmaceutical Chemistry and Applications
University of Oulu
2016-2025
Oulu University Hospital
2014-2025
NordLab
2013-2021
Low plasma level of 25-hydroxyvitamin D (25-OH-D), namely vitamin deficiency, is associated with obesity and weight loss improves 25-OH-D status. However, the mechanism behind obesity-induced deficiency remains unclear. Here, we report that suppresses expression cytochrome P450 (CYP) 2R1, main 25-hydroxylase, in both mice humans. In humans, induced by gastric bypass surgery increased CYP2R1 s.c. adipose tissue suggesting recovery after suppression. At same time, CYP27B1, 1α-hydroxylase, was...
Malondialdehyde acetaldehyde (MAA) adducts are generated under oxidative stress and shown to be highly immunogenic. Our aim was investigate the recognition of MAA by human natural antibodies in newborns before or at time full-term pregnancy. Plasma samples pre-term (n = 11) 36) were enriched specific IgM binding compared with maternal plasma levels. Umbilical cord blood lymphocyte phage display library clone Fabs that specifically recognized without cross-reactivity malondialdehyde. Fab...
Objective Increased risk for atherosclerosis is associated with infectious diseases including periodontitis. Natural IgM antibodies recognize pathogen-associated molecular patterns on bacteria, and oxidized lipid protein epitopes low-density lipoprotein (LDL) apoptotic cells. We aimed to identify periodontal pathogen Porphyromonas gingivalis recognized by natural binding malondialdehyde (MDA) modified LDL. Methods Results Mouse monoclonal (MDmAb) specific MDA-LDL P. flow cytometry...
Low 25-hydroxyvitamin D levels correlate with the prevalence of diabetes; however, mechanisms remain uncertain. Here, we show that nutritional deprivation–responsive regulate vitamin metabolism. Both fasting and diabetes suppressed hepatic cytochrome P450 (CYP) 2R1, main 25-hydroxylase responsible for first bioactivation step. Overexpression coactivator peroxisome proliferator–activated receptor γ 1-α (PGC-1α), induced physiologically by pathologically in diabetes, resulted dramatic...
Background and Purpose Many drugs environmental contaminants induce hypercholesterolemia promote the risk of atherosclerotic cardiovascular disease. We tested hypothesis that pregnane X receptor (PXR), a xenobiotic‐sensing nuclear receptor, regulates level circulating atherogenic lipids in humans utilized mouse experiments to identify mechanisms involved. Experimental Approach performed serum NMR metabolomics healthy volunteers administered rifampicin, prototypical human PXR ligand or...
Abstract Environmental exposure to endocrine-disrupting chemicals (EDCs) can lead metabolic disruption, resulting in complications including adiposity, dyslipidemia, hepatic lipid accumulation, and glucose intolerance. Hepatic nuclear receptor activation is one of the mechanisms mediating effects EDCs. Here, we investigated potential use a repeated dose 28-day oral toxicity test for identification EDCs with endpoints. Bisphenol A (BPA), pregnenolone-16α-carbonitrile (PCN), perfluorooctanoic...
LIM and Src homology 3 (SH3) protein 2 (LASP2) is a small focal adhesion first identified as splice variant of the nebulette gene (Nebl). As newest member nebulin family, regulation function LASP2 remain largely unknown. Our previous RNA-sequencing results Nebl one most highly induced genes in mouse liver response to activation pregnane X receptor (PXR). In this study, we investigated phenomenon further show that PXR induces Lasp2 instead Nebl, which partially use same exons. was found be...
In aortic stenosis plasma lipoprotein-derived lipids accumulate in valves. Here, we first compared the lipid compositions of stenotic valves and atherosclerotic plaque cores. Both pathological tissues were found to be enriched cholesteryl linoleate, a marker extracellularly accumulated lipoproteins. addition, large proportion phospholipids contain arachidonic acid, common precursor number proinflammatory mediators. Next, isolated characterized extracellular particles from human non-stenotic...
Both obesity and exposure to chemicals may induce non-alcoholic fatty liver disease (NAFLD). Pregnane X Receptor (PXR) is a central target of metabolism disrupting disturbs hepatic glucose lipid metabolism. We hypothesized that the metabolic consequences PXR activation be modified by existing associated dysfunction.Wildtype knockout male mice were fed high-fat diet dysfunction. was activated with pregnenolone-16α-carbonitrile. Glucose metabolism, hepatosteatosis, insulin signaling, uptake,...
Periodontal infections increase the risk of atherosclerotic vascular disease via partly unresolved mechanisms. Of natural IgM Abs that recognize molecular mimicry on bacterial epitopes and modified lipid protein structures, directed against oxidized low-density lipoprotein (LDL) is associated with atheroprotective properties. Here, effect immune responses to malondialdehyde-modified LDL (MDA-LDL) in conferring protection atherosclerosis, which was accelerated by major periodontopathogen...
Blockade of activin 2 receptor (ACVR2) signaling has been shown to improve insulin sensitivity and aid in weight loss. Inhibition ACVR2 restores cardiac function multiple heart failure models. However, its potential the treatment obesity-related cardiometabolic disease remains unknown. Here, we investigated targeting manifested with metabolic dysfunction-associated steatotic liver (MASLD).
Aims: Post-translational modification of proteins via carbamylation predicts increased risk for coronary artery disease. Uremia and smoke exposure are known to increase carbamylation. The aim was investigate the role carbamylated low-density lipoprotein (LDL) immunization on antibody formation atherogenesis in LDL receptor-deficient (LDLR−/−) mice, study autoantibodies humans with carbamylative load. Results:LDLR−/− mice immunized mouse (msLDL; n=10) without adjuvant showed specific...
Oxidized low-density lipoproteins (oxLDL) are formed as a result of lipid peroxidation and highly immunogenic proatherogenic. In this study, saliva antibodies binding to oxLDL, Porphyromonas gingivalis (Pg) Aggregatibacter actinomycetemcomitans (Aa) were characterized their cross-reactivity was evaluated.Resting stimulated samples collected from 36 healthy adults (mean age 26 years). Saliva IgA, IgG IgM autoantibody levels copper oxidized LDL (CuOx-LDL) malondialdehyde acetaldehyde-modified...
Summary Oxidized low‐density lipoprotein ( O x LDL ) plays a crucial role in the development of atherosclerosis. Carbamylated has been suggested to promote atherogenesis patients with chronic kidney disease. Here we observed that plasma IgG and IgM antibodies carbamylated epitopes were associated oxidation‐specific ρ = 0·65–0·86, P < 0·001) healthy adults, suggesting cross‐reaction between recognizing carbamyl‐epitopes malondialdehyde MDA )/malondialdehyde acetaldehyde MAA ‐adducts. We...
Pregnane X receptor (PXR) regulates glucose and lipid metabolism, but little is known of the nutritional regulation PXR function. We investigated genome wide effects status on mediated gene in liver. Mice were treated with a ligand pregnenolone 16α-carbonitrile (PCN) for 4 days subsequently either fasted 5 hours or after 4-hour fast intragastric 1 hour before sample collection. Gene expression microarray study indicated that PCN both induced repressed much higher number genes fed mice...
Treatment of periodontitis has beneficial effects on systemic inflammation markers that relate to progression atherosclerosis. We aimed investigate whether immunization with A hemagglutinin domain (Rgp44) Porphyromonas gingivalis (Pg), a major etiologic agent periodontitis, would lead an antibody response cross-reacting oxidized low-density lipoprotein (OxLDL) and how it affect the atherosclerosis in receptor-deficient (LDLR-/-) mice. The data revealed prominent IgM but not IgG...
Background Mechanisms mediating hypertensive effects of overweight and obesity have not been fully elucidated. We showed previously that activation pregnane X receptor (PXR) by rifampicin elevates 24‐hour blood pressure (BP) plasma 4β‐hydroxycholesterol (4βHC), agonist for liver (LXR). Methods Results In combined “PXR data set” (n=62) 4 clinical trials, 1 week dosing increased office systolic BP (SBP) 3.1 mm Hg, DBP 1.8 mean arterial 2.2 Hg in comparison with placebo ( P <0.01). Plasma...