Levels Of Advanced Glycation End Products Research Articles

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.

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.
 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.
 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.
 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.

Effects of a high-fat and high-carbohydrate diet on appetite regulation and central AMPK in the hypothalamus of blunt snout bream (Megalobrama amblycephala).

Adenosine monophosphate-activated protein kinase (AMPK) is a sensor of cellular energy changes and controls food intake. This study investigates the effect of a high-calorie diet (high fat diet [HFD], high carbohydrate diet [HCD]and high energy diet [HED]) on appetite and central AMPK in blunt snout bream. In the present study, fish (average initial weight 45.84 ± 0.07 g) were fed the control, HFD, HCDand HED in four replicates for 12 weeks. At the end of the feeding trial, the result showed that body mass index, specific growth rate, feed efficiency ratioand feed intakewere not affected (p > 0.05) by dietary treatment. However, fish fed the HFD obtained a significantly higher (p < 0.05) lipid productive value, lipid gainand lipid intakethan those fed the control diet, but no significant difference was attributed to others. Also, a significantly higher (p < 0.05) energy intake content was found in fish-fed HFD, HCDand HED than those given the control diet. Long-term HFD and HCD feeding significantly increased (p < 0.05) plasma glucose, glycated serum protein, advanced glycation end product, insulinand leptin content levels than the control group. Moreover, a significantly lower (p < 0.05) complex 1, 2and 3 content was found in fish-fed HFD and HCD than in the control, but no differences (p > 0.05) were attributed to those in HED. Fish-fed HED significantly upregulated (p < 0.05) hypothalamic ampα 1 and ampα 2 expression, whereas the opposite trend was observed in the hypothalamic mammalian target of rapamycinthan those in HFD and HCD compared to the control. However, hypothalamic neuropeptide y, peroxisome proliferator-activated receptor α (pparα), acetyl-coa oxidase and carnitine palmitoyltransferase 1 were significantly upregulated (p < 0.05) in the HCD group, while the opposite was seen in cholecystokininexpression compared to those in the control group. Our findings indicated that the central AMPK signal pathway and appetite were modulated according to the diet's energy level to regulate nutritional status and maintain energy homoeostasis in fish.

L-Theanine delays d-galactose-induced senescence by regulating the cell cycle and inhibiting apoptosis in rat intestinal cells.

Intestinal senescence is associated with several aging-related diseases. l-Theanine (LTA) has demonstrated strong potential as an antioxidant and antisenescence agent. This study investigated the regulatory effect of LTA on cellular senescence using an in vitro model of d-galactose (D-Gal)-induced senescence in the rat epithelial cell line, intestinal epithelioid cell-6 (IEC-6). Treatment of IEC-6 cells with 40 mg/mL D-Gal for 48 h resulted in the successful development of the senescent cell model. Compared with D-Gal alone, both LTA preventive and delayed intervention increased cell viability and the ratio of JC-1 monomers to aggregates, increased the antioxidant capacity, and decreased the advanced glycation end product (AGE) levels and the overall number of senescent cells. Preventive and delayed intervention with 1000 μM LTA alleviated the D-Gal-induced cell cycle arrest by regulating p38, p53, CDK4, and CDK6 expression at the mRNA and protein levels, and further induced CycD1 proteins. Moreover, LTA preventive intervention reduced apoptosis to a greater degree than delayed intervention by upregulating the expression of the receptors of AGEs, Bax, Bcl-2, and NF-κB at the mRNA and protein levels. Our findings indicate that LTA intervention could attenuate senescence in IEC-6 cells by regulating the cell cycle and inhibiting apoptosis. © 2023 Society of Chemical Industry.

The Relationship between Resistant Hypertension and Advanced Glycation End-Product Levels Measured Using the Skin Autofluorescence Method: A Case-Control Study.

Resistant hypertension is hypertension that cannot be controlled despite the use of three antihypertensive drugs, one of which is a diuretic. Resistant hypertension often coexists with advanced age, obesity, smoking, and diabetes. Advanced glycation end products (AGEs) are substances that are generated as a result of the glycation of proteins, lipids, and nucleic acids due to conditions such as hyperlipidemia, oxidative stress, and hyperglycemia. There are studies showing the relationships between AGE levels and aortic stiffness, hypertension, and microvascular and macrovascular complications in diabetes. In our study, we examined the relationship between resistant hypertension and AGE levels. Our study was planned as a case-control study, and 88 patients with resistant hypertension were included in the focus group, while 88 patients with controlled hypertension were included in the control group. The AGE levels of the patients were measured using the skin autofluorescence method. AGE levels were found to be significantly higher in patients with resistant hypertension than those recorded in the control group. A significant increase in AGE levels was also observed in patients with resistant hypertension and without diabetes compared with the control group. The levels of AGEs, which can be measured cheaply, noninvasively, and quickly with the skin autofluorescence method, may provide benefits in identifying these patients with resistant hypertension.

Circulating Concentrations of advanced Glycation end Products, Carboxymethyl Lysine and Methylglyoxal are Associated With Renal Function in Individuals With Diabetes

Diabetic kidney disease (DKD) is one of the most severe chronic complications of diabetes and is associated with higher level of advanced glycation end products (AGEs). The aim of this study was to investigate the diagnostic potential of combined detection of multiple serum AGEs in diagnosing DKD. Serum AGEs, Nε-(carboxymethyl) lysine (CML), Nε-(carboxyethyl) lysine, and methylglyoxal (MGO) levels were measured by enzyme-linked immunosorbent assay in 176 individuals with type 2 diabetes. Participants were classified into normoalbuminuria, microalbuminuria, and macroalbuminuria group according to their urinary albumin to creatinine ratio (UACR). Higher serum AGEs levels were found to be positively correlated with U-Alb, UACR, and blood urea nitrogen in the study of 176 individuals with type 2 diabetes. CML and MGO levels were positively correlated with U-Alb, UACR, blood urea nitrogen, Scr, and uric acid, and negatively correlated with estimated glomerular filtration rate (P<.05). Multivariate logistic regression analysis showed that elevated levels of AGEs, CML, and MGO were independent risk factors for the progression of DKD (odds ratio=1.861, 1.016, 7.607, P<.01). The sensitivity, specificity, and area under receiver operating characteristic curve of combined detection of AGEs, MGO, and CML were higher than those of three individual detections (area under the curve=0.952, 0.772, 0.868, 0905, respectively, P<.05). The combined detection of AGEs, CML, and MGO may improve the reliability of early diagnosis of DKD.

Dapagliflozin/Hesperidin Combination Mitigates Lipopolysaccharide-Induced Alzheimer's Disease in Rats.

Alzheimer's disease (AD) is the most common form of neurodegenerative disorders worldwide. Its pathologic features include massive neuroinflammation with abnormal deposition of β-amyloid peptide in the cerebral tissues leading to degeneration of the brain neurons. Adverse effects associated with the traditional drugs used for the treatment of this pathological condition have directed the research efforts towards searching for alternative effective agents with minimal adverse effects. The aim of this study was to elucidate the potential ameliorative effects of dapagliflozin and/or hesperidin on Alzheimer's disease (AD) induced by lipopolysaccharide (LPS) injection in rats. In a rodent model of AD, the effect of dapagliflozin with or without hesperidin on the biochemical parameters and the behavioral tests as well as the histopathological parameters was determined. Each of dapagliflozin and hesperidin restored the behavioral tests to the reference values, augmented the antioxidant defense mechanisms, ameliorated the neuronal inflammatory responses, combatted the changes in Toll-like receptor-4 (TLR-4)/High-mobility group box 1 (HMGB1) protein signaling and receptors of advanced glycation end products (RAGE) levels, and restored the balance between the apoptotic signals and autophagy in the hippocampal tissues. Additionally, both agents exhibited an outstanding ability to combat LPS-induced perturbations in the histopathological and electron microscopic image of the brain tissues. These favorable effects were significantly encountered in the group treated with dapagliflozin/hesperidin combination when compared versus animals treated with either dapagliflozin or hesperidin. In conclusion, inhibition of the hippocampal HMGB1/TLR4/RAGE signaling, the pro-inflammatory axis, and apoptosis alongside augmentation of the antioxidant defenses and autophagy can be regarded as beneficial effects by which dapagliflozin/hesperidin combination may combat LPS-triggered AD.

The Role of Advanced Glycation End-Product Levels Measured by Skin Autofluorescence in the Development of Mitral Annular Calcification.

As a person ages, mitral annular calcification develops in the mitral annulus with increasing frequency. Lipid deposition, inflammation, and aging-related degeneration have been cited as potential causes of this pathophysiology, though there is currently no conclusive evidence to support this. AGEs accumulate in tissues due to the glycation of proteins and lipids, increasing the release of proinflammatory cytokines secondary to oxidative stress through the AGE receptor. The AGE levels increase in diabetic microvascular complications and degenerative aortic valve disease. Our study was planned prospectively as a case-control study involving 94 MAC-positive patients and 94 MAC-negative patients. The demographics, echocardiographic data and AGE levels of the patients were measured and recorded using the skin autofluorescence method. AGE levels were significantly higher in the MAC-positive patient group (3.2 vs. 2.7; p < 0.001). The AGE levels were observed as an independent predictor of MAC development in a regression analysis (OR: 8.05, 95% CI: 3.74-17.33, p < 0.001). In a ROC-curve analysis, the AUC was 0.79 (95% CI: 0.72-0.85). At a cut-off value of 2.7, 79.7% sensitivity and 69.1% specificity were observed. AGE levels can be used to cheaply, easily and non-invasively identify patients at risk of developing MAC.

Trajectories of Host-Response Subphenotypes in Patients With COVID-19 Across the Spectrum of Respiratory Support

Hospitalized patients with severe COVID-19 follow heterogeneous clinical trajectories, requiring different levels of respiratory support and experiencing diverse clinical outcomes. Differences in host immune responses to SARS-CoV-2 infection may account for the heterogeneous clinical course, but we have limited data on the dynamic evolution of systemic biomarkers and related subphenotypes. Improved understanding of the dynamic transitions of host subphenotypes in COVID-19 may allow for improved patient selection for targeted therapies. We examined the trajectories of host-response profiles in severe COVID-19 and evaluated their prognostic impact on clinical outcomes. In this prospective observational study, we enrolled 323 inpatients with COVID-19 receiving different levels of baseline respiratory support: (1) low-flow oxygen (37%), (2) noninvasive ventilation (NIV) or high-flow oxygen (HFO; 29%), (3) invasive mechanical ventilation (27%), and (4) extracorporeal membrane oxygenation (7%). We collected plasma samples on enrollment and at days 5 and 10 to measure host-response biomarkers. We classified patients by inflammatory subphenotypes using two validated predictive models. We examined clinical, biomarker, and subphenotype trajectories and outcomes during hospitalization. IL-6, procalcitonin, and angiopoietin 2 persistently were elevated in patients receiving higher levels of respiratory support, whereas soluble receptor of advanced glycation end products (sRAGE) levels displayed the inverse pattern. Patients receiving NIV or HFO at baseline showed the most dynamic clinical trajectory, with 24% eventually requiring intubation and exhibiting worse 60-day mortality than patients receiving invasive mechanical ventilation at baseline (67% vs 35%; P < .0001). sRAGE levels predicted NIV failure and worse 60-day mortality for patients receiving NIV or HFO, whereas IL-6 levels were predictive in all patients regardless of level of support (P < .01). Patients classified to a hyperinflammatory subphenotype at baseline (< 10%) showed worse 60-day survival (P < .0001) and 50% of them remained classified as hyperinflammatory at 5 days after enrollment. Longitudinal study of the systemic host response in COVID-19 revealed substantial and predictive interindividual variability influenced by baseline levels of respiratory support.

The relationships between plasma advanced glycation end products level and cognitive function in middle-aged and elderly Chinese subjects.

To determine the relationships between circulating representative advanced glycation end products (AGEs) and cognitive performance in middle-aged and elderly Chinese adults. A cross-sectional study with 1834 participants were included. Cognitive performance was assessed using the Mini-Mental State Examination (MMSE). Plasma free AGEs including Nε-carboxymethyl-L-lysine (CML), Nε-(1-carboxyethyl) lysine (CEL), S-carboxymethyl-L-cysteine (CMC) and Nδ-(5-hydro-5-methyl-4-imidazolon-2-yl)-ornithine (MG-H1) were measured by ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Multivariate adjusted linear and logistic regression analysis were used to explore the associations between plasma AGEs and cognitive function. The prevalence of mild cognitive impairment (MCI) was 17.94%. Plasma CMC and MG-H1 level were negatively associated with MMSE score (β=-0.42, p<0.001 for all) in the multivariate linear regression analysis. In the multivariate logistic regression analysis, compared to the lowest tertile, participants within the highest tertile of CMC and MG-H1 had increased risk of MCI [ORs (95% CI): 1.62 (1.21-2.17), P trend <0.001, and ORs (95% CI): 1.30 (0.97-1.76), P trend=0.069, respectively]. In addition, the weighted quantile sum (WQS) index was negatively associated with MMSE (β=-0.48, P<0.001) and increased risk of MCI [ORs (95% CI): 1.35 (1.20-1.52), P<0.001]. Combined exposure of plasma free AGEs including CML, CEL, CMC and MG-H1 were associated with increased risk of cognitive impairment. Plasma CMC and MG-H1 might the main contributors for cognitive impairment, while further longitudinal studies are required to verify the associations.

Nuclear factor erythrogen-2 associated factor 2 (Nrf2) signaling is an essential molecular pathway for the anti-aging effect of whey protein in the prefrontal cortex of aging rat model (Histological and Biochemical Study)

Aging is a highly complicated natural process. Brain aging is associated with remarkable neurodegenerative changes and oxidative damage. Whey protein (WP) has been mentioned to have an antioxidant property. Nuclear factor erythrogen-2 associated factor 2 (Nrf2) signaling pathway is an antioxidant defense system. Nrf2 activity declines with age so, its activation could be a promising therapeutic strategy for aging. This study aimed to explore the anti-aging role of WP against D-galactose (D-gal) induced age-related degenerative changes and oxidative damage in the prefrontal cortex (PFC) and investigate its underlying mechanisms. Forty adult male rats were divided into 4 groups; control, WP group received WP (28.77 mg/kg/day) by gastric tube on the 4th experimental week; D-gal (model group) received D-gal (300 mg/kg/day) intraperitoneally for 8 weeks and D-gal +WP group received WP on the 4th week of D-gal treatment. Specimens from PFC were obtained for biochemical, histological, immunohistochemical and western blot analysis. WP treatment in D-gal +WP group reduced lipid peroxidation, enhanced antioxidant enzyme activities, decreased advanced glycation end products level and improved the histological and ultrastructural alterations. Moreover, the number of neurons expressed the senescence marker; p21 and percentage area of the astrocytic marker; glial fibrillary acidic protein were significantly reduced. WP also enhanced Nrf2 pathway and its downstream targets; heme oxygenase-1 and NADPH quinone oxidoreductase 1. In conclusion WP alleviates the D-gal-induced PFC aging through activating Nrf2 pathway, reducing cell senescence and gliosis. So, it may be a potential therapeutic target to retard the aging process.