Explore the vast range of titles available.

Exogenous and endogenous advanced glycation end products (AGEs) contribute to the pathogenesis and progression of renal disease. This is a one-month controlled dietary counseling trial that restricts nutritional AGEs in patients with end-stage renal disease (ESRD) undergoing haemodialysis (n = 22 participants in the intervention and n = 20 participants in the control group). Haematological, biochemical markers, the soluble form of the receptor for AGEs (sRAGE), and carboxymethyl lysine (CML) were measured at baseline and at follow-up. Mononuclear cells were isolated and the protein expression of RAGE and the inflammatory marker COX-2 was measured using Western immunoblotting. The intervention group presented a lower increase in CML compared to the control group (12.39% median change in the intervention vs. 69.34% in the control group, p = 0.013), while RAGE (% mean change −56.54 in the intervention vs. 46.51 in the control group, p < 0.001) and COX-2 (% mean change −37.76 in the intervention vs. 0.27 in the control group, p < 0.001) were reduced compared to the control group. sRAGE was reduced in both groups. In addition, HbA1c (at two months), total cholesterol, and triglycerides were reduced in the intervention versus the control group. The adoption of healthy cooking methods deserves further research as a possible way of modulating inflammatory markers in patients with CKD.

The purpose of this pilot study was to determine whether macronutrient content (low-fat v. high-fat diet) influences an indicator of advanced glycation end products (AGE), N ε carboxymethyl-lysine (CML), in the context of a 1-d, high-AGE diet. The effect of the diets on inflammatory markers was also assessed. A total of nineteen overweight and obese adults (nine men and ten women) without known disease were recruited to participate in a crossover challenge of a high-fat, high-AGE (HFHA) and low-fat, high-AGE (LFHA) diet. In each phase patients had fasting blood drawn, followed by consumption of a high-fat or low-fat breakfast test meal, then three postprandial blood draws at 1, 2 and 3 h after consuming the test meal. After consuming high-AGE meals for the remainder of the day, participants returned the next day for a follow-up analysis. A different pattern in the 3-h post-meal CML and soluble receptor for AGE response to the two diets was observed (P=0·01 and 0·05, respectively). No change in serum CML was observed following consumption of a LFHA breakfast (535 (25th–75th percentile 451–790) to 495 (25th–75th percentile 391–682) ng/ml; P=0·36), whereas a rise in CML occurred after the HFHA breakfast (463 (25th–75th percentile 428–664) to 578 (25th–75th percentile 474–865) ng/ml; P=0·05). High sensitivity C-reactive protein and high molecular weight adiponectin were not affected by either diet. These findings suggest that dietary CML may not be as important in influencing serum CML as other dietary factors. In addition, acute exposure to dietary CML may not influence inflammation in adults without diabetes or kidney disease. This is contrary to previous findings.

Background Although dyslipidemia has been acknowledged as a risk factor for Alzheimer’s disease (AD), the effects of lipid-lowering drugs on AD have not been determined. The primary pathophysiological hallmark of AD is the deposition of amyloid-β (Aβ) plaques in the brain. Plasma Aβ levels are influenced by the transport of Aβ from the central nervous system to the peripheral blood. This study investigates the effects of Probucol, a lipid-lowering and antioxidant drug, on plasma Aβ transport. Methods A total of 120 hyperlipidemic patients with normal cognition were randomly assigned (1:1 ratio) to receive either Probucol (1000 mg daily for 12 weeks) or a placebo. Plasma Aβ, soluble receptor of advanced glycation end products (sRAGE), and fasting lipid profiles were measured at baseline and every 6 weeks. Results A total of 108 participants completed the study, with 55 in the Probucol group. The cohort consisted of 58 (53.7%) women, with a mean age of 58.4 ± 8.0 (range, 45–80) years. After 12 weeks of treatment, the changes in plasma Aβ 42 and sRAGE levels significantly differed between the Probucol and placebo groups (ΔAβ 42 : β = 6.827, P  = 0.030; ΔsRAGE: β = 98.668, P  = 0.004). Furthermore, ΔsRAGE was positively correlated with the change in Aβ 42 (β = 0.018, P  = 0.048). When adjusted for ΔsRAGE, the effect of Probucol on plasma Aβ 42 levels was attenuated (β = 5.065, P  = 0.116). In the Probucol group only, ΔsRAGE was significantly correlated with oxidized low-density lipoproteins (β = 4.27, P  = 0.011), total cholesterol (β = 67.50, P  = 0.046), and low-density lipoproteins (β = − 91.01, P  = 0.011). Conclusions Daily oral administration of Probucol (1000 mg) for 12 weeks significantly increased plasma Aβ 42 levels, likely through modulation of sRAGE. This effect may be attributed to the antioxidant and lipid-lowering properties of Probucol. These findings suggest that Probucol could potentially serve as a protective agent against the pathological processes of AD. Trial registration This study was registered on the Chinese Clinical Trial Registry platform in June 2019 (Trial registration number: ChiCTR-1900023542).

Advanced glycation end-products (AGEs) constitute a non-homogenous, chemically diverse group of compounds formed either exogeneously or endogeneously on the course of various pathways in the human body. In general, they are formed non-enzymatically by condensation between carbonyl groups of reducing sugars and free amine groups of nucleic acids, proteins, or lipids, followed by further rearrangements yielding stable, irreversible end-products. In the last decades, AGEs have aroused the interest of the scientific community due to the increasing evidence of their involvement in many pathophysiological processes and diseases, such as diabetes, cancer, cardiovascular, neurodegenerative diseases, and even infection with the SARS-CoV-2 virus. They are recognized by several cellular receptors and trigger many signaling pathways related to inflammation and oxidative stress. Despite many experimental research outcomes published recently, the complexity of their engagement in human physiology and pathophysiological states requires further elucidation. This review focuses on the receptors of AGEs, especially on the structural aspects of receptor–ligand interaction, and the diseases in which AGEs are involved. It also aims to present AGE classification in subgroups and to describe the basic processes leading to both exogeneous and endogeneous AGE formation.

Persistent hyperglycemic state in type 2 diabetes mellitus leads to the initiation and progression of non-enzymatic glycation reaction with proteins and lipids and nucleic acids. Glycation reaction leads to the generation of a heterogeneous group of chemical moieties known as advanced glycated end products (AGEs), which play a central role in the pathophysiology of diabetic complications. The engagement of AGEs with its chief cellular receptor, RAGE, activates a myriad of signaling pathways such as MAPK/ERK, TGF-β, JNK, and NF-κB, leading to enhanced oxidative stress and inflammation. The downstream consequences of the AGEs/RAGE axis involve compromised insulin signaling, perturbation of metabolic homeostasis, RAGE-induced pancreatic beta cell toxicity, and epigenetic modifications. The AGEs/RAGE signaling instigated modulation of gene transcription is profoundly associated with the progression of type 2 diabetes mellitus and pathogenesis of diabetic complications. In this review, we will summarize the exogenous and endogenous sources of AGEs, their role in metabolic dysfunction, and current understandings of AGEs/RAGE signaling cascade. The focus of this review is to recapitulate the role of the AGEs/RAGE axis in the pathogenesis of type 2 diabetes mellitus and its associated complications. Furthermore, we present an overview of future perspectives to offer new therapeutic interventions to intervene with the AGEs/RAGE signaling pathway and to slow down the progression of diabetes-related complications.

Alpha-lipoic acid (ALA) has been used as a dietary supplement at different doses in patients with diabetes mellitus type 2 (T2DM) due to its antioxidant, anti-inflammatory, and hypoglycemic effects. However, the reports on the effects of ALA are controversial. For this reason, the purpose of the present study was to determine the effect of 600 mg/day of ALA on the markers of oxidative stress (OxS) and inflammation and RAGE in older adults with T2DM. A quasiexperimental study was carried out with a sample of 135 sedentary subjects (98 women and 37 men) with a mean age of 64±1 years, who all had T2DM. The sample was divided into three groups: (i) experimental group (EG) with 50 subjects, (ii) placebo group (PG) with 50 subjects, and control group (CG) with 35 subjects. We obtained the following measurements in all subjects (pre- and posttreatment): glycosylated hemoglobin (HbA1c), receptor for advanced glycation end products (RAGE), 8-isoprostane, superoxide dismutase (SOD), glutathione peroxidase (GPx), total antioxidant status (TAS), and inflammatory (CRP, TNF-α, IL-6, IL-8, and IL-10) markers. Regarding the effect of ALA on HbA1c, a decrease was observed in the EG (baseline 8.9±0.2 vs. posttreatment 8.6±0.3) and the PG (baseline 8.8±0.2 vs. posttreatment 8.4±0.3) compared to the CG (baseline 8.8±0.3 vs. six months 9.1±0.3) although the difference was not statistically significant (p<0.05). There was a statistically significant decrease (p<0.05) in the blood concentration of 8-isoprostane in the EG and PG with respect to the CG (EG: baseline 100±3 vs. posttreatment 57±3, PG: baseline 106±7 vs. posttreatment 77±5, and CG: baseline 94±10 vs. six months 107±11 pg/mL). Likewise, a statistically significant decrease (p<0.05) in the concentration of the RAGE was found in the EG (baseline 1636±88 vs. posttreatment 1144±68) and the PG (baseline 1506±97 vs. posttreatment 1016±82) compared to CG (baseline 1407±112 vs. six months 1506±128). A statistically significant decrease was also observed in all markers of inflammation and in the activity of SOD and GPx in the CG with respect to the EG and PG. Our findings suggest that the administration of ALA at a dose of 600 mg/day for six months has a similar effect to that of placebo on oxidative stress, inflammation, and RAGE in older adults with T2DM. Therefore, higher doses of ALA should be tried to have this effect. This trial is registered with trial registration number ISRCTN13159380.

Sirtuin-1 (Sirt-1) and an endogenous secretory receptor for an advanced glycation end product (esRAGE) are associated with vascular protection. The purpose of this study was to examine the effects of resveratrol (RSV) and caloric restriction (CR) on gene expression of Sirt-1 and esRAGE on serum levels of Sirt1 and esRAGE in healthy and slightly overweight subjects. The study included 48 healthy subjects randomized to 30 days of RSV (500 mg/day) or CR (1000 cal/day). Waist circumference (p = 0.011), TC (p = 0.007), HDL (p = 0.031), non-HDL (p = 0.025), ApoA1 (p = 0.011), and ApoB (p = 0.037) decreased in the CR group. However, TC (p = 0.030), non-HDL (p = 0.010), ApoB (p = 0.034), and HOMA-IR (p = 0.038) increased in the RSV group. RSV and CR increased serum levels of Sirt-1, respectively, from 1.06 ± 0.71 ng/mL to 5.75 ± 2.98 ng/mL (p < 0.0001) and from 1.65 ± 1.81 ng/mL to 5.80 ± 2.23 ng/mL (p < 0.0001). esRAGE serum levels were similar in RSV (p = NS) and CR (p = NS) groups. Significant positive correlation was observed between gene expression changes of Sirt-1 and esRAGE in RSV (r = 0.86; p < 0.0001) and in CR (r = 0.71; p < 0.0001) groups, but not for the changes in serum concentrations. CR promoted increases in the gene expression of esRAGE (post/pre). Future long-term studies are needed to evaluate the impact of these outcomes on vascular health.

Advanced glycation end products (AGEs) are potentially harmful and heterogeneous molecules derived from nonenzymatic glycation. The pathological implications of AGEs are ascribed to their ability to promote oxidative stress, inflammation, and apoptosis. Recent studies in basic and translational research have revealed the contributing roles of AGEs in the development and progression of various aging-related pathological conditions, such as diabetes, cardiovascular complications, gut microbiome-associated illnesses, liver or neurodegenerative diseases, and cancer. Excessive chronic and/or acute binge consumption of alcohol (ethanol), a widely consumed addictive substance, is known to cause more than 200 diseases, including alcohol use disorder (addiction), alcoholic liver disease, and brain damage. However, despite the considerable amount of research in this area, the underlying molecular mechanisms by which alcohol abuse causes cellular toxicity and organ damage remain to be further characterized. In this review, we first briefly describe the properties of AGEs: their formation, accumulation, and receptor interactions. We then focus on the causative functions of AGEs that impact various aging-related diseases. We also highlight the biological connection of AGE–alcohol–adduct formations to alcohol-mediated tissue injury. Finally, we describe the potential translational research opportunities for treatment of various AGE- and/or alcohol-related adduct-associated disorders according to the mechanistic insights presented. Metabolism: AGEs in aging- and alcohol-related diseases Advanced glycation end products (AGEs), molecules formed when proteins and lipids combine with sugar, play key roles in aging-related diseases and in alcohol-induced tissue damage. AGEs naturally accumulate in the body with aging, and are also present in food, particularly in fried and processed foods. They are also produced by alcohol metabolism and cigarette smoking. Byoung-Joon Song and Wiramon Rungratanawanich at the National Institute on Alcohol Abuse and Alcoholism in Bethesda, USA, have reviewed how AGEs accumulate and their roles in aging-related diseases and alcohol-related health effects. They report that AGEs are linked to promotion or exacerbation of many diseases such as cardiovascular and kidney disease, adult-onset diabetes, cancer, and neurodegenerative conditions like Alzheimer’s and Parkinson’s diseases. The authors highlight opportunities for further research and for reducing AGE accumulation through changes in diet and behavior.

Diabetic retinopathy is a tissue-specific neurovascular impairment of the retina in patients with both type 1 and type 2 diabetes. Several pathological factors are involved in the progressive impairment of the interdependence between cells that consist of the neurovascular units (NVUs). The advanced glycation end-products (AGEs) are one of the major pathological factors that cause the impairments of neurovascular coupling in diabetic retinopathy. Although the exact mechanisms for the toxicities of the AGEs in diabetic retinopathy have not been definitively determined, the AGE-receptor of the AGE (RAGE) axis, production of reactive oxygen species, inflammatory reactions, and the activation of the cell death pathways are associated with the impairment of the NVUs in diabetic retinopathy. More specifically, neuronal cell death is an irreversible change that is directly associated with vision reduction in diabetic patients. Thus, neuroprotective therapies must be established for diabetic retinopathy. The AGEs are one of the therapeutic targets to examine to ameliorate the pathological changes in the NVUs in diabetic retinopathy. This review focuses on the basic and pathological findings of AGE-induced neurovascular abnormalities and the potential therapeutic approaches, including the use of anti-glycated drugs to protect the AGE-induced impairments of the NVUs in diabetic retinopathy.

As a critical molecule in the onset and sustainment of inflammatory response, the receptor for advanced glycation end products (RAGE) has a variety of ligands, such as advanced glycation end products (AGEs), S100/calcium granule protein, and high-mobility group protein 1 (HMGB1). Recently, an increasing number studies have shown that RAGE ligand binding can initiate the intracellular signal cascade, affect intracellular signal transduction, stimulate the release of cytokines, and play a vital role in the occurrence and development of immune-related diseases, such as systemic lupus erythematosus, rheumatoid arthritis, and Alzheimer’s disease. In addition, other RAGE signaling pathways can play crucial roles in life activities, such as inflammation, apoptosis, autophagy, and endoplasmic reticulum stress. Therefore, the strategy of targeted intervention in the RAGE signaling pathway may have significant therapeutic potential, attracting increasing attention. In this paper, through the systematic induction and analysis of RAGE-related signaling pathways and their regulatory mechanisms in immune-related diseases, we provide theoretical clues for the follow-up targeted intervention of RAGE-mediated diseases.