| 1. |
- Uusitupa, M., et al.
(författare)
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Effects of an isocaloric healthy Nordic diet on insulin sensitivity, lipid profile and inflammation markers in metabolic syndrome : a randomized study (SYSDIET)
- 2013
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Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 274:1, s. 52-66
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Tidskriftsartikel (refereegranskat)abstract
- Background Different healthy food patterns may modify cardiometabolic risk. We investigated the effects of an isocaloric healthy Nordic diet on insulin sensitivity, lipid profile, blood pressure and inflammatory markers in people with metabolic syndrome. Methods We conducted a randomized dietary study lasting for 18-24weeks in individuals with features of metabolic syndrome (mean age 55years, BMI 31.6kgm-2, 67% women). Altogether 309 individuals were screened, 200 started the intervention after 4-week run-in period, and 96 (proportion of dropouts 7.9%) and 70 individuals (dropouts 27%) completed the study, in the Healthy diet and Control diet groups, respectively. Healthy diet included whole-grain products, berries, fruits and vegetables, rapeseed oil, three fish meals per week and low-fat dairy products. An average Nordic diet served as a Control diet. Compliance was monitored by repeated 4-day food diaries and fatty acid composition of serum phospholipids. Results Body weight remained stable, and no significant changes were observed in insulin sensitivity or blood pressure. Significant changes between the groups were found in non-HDL cholesterol (-0.18, mmolL-1 95% CI -0.35; -0.01, P=0.04), LDL to HDL cholesterol (-0.15, -0.28; -0.00, P=0.046) and apolipoprotein B to apolipoprotein A1 ratios (-0.04, -0.07; -0.00, P=0.025) favouring the Healthy diet. IL-1 Ra increased during the Control diet (difference -84, -133; -37ngL-1, P= 0.00053). Intakes of saturated fats (E%, beta estimate 4.28, 0.02; 8.53, P=0.049) and magnesium (mg, -0.23, -0.41; -0.05, P=0.012) were associated with IL-1 Ra. Conclusions Healthy Nordic diet improved lipid profile and had a beneficial effect on low-grade inflammation.
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| 2. |
- Kirsebom, O. S., et al.
(författare)
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Measurement of the 2+→0+ ground-state transition in the β decay of F 20
- 2019
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Ingår i: Physical Review C. - 2469-9985. ; 100:6
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Tidskriftsartikel (refereegranskat)abstract
- We report the first detection of the second-forbidden, nonunique, 2+→0+, ground-state transition in the β decay of F20. A low-energy, mass-separated F+20 beam produced at the IGISOL facility in Jyväskylä, Finland, was implanted in a thin carbon foil and the β spectrum measured using a magnetic transporter and a plastic-scintillator detector. The β-decay branching ratio inferred from the measurement is bβ=[0.41±0.08(stat)±0.07(sys)]×10-5 corresponding to logft=10.89(11), making this one of the strongest second-forbidden, nonunique β transitions ever measured. The experimental result is supported by shell-model calculations and has significant implications for the final evolution of stars that develop degenerate oxygen-neon cores. Using the new experimental data, we argue that the astrophysical electron-capture rate on Ne20 is now known to within better than 25% at the relevant temperatures and densities.
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| 3. |
- Vilen, ST, et al.
(författare)
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Intracellular co-localization of trypsin-2 and matrix metalloprotease-9: Possible proteolytic cascade of trypsin-2, MMP-9 and enterokinase in carcinoma
- 2008
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Ingår i: Experimental Cell Research. - : Elsevier BV. - 1090-2422 .- 0014-4827. ; 314:4, s. 914-926
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Tidskriftsartikel (refereegranskat)abstract
- Tumor-associated trypsin-2 and matrix metalloprotease-9 (MMP-9) are associated with cancer, particularly with invasive squamous cell carcinomas. They require activation for catalytical competence via proteolytic cascades. One cascade is formed by enterokinase, trypsin-2 and MMP-9; enterokinase activates trypsinogen-2 to trypsin-2, which is an efficient proMMP-9 activator. We describe here that oral squamous cell carcinomas express all members of this cascade: MMP-9, trypsin-2 and enterokinase. The expression of enterokinase in a carcinoma cell line not derived from the duodenum was shown here for the first time. Enterokinase directly cleaved proMMP-9 at the Lys(65)-Ser(66) site, but failed to activate it in vitro. We demonstrated by confocal microscopy that MMP-9 and trypsin-2 co-localized in intracellular vesicles of the carcinoma cells. This co-localization of trypsin-2 and MMP-9 resulted in intracellular proMMP-9 processing that represented fully or partially activated MMP-9. However, although both proteases were present also in various bone tumor tissues, MMP-9 and trypsin-2 never co-localized at the cellular level in these tissues. This suggests that the intracellular vesicular co-localization, storage and possible activation of these proteases may be a unique feature for aggressive epithelial tumors, such as squamous cell carcinomas, but not for tumors of mesenchymal origin.
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| 4. |
- Virtanen, Ismo, et al.
(författare)
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Blood vessels of human islets of Langerhans are surrounded by a double basement membrane
- 2008
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Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 0012-186X .- 1432-0428. ; 51:7, s. 1181-91
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Tidskriftsartikel (refereegranskat)abstract
- AIMS/HYPOTHESIS: Based on mouse study findings, pancreatic islet cells are supposed to lack basement membrane (BM) and interact directly with vascular endothelial BM. Until now, the BM composition of human islets has remained elusive. METHODS: Immunohistochemistry with specific monoclonal and polyclonal antibodies as well as electron microscopy were used to study BM organisation and composition in human adult islets. Isolated islet cells and function-blocking monoclonal antibodies and recombinant soluble Lutheran peptide were further used to study islet cell adhesion to laminin (Lm)-511. Short-term cultures of islets were used to study Lutheran and integrin distribution. RESULTS: Immunohistochemistry revealed a unique organisation for human Lm-511/521 as a peri-islet BM, which co-invaginated into islets with vessels, forming an outer endocrine BM of the intra-islet vascular channels, and was distinct from the vascular BM that additionally contained Lm-411/421. These findings were verified by electron microscopy. Lutheran glycoprotein, a receptor for the Lm alpha5 chain, was found prominently on endocrine cells, as identified by immunohistochemistry and RT-PCR, whereas alpha(3) and beta(1) integrins were more diffusely distributed. High Lutheran content was also found on endocrine cell membranes in short-term culture of human islets. The adhesion of dispersed beta cells to Lm-511 was inhibited equally effectively by antibodies to integrin and alpha(3) and beta(1) subunits, and by soluble Lutheran peptide. CONCLUSIONS/INTERPRETATION: The present results disclose a hitherto unrecognised BM organisation and adhesion mechanisms in human pancreatic islets as distinct from mouse islets.
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| 5. |
- Bowen, C. D., et al.
(författare)
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Comparison of Herpes Simplex Virus 1 Strains Circulating in Finland Demonstrates the Uncoupling of Whole-Genome Relatedness and Phenotypic Outcomes of Viral Infection
- 2019
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Ingår i: Journal of Virology. - : American Society for Microbiology. - 0022-538X .- 1098-5514. ; 93:8
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Tidskriftsartikel (refereegranskat)abstract
- A majority of adults in Finland are seropositive carriers of herpes simplex viruses (HSV). Infection occurs at epithelial or mucosal surfaces, after which virions enter innervating nerve endings, eventually establishing lifelong infection in neurons of the sensory or autonomic nervous system. Recent data have highlighted the genetic diversity of HSV-1 strains and demonstrated apparent geographic patterns in strain similarity. Though multiple HSV-1 genomes have been sequenced from Europe to date, there is a lack of sequenced genomes from the Nordic countries. Finland's history includes at least two major waves of human migration, suggesting the potential for diverse viruses to persist in the population. Here, we used HSV-1 clinical isolates from Finland to test the relationship between viral phylogeny, genetic variation, and phenotypic characteristics. We found that Finnish HSV-1 isolates separated into two distinct phylogenetic groups, potentially reflecting historical waves of human (and viral) migration into Finland. Each HSV-1 isolate harbored a distinct set of phenotypes in cell culture, including differences in the amount of virus production, extracellular virus release, and cell-type-specific fitness. Importantly, the phylogenetic clusters were not predictive of any detectable pattern in phenotypic differences, demonstrating that whole-genome relatedness is not a proxy for overall viral phenotype. Instead, we highlight specific gene-level differences that may contribute to observed phenotypic differences, and we note that strains from different phylogenetic groups can contain the same genetic variations. IMPORTANCE Herpes simplex viruses (HSV) infect a majority of adults. Recent data have highlighted the genetic diversity of HSV-1 strains and demonstrated apparent genomic relatedness between strains from the same geographic regions. We used HSV-1 clinical isolates from Finland to test the relationship between viral genomic and geographic relationships, differences in specific genes, and characteristics of viral infection. We found that viral isolates from Finland separated into two distinct groups of genomic and geographic relatedness, potentially reflecting historical patterns of human and viral migration into Finland. These Finnish HSV-1 isolates had distinct infection characteristics in multiple cell types tested, which were specific to each isolate and did not group according to genomic and geographic relatedness. This demonstrates that HSV-1 strain differences in specific characteristics of infection are set by a combination of host cell type and specific viral gene-level differences.
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| 6. |
- Bulanova, Daria, et al.
(författare)
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Antiviral Properties of Chemical Inhibitors of Cellular Anti-Apoptotic Bcl-2 Proteins
- 2017
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Ingår i: Viruses. - : MDPI AG. - 1999-4915. ; 9:10
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Tidskriftsartikel (refereegranskat)abstract
- Viral diseases remain serious threats to public health because of the shortage of effective means of control. To combat the surge of viral diseases, new treatments are urgently needed. Here we show that small-molecules, which inhibit cellular anti-apoptotic Bcl-2 proteins (Bcl-2i), induced the premature death of cells infected with different RNA or DNA viruses, whereas, at the same concentrations, no toxicity was observed in mock-infected cells. Moreover, these compounds limited viral replication and spread. Surprisingly, Bcl-2i also induced the premature apoptosis of cells transfected with viral RNA or plasmid DNA but not of mock-transfected cells. These results suggest that Bcl-2i sensitizes cells containing foreign RNA or DNA to apoptosis. A comparison of the toxicity, antiviral activity, and side effects of six Bcl-2i allowed us to select A-1155463 as an antiviral lead candidate. Thus, our results pave the way for the further development of Bcl-2i for the prevention and treatment of viral diseases.
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| 7. |
- Hukkanen, J., et al.
(författare)
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The effect of atorvastatin treatment on serum oxysterol concentrations and cytochrome P450 3A4 activity
- 2015
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Ingår i: British Journal of Clinical Pharmacology. - : Blackwell Publishing. - 0306-5251 .- 1365-2125. ; 80:3, s. 473-479
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Tidskriftsartikel (refereegranskat)abstract
- Aims: Atorvastatin is known to both inhibit and induce the cytochrome P450 3A4 (CYP3A4) enzyme in vitro. Some clinical studies indicate that atorvastatin inhibits CYP3A4 but there are no well-controlled longer term studies that could evaluate the inducing effect of atorvastatin. We aimed to determine if atorvastatin induces or inhibits CYP3A4 activity as measured by the 4β-hydroxycholesterol to cholesterol ratio (4βHC : C).Methods: In this randomized, double-blind, placebo-controlled 6 month study we evaluated the effects of atorvastatin 20mg day1 (n=15) and placebo (n = 14) on oxysterol concentrations and determined if atorvastatin induces or inhibits CYP3A4 activity as assessed by the 4βHC : C index. The respective 25-hydroxycholesterol and 5α,6α- epoxycholesterol ratios were used as negative controls.Results: Treatment with atorvastatin decreased 4βHC and 5α,6α-epoxycholesterol concentrations by 40% and 23%, respectively. The mean 4βHC : C ratio decreased by 13% (0.214 ± 0.04 to 0.182 ± 0.04, P = 0.024, 95% confidence interval (CI) of the difference –0.0595, –0.00483) in the atorvastatin group while no significant change occurred in the placebo group. The difference in change of 4βHC : C between study arms was statistically significant (atorvastatin –0.032, placebo 0.0055, P = 0.020, 95% CI of the difference – 0.069, –0.0067). The ratios of 25-hydroxycholesterol and 5α,6α- epoxycholesterol to cholesterol did not change.Conclusions: The results establish atorvastatin as an inhibitor of CYP3A4 activity.Furthermore, 4βHC : C is a useful index of CYP3A4 activity, including theconditions with altered cholesterol concentrations.
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| 8. |
- Kirsebom, O. S., et al.
(författare)
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Discovery of an Exceptionally Strong β -Decay Transition of F 20 and Implications for the Fate of Intermediate-Mass Stars
- 2019
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Ingår i: Physical Review Letters. - 0031-9007. ; 123:26
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Tidskriftsartikel (refereegranskat)abstract
- A significant fraction of stars between 7 and 11 solar masses are thought to become supernovae, but the explosion mechanism is unclear. The answer depends critically on the rate of electron capture on Ne20 in the degenerate oxygen-neon stellar core. However, because of the unknown strength of the transition between the ground states of Ne20 and F20, it has not previously been possible to fully constrain the rate. By measuring the transition, we establish that its strength is exceptionally large and that it enhances the capture rate by several orders of magnitude. This has a decisive impact on the evolution of the core, increasing the likelihood that the star is (partially) disrupted by a thermonuclear explosion rather than collapsing to form a neutron star. Importantly, our measurement resolves the last remaining nuclear physics uncertainty in the final evolution of degenerate oxygen-neon stellar cores, allowing future studies to address the critical role of convection, which at present is poorly understood
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| 9. |
- Kolehmainen, Marjukka, et al.
(författare)
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Healthy Nordic diet downregulates the expression of genes involved in inflammation in subcutaneous adipose tissue in individuals with features of the metabolic syndrome.
- 2015
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Ingår i: American Journal of Clinical Nutrition. - : Elsevier BV. - 0002-9165 .- 1938-3207. ; 101:1, s. 228-239
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Previously, a healthy Nordic diet (ND) has been shown to have beneficial health effects close to those of Mediterranean diets.OBJECTIVE: The objective was to explore whether the ND has an impact on gene expression in abdominal subcutaneous adipose tissue (SAT) and whether changes in gene expression are associated with clinical and biochemical effects.DESIGN: Obese adults with features of the metabolic syndrome underwent an 18- to 24-wk randomized intervention study comparing the ND with the control diet (CD) (the SYSDIET study, carried out within Nordic Centre of Excellence of the Systems Biology in Controlled Dietary Interventions and Cohort Studies). The present study included participants from 3 Nordic SYSDIET centers [Kuopio (n = 20), Lund (n = 18), and Oulu (n = 18)] with a maximum weight change of ±4 kg, highly sensitive C-reactive protein concentration <10 mg/L at the beginning and the end of the intervention, and baseline body mass index (in kg/m(2)) <38. SAT biopsy specimens were obtained before and after the intervention and subjected to global transcriptome analysis with Gene 1.1 ST Arrays (Affymetrix).RESULTS: Altogether, 128 genes were differentially expressed in SAT between the ND and CD (nominal P < 0.01; false discovery rate, 25%). These genes were overrepresented in pathways related to immune response (adjusted P = 0.0076), resulting mainly from slightly decreased expression in the ND and increased expression in the CD. Immune-related pathways included leukocyte trafficking and macrophage recruitment (e.g., interferon regulatory factor 1, CD97), adaptive immune response (interleukin32, interleukin 6 receptor), and reactive oxygen species (neutrophil cytosolic factor 1). Interestingly, the regulatory region of the 128 genes was overrepresented for binding sites for the nuclear transcription factor κB.CONCLUSION: A healthy Nordic diet reduces inflammatory gene expression in SAT compared with a control diet independently of body weight change in individuals with features of the metabolic syndrome. The study was registered at clinicaltrials.gov as NCT00992641.
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| 10. |
- Leder, Lena, et al.
(författare)
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Effects of a healthy Nordic diet on gene expression changes in peripheral blood mononuclear cells in response to an oral glucose tolerance test in subjects with metabolic syndrome : A SYSDIET sub-study
- 2016
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Ingår i: Genes & Nutrition. - : Springer Science and Business Media LLC. - 1555-8932 .- 1865-3499. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Diet has a great impact on the risk of developing features of metabolic syndrome (MetS), type 2 diabetes mellitus (T2DM), and cardiovascular diseases (CVD). We evaluated whether a long-term healthy Nordic diet (ND) can modify the expression of inflammation and lipid metabolism-related genes in peripheral blood mononuclear cells (PBMCs) during a 2-h oral glucose tolerance test (OGTT) in individuals with MetS. Methods: A Nordic multicenter randomized dietary study included subjects (n = 213) with MetS, randomized to a ND group or a control diet (CD) group applying an isocaloric study protocol. In this sub-study, we included subjects (n = 89) from three Nordic centers: Kuopio (n =26), Lund (n = 30), and Oulu (n = 33) with a maximum weight change of ±4 kg, high-sensitivity C-reactive protein concentration ≤10 mg L-1, and baseline body mass index -2. PBMCs were isolated, and the mRNA gene expression analysis was measured by quantitative real-time polymerase chain reaction (qPCR). We analyzed the mRNA expression changes of 44 genes before and after a 2hOGTT at the beginning and the end of the intervention. Results: The healthy ND significantly down-regulated the expression of toll-like receptor 4 (TLR4), interleukin 18 (IL18), and thrombospondin receptor (CD36) mRNA transcripts and significantly up-regulated the expression of peroxisome proliferator-activated receptor delta (PPARD) mRNA transcript after the 2hOGTT compared to the CD. Conclusions: A healthy ND is able to modify the gene expression in PBMCs after a 2hOGTT. However, more studies are needed to clarify the biological and clinical relevance of these findings.
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| 11. |
- Myhrstad, Mari C. W., et al.
(författare)
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Healthy Nordic Diet Modulates the Expression of Genes Related to Mitochondrial Function and Immune Response in Peripheral Blood Mononuclear Cells from Subjects with Metabolic Syndrome-A SYSDIET Sub-Study
- 2019
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Ingår i: Molecular Nutrition & Food Research. - : John Wiley & Sons. - 1613-4125 .- 1613-4133. ; 63:13
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Tidskriftsartikel (refereegranskat)abstract
- Scope To explore the effect of a healthy Nordic diet on the global transcriptome profile in peripheral blood mononuclear cells (PBMCs) of subjects with metabolic syndrome. Methods and results Subjects with metabolic syndrome undergo a 18/24 week randomized intervention study comparing an isocaloric healthy Nordic diet with an average habitual Nordic diet served as control (SYSDIET study). Altogether, 68 participants are included. PBMCs are obtained before and after intervention and total RNA is subjected to global transcriptome analysis. 1302 probe sets are differentially expressed between the diet groups (p-value < 0.05). Twenty-five of these are significantly regulated (FDR q-value < 0.25) and are mainly involved in mitochondrial function, cell growth, and cell adhesion. The list of 1302 regulated probe sets is subjected to functional analyses. Pathways and processes involved in the mitochondrial electron transport chain, immune response, and cell cycle are downregulated in the healthy Nordic diet group. In addition, gene transcripts with common motifs for 42 transcription factors, including NFR1, NFR2, and NF-kappa B, are downregulated in the healthy Nordic diet group. Conclusion These results suggest that benefits of a healthy diet may be mediated by improved mitochondrial function and reduced inflammation.
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| 12. |
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| 13. |
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| 14. |
- Ulven, Stine M., et al.
(författare)
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An isocaloric nordic diet modulates rela and tnfrsf1a gene expression in peripheral blood mononuclear cells in individuals with metabolic syndrome—a sysdiet sub-study
- 2019
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Ingår i: Nutrients. - : MDPI AG. - 2072-6643. ; 11:12
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Tidskriftsartikel (refereegranskat)abstract
- A healthy dietary pattern is associated with a lower risk of metabolic syndrome (MetS) and reduced inflammation. To explore this at the molecular level, we investigated the effect of a Nordic diet (ND) on changes in the gene expression profiles of inflammatory and lipid-related genes in peripheral blood mononuclear cells (PBMCs) of individuals with MetS. We hypothesized that the intake of an ND compared to a control diet (CD) would alter the expression of inflammatory genes and genes involved in lipid metabolism. The individuals with MetS underwent an 18/24-week randomized intervention to compare a ND with a CD. Eighty-eight participants (66% women) were included in this sub-study of the larger SYSDIET study. Fasting PBMCs were collected before and after the intervention and changes in gene expression levels were measured using TaqMan Array Micro Fluidic Cards. Forty-eight pre-determined inflammatory and lipid related gene transcripts were analyzed. The expression level of the gene tumor necrosis factor (TNF) receptor superfamily member 1A (TNFRSF1A) was down-regulated (p = 0.004), whereas the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) subunit, RELA proto-oncogene, was up-regulated (p = 0.016) in the ND group compared to the CD group. In conclusion, intake of an ND in individuals with the MetS may affect immune function.
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