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CAF-like state in primary skin fibroblasts with constitutional BRCA1 epimutation sheds new light on tumor suppressor deficiency-related changes in he…
2016
Constitutive epimutations of tumor suppressor genes are increasingly considered as cancer predisposing factors equally to sequence mutations. In light of the emerging role of the microenvironment for cancer predisposition, initiation, and progression, we aimed to characterize the consequences of a BRCA1 epimutation in cells of mesenchymal origin. We performed a comprehensive molecular and cellular comparison of primary dermal fibroblasts taken from a monozygous twin pair discordant for recurrent cancers and BRCA1 epimutation, whose exceptional clinical case we previously reported in this journal. Comparative transcriptome analysis identified differential expression of extracellular matrix-r…
Common missense variant in the glucokinase regulatory protein gene is associated with increased plasma triglyceride and C-reactive protein but lower …
2008
OBJECTIVE—Using the genome-wide association approach, we recently identified the glucokinase regulatory protein gene (GCKR, rs780094) region as a novel quantitative trait locus for plasma triglyceride concentration in Europeans. Here, we sought to study the association of GCKR variants with metabolic phenotypes, including measures of glucose homeostasis, to evaluate the GCKR locus in samples of non-European ancestry and to fine- map across the associated genomic interval. RESEARCH DESIGN AND METHODS—We performed association studies in 12 independent cohorts comprising >45,000 individuals representing several ancestral groups (whites from Northern and Southern Europe, whites from the …
Physical Activity, Fitness, Glucose Homeostasis, and Brain Morphology in Twins
2014
The main aim of the present study (FITFATTWIN) was to investigate how physical activity level is associated with body composition, glucose homeostasis, and brain morphology in young adult male monozygotic twin pairs discordant for physical activity.From a population-based twin cohort, we systematically selected 10 young adult male monozygotic twin pairs (age range, 32-36 yr) discordant for leisure time physical activity during the past 3 yr. On the basis of interviews, we calculated a mean sum index for leisure time and commuting activity during the past 3 yr (3-yr LTMET index expressed as MET-hours per day). We conducted extensive measurements on body composition (including fat percentage …
The effect of growth hormone ( GH ) replacement on blood glucose homeostasis in adult nondiabetic patients with GH deficiency: real‐life data from th…
2015
SummaryObjective To assess the effect of 4 years’ growth hormone (GH) replacement on glucose homeostasis and evaluate factors affecting glycosylated haemoglobin (HbA1c) in adults with growth hormone deficiency (GHD). Design NordiNet® International Outcome Study, a noninterventional study, monitors long-term effectiveness and safety of GH replacement [Norditropin® (somatropin), Novo Nordisk A/S] in real-life clinical practice. Patients Nondiabetic patients (n = 245) with adult-onset GHD (age ≥20 years at GH start), ≥4 years’ GH replacement and HbA1c values at baseline and 4 years were included in the analysis. Measurements Changes from baseline (∆) to 4 years in HbA1c, fasting plasma glucose…
The transcription factor ZEB1 (deltaEF1) promotes tumour cell dedifferentiation by repressing master regulators of epithelial polarity.
2007
Epithelial to mesenchymal transition (EMT) is implicated in the progression of primary tumours towards metastasis and is likely caused by a pathological activation of transcription factors regulating EMT in embryonic development. To analyse EMT-causing pathways in tumouri-genesis, we identified transcriptional targets of the E-cadherin repressor ZEB1 in invasive human cancer cells. We show that ZEB1 repressed multiple key determinants of epithelial differentiation and cell–cell adhesion, including the cell polarity genes Crumbs3, HUGL2 and Pals1-associated tight junction protein. ZEB1 associated with their endogenous promoters in vivo, and strongly repressed promotor activities in reporter …
Experiences with the use of complementary and alternative medicine in nursing homes: A focus group study.
2016
Abstract Introduction The use of complementary and alternative medicine is increasing outside the Norwegian public health service. The purpose of this study was to gain insight into the experiences of nurses and auxiliary nurses with the use of CAM in care for nursing home residents. Method Focus group interviews with a total of thirteen nurses and auxiliary nurses from three nursing homes were conducted. Data were analyzed using systematic text condensation. Results Participants had experiences from aromatherapy, plant medicine, music therapy and pet therapy. They experienced the use of CAM as effective, exciting and rewarding, but also challenging and dependent on supportive leaders. CAM …
Knockdown of NANOG Reduces Cell Proliferation and Induces G0/G1 Cell Cycle Arrest in Human Adipose Stem Cells
2019
The core components of regenerative medicine are stem cells with high self-renewal and tissue regeneration potentials. Adult stem cells can be obtained from many organs and tissues. NANOG, SOX2 and OCT4 represent the core regulatory network that suppresses differentiation-associated genes, maintaining the pluripotency of mesenchymal stem cells. The roles of NANOG in maintaining self-renewal and undifferentiated status of adult stem cells are still not perfectly established. In this study we define the effects of downregulation of NANOG in maintaining self-renewal and undifferentiated state in mesenchymal stem cells (MSCs) derived from subcutaneous adipose tissue (hASCs). hASCs were expanded…
Extracellular Vesicles from Healthy Cells Improves Cell Function and Stemness in Premature Senescent Stem Cells by miR-302b and HIF-1α Activation.
2020
Aging is accompanied by the accumulation of senescent cells that alter intercellular communication, thereby impairing tissue homeostasis and reducing organ regenerative potential. Recently, the administration of mesenchymal stem cells (MSC)-derived extracellular vesicles has proven to be more effective and less challenging than current stem cell-based therapies. Extracellular vesicles (EVs) contain a cell-specific cargo of proteins, lipids and nucleic acids that are released and taken up by probably all cell types, thereby inducing functional changes via the horizontal transfer of their cargo. Here, we describe the beneficial properties of extracellular vesicles derived from non-senescent M…
B and T cell immune responses elicited by the Comirnaty® COVID-19 vaccine in nursing home residents
2021
Objectives The immunogenicity of the Comirnaty® COVID-19 vaccine is understudied in elderly people with comorbidities. SARS-CoV-2-S-targeted antibody and T cell responses following full vaccination were assessed in nursing home residents. Methods Sixty nursing home residents (44 female; age, 53-100 years), of whom 10 had previously been diagnosed of COVID-19, and 18 healthy controls (15 female; age, 27-54 years) were recruited. Pre- and post-vaccination blood specimens were available for quantitation of total antibodies binding SARS-CoV-2 S protein and enumeration of SARS-CoV-2-S-reactive IFN-γ CD4+ and CD8+ T cells by flow cytometry. Results The seroconversion rate in presumably SARS-CoV-2…
Erratum to: Donor age and long-term culture do not negatively influence the stem potential of limbal fibroblast-like stem cells
2016
In regenerative medicine the maintenance of stem cell properties is of crucial importance. Ageing is considered a cause of reduced stemness capability. The limbus is a stem niche of easy access and harbors two stem cell populations: epithelial stem cells and fibroblast-like stem cells. Our aim was to investigate whether donor age and/or long-term culture have any influence on stem cell marker expression and the profiles in the fibroblast-like stem cell population.Fibroblast-like stem cells were isolated and digested from 25 limbus samples of normal human corneo-scleral rings and long-term cultures were obtained. SSEA4 expression and sphere-forming capability were evaluated; cytofluorimetric…