BACKGROUND: Consumption of ultra-processed foods [UPFs] may be associated with negative health outcomes. Limited data exist regarding the potential role of UPFs in the occurrence of allergic diseases. The underlying mechanisms underpinning any such associations are also poorly elucidated.
METHODS: We performed a systematic review and narrative evidence synthesis of the available literature to assess associations between UPF consumption and pediatric allergy outcomes (n = 26 papers), including data on the association seen with the gut microbiome (n = 16 papers) or immune system (n = 3 papers) structure and function following PRISMA guidelines.
RESULTS: Dietary exposure to fructose, carbonated soft drinks, and sugar intake was associated with an increased risk of asthma, allergic rhinitis, and food allergies in children. Commercial baby food intake was associated with childhood food allergy. Childhood intake of fructose, fruit juices, sugar-sweetened beverages, high carbohydrate UPFs, monosodium glutamate, UPFs, and advanced glycated end-products (AGEs) was associated with the occurrence of allergic diseases. Exposure to UPFs and common ingredients in UPFs seem to be associated with increased occurrence of allergic diseases such as asthma, wheezing, food allergies, atopic dermatitis, and allergic rhinitis, in many, but not all studies.
CONCLUSIONS: More preclinical and clinical studies are required to better define the link between UPF consumption and the risk of allergies and asthma. These observational studies ideally require supporting data with clearly defined UPF consumption, validated dietary measures, and mechanistic assessments to definitively link UPFs with the risk of allergies and asthma.

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.
BACKGROUND: 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.

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.

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.

UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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 (β = -0.218, P = 0.05). In addition, a significant positive relationship was found between molybdenum (Mo) intake and diastolic BP (β =0.229, P = 0.036).
UNASSIGNED: 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.

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.
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.
CONCLUSIONS: 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.

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.

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.
CONCLUSIONS: 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.

Glycation is an important nonenzymatic reaction between reducing sugars and amines. Advanced glycation end products (AGEs) accumulation in the human body is associated with secondary complications related to diabetes in hyperglycemic environments. These observations suggest that the inhibition of AGEs formation is important for preventing diabetes mellitus (DM) progression and the development of diabetes-related complications. Lactic acid bacteria (LAB) are probiotics commonly used in fermented foods and food additives. Therefore, it is necessary to identify starter strains of LAB to produce fermented food to decrease the risk of DM and its complications. This chapter introduces the protocols that are inhibition assay of fermented food using LAB on AGEs such as Nω-(carboxymethyl) arginine (CMA), Nε-(carboxymethyl) lysine (CML), and fluorescent AGEs.

Depressive disorders are highly prevalent among subjects suffering from chronic kidney disease (CKD). The aim of the present study is to evaluate clinical and biochemical factors associated with depressive disorders in a sample of older CKD patients, with a focus on advanced glycation end products (AGEs) and their soluble receptors (sRAGEs). A total of 115 older subjects affected by CKD (stages 3 to 5, not in dialysis) were selected for this study. These patients were divided into two groups according to the presence of depressive disorders defined by a score ≥ 10 on the 30-item Geriatric Depression Scale (GDS). The two groups were compared by independent sample t tests for continuous variables and χ2 tests for qualitative ones. Significant variables at univariate analyses were then inserted as predictors of a binary logistic regression model, with the presence or absence of depressive disorders as a dependent variable. The binary logistic regression model showed that patients with concomitant depressive disorders were more frequently of female gender (p < 0.01) and had lower MCP1 (p < 0.01) and AGE circulating levels (p < 0.01) than their counterparts. Depressive disorders in older CKD patients are more prevalent in women and seem to be inversely associated with systemic inflammation and circulating AGEs.