A5081699544- Advanced Glycation End Products research
- Pain Mechanisms and Treatments
- Biochemical effects in animals
- Diabetes, Cardiovascular Risks, and Lipoproteins
- Neurological Disorders and Treatments
- Botulinum Toxin and Related Neurological Disorders
- Diet and metabolism studies
- Metabolism, Diabetes, and Cancer
- Natural Antidiabetic Agents Studies
- Alcohol Consumption and Health Effects
- Diabetes and associated disorders
- Diabetes Treatment and Management
- Retinal Diseases and Treatments
- Ion Channels and Receptors
- Neuroinflammation and Neurodegeneration Mechanisms
- Genetics, Aging, and Longevity in Model Organisms
- Atherosclerosis and Cardiovascular Diseases
- Aldose Reductase and Taurine
- Crystallization and Solubility Studies
- X-ray Diffraction in Crystallography
- Adipose Tissue and Metabolism
- Pancreatic function and diabetes
- Chronic Kidney Disease and Diabetes
- Adipokines, Inflammation, and Metabolic Diseases
- Liver Disease Diagnosis and Treatment
University Hospital Heidelberg
2015-2024
Heidelberg University
2015-2024
Heinrich Heine University Düsseldorf
2016-2024
Deutsches Diabetes-Zentrum e.V.
2016-2024
German Center for Diabetes Research
2016-2024
Johns Hopkins University
2021
National Health Service
2018
North Bristol NHS Trust
2018
Helmholtz Zentrum München
2017-2018
University of Leeds
2016-2018
The HER2 gene, which encodes the growth factor receptor HER2, is amplified and overexpressed in 25 to 30 percent of breast cancers, increasing aggressiveness tumor.
Acute brain lesions induce profound alterations of the peripheral immune response comprising opposing phenomena early activation and subsequent immunosuppression. The mechanisms underlying this brain-immune signaling are largely unknown. We used animal models for experimental ischemia as a paradigm acute additionally investigated large cohort stroke patients. inflammatory potency HMGB1 its pathways by immunological in vivo vitro techniques. Features complex behavioral sickness behavior...
OBJECTIVE Establishing Caenorhabditis elegans as a model for glucose toxicity–mediated life span reduction. RESEARCH DESIGN AND METHODS C. were maintained to achieve concentrations resembling the hyperglycemic conditions in diabetic patients. The effects of high on span, glyoxalase-1 activity, advanced glycation end products (AGEs), and reactive oxygen species (ROS) formation mitochondrial function studied. RESULTS High reduced mean from 18.5 ± 0.4 16.5 0.6 days maximum 25.9 23.2 days,...
OBJECTIVE To study incident diabetic polyneuropathy (DPN) prospectively during the first 13 years after a screening-based diagnosis of type 2 diabetes and determine associated risk factors for development DPN. RESEARCH DESIGN AND METHODS We assessed DPN longitudinally in Danish arm Anglo-Danish-Dutch Intensive Treatment Diabetes Primary Care (ADDITION) using Michigan Neuropathy Screening Instrument questionnaire (MNSIQ), defining with scores ≥4. Risk present at were estimated Cox...
Diabetic neuropathy is a severe complication of long-standing diabetes and one the major etiologies neuropathic pain. Diabetes associated with an increased formation reactive oxygen species electrophilic dicarbonyl compound methylglyoxal (MG). Here we show that MG stimulates heterologously expressed TRPA1 in CHO cells natively MDCK DRG neurons. evokes [Ca(2+)]i-responses expressing neurons but without effect cultured from Trpa1(-/-) mice. Consistent direct, intracellular action,...
Background: Worldwide, diabetes mellitus and heart failure represent frequent comorbidities with high socioeconomic impact steadily growing incidence, calling for a better understanding of how diabetic metabolism promotes cardiac dysfunction. Paradoxically, some glucose-lowering drugs have been shown to worsen failure, raising the question glucose mediates protective versus detrimental signaling. Here, we identified histone deacetylase 4 (HDAC4) subdomain as molecular checkpoint adaptive...
Abstract Long-lasting pain stimuli can trigger maladaptive changes in the spinal cord, reminiscent of plasticity associated with memory formation. Metabolic coupling between astrocytes and neurons has been implicated neuronal formation central nervous system, but neither its involvement pathological nor tested. Here we report a form neuroglia signalling involving astrocytic glycogen dynamics triggered by persistent noxious stimulation via upregulation Protein Targeting to Glycogen (PTG)...
Glyoxal and methylglyoxal are reactive dicarbonyl metabolites formed metabolized in physiological systems. Increased exposure to these dicarbonyls is linked mutagenesis cytotoxicity enhanced metabolism by overexpression of glyoxalase 1 tumour multidrug resistance cancer chemotherapy. We report herein that glycation DNA glyoxal produces a quantitatively important class nucleotide adduct systems-imidazopurinones. The derived from...
Surprisingly, 40% to 95% of patients with type 2 diabetes mellitus (T2DM) show early remission hyperglycemia after obesity surgery. It is unknown what extent other diabetes-associated comorbidities such as distal peripheral neuropathy (DPN) might be influenced by This pilot study aimed at providing further evidence for the impact Roux-en-Y gastric bypass (RYGB) on both glycemic control and DPN in non-severely obese insulin-dependent T2DM.In present prospective cohort study, 20 long-standing,...
The integrity of genome is a prerequisite for healthy life. Indeed, defects in DNA repair have been associated with several human diseases, including tissue-fibrosis, neurodegeneration and cancer. Despite decades extensive research, the spatio-mechanical processes double-strand break (DSB)-repair, especially auxiliary factor(s) that can stimulate accurate timely repair, remained elusive. Here, we report an ATM-kinase dependent, unforeseen function nuclear isoform Receptor Advanced Glycation...
The receptor for AGEs (RAGE) is linked to proinflammatory pathology in a range of tissues. objective this study was assess the potential modulatory role RAGE diabetic retinopathy.Diabetes induced wild-type (WT) and Rage (-/-) mice (also known as Ager mice) using streptozotocin while non-diabetic control received saline. For all groups, blood glucose, HbA1c retinal levels methylglyoxal (MG) were evaluated up 24 weeks post diabetes induction. After killed, glia microglial activation,...
Dipeptidyl peptidase 4 (DPP4) inhibitors improve glycemic control in type 2 diabetes, however, their influence on the retinal neurovascular unit remains unclear.Vasculo- and neuroprotective effects were assessed experimental diabetic retinopathy high glucose-cultivated C. elegans, respectively. In STZ-diabetic Wistar rats (diabetes duration of 24 weeks), DPP4 activity (fluorometric assay), GLP-1 (ELISA), methylglyoxal (LC-MS/MS), acellular capillaries pericytes (quantitative morphometry),...
The deficit of Glyoxalase I (Glo1) and the subsequent increase in methylglyoxal (MG) has been reported to be one five mechanisms by which hyperglycemia causes diabetic late complications. Aldo-keto reductases (AKR) have shown metabolize MG; however, relative contribution this superfamily detoxification MG vivo, particularly within state, remains unknown. CRISPR/Cas9-mediated genome editing was used generate a Glo1 knock-out (Glo1−/−) mouse line. Streptozotocin then applied investigate...
The individual risk of progression diabetic peripheral neuropathy is difficult to predict for each individual. Mutations in proteins that are responsible the process myelination known cause neurodegeneration and display alteration experimental models neuropathy. In a prospective observational human pilot study, we investigated myelin-specific circulating mRNA targets, which have been identified vitro, their capacity diagnosis prediction most promising candidate was tested against recently...
OBJECTIVE Individuals with type 2 diabetes are at higher risk of progression nonalcoholic fatty liver (steatosis) to steatohepatitis (NASH), fibrosis, and cirrhosis. The hepatic metabolism obese individuals adapts by upregulation mitochondrial capacity, which may be lost during the steatosis. However, role regard function in NASH remains unclear. RESEARCH DESIGN AND METHODS We therefore examined histologically proven without (OBE) (n = 30; BMI 52 ± 9 kg/m2) or (T2D) 15; 51 7 as well healthy...