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.

UNASSIGNED: Some cardiovascular risk markers have been associated with alterations in sleep duration in different populations; however, there is little evidence in a healthy population.
UNASSIGNED: The aim of the present study was to analyze the associations between sleep duration and cardiovascular risk biomarkers, including advanced glycation end-products (AGEs) measured by skin autofluorescence (SAF), maximum carotid intima-media thickness (IMTMax), aortic pulse wave velocity (a-PWV), pulse pressure (PP), and low-density lipoprotein cholesterol (LDL-C), in healthy adults (EVasCu study).
UNASSIGNED: The EVasCu study included 390 participants. Simple and multiple linear regressions were performed between sleep duration and cardiovascular risk markers. ANOVA analysis and ANCOVA analysis adjusted for various covariates were then performed after categorizing sleep into 6 h, 6-8 h, and >8 h.
UNASSIGNED: 296 participants were included in the analyses (43.97 ± 12.60 years, 63.9% female). Simple linear regressions showed an inverse association between sleep duration and SAF, IMTMax, aPWV and PP. However, in the multiple linear regression with all the covariates, the statistical significance was lost. For its part, in the ANOVA analyses, sleep duration was also associated with the same parameters, but when performing the fully adjusted ANCOVA analyses, the statistical significance for SAF was maintained (p = 0.015), obtaining a difference of 0.223 arbitrary units (p = 0.017) when comparing the group <6 h vs. > 8 h. Finally, there was no association for LDL-C.
UNASSIGNED: An inverse association was found between sleep duration and APS, which is considered a marker of cardiovascular risk. Although prospective studies are needed, it is suggested that insufficient sleep may increase cardiovascular risk, which could be a key factor in future public health policies to promote health and prevent CVD.

The aim of this study was to evaluate the association between the Mediterranean diet (MD) and the accumulation of advanced glycation end products (AGEs) measured by skin autofluorescence. This cross-sectional study included 1016 healthy students from the University of Split, Croatia. Participants completed a self-administered questionnaire. Adherence to the MD was assessed using the Mediterranean Diet Serving Score (MDSS), and tissue AGEs accumulation was measured using the AGE Reader mu (DiagnOptics). Multivariate linear regression was used in the analysis. Students\' age and female gender were associated with higher levels of AGEs, which was likewise found for greater coffee intake, adequate olive oil consumption, smoking, and lower levels of physical activity. Higher consummation of vegetables and eating breakfast regularly were associated with lower AGEs levels. The overall MD adherence was not associated with AGEs, possibly due to very low overall compliance to the MD principles among students (8.3% in women and 3.8% in men). Health perception was positively associated with the MD and nonsmoking and negatively with the perceived stress level, while AGEs did not show significant association with self-rated students\' health. These results indicate that various lifestyle habits are associated with AGEs accumulation even in young and generally healthy people. Hence, health promotion and preventive measures are necessary from an early age.

Advanced glycation end products (AGEs) have been reported to be associated with osteoporosis, aging, sarcopenia, and frailty. This study aimed to investigate the association AGEs with locomotive syndrome (LS). Participants were Japanese individuals aged 39 years or older who participated in the Yakumo Study (n=230). AGEs were measured by skin autofluorescence (SAF) using an AGE reader. We investigated SAF values for each locomotive stage. Multivariate logistic regression models were used to calculate the odds ratios of LS-associated factors. The relationships between SAF and physical performance and bone mineral density (BMD) were investigated. A receiver operating characteristic (ROC) curves were generated to determine the optimal cut-off value of SAF for predicting LS. SAF values tended to increase correspondingly with LS severity. SAF was an independently explanatory factor for LS (odds ratio 2.70; 95% confidence interval [CI] 1.040-6.990). SAF was positively correlated with the 10-m walking speed, The Timed Up and Go test results, and was negatively correlated with BMD. ROC curve represented by SAF for the presence or absence of LS risk had an area under the curve of 0.648 (95% CI: 0.571-0.726). High SAF values were identified as an independent risk factor for LS. AGEs could be a potential screening tool for people for LS.

UNASSIGNED: The current research on advanced glycosylation end products (AGEs) and cognitive function is limited.
UNASSIGNED: We aimed to investigate the relationship between multiple plasma AGEs and cognitive function and mild cognitive impairment (MCI).
UNASSIGNED: Baseline data from The Lifestyle and Healthy Aging of Chinese Square Dancer Study was used in this cross-sectional study. Ultra-high-performance liquid chromatography tandem mass spectrometry was used to determine plasma levels of carboxymethyl lysine (CML), carboxyethyl lysine (CEL), and methyl imidazolinone (MG-H1). Four cognitive tests were used to obtain the four cognitive domain scores and the composite z scores. The Petersen criteria were used to diagnose MCI. The data were analyzed by multivariable linear and logistic regression models.
UNASSIGNED: This study included 1,018 participants (median age 61.0 years, 87.3% female). After multivariate adjustment, the βs of the highest quartile of CML and CEL compared to the lowest quartile were -0.28 (-0.38, -0.17) and -0.13 (-0.23, -0.03), respectively, for the composite z score. For the four cognitive domains, CML was negatively correlated with memory, attention, and executive function, and CEL was negatively associated with memory and language function. In addition, higher CML was associated with a higher odds of MCI. MG-H1 was not associated with cognitive function.
UNASSIGNED: High plasma AGE levels were correlated with poorer cognitive function, particularly CML and CEL, higher levels of CML were also associated with higher odds of MCI. To clarify the effects of different AGEs on cognitive function and the underlying mechanisms, further longitudinal and experimental studies are needed.

OBJECTIVE: The skeletal effects of metformin monotherapy and in combination with teneligliptin are not well illustrated in patients with T2DM. To address this, we conducted an observational study to evaluate the effect of these oral hypoglycemic agents on bone turnover markers.
METHODS: We recruited patients with T2DM and first-ever prescribed metformin monotherapy or metformin combined with teneligliptin from a tertiary care teaching hospital in New Delhi, North India. Both bone formation and resorption markers, IL-6 and PTD, were estimated along with glycated hemoglobin at baseline and 12 weeks.
RESULTS: In both groups, hbA1c levels decreased significantly from baseline to 12 weeks. In the metformin-treated group, β-CTX, sRANKL, IL-6, and PTD decreased significantly, and no significant changes were observed in P1NP, OC, BAP, or OPG at 12 weeks from baseline. In the metformin + teneligliptin group, BAP, β-CTX, sRANKL, IL-6, and PTD decreased significantly, and no significant changes were observed in P1NP, OC, or OPG after 12 weeks from baseline.
CONCLUSIONS: The positive bone outcome of metformin or teneligliptin was linked to bone resorption rather than bone formation and was independent of changes in HbA1c or PTD. However, these results must be confirmed with well-designed RCTs with more extended follow-up periods.

The present study evaluated a range of biological activities of Euphorbia tithymaloides L. (Family: Euphorbiaceae) in relation to diabetes and associated complications. This plant has antioxidant and anti-inflammatory properties, but its potential for the management of hyperglycaemia and subsequently, the inhibition and reversal of advanced glycation end products has not yet been pinpointed. The objectives of this work centred around comparative iv-vitro phytochemical screening of different plant parts, followed by antidiabetic, antiglycation and glycation-reversing activities of Euphorbia tithymaloides. Rutin and luteolin, two main bioactive compounds with significant antiglycation potentials, were also quantified using a recently developed and validated HPLC-PDA method. Leaf extract showed significantly higher potency than root and stem extracts in terms of antioxidant, anti-inflammatory, antidiabetic and antiglycation activity. A combination of enzymatic inhibition and HPLC phytochemical screening provided additional evidence to consider this plant a promising source for deepening the investigation on antidiabetic plant agents.

Excessive accumulation of advanced glycation end products (AGEs) in the body is associated with diabetes and its complications. In this study, we aimed to explore the potential and mechanism of coffee leaf extract (CLE) in inhibiting the generation of AGEs and their precursors in an in vitro glycation model using bovine serum albumin and glucose (BSA-Glu) for the first time. High-performance liquid chromatography analysis revealed that CLE prepared with ultrasound pretreatment (CLE-U) contained higher levels of trigonelline, mangiferin, 3,5-dicaffeoylquinic acid, and γ-aminobutyric acid than CLE without ultrasound pretreatment (CLE-NU). The concentrations of these components, along with caffeine and rutin, were dramatically decreased when CLE-U or CLE-NU was incubated with BSA-Glu reaction mixture. Both CLE-U and CLE-NU exhibited a dose-dependent inhibition of fluorescent AGEs, carboxymethyllysine, fructosamine, 5-hydroxymethylfurfural, 3-deoxyglucosone, glyoxal, as well as protein oxidation products. Notably, CLE-U exhibited a higher inhibitory capacity compared to CLE-NU. CLE-U effectively quenched fluorescence intensity and increased the α-helix structure of the BSA-Glu complex. Molecular docking results suggested that the key bioactive compounds present in CLE-U interacted with the arginine residues of BSA, thereby preventing its glycation. Overall, this research sheds light on the possible application of CLE as a functional ingredient in combating diabetes by inhibiting the generation of AGEs.

OBJECTIVE: Several studies have demonstrated a significant association between the presence of the ear lobe crease (ELC) and cardiovascular disease. Advanced glycation end-products (AGEs) can affect the structures and functions of proteins and contribute to the development of diabetic complications. However, few studies have reported the relationship between AGEs and ELC. The purpose of this study was to investigate the correlation of skin autofluorescence (SAF)-AGEage (SAF-AGEs × age/100) with ELC.
METHODS: This cross-sectional study enrolled 6500 eligible participants from two communities in Beijing. Skin autofluorescence (SAF) was used to measure skin AGEs (SAF-AGEs). SAF-AGEage was defined as AGEs × age/100. Binary logistic regression analysis and linear regression analysis nested in logistic models were applied to test outcomes.
RESULTS: The overall prevalence of ELC with an average age of 62.7 years participants was 57.1% (n = 3714). Age, fasting blood glucose, systolic blood pressure, and lipoprotein cholesterol were all greater in participants with ELC. ELC-positive participants had higher prevalence of coronary heart disease. Logistic analysis showed a significantly positive relationship between quartiles of SAF-AGEage and ELC (odds ratio [OR] 1.526, 95% CI 1.324-1.759; OR 2.072, CI 1.791-2.396; and OR 2.983, CI 2.551-3.489) for the multivariate-adjusted models, respectively. Stratified research revealed that those with a history of diabetes, hypertension, or coronary heart disease experienced the connection between SAF-AGEage and ELC.
CONCLUSIONS: ELC is associated with coronary heart disease, and the SAF-AGE has a potential role in ELC development in elder people.

Nε-carboxymethyllysine (CML) is produced by a nonenzymatic reaction between reducing sugar and ε-amino group of lysine in food and exists as free and bound forms with varying digestibility and absorption properties in vivo, causing diverse interactions with gut microbiota. The effects of different forms of dietary CML on the gut microbiota and intestinal barrier of mice were explored. Mice were exposed to free and bound CML for 12 weeks, and colonic morphology, gut microbiota, fecal short-chain fatty acids (SCFAs), intestinal barrier, and receptor for AGE (RAGE) signaling cascades were measured. The results indicated that dietary-free CML increased the relative abundance of SCFA-producing genera including Blautia, Faecalibacterium, Agathobacter, and Roseburia. In contrast, dietary-bound CML mainly increased the relative abundance of Akkermansia. Moreover, dietary-free and -bound CML promoted the gene and protein expression of zonula occludens-1 and claudin-1. Additionally, the intake of free and bound CML caused an upregulation of RAGE expression but did not activate downstream inflammatory pathways due to the upregulation of oligosaccharyl transferase complex protein 48 (AGER1) expression, indicating a delicate balance between protective and proinflammatory effects in vivo. Dietary-free and -bound CML could modulate the gut microbiota community and increase tight-junction expression, and dietary-free CML might exert a higher potential benefit on gut microbiota and SCFAs than dietary-bound CML.