Advanced glycation end products in gastric cancer: A promising future.

In this editorial, we delve into the article and offer valuable insights into a crucial aspect of gastric cancer aetiology. Gastric cancer is a malignancy emanating from the epithelial lining of the gastric mucosa and one of the most prevalent forms of cancer worldwide. The development of gastric cancer is associated with multiple risk factors, including Helicobacter pylori infection, advanced age, a diet rich in salt, and suboptimal eating patterns. Despite notable reductions in morbidity and mortality rates, gastric cancer remains a formidable public health concern, impacting patients' lives. Advanced glycation end products (AGEs) are complex compounds arising from nonenzymatic reactions within living organisms, the accumulation of which is implicated in cellular and tissue damage; thus, the levels are AGEs are correlated with the risk of diverse diseases. The investigation of AGEs is of paramount importance for the treatment of gastric cancer and can provide pivotal insights into disease pathogenesis and preventive and therapeutic strategies. The reduction of AGEs levels and suppression of their accumulation are promising avenues for mitigating the risk of gastric cancer. This approach underscores the need for further research aimed at identifying innovative interventions that can effectively lower the incidence and mortality rates of this malignancy.

Metabolic dysfunction-associated steatotic liver disease: A pathophysiology and clinical framework to face the present and the future.

AIMS: This review aims to provide a straightforward conceptual framework for the knowledge and understanding of Metabolic dysfunction-associated steatotic liver disease (MASLD) in the broad spectrum of steatotic liver disease and to point out the need to consider metabolic dysfunction and comorbidities as interrelated factors for a holistic approach to fatty liver disease. DATA SYNTHESIS: MASLD is the new proposed term for steatotic liver disease that replaces the old terminology of non-alcoholic fatty liver disease. This term focused on the relationship between metabolic alteration and hepatic steatosis, reflecting a growing comprehension of the association between metabolic dysfunction and hepatic steatosis. Numerous factors and conditions contribute to the underlying mechanisms, including central obesity, insulin resistance, adiponectin, lipid metabolism, liver function, dietary influences, the composition of intestinal microbiota, and genetic factors. The development of the condition, however, involves a more intricate network of components, such as neurotensin and Advanced Glycation End Products, highlighting the complexity of its pathogenesis. CONCLUSIONS: MASLD must be regarded as a complex clinical problem in which only a holistic approach can win through the coordination of multi-professional and multi-speciality interventions.

Lens capsule advanced glycation end products induce senescence in epithelial cells: Implications for secondary cataracts.

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.

Efficient purification of soluble receptor for advanced glycation end-products from Sus scrofa lung tissue and synthesis of its binding ligand, glycated bovine serum albumin.

A receptor for advanced glycation end products (RAGE) has emerged as a crucial player in various pathological conditions due to its involvement in inflammation and cellular dysfunction. Its soluble isoform, sRAGE, has garnered significant attention for its competitive inhibitory effects and potential therapeutic applications. However, obtaining sRAGE with appropriate glycosylation patterns for binding to glycated proteins has been challenging, often requiring costly expression systems. Here, we present a novel approach for producing and purifying sRAGE from Sus scrofa lungs, bypassing the need for expensive expression systems. Previous protocols for sRAGE extraction faced reproducibility issues due to high viscosity and haemoglobin content of the solution. To address this, we developed a method for selective haemoglobin precipitation using a zinc-containing buffer, enabling purification via various chromatographic methods. Through a combination of chromatographic techniques, we obtained sRAGE in suitable purity, identified using HPLC-MS/MS. Additionally, producing glycated proteins for RAGE receptor activation often involved lengthy protocols or inadequate separation from reactants. Thus, we devised a rapid method for producing and purifying pure BSA glycated with ribose, addressing a critical gap in the field. Functional studies, conducted using Native PAGE, demonstrated the capability of purified proteins to bind to each other.

Peptide-Bound Glycative, AGE and Oxidative Modifications as Biomarkers for the Diagnosis of Alzheimer's Disease-A Feasibility Study.

Background: The diagnosis of Alzheimer's disease (AD) relies on core cerebrospinal fluid (CSF) biomarkers, amyloid beta (Aß) and tau. As the brain is then already damaged, researchers still strive to discover earlier biomarkers of disease onset and the progression of AD. Glycation, advanced glycation end products (AGEs) and oxidative modifications on proteins in CSF mirror the underlying biological mechanisms that contribute to early AD pathology. However, analyzing free AGEs in the body fluids of AD patients has led to controversial results. Thus, this pilot study aimed to test the feasibility of detecting, identifying and quantifying differentially glycated, AGE or oxidatively modified peptides in CSF proteins of AD patients (n = 5) compared to a control group (n = 5). Methods: To this end, we utilized a data-dependent (DDA) nano liquid chromatography (LC) linear ion trap-Orbitrap tandem mass spectrometry (MS/MS) ) approach and database search that included over 30 glycative and oxidative modifications in four search nodes to analyze endogenous modifications on individual peptides. Furthermore, we quantified candidate peptide abundance using LC Quan. Results: We identified 299 sites of early and advanced glycation and 53 sites of oxidatively modified tryptophan. From those, we identified 17 promising candidates as putative biomarkers (receiver operating curve-area under the curve (ROC-AUC) > 0.8), albeit without statistical significance. Conclusions: The potential candidates with higher discrimination power showed correlations with established diagnostic markers, thus hinting toward the potential of those peptides as biomarkers.

Navigating the Intersection of Glycemic Control and Fertility: A Network Perspective.

The rising incidence of metabolic diseases is linked to elevated blood glucose levels, contributing to conditions such as diabetes and promoting the accumulation of advanced glycation end products (AGEs). AGEs, formed by non-enzymatic reactions between sugars and proteins, build up in tissues and are implicated in various diseases. This article explores the relationship between glycemic control and AGE accumulation, focusing on fertility implications. A computational model using network theory was developed, featuring a molecular database and a network with 145 nodes and 262 links, categorized as a Barabasi-Albert scale-free network. Three main subsets of nodes emerged, centered on glycemic control, fertility, and immunity, with AGEs playing a critical role. The transient receptor potential vanilloid 1 (TRPV1), a receptor expressed in several tissues including sperm, was identified as a key hub, suggesting that the modulation of TRPV1 in sperm by AGEs may influence fertility. Additionally, a novel link between glycemic control and immunity was found, indicating that immune cells may play a role in endocytosing specific AGEs. This discovery underscores the complex interplay between glycemic control and immune function, with significant implications for metabolic, immune health, and fertility.

Bixin Combined with Metformin Ameliorates Insulin Resistance and Antioxidant Defenses in Obese Mice.

Bixin (C25H30O4; 394.51 g/mol) is the main apocarotenoid found in annatto seeds. It has a 25-carbon open chain structure with a methyl ester group and carboxylic acid. Bixin increases the expression of antioxidant enzymes, which may be interesting for counteracting oxidative stress. This study investigated whether bixin-rich annatto extract combined with metformin was able to improve the disturbances observed in high-fat diet (HFD)-induced obesity in mice, with an emphasis on markers of oxidative damage and antioxidant defenses. HFD-fed mice were treated for 8 weeks with metformin (50 mg/kg) plus bixin-rich annatto extract (5.5 and 11 mg/kg). This study assessed glucose tolerance, insulin sensitivity, lipid profile and paraoxonase 1 (PON-1) activity in plasma, fluorescent AGEs (advanced glycation end products), TBARSs (thiobarbituric acid-reactive substances), and the activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) in the liver and kidneys. Treatment with bixin plus metformin decreased body weight gain, improved insulin sensitivity, and decreased AGEs and TBARSs in the plasma, liver, and kidneys. Bixin plus metformin increased the activities of PON-1, SOD, CAT, and GSH-Px. Bixin combined with metformin improved the endogenous antioxidant defenses in the obese mice, showing that this combined therapy may have the potential to contrast the metabolic complications resulting from oxidative stress.

Methylglyoxal alters collagen fibril nanostiffness and surface potential.

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. STATEMENT OF SIGNIFICANCE: 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.

HMGB1 derived from lung epithelial cells after cobalt nanoparticle exposure promotes the activation of lung fibroblasts.

We have previously demonstrated that exposure to cobalt nanoparticles (Nano-Co) caused extensive interstitial fibrosis and inflammatory cell infiltration in mouse lungs. However, the underlying mechanisms of Nano-Co-induced pulmonary fibrosis remain unclear. In this study, we investigated the role of high-mobility group box 1 (HMGB1) in the epithelial cell-fibroblast crosstalk in Nano-Co-induced pulmonary fibrosis. Our results showed that Nano-Co exposure caused remarkable production and release of HMGB1, as well as nuclear accumulation of HIF-1α in human bronchial epithelial cells (BEAS-2B) in a dose- and a time-dependent manner. Pretreatment with CAY10585, an inhibitor against HIF-1α, significantly blocked the overexpression of HMGB1 in cell lysate and the release of HMGB1 in the supernatant of BEAS-2B cells induced by Nano-Co exposure, indicating that Nano-Co exposure induces HIF-1α-dependent HMGB1 overexpression and release. In addition, treatment of lung fibroblasts (MRC-5) with conditioned media from Nano-Co-exposed BEAS-2B cells caused increased RAGE expression, MAPK signaling activation, and enhanced expression of fibrosis-associated proteins, such as fibronectin, collagen 1, and α-SMA. However, conditioned media from Nano-Co-exposed BEAS-2B cells with HMGB1 knockdown had no effects on the activation of MRC-5 fibroblasts. Finally, inhibition of ERK1/2, p38, and JNK all abolished MRC-5 activation induced by conditioned media from Nano-Co-exposed BEAS-2B cells, suggesting that MAPK signaling might be a key downstream signal of HMGB1/RAGE to promote MRC-5 fibroblast activation. These findings have important implications for understanding the pro-fibrotic potential of Nano-Co.

The contribution of adiponectin to diabetic retinopathy progression: Association with the AGEs-RAGE pathway.

Diabetic retinopathy (DR) is a chronic complication of diabetes. Given that adiponectin plays a key role in DR progression, this study aims to elucidate the molecular mechanisms of sDR progression related to adiponectin. First, we extracted the microarray dataset GSE60436 from the Gene Expression Omnibus (GEO) database to identify hub genes associated with DR. Pathway enrichment analysis revealed a focus on inflammation, oxidative stress, and metabolic disease pathways. Gene Set Enrichment Analysis (GSEA) identified nine significant pathways related to DR. Immune infiltration analysis indicated increased infiltration of fibroblasts and endothelial cells in DR patients. Second, at the gene level, single-cell RNA sequencing (scRNA-seq) results showed a decrease in ADIPOQ gene expression as the disease progressed in our mouse models. At the protein level, ELISA results from sera of 31 patients and 11 control subjects demonstrated significantly lower adiponectin expression in the proliferative diabetic retinopathy (PDR) group compared to controls. Our findings reveal that adiponectin is involved in the advanced glycation end products (AGEs) and receptor of advanced glycation end products (RAGE) axis, as evidenced by hub gene analysis, scRNA-seq, and ELISA. In conclusion, adiponectin acts as a central molecule in the AGEs-RAGE axis, regulated by ADIPOQ, to influence DR progression.

Generation of advanced glycation end products from glycated protein or fructose/glyoxal-protein adducts under in vitro simulated gastrointestinal digestion.

Advanced glycation end products (AGEs) are a heterogeneous group of compounds formed both endogenously and exogenously through reactions between reducing sugars and amino acids within the proteins. The digestive tract may also serve as a site for endogenous AGEs generation. This study examined whether additional AGEs are formed during the digestion of glycated protein diets and meal-resembling systems (dietary proteins with fructose or glyoxal). The digestion of glycated protein showed that free AGEs were gradually released, but no additional AGEs were generated. In contrast, co-digestion of dietary proteins with fructose or glyoxal resulted in the formation of additional AGEs, and the reaction substrates (fructose or glyoxal) were depleted during digestion. Additionally, the lysine released from proteins decreased, leading to a loss of nutritional value of the food during co-digestion. The formation of AGEs and the depletion of essential amino acids in the gut may have significant implications for human health.

Citral: A potent inhibitor of advanced glycation end products.

Advanced glycation end products (AGEs), which are produced during food processing, pose health risks to humans. This study found that citral (Cit) effectively inhibited the formation of both fluorescent and non-fluorescent AGEs in the bovine serum albumin (BSA)-glucose (Glc) system. Cit achieved an average inhibition rate of over 80 % for fluorescent AGEs and reduced the levels of N-ε-carboxymethyllysine (CML) and N-ε-carboxyethyllysine (CEL) by up to 45.85 % and 59.32 %, respectively. The comprehensive characterizations and high-resolution mass spectrometry analysis demonstrated that the carbonyl group and CC group present on Cit could compete with Glc for the amino groups on BSA, thereby reducing the formation of AGEs. Additionally, the cytotoxicity assay demonstrated that the BSA-Cit adducts were non-toxic. This research indicated that Cit was a potent and safe inhibitor of AGEs.

Advanced glycation end products and reactive oxygen species: uncovering the potential role of ferroptosis in diabetic complications.

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.

Association between endothelial function and skin advanced glycation end-products (AGEs) accumulation in a sample of predominantly young and healthy adults.

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 < 0.001) and chronological age (ρ = -0.51, P < 0.001). In the multivariable analysis, SAF, chronological age, and male sex were independently associated with reduced FMD (B [95% CI]; -2.60 [-4.40, -0.80]; -0.10 [-0.16, -0.03]; 1.40 [0.14, 2.67], respectively), with the multivariable model adjusted R2 = 0.31, P < 0.001. CONCLUSIONS: Higher skin AGE levels, as measured by SAF, were associated with lower FMD values, in a predominantly young, healthy population. Additionally, older age and male participants exhibited significantly lower FMD values, corresponding with compromised endothelial function. These results suggest that SAF, a simple and inexpensive marker, could be used to predict endothelial impairment before the emergence of any structural artery pathophysiology or classic cardiovascular disease risk markers. TRIAL REGISTRATION: The study was prospectively registered with the Australian New Zealand Clinical Trials Registry (ACTRN12621000821897) and concurrently entered into the WHO International Clinical Trials Registry Platform under the same ID number.

Application of self-assembled antibacterial nanofiber loaded oriented artificial skin in infected diabetic-related wound regeneration.

Diabetic patients develop wounds that exhibit delayed healing, prolonged inflammatory responses, and slower epithelialization kinetics compared to non-diabetic patients. Diabetic foot ulcers(DFUs) affect approximately 18.6 million people worldwide. The presence of a high glucose microenvironment in DFUs results in the significant accumulation of bacterial infection and advanced glycation end products (AGEs). To solve this, a self-assemble antibacterial nanofiber(ANF) loaded oriential artificial skin (ANF@OAS) was introduced in this research, which is consisted of L/D-phenylalanine derivatives coupled the natural antimicrobial peptides.The ANF@OAS can effectively reduce AGEs production and suppress multiple resistant bacteria. Additionally, the ANF@OAS can suppress infection and stimulate wound healing in infected diabetic mice.

Sodium Tungstate Promotes Neurite Outgrowth and Confers Neuroprotection in Neuro2a and SH-SY5Y Cells.

Sodium tungstate (Na2WO4) normalizes glucose metabolism in the liver and muscle, activating the Mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) pathway. Because this pathway controls neuronal survival and differentiation, we investigated the effects of Na2WO4 in mouse Neuro2a and human SH-SY5Y neuroblastoma monolayer cell cultures. Na2WO4 promotes differentiation to cholinergic neurites via an increased G1/G0 cell cycle in response to the synergic activation of the Phosphatidylinositol 3-kinase (PI3K/Akt) and ERK1/2 signaling pathways. In Neuro2a cells, Na2WO4 increases protein synthesis by activating the mechanistic target of rapamycin (mTOR) and S6K kinases and GLUT3-mediated glucose uptake, providing the energy and protein synthesis needed for neurite outgrowth. Furthermore, Na2WO4 increased the expression of myocyte enhancer factor 2D (MEF2D), a member of a family of transcription factors involved in neuronal survival and plasticity, through a post-translational mechanism that increases its half-life. Site-directed mutations of residues involved in the sumoylation of the protein abrogated the positive effects of Na2WO4 on the MEF2D-dependent transcriptional activity. In addition, the neuroprotective effects of Na2WO4 were evaluated in the presence of advanced glycation end products (AGEs). AGEs diminished neurite differentiation owing to a reduction in the G1/G0 cell cycle, concomitant with lower expression of MEF2D and the GLUT3 transporter. These negative effects were corrected in both cell lines after incubation with Na2WO4. These findings support the role of Na2WO4 in neuronal plasticity, albeit further experiments using 3D cultures, and animal models will be needed to validate the therapeutic potential of the compound.

Thermal treatment under oxidative conditions increases the antioxidant and antiglycation activity of Chilean Tórtola beans (Phaseolus vulgaris).

The influence of oxygen on the thermal treatment (TT) of secondary metabolite-enriched extracts (SMEEs) from Tórtola beans and procyanidin C1 (PC1) on the inhibition of advanced glycation end products (AGEs) generation in proteins was investigated. SMEE was incubated at 4 °C (control) or thermally treated at 60 °C for 2 h, at either 0 % O2 (I) or 20 % O2 (II). Treatments I and II increased the content of procyanidin dimers B2. Treatment II was more effective than the control or treatment I in preventing homocysteine oxidation and AGEs generation. TT of PC1 at 0 % or 20 % O2 generated procyanidin dimers and tetramers. PC1 TT at 20 % O2 exhibited higher oxidation potentials and lower IC50 values of fluorescent AGEs than those of controls or TT at 0 % O2. These findings indicate that SMEE from Tórtola beans after treatment II changes the degree of polymerization and oxidation procyanidins, thereby increasing their antiglycation activity.

Association between Dietary Intake, Profibrotic Markers, and Blood Pressure in Patients with Chronic Kidney Disease.

Background: Among profibrotic and oxidant factors, matrix metalloproteinases (MMPs) and advanced glycation end products (AGEs) have a major impact on the progression of chronic kidney disease (CKD). However, very limited studies evaluated the relationships between nutrient intake and the mentioned factors in patients with CKD. Therefore, the present study aimed to investigate the correlation between dietary intake and the levels of MMPs, AGEs, and blood pressure (BP) in these patients. Materials and Methods: This cross-sectional study was performed on 90 patients with CKD (stages 2-5). To evaluate the dietary intake of patients, three days of 24-hour food recall were completed through face-to-face and telephone interviews. Measurement of MMP-2 and MMP-9 concentration was done by enzyme-linked immunosorbent assay. The fluorimetric technique was used to measure the total serum AGEs. Results: The patients' average dietary intake of sodium, potassium, phosphorus, energy, and protein was 725 mg/day, 1600 mg/day, 703 mg/day, 1825 kcal/day, and 64.83 g/day, respectively. After adjustment of confounding variables, a significant inverse relationship was observed between dietary intake of insoluble fiber and serum levels of MMP-2 (ß = -0.218, P = 0.05). In addition, a significant positive relationship was found between molybdenum (Mo) intake and diastolic BP (ß =0.229, P = 0.036). Conclusion: A higher intake of insoluble fiber might be associated with lower serum levels of MMP-2. Also, a higher Mo intake can be correlated to a higher DBP in patients with CKD. It is suggested to conduct future studies with longitudinal designs and among various populations to better elucidate the observed relationships.

Advanced glycation end products impair the repair of injured tendon: a study in rats.

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<0.001). TNF- α and IL-6 in the Achilles tendon increased (p<0.001, p<0.001), and the production of collagen-I decreased with the accumulation of AGEs in the repaired Achilles tendon (p<0.001). The tensile strength of Achilles tendon in the high dose group was impaired significantly. CONCLUSION: In current study, the compromised tendon repair model induced by AGEs was successfully established in rat. The study demonstrated that AGEs significantly impair Achilles tendon repair.

Multi-response kinetic study of Maillard reaction hazards in the glucose-lysine model system.

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.