Serum Levels Of AGEs Research Articles

Association between serum level of advanced glycation end products and obstructive sleep apnea-hypopnea syndrome: a meta-analysis.

ObjectiveThis meta-analysis was performed to assess the difference in the serum level of advanced glycation end products (AGEs) between patients with obstructive sleep apnea–hypopnea syndrome (OSAHS) and controls.MethodsA systematic literature search was performed using PubMed, Elsevier, SCI, Wanfang, Weipu, and China National Knowledge Internet. Eligible studies that reported the serum AGE level in patients with OSAHS were identified by two reviewers. Review Manager version 5.2 (The Nordic Cochrane Centre, The Cochrane Collaboration, Copenhagen, Denmark) and R version 3.10 (www.r-project.org) were employed for data synthesis.ResultsFive studies involving 670 subjects were identified. The meta-analysis showed that the mean serum AGE level in the OSAHS group was 0.98 mmol/L higher than those in the control group (95% confidence interval, 0.69–1.27).ConclusionsThis meta-analysis showed that the serum AGE level was elevated in patients with OSAHS. This finding suggests that AGEs may play an important role in insulin resistance in OSAHS and serve as a biomarker for patients with OSAHS with a high risk of type 2 diabetes mellitus.

Voluntary exercise reverses immune aging induced by oxidative stress in aging mice.

Excessive oxidative stress leads to aging due to persistent damage to the cells, tissues, and the entire organism. Immunosenescence is also a devastating consequence of oxidative stress, but there is a lack of research on effective ways to overcome it. In this study, we used physiologic and immunological aging mouse models that had sustained oxidative stress to investigate whether voluntary exercise and/or antioxidant treatment could overcome oxidative damage as well as aging. We established an aging model induced by continuously administering d-galactose (d-gal) to 6-week-old female C57BL/6J mice. We also assessed reversal of immunosenescence by providing free-wheel running and vitamin E (vit E) supplementation to this aging model. As an aging index, the level of advanced glycation end products (AGEs) in the blood was measured. Phenotypes of T cells in the thymus and spleen were examined as an index of immunosenescence. Intracellular reactive oxygen species (ROS) levels in the mouse spleen and levels of AGEs in the blood were significantly higher after 6 weeks of d-gal administration. In addition, immunosenescence was observed, in which the naïve:effector cell ratio in the spleen decreased. After 4 weeks of free-wheel running and vit E administration, both intracellular ROS and serum AGE levels decreased. Above all, free-wheel running restored the naïve:effector ratio of cytotoxic T lymphocytes reduced by d-gal administration. Taken together, these results suggest that voluntary exercise may be effective in restoring immunosenescence induced by oxidative stress.

Role of peroxisome proliferator-activated receptor-gamma activation on visfatin, advanced glycation end products, and renal oxidative stress in obesity-induced type 2 diabetes mellitus.

The present study focused on the role of peroxisome proliferator-activated receptor-gamma (PPAR-γ) activation on renal oxidative damages, serum visfatin, and advanced glycation end products (AGEs) in high-fat diet (HFD)-induced type 2 diabetes mellitus. Following the institutional animal ethics committee guidelines, Wistar rats were categorized into five groups: group 1: fed on a normal rat diet; group 2: HFD-induced obese rats (HFD for 8 weeks); group 3: HFD-fed rats treated with rosiglitazone (RSG; 3 mg/kg orally for 7 days); group 4: T2DM rats induced by HFD and low dose of streptozotocin (i.p. 35 mg/kg); group 5: T2DM rats treated with RSG (3 mg/kg orally for 7 days). Serum levels of AGEs and visfatin, renal damage, and oxidative stress were analyzed. Results showed that HFD-induced obesity and T2DM caused an elevated blood glucose, serum AGEs, visfatin, insulin, urea, creatinine, and tissue malondialdehyde, whereas a decreased catalase and superoxide dismutase activity were observed. The PPAR-γ activation via agonist restored these changes. Our findings suggest that AGEs and visfatin possess an important role in the progression of renal oxidative stress, which can be reduced by the PPAR-γ agonist that impede deleterious effects of HFD and HFD-induced T2DM on renal damage.

Serum levels of advanced glycation end products in type II diabetic patients with acute cerebral infarction

Background: Advanced glycation end products (AGEs) are reported to be associated with diabetic vascular complications. However, the role of AGEs in the pathogenesis of cerebral thrombosis remains unclear. This study aimed to investigate the relationship between advanced glycation end products (AGEs) generation and pathogenesis of cerebral thrombosis. Methods: 100 patients with cerebral thrombosis were recruited and 50 healthy controlled individuals were served as a control group. Enzyme Linked Immunosorbent Assay (ELISA) was applied for measuring serum AGEs level. The condition of carotid intima was examined by carotid ultrasonography. Serum AGEs levels were compared among patients with certain conditions of carotid atherosclerosis. Results: AGEs levels in carotid plaque or thickening groups showed significant difference compared with those in control group. Carotid plaque patients showed remarkably different AGEs levels compared to thickening patients. AGEs levels were significantly elevated with higher severity of carotid plaque. Moderate or severe stenosis patients, or blocked group showed significantly different AGEs compared to mild stenosis group. Severe stenosis or blockade group showed remarkably different AGEs compared with moderate stenosis patients. In addition, severe stenosis group had statistically different AGEs compared with blockade group. Conclusion: AGEs level is correlated with pathogenesis of cerebral thrombosis and they are further elevated with aggravation of carotid atherosclerosis in patients, suggesting they might be used as a biomarker to evaluate the severity of atherosclerosis.

QUERCETIN AND ELLAGIC ACID IN GASTRIC ULCER PREVENTION: AN INTEGRATED SCHEME OF THE POTENTIAL MECHANISMS OF ACTION FROM IN VIVO STUDY

Objective: The present study was initiated to describe the gastroprotective role of quercetin (Qu) and ellagic acid (EA) on aspirin-induced gastric ulcer (GU) in rats.Methods: Forty adult female albino rats of Wistar strain were distributed into: Control group, GU group, Omeprazole group, Qu group, and EA group. Gross examination, biochemical analyses including serum adrenocorticotropic hormone (ACTH), serotonin (ST), ferritin, heme oxygenase-1 (HO-1), interleukin-2 (IL-2), advanced glycosylation end products (AGEs), and fibronectin (FN) levels were estimated. Moreover, histopathological and histochemical examinations of stomach tissue samples were carried out.Results: Gross examination of gastric mucosa of rats in GU group revealed hyperemia of the stomach mucosa. Furthermore, rats in GU group experienced a significant rise in serum ACTH, ferritin, HO-1, IL-2 and AGEs levels accompanied with significant drop in serum ST and FN levels versus control counterparts. Pre-treatment of GU group with Omeprazole, Qu or EA caused marked improvement in the measured biochemical parameters. Histopathological and histochemical examinations of stomach tissue samples documented the protective action of Omeprazole, Qu and EA with different degrees against GU caused by aspirin.Conclusion: As a conclusion to this study, we can state that both Qu and EA have gastroprotective effect against aspirin-induced GU in rat model. Of note, Qu showed superior impact than EA as an antiulcer agent in this study. The corresponding mechanisms are speculated to be associated with inhibiting stress-induced gastric lesion, attenuating the oxidative stress, iron chelation and blunting ferritin level, modulating inflammatory cascade, and promoting the healing process.

QUERCETIN AND ELLAGIC ACID IN GASTRIC ULCER PREVENTION: AN INTEGRATED SCHEME OF THE POTENTIAL MECHANISMS OF ACTION FROM IN VIVO STUDY

Objective: The present study was initiated to describe the gastroprotective role of quercetin (Qu) and ellagic acid (EA) on aspirin-induced gastric ulcer (GU) in rats.Methods: Forty adult female albino rats of Wistar strain were distributed into: Control group, GU group, Omeprazole group, Qu group, and EA group. Gross examination, biochemical analyses including serum adrenocorticotropic hormone (ACTH), serotonin (ST), ferritin, heme oxygenase-1 (HO-1), interleukin-2 (IL-2), advanced glycosylation end products (AGEs), and fibronectin (FN) levels were estimated. Moreover, histopathological and histochemical examinations of stomach tissue samples were carried out.Results: Gross examination of gastric mucosa of rats in GU group revealed hyperemia of the stomach mucosa. Furthermore, rats in GU group experienced a significant rise in serum ACTH, ferritin, HO-1, IL-2 and AGEs levels accompanied with significant drop in serum ST and FN levels versus control counterparts. Pre-treatment of GU group with Omeprazole, Qu or EA caused marked improvement in the measured biochemical parameters. Histopathological and histochemical examinations of stomach tissue samples documented the protective action of Omeprazole, Qu and EA with different degrees against GU caused by aspirin.Conclusion: As a conclusion to this study, we can state that both Qu and EA have gastroprotective effect against aspirin-induced GU in rat model. Of note, Qu showed superior impact than EA as an antiulcer agent in this study. The corresponding mechanisms are speculated to be associated with inhibiting stress-induced gastric lesion, attenuating the oxidative stress, iron chelation and blunting ferritin level, modulating inflammatory cascade, and promoting the healing process.

Effect of L-Arginine on the Serum Level of Advanced Glycation End Products in Patients with Post Infarction Chronic Heart Failure

Post-infarction heart failure with preserved ejection fraction (HFpEF) determines a great morbidity and mortality, and given the physiopathology implications of advanced glycation end products (AGEs) in the genesis of myocardial dysfunction. As known endothelial dysfunction is an independent predictor for cardiovascular disease. L-Arginine is the amino acid with potential to improve endothelial function which leading to prevention and treatment of cardiovascular diseases, and we think that L-Arginine may decrease the serum AGEs. We aimed to estimate the value of AGEs in post-infarction HFpEF patients, and detect the effect of L-Arginine on the serum level of AGEs in post-infarction HFpEF pts. all individuals (25) included aged 40 to 80 years, 20(80%) males and 5(20%) females were diagnosed with (HFpEF) according to ESC guidelines (2012), and their functional class according to NYHA classification for HF. 20(80%) patients of them have myocardial infarction in anamnesis. 1st group:13 patients with HFpEF and history of myocardial infarction with L-Arginine added to their standard treatment. 2nd group:7 patients with HFpEF and history of myocardial infarction with standard treatment (without L-Arginine). Comparsion group: 5 patients with HFpEF with standard treatment. We prescribed L. Arginine aspartate (Tivortin 4.2gm) intravenously once daily for 10 days for all 1st group patients. The levels of total cholesterol, triglycerides, glucose, white blood cells, erythrocyte sedimentation rate and AGEs serum level were deterimined. AGEs serum level increased markedly increased in middle-age pts with post infarction HFpEF. Inclusion of L-arginine aspartate in complex of treatment for post infarction HFpEF contributed to the significant decrease AGEs level in >60 years old patients.

Ratio of serum levels of AGEs to soluble RAGE is correlated with trimethylamine-N-oxide in non-diabetic subjects

Trimethylamine (TMA), an intestinal microflora-dependent metabolite formed from phosphatidylcholine- and L-carnitine-rich food, such as red meat, is further converted to trimethylamine-N-oxide (TMAO), which could play a role in cardiometabolic disease. Red meat-derived products are one of the major environmental sources of advanced glycation end products (AGEs) that may also contribute to the pathogenesis of cardiometabolic disorders through the interaction with receptor for AGEs (RAGE). However, the relationship among AGEs, soluble form of RAGE (sRAGE) and TMAO in humans remains unclear. Non-diabetic subjects underwent a physical examination, determination of blood chemistry and anthropometric variables, including AGEs, sRAGE, TMA and TMAO. Multiple regression analyses revealed that HbA1c, uric acid and AGEs were independently associated with log TMA, whereas log AGEs to sRAGE ratio and statin non-use were independently correlated with log TMAO. Our present findings indicated that AGEs to sRAGE ratio was correlated with log TMAO, a marker of cardiometabolic disorders.

Glucagon-like peptide-1 analogue liraglutide ameliorates atherogenesis via inhibiting advanced glycation end product-induced receptor for advanced glycosylation end product expression in apolipoprotein-E deficient mice.

Glucagon-like peptide-1 (GLP-1) can protect arteriosclerotic lesions in apolipoprotein-E deficient (ApoE-/-) mice. Advanced glycation end products (AGEs)/receptor for advanced glycation end products (RAGE) interaction serves a key role in the development of diabetic vascular complications. The present study examined whether the GLP-1 analogue liraglutide can ameliorate atherogenesis via inhibiting AGEs-induced RAGE expression. Male ApoE-/- mice (age, 10weeks) were divided into control, GLP-1, AGEs and AGEs+GLP-1 group. All mice were fed a high-fat diet. The AGEs and AGEs+GLP-1 groups were treated with intraperitoneal injection of AGEs (30mg/kg/day). The GLP-1 and AGEs+GLP-1 groups were treated with subcutaneous injections of liraglutide (0.4mg/kg/day). After 9weeks, blood was drawn and the aortas were rapidly procured. The serum levels of AGEs, soluble RAGE (sRAGE), stromal cell-derived factor-1α (SDF-1α), total cholesterol and triacylglycerol were measured. Atherosclerotic plaque area was determined by Sudan IV staining. The mRNA and protein expression levels of RAGE were determined using reverse transcription-quantitative polymerase chain reaction and western blotting, respectively. The results demonstrated that AGEs treatment increased serum AGEs levels, increased the expression of RAGE in the aorta, and aggravated atherosclerotic lesions compared with the control. Liraglutide treatment reduced serum AGEs levels, reduced the expression of RAGE in aorta, and relieved atherosclerotic lesions compared with the control. In conclusion, these data suggested that liraglutide serves an anti-atherosclerotic effect via inhibiting AGEs-induced RAGE expression in ApoE-/- mice. These findings provide novel evidence for the use of GLP-1-type agents for the treatment of diabetic vascular complications.

A Study of Microalbuminuria (MAU) and Advanced Glycation End Products (AGEs) Levels in Diabetic and Hypertensive Subjects.

The prevalence of non-communicable diseases like diabetes mellitus (DM) and hypertension (HTN) is growing worldwide. Both lead to nephropathy if not controlled effectively. Microalbuminuria (MAU) is recognized as an early predictor for nephropathy. Additionally, the timely detection of advanced glycation end products (AGEs) is also considered to be an important prognostic factor for diabetic nephropathies. Hence, screening for the early detection of MAU and AGEs would be an useful and relatively inexpensive laboratory test for early clinical diagnosis for the incidence of nephropathy in these diseases. This study was conducted in DM, HTN and pregnancy induced hypertensive (PIH) subjects. MAU and Nε-Carboxymethyllysine (CML) levels were estimated by in-house RIA kits in the patient groups and controls, while the total AGEs level in serum was determined by ELISA. The levels of MAU, CML and AGE-BSA were observed to be significantly higher in DM, HTN and PIH subjects compared to controls (p<0.001). Increased serum CML and AGEs levels in DM, HTN and PIH subjects indicated ongoing glycemic damage and their susceptibility to develop renal complications.

An inverse association between serum soluble receptor of advanced glycation end products and hyperandrogenism and potential implication in polycystic ovary syndrome patients

BackgroundStudies found that AGE-RAGE system is closely related to insulin resistance and hyperandrogenemia, which are two core pathophysiological processes in polycystic ovary syndrome (PCOS). This study is to investigate the relationship among advanced glycation end-products/soluble receptor of advanced glycation end-products (AGEs/sRAGE) and anthropometric evaluation, homeostatic model assessment-insulin resistance (HOMA-IR), free androgen index (FAI) in reproductive-aged PCOS patients.MethodsOne hundred and forty-eight Chinese women with PCOS were enrolled in this study. Subgroups were divided according to body mass index (BMI), waist circumference (WC), quartile intervals of HOMA-IR and androgen levels. The relationships between AGEs/sRAGE and above clinical markers were assessed by Pearson’s correlation analyses.ResultsSerum AGEs showed a gradually increased tendency with BMI and WC. It reached statistical significant between the normal weight group (BMI < 24 kg/m2) and the obesity group (BMI ≥ 28 kg/m2) . The sRAGE levels gradually decreased with increasing BMI, WC, HOMA-IR and FAI respectively. Furthermore, the differences between each group were statistical significant. The correlation analysis showed a positive correlation between BMI and serum AGEs levels. On the contrary, the sRAGE levels showed significantly inverse correlations with BMI, WC, HOMA-IR and FAI. The optimal point of sRAGE for the presence of insulin resistance was 704.097 pg/ml by ROC curve analysis.ConclusionsAlong with the body fat accumulation, the serum levels of AGEs were increased, whereas, the serum levels of sRAGE were reduced in obese PCOS patients. The serum levels of sRAGE, which is a decoy receptor, dramatically decreased in the patients with more severe insulin resistant states and higher FAI, which might be a potential biomarker and a promising therapeutic target in the treatment of PCOS, especially in obese subjects.

Serum Levels of Intact Parathyroid Hormone, Calcium, and Phosphorus and Risk of Mortality in Hemodialysis Patients

Background: Abnormal mineral metabolism is common among hemodialysis patients and has been associated with higher morbidity and mortality rates. Methods: A cohort of 532 hemodialysis patients was selected from nine hemodialysis centers in September 2012 and were prospectively followed-up for a median of 28 months. Unadjusted and adjusted (in terms of age, gender, dialysis vintage, body mass index, albumin level, and comorbidities) hazard ratios (HRs) of mortality associated with serum phosphorus, calcium, and parathyroid hormone (PTH) levels were calculated, using Cox proportional hazards model. Results: In the unadjusted model, HRs of mortality for serum phosphorus < 4 mg/dL (reference: 4 - 6) and iPTH < 200 pg/mL (reference: 200 - 600) were 1.61 (95% CI: 1 - 2.46) and 1.55 (95% CI: 1.06 - 2.27), respectively. After adjustment, the foregoing values were no longer significant, and HRs for serum phosphorus level ≥ 6 mg/dL (reference: 4 - 6), calcium level ≥ 10 (reference: < 10), and iPTH ≥ 600 (reference: 200 - 600) were calculated to be 1.56 (95% CI: 1.09 - 2.22), 2.34 (95% CI: 1.21 - 4.51), and 1.59 (95% CI: 1.03-2.45), respectively. Meanwhile, significant adjusted correlates of iPTH were serum alkaline phosphatase (r = 0.49), phosphorus (r=0.24), dialysis vintage (r = 0.21), age (r = -0.20), diabetes (r = -0.16), and serum calcium level (r = -0.13). Conclusions: While high serum PTH, calcium, and phosphorus levels could determine the mortality risk in hemodialysis patients, decreased serum phosphorus and PTH levels were in association with malnutrition and comorbidities and were not independent risk factors for mortality.

Three-year efficacy and safety of tenofovir in nucleos(t)ide analog-naïve and nucleos(t)ide analog-experienced chronic hepatitis B patients.

This study compared the efficacy and safety of tenofovir disoproxil fumarate (TDF) up to 3 years of innucleos(t)ide analog (NA)-naïve and NA-experienced chronic hepatitis B (CHB) patients. Tenofovir disoproxil fumarate-treated NA-naïve and NA-experienced CHB patients were retrospectively analyzed. After 3 years of TDF therapy, 97.7%, 71%, and 45.5% NA-naïve patients achieved a virological response, alanine aminotransferase normalization, and hepatitis B e antigen seroconversion, respectively. Compared with NA-naïve patients, NA-experienced patients without drug resistance and infected with lamivudine/telbivudine-resistant mutants showed similar results. In contrast, patients previously infected with adefovir-resistant mutants and with a suboptimal entecavir response showed significantly lower rates of virological response and hepatitis B e antigen loss/seroconverion than NA-naïve patients. Mean estimated glomerular filtration rate markedly reduced within 12 months of TDF therapy; however, it did not decrease significantly during 12-36 months of treatment. Diabetes mellitus was an independent predictor of a ≥ 0.5 mg/dL increase above baseline in serum creatinine level, and age, hypertension, diabetes mellitus, and baseline creatinine level were independent factors for > 20% decline in estimated glomerular filtration rate from baseline. Liver stiffness measurements improved significantly, but bone mineral density did not change significantly during treatment. Hepatocellular carcinoma incidence was low at 36 months. Age of > 60 years, cirrhosis, a low baseline platelet count and a high α-fetoprotein level at 12 months were significant predictors of hepatocellular carcinoma development. Tenofovir disoproxil fumarate is effective and safe for NA-naïve and NA-experienced CHB patients and should be used cautiously in patients with comorbidities because of a renal dysfunction risk.

Effects of Long-Term Exposure of Exogenous Advanced Glycation Endproducts on Vertebral Bone Microarchitecture; Sex-Differences on Structure Derived Mechanical Properties

Introduction Accumulation of advanced glycation end products (AGE) are commonly associated with diabetic complications, including increased painful intervertebral disc pathologies, osteoporosis, and bone fracture risk. Exogenous AGEs develop by processing food at high temperatures and can accumulate in bone where they crosslink collagen. A clinical study reported association of increased serum AGE levels with vertebral fracture risk in women but not in men, highlighting gender effects. The purpose of this study was to investigate the sex-dependent effects of exogenous AGEs on vertebral bone quantity, quality, and mechanical behavior. Material and Methods C57BL/6 mice (female, n = 8/group; male, n = 4/group) were pair-fed isocaloric diets containing low AGE amounts (LAGE, 7.6 μg/mg chow) or high AGE amounts (HAGE, 40.9 μg/mg chow) for 6 months; after euthanasia, blood glucose and serum AGEs were analyzed. Lumbar spines were μCT-scanned (resolution=4.9μm; SkyScan 1172, Bruker Corp., Belgium). Hydroxyapatite phantoms were similarly scanned for density calibration. Cortical bone analysis included tissue mineral density (TMD), BMD, cross sectional thickness (Ct.Th), bone surface are (BSA) and porosity. Trabecular bone analysis included trabecular thickness, separation (Tb.Sp), number (Tb.Nm), TMD, BMD, BVF, bone surface to volume ratio (BS/BV), Structure Model Index (SMI) and fabric anisotropy. A validated analytical model was used to calculate trabecular bone anisotropic compressive and shear moduli. Male/female and HAGE/LAGE differences were analyzed via Student's t-tests ( p &lt; 0.05). All experiments were approved by the Institutional Animal Care and Use Committee. Results Serum AGE levels were significantly increased in female HAGE mice compared with LAGE mice ( p &lt; 0.01). No differences were observed between blood glucose levels among groups. Dietary comparisons indicated that female trabecular BS/BV and porosity were significantly increased by HAGE-diet whereas trabecular BMD, compressive and shear moduli, and cortical BMD were decreased. In males dietary comparisons revealed only a significant increase in trabecular porosity. Male cortical bone remained unchanged. Sex comparisons within LAGE-diet group revealed that female trabecular bone had significantly reduced Tb.Nm, BMD, degree of anisotropy, compressive and shear moduli, and significantly increased Tb.Sp, porosity, and SMI compared with LAGE males. LAGE females also had significantly decreased cortical BSA and significantly increased Ct.Th compared with LAGE males. Sex comparisons of female versus male HAGE-diet groups revealed no significant differences. Conclusion Results indicated more pronounced detrimental effects on cortical and trabecular bone in females on HAGE-diet than in males. These sex-dependent effects suggest that AGEs effects on vertebral bone may be hormonally mediated. This work showed for the first time significant alterations to the elastic compressive and shear properties of vertebra following variations in dietary AGE levels. Changes in trabecular architecture and density manifested as functional changes, especially in females, warranting further post-yield and fracture analysis. Importantly, this study investigated the sex dependent effects of AGEs on vertebral bone quality and quantity independent from serum glucose (diabetes). Further research of AGE effects on cell turnover and cellular modifications to bone microarchitecture and mineralization is necessary to validate the link between changes in bone quality, quantity and function.

Advanced glycation end products and soluble receptor as markers of oxidative stress in children on hemodialysis

Background: Advanced glycation end products (AGEs) have biological properties that may contribute to the mortality of children on hemodialysis (HD). This study examines the relationship of LMW fluorescence AGEs, oxidized LDL (ox-LDL), soluble receptor AGE (sRAGE) as markers of oxidative stress in children with end stage renal disease (ESRD) undergoing HD. Method: Thirty children with ESRD undergoing HD, and 30 healthy, age- and sex-matched children were included. Serum levels of LMW fluorescence AGEs, sRAGE, oxidized LDL (ox-LDL), pre- and post-dialysis urea, high-sensitivity C-reactive protein (hs-CRP), hemoglobin (Hb) and serum albumin (ALB), were measured. Results: Abnormal serum inflammatory changes: elevated levels of LMW AGEs, sRAGE, oxLDL, CRP and urea were exhibited in HD children compared with healthy controls; more so in anemic when compared to non-anemic patients. Significant positive correlation was found between serum levels of AGEs and sRAGE. Conclusion: The low molecular weight form of AGEs is associated with oxidative stress in children receiving chronic HD, and may be important in the mechanisms leading to atherosclerosis and inflammation in such patients. LMW AGEs levels showed a negative correlation with sRAGE and both exhibit a significant negative relation to seum urea.

Oxidative stress biomarkers and paraoxonase 1 polymorphism frequency in farmers occupationally exposed to pesticides.

Previous evidence has demonstrated that chemical classes of pesticides, including organophosphates (OP), can induce oxidative stress in exposed workers. The resulting increase in free radicals causes damage to biological macromolecules, and promotes the formation of novel compounds, including advanced glycation end products (AGE) and advanced oxidation protein products (AOPP). The present study aimed to evaluate the common genetic polymorphisms of the paraoxonase 1 (PON1) gene in a group of 55 farmers exposed to pesticides, as well as the association between these polymorphisms and serum levels of AGE and AOPP. The 192Q wild‑type (WT) allele was present at a significantly higher frequency, compared with the 192R mutated allele (0.74 and 0.26, respectively). The WT allele was predominantly represented by the homozygote 192QQ genotype (51%). The mutated 192QR heterozygotic allele was prevalent, at a frequency of 45.4%, whereas the mutated homozygotes were present at a frequency of 3.6%. A significant decrease in the levels of AGE and AOPP was observed in farmers exhibiting the homozygotic 192RR mutated genotype (14,7221 AU/ml and 0.64 nmol/ml, respectively), compared with the WT genotype (16,1400 AU/ml and 1.76 nmol/ml, respectively), and 192QR genotype (15,2312 AU/ml and 1.60 nmol/ml, respectively). Therefore, due to the high catalytic activity of PON1, the 192RR genotype provides an important genetic predictor of the toxic effects associated with OP pesticide exposure. It determines a minor risk of developing oxidative damage following pesticide exposure, and measuring the levels of AOPP may provide a novel biomarker for oxidative damage in subjects exposed to OP.

Immunization of AGE-modified albumin inhibits diabetic nephropathy progression in diabetic mice.

BackgroundDiabetic nephropathy (DN) is a serious vascular complication of diabetes and an important cause of end-stage renal disease. One mechanism by which hyperglycemia causes nephropathy is through the formation of advanced glycation end products (AGE). Development of vaccination would be a promising therapy for the future, while to date, anti-AGE therapy is based on medicines that are needed to be consumed lifelong. This study aimed to find out the effect of immunization of AGE-modified albumin against DN pathogenesis in streptozotocin-induced diabetic in mice.MethodsWe used 24 BALB/c male mice as experimental animals, which were divided into six groups, two nondiabetic groups (negative control and AGE-modified bovine serum albumin [BSA] preimmunized groups) and four streptozotocin-induced diabetic groups (diabetic control group and diabetic preimmunized groups for AGE-BSA, Keyhole limpet hemocyanin (KLH), and AGE-BSA-KLH, respectively).ResultsDiabetic preimmunized groups for AGE-BSA, KLH, and AGE-BSA-KLH showed amelioration in renal function and histopathology compared with the diabetic control group. Preimmunization also maintained nephrin intensity and decreased serum AGE level, kidney AGE deposition, and kidney cells apoptosis.ConclusionAGE-BSA and AGE-BSA-KLH immunizations inhibit the progression of DN. Our results strengthen the evidence that the anti-AGE antibodies have a protective role against diabetic vascular complication, especially DN. This study provides a basis for the development of DN-based immunotherapy with AGE immunization as a potential candidate.

Correlation of the expressions of advanced glycation end products and its receptor in serum and placenta with the pathogenesis of preeclampsia

To investigate the correlation of the expressions of advanced glycation end products (AGE) and the receptor for advanced glycation end products (RAGE) in serum and placenta with the pathogenesis of preeclampsia. From December 2013 to June 2014, 32 women with severe preeclampsia who received cesarean section in the Affiliated Hospital of Qingdao University were recruited in the study, defined as the severe preeclampsia group. 30 healthy pregnant women who received cesarean section in the same hospital were recruited as the control group. ELISA was used to measure the maternal serum AGE, soluble receptor for advanced glycation end products (sRAGE) and tumor necrosis factor-α (TNF-α) in these women. Furthermore, ELISA was also used to measure AGE and TNF-α in the placenta. The localizations of AGE and RAGE protein in placentas were detected by immunohistochemical SP method. RAGE and TNF-α mRNA expression in placentas were measured by real-time quantitative PCR. AGE, RAGE and TNF-α protein expression in placentas were measured by western blot, respectively. (1) The serum levels of AGE, sRAGE and TNF-α in the severe preeclampsia group were (538 ± 75), (367 ± 86) and (322 ± 40) ng/L, respectively. They were significantly higher than those in the control group [(454 ± 50), (286 ± 35) and (270 ± 35) ng/L, respectively] (P < 0.05). The levels of AGE showed positive correlation with the levels of TNF-α (r = 0.588, P < 0.05), while the levels of sRAGE showed no correlation with TNF-α (r = -0.041, P > 0.05). (2) In the severe preeclampsia group, the levels of AGE and TNF-α in placentas were (500 ± 82) and (334 ± 57) ng/L, which were higher than those in the control group [(431 ± 74) and (263 ± 46) ng/L, respectively] (P < 0.05). The levels of AGE showed positive correlation with the levels of TNF-ɑ (r = 0.406, P < 0.05). (3) AGE and RAGE protein mainly located in the syncytiotrophoblasts, macrophages and vascular endothelial cells in the placentas of the two groups. AGE expressed mainly in the cytoplasm, and RAGE expressed in the cytoplasm and cell membranes. (4) RAGE and TNF-α mRNA expression in the placentas of the severe preeclampsia group were 12.6 ± 4.6 and 10.4 ± 2.4, which were significantly higher than those in the control group (0.9 ± 0.4 and 3.5 ± 0.9, P < 0.01). (5) The expressions of AGE, RAGE and TNF-α protein in placentas of the severe preeclampsia group were 0.68 ± 0.06, 0.82 ± 0.08 and 0.76 ± 0.08. All were significantly higher than those of the control group (0.46 ± 0.05, 0.42 ± 0.09 and 0.52 ± 0.07; P < 0.01). The levels of AGE and RAGE in serum and placentas elevated in the severe preeclampsia group, and the expression of TNF-α also elevated. These indicated that AGE and RAGE might be involved in the systemic inflammatory response and local inflammatory response in placentas, and then caused the preeclampsia.

Advanced glycation end product (AGE)-induced hepatic stellate cell activation via autophagy contributes to hepatitis C-related fibrosis.

Advanced glycation end products (AGEs) have been implicated in pulmonary and renal fibrosis. Herein, we investigated whether AGEs are associated with liver fibrosis and examined the underlying mechanism by focusing on hepatic stellate cell (HSC) activation and autophagy induction. Liver fibrosis was assessed by transient elastography (FibroScan). Serum AGE levels were determined by ELISA. Rat primary HSCs and HSC-T6 were treated with BSA-AGEs, cell proliferation was examined by WST-1 assay, and cell activation was evaluated by qPCR for transcripts of α-SMA and collagen type Iα1 and by Western blotting. Autophagy was measured by detection of LC3-II lipidation, p62 degradation, and puncta GFP-LC3 formation. Receptor of AGE (RAGE)-blocking antibodies and soluble RAGE were employed to inhibit AGE-RAGE signaling. First, elevated AGE levels were observed in CHC patients than patients with chronic hepatitis B, especially in those with insulin resistance. Second, compared to controls, AGE-treated rat primary HSCs displayed an enhanced cell proliferation (1.39-fold), increased transcripts of α-SMA (2.40-fold) and proCOL1A1 (1.76-fold), and a higher level of α-SMA protein (1.85-fold). Moreover, AGE-induced HSC activation improved autophagy flux, as evidenced by significantly more LC3-II lipidation, p62 degradation, as well as GFP-LC3 puncta formations. In addition, our results showed that AGE-induced HSC autophagy and HSC activation could be reduced by RAGEs. AGEs were found to induce autophagy and activation of HSCs, which subsequently contributes to the fibrosis in CHC patients. Blocking AGE-RAGE signaling may be a promising way to alleviate fibrosis.

Clinical and biochemical factors associated with area and metabolic activity in the visceral and subcutaneous adipose tissues by FDG-PET/CT.

Body fat distribution and inflammation may play a role in metabolic derangements and cardiovascular disease in obesity. The aim of this study is to investigate clinical and biochemical factors associated with area and metabolic activity in the visceral and subcutaneous adipose tissues (VAT and SAT). (18)F-fluorodeoxyglucose-positron emission tomography and computed tomography imaging was performed in 251 consecutive subjects (62.6 ± 9.3 y) for risk screening. We examined which clinical, anthropometric, metabolic, and inflammatory variables including advanced glycation end products (AGEs) and pigment epithelium-derived factor (PEDF) were independently associated with area and metabolic activity in VAT and SAT. Adipose tissue area was determined with computed tomography, whereas metabolic activity was assessed by (18)F-fluorodeoxyglucose uptake expressed as a target to background ratio (TBR) of blood-normalized standardized uptake. Serum levels of AGEs and PEDF were 9.81 ± 3.21 U/mL and 14.0 (range 10.8-17.7) μg/mL, respectively. Although the area in VAT and SAT was associated with waist circumference and sex, each adipose tissue area and TBR had different metabolic risk profiles. The TBR value in VAT was higher than that in SAT. In a multiple stepwise regression analysis, AGEs and medication for hypertension were independently associated with VAT TBR (R(2) = 0.102), whereas medication for diabetes, mean intima-media thickness, AGEs, and PEDF were the independent correlates of SAT TBR (R(2) = 0.132). The present study demonstrated that area and metabolic activity in VAT and SAT could be differently regulated, suggesting the involvement of AGEs and PEDF in adipose tissue inflammation.