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BACKGROUND: Nε‐carboxymethyllysine (CML), Nε‐carboxyethyllysine (CEL) and α‐aminoadipic acid (AAA) are important foodborne hazards and their intake can cause a variety of diseases in humans. It is extremely important to investigate the formation mechanism of CML, CEL and AAA, as well as their association with each other when aiming to control their production. RESULTS: A multi‐response kinetic model was developed within the glucose‐lysine Maillard reaction model system. The concentrations of glucose, lysine, glyoxal (GO), methylglyoxal (MGO), CML, CEL and AAA were quantified at different temperature (100–160 °C) and at different intervals (0–60 min). The experimental data were fitted to the proposed model to calculate kinetic parameters for the corresponding steps. The results indicated that the production of CML was primarily relied on the direct oxidative cleavage of the Amadori product, rather than the reaction between GO and Lys, whereas CEL and AAA were generated through the reaction of MGO with Lys. Significantly, the reaction between α‐dicarbonyl compounds and Lys preferentially generated CML and CEL, resulting in the lower concentrations of AAA compared to CML and CEL. CONCLUSION: The multi‐response kinetic model developed in the present study can be applied well to the Maillard reaction. The relationship between the formation mechanisms of CML, CEL and AAA is also explained. © 2024 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

In recent years, stem cell therapy has become a pivotal component of regenerative medicine. Stem cells, characterized by their self-renewal capacity and multidirectional differentiation potential, can be isolated from a variety of biological tissues, including adipose tissue, bone marrow, the umbilical cord, and the placenta. The classic applications of stem cells include human pluripotent stem cells (hPSCs) and mesenchymal stem cells (MSCs). However, numerous factors can influence the normal physiological function of stem cells. For instance, in diabetes mellitus, advanced glycation end products (AGEs) accumulate in the extracellular matrix (ECM), impairing the physiological function of stem cells. These substances are closely associated with aging and the progression of numerous degenerative diseases. AGEs can create an environment that is detrimental to the normal physiological functions of stem cells. By binding to the primary cellular receptor for advanced glycation end products (RAGE), AGEs disrupt the physiological activities of stem cells. The binding of RAGE to various ligands triggers the activation of downstream signaling pathways, contributing to the pathophysiological development of diabetes, aging, neurodegenerative diseases, and cancer. Therefore, there is an urgent need for comprehensive research on the impact of AGEs on stem cells, which could provide new insights into the therapeutic application of stem cells in regenerative medicine. [ABSTRACT FROM AUTHOR]

Isothiocyanates (ITCs), found in edible plants such as cruciferous vegetables, are a group of reactive organo-sulfur phytochemicals produced by the hydrolysis of precursors known as glucosinolates. ITCs have been studied extensively both in vivo and in vitro to define their therapeutic potential for the treatment of chronic health conditions. Therapeutically, they have shown an intrinsic ability to inhibit oxidative and inflammatory phenotypes to support enhanced health. This review summarizes the current evidence supporting the observation that the antioxidant and anti-inflammatory activities of ITCs temper the pathogenic effects of a group of reactive metabolites called advanced glycation end products (AGEs). AGE exposure has significantly increased across the lifespan due to health risk factors that include dietary intake, a sedentary lifestyle, and comorbid conditions. By contributing to a chronic cycle of inflammatory stress through the aberrant activation of the transmembrane receptor for AGE (RAGE), increased AGE bioavailability is associated with chronic disease onset, progression, and severity. This review debates the potential molecular mechanisms by which ITCs may inhibit AGE bioavailability to reduce RAGE-mediated pro-oxidant and pro-inflammatory phenotypes. Bringing to light the molecular impact that ITCs may have on AGE biogenesis may stimulate novel intervention strategies for reversing or preventing the impact of lifestyle factors on chronic disease risk. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Food Safety & Quality is the property of Journal of Food Safety & Quality Editorial Department and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Advanced glycation end products (AGEs) are produced in foods during their thermal treatment through routes like the Maillard reaction. They have been linked to various health issues such as diabetes, neurodegenerative disorders, and cardiovascular diseases. There are multiple pathways through which AGEs can form in foods and the body. Therefore, this review work aims to explore multiple formation pathways of AGEs to gain insights into their generation mechanisms. Furthermore, this review work has analyzed the recent trends in the detection and inhibition of AGEs in food matrices. It can be highlighted, based on the surveyed literature, that UHPLC-Orbitrap-Q-Exactive-MS and UPLC-ESI-MS/MS can produce highly sensitive results with a low limit of detection levels for AGEs in food matrices. Moreover, various works on inhibitory agents like spices, herbs, fruits, vegetables, hydrocolloids, plasma-activated water, and probiotic bacteria were assessed for their capacity to suppress the formation of AGEs in food products and simulation models. Overall, it is essential to decrease the occurrence of AGEs in food products, and future scope might include studying the interaction of macromolecular components in food products to minimize the production of AGEs without sacrificing the organoleptic qualities of processed foods. [ABSTRACT FROM AUTHOR]

The prevalence of high-sugar diets and unhealthy habits exacerbates the production of advanced glycation end products (AGEs) in the body. When AGEs excessively accumulate in the body, they accelerate the aging process while directly or indirectly causing other complications that can seriously damage the body. Prevention of glycation damage is gaining increasing attention; however, a systematic strategy to combat glycation and specific glycation inhibitors is still lacking. By analyzing the process of glycation damage, we suggest that glycation damage can be mitigated by the inhibition of AGEs production, binding to proteins, and binding to receptors for advanced glycation end products, as well as the attenuation of downstream linkage reactions. This review summarizes the process of glycation damage. According to each step of the process, the review presents the corresponding anti-glycation strategies. Based on recent anti-glycation studies, we support the fabrication of glycation inhibitors by using natural plant products and fermentation products of lactic acid bacteria that partially exhibit anti-glycation properties. This review summarizes the mechanisms by which these dietary ingredients perform anti-glycation functions, providing relevant research evidence. We hope that this review will support and assist subsequent investigations in the development of anti-glycation inhibitors. [ABSTRACT FROM AUTHOR]

Background: Male factors contribute to approximately 50% of infertile couples. However, obvious causes remain unknown in many cases. This observational study aimed to investigate the associations of clinical and lifestyle parameters with sperm parameters. Methods: This study enrolled 41 men in infertile couples without obvious causes for male infertility from July 2023 to April 2024. Semen samples were evaluated for sperm number, motility, DNA fragmentation, and oxidative stress (OS) marker oxidation–reduction potential (ORP). Blood samples were analyzed for biochemical parameters, including advanced glycation end products (AGEs), and systemic OS marker diacron-reactive oxygen metabolites (d-ROMs). Skin-accumulated AGE levels were identified with an autofluorescence method. Lifestyle factors were assessed with a lifestyle questionnaire. Results: Most of the participants were under 40 years old and non-obese with normal clinical parameters. Multiple regression analyses revealed that body mass index, serum d-ROMs, and semen ORP levels were independently associated with decreased sperm number. Additionally, serum zinc and semen ORP levels were associated with sperm motility. Furthermore, serum zinc and high-density lipoprotein cholesterol levels were associated with sperm progressive motility and DNA fragmentation, respectively. The rest of the clinical and lifestyle factors, including skin-accumulated and serum AGE levels, were not correlated with any sperm parameters. Furthermore, serum d-ROM and semen ORP levels were not correlated with each other or any of the clinical and lifestyle factors. Conclusions: Our present study indicates that both systemic and local OS may be independently involved in sperm abnormality in healthy men without obvious causes for male infertility. [ABSTRACT FROM AUTHOR]

Advanced glycation end products (AGEs) have attracted interest as therapeutic targets for neurodegenerative diseases. AGEs facilitate the onset and progression of various neurogenerative disorders due to their ability to promote cross-linking and aggregation of proteins. Further, the interaction between AGEs and receptor for AGEs (RAGE) activates neuroinflammatory, oxidative stress and excitotoxicity processes that contribute to neuronal cell death. Various therapeutic efforts have targeted lowering the production of AGEs, inhibiting RAGE or inhibiting some of the processes of the AGE-RAGE axis as potential treatments for these disorders. Whereas effective treatments for many neurodegenerative disorders remain elusive, such efforts offer promise to slow the progression of diseases such as Alzheimer’s disease (AD), Parkinson’s disease (PD) and Huntington’s disease (HD). [ABSTRACT FROM AUTHOR]

Background: Glomerular fibrosis is a tissue damage that occurs within the kidneys of chronic and diabetic kidney disease patients. Effective treatments are lacking, and the mechanism of glomerular damage reversal is poorly understood. Methods: A mathematical model suitable for hypothesis-driven systems pharmacology of glomerular fibrosis in diabetes was developed from a previous model of interstitial fibrosis. The adapted model consists of a system of ordinary differential equations that models the complex disease etiology and progression of glomerular fibrosis in diabetes. Results: Within the scope of the mechanism incorporated, advanced glycation end products (AGE)—matrix proteins that are modified due to high blood glucose—were identified as major contributors to the delay in the recovery from glomerular fibrosis after glucose control. The model predicted that inhibition of AGE production is not an effective approach for accelerating the recovery from glomerular fibrosis. Further, the model predicted that treatment breaking down accumulated AGE is the most productive at reversing glomerular fibrosis. The use of the model led to the identification that glucose control and aminoguanidine are ineffective treatments for reversing advanced glomerular fibrosis because they do not remove accumulated AGE. Additionally, using the model, a potential explanation was generated for the lack of efficacy of alagebrium in treating advanced glomerular fibrosis, which is due to the inability of alagebrium to reduce TGF- β. Impact: Using the mathematical model, a mechanistic understanding of disease etiology and complexity of glomerular fibrosis in diabetes was illuminated, and then hypothesis-driven explanations for the lack of efficacy of different pharmacological agents for treating glomerular fibrosis were provided. This understanding can enable the development of more efficacious therapeutics for treating kidney damage in diabetes. [ABSTRACT FROM AUTHOR]

BACKGROUND RESULTS CONCLUSION Advanced glycation end products (AGEs) are compounds formed by non‐enzymatic processes in the Maillard reaction and can cause various chronic diseases. This study explores the AGE formation process in a glucose–amino acid system under both wet‐ and dry‐heating conditions, and analyzes the effect of cysteine in AGE formation.Under wet‐heating conditions, Nε‐carboxymethyllysine (CML) and Nε‐carboxyethyllysine (CEL) concentrations rose for the initial 90 min and subsequently declined after 120 min; after 90 min of heating, the maximum yields in the absence of cysteine were 1151.04 ± 14.01 and 3386.90 ± 26.55 ng mL−1, respectively. The concentration of pyrraline (Pyr) increased after 30 min and then decreased after 60 min with a maximum yield of 777.68 ± 23.36 ng mL−1. However, in dry‐heating models, the AGE concentrations consistently increased with increasing heating time; the maximum yields for CML, CEL and Pyr were 468.66 ± 10.96, 1993.57 ± 14.81 and 1085.74 ± 58.06 ng mL−1, respectively. The addition of cysteine showed an inhibitory effect on AGE formation, especially for Pyr in the dry‐heating model, with inhibition rates ranging from 17.14% to 95.60%.Although wet‐heating models produced more CML and CEL, they produced less Pyr than dry‐heating models. The AGE formation in wet‐heating models positively correlated with the reaction rate; however, the dry‐heating reaction demonstrated a more complex relationship between reaction rate and reaction protocol. Moreover, cysteine exhibited a significant inhibitory effect on AGE production, and the degree of inhibition was proportional to the cysteine concentration. This study provides important insights into the mechanisms for AGE formation under various heating conditions, such as those representing baking (dry‐heating) and steaming conditions (wet‐heating). © 2024 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Background: Existing studies predominantly focused on the relationship between periodontitis and type 2 diabetes mellitus (T2DM), with limited data on the association between periodontitis and type 1 diabetes mellitus (T1DM). This study aimed to examine the impact of T1DM and periodontitis on the subgingival microbiome and levels of advanced glycation end-products (AGEs). Methods: Samples were collected from four groups: T1DM, periodontitis (P), T1DM with periodontitis (DP), and periodontally and systemically healthy controls (Control). Subgingival microbiome composition and AGE levels were assessed using 16S rRNA gene sequencing and enzyme-linked immunosorbent assay (ELISA), respectively. Correlations between clinical indexes, microbiome composition, and AGEs were analyzed using Spearman correlation coefficient. Results: Alpha and beta diversity analyses revealed significant differences in bacterial diversity between the DP group and other groups. Linear discriminant analysis effect size (LEfSe) analysis identified specific bacteria influencing each group: Acinetobacter, Leptotrichia, Raoultibacter, and Veillonella in the Control group; Tannerella, Porphyromonas, Filifactor, and Treponema in the P group; and Lactobacillales in T1DM individuals. Prevotella and Selenomonas were notably influential in the DP group. PICRUSt2 analysis showed pathways alterations were concentrated in cell motility, translation, cell growth and death and metabolism in the DP and P groups. Spearman correlation analysis indicated a positive correlation between AGEs and periodontitis or diabetes-related parameters and AGEs were positively correlated with Haemophilus and Arachnia. Conclusions: The findings suggested that the composition and function of the subgingival microbiome in the P group with or without T1DM were significantly different. Additionally, AGEs were involved in the development of periodontitis even in absence of hyperglycemia. [ABSTRACT FROM AUTHOR]

An approach to the synthesis of pyridoxine azo derivatives based on aminophenols was developed. 52 new pyridoxine derivatives were synthesized. An in vitro study of antiglycation properties showed that most of the prepared pyridoxine azo derivatives (IC50 = 10–191 μM) significantly exceed the phase I-II clinical trials drugs aminoguanidine (IC50 = 526 μM) and pyridoxamine (IC50 = 834 μM) in their activity. Some of the obtained compounds also have high antioxidant activity and effectively inhibit lipid peroxidation. [ABSTRACT FROM AUTHOR]

Simple Summary: Physiological equilibrium preservation is essential for an animal's survival, and any event that may disturb this equilibrium is defined as a stressor. Here, we aimed to evaluate the effect of scratch brushes and stages as an environmental enrichment to reduce stress in dairy goats. Twenty-four mixed-breed goats were divided into two groups according to common physiological conditions in breeding farms: milking and dry (milk-producing and non-milk-producing, respectively). Blood was sampled ten days post-exposure to enrichment treatment or not (control). Following the enrichment, we observed a reduction in dry goats' oxidative stress products and their binding protein, transferrin. In contrast, no change in these products, along with an increase in transferrin levels, was observed in milking goats. Moreover, the anti-stress hormones, oxytocin and serotonin, levels changed differentially between the dry- and milking-goat groups. Additionally, gene expression of immune-related and antioxidant molecules in white blood cells isolated from the goats' blood presented the same pattern: down-regulation in dry or up-regulation in milking goats. In conclusion, a reliable methodology was developed for measuring husbandry stress in goats. Current environmental enrichment produced different responsiveness in goats correlated to their physiological status: beneficial effect in dry goats, detrimental effect in milking goats. Homeostasis preservation is essential for animal survival, and any event that causes a disturbance in homeostasis is defined as a stressor. Here, we aimed to evaluate the effect of scratch brushes and stages as an environmental enrichment to alleviate stress in dairy goats. Twenty-four mixed-breed goats were divided into two groups according to common physiological conditions in breeding farms: milking and dry (milk-producing and non-milk-producing, respectively). Ten days after exposure to environmental enrichment treatment or not (control), blood was sampled. Following the enrichment, we observed a reduction in reactive oxidative stress metabolites, advanced glycation end products (AGEs), and their binding protein (transferrin) in the dry goats, as determined by an ELISA. In contrast, no change in AGEs, along with an increase in transferrin levels, was observed in the milking goats. Moreover, oxytocin levels decreased in the dry and increased in the milking goats, while serotonin levels increased in the dry and remained unchanged in the milking goats. Additionally, gene expression of the cytokines, IL-6 and IL-1ß, and anti-oxidative proteins, lysozyme and transferrin (in peripheral blood leukocytes), as determined by qPCR, presented the same pattern: down-regulation in the dry or up-regulation in the milking goats. In conclusion, a reliable methodology was developed for measuring husbandry stress in goats and to improve dairy goats' husbandry practice. Current environmental enrichment produced different responsiveness in goats correlated to their physiological status: beneficial effect in dry goats, detrimental effect in milking goats. [ABSTRACT FROM AUTHOR]

Collagen fibrils are fundamental to the mechanical strength and function of biological tissues. However, they are susceptible to changes from non-enzymatic glycation, resulting in the formation of advanced glycation end-products (AGEs) that are not reversible. AGEs accumulate with aging and disease and can adversely impact tissue mechanics and cell-ECM interactions. AGE-crosslinks have been related, on the one hand, to dysregulation of collagen fibril stiffness and damage and, on the other hand, to altered collagen net surface charge as well as impaired cell recognition sites. While prior studies using Kelvin probe force microscopy (KPFM) have shown the effect glycation has on collagen fibril surface potential (i.e., net charge), the combined effect on individual and isolated collagen fibril mechanics, hydration, and surface potential has not been documented. Here, we explore how methylglyoxal (MGO) treatment affects the mechanics and surface potential of individual and isolated collagen fibrils by utilizing atomic force microscopy (AFM) nanoindentation and KPFM. Our results reveal that MGO treatment significantly increases nanostiffness, alters surface potential, and modifies hydration characteristics at the collagen fibril level. These findings underscore the critical impact of AGEs on collagen fibril physicochemical properties, offering insights into pathophysiological mechanical and biochemical alterations with implications for cell mechanotransduction during aging and in diabetes. Collagen fibrils are susceptible to glycation, the irreversible reaction of amino acids with sugars. Glycation affects the mechanical properties and surface chemistry of collagen fibrils with adverse alterations in biological tissue mechanics and cell-ECM interactions. Current research on glycation, at the level of individual collagen fibrils, is sparse and has focused either on collagen fibril mechanics, with contradicting evidence, or surface potential. Here, we utilized a multimodal approach combining Kelvin probe force (KPFM) and atomic force microscopy (AFM) to examine how methylglyoxal glycation induces structural, mechanical, and surface potential changes on the same individual and isolated collagen fibrils. This approach helps inform structure-function relationships at the level of individual collagen fibrils. [Display omitted] [ABSTRACT FROM AUTHOR]

Copyright of Shipin Kexue/ Food Science is the property of Food Science Editorial Department and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

It is of great significance to search for advanced glycation end products (AGEs) inhibitors with high activity and low side effects from food-borne natural products for the prevention and improvement of related diseases. To elucidate the inhibitory effect of tectoridin on the generation of advanced glycation end products (AGEs), the glycation system of bovine serum protein (BSA)-methylglyoxal (MGO) was established, the effects of tectoridin on the AGEs inhibition, glycation degree, protein oxidation products, protein cross-linking and MGO trapping were investigated by spectroscopy, SDS-PAGE, HPLC, LTQ-Orbitrap MS, and molecular docking. The results showed that tectoridin increased the content of lysine and thiol, reduced the contents of protein carbonylation and protein oxidation products, alleviated the cross-linking structure of BSA. The mono-MGO adduct of tectoridin was identified in the incubation of MGO with tectoridin. Molecular docking results showed that hydrogen bonding and hydrophobic interactions were the major driving forces for stabilizing tectoridin-BSA complexes. Tectoridin was a promising natural AGEs inhibitor. Mechanism analysis revealed that tectoridin alleviated AGEs formation by trapping MGO to form mono-tectoridin-MGO complexes and forming stable tectoridin-BSA complexes. These findings would provide the theoretical basis for the development of tectoridin as a novel, natural and effective inhibitor of AGEs.

Reactive carbonyl species (RCSs) are a class of active aldehydes and ketones. RCSs are formed in the body through a serious of reactions such as lipid oxidation and glycolysis as well as through lipid oxidation and the Maillard reaction during food processing. RCSs are usually kept at a low concentration level in the body, while high level of these substances can cause diseases in the body. The intake of RCSs by the human body mainly comes from processed foods. Furthermore, RCSs can induce the formation of other hazards during food processing. Therefore, controlling the formation of RCSs in foods is crucial for nutritional health. This article reviews the formation and biological activity of RCSs as well as their impacts on the formation of chemical hazards such as heterocyclic amines, advanced glycation end products (AGEs), acrylamide, and polycyclic aromatic hydrocarbons in food processing. The aim of this study is to provide a reference for the safety control of RCSs during food processing.

Abstract Background Existing studies predominantly focused on the relationship between periodontitis and type 2 diabetes mellitus (T2DM), with limited data on the association between periodontitis and type 1 diabetes mellitus (T1DM). This study aimed to examine the impact of T1DM and periodontitis on the subgingival microbiome and levels of advanced glycation end-products (AGEs). Methods Samples were collected from four groups: T1DM, periodontitis (P), T1DM with periodontitis (DP), and periodontally and systemically healthy controls (Control). Subgingival microbiome composition and AGE levels were assessed using 16S rRNA gene sequencing and enzyme-linked immunosorbent assay (ELISA), respectively. Correlations between clinical indexes, microbiome composition, and AGEs were analyzed using Spearman correlation coefficient. Results Alpha and beta diversity analyses revealed significant differences in bacterial diversity between the DP group and other groups. Linear discriminant analysis effect size (LEfSe) analysis identified specific bacteria influencing each group: Acinetobacter, Leptotrichia, Raoultibacter, and Veillonella in the Control group; Tannerella, Porphyromonas, Filifactor, and Treponema in the P group; and Lactobacillales in T1DM individuals. Prevotella and Selenomonas were notably influential in the DP group. PICRUSt2 analysis showed pathways alterations were concentrated in cell motility, translation, cell growth and death and metabolism in the DP and P groups. Spearman correlation analysis indicated a positive correlation between AGEs and periodontitis or diabetes-related parameters and AGEs were positively correlated with Haemophilus and Arachnia. Conclusions The findings suggested that the composition and function of the subgingival microbiome in the P group with or without T1DM were significantly different. Additionally, AGEs were involved in the development of periodontitis even in absence of hyperglycemia.

Advanced Glycation End (AGE) products are one such factor that accumulates during aging and age-related diseases. However, how exogenous AGE compounds cause aging is an area that needs to be explored. Specifically, how an organ undergoes aging and aging-related phenomena that need further investigation. The intestine is the most exposed area to food substances. How AGEs affect the intestine in terms of aging need to be explored. Drosophila melanogaster, a well-known model organism, is used to decode aging and age-associated phenomena. In this study, we fed Ribose induced Advanced Glycation End products (Rib-AGE) to D. melanogaster to study the aging mechanism. The Rib-AGE-induced aging was checked in Drosophila. We found a series of changes in Rib-AGE-fed flies. Reactive oxygen species (ROS) and nitric oxide species (NOs) were higher in the Rib-AGE-fed flies, and the antioxidant level was lower. The intestinal permeability was altered. The microorganism load was higher inside the gut. The structural arrangement of the gut’s microfilament was found to be damaged, and the nuclear shape was found to be irregular. Cell death within the gut was elevated in comparison to control. The food intake was found to be reduced. The relative mRNA expression of the Sirtuin 2 and Sirtuin 6 gene of D. melanogaster was downregulated in Rib-AGE-fed flies compared to the control. All these findings strongly suggest that Rib-AGE accelerates aging and age-related disorders in D. melanogaster. [ABSTRACT FROM AUTHOR]

Abstract Background Increasing evidence supports the role of advanced glycation end products (AGEs) in atherosclerosis in both diabetic and non-diabetic patients, suggesting that therapeutic strategies targeting AGEs may offer potential benefits in this population. The Mediterranean diet is associated with improved biomarkers and anthropometric measurements related with atherosclerosis in addition to its ability to modulate AGE metabolism. Our aim was to determine whether the reduction in atherosclerosis progression (measured by changes in intima-media thickness of both common carotid arteries (IMT-CC)), observed after consumption of a Mediterranean diet compared to a low-fat diet, is associated with a modulation of circulating AGE levels in patients with coronary heart disease (CHD). Methods 1002 CHD patients were divided in: (1) Non-increased IMT-CC patients, whose IMT-CC was reduced or not changed after dietary intervention and (2) Increased IMT-CC patients, whose IMT-CC was increased after dietary intervention. Serum AGE levels (methylglyoxal–MG and Nε-Carboxymethyllysine-CML) and parameters related to AGE metabolism (AGER1 and GloxI mRNA and sRAGE levels) and reduced glutathione (GSH) levels were measured before and after 5-years of dietary intervention. Results The Mediterranean diet did not affect MG levels, whereas the low-fat diet significantly increased them compared to baseline (p = 0.029), leading to lower MG levels following the Mediterranean diet than the low-fat diet (p

Abstract Background In populations with chronic disease, skin autofluorescence (SAF), a measure of long-term fluorescent advanced glycation end-products (AGEs) accumulation in body tissues, has been associated with vascular endothelial function, measured using flow-mediated dilation (FMD). The primary aim of this study was to quantify the relationship between endothelial function and tissue accumulation of AGEs in adults from the general population to determine whether SAF could be used as a marker to predict early impairment of the endothelium. Methods A cross-sectional study was conducted with 125 participants (median age: 28.5 y, IQR: 24.4–36.0; 54% women). Endothelial function was measured by fasting FMD. Skin AGEs were measured as SAF using an AGE Reader. Participant anthropometry, blood pressure, and blood biomarkers were also measured. Associations were evaluated using multivariable regression analysis and were adjusted for significant covariates. Results FMD was inversely correlated with SAF (ρ = -0.50, P

Abstract Advanced glycation end products (AGEs) are a diverse range of compounds that are formed when free amino groups of proteins, lipids, and nucleic acids are carbonylated by reactive carbonyl species or glycosylated by reducing sugars. Hyperglycemia in patients with diabetes can cause an overabundance of AGEs. Excess AGEs are generally acknowledged as major contributing factors to the development of diabetic complications because of their ability to break down the extracellular matrix directly and initiate intracellular signaling pathways by binding to the receptor for advanced glycation end products (RAGE). Inflammation and oxidative stress are the two most well-defined pathophysiological states induced by the AGE–RAGE interaction. In addition to oxidative stress, AGEs can also inhibit antioxidative systems and disturb iron homeostasis, all of which may induce ferroptosis. Ferroptosis is a newly identified contributor to diabetic complications. This review outlines the formation of AGEs in individuals with diabetes, explores the oxidative damage resulting from downstream reactions of the AGE-RAGE axis, and proposes a novel connection between AGEs and the ferroptosis pathway. This study introduces the concept of a vicious cycle involving AGEs, oxidative stress, and ferroptosis in the development of diabetic complications.

Abstract Background The AGEs levels in tissues of diabetics and elderly tend to be higher than in normal individuals. This study aims to determine the effects of AGEs on Achilles tendon repair. Materials and methods Thirty-six male eight-week-old Sprague Dawley rats were selected in this study. The rats were randomly divided into two experimental groups and a control group after the transection of the Achilles tendon. During the tendon repair, the experimental groups were injected around the Achilles tendon with 350mmol/L (low dose group) and 1000mmol/L (high dose group) D-ribose 0.2 ml respectively to increase the AGEs level, while in the control group were given the same amount of PBS. The injections were given twice a week for six weeks. Collagen-I, TNF-α, and IL-6 expression in the healed Achilles tendon was assessed. Additionally, macroscopic, pathological, and biomechanical evaluations of Achilles tendon repair were conducted. Results The repaired Achilles tendons in the high dose group showed severe swelling and distinctive adhesions. The histological score went up with the increase of the AGEs in the Achilles tendon (p

Abstract Background Nonalcoholic fatty liver disease (NAFLD) shares common pathogenic mechanisms of type 2 diabetes mellitus (T2DM) with upregulated advanced glycation end products (AGEs). Here, we aim to investigate the effect of FPS-ZM1, an inhibitor for receptor for AGEs (RAGE), on lipid deposition in the liver of mice. Methods KK-Ay mice were used as models of T2DM with NAFLD, while C57BL/6j mice were controls. Additionally, KK-Ay mice were treated with DMSO (with a concentration of 1%), with or without FPS-ZM1 (3 mg/kg/day, i.p). Lipid deposition in hepatocytes was observed using oil red O stain. Levels of AGEs and RAGE were measured. Sterol regulatory element-binding protein-1c (SREBP-1c), as well as nuclear factor κB p65 (p65 nfκb) and mitogen-activated protein kinase p38 (p38 MAPK), were also detected. Results Lipid deposition is increased in the hepatocytes of KK-Ay mice compared to C57BL/6j mice. In addition, not only were the levels of AGEs elevated in plasma, but also the levels of RAGE in liver tissue. Although total SREBP-1c levels did not change in the liver of diabetic mice, mature SREBP-1c increased in KK-Ay mice with diabetes mellitus. Moreover, diabetic mice showed increased levels of phosphorylated-p65 nfκb (p-p65 nfκb) and phosphorylated-p38 MAPK (p-p38 MAPK). On the contrary, FPS-ZM1 decreased lipid deposition in liver cells, as well as mature SREBP-1c, p-p65 nfκb and p-p38 MAPK levels in liver tissue. Conclusion Generally, FPS-ZM1 may attenuate lipid deposition in hepatocytes of diabetic mice via SREBP-1c down-regulation. This may depend on the downregulation of p65 nfκb and p38 MAPK phosphorylation.

Abstract Background Accumulation of advanced glycation end products (AGEs) has contribution in development of Alzheimer’s disease (AD), vascular dementia (VAD), and mild cognitive impairment (MCI). AGEs activate several signaling pathways that have roles in development of those diseases via receptor for advanced glycation end product (RAGE), this receptor has its soluble form called sRAGE which has ability to bind AGEs but could not induce molecular signaling. Based on this property, sRAGE could work as RAGE decoy and prevent pathological effect of AGEs accumulation. This meta-analysis is aimed to evaluate correlation between sRAGE plasma level and risk of AD, VAD, and MCI. Methods Standardized mean difference with 95% coincidence interval was used as effect size. Inverse variance was used as analysis method with random effect model. Egger test and funnel plot were used to assess publication bias. Results We found 424 articles through database searching. Among those articles, 15 articles that fulfilled our eligibility criteria. After selection based on inclusion and exclusion criteria, only 5 articles were included in this meta-analysis. Our analysis found that AD and VAD patients have lower levels of plasma sRAGE when compared to healthy control. Significant correlation between low sRAGE plasma level and MCI was not found. However, publication bias is found in MCI group. Publication bias of VAD group could not be assessed due to limited number of studies. Conclusions Here, we show inverse relationship between sRAGE and the incidence of AD alongside VAD suggests that lower sRAGE plasma levels may be associated with a higher incidence of AD and VAD. However, some limitations in sample size and minimal studies may introduce bias into our results.

Abstract Advanced glycation end products (AGEs) are the final products of the Maillard reaction, formed through the interaction of carbohydrates and proteins. Reactive dicarbonyl compounds such as methylglyoxal (MGO) serve as precursors for AGEs formation. Elevated levels of MGO/AGEs are observed in conditions like obesity, polycystic ovarian syndrome (PCOS), and diabetes, negatively impacting oocyte development. Previous studies have shown that hydrogen sulfide, a gasotransmitter with anti-AGEs effects, is produced in a process influenced by vitamin B6. R-α-lipoic acid (ALA) inhibits protein glycation and AGEs formation while stimulating glutathione (GSH) production. Taurine mitigates oxidative stress and acts as an anti-glycation compound, preventing in vitro glycation and AGEs accumulation. This study aimed to explore the ameliorative effects of a micronutrient support (Taurine, ALA and B6: TAB) on mouse oocytes challenged with MGO. Our results indicate that MGO reduces oocyte developmental competence, while TAB supplementation improves maturation, fertilization, and blastocyst formation rates. TAB also restores cell lineage allocation, redox balance and mitigates mitochondrial dysfunction in MGO-challenged oocytes. Furthermore, cumulus cells express key enzymes in the transsulfuration pathway, and TAB enhances their mRNA expression. However, TAB does not rescue MGO-induced damage in denuded oocytes, emphasizing the supportive role of cumulus cells. Overall, these findings suggest that TAB interventions may have significant implications for addressing reproductive dysfunctions associated with elevated MGO/AGEs levels. This study highlights the potential of TAB supplementation in preserving the developmental competence of COCs exposed to MGO stress, providing insights into mitigating the impact of dicarbonyl stress on oocyte quality and reproductive outcomes.

Advanced glycation end products (AGEs), the products of non-enzymatic browning reactions between the active carbonyl groups of reducing sugars and the free amines of amino acids, are largely considered oxidative derivatives resulting from diabetic hyperglycemia, which are further recognized as a potential risk for insulin resistance (IR) and type 2 diabetes (T2D). The accumulation of AGEs can trigger numerous negative effects such as oxidative stress, carbonyl stress, inflammation, autophagy dysfunction and imbalance of gut microbiota. Recently, studies have shown that cereal polyphenols have the ability to inhibit the formation of AGEs, thereby preventing and alleviating T2D. In the meanwhile, phenolics compounds could produce different biological effects due to the quantitative structure activity-relationship. This review highlights the effects of cereal polyphenols as a nonpharmacologic intervention in anti-AGEs and alleviating T2D based on the effects of oxidative stress, carbonyl stress, inflammation, autophagy, and gut microbiota, which also provides a new perspective on the etiology and treatment of diabetes. [ABSTRACT FROM AUTHOR]

Advanced glycation end products (AGEs) with multiple structures are formed at the sites where carbonyl groups of reducing sugars bind to free amino groups of proteins through the Maillard reaction. In recent years, it has been highlighted that the accumulation of AGEs, which are generated when carbonyl compounds produced in the process of sugar metabolism react with proteins, is involved in various diseases. Creatine is a biocomponent that is homeostatically present throughout the body and is known to react nonenzymatically with α-dicarbonyl compounds. This study evaluated the antiglycation potential of creatine against methylglyoxal (MGO), a glucose metabolite that induces carbonyl stress with formation of AGEs in vitro. Further, to elucidate the mechanism of the cytoprotective action of creatine, its effect on the accumulation of carbonyl proteins in the cells and the MGO-induced cellular damage were investigated using neuroblastoma cells. The results revealed that creatine significantly inhibits protein carbonylation by directly reacting with MGO, and creatine added to the culture medium suppressed MGO-derived carbonylation of intracellular proteins and exerted a protective effect on MGO-induced cytotoxicity. These findings suggest that endogenous and supplemented creatine may contribute to the attenuation of carbonyl stress in vivo. [ABSTRACT FROM AUTHOR]

Objective: We aimed to investigate the relationship between advanced glycation end product (AGE) levels in patients with saphenous vein graft (SVG) failure and in patients without SVG failure. Subjects and Methods: In our study, 55 patients with a history of previous coronary artery bypass grafting (CABG) surgery, who subsequently underwent coronary angiography for any reason and were found to have either SVG occlusion or significant lesions, were included as study patients. Additionally, 55 patients who have had CABG surgery without SVG failure for at least 1 year served as the control group. AGE values of the patients were measured using the skin autofluorescence method. Results: In our study results, we observed a significant difference in AGE levels between the two groups of patients with similar demographic characteristics (SVG failure groups AGE 3.2 [2.8–3.6] vs. control groups AGE 2.4 [2.1–2.7] p < 0.001). In the receiver operating characteristic curve analysis, we determined the ability of AGE levels to detect SVG failure with an area under the curve of 0.869. We found that in patients with AGE >3, it could detect SVG failure with a sensitivity of 70.9% and a specificity of 87.3%. Conclusions: Our results demonstrate that AGE levels can predict SVG failure risk inexpensively, easily, and quickly. [ABSTRACT FROM AUTHOR]

Posterior capsule opacification (PCO) is a common complication after cataract surgery. Residual lens epithelial cells (LECs) on the anterior lens capsule, after cataract surgery, migrate to the posterior lens capsule and undergo transdifferentiation into myofibroblast‐like cells. Those cells synthesize excessive amounts of extracellular matrix and contribute to fibrosis during PCO. Cellular senescence, a phenomenon that increases with aging, has been implicated in several fibrotic diseases. Here, we have investigated the prevalence of senescent LECs within the lens posterior capsule and the ability of advanced glycation end products (AGEs) in lens capsules to induce senescence, contributing to PCO. Aged lens capsules from pseudophakic human cadaver eyes showed the presence of senescent LECs. In human capsular bags, LECs showed an age‐dependent increase in senescence after 28 days of culture. Human LECs cultured on aged lens capsules for 3 days underwent senescence; this effect was not seen in LECs cultured on young lens capsules. Human LECs cultured on an AGE‐modified extracellular matrix (ECM‐AGEs) showed an AGE‐concentration‐dependent increase in the expression of senescence markers and reactive oxygen species (ROS) levels. Treatment with a RAGE antagonist and ROS inhibitor reduced the expression of senescence and fibrotic markers. Additionally, conditioned media from ECM‐AGEs‐treated cells induced the expression of fibrotic markers in naïve LECs. Together, these suggest that AGEs in the capsule induce senescence of LECs, which triggers the mesenchymal transition of neighboring non‐senescent LECs and contributes to PCO. [ABSTRACT FROM AUTHOR]

Advanced glycation endproducts (AGEs) contribute to cellular damage of various pathologies, including kidney diseases. Acute kidney injury (AKI) represents a syndrome seldom characterized by a single, distinct pathophysiological cause. Rhabdomyolysis-induced acute kidney injury (RIAKI) constitutes roughly 15% of AKI cases, yet its underlying pathophysiology remains poorly understood. Using a murine model of RIAKI induced by muscular glycerol injection, we observed elevated levels of AGEs and the AGE receptor galectin-3 (LGALS3) in the kidney. Immunofluorescence localized LGALS3 to distal nephron segments. According to transcriptomic profiling via next-generation sequencing, RIAKI led to profound changes in kidney metabolism, oxidative stress, and inflammation. Cellular stress was evident in both proximal and distal tubules, as shown by kidney injury markers KIM-1 and NGAL. However, only proximal tubules exhibited overt damage and apoptosis, as detected by routine morphology, active Caspase-3, and TUNEL assay, respectively. In vitro, distal convoluted tubule (DCT) cells challenged with AGEs underwent apoptosis, which was markedly enhanced by Lgals3 siRNA treatment. Thus, in RIAKI, the upregulation of LGALS3 may protect the distal nephron from AGE-mediated damage, while proximal tubules lacking LGALS3 stay at risk. Thus, stimulating LGALS3 in the proximal nephron, if achievable, may attenuate RIAKI. [ABSTRACT FROM AUTHOR]

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Background: Advanced glycation end products (AGEs), a group of food processing byproducts, have been implicated in the development of various diseases. However, the relationship between circulating AGEs and sleep disorders remains uncertain. Methods: This cross-sectional study elucidated the association of plasma AGEs with sleep disorders among 1732 Chinese adults who participated in the initial visit (2019–2020) of the Tongji–Shenzhen Cohort (TJSZC). Sleep behavior was assessed using self-reported questionnaires and precise accelerometers. Plasma levels of AGEs, including Nε-(Carboxymethyl)lysine (CML), Nε-(Carboxyethyl)lysine (CEL), and Nδ-(5-hydro-5-methyl-4-imidazolone-2-yl)-ornithine (MG-H1), were quantified by ultra-high performance liquid chromatography–tandem mass spectrometry (UPLC-MS/MS). Results: In logistic regression, per IQR increment in individual AGEs was associated with an increased odds ratio of short sleep duration (CML: 1.11 [1.00, 1.23]; CEL: 1.16, [1.04, 1.30]), poor sleep quality (CML: 1.33 [1.10, 1.60]; CEL: 1.53, [1.17, 2.00]; MG-H1: 1.61 [1.25, 2.07]), excessive daytime sleepiness (CML: 1.33 [1.11, 1.60]; MG-H1: 1.39 [1.09, 1.77]), and insomnia (CML: 1.29 [1.05, 1.59]). Furthermore, in weighted quantile sum regression and Bayesian kernel machine regression analyses, elevated overall exposure levels of plasma AGEs were associated with an increased risk of sleep disorders, including short sleep duration, poor sleep quality, excessive daytime sleepiness, and insomnia, with CML being identified as the leading contributor. Insufficient vegetable intake and higher dietary fat intake was associated with an increase in plasma CEL. Conclusions: These findings support a significant association between plasma AGEs and sleep disorders, indicating that AGEs may adversely influence sleep health and reducing the intake of AGEs may facilitate preventing and ameliorating sleep disorders. [ABSTRACT FROM AUTHOR]

High concentrations of advanced glycation end products (AGEs) have been linked to diseases, including diabetic complications. The pathophysiological effects of AGEs are mainly due to oxidative stress and inflammatory processes. Among the proteins most affected by glycation are albumin, the most abundant circulating protein, and collagen, which has a long biological half-life and is abundant in the extracellular matrix. The potential cellular damage caused by AGEs underscores the importance of identifying and developing natural AGE inhibitors. Indeed, despite initial promise, many synthetic inhibitors have been withdrawn from clinical trials due to issues such as cytotoxicity and poor pharmacokinetics. In contrast, natural products have shown significant potential in inhibiting AGE formation. Olea europaea L. leaves, rich in bioactive compounds like oleuropein and triterpenoids, have attracted scientific interest, emphasizing the potential of olive leaf extracts in health applications. This study investigates the anti-glycation properties of two polyphenol-rich extracts (OPA40 and OPA70) and a triterpene-enriched extract (TTP70) from olive leaves. Using in vitro protein glycation methods with bovine serum albumin (BSA)–glucose and gelatin–glucose systems, this study assesses AGE formation inhibition by these extracts through native polyacrylamide gel electrophoresis (N-PAGE) and autofluorescence detection. OPA40 and OPA70 exhibited strong, dose-dependent anti-glycation effects. These effects were corroborated by electrophoresis and further supported by similar results in a gelatin–glucose system. Additionally, TTP70 showed moderate anti-glycation activity, with a synergistic effect of its components. The results support the real possibility of using olive leaf bioproducts in ameliorating diabetic complications, contributing to sustainable bio-economy practices. [ABSTRACT FROM AUTHOR]