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Ulkomaisen yhteisön käyttämien suullisten sopimusten verorikosoikeudelliset riskit rakennustoimeksiannossa Suomessa
No full textEarly in vivo target genes in human immune cells highlight vitamin D’s role in antioxidant defense
No full textIntroduction: Vitamin D plays a vital role in modulating innate and adaptive immunity. This study investigated the gene regulatory mechanisms underlying this modulation in vivo.
Methods: We conducted a proof-of-principle intervention in which a participant received a bolus of vitamin D3 (80,000 IU) monthly for three months. Peripheral blood mononuclear cells (PBMCs) were collected immediately before and at 4, 24, and 48 hours post-supplementation for transcriptome-wide differential gene expression analysis.
Results: We identified 570 genes significantly responsive to vitamin D3 (p < 0.05) at one or more timepoints. In vitro experiments using PBMCs of the 0-hour time point of the same individual validated 303 of these as targets of the vitamin D receptor ligand 1α,25-dihydroxyvitamin D3. Among these, 55 primary target genes exhibited significant changes as early as 4 hours post-supplementation, including genes like SELENOS (selenoprotein S), which plays a key role in the selenium micronutrient network. Moreover, genes such as PRDX1 (peroxiredoxin 1), TXNRD1 (thioredoxin reductase 1), and SOD2 (superoxide dismutase 2), involved in antioxidant defense, were prominently regulated.
Discussion: These findings highlight a potential early and primary role for vitamin D in regulating detoxification processes, suggesting its critical involvement in maintaining redox homeostasis in immune cells of healthy individuals
From urban policy concept to practice in the periphery: smart shrinkage in peripheral Finland
No full textRegional development policies are often designed for urban cores, disregarding their applicability in peripheral areas. Copying such policies to less-favoured contexts is ineffective. Thus, policymakers in peripheral areas struggle to adapt urban policy concepts to fit the characteristics of their regions. This chapter investigates one such policy concept, “smart shrinkage” originally designed to cope with urban depopulation. The concept was adopted into the Finnish regional development lexicon by the central government. It has resonated with policymakers struggling with depopulation and has subsequently been adapted to the strategies of some peripheral areas. This chapter investigates these strategies to determine how the policy concept of smart shrinkage has been understood and translated into practice in three geographical levels: national, regional and local. The results reveal that while the smart shrinkage concept does have potential utility in the planning of depopulating peripheral areas, the concrete tools to implement it are missing
Prognostic Value of Relative Enhancement Metrics Based on Pre-CCRT MRI Volumetric Segmentation in Glioblastoma
No full textAIM
The purpose of this study was to identify the impact of relative contrast enhancement (rCE), based on volumetric segmentation from preconcurrent chemoradiotherapy magnetic resonance imaging (pre-CCRT MRI), in predicting tumour progression and unfavourable survival in glioblastoma (GBM) patients.
MATERIALS AND METHODS
Seventy-seven GBM patients underwent conventional MRI before and after radiochemotherapy. Residual cavity wall enhancement was segmented using Image J software, and rCE was calculated. Clinical and imaging variables were compared between shorter and longer overall survival (OS) groups. Multivariable logistic regression was performed to identify the significant predictors of survival outcomes. Diagnostic performance was evaluated using receiver operating characteristic curve (ROC) analysis. Survival outcomes based on rCE were compared using Kaplan-Meier analysis.
RESULTS
Older age, nodular and thick linear enhancement, larger orthogonal lesion size on fluid-attenuated inversion recovery (FLAIR) and contrast-enhanced T1-weighted imaging, and higher rCE (≥1.265) were significant predictors of tumour progression. Multivariate analysis showed that higher rCE was an independent predictor of shorter progression-free survival (HR = 4.829). Additionally, older age and higher rCE were independent predictors of shorter OS (HR = 1.048 and 3.792, respectively). A combined model incorporating rCE with clinical and conventional MR variables achieved an area under the ROC curve (AUC) of 0.845 and an accuracy of 79.6% in predicting shorter OS.
CONCLUSION
Pre-CCRT volumetric segmentation-based rCE may improve the prediction of GBM progression and survival, and holds potential as a practical imaging biomarker to guide personalised precision treatme
Vitamin D and lipopolysaccharide jointly induce a distinct epigenetic and transcriptional program in human monocytes
No full textPathogen-associated molecular patterns such as lipopolysaccharide (LPS) mimic immune responses triggered by bacterial infections. The hormonally active form of vitamin D3, 1α,25-dihydroxyvitamin D3 [1,25(OH)2D3], supports innate immunity, but its molecular mechanisms remain incompletely understood. We investigated epigenomic and transcriptomic changes in THP-1 monocytes that were either unprimed or primed for 24 h with 1,25(OH)2D3 or LPS, followed by a second 24-hour stimulation with 1,25(OH)2D3, LPS, or their combination. Epigenome profiling via ATAC-seq revealed that co-stimulation with 1,25(OH)2D3 and LPS induces substantially more chromatin accessibility changes than either treatment alone, with up to 81% of altered regions uniquely responsive to the combination. Motif enrichment analysis highlighted JUN/FOS transcription factors as key regulators of this synergistic response. Transcriptomic analysis via RNA-seq mirrored these findings, though fewer genes than chromatin regions were affected. Notably, under 1,25(OH)2D3-primed conditions, 331 genes exhibited synergistic expression changes upon co-treatment, meaning that their responses significantly deviates from the additive effects of the individual stimulations. This includes 264 genes previously unrecognized as vitamin D targets. Functional annotation revealed that these genes are primarily linked to monocyte and T cell differentiation, in contrast to classical vitamin D targets associated with inflammation. In conclusion, our findings provide mechanistic insight into how vitamin D modulates inflammation through epigenetic and transcriptional reprogramming
