Levels Of Advanced Glycation End Products Research Articles

Alterations in subgingival microbiome and advanced glycation end-products levels in periodontitis with and without type 1 diabetes mellitus: a cross-sectional study.

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

The Role of Advanced Glycation End Products in Saphenous Vein Graft Failure

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

6870 Cardiac Imaging And Metabolomics Studies Suggest Differential Risk And Protective Biomarkers For Cardiovascular Disease In Renoprotected, Long-Duration Type 1 Diabetes

Abstract Disclosure: M. Yu: None. S. Jangolla: None. N. Ziemniak: None. E. Viebranz: None. T. Chokshi: None. K. Park: None. I. Wu: None. H. Shah: None. G.L. King: None. Cardiovascular disease (CVD) is a major cause of mortality in people with Type 1 diabetes (T1D), especially in those with nephropathy (DN). However, in long-duration T1D, a substantial proportion of individuals without DN still exhibit excessive CVD risks. The Joslin 50-Year “Medalist” Study (n=1043), composed of people with T1D≥50 years, are ideal for studying CVD in a renoprotected T1D cohort, as only 13% have DN, and yet 40% have CVD, despite excellent control of lipids and blood pressure. Stratifying the Medalists by DN revealed that exercise was cardioprotective in the group with DN (OR 0.60, p=0.04); while age at T1D diagnosis (OR 1.03, p=0.01), HbA1c (OR 1.25, p=0.01), C-reactive protein (OR 1.14, p=0.01), and interleukin-6 (OR 1.13, p=0.01) all increased CVD risk in Medalists without DN. A subset of Medalists also underwent coronary artery calcification scans (CAC; n=153) and cardiac magnetic resonance imaging of left ventricular (LV) structure and function (CMR; n=111). The majority of these Medalists (97.8%) had detectable CAC&amp;gt;0; furthermore, the median CAC score of 1000 was higher at any cutoff compared to similar age-matched T1D and Type 2 diabetes (T2D) populations with higher DN prevalence. In contrast, mean CMR values in this Medalist subset were comparable to other cohorts. Continuous glucose monitoring (CGM) metrics for hyperglycemia (mean glucose, β=0.002, p=0.03; glucose management indicator, β=0.09, p=0.03; and time above range&amp;gt;180 mg/dL, β=0.003, p=0.02), but not glucose variability or hypoglycemia, were associated with LV remodeling in the Medalists, even after adjusting for eGFR. Likewise, plasma levels of advanced glycation end-products (AGEs) N-carboxyethyl-lysine (CEL), N-carboxymethyl-lysine (CML), and methylglyoxal-derived hydroimidazolone (MGH1) were associated with CAC (β=16.22, p=0.05; β=15.21, p=0.01; and β=10.18, p=0.01, respectively) and LV remodeling (β=0.001, p=0.09; β=0.001, p=0.05; and β=0.001, p=0.04, respectively) in the Medalists. The association of CEL with CVD replicated in a separate Medalist subset (n=311) with self-reported CVD data (OR 1.26, p=0.01). Plasma global metabolomics studies (n=140) revealed that amino acid activation pathways, with lower levels of branched chain amino acids, were associated with CAC (FDR=0.002); while amino acid metabolism pathways were associated with less favorable LV volumes (FDR=0.03). In this comprehensive study of aging T1D people with no substantial DN, hyperlipidemia, or hypertension, cardiac imaging and metabolomics studies suggest disproportionate advanced CAC, as compared to subclinical LV remodeling or dysfunction, and highlight the importance of targeting hyperglycemia for CVD risk reduction. Plasma metabolites associated with CVD in T1D are different from those in T2D, and may provide novel information on potential therapeutic targets for CVD in T1D. Presentation: 6/1/2024

Persistent Post COVID-19 Endothelial Dysfunction and Oxidative Stress in Women.

The assessment of endothelial dysfunction and free radical homeostasis parameters were performed in 92 women, aged 45 to 69 years, divided into the following groups: women without COVID-19 (unvaccinated, no antibodies, control); women with acute phase of COVID-19 infection (main group, COVID-19+); 12 months post COVID-19+; women with anti-SARS-CoV-2 IgG with no symptoms of COVID-19 in the last 12 months (asymptomatic COVID-19). Compared to the control, patients of the main group had lower glutathione peroxidase (GPx) and superoxide dismutase (SOD) activities, decreased advanced glycation end products (AGEs) level, higher glutathione reductase (GR) activity, and higher glutathione S transferases pi (GSTpi), thiobarbituric acid reactants (TBARs), endothelin (END)-1, and END-2 concentrations (all p ≤ 0.05). The group with asymptomatic COVID-19 had lower 8-OHdG and oxidized glutathione (GSSG) levels, decreased total antioxidant status (TAS), and higher reduced glutathione (GSH) and GSH/GSSG levels (all p ≤ 0.05). In the group COVID-19+, as compared to the group without clinical symptoms, we detected lower GPx and SOD activities, decreased AGEs concentration, a higher TAS, and greater GR activity and GSTpi and TBARs concentrations (all p ≤ 0.05). The high content of lipid peroxidation products 12 months post COVID-19+, despite decrease in ENDs, indicates long-term changes in free radical homeostasis. These data indicate increased levels of lipid peroxidation production contribute, in part, to the development of free radical related pathologies including long-term post COVID syndrome.

Low bone turnover is associated with advanced glycation end-products, oxidative stress, and inflammation induced by type 2 diabetes mellitus.

Type 2 diabetes mellitus (T2DM) can lead to multiple complications. T2DM-related bone damage has been linked to abnormal bone turnover, but it cannot fully explain the mechanisms of T2DM bone disease. This study attempts to elucidate the underlying mechanisms of poor bone quality in T2DM. Hence, T2DM model was induced by a high-fat diet combined with a single streptozotocin injection in 7-week-old male SD rats. Osteoblasts derived from SD rats were cultured in high glucose to mimic hyperglycemia. Low bone turnover was observed in T2DM bone with elevated levels of advanced glycation end-products (AGEs) and receptor for AGEs (RAGE). Additionally, higher levels of oxidative stress and inflammatory factors were found in T2DM bone. AGEs content in bone was pairwise correlated with RAGE, hydrogen peroxide, and inflammatory factors. Serum levels of RAGE, oxidative stress, and inflammatory factors were higher in T2DM, while AGEs content tended to be lower. Besides, 35 differentially expressed metabolites were screened in T2DM serum. Osteoblasts exposed to high glucose displayed analogous abnormal changes in these biomarkers. Thus, low bone turnover in T2DM might be partially due to excess oxidative stress and inflammation induced by AGE-RAGE signaling. Furthermore, these biomarker levels in serum were mostly consistent with bone, demonstrating their possibility for predicting bone quality in T2DM.

Improvement of skin condition and intestinal microbiota via Heyndrickxia coagulans SANK70258 intake: A placebo-controlled, randomized, double-blind, parallel-group comparative study

ObjectiveHeyndrickxia coagulans SANK70258, a representative probiotic, is known for alleviating inflammation caused by cedar pollen, improving the intestinal environment and bowel movements. A previous study on consuming H. coagulans SANK70258 together with galactooligosaccharides showed a trend toward improvement in skin scaliness scores and subjective assessments of skin roughness. However, the effect of H. coagulans SANK70258 alone on the skin remains unclear. Thus, we aimed to re-evaluate the effects of the intake of H. coagulans SANK70258 alone on skin conditions and the intestinal environment through a clinical trial. MethodsThis placebo-controlled, double-blind clinical trial involved 80 Japanese women aged 30 to 65 with perceived skin roughness. Participants were divided into placebo and test groups. Over eight weeks, the test group consumed H. coagulans SANK70258, and its effects on skin condition and intestinal health were examined. ResultsThe probiotic group showed significant intestinal improvements, with reduced fecal phenol levels (p = 0.044) and pH (p = 0.022), as well as enhanced skin lightness (L* value) (p = 0.040) and liver function tests. Metabolic analyses revealed decreases in fecal Nε-(carboxymethyl)lysine and plasma hydroxyproline, suggesting skin health benefits. There were also significant improvements in skin scaliness (p = 0.015) and bowel movement frequency (p = 0.032) in subgroup analysis. ConclusionsH. coagulans SANK70258 can improve skin health by improving the intestinal lining. This probiotic reduces the levels of intestinal putrefactive products and advanced glycation end-product levels in feces, suggesting that it may affect not only skin health but also systemic tissues such as the liver.

Are There Differences in Skin Autofluorescence-Measured Advanced Glycation End-Product Levels between Chronic Kidney Disease and Kidney Transplant Recipients?

The aim of this cross-sectional study was to evaluate the differences in the levels of advanced glycation end products (AGE) between patients with chronic kidney disease (CKD) and kidney transplant recipients (KTRs) and to investigate the risk factors for the AGE levels in each group of these patients. There were 217 participants total, of which 99 (45.6%) were KTRs and 118 (54.4%) had CKD. Data on the levels of AGE, body mass composition, anthropometric parameters, central and peripheral blood pressure, and clinical and laboratory parameters were gathered for each study participant. The AGE values of the CKD and KTRs groups did not differ from one another. In both groups, a lower estimated glomerular filtration rate, male sex, and older age were positive predictors for increased AGE values. Furthermore, higher levels of AGE were linked to lower central systolic blood pressure (cSBP) in the CKD group, whilst, in the KTRs group, higher levels of AGE were linked to a shorter time since kidney transplantation (KTx), more years of dialysis prior to KTx, lower levels of trunk visceral fat, the presence of arterial hypertension, and the absence of prescriptions for the antihypertensive medications urapidil and angiotensin II receptor blockers. Further studies are needed to better understand the above associations. Consequently, a personalised multidisciplinary approach to assess the cardiovascular as well as dietary and lifestyle risk factors to reduce the AGE levels in both KTRs and CKD patients may be implemented.

Association between sex hormones and erectile dysfunction in men without hypoandrogenism

In addition to testosterone, various endocrine hormones, such as dehydroepiandrosterone sulfate (DHEA-S) and estradiol, may be involved in erectile function. However, the role of these sex hormones in the erectile function of men without hypoandrogenism remains unclear. This cross-sectional study included 398 community-dwelling men without hypoandrogenism. The participants were categorized into the non-ED and ED groups. Multivariable logistic regression analyses were performed to investigate the relationship between ED and serum sex hormone levels, including total testosterone, DHEA-S, estradiol, luteinizing hormone (LH), follicle-stimulating hormone (FSH), and prolactin. Among the 398 men, 66 (17%) and 332 (83%) were categorized into the non-ED and ED groups, respectively. In the multivariable analyses, serum DHEA-S and estradiol levels were significantly associated with ED (odds ratio [OR]: 0.996, P = 0.030; OR: 1.082, P = 0.002; respectively), whereas serum total testosterone, LH, FSH, and prolactin levels did not demonstrate significant association. After adjusting for age, none of neutrophil-to-lymphocyte ratio, serum plasminogen activator inhibitor-1 levels, and skin advanced glycation end-products levels demonstrated significant correlation with serum DHEA-S and estradiol levels. In conclusion, lower testosterone levels did not affect ED in men with normal testosterone levels, whereas serum DHEA-S and estradiol levels were significantly associated with ED.

Investigation of Advanced Glycation End Products in Liver, Adipose, and Renal Tissue of Mice on a High-Fat Diet.

Obesity is a complex condition associated with disruptions in carbohydrate, protein, and fat metabolism, linked to increased insulin resistance and glucose intolerance. High levels of Advanced Glycation End-products (AGEs) are associated with a range of chronic diseases, including kidney diseases, diabetic complications, cardiovascular diseases, and neurodegenerative diseases. Our study aims to investigate the accumulation of AGEs in the liver, renal and adipose tissues of mice fed a high-fat diet, contributing to a deeper understanding of obesity and its related metabolic disorders. Our study consists of three different groups fed with diets containing 60% and 10% fat. The Experiment 1 group was maintained on their diet for 12 weeks, while the obese 2 and control groups continued their diets for 24 weeks. AGEs in the liver and kidney tissues obtained were measured using the High-performance liquid chromatography grade (HPLC) method. Higher accumulation of AGEs has been observed in kidney tissue compared to adipose and liver tissues (p < 0.05). Moreover, the GO levels were notably higher in liver tissue than in adipose tissue of the D1 and D2 groups (p < 0.0001). Our results suggest that particularly in kidney tissue, increased filtration burden, functional impairment, and receptor interaction due to obesity may be effective. The lower levels of AGEs detected, especially in the obese groups compared to the control, can be attributed to the inability to metabolize AGEs due to tissue damage caused by obesity.

An Intensive Culinary Intervention Programme to Promote Healthy Ageing: The SUKALMENA-InAge Feasibility Pilot Study.

Dietary interventions are a key strategy to promote healthy ageing. Cooking skills training emerges as a promising approach to acquiring and maintaining healthy eating habits. The purpose was to evaluate the effectiveness of a culinary programme to improve healthy eating habits among overweight/obese adults (55-70 years old). A total of 62 volunteers were randomly (1:1) assigned to an culinary intervention group (CIG) or a nutritional intervention group (NIG). Dietary, cooking, and health-related outcomes, including body advanced glycation end product (AGE) levels, were evaluated at baseline and after four weeks. Mixed-effects linear models were used to assess the effects of the interventions within and between groups. Among the 56 participants who completed the trial, CIG participants achieved a significant improvement in Mediterranean diet adherence (1.2; 95%CI, 0.2 to 2.2) and a reduction in the use of culinary techniques associated with a higher AGE formation in foods (-2.8; 95%CI, -5.6 to -0.2), weight (-1.5; 95%CI, -2.5 to -0.5), body mass index (-0.5; 95%CI, -0.8 to -0.2), waist circumference (-1.4; 95%CI, -2.6 to -0.2), and hip circumference (-1.4; 95%CI, -2.4 to -0.4) compared with the NIG participants. Although a greater confidence in cooking in the CIG was found, attitudes and cooking habits did not improve. No significant differences in biochemical parameters or AGEs were found between groups. In conclusion, a culinary intervention could be successful in promoting healthy eating and cooking habits compared to a programme based on nutrition education alone. Nevertheless, further efforts are needed to strengthen attitudes and beliefs about home cooking, to address potential barriers and understand the impact of cooking interventions on biological parameters. Larger studies with longer follow-ups are needed to evaluate the relationship between cooking, diet, and health.

Inhibitory mechanism of carboxymethyl cellulose on advanced glycation end products in plant-based meat alternatives

Plant-based meat alternatives (PBMA) were detected with high advanced glycation end products (AGEs) levels in our previous study, threatening human health. In this study, carboxymethyl cellulose (CMC) exhibited excellent inhibitory effects on AGEs in both PBMA and chemical model systems. Moreover, the inhibitory effects were dependent on the levels of CMC addition. With 4% CMC addition, the contents of Nε-carboxymethy-l-lysine (CML) and Nε-carboxyethy-l-lysine (CEL) in PBMA decreased by 75% and 83%, respectively. Through comprehensive characterizations and high-resolution mass spectrometry analysis, three possible inhibitory pathways were proposed at the molecular level: CMC improved the thermal stability of soy protein isolates (SPI) via covalent bond; CMC occupied the amino reaction sites on SPI and competitively inhibited the reaction between SPI and glucose; CMC scavenged the intermediates of AGEs (i.e glyoxal and methylglyoxal). This research lays a theoretical foundation on the inhibition of AGEs in PBMA through the regulation of hydrocolloids.

Fracture behavior of human cortical bone with high glycation content under dynamic loading

The present study simulates the fracture behavior of diabetic cortical bone with high levels of advanced glycation end-products (AGEs) under dynamic loading. We consider that the increased AGEs in diabetic cortical bone degrade the materials heterogeneity of cortical bone through a reduction in critical energy release rates of the microstructural features. To simulate the initiation and propagation of cracks, we implement a phase field fracture framework on 2D models of human tibia cortical microstructure. The simulations show that the mismatch between the fracture properties (e.g., critical energy release rate) of osteons and interstitial tissue due to high AGEs contents can change crack growth trajectories. The results show crack branching in the cortical microstructure under dynamic loading is affected by the mismatches related to AGEs. In addition, we observe cortical features such as osteons and cement lines can prevent multiple cracking under dynamic loading even with changing the mismatches due to high AGEs. Furthermore, under dynamic loading, some toughening mechanisms can be activated and deactivated with different AGEs contents. In conclusion, the current findings present that the combination of the loading type and materials heterogeneity of microstructural features can change the fracture response of diabetic cortical bone and its fragility.

Synergistic Osteogenic and Antiapoptotic Framework Nucleic Acid Complexes Prevent Diabetic Osteoporosis

AbstractDiabetes mellitus (DM) is characterized by elevated blood glucose and advanced glycation end product (AGEs) levels. Increased AGEs in bone tissue inhibit osteogenic differentiation by bone marrow mesenchymal stem cells (BMSCs), leading to bone loss and osteoporosis in diabetic patients. Enhancing the osteogenic differentiation capacity of BMSCs in the presence of abundant AGEs can improve bone health and prevent osteoporosis in DM patients. The flavonoid, Quercetin, has anti‐inflammatory, antibacterial, and antitumor properties; however, it is insoluble in water and thus not easily absorbed by the body. Nanodrug delivery systems such as tetrahedral framework nucleic acids (tFNAs) exhibit excellent biocompatibility, efficient cell uptake, and drug piggybacking. In the present study, tFNAs with quercetin is complexed to form a novel nanodrug (tFNAs/Que) that combined the features of both components. tFNAs/Que promote osteogenic differentiation by BMSCs in an in vitro AGEs‐rich environment, maintain bone mass, and prevent diabetic osteoporosis in DM mice in vivo. The mechanism of tFNAs/Que against AGEs may be related to the JNK signaling pathway. In conclusion, it is shown that tFNAs/Que has a dual regulatory role by promoting osteogenic differentiation and inhibiting apoptosis. Such a feature is promising for the prevention and treatment of diabetic osteoporosis.

Soluble Receptor for Advanced Glycation End Products (sRAGE) Level and Its Prognostic Significance in Children with Acute Lymphoblastic Leukemia.

Acute lymphoblastic leukemias are the most common malignancies in childhood. Although its etiology is still unclear, it is thought that disorders in oxidative stress metabolism may contribute to leukemogenesis. Advanced glycation end products (AGEs) are formed as a result of the non-enzymatic binding of sugars to biomolecules. Oxidation reactions are triggered through AGE-Receptor (RAGE) interaction, resulting in the formation of reactive oxygen species. These can play crucial roles in cancer pathogenesis and leukemogenesis. It is thought that sRAGE (soluble RAGE) is the end product of glycation and circulates freely in the circulation by binding to RAGE ligands. We investigate novel leukemia biomarkers and focus on soluble RAGE (sRAGE) for acute lymphoblastic leukemia (ALL) diagnosis and prognosis. Thirty children (1-17 years) diagnosed with ALL were included in the study. Patients were divided into standard, medium, and high risk groups according to the Berlin-Frankfurt-Münster (BFM) treatment protocol. Patients were evaluated twice; at the time of diagnosis and at the sixth month of remission. sRAGE and blood parameters were compared with healthy controls (n = 30, 1-17 years). The sRAGE levels in ALL patients at diagnosis (138.7 ± 177.3 pg/mL) were found to be significantly higher than they were during the sixth month of remission (17.6 ± 21.1 pg/mL) and in healthy controls (22.2 ± 23.7 pg/mL). The cut-off value of the sRAGE level for the diagnosis of ALL was found to be 45 pg/mL in ROC analysis (sensitivity: 73.3%, specificity: 86.7%, AUC: 0.681). At the same time, the sRAGE level was found to be significantly higher in T-ALL patients (490.9 ± 236.9 pg/mL) than in B-ALL patients (84.5 ± 82.7 pg/mL). No significant difference was found in terms of the sRAGE level between standard (45.8± 33.1 pg/mL), medium (212 ± 222.1 pg/mL), and high (143.9 ± 111.5 pg/mL) risk group ALL patients classified according to the BFM protocol. Despite the fact that this was a small, single-center study, our findings highlight the potential use of sRAGE as a biomarker for diagnosing ALL and assessing response to treatment.

Oxidative stress is associated with Aβ accumulation in chronic sleep deprivation model

Amyloid-β (Aβ) accumulation is the main pathological change in Alzheimer's disease (AD), which results from the imbalance of production and clearance of Aβ in the brain. Our previous study found that chronic sleep deprivation (CSD) led to the deposition of Aβ in the brain by disrupting the balance of Aβ production and clearance, but the specific mechanism was not clear. In the present study, we investigated the effects of oxidative stress on Aβ accumulation in CSD rats. We found that the levels of reactive oxygen species (ROS) and malondialdehyde (MDA) significantly increased after CSD, while superoxide dismutase (SOD) decreased in the brain. Furthermore, the serum ROS was elevated and SOD declined after CSD. The levels of oxidative stress in the brain were significantly correlated with β-site APP-cleaving enzyme 1 (BACE1), low-density lipoprotein receptor-related protein-1 (LRP1), and receptor of advanced glycation end products (RAGE) levels in hippocampus and prefrontal lobe, and the concentration of serum oxidative mediators were strongly correlated with plasma levels of soluble LRP1 (sLRP1) and soluble RAGE (sRAGE). These results suggested that the oxidative stress in the brain and serum may involved in the CSD-induced Aβ accumulation. The underlying mechanism may be associated with disrupting the balance of Aβ production and clearance.

An Oversampling Technique for Handling Imbalanced Data in Patients with Metabolic Syndrome and Periodontitis

Objectives: Periodontitis has been suggested to be associated with several systemic diseases and conditions including obesity, metabolic syndrome, diabetes, chronic renal disease, respiratory disorders, and cardiovascular diseases. Metabolic syndrome (MetS) is a collection of impairment and is a risk factor for type 2 diabetes and cardiovascular disease. Our study is aimed to handle MetS unbalanced data using the synthetic minority over-sampling technique (SMOTE) to increase accuracy and reliability.&#x0D; Materials and Methods: Six metabolic syndrome patients and 26 systemically healthy subjects with periodontitis were recruited in this study. Clinical parameters (Plaque index (PI), gingival index (GI), probing pocket depth (PPD), clinical attachment loss (CAL), and bleeding on probing (BOP)) were obtained, smoking status and body-mass index (BMI), systemic diseases, fasting glucose levels, hemoglobin A1c (HbA1c) levels and serum advanced glycation end-products (AGE) levels were recorded by one examiner. First, the data was pre-processed by removing missing values, outliers and normalizing the data. Then, SMOTE technique was used to oversample the minority class. SMOTE works by creating synthetic data points that are similar to the existing minority class instances. The experimental dataset included numerous machine learning algorithms and assessed accuracy using both pre- and post-oversampling methods.&#x0D; Results: Our findings suggest that by increasing the sample size of a study, researchers can gain more accurate and reliable results. This is especially important when studying a population with a lower sample size, as the results may be skewed.&#x0D; Conclusion: SMOTE may result in over fitting on numerous copies of minority class samples.

Exploring the role of Maillard reaction and lipid oxidation in the advanced glycation end products of batter-coated meat products during frying

The Maillard reaction occurs during the frying of batter-coated meat products, resulting in the production of advanced glycosylation products that are harmful to human health. This study investigated the effects of frying temperature (140, 150, 160, 170 and 180 ℃) and time (80, 100, 120, 140 and 160 s) on the quality, advanced glycation end product (AGE) level and the relationship between these parameters in batter-coated meat products were investigated. The results showed that with an increase in frying temperature and time, the moisture content of the batter-coated meat products gradually decreased, the thiobarbituric Acid Reactive Substance (TBARS) values and oil content increased to 0.37 and 21.7 %, respectively, and then decreased, and CML and CEL content increased to 7.30 and 4.86 mg/g, respectively. Correlation analysis showed that the moisture content and absorbance at 420 nm, as well as TBARS values, were highly correlated with the oil content in batter-coated meat products. Additionally, the absorbance at 420 nm and TBARS levels were significantly correlated with AGE levels. Moreover, the AGE content in batter-coated meat products was less variable at lower frying temperatures or shorter frying times, and the influence of temperature on AGE formation was greater than that of time. Overall, these findings may help to better control the cooking conditions of batter-coated meat products based on AGE profiles.

Baicalin ameliorates insulin resistance and regulates hepatic glucose metabolism via activating insulin signaling pathway in obese pre-diabetic mice

BackgroundDiabetes belongs to the most prevalent metabolic diseases worldwide, which is featured with insulin resistance, closely associated with obesity and urgently needs to be treated. Baicalin, belonging to natural flavonoids, has been reported to inhibit oxidative stress or inflammatoin. PurposeThis study investigated the properties of baicalin on modulating abnormal glucolipid metabolism, as well as the underlying in-vitro and in-vivo mechanisms. MethodsInsulin-resistant (IR)-HepG2 cells were stimulated by dexamethasone (20 µM) and high glucose (50 mM) for 48 h and incubated with or without baicalin or metformin for another 16 h. Male C57BL/6 J mice were fed with a high-fat diet (HFD, 60 % kcal% fat) during the total 14 weeks. Obese mice were then administered with baicalin (50 and 100 mg/kg) or vehicle solution everyday through oral gavage during the last 4-week period. Moreover, baicalin metabolisms in vitro and in vivo were determined using UPLC/MS/MS to study its metabolism situation. ResultsExposure to dexamethasone and high glucose damaged the abilities of glycogen synthesis and glucose uptake with elevated oxidative stress and increased generation levels of advanced glycation end-products (AGEs) in HepG2 cells. These impairments were basically reversed by baicalin treatment. Four-week oral administration with baicalin ameliorated hyperglycemia and dyslipidemia in HFD-induced obese and pre-diabetic mice. Downregulation of IRS/PI3K/Akt signaling pathway accomplished with reduced GLUT4 expression and enhanced GSK-3β activity was observed in insulin resistant HepG2 cells as well as liver tissues from pre-diabetic mice; and such effect was prevented by baicalin. Moreover, baicalin and its matabolites were detected in IR-HepG2 cells and mouse plasma. ConclusionThe study illustrated that baicalin alleviated insulin resistance by activating insulin signaling pathways and inhibiting oxidative stress and AGEs production, revealing the potential of baicalin to be a therapeutic natural flavonoid against hepatic insulin and glucose-lipid metabolic disturbance in pre-diabetes accompanied with obesity.

Mechanism and application of Lactobacillus in type 2 diabetes-associated periodontitis.

Type 2 diabetes mellitus (T2DM) accelerates the progression of periodontitis through diverse pathways. Abnormal immune responses, excessive activation of inflammation, increased levels of advanced glycation end products, and oxidative stress have defined roles in the pathophysiological process of T2DM-associated periodontitis. Furthermore, in the periodontium of diabetic individuals, there are high levels of advanced glycation end-products and glucose. Meanwhile, progress in microbiomics has revealed that dysbacteriosis caused by T2DM also contributes to the progression of periodontitis. Lactobacillus, owing to its fine-tuning function in the local microbiota, has sparked tremendous interest in this field. Accumulating research on Lactobacillus has detailed its beneficial role in both diabetes and oral diseases. In this study, we summarize the newly discovered mechanisms underlying Lactobacillus-mediated improvement of T2DM-associated periodontitis and propose the application of Lactobacillus in the clinic.

How dietary advanced glycation end products could facilitate the occurrence of food allergy

BackgroundFood allergy (FA) is one of the most common chronic conditions in the pediatric age with an increasing prevalence under the pressure of environmental factors in predisposed individuals. It has been hypothesized that the increased consumption of ultra-processed foods, containing high levels of dietary advanced glycation end-products (AGEs), could facilitate the occurrence of food allergy. ObjectiveHere we provide preclinical and clinical evidence on the potential role of AGEs in facilitating the occurrence of FA. MethodsHuman enterocytes, human small intestine organ culture, and peripheral mononuclear blood cells (PBMCs) from children at risk for allergy were used to investigate the direct effect of AGEs on gut barrier, inflammation, Th2 cytokines response and mitochondrial function.The intake of the three most commonly glycation products in Western diet-foods Nε -(carboxymethyl) lysine (CML), Nε -(1-carboxyethyl) lysine (CEL), and Nδ -(5-hydro-5- methyl-4-imidazolon-2-yl)-ornithine (MG-H1), and the skin AGEs accumulation were comparatively investigated in children with FA and in age-matched healthy controls. ResultsHuman enterocytes exposed to AGEs showed alteration in gut barrier, AGEs receptor expression, reactive oxygen species production and autophagy, with increased transepithelial passage of food antigens. Small intestine organ culture exposed to AGEs showed an increase of CD25+ cells and proliferating crypt enterocytes. PBMCs exposed to AGEs showed alteration in proliferation rate, AGEs receptor activation, release of inflammatory and Th2 cytokines, and mitochondrial metabolism.Significant higher dietary AGEs intake and skin accumulation were observed in FA children (n=42) compared with age-matched healthy controls (n=66). ConclusionsThese data, supporting a potential role for dietary AGEs in facilitating the occurrence of FA, suggest the importance of limiting the AGEs exposure in the pediatric age as potential preventive strategy against this common condition.