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Purpose: To investigate the association between skin advanced glycation end-products (AGEs) levels, blood antioxidative vitamin and carotenoid concentrations, and severe erectile dysfunction (ED) in community-dwelling men. Materials and Methods: This cross-sectional study used the 5-Item International Index of Erectile Function to identify 335 community-dwelling men with ED. The accumulation of skin AGEs was assessed noninvasively by measuring skin autofluorescence. Background-adjusted multivariable logistic regression analyses using the inverse probability of treatment weighting method were performed to evaluate the effects of AGEs, vitamins, and carotenoids on severe ED. Moreover, multiple linear regression analyses were performed to assess the association between skin AGEs levels and serum carotenoid concentrations. Results: The median age of study participants was 57 years. Of the 335 men, 289 (86.3%) and 46 (13.7%) were classified into the mild/moderate and severe ED groups, respectively. Multivariable analyses revealed that skin AGEs levels, blood vitamins C and E, lutein, zeaxanthin, β-cryptoxanthin, α-carotene, β-carotene, total lycopene, and cis-lycopenes concentrations were significantly associated with severe ED, whereas all-trans lycopene concentrations were not. In the multiple linear regression analyses, serum zeaxanthin concentrations were negatively and significantly correlated with skin AGEs levels. Conclusions: Higher skin AGEs levels and lower blood antioxidative vitamin and carotenoid concentrations were significantly associated with severe ED. Serum zeaxanthin levels were negatively and significantly correlated with skin AGEs levels, suggesting the possible effects of zeaxanthin on ED by decreasing tissue AGEs levels. [ABSTRACT FROM AUTHOR]

Abstract Diabetes mellitus and arterial hypertension are among the five risk factors that increase mortality in the world. Both are chronic, non-communicable diseases (NCDs), that have a pathophysiological association. Advanced glycation end products (AGEs), produced by the lack of glycemic control in diabetic patients, interact with their AGE receptors (AGER) resulting in increased arterial stiffness, inflammation and endothelial changes - which increases the risk of developing hypertension and other complications. We ran a systematic review in Pubmed, SciELO, Cochrane Library and Web of Science databases using keywords and Boolean operators to optimize the search, with the objective of assessing the mechanism of non-enzymatic glycation of proteins present in patients with diabetes and its correlation with the onset of hypertension, exposing all the endothelial and cellular damage caused by AGEs. We found 719 papers, of which 99 were read in full, and 26 met the eligibility criteria and were included in the present review. AGEs should be considered one of the main cardiometabolic risk factors. Reducing the AGE-AGER interaction will result in cardiovascular protection and increased life expectancy.

This study investigated the impact of processing temperatures (190 °C, 210 °C, and 230 °C) and durations (7 min, 10 min, and 14 min) on the formation of Maillard reaction products (MRPs) and antioxidant activities in pan baked buns. Key Maillard reaction indicators, including glyoxal (GO), methylglyoxal (MGO), 5-hydroxymethylfurfural (5-HMF), melanoidins, and fluorescent advanced glycation end products (AGEs) were quantified. The results demonstrated significant increases in GO, MGO, 5-HMF contents (p < 0.05), and antioxidant activities (p < 0.05) when the buns were baked at 210 °C for 14 min, 230 °C for 10 min and 14 min. However, the interior MRPs of baked buns were minimally affected by the baking temperature and duration. Prolonged heating temperatures and durations exacerbated MRPs production (43.8 %-1038 %) in the bottom crust. Nonetheless, this process promoted the release of bound phenolic compounds and enhanced the antioxidant activity. Heating induces the thermal degradation of macromolecules in food, such as proteins and polysaccharides, which releases bound phenolic compounds by disrupting their chemical bonds within the food matrix. Appropriate selections of baking parameters can effectively reduce the formation of MRPs while simultaneously improve sensory quality and health benefit of the pan baked buns. Considering the balance between higher antioxidant properties and lower MRPs, the optimal thermal parameters for pan baked buns were 210 °C for 10 min. Furthermore, a normalized analysis revealed a consistent trend for GO, MGO, 5-HMF, fluorescent AGEs, and melanoidins. Moreover, MRPs were positively correlated with total contents of phenolic compounds, ferric-reducing antioxidant power (FRAP), and color, but negatively correlated with moisture contents and reducing sugars. Additionally, the interaction between baking conditions and Maillard reactions probably contributed to enhanced primary flavors in the final product. This study highlights the importance of optimizing baking parameters to achieve desirable MRPs levels, higher antioxidant activity, and optimal sensory attributes in baked buns., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The identification of bioactive natural products (NPs) in complex mixtures has become an important subject of contemporary NP research. In an attempt to address this challenge, the present work proposes an integrated strategy that combines tandem mass spectrometry (MS 2 )-based molecular networking (MN), a partial least-squares (PLS) chemometric model, as well as 13 C NMR-based dereplication using MixONat software. In addition, an advanced glycation end product (AGEs) assay was used for activity evaluation. The approach was implemented on a Garcinia parvifolia bark extract that comprised a high content of prenylated xanthones and had previously shown a notable inhibitory effect on AGE formation. As a main result, the proposed strategy permitted the identification of potentially active metabolites within complex mixtures and their annotation with a higher level of confidence by NMR data. Overall, this comprehensive approach provides a powerful and efficient solution for the targeting and annotating of active compounds in complex NP mixtures.

Background: Glycated albumin (GA), 1,5-anhydroglucitol (1,5-AG), and fructosamine have attracted considerable interest as markers of hyperglycemia. This study aimed to evaluate the optimal cutoff values for GA, 1,5-AG, and fructosamine and to determine their respective diagnostic efficacies in relation to hyperglycemia., Methods: We enrolled 6012 individuals who had undergone fasting blood glucose (FBG) and Hemoglobin A1c (HbA1c) tests along with at least one alternative glycemic marker. Receiver operating characteristic (ROC) curves and the upper or lower limit of the reference range (97.5 or 2.5 percentiles) were used to ascertain the optimal cutoff values. Follow-up data from healthy individuals were used to identify patients who developed diabetes mellitus (DM)., Results: The ROC cutoff values for GA, 1,5-AG, and fructosamine were 13.9%, 13.3 μg/mL, and 278 μmol/L, respectively, with corresponding area under the curve (AUC) values of 0.860, 0.879, and 0.834. The upper limits of the reference intervals for GA and fructosamine were 15.1% and 279 μmol/L, respectively, and the lower limit for 1,5-AG was 5.3 μg/mL. Among the GA cutoff values, the ROC cutoff had the highest sensitivity. Analyzing the follow-up data showed that lowering the GA cutoff from 16.0% to 13.9% identified an additional 40 people with DM progression., Conclusions: Lowering the GA cutoff values significantly increased the sensitivity of DM diagnosis and enhanced its potential as a screening marker by identifying more individuals with diabetes progression. Conversely, modifications to the cutoff values for 1,5-AG and fructosamine did not confer any discernible diagnostic or predictive advantages., (© 2024 The Author(s). Journal of Clinical Laboratory Analysis published by Wiley Periodicals LLC.)

Aims/introduction: Diabetes mellitus is a traditional risk factor for heart failure (HF), and glycated albumin (GA) is a marker to assess short-term glycemic control. Whether GA has prognostic significance in patients with HF remains unclear., Materials and Methods: A total of 717 patients with HF were enrolled in the prospective cohort study. Patients were grouped by the normal upper limit of GA (17%). Kaplan-Meier analysis and Cox proportional hazards regression were used to evaluate the association between GA and prognosis., Results: During a mean follow-up of 387 days, 232 composite endpoint events of hospitalization for HF or all-cause death occurred. Kaplan-Meier analysis showed a higher rate of adverse events in the higher GA group (GA >17%; log-rank test P < 0.001). GA was an independent predictor of adverse events, both as a continuous variable (per 1% change: hazard ratio [HR] 1.03, 95% confidence interval [CI] 1.00-1.06, P = 0.030) and as a categorical variable (GA >17%: HR 1.36, 95% CI 1.03-1.80, P = 0.032). Restricted cubic splines showed a linear association between GA and adverse events (P for non-linearity = 0.231). There was no significant difference in adverse outcome risk between those with diabetes and GA ≤17% and those without diabetes, whereas the prognosis was worse in those with diabetes and GA >17% (HR 1.56, 95% CI 1.16-2.11, P = 0.004). Compared to the group with normal levels of GA and glycated hemoglobin, the group with GA >17% and glycated hemoglobin >6.5% had a higher risk of adverse events (HR 1.49, 95% CI 1.06-2.10, P = 0.022)., Conclusions: GA was an independent predictor of HF prognosis. Combining GA and glycated hemoglobin might improve the predictive power of adverse outcomes in patients with HF., (© 2024 The Author(s). Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.)

Background: Dietary advanced glycation end products (AGEs) may promote oxidative stress and inflammation in the gastrointestinal tract., Aims: The aim of this study is to investigate the association between dietary AGE intake and the risk of inflammatory bowel disease (IBD)., Methods: We included 121,978 participants without IBD at baseline from the UK Biobank. We estimated consumption of three common AGEs (Nε-(carboxymethyl)-lysine (CML), Nε-(1-carboxyethyl)-lysine (CEL), and Nδ-(5-hydro-5-methyl-4-imidazolon-2-yl)-ornithine (MG-H1)) by matching 24-h dietary questionnaires to a validated dietary AGE database. We used Cox proportional hazards regression models to calculate the hazard ratio (HR) and 95% CI of the association between dietary AGEs and IBD risk., Results: During a median follow-up of 13.72 years, 671 participants developed IBD (192 with Crohn's disease (CD) and 478 with ulcerative colitis (UC)). Among the assessed dietary AGEs, only CEL was associated with an increased risk of IBD (HR = 1.09, 95% CI: 1.01-1.18, p = 0.020) and CD (HR = 1.18, 95% CI: 1.03-1.36, p = 0.014), particularly for participants who were overweight, physically inactive, and non-smokers. Among participants at a high genetic risk of CD, HRs (95% CI) of CD were 1.26 (1.00-1.57) for CML, 1.41 (1.12-1.77) for CEL, and 1.28 (1.01-1.62) for MG-H1 (p < 0.05 for each). However, none of the dietary AGEs was significantly associated with UC risk, irrespective of genetic predisposition., Conclusions: Dietary CEL was associated with an increased risk of IBD and CD, but not UC. Further interventional studies are required to support the potential benefit of AGE restriction, especially for individuals at a high genetic risk of CD., (© 2024 The Author(s). Alimentary Pharmacology & Therapeutics published by John Wiley & Sons Ltd.)

Aim: To assess the direct effect of intensive glycaemic control on periodontal tissues in patients with diabetes mellitus., Materials and Methods: Twenty-nine patients with type 2 diabetes were enrolled and hospitalized to receive a 2-week intensive glycaemic control regimen. We observed and analysed the systemic and oral disease indicators before and after treatment and clarified the indicators related to periodontal inflammation., Results: A significant reduction in glycaemic and periodontal parameters, including glycated albumin levels and periodontal inflamed surface area (PISA), was observed after treatment. The changes in PISA per tooth, indicative of periodontal healing, exhibited a bimodal distribution; the patients were divided into two groups on this basis. Correlations were observed between the changes in PISA per tooth and fasting plasma glucose, acetoacetic acid, and beta-hydroxybutyrate levels in the PISA-improved group. Significantly lower levels of C-peptide, coefficient of variation of R-R interval, and ankle-brachial pressure index were observed before treatment in the PISA non-improved group., Conclusions: Glycaemic control treatment can effectively improve periodontitis in patients with type 2 diabetes, even in the absence of specific periodontal treatments. However, the periodontal responsiveness to glycaemic control treatment depends on the systemic condition of the patient., (© 2024 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Objective: To explore the diagnostic value of glycated CD59 (gCD59) in gestational diabetes mellitus (GDM)., Methods: A total of 707 pregnant women who underwent the first visit in the obstetric outpatient clinic of the Affliated Suqian Hospital of Xuzhou Medical University from January 2022 to July 2023 were included, and were grouped according to the International Association of the Diabetes and Pregnancy Study Groups(IADPSG) diagnostic criteria, and finally 113 cases in the GDM group and 559 cases in the normal glucose tolerance (NGT) group were included, and the concentration of gCD59 was determined by enzyme-linked immunosorbent assay (ELISA). The baseline data characteristics of the two groups were compared, the risk factors for GDM were explored by multivariate binary logistic analysis, and the diagnostic value of gCD59 in predicting GDM was explored by receiver operating characteristic (ROC) curve analysis., Results: The level of gCD59 in the GDM group was significantly higher than that in the NGT group (1.49 SPU vs 0.87 SPU). Multivariate regression analysis showed that gCD59, diastolic blood pressure (DBP) and thyroid stimulating hormone (TSH) were independent risk factors for GDM.The area under the curve (AUC) of gCD59 for the diagnosis of GDM was 0.681 (95% CI : 0.583-0.717), with a sensitivity of 71.7% and a specificity of 58.3%. In combination with fasting glucose, gCD59 effectively diagnosed GDM with higher AUC of 0.871 (95% CI : 0.708-1.000)., Conclusion: gCD59 is an independent risk factor for GDM and a good biomarker for the diagnosis of GDM., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Wang, Xu, Lu, Cao, Zuo, Zhang, Zou and Sun.)

The burden of diabetes is rising in developing countries, and this is significantly linked to the increasing prevalence of poor glycemic control. The cost of glycated haemoglobin (HbA1c) testing is a barrier to timely glycemic assessments, but newer tests such as glycated albumin may be cheaper and tempting alternatives. Additional research must ascertain if glycated albumin (GA) can act as a viable supplement or alternative to conventional HbA1c measurements for glycemic control in diabetic individuals. GA as a biomarker is an emerging area of interest, particularly for those who display unreliable HbA1c levels or cannot afford the test. This study aims to investigate the prevalence of poor glycemic control in outpatient diabetic patients and the utility of glycated albumin in this population's monitoring of glycemic control. Method. A cross-sectional study of 203 diabetic patients will be conducted at the Dodoma Regional Referral Hospital and Benjamin Mkapa Hospital from August 1st, 2023, to August 31st, 2024. Patients diagnosed with diabetes mellitus for over six months will be screened for eligibility. Informed consent, history, clinical examination, and voluntary blood sample collection will be obtained from all eligible patients. Glycated Albumin levels will be obtained from the same blood samples collected. The glycemic status of all patients will be defined as per HbA1c, and a level of greater than 7% will considered as a poor control. The analysis will be computed with SPSS version 28.0, and a predictor variable, P<0.05, will be regarded as statistically significant, with the utility of GA determined by plotting the area under the ROC curve and the confusion matrix., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Mkumbi, Boaz. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Advanced glycation end products (AGEs), heterocyclic aromatic amines (HAAs), acrylamide (AA), 5-hydroxymethylfurfural (5-HMF), and polycyclic aromatic hydrocarbons (PAHs) are toxic substances that are produced in certain foods during thermal processing by using common high-temperature unit operations such as frying, baking, roasting, grill cooking, extrusion, among others. Understanding the formation pathways of these potential risk factors, which can cause cancer or contribute to the development of many chronic diseases in humans, is crucial for reducing their occurrence in thermally processed foods. During thermal processing, food rich in carbohydrates, proteins, and lipids undergoes a crucial Maillard reaction, leading to the production of highly active carbonyl compounds. These compounds then react with other substances to form harmful substances, which ultimately affect negatively the health of the human body. Although these toxic compounds differ in various forms of formation, they all partake in the common Maillard pathway. This review primarily summarizes the occurrence, formation pathways, and reduction measures of common toxic compounds during the thermal processing of food, based on independent studies for each specific contaminant in its corresponding food matrix. Finally, it provides several approaches for the simultaneous reduction of multiple toxic compounds., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Rationale & Objective: Hemoglobin A 1c (HbA 1c ) is widely used to estimate glycemia, yet it is less reliable in patients with chronic kidney disease (CKD). There is growing interest in the complementary use of glycated albumin (GA) to improve glycemic monitoring and risk stratification. However, whether GA associates with clinical outcomes in a non-dialysis-dependent CKD population remains unknown., Study Design: Prospective cohort study., Setting & Participants: 3,110 participants with CKD from the Chronic Renal Insufficiency Cohort study., Exposure: Baseline GA levels., Outcome: Incident end-stage kidney disease (ESKD), cardiovascular disease (CVD) events, and all-cause mortality., Analytical Approach: Cox proportional hazards regression., Results: Participant characteristics included mean age 59.0±10.8 SD years; 1,357 (43.6%) female; and 1,550 (49.8%) with diabetes. The median GA was 18.7% (IQR, 15.8%-23.3%). During an average 7.9-year follow-up, there were 980 ESKD events, 968 CVD events, and 1,084 deaths. Higher GA levels were associated with greater risks of all outcomes, regardless of diabetes status: hazard ratios for ESKD, CVD, and death among participants with the highest quartile compared with quartile 2 (reference) were 1.42 (95% CI, 1.19-1.69), 1.67 (95% CI, 1.39-2.01), and 1.63 (95% CI, 1.37-1.94), respectively. The associations with CVD and death appeared J-shaped, with increased risk also seen at the lowest GA levels. Among patients with coexisting CKD and diabetes, the associations of GA with outcomes remained significant even after adjusting for HbA 1c . For each outcome, we observed a significant increase in the fraction of new prognostic information when both GA and HbA 1c were added to models., Limitations: Lack of longitudinal GA measurements; and HbA 1c measurements were largely unavailable in participants without diabetes., Conclusions: Among patients with CKD, GA levels were independently associated with risks of ESKD, CVD, and mortality, regardless of diabetes status. GA added prognostic value to HbA 1c among patients with coexisting CKD and diabetes., Plain-Language Summary: Hemoglobin A 1c (HbA 1c ) is widely used to estimate glycemia, yet it is less reliable in patients with chronic kidney disease (CKD). There is growing interest in the complementary use of glycated albumin (GA) to improve glycemic monitoring and risk stratification. However, whether GA associates with clinical outcomes in a non-dialysis-dependent CKD population remains unknown. In this cohort study of 3,110 individuals with non-dialysis-dependent CKD, GA levels were independently associated with risks of end-stage kidney disease, cardiovascular disease (CVD), and mortality. The associations with CVD and mortality appeared to be J-shaped. Among patients with coexisting CKD and diabetes, GA added prognostic value to HbA 1c. Thus, GA may be a valuable complementary test to HbA 1c in patients with CKD., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Type 2 diabetes mellitus is a global health problem, placing patients at a higher risk of developing cardiovascular diseases and cancer. This study investigates the antidiabetic potential of Cassia bakeriana bark extracts and fractions. We evaluate their ability to inhibit α-amylase and α-glucosidase enzymes and advanced glycation end-products (AGEs). The antioxidant potential was also examined. Extracts were prepared through maceration with hexane (HE) and ethanol (EE), and the fractions were obtained via liquid-liquid extraction from EE. Anti-enzymatic, anti-glycation, antioxidant, and cytotoxic assays were conducted in 96-well plates using different concentrations of samples to determine the half-maximal inhibitory concentration (IC 50 ). Active samples were further analyzed using HPLC-(-)-ESI-MS/MS. The ethyl acetate fraction (EAF) demonstrated a high percentage of α-amylase inhibition (94.0%) with a promising IC 50 value of 1.05 μg mL -1 . Additionally, EAF displayed 61.5% inhibition of α-glucosidase, with an IC 50 value of 537 μg mL -1 . The EE, EAF, and n-butanol fraction (BF) exhibited strong anti-glycation capacities. Furthermore, the EE, EAF, BF, and dichloromethane fractions showed promising antioxidant activity using the DPPH and ORAC methodologies. Cytotoxic activity was also evaluated with Vero cells, revealing no adverse effects on cell viability (CC 50  > 512.0 μg mL -1 ). Active samples predominantly comprised proanthocyanidins, flavonoids, and anthraquinone, representing the main constituents of C. bakeriana bark. This study provides the first assessment of the antidiabetic potential of C. bakeriana bark and a comprehensive analysis of the chemical composition of its active extracts and fractions, offering hope for future treatments., (© 2024 John Wiley & Sons Ltd.)

Type 2 diabetes mellitus (T2DM) and periodontitis are two biologically linked diseases that often coexist in complex interaction. While periodontitis may lead to insulin receptor desensitization, diabetes may increase the expression of inflammatory cytokines, such as Tumor Necrosis Factor-α (TNF-α) and Interleukin 6 (IL-6), in the gingival crevicular fluid and activate osteoclasts via Receptor activator of nuclear factor kappa-Β ligand (RANK-L) production, leading to bone resorption. However, the association between the two diseases processes, where one may exacerbate the progression of the other, is unclear. In addition, both diseases have similar mechanistic themes, such as chronic inflammation and oxidative stress. This review aimed to investigate the pathophysiological and molecular mechanisms underlying T2DM and periodontitis. Uncontrolled diabetes is often associated with severe periodontitis, measured by clinical attachment loss. Alteration in the oral microbiome composition, which may activate the host inflammatory response and lead to irreversible oxidative stress, is a common finding in both diseases. An understanding of the molecular crosstalk between the two disease processes is crucial for developing therapeutic targets that inhibit bone resorption and halt the progression of periodontitis in patients with diabetes. The Oral microbiome composition in T2DM and periodontitis shifts toward dysbiosis, favoring bacterial pathogens, such as Fusobacteria and Porphyromonas species. Both conditions are marked by pro-inflammatory immune activity via the activation of Interleukin 17 (IL-17), Interleukin 1 (IL-1), TNF-α, and Nuclear Factor Kappa Beta (NF-κB). Common molecular crosstalk signaling appears to involve advanced glycation end products (AGEs) and oxidative stress. Thus, future drug targets are multifactorial, ranging from modulatory of host inflammatory response to preventing the accumulation of AGEs and oxidative free radicals. [ABSTRACT FROM AUTHOR]

Abstract Background Rubeosis faciei diabeticorum is a persistent facial erythema in patients with diabetes mellitus. The actual pathogenesis has not been studied. However, it is speculated to be a cutaneous diabetic microangiopathy. Objective Examine the correlation between the severity of facial erythema and the possible causes of microvascular diabetic complications, namely oxidative stress, hyperglycemia, and cutaneous accumulation of advanced glycation end-products . Methods Patients diagnosed with Type 2 diabetes mellitus (n = 32) were enrolled in the study. The facial erythema index was measured using the Mexameter MX18; cutaneous accumulation of advanced glycation end-products was estimated by measuring skin auto fluorescence with the AGE Reader (DiagnOptics Technologies B.V. - Groningen, Netherlands). Glycated haemoglobin, total antioxidant status, and malondialdehyde were measured in blood by TBARS assay. The correlation between the selected variables was assessed by Spearman's rank test; p ≤ 0.05 was considered statistically significant. Results There was a statistically significant correlation between total antioxidant status and the facial erythema index (ρ = 0.398, p = 0.024). Malondialdehyde, skin autofluorescence, glycated haemoglobin, body mass index, duration of diabetes, and age did not demonstrate statistically significant correlation with the facial erythema index. Study limitations This is an observational study. Elevation of total antioxidant status could have been caused by several factors that might have also influenced the development of rubeosis faciei, including hyperbilirubinemia and hyperuricemia. Conclusions The results contradicted expectations. Total antioxidant status correlated positively with facial erythema index; however, there was no correlation with oxidative stress and skin autofluorescence. Further investigations should be conducted to reveal the cause of total antioxidant status elevation in patients with rubeosis faciei.

Background: Glycated albumin (GA) is an indicator of glycemic variability over the past 2-4 weeks and has suitable characteristics for predicting the prognosis of ischemic stroke during the acute phase. This study evaluated the association between early neurological deterioration (END) and GA values in patients with acute ischemic stroke (AIS)., Methods: We assessed consecutive patients with AIS between 2022 and 2023 at two large medical centers in Korea. END was defined as an increase of ≥ 2 in the total National Institutes of Health Stroke Scale (NIHSS) score or ≥ 1 in the motor NIHSS score within the first 72 h of admission. We evaluated various glycemic parameters including fasting glucose (mg/dL), hemoglobin A1c (%), and GA (%)., Results: In total, 531 patients with AIS were evaluated (median age: 69 years, male sex: 66.3%). In the multivariable logistic regression analysis, GA value was positively associated with END (adjusted odds ratio [aOR] = 3.24, 95% confidence interval [CI]: 1.10-9.50). Initial NIHSS score (aOR = 1.04, 95% CI: 1.01-1.08) and thrombolytic therapy (aOR = 2.06, 95% CI: 1.14-3.73) were also associated with END. In a comparison of the predictive power of glycemic parameters for END, GA showed a higher area under the curve value on the receiver operating characteristic curve than fasting glucose and hemoglobin A1c., Conclusions: High GA values were associated with END in patients with AIS. Furthermore, GA was a better predictor of END than fasting glucose or hemoglobin A1c., (© 2024. The Author(s).)

Introduction: Effective tools to evaluate bone quality preoperatively are scarce and the standard method to determine bone quality requires an invasive biopsy. A non-invasive, and preoperatively available method for bone quality assessment would be of clinical value. The purpose of this study is to investigate the associations of bone formation marker, serum bone alkaline phosphatase (BAP), and bone resorption marker, urine collagen cross-linked N-telopeptide (uNTX) to volumetric bone mineral density (vBMD), fluorescent advanced glycation endproducts (fAGEs) and bone microstructure., Materials and Methods: A cross-secional analysis using prospective data of patients undergoing lumbar spinal fusion was performed. BAP and uNTX were preoperatively collected. Quantitative computed tomography (QCT) was performed at the lumbar spine (vBMD ≤ 120 mg/cm 3 osteopenic/osteoporotic). Bone biopsies from the posterior superior iliac spine were obtained and evaluated with multiphoton fluorescence microscopy for fAGEs and microcomputed tomography (µCT) for bone microarchitecture. Correlations between BAP/uNTX to vBMD, fAGEs and µCT parameters were assessed with Spearman's ρ. Receiver operating characteristic (ROC) analysis evaluated BAP and uNTX as predictors for osteopenia/osteoporosis. Multivariable linear regression models adjusting for age, sex, BMI, race and diabetes mellitus determined associations between BAP/uNTX and fAGEs., Results: 127 prospectively enrolled patients (50.4% female, 62.5 years, BMI 28.7 kg/m 2 ) were analyzed. uNTX (ρ=-0.331,p < 0.005) and BAP (ρ=-0.245,p < 0.025) decreased with cortical fAGEs, and uNTX (ρ=-0.380,p < 0.001) decreased with trabecular fAGEs. BAP and uNTX revealed no significant correlation with vBMD. ROC analysis for BAP and uNTX discriminated osteopenia/osteoporosis with AUC of 0.477 and 0.561, respectively. In the multivariable analysis, uNTX decreased with increasing trabecular fAGEs after adjusting for covariates (β = 0.923;p = 0.031)., Conclusion: This study demonstrated an inverse association of bone turnover markers and fAGEs. Both uNTX and BAP could not predict osteopenia/osteoporosis in the spine. uNTX reflects collagen characteristics and might have a complementary role to vBMD, as a non-invasive tool for bone quality assessment in spine surgery., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

α-Dicarbonyl compounds (α-DCs) are important intermediates and precursors of harmful Maillard reaction products (e.g., acrylamide and late glycosylation end-products), and they exist widely in thermoprocessed sugar- or fat-rich foods. α-DCs and their end-products are prone to accumulation in the human body and lead to the development of various chronic diseases. Therefore, detection of α-DCs and their associated hazards in food samples is crucial. This paper reviews the preparation of molecularly imprinted polymers (MIPs) enabling visual intelligent responses and the strategies for recognition and capture of α-DCs and their associated hazards, and provides a comprehensive summary of the development of visual MIPs, including integration strategies and applications with real food samples. The visual signal responses as well as the mechanisms for hazard recognition and capture are highlighted. Current challenges and prospects for visual MIPs with advanced applications in food, agricultural and environmental samples are also discussed. This review will open new horizons regarding visual MIPs for recognition and inhibition of hazards in food safety., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Synthesis of metal nanoparticles using plant extracts is environmentally friendly and of increasing interest. However, not all plant extracts can meet successfully on the synthesis. Therefore, searching for the high potential extracts that can reduce the metal salt precursor in the synthesis reaction is essential. The present study explores the synthesis of copper oxide nanoparticles (CuONPs) using Caesalpinia sappan heartwood extract. Phytochemical analysis and determination of the total phenolic content of the extract were performed before use as a reducing agent. Under the suitable synthesized condition, a color change in the color of the solutions to brown confirmed the formation of CuONPs. The obtained CuONPs were confirmed using ultraviolet-visible spectroscopy, photon correlation spectroscopy, X-ray diffraction, scanning electron microscope, energy dispersive X-ray, and Fourier transform infrared analysis. The synthesized CuONPs investigated for antioxidant, antiglycation, and antibacterial activities. CuONPs possessed antioxidant activities by quenching free radicals with an IC 50 value of 63.35 µg/mL and reducing activity with an EC range of 3.19-10.27 mM/mg. CuONPs also inhibited the formation of advanced glycation end products in the bovine serum albumin/ribose model with an IC 50 value of 17.05 µg/mL. In addition, CuONPs showed inhibition of human pathogens, including Gram-positive Staphylococcus aureus and Gram-negative Escherichia coli, and prevention of biofilm formation and biofilm eradication, with maximum inhibition of approx. 75%. Our findings suggest that C. sappan extract can be used to obtain highly bioactive CuONPs for the development of certain medical devices and therapeutic agents.

Background: Preeclampsia is a multifaceted syndrome that includes maternal vascular dysfunction. We hypothesize that increased placental glycolysis and hypoxia in preeclampsia lead to increased levels of methylglyoxal (MGO), consequently causing vascular dysfunction., Methods: Plasma samples and placentas were collected from uncomplicated and preeclampsia pregnancies. Uncomplicated placentas and trophoblast cells (BeWo) were exposed to hypoxia. The reactive dicarbonyl MGO and advanced glycation end products (N ε -(carboxymethyl)lysine [CML], N ε -(carboxyethyl)lysine [CEL], and MGO-derived hydroimidazolone [MG-H]) were quantified using liquid chromatography-tandem mass spectrometry. The activity of GLO1 (glyoxalase-1), that is, the enzyme detoxifying MGO, was measured. The impact of MGO on vascular function was evaluated using wire/pressure myography. The therapeutic potential of the MGO-quencher quercetin and mitochondrial-specific antioxidant mitoquinone mesylate (MitoQ) was explored., Results: MGO, CML, CEL, and MG-H2 levels were elevated in preeclampsia-placentas (+36%, +36%, +25%, and +22%, respectively). Reduced GLO1 activity was observed in preeclampsia-placentas (-12%) and hypoxia-exposed placentas (-16%). Hypoxia-induced MGO accumulation in placentas was mitigated by the MGO-quencher quercetin. Trophoblast cells were identified as the primary source of MGO. Reduced GLO1 activity was also observed in hypoxia-exposed BeWo cells (-26%). Maternal plasma concentrations of CML and the MGO-derived MG-H1 increased as early as 12 weeks of gestation (+16% and +17%, respectively). MGO impaired endothelial barrier function, an effect mitigated by MitoQ, and heightened vascular responsiveness to thromboxane A2., Conclusions: This study reveals the accumulation of placental MGO in preeclampsia and upon exposure to hypoxia, demonstrates how MGO can contribute to vascular impairment, and highlights plasma CML and MG-H1 levels as promising early biomarkers for preeclampsia., Competing Interests: Disclosures None.

α-Dicarbonyl compounds (α-DCs) are predominantly generated through the thermal processing of carbohydrate and protein-rich food. They are pivotal precursors to hazard formation, such as advanced glycation end products (AGEs), acrylamide, and furan. Their accumulation within the body will be genotoxicity and neurotoxicity. Recently, significant advancements have been made in nanotechnology, leading to the widespread utilization of nanomaterials as functional components in addressing the detrimental impact of α-DCs. This review focuses on the control of α-DCs through the utilization of nanoparticle-based functional factors, which were prepared by using edible components as resources. Four emerging nanoparticles are introduced including phenolic compounds-derived nanoparticle, plant-derived nanoparticle, active peptides-derived nanoparticle, and functional minerals-derived nanoparticle. The general control mechanisms as well as the recent evidence pertaining to the aforementioned aspects were also discussed, hoping to valuable helpful references for the development of innovative α-DCs scavengers and identifying the further scope of research., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Skin autofluorescence (sAF) measurement is a non-invasive method used to assess tissue advanced glycation end product (AGE) accumulation. This study aims to characterize sAF's association with (1) glycated hemoglobin (HbA1c) values, (2) cardiovascular risk markers, and (3) common comorbidities (autoimmune thyroiditis, celiac disease) in children with type 1 diabetes (T1D)., Materials and Methods: A total of 348 children with T1D aged 3-18 years and 85 age- and gender-matched control subjects were enrolled. sAF was quantified using an AGE Reader (Diagnoptics BV, The Netherlands). The analysis covered HbA1c, blood lipid, and C-reactive protein (CRP) levels, ambulatory blood pressure monitoring records, and body composition parameters. The associations between variables and sAF were assessed using the Mann-Whitney U test and Spearman correlation., Results: We observed significantly higher sAF values in the T1D group compared to the control (1.40 [1.27-1.53] vs. 1.20 [1.07-1.30, AU]; p = 0.004), consistent across all tested age groups. In the T1D group, sAF was positively correlated with current HbA1c, mean of historical HbA1c values, and T1D duration (r values, respectively: 0.27, 0.22, 0.14, all p < 0.01). Percentage of body fat was positively correlated with sAF (r = 0.120; p = 0.044). No significant correlations were found between sAF and lipid fractions, Z-score of BMI, parameters from 24 h ambulatory blood pressure monitoring, or the amount of albumin excreted in urine. sAF was positively correlated with CRP (r = 0.17, p < 0.05). sAF was significantly higher in patients with concomitant celiac disease (1.53 [1.43-1.63] vs. 1.40 [1.27-1.53, AU], p = 0.001)., Conclusion: Among young T1D patients with relatively brief diabetes duration, sAF effectively mirrors prior glycemic control, as presented by historical average HbA1c. However, associations with conventional CV risk markers are not evident. The higher sAF values in patients with celiac disease warrant further exploration.

Objectives: Glycated albumin (GA) has potential value in the management of people with diabetes; however, to draw meaningful conclusions between clinical studies it is important that the GA values are comparable. This study investigates the standardization of the Norudia Glycated Albumin and Lucica Glycated Albumin-L methods., Methods: The manufacturer reported imprecision was verified by performing CLSI-EP15-A3 protocol using manufacturer produced controls. The Japanese Clinical Chemistry Reference Material (JCCRM)611-1 was measured 20 times to evaluate the accuracy of both methods. GA was also measured in 1,167 patient samples and results were compared between the methods in mmol/mol and %., Results: Maximum CV for Lucica was ≤0.6 % and for Norudia ≤1.8 % for control material. Results in mmol/mol and % of the JCCRM611-1 were within the uncertainty of the assigned values for both methods. In patient samples the relative difference in mmol/mol between the two methods ranged from -10.4 % at a GA value of 183 mmol/mol to +8.7 % at a GA value of 538 mmol/mol. However, the relative difference expressed in percentage units ranged from of 0 % at a GA value of 9.9 % to +1.7 % at a GA value of 30 %., Conclusions: The results in mmol/mol between the two methods for the patient samples were significantly different compared to the results in %. It is not clear why patient samples behave differently compared to JCCRM611-1 material. Valuable lessons can be learnt from comparing the standardization process of GA with that of HbA 1c ., (© 2024 Walter de Gruyter GmbH, Berlin/Boston.)

Dicarbonyl compounds are highly reactive precursors of advanced glycation end products (AGE), produced endogenously, present in certain foods and formed during food processing. AGE contribute to the development of adverse metabolic outcomes, but health effects of dietary dicarbonyls are largely unexplored. We investigated associations between three dietary dicarbonyl compounds, methylglyoxal (MGO), glyoxal (GO) and 3-deoxyglucosone (3-DG), and body weight changes in European adults. Dicarbonyl intakes were estimated using food composition database from 263 095 European Prospective Investigation into Cancer and Nutrition-Physical Activity, Nutrition, Alcohol, Cessation of Smoking, Eating Out of Home in Relation to Anthropometry participants with two body weight assessments (median follow-up time = 5·4 years). Associations between dicarbonyls and 5-year body-weight changes were estimated using mixed linear regression models. Stratified analyses by sex, age and baseline BMI were performed. Risk of becoming overweight/obese was assessed using multivariable-adjusted logistic regression. MGO intake was associated with 5-year body-weight gain of 0·089 kg (per 1-sd increase, 95 % CI 0·072, 0·107). 3-DG was inversely associated with body-weight change (-0·076 kg, -0·094, -0·058). No significant association was observed for GO (0·018 kg, -0·002, 0·037). In stratified analyses, GO was associated with body-weight gain among women and older participants (above median of 52·4 years). MGO was associated with higher body-weight gain among older participants. 3-DG was inversely associated with body-weight gain among younger and normal-weight participants. MGO was associated with a higher risk of becoming overweight/obese, while inverse associations were observed for 3-DG. No associations were observed for GO with overweight/obesity. Dietary dicarbonyls are inconsistently associated with body weight change among European adults. Further research is needed to clarify the role of these food components in overweight and obesity, their underlying mechanisms and potential public health implications.

As accumulated evidence suggests that individuals with post-traumatic stress disorder (PTSD) encounter earlier and more frequent occurrences of cardiovascular diseases, the aim of this study was to ascertain the differences in lifestyle and cardiovascular risk between PTSD and complex PTSD patients. We enrolled 137 male war veterans with PTSD (89 had complex PTSD). The diagnosis was established based on 11th revision of International Classification of Diseases (ICD-11), and cardiovascular risk was estimated by the measurement of advanced glycation end products. Adherence to Mediterranean diet (MD) was lower in the complex PTSD group (2.2% vs. 12.5%, p = 0.015). Accordingly, patients with complex PTSD had lower healthy lifestyle scores in comparison to PTSD counterparts (50.6 ± 9.7 vs. 59.6 ± 10.1, p < 0.001), and a positive association was noted between MD adherence and a healthy lifestyle (r = 0.183, p = 0.022). On the other hand, differences were not noted in terms of physical activity ( p = 0.424), fat % ( p = 0.571) or cardiovascular risk ( p = 0.573). Although complex PTSD patients exhibit worse adherence to MD and lower healthy lifestyle scores, these differences do not seem to impact physical activity, body composition, or estimated cardiovascular risk. More research is needed to clarify if this lack of association accurately reflects the state of the PTSD population or results from insufficient statistical power.

Here, we presented a second-order scattering sensor based on the Zn 0.97 La 0.03 O compound (LaZnO) for selective and stable detection of glycated albumin (GA, glycemic long-term biomarker). The LaZnO sample was obtained through the co-precipitation method and then characterized using microscopic and spectroscopic techniques. Furthermore, the selectivity, molecular interference, temporal stability, and pH effects of the LaZnO SOS signal in the absence and presence of GA were investigated. The results indicate the stability of the SOS signal over more than 60 days. Assays conducted within the pH range of 5 to 8 indicate that the detection of GA remains unaffected under the given conditions. Selectivity studies show that the SOS signal of LaZnO is reduced only upon contact with GA, while interference studies show that detection is not affected by other chemical species. Additionally, the calibration curve test showed high sensitivity of the material, with a detection limit of 0.55 µg/ml. All the results suggest that LaZnO can deliver efficiency, selectivity, accuracy, and fast response as a GA biosensor, emphasizing LaZnO's usefulness in detecting protein biomarkers., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The objective of our study was to analyse the extracts from six medicinal herb roots (marshmallow, dandelion, liquorice, angelica, burdock, and comfrey) in terms of antioxidant capacity (ABTS, DPPH) and inhibition of advanced glycation end product (AGEs) formation. The quantification of phenolic acids and flavonoids was analysed using the UHPLC-DAD-MS method. Fifteen polyphenolic compounds were detected in the studied herbs. The higher number of polyphenols were found in marshmallows (ten polyphenols), while the lowest was in comfrey (five compounds). Liquorice root revealed the highest individual phenolic concentration (382 µg/g dm) with the higher contribution of kaempferol-3-O-rutinoside. Comfrey root extract was characterised by the most abundant TPC (Total Phenolic Content) value (29.79 mg GAE/ g dm). Burdock and comfrey showed the strongest anti-AGE activity studies with the BDA-GLU model. Burdock root was also characterised by the highest anti-AGE activity in the BSA-MGO model. The highest antioxidant capacity was determined by ABTS (72.12 µmol TE/g dw) and DPPH (143.01 µmol TE/g dw) assays for comfrey extract. The p-coumaric acid content was significantly correlated with anti-AGE activity determined by the BSA-MGO model. This research sheds new light on the bioactivity of root herbs, explaining the role of p-coumaric acid in preventing diabetes., (© 2024. The Author(s).)

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., (© 2024 Institute of Food Technologists.)

This study aimed to explore the inhibitory effect of pyrogallol on AGE formation in the bovine serum albumin (BSA)/glucose system for 21 days at 37 °C. The AGEs formation was measured in terms of Amadori products, total AGEs, argpyrimidine, and pentosidine. Molecular docking was used to investigate the interaction between pyrogallol and BSA. According to the results, in the presence of pyrogallol, the formation of pentosidine and argpyrimidine AGEs decreased. The molecular interaction studies demonstrated that pyrogallol has a high affinity towards arginine residues of albumin. Finally, results proved pyrogallol is a vigorous antiglycation compound and fruitful for AGE inhibition.

Diabetic kidney disease (DKD) is the major cause of end-stage kidney disease. However, only renin-angiotensin system inhibitor with multidisciplinary treatments is effective for DKD. In 2019, sodium-glucose cotransporter 2 (SGLT2) inhibitor showed efficacy against DKD in Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation (CREDENCE) trial, adding a new treatment option. However, the progression of DKD has not been completely controlled. The patients with transient exposure to hyperglycemia develop diabetic complications, including DKD, even after normalization of their blood glucose. Temporary hyperglycemia causes advanced glycation end product (AGE) accumulations and epigenetic changes as metabolic memory. The drugs that improve metabolic memory are awaited, and AGE inhibitors and histone modification inhibitors are the focus of clinical and basic research. In addition, incretin-related drugs showed a renoprotective ability in many clinical trials, and these trials with renal outcome as their primary endpoint are currently ongoing. Hypoxia-inducible factor prolyl hydroxylase inhibitors recently approved for renal anemia may be renoprotective since they improve tubulointerstitial hypoxia. Furthermore, NF-E2-related factor 2 activators improved the glomerular filtration rate of DKD patients in Bardoxolone Methyl Treatment: Renal Function in chronic kidney disease/Type 2 Diabetes (BEAM) trial and Phase II Study of Bardoxolone Methyl in Patients with Chronic Kidney Disease and Type 2 Diabetes (TSUBAKI) trial. Thus, following SGLT2 inhibitor, numerous novel drugs could be utilized in treating DKD. Future studies are expected to provide new insights. [ABSTRACT FROM AUTHOR]

Background and Aims: This study, drawing on Global Burden of Disease (GBD) data, examines spatiotemporal trends in mortality and disability-adjusted life years (DALYs) linked to aortic aneurysm (AA) from high sodium intake. The aim is a comprehensive analysis globally, regionally, and nationally spanning 1990 to 2019., Methods and Results: Quantifying AA deaths and DALYs due to high sodium intake, incorporating age-standardized mortality rate (ASMR) and age-standardized DALYs rate (ASDR), revealed a global surge. Deaths rose by 86.09 %, DALYs by 74.02 % from 1990 to 2019. EAPC for ASMR and ASDR displayed negative trends (-0.72 and -0.77). High/middle-high Socio-demographic Index (SDI) regions bore higher burdens than lower SDI regions. Males consistently had higher burdens across SDI regions, with both genders showing a slight downward trend. Age-wise, AA deaths and DALYs rose with age, followed by decline. A positive correlation existed between SDI and global burden, inversely related to EAPC for ASMR and ASDR., Conclusion: AA burden from high sodium intake is pronounced in high SDI regions, necessitating targeted interventions. The global data highlights a significant increase in AA deaths and DALYs due to high sodium intake, urging prompt and effective control measures., Competing Interests: Conflict of interest The authors have no conflicts of interest to declare., (Copyright © 2023 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Glycated albumin (GA), defined as the percentage of serum albumin glycation, is a mid-term glycemic control marker for diabetes. The concentrations of both glycated human serum albumin (GHSA) and total human serum albumin (HSA) are required to calculate GA. Here, we report the development of a GA sensor employing two albumin aptamers: anti-GHSA aptamer which is specific to GHSA and anti-HSA aptamer which recognizes both glycated and non-glycated HSA. We combine these aptamers with extended gate field effect transistors (EGFETs) to realize GA monitoring without the need to pretreat serum samples, and therefore suitable for point of care and home-testing applications. Using anti-GHSA aptamer-immobilized electrodes and EGFETs, we measured GHSA concentrations between 0.1-10 μM within 20 min. The sensor was able to measure GHSA concentration in the presence of BSA for a range of known GA levels (5-29%). With anti-HSA aptamer-immobilized electrodes and EGFETs, we measured total HSA concentrations from 1-17 μM. Furthermore, GHSA and total HSA concentrations of both healthy and diabetic-level samples were determined with GHSA and HSA sensors. The measured GHSA and total HSA concentrations in three samples were used to determine respective GA percentages, and our calculations agreed with GA levels determined by reference methods. Thus, we developed simple and rapid dual aptamer-based EGFET sensors to monitor GA through measuring GHSA and total HSA concentration, without the need for sample pretreatment, a mandatory step in the current standard of enzymatic GA monitoring., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Koji Sode reports financial support was provided by University of North Carolina and NC State University Joint Department of Biomedical Engineering. Spyridon Pavlidis reports financial support was provided by the National Science Foundation. Mika Hatada reports financial support was provided by The Uehara Memorial Foundation. The authors declare no other competing interests. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Foods rich in carbohydrates or fats undergo the Maillard reaction during frying, which promotes the color, flavor and sensory characteristics formation. In the meanwhile, Maillard reaction intermediates and advanced glycation end products (AGEs) have a negative impact on food sensory quality and gut homeostasis. This negative effect can be influenced by food composition and other processing factors. Whole grain products are rich in polyphenols, which can capture carbonyl compounds in Maillard reaction, and reduce the production of AGEs during frying. This review summarizes the Maillard reaction production intermediates and AGEs formation mechanism in fried food and analyzes the factors affecting the sensory formation of food. In the meanwhile, the effects of Maillard reaction intermediates and AGEs on gut homeostasis were summarized. Overall, the innovative processing methods about the Maillard reaction are summarized to optimize the sensory properties of fried foods while minimizing the formation of AGEs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Diabetes mellitus is recognized as a major predisposing factor for Moraxella keratitis. However, how diabetes mellitus contributes to Moraxella keratitis remains unclear. In this study, we examined Moraxella keratitis; based on the findings, we investigated the impact of advanced glycation end products (AGEs) deposition in the cornea of individuals with diabetic mellitus on the adhesion of Moraxella isolates to the cornea. A retrospective analysis of 27 culture-proven cases of Moraxella keratitis at Ehime University Hospital (March 2006 to February 2022) was performed. Moraxella isolates were identified using matrix-assisted laser desorption ionization time-of-flight mass spectrometry. Among the patients, 30.4% had diabetes mellitus and 22.2% had the predominant ocular condition of using steroid eye drops. The species identified were Moraxella nonliquefaciens in 59.3% and Moraxella lacunata in 40.7% of patients. To investigate the underlying mechanisms, we assessed the effects of M. nonliquefaciens adherence to simian virus 40-immortalized human corneal epithelial cells (HCECs) with or without AGEs. The results demonstrated the number of M. nonliquefaciens adhering to HCECs was significantly increased by adding AGEs compared with that in controls (p < 0.01). Furthermore, in the corneas of streptozotocin-induced diabetic C57BL/6 mice treated with or without pyridoxamine, an AGE inhibitor, the number of M. nonliquefaciens adhering to the corneas of diabetic mice was significantly reduced by pyridoxamine treatment (p < 0.05). In conclusion, the development of Moraxella keratitis may be significantly influenced by the deposition of AGEs on the corneal epithelium of patients with diabetes mellitus., (© 2024. The Author(s).)

Neuropathological assessment was conducted on 1630 subjects, representing 5% of all the deceased that had been sent to the morgue of Uppsala University Hospital during a 15-year-long period. Among the 1630 subjects, 1610 were ≥41 years of age (range 41 to 102 years). Overall, hyperphosphorylated (HP) τ was observed in the brains of 98% of the 1610 subjects, and amyloid β-protein (Aβ) in the brains of 64%. The most common alteration observed was Alzheimer disease neuropathologic change (ADNC) (56%), followed by primary age-related tauopathy (PART) in 26% of the subjects. In 16% of the subjects, HPτ was limited to the locus coeruleus. In 14 subjects (<1%), no altered proteins were observed. In 3 subjects, only Aβ was observed, and in 17, HPτ was observed in a distribution other than that seen in ADNC/PART. The transactive DNA-binding protein 43 (TDP43) associated with limbic-predominant age-related TDP encephalopathy (LATE) was observed in 565 (35%) subjects and α-synuclein (αS) pathology, i.e., Lewy body disease (LBD) or multi system atrophy (MSA) was observed in the brains of 21% of the subjects. A total of 39% of subjects with ADNC, 59% of subjects with PART, and 81% of subjects with HPτ limited to the locus coeruleus lacked concomitant pathologies, i.e., LATE-NC or LBD-NC. Of the 293 (18% of the 1610 subjects) subjects with dementia, 81% exhibited a high or intermediate level of ADNC. In 84% of all individuals with dementia, various degrees of concomitant alterations were observed; i.e., MIXED-NC was a common cause of dementia. A high or intermediate level of PART was observed in 10 subjects with dementia (3%), i.e., tangle-predominant dementia. No subjects exhibited only vascular NC (VNC), but in 17 subjects, severe VNC might have contributed to cognitive decline. Age-related tau astrogliopathy (ARTAG) was observed in 37% of the 1610 subjects and in 53% of those with dementia.

Advanced glycation end-products (AGEs) stochastically accrue in skeletal muscle and on collagen over an individual's lifespan, stiffening the muscle and modifying the stem cell (MuSC) microenvironment while promoting proinflammatory, antiregenerative signaling via the receptor for advanced glycation end-products (RAGEs). In the present study, a novel in vitro model was developed of this phenomenon by cross linking a 3-D collagen scaffold with AGEs and investigating how myoblasts responded to such an environment. Briefly, collagen scaffolds were incubated with d-ribose (0, 25, 40, 100, or 250 mM) for 5 days at 37°C. C2C12 immortalized mouse myoblasts were grown on the scaffolds for 6 days in growth conditions for proliferation, and 12 days for differentiation and fusion. Human primary myoblasts were also used to confirm the C2C12 data. AGEs aberrantly extended the DNA production stage of C2C12s (but not in human primary myoblasts) which is known to delay differentiation in myogenesis, and this effect was prevented by RAGE inhibition. Furthermore, the differentiation and fusion of myoblasts were disrupted by AGEs, which were associated with reductions in integrins and suppression of RAGE. The addition of S100b (RAGE agonist) recovered the differentiation and fusion of myoblasts, and the addition of RAGE inhibitors (FPS-ZM1 and Azeliragon) inhibited the differentiation and fusion of myoblasts. Our results provide novel insights into the role of the AGE-RAGE axis in skeletal muscle aging, and future work is warranted on the potential application of S100b as a proregenerative factor in aged skeletal muscle. NEW & NOTEWORTHY Collagen cross-linked by advanced glycation end-products (AGEs) induced myoblast proliferation but prevented differentiation, myotube formation, and RAGE upregulation. RAGE inhibition occluded AGE-induced myoblast proliferation, while the delivery of S100b, a RAGE ligand, recovered fusion deficits.

We previously found that ribosomal protein L9 (RPL9) is a novel advanced glycation end product (AGE)-binding protein that can decrease pro-inflammatory TNF-α expression stimulated by lipopolysaccharide (LPS) plus high-mobility group box 1 (HMGB1), suggesting that RPL9 has a role in regulating LPS+HMGB1-stimulated inflammatory reactions. Among the various ribosomal proteins, it was found that RPS5 reproduced the regulatory activity of RPL9 on LPS+HMGB1-stimulated TNF-α expression in macrophage-like RAW264.7 cells. RPL9 and RPS5 share a common feature as cationic proteins. Polylysine, a cationic polypeptide, and a synthetic peptide of the cationic region from RPL9 also exhibited reducing activity on LPS+HMGB1-induced TNF-α expression. By pull-down assay, RPL9 and RPS5 were confirmed to interact with AGEs. When AGEs coexisted with LPS, HMGB1, plus RPL9 or RPS5, the reducing effect of TNF-α expression by these cationic ribosomal proteins was shown to be abrogated. The results suggest that cationic ribosomal proteins have a regulatory role in the pro-inflammatory response induced by LPS+HMGB1, and in the pathophysiological condition of accumulating AGEs, this regulatory effect is abolished, which exacerbates inflammation., (© 2023 International Union of Biochemistry and Molecular Biology, Inc.)

Nε-(carboxyethyl)lysine (CML), a typical advanced glycosylation end product produced during the processing of meat under high temperature, poses health risks. Active substances like polyphenols are known to inhibit the formation of harmful products during the processing of food. In this study, our objective was to prepare a double network hydrogel (DN) loaded with gallic acid using amyloid fibers and chitosan as a rigid and flexible network, respectively. The network as well as the interactions between the two networks were observed and analyzed. Chitosan concentration was the key factor regulating the structure and properties of the DN. At a chitosan concentration of 0.7%wt, the structure of DN became dense and its mechanical properties were improved, with the loading capacity and loading efficiency being increased by 143.79 % and 128.21 %, compared with those of amyloid fibril alone. Furthermore, the digestibility of gallic acid in simulated intestinal fluid was increased by 215.10 %. Moreover, adding DN to the beef patties effectively inhibited the formation of CML in a dose-response dependent manner. Addition of 3 wt% DN resulted in the inhibitory rate of CML in roast beef patties reaching a high 73.09 %. The quality and palatability of beef patties were improved. These findings suggest that DN shows great potential as an application that may be utilized to deliver active substances aimed at inhibiting CML in the meat processing industry., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Advanced glycation end-products (AGEs) are implicated in the pathogenesis of vascular disease. In previous studies we have found increased deposition of N(e)-(carboxymethyl)lysine (CML) in intramyocardial vasculature in the heart in acute myocardial infarction and myocarditis. It is known that the process of inflammation plays a role in the formation of AGEs. In this study we have explored the presence of CML (a major AGE) in the heart of patients with epicarditis using a monoclonal anti-CML antibody. Nine patients with epicarditis (n = 9) died and their hearts were used for this study, control were hearts from patients who died from conditions unrelated to heart disease and without signs of myocarditis or epicarditis CML deposition and complement were significantly increased in patients with epicarditis compared to control hearts. Thus epicarditis increases CML depositions in the intramyocardial vasculature., (© 2023 The Authors. International Journal of Experimental Pathology published by John Wiley & Sons Ltd on behalf of Company of the International Journal of Experimental Pathology (CIJEP).)

Background: The objective of this study was to provide a comprehensive analysis of the spatial distribution and temporal trends in the age-standardized incidence rates (ASIRs) of depression in adolescents aged 10-24 worldwide., Methods: Data from the Global Burden of Disease Study (GBD) 2019 were analyzed, adopting Sawyer's broad definition of adolescence encompassing ages 10 to 24. Estimated annual percentage changes (EAPCs) were used to assess temporal trends., Results: Globally, from 1990 to 2019, there was a decrease in the ASIR of depression in adolescents (EAPC = -0.23). Notably, this decrease was more pronounced in female adolescents compared to their male counterparts (EAPC = -0.12 and - 0.29, respectively). Conversely, high Sociodemographic Index (SDI) regions experienced a significant increase in the ASIR of depression among adolescents (EAPC = 0.87). Furthermore, it is worth mentioning that individuals aged 20-24 exhibited the highest incidence rate for depression followed by those aged 15-19 and then those aged 10-14. The largest increases in the ASIRs of depression occurred in High-income North America (EAPC = 1.19) and Malaysia (EAPC = 2.4), respectively., Limitations: Mathematical models were used to reconstruct and adjust data of different qualities, which might have introduced bias., Conclusions: The global burden of disease for depression among adolescents aged 10-24 years declined from 1990 to 2019. Special attention must be paid to older adolescents and areas with higher SDIs., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to disclose. All data generated or analyzed during this study are included in this published article and its supplementary information files., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Aims: Cyclophilin A (CyPA) induces leucocyte recruitment and platelet activation upon release into the extracellular space. Extracellular CyPA therefore plays a critical role in immuno-inflammatory responses in tissue injury and thrombosis upon platelet activation. To date, CD147 (EMMPRIN) has been described as the primary receptor mediating extracellular effects of CyPA in platelets and leucocytes. The receptor for advanced glycation end products (RAGE) shares inflammatory and prothrombotic properties and has also been found to have similar ligands as CD147. In this study, we investigated the role of RAGE as a previously unknown interaction partner for CyPA., Methods and Results: Confocal imaging, proximity ligation, co-immunoprecipitation, and atomic force microscopy were performed and demonstrated an interaction of CyPA with RAGE on the cell surface. Static and dynamic cell adhesion and chemotaxis assays towards extracellular CyPA using human leucocytes and leucocytes from RAGE-deficient Ager-/- mice were conducted. Inhibition of RAGE abrogated CyPA-induced effects on leucocyte adhesion and chemotaxis in vitro. Accordingly, Ager-/- mice showed reduced leucocyte recruitment and endothelial adhesion towards CyPA in vivo. In wild-type mice, we observed a downregulation of RAGE on leucocytes when endogenous extracellular CyPA was reduced. We furthermore evaluated the role of RAGE for platelet activation and thrombus formation upon CyPA stimulation. CyPA-induced activation of platelets was found to be dependent on RAGE, as inhibition of RAGE, as well as platelets from Ager-/- mice showed a diminished activation and thrombus formation upon CyPA stimulation. CyPA-induced signalling through RAGE was found to involve central signalling pathways including the adaptor protein MyD88, intracellular Ca2+ signalling, and NF-κB activation., Conclusion: We propose RAGE as a hitherto unknown receptor for CyPA mediating leucocyte as well as platelet activation. The CyPA-RAGE interaction thus represents a novel mechanism in thrombo-inflammation., Competing Interests: Conflict of interest: D.H. received compensation for travel expenses and participation fees from Abbott and speaker fees from Pfizer., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Purpose: Given the rising prevalence of high fasting plasma glucose (HFPG) over the past three decades, it is crucial to assess its global, national, and regional impact on chronic kidney disease (CKD). This study aims to investigate the burden of CKD attributed to HFPG and its distribution across various levels., Methods and Materials: The data for this research was sourced from the Global Burden of Diseases Study 2019. To estimate the burden of CKD attributed to HFPG, we utilized DisMod-MR 2.1, a Bayesian meta-regression tool. The burden was measured using age-standardized mortality rate (ASMR) and age-standardized disability-adjusted life years (DALYs) rate. Correlation analysis was performed using the Spearman rank order correlation method. Temporal trends were analyzed by estimating the estimated annual percentage change (EAPC)., Results: Globally in 2019, there were a total of 487.97 thousand deaths and 13,093.42 thousand DALYs attributed to CKD attributed to HFPG, which represent a substantial increase of 153.8% and 120%, respectively, compared to 1990. Over the period from 1990 to 2019, the burden of CKD attributable to HFPG increased across all regions, with the highest increases observed in regions with high socio-demographic index (SDI) and middle SDI. Regions with lower SDI exhibited higher ASMR and age-standardized DALYs (ASDR) compared to developed nations at the regional level. Additionally, the EAPC values, which indicate the rate of increase, were significantly higher in these regions compared to developed nations. Notably, high-income North America, belonging to the high SDI regions, experienced the greatest increase in both ASMR and ASDR over the past three decades. Furthermore, throughout the years from 1990 to 2019, males bore a greater burden of CKD attributable to HFPG., Conclusion: With an increasing population and changing dietary patterns, the burden of CKD attributed to HFPG is expected to worsen. From 1990 to 2019, males and developing regions have experienced a more significant burden. Notably, the EAPC values for both ASMR and ASDR were higher in males and regions with lower SDI (excluding high-income North America). This emphasizes the pressing requirement for effective interventions to reduce the burden of CKD attributable to HFPG., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Wei, Ren, Li, Qi, Yang and Li.)

The relationship between diabetes mellitus and ocular complications has been extensively studied by many authors. Diabetic keratopathy has already been well characterized and defined as a clinical entity. This review focuses on exploring corneal epithelial changes in diabetic patients, aiming to provide a pragmatic overview of the existing knowledge on this topic. The paper systematically examines alterations in corneal epithelial structure and their impact on diabetic patients. Advanced imaging techniques are also discussed for their role in precise characterization and improved diagnostics. Additionally, the paper explores the mechanisms behind corneal epithelial changes in diabetes, looking at factors such as hyperglycemia, oxidative stress, and Advanced Glycation End-Products. The impact of altered corneal epithelial integrity on barrier function and susceptibility to external issues is considered, addressing potential links to heightened proteolytic enzyme activities and delayed wound healing observed in diabetic individuals. The review also covers the practical implications of corneal epithelial changes, including the association with corneal erosions, persistent epithelial defects, and an increased risk of dry eye syndrome in diabetic patients.

Background: Diabetes has emerged as an important risk factor for COVID-19 adverse outcomes during hospitalization. We investigated whether the measurement of glycated albumin (GA) may be useful in detecting newly diagnosed diabetes during COVID-19 hospitalization., Methods: In this cross-sectional test accuracy study we evaluated HCPA Biobank data and samples from consecutive in-patients, from 30 March 2020 to 20 December 2020. ROC curves were used to analyse the performance of GA to detect newly diagnosed diabetes (patients without a previous diagnosis of diabetes and admission HbA1c ≥6.5%)., Results: A total of 184 adults (age 58.6 ± 16.6years) were enrolled, including 31 with newly diagnosed diabetes. GA presented AUCs of 0.739 (95% CI 0.642-0.948) to detect newly diagnosed diabetes. The GA cut-offs of 19.0% was adequate to identify newly diagnosed diabetes with high specificity (85.0%) but low sensitivity (48.4%)., Conclusions: GA showed good performance to identify newly diagnosed diabetes and may be useful for identifying adults with the condition in COVID-19-related hospitalization., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Chume et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Advanced glycation end-products (AGEs) may play a relevant role as inducers in the chronic inflammatory pathway present in immune-mediated diseases, such as systemic lupus erythematosus (SLE). AGEs concentrations have been associated, with discrepant results to date, with some parameters such as disease activity or accrual damage, suggesting their potential usefulness as biomarkers of the disease. Our objectives are to confirm differences in AGEs levels measured by cutaneous autofluorescence between SLE patients and healthy controls (HC) and to study their correlation with various disease parameters. Cross-sectional study, where AGEs levels were measured by skin autofluorescence, and SLE patients' data were compared with those of sex- and age-matched HC in a 1:3 proportion through a multiple linear regression model. Associations of AGEs levels with demographic and clinical data were analyzed through ANOVA tests. Both analyses were adjusted for confounders. AGEs levels in SLE patients were significantly higher than in HC ( p < 0.001). We found statistically significant positive associations with SLE disease activity index (SLEDAI) and damage index (SDI), physician and patient global assessment, C-reactive protein, leukocyturia, complement C4, IL-6 and oral ulcers. We also found a negative statistically significant association with current positivity of anti-nuclear and anti-Ro60 antibodies. AGEs seem to have a contribution in LES pathophysiology, being associated with activity and damage and having a role as a new management and prognosis biomarker in this disease. The association with specific antibodies and disease manifestations may indicate a specific clinical phenotype related to higher or lower AGEs levels.