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Immunoglobulin subclass profiles of anti-idiotypic antibodies to GAD65Ab differ between type 1 diabetes patients and healthy individuals.

Previously we reported the presence of anti-idiotypic antibodies (anti-Id) specific to autoantibodies against GAD65 (GAD65Ab) in healthy individuals while the activity of anti-Id directed to GAD65Ab in T1D patients was significantly lower. These anti-Id recognize the antigen binding site of GAD65Ab, thus preventing their binding to GAD65. Here we characterized the IgG subclass profile of these ant

Relations between coping strategies and health-related quality of life in patients with spinal cord lesion

Objective: Although the use of appropriate coping strategies has been suggested to be a key factor in determining successful adjustment to severe physical illness/disability, little systematic support for this link has been found. We investigated relationships between spinal cord lesion-related coping strategies and health-related quality of life when studying for sociodemographic, disability-rela

Epigenome-wide cross-tissue correlation of human bone and blood DNA methylation–can blood be used as a surrogate for bone?

Difficulty in obtaining bone tissue is an obstacle to studying epigenetics to understand gene–environment interactions, and their role in disease pathogenesis. Blood is an obvious alternative and in this proof of principle study, our aim was to systematically investigate whether blood is a viable surrogate for bone. We measured epigenome-wide DNA methylation at 850 K CpG sites in matched trabecula

Diagnostic potential of miR-483 family for IGF-II producing non-islet cell tumor hypoglycemia

Objective: In insulin-like growth factor II (IGF-II) producing non-islet cell tumor hypoglycemia (NICTH), high molecular weight forms of IGF-II (big IGF-II) are produced as a cause of spontaneous hypoglycemia. MicroRNA (miRNA)-483 family, encoded in an intron lesion of IGF2 gene, is suggested to be co-expressed with IGF-II. Here, we tested whether serum miR-483-5p and -3p levels are associated wit

CD59 double knockout mice express a CD59ba hybrid fusion protein that mediates insulin secretion

CD59 is a cell-surface inhibitor of the terminal step in the complement cascade. However, in addition to its complement inhibitory function, a non-canonical role of CD59 in pancreatic beta cells has been identified. Two recently discovered intracellular alternative splice forms of CD59, IRIS-1 and IRIS-2, are involved in insulin exocytosis through interactions with SNARE-complex components. In mic

Apolipoprotein A-IV is induced by high-fat diets and mediates positive effects on glucose and lipid metabolism

Objective: Low-carbohydrate, high-fat diets under eucaloric conditions are associated with several health-beneficial metabolic effects in humans, particularly in the liver. We recently observed that apolipoprotein A-IV (apoA-IV), a highly abundant apolipoprotein, was among the most upregulated proteins in circulation after six weeks of consuming a high-fat diet in humans. However, the impact of di

Beyond boundaries: exploring the role of extracellular vesicles in organ-specific metastasis in solid tumors

Extracellular vesicles (EVs) have been identified as important mediators of cancer metastasis, especially in the establishment of organ-specific metastatic niches. These membranous vesicles secreted by tumor cells release diverse bioactive cargo, including proteins, nucleic acids, and lipids, thereby allowing for intercellular communication and microenvironment modulation. Recent evidence demonstr

Conversion of glutamate into proline by the leucine analog BCH enhances biphasic insulin secretion in pancreatic β-cells

Biphasic insulin secretion, which fails in type 2 diabetes, can be provoked by various nutrient stimuli, glucose being the superior physiological one. To identify pathways that may play a role in β-cell stimulus-secretion coupling, we compared β-cell and islet functional, secretory, and metabolic responses to glucose and 2-aminobicyclo-(2,2,1)-heptane-2-carboxylic acid (BCH), a leucine analog, tha

Mini-review of the EAT-Lancet planetary health diet and its role in cardiometabolic disease prevention

Human diets play a crucial role in both human health and environmental sustainability. In 2019, the EAT-Lancet Commission on healthy diets from sustainable food systems introduced the EAT-Lancet planetary health diet, a universal reference diet designed to promote human health while minimizing environmental degradation. It is a predominantly plant-based dietary pattern, rich in whole grains, veget

ApoAI-derived peptide increases glucose tolerance and prevents formation of atherosclerosis in mice

AIMS/HYPOTHESIS: Finding new treatment alternatives for individuals with diabetes with severe insulin resistance is highly desired. To identify novel mechanisms that improve glucose uptake in skeletal muscle, independently from insulin levels and signalling, we have explored the therapeutic potential of a short peptide sequence, RG54, derived from apolipoprotein A-I (ApoA-I).METHODS: INS-1E rat cl

Phenotypic Refinement of Heart Failure in a National Biobank Facilitates Genetic Discovery

Heart failure (HF) is a morbid and heritable disorder for which the biological mechanisms are incompletely understood. We therefore examined genetic associations with HF in a large national biobank, and assessed whether refined phenotypic classification would facilitate genetic discovery. Methods: We defined all-cause HF among 488 010 participants from the UK Biobank and performed a genome-wide a

Antibodies against neo-epitope of microbial and human transglutaminase complexes as biomarkers of childhood celiac disease

Tissue transglutaminase (tTG) and microbial transglutaminase (mTG) cross-link gliadins to form complexes that expose immunogenic neo-epitopes to produce tTG and mTG-neo-epitope antibodies. The aim of this study was to test the diagnostic performance of antibodies against non-complexed and complexed forms of transglutaminases, to correlate their activities to the intestinal damage and to explore ag

Metabolomics Analysis of Nutrient Metabolism in β-Cells

The islets of Langerhans harbor multiple endocrine cell types that continuously respond to circulating nutrient levels in order to adjust their secretion of catabolic and anabolic hormones. Stimulus–secretion coupling in these cells is largely of metabolic nature; that is, metabolism of nutrient fuels yields signals that trigger and amplify secretion of hormones. Hence, metabolism in this micro-or

Autoantibodies in Pandemrix®-induced narcolepsy : Nine candidate autoantigens fail the conformational autoantibody test

Study objectives: Narcolepsy type 1 (NT1) is a chronic sleep disorder characterized by loss of hypocretin-producing neurons. Increased NT1 incidence was observed in Sweden following mass-vaccination with Pandemrix®. Genetic association to HLA DQB1*06:02 implies an autoimmune origin, but target autoantigen remains unknown. Candidate autoantigens for NT1 have previously been identified in solid-phas

Development and validation of a quantitative electron microscopy score to assess acute cellular stress in the human exocrine pancreas

The pancreas is particularly sensitive to acute cellular stress, but this has been difficult to evaluate using light microscopy. Pancreatic ischaemia associated with deceased organ donation negatively impacts whole-organ and isolated-islet transplantation outcomes. Post-mortem changes have also hampered accurate interpretation of ante-mortem pancreatic pathology. A rigorous histological scoring sy

Effect of motor imagery on enjoyment in knee-injury prevention and rehabilitation training : A randomized crossover study

Objectives: The novel MOTor Imagery to Facilitate Sensorimotor Re-Learning (MOTIFS) model takes a uniquely holistic approach by integrating mental and physical aspects into current training programs. The aim of this trial was to evaluate enjoyment of MOTIFS training as compared to Care-as-Usual (CaU) knee injury and/or rehabilitation training. The primary hypothesis was that enjoyment would be gre