A5061458745- Biochemical effects in animals
- Adipose Tissue and Metabolism
- Cell Image Analysis Techniques
- Free Radicals and Antioxidants
- Diet and metabolism studies
- Single-cell and spatial transcriptomics
- CRISPR and Genetic Engineering
- RNA Interference and Gene Delivery
- Adipokines, Inflammation, and Metabolic Diseases
- Heat shock proteins research
- Dietary Effects on Health
- Advanced Fluorescence Microscopy Techniques
- Diet, Metabolism, and Disease
- Microfluidic and Bio-sensing Technologies
- RNA Research and Splicing
- Molecular Biology Techniques and Applications
- Redox biology and oxidative stress
- Stress Responses and Cortisol
- Hippo pathway signaling and YAP/TAZ
- Advanced Glycation End Products research
- Cancer, Hypoxia, and Metabolism
- Virus-based gene therapy research
- Ubiquitin and proteasome pathways
- Muscle metabolism and nutrition
University Hospital Heidelberg
2020-2024
Heidelberg University
2016-2024
3D cell cultures enable the in vitro study of dynamic biological processes such as cycle, but their use high-throughput screens remains impractical with conventional fluorescent microscopy. Here, we present a screening workflow for automated evaluation mitotic phenotypes by light-sheet After sample preparation liquid handling robot, spheroids are imaged 24 h toto dual-view inverted selective plane illumination microscope (diSPIM) much improved signal-to-noise ratio, higher imaging speed,...
Carnosinase 1 (CN1) is encoded by the Cndp1 gene and degrades carnosine anserine, two natural histidine-containing dipeptides. In vitro in vivo studies suggest carnosine- anserine-mediated protection against long-term sequelae of reactive metabolites accumulating, e.g., diabetes mellitus. We have characterized metabolic impact CN1 11- 55-week-old Cndp1-knockout (Cndp1-KO) mice litter-matched wildtypes (WT). Cndp1-KO mice, renal anserine concentrations were gender-specifically increased 2- to...
Carnosine and anserine supplementation markedLy reduce diabetic nephropathy in rodents. The mode of nephroprotective action both dipeptides diabetes, via local protection or improved systemic glucose homeostasis, is uncertain. Global carnosinase-1 knockout mice (Cndp1-KO) wild-type littermates (WT) on a normal diet (ND) high fat (HFD) (n = 10/group), with streptozocin (STZ)-induced type-1 diabetes 21-23/group), were studied for 32 weeks. Independent diet, Cndp1-KO had 2- to 10-fold higher...
Prolonged catabolic states in type 2 diabetes (T2D), exacerbated by excess substrate flux and hyperglycemia, can challenge metabolic flexibility antioxidative capacity. We investigated cellular responses to glucose load after prolonged fasting T2D.
Delivery of large and functionally active biomolecules across cell membranes presents a challenge in biological experimentation. For this purpose, we developed novel solid-phase reverse transfection method that is suitable for the intracellular delivery proteins into mammalian cells with preservation their function. We show results diverse application areas method, ranging from antibody-mediated inhibition protein function to CRISPR/Cas9-based gene editing living cells. Our enables...
Anserine and carnosine have nephroprotective actions; hydrogen sulfide (H2S) protects from ischemic tissue damage, the underlying mechanisms are debated. In view of their common interaction with HSP70, we studied possible interactions both dipeptides H2S. H2S formation was measured in human proximal tubular epithelial cells (HK-2); three endothelial cell lines (HUVEC, HUAEC, MCEC); renal murine wild-type (WT), carnosinase-1 knockout (Cndp1-KO) Hsp70-KO mice. Diabetes induced by streptozocin....
Aim: There is a growing body of evidence indicating that individuals with diabetic complications may not experience advantages from an intensified lifestyle intervention. Our study delved into how cells respond to glucose load after extended fasting in T2D individuals. We investigated cellular resistance against methylglyoxal (MG) stress tolerant (CON), (T2D+) and without (T2D-) whether this affected by caloric restriction.
<p dir="ltr"><b>Objective: </b>Prolonged catabolic states in type 2 diabetes (T2D), exacerbated by excess substrate flux and hyperglycaemia, can challenge metabolic flexibility antioxidative capacity. We investigated cellular responses to glucose load after prolonged fasting T2D.</p><p dir="ltr"><b>Research Design Methods: </b>Glucose-tolerant individuals (CON, n=10), T2D with (T2D+, n=10) without diabetic complications (T2D-, underwent oral...
<p dir="ltr"><b>Objective: </b>Prolonged catabolic states in type 2 diabetes (T2D), exacerbated by excess substrate flux and hyperglycaemia, can challenge metabolic flexibility antioxidative capacity. We investigated cellular responses to glucose load after prolonged fasting T2D.</p><p dir="ltr"><b>Research Design Methods: </b>Glucose-tolerant individuals (CON, n=10), T2D with (T2D+, n=10) without diabetic complications (T2D-, underwent oral...
Due to high associated costs and considerable time investments of cell-based screening, there is a strong demand for new technologies that enable preclinical development tests diverse biologicals in cost-saving time-efficient manner. For those reasons we developed the high-density cell array (HD-CA) platform, which miniaturizes screening form preprinted ready-to-run arrays. With HD-CA technology, up 24,576 samples can be tested single experiment, thereby saving microscopy-based by 75%....
Abstract 3D cell cultures enable the in vitro study of dynamic biological processes such as cycle, but their use high-throughput screens remains impractical with conventional fluorescent microscopy. Here, we present a screening workflow for automated evaluation mitotic phenotypes by light-sheet After sample preparation liquid handling robot, three-dimensional spheroids are imaged 24 hours toto dual inverted selective plane illumination (diSPIM) microscope much improved signal-to-noise ratio,...
Background The stress-inducible heat shock protein 70 (Hspa1a/Hspa1b) is involved in refolding of misfolded proteins as well disaggregation aggregates. Posttranslational modifications, for example by glycation during hyperglycemia, can lead to misfolding, aggregation and loss-of-function the protein.The aim this study was investigate loss Hspa1a/Hspa1b a STZ-induced diabetic mouse model terms development nephropathy. Methods: Diabetes induced at age 10 weeks; mice were sacrificed 28 weeks....
Introduction and open questions Methylglyoxal-derived hydroimidazolone (MG-H1) is formed in a reaction of the reactive dicarbonyl Methylglyoxal (MG) with arginine residues proteins leading to misfolding, aggregation loss of-function protein. Heat shock (Hsp) mediate refolding disaggregation misfolded proteins.
Abstract Increased metabolic flux produces potentially harmful side-products, such as reactive dicarbonyl and oxygen species. The dicarbonly methylglyoxal (MG) can impair oxidative capacity, which is downregulated in type 2 diabetes. Heat shock proteins (HSPs) of subfamily A (Hsp70s) promote ATP-dependent processing damaged during MG exposure also involve mitochondrial proteins. Since the protection could higher production metabolites due to increased substrate flux, tight regulation...