Advanced glycation endproduct

Progress in the development of effective chemotherapy is producing a growing population of patients with acute and chronic painful chemotherapy-induced peripheral neuropathy (CIPN), a serious treatment limiting side effect for which there is currently no FDA approved treatment. CIPN induced by diverse classes of chemotherapy drugs have remarkably similar clinical presentations leading to the suggestion they share underlying mechanisms. Sensory neurons share with immune cells, the ability to detect Damage Associated Molecular Patterns (DAMPs), molecules produced by diverse cell types in response to cellular stress and injury, including by chemotherapy drugs...

Diabetic kidney disease (DKD) is a leading cause of kidney failure. Previous studies demonstrated the therapeutic potential of Astragalus polysaccharide in treating diabetic nephropathy. Astragalus and Hongqi both come from the leguminous plant Astragalus, but their species and genera are different, belonging to the same family and different genera of traditional Chinese medicinal plants. However, the effects of Hedysarum polybotrys polysaccharide (HPS), a polysaccharide compound from Hongqi, on DKD, including its components and efficacy, have remained elusive...

Nearly 40% of Americans have obesity and are at increased risk for developing type 2 diabetes. Skeletal muscle is responsible for >80% of insulin-stimulated glucose uptake which is attenuated by the inflammatory milieu of obesity and augmented by exercise. The Receptor for Advanced Glycation Endproducts (RAGE) is an inflammatory receptor directly linking metabolic dysfunction with inflammation. Circulating soluble isoforms of RAGE (sRAGE) formed either by proteolytic cleavage (cRAGE) or alternative splicing (esRAGE) act as decoys for RAGE ligands thereby counteracting RAGE-mediated inflammation...

Advanced-Glycation-Endproducts (AGEs) are known to be a major cause of impaired tissue material properties. In collagen fibrils, the main building component of human tissue, these AGEs appear as fibrillar cross-links. When AGEs accumulate in collagen fibrils, a process often caused by diabetes and aging, the mechanical properties of the collagen fibril are altered. However, current knowledge about the mechanical properties of different types of AGEs, and their quantity in collagen fibrils is limited owing to the scarcity of available experimental data...

Although glomerular endothelial dysfunction is well recognized as contributing to the pathogenesis of diabetic kidney disease (DKD), the molecular pathways contributing to DKD pathogenesis in glomerular endothelial cells (GECs) are only partially understood. To uncover pathways that are differentially regulated in early DKD that may contribute to disease pathogenesis, we recently conducted a transcriptomic analysis of isolated GECs from diabetic NOS3-null mice. The analysis identified several potential mediators of early DKD pathogenesis, one of which encoded an adhesion G protein-coupled receptor-56 (GPR56), also known as ADGRG1...

AIMS/HYPOTHESIS: These secondary analyses aimed to investigate the effects of different volumes of exercise in adjunct to diet-induced weight loss and standard care on advanced glycation end-products (AGEs) and receptor for AGE (RAGE). We hypothesized that exercise in adjunct to a diet-induced weight loss would dose-dependently increase the soluble decoy receptor for AGE (sRAGE) more than diet-induced weight loss and standard care alone. Secondarily, we expected changes in sRAGE to be associated with improved glycaemic control and inversely associated with low-grade inflammation...

Cannabidiol (CBD), the most abundant nonpsychoactive constituent of Cannabis sativa plant, is a promising potential pharmacotherapy for the treatment of diabetes and associated comorbidities. Previous studies have shown the potential of CBD to prevent diabetes in mice, the precise mechanisms of action remain unclear. The purpose of this study was to explore the mechanism of CBD alleviating hyperglycemia. The results demonstrated that CBD reduced blood glucose of STZ-induced diabetic mice without causing hypoglycemia...

SARS-CoV-2 nucleocapsid protein (N-protein) rises early in body fluids during infection and has recently been identified as a direct inducer for lung injury. However, the signal mechanism of N-protein in lung inflammatory response remains poorly understood. The goal of this study was to determine whether receptor for advanced glycation endproducts (RAGE) participated in N-protein-induced acute lung injury. The binding between N-protein and RAGE was examined via assays for protein-protein interaction. To determine the signaling mechanism in vitro, cells were treated with recombinant N-protein and assayed for the activation of RAGE/mitogen-activated protein kinase/NF-ĸB pathway...

SCOPE: Maillard reaction products (MRPs) are believed to interact with the receptor for advanced glycation endproducts (RAGE) and lead to a pro-inflammatory cellular response. The structural basis for this interaction is scarcely understood. This study investigates the effect of individual lysine modifications in free form or bound to casein on human colon cancer cells. METHODS AND RESULTS: Selectively glycated casein containing either protein-bound N-ε-carboxymethyllysine (CML), N-ε-fructosyllysine (FL), or pyrraline is prepared and up to 94%, 97%, and 61% of lysine modification could be attributed to CML, FL, or pyrraline, respectively...

Puffy fingers and Raynaud's phenomenon (RP) are important clinical predictors of the development of systemic sclerosis (SSc). We aim to assess the prevalence of SSc-related symptoms, explore pulmonary symptoms, and test the usefulness of skin autofluorescence (SAF) as a non-invasive marker for Advanced Glycation Endproducts (AGEs). Subjects from the Lifelines Cohort Study with known connective tissue disease (CTD) were excluded. Patient characteristics, SAF, self-reported pulmonary symptoms, and spirometry were obtained...

OBJECTIVE: The paper reports an attempt to develop and validate a HILIC UPLC/ QTof MS method for quantifying N-ε-carboxymethyl-L-lysine (CML) in vitro, testing N-ε-carboxy[D2]methyl-L-lysine (d2-CML), and N-ε-carboxy[4,4,5,5-D4]methyl-L-lysine (d4-CML) as internal standards. METHOD: During the method development, several challenging questions occurred that hindered the successful completion of the method. The study emphasizes the impact of issues, generally overlooked in the development of similar analytical protocols...

The incidence of diabetes mellitus and the associated complications are growing worldwide, affecting the patients' quality of life and exerting a considerable burden on health systems. Yet, the increase in fracture risk in type 1 diabetes (T1D) patients is not fully captured by bone mineral density (BMD), leading to the hypothesis that alterations in bone quality are responsible for the increased risk. Material/compositional properties are important aspects of bone quality, yet information on human bone material/compositional properties in T1D is rather sparse...

BACKGROUND: Back and neck pain are leading causes of global disability that are associated with intervertebral disc (IVD) degeneration. Causes of IVD degeneration are multifactorial, and diet, age, and diabetes have all been linked to IVD degeneration. Advanced glycation endproducts (AGEs) accumulate in the IVD as a result of aging, diet, and diabetes, and AGE accumulation in the IVD has been shown to induce oxidative stress and catabolic activity that result in collagen damage. An association between AGE accumulation and IVD degeneration is emerging, yet mechanism behind this association remains unclear...

The receptor for advanced glycation end-products (RAGE) may serve as a diagnostic and prognostic biomarker of lung cancer and lung injury. We explored whether the serum and bronchial levels of soluble RAGE (sRAGE) distinguished infectious lung diseases from lung cancer. We collected serum and bronchial washing fluids (BWFs) from patients diagnosed with pneumonia, tuberculosis, or preoperative lung cancer from April 2016 to March 2022. sRAGE levels were measured using an enzyme-linked immunosorbent assay and we drew receiver operating characteristic (1) curves to determine the cut-off values affording the best diagnostic sensitivities...

BACKGROUND & AIMS: A diet high in advanced glycation endproducts (AGEs) is a potential risk factor for insulin resistance, beta cell dysfunction, and ultimately type 2 diabetes. We investigated associations between habitual intake of dietary AGEs and glucose metabolism in a population-based setting. METHODS: In 6275 participants of The Maastricht Study (mean ± SD age: 60 ± 9, 15.1% prediabetes and 23.2% type 2 diabetes), we estimated habitual intake of dietary AGEs Nε -(carboxymethyl)lysine (CML), Nε -(1-carboxyethyl)lysine (CEL), and Nδ -(5-hydro-5-methyl-4-imidazolon-2-yl)-ornithine (MG-H1) by combining a validated food frequency questionnaire (FFQ) with our mass-spectrometry dietary AGE database...

BACKGROUND: Lung cancer is the second leading cause of death in the United States. Lung cancer is often diagnosed in its late stage leading to a poor prognosis. Lung nodules are often described as indeterminate from CT scans resulting in lung biopsies that are invasive and may lead to complications. The need for noninvasive methods to assess malignancy risk in lung nodules is great. METHODS: The lung nodule risk reclassifier assay consists of 7 protein biomarkers: Carcinoembryonic Antigen (CEA), C-X-C Motif Chemokine Ligand 10 (CXCL10), Epidermal Growth Factor Receptor (EGFR), Neutrophil Activating Protein-2 (NAP2), Pro-surfactant Protein B (ProSB), Receptor for Advanced Glycation Endproducts (RAGE), and Tissue Inhibitor of Metalloproteinase Inhibitor 1 (TIMP1) and 6 clinical factors (subject age, smoking pack years, and sex, and lung nodule size, location, and spiculated appearance)...

Nonenzymatic reactions of reducing sugars with primary amino groups of amino acids, proteins, and nucleic acids, followed by oxidative degradations would lead to the formation of advanced glycation endproducts (AGEs). The AGEs exert multifactorial effects on cell damage leading to the onset of neurological disorders. The interaction of AGEs with the receptors for advanced glycation endproducts (RAGE) contribute to the activation of intracellular signaling and the expression of the pro-inflammatory transcription factors and various inflammatory cytokines...

Collagen, one of the main building blocks for various tissues, derives its mechanical properties directly from its structure of cross-linked tropocollagen molecules. The cross-links are considered to be a key component of collagen fibrils as they can change the fibrillar behavior in various ways. For instance, enzymatic cross-links (ECLs), one particular type of cross-links, are known for stabilizing the structure of the fibril and improving material properties, while cross-linking AGEs (Advanced-Glycation Endproducts) have been shown to accumulate and impair the mechanical properties of collageneous tissues...

CONTEXT: The risk of fragility fractures is increased in both type 1 and type 2 diabetes. Numerous biochemical markers reflecting bone and/or glucose metabolism have been evaluated in this context. This review summarizes current data on biochemical markers in relation to bone fragility and fracture risk in diabetes. METHODS: Literature review by a group of experts from the International Osteoporosis Foundation (IOF) and European Calcified Tissue Society (ECTS) focusing on biochemical markers, diabetes, diabetes treatments and bone in adults...

Ma, H., Li, S.-Y., Xu, P., Babcock, S.A., Dolence, E.K., Brownlee, M., Li, J. and Ren, J. (2009), Advanced glycation endproduct (AGE) accumulation and AGE receptor (RAGE) up-regulation contribute to the onset of diabetic cardiomyopathy. Journal of Cellular and Molecular Medicine, 13: 1751-1764. https://doi.org/10.1111/j.1582-4934.2008.00547.x. The above article, published online on 13 October 2008 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between, the journal Editor in Chief, Stefan Constantinescu, The Foundation for Cellular and Molecular Medicine, and John Wiley and Sons Ltd...