Comprehensive analysis of advanced glycation end-products in commonly consumed foods:presenting a database for dietary AGEs and associated exposure assessment

Advanced glycation end-products(AGEs)are a group of heterogeneous compounds formed in heatprocessed foods and are proven to be detrimental to human health.Currently,there is no comprehensive database for AGEs in foods that covers the entire range of food categories,which limits the accurate risk assessment of dietary AGEs in human diseases.In this study,we first established an isotope dilution UHPLCQq Q-MS/MS-based method for simultaneous quantification of 10 major AGEs in foods.The contents of these AGEs were detected in 334 foods covering all main groups consumed in Western and Chinese populations.Nε-Carboxymethyllysine,methylglyoxal-derived hydroimidazolone isomers,and glyoxal-derived hydroimidazolone-1 are predominant AGEs found in most foodstuffs.Total amounts of AGEs were high in processed nuts,bakery products,and certain types of cereals and meats(>150 mg/kg),while low in dairy products,vegetables,fruits,and beverages(<40 mg/kg).Assessment of estimated daily intake implied that the contribution of food groups to daily AGE intake varied a lot under different eating patterns,and selection of high-AGE foods leads to up to a 2.7-fold higher intake of AGEs through daily meals.The presented AGE database allows accurate assessment of dietary exposure to these glycotoxins to explore their physiological impacts on human health.

Receptor for advanced glycation end-products axis and coronavirus disease 2019 in inflammatory bowel diseases:A dangerous liaison?

Compelling evidence supports the crucial role of the receptor for advanced glycation end-products(RAGE)axis activation in many clinical entities.Since the beginning of the coronavirus disease 2019 pandemic,there is an increasing concern about the risk and handling of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection in inflammatory gastrointestinal disorders,such as inflammatory bowel diseases(IBD).However,clinical data raised during pandemic suggests that IBD patients do not have an increased risk of contracting SARS-CoV-2 infection or develop a more severe course of infection.In the present review,we intend to highlight how two potentially important contributors to the inflammatory response to SARS-CoV-2 infection in IBD patients,the RAGE axis activation as well as the cross-talk with the renin-angiotensin system,are dampened by the high expression of soluble forms of both RAGE and the angiotensin-converting enzyme(ACE)2.The soluble form of RAGE functions as a decoy for its ligands,and soluble ACE2 seems to be an additionally attenuating contributor to RAGE axis activation,particularly by avoiding the transactivation of the RAGE axis that can be produced by the virus-mediated imbalance of the ACE/angiotensin II/angiotensin II receptor type 1 pathway.

Receptor of advanced glycation end-products axis and gallbladder cancer:A forgotten connection that we should reconsider

Compelling evidence derived from clinical and experimental research has demonstrated the crucial contribution of chronic inflammation in the development of neoplasms,including gallbladder cancer.In this regard,data derived from clinical and experimental studies have demonstrated that the receptor of advanced glycation end-products(RAGE)/AGEs axis plays an important role in the onset of a crucial and long-lasting inflammatory milieu,thus supporting tumor growth and development.AGEs are formed in biological systems or foods,and food-derived AGEs,also known as dietary AGEs are known to contribute to the systemic pool of AGEs.Once they bind to RAGE,the activation of multiple and crucial signaling pathways are triggered,thus favoring the secretion of several proinflammatory cytokines also involved in the promotion of gallbladder cancer invasion and migration.In the present review,we aimed to highlight the relevance of the association between high dietary AGEs intakes and high risk for gallbladder cancer,and emerging data supporting that dietary intervention to reduce gallbladder cancer risk is a very attractive approach that deserves much more research efforts.

Dietary advanced glycation end-products aggravate non-alcoholic fatty liver disease

AIM To determine if manipulation of dietary advanced glycation end product(AGE), intake affects nonalcoholic fatty liver disease(NAFLD) progression and whether these effects are mediated via RAGE. METHODS Male C57Bl6 mice were fed a high fat, high fructose, high cholesterol(HFHC) diet for 33 wk and compared with animals on normal chow. A third group were given a HFHC diet that was high in AGEs. Another group was given a HFHC diet that was marinated in vinegar to prevent the formation of AGEs. In a second experiment, RAGE KO animals were fed a HFHC diet or a high AGE HFHC diet and compared with wildtype controls. Hepatic biochemistry, histology, picrosirius red morphometry and hepatic mR NA were determined. RESULTS Long-term consumption of the HFHC diet generated significant steatohepatitis and fibrosis after 33 wk. In this model, hepatic 4-hydroxynonenal content(a marker of chronic oxidative stress), hepatocyte ballooning, picrosirius red staining, α-smooth muscle actin and collagen type 1A gene expression were all significantly increased. Increasing the AGE content of the HFHC diet by baking further increased these markers of liver damage, but this was abrogated by pre-marination in acetic acid. In response to the HFHC diet, RAGE-/-animals developed NASH of similar severity to RAGE+/+ animals but were protected from the additional harmful effects of the high AGE containing diet. Studies in isolated Kupffer cells showed that AGEs increase cell proliferation and oxidative stress, providing a likely mechanism through which these compounds contribute to liver injury. CONCLUSION In the HFHC model of NAFLD, manipulation of dietary AGEs modulates liver injury, inflammation, and liver fibrosis via a RAGE dependent pathway. This suggests that pharmacological and dietary strategies targeting the AGE/RAGE pathway could slow the progression of NAFLD.

Lactobacillus fermentum as a new inhibitor to control advanced glycation end-product formation during vinegar fermentation

The inhibitory activity of lactic acid bacteria(LAB)toward advanced glycation end-products(AGEs)during vinegar fermentation was studied,and its relationships with the substrate consumption,antioxidant capacity,total phenolic content,total flavonoid compounds,α-glucosidase,andα-amylase activity inhibition were evaluated.The vinegar was made from rice powder flour by liquid-state fermentation(LSF).The selected LAB strains were separately co-cultivated with Saccharomyces cerevisiae and Acetobacter pasteurianus 1.41 in alcoholic and acetic acid fermentation,respectively.Among 3 strains,Lactobacillus fermentum showed the strongest inhibitory effect on the formation of total fluorescent AGEs and carboxymethyl lysine(CML)/carboxyethyl lysine(CEL)in the fermentation process.The corresponding mechanisms included the acceleration of substrate consumtion,improvement of antioxidant activities,and inhibition ofα-glucosidase andα-amylase.In addition,the fluorescent AGEs and the CML/CEL were negatively correlated with the antioxidant activities,while theα-glucosidase andα-amylase activities were positively correlated with the total phenols and total flavonoids.Moreover,the variety of main flavor compounds increased,including esters,alcohols,phenols and acids.The results of the study support the potential use of screened LAB strains to inhibit the formation of fluorescent AGEs,CML and CEL on fermented products and in the food processing industry,without associated risks to consumers.

Increased expression of receptor for advanced glycation end-products worsens focal brain ischemia in diabetic rats

A rat model of diabetes mellitus was induced by a high fat diet, followed by focal brain ischemia induced using the thread method after 0.5 month. Immunohistochemistry showed that expression of receptor for advanced glycation end-products was higher in the ischemic cortex of diabetic rats compared with non-diabetic rats with brain ischemia. Western blot assay revealed increased phosphorylated c-Jun N-terminal kinase expression, and unchanged phosphorylated extracellular signal-regulated protein kinase protein expression in the ischemic cortex of diabetic rats compared with non-diabetic rats with brain ischemia. Additionally, phosphorylated p38 mitogen-activated protein kinase protein was not detected in any rats in the two groups. Severity of limb hemiplegia was worse in diabetic rats with brain ischemia compared with ischemia alone rats. The results suggest that increased expression of receptor for advanced glycation end-products can further activate the c-Jun N-terminal kinase pathway in mitogen-activated protein kinase, thereby worsening brain injury associated with focal brain ischemia in diabetic rats.

Advanced glycation end-products change placental barrier function and tight junction in rats with gestational diabetes mellitus via the receptor for advanced glycation end products/nuclear factor-κB pathway

The placenta plays an important role in nutrient transport to maintain the growth and development of the embryo.Gestational diabetes mellitus(GDM),the most common complication during pregnancy,highly affects placental function in late gestation.Advanced glycation end-products(AGEs),a complex and heterogeneous group of compounds engaged by the receptor for AGEs(RAGE),are closely associated with diabetes-related complications.In this study,AGEs induced a decrease in the expression of tight junction(TJ)proteins in BeWo cells and increased the paracellular permeability of trophoblast cells by regulating RAGE/NF-κB.Sprague-Dawley(SD)rats injected with 100 mg/kg AGEs-rat serum albumin(RSA)via the tail vein from embryo day 2 were set as the placental barrier dysfunction model group(n=10).The effect of AGEs on placental permeability was determined using the Evans-Blue dye extravasation method.The ultrastructure of the placenta samples was observed by transmission electron microscopy.The effects of AGEs on the placenta were confirmed by treating rats with RAGE antagonist FPS-ZM1 and soluble forms of RAGE(sRAGE).AGEs treatment increased placental permeability and disrupted the tight junctions in pregnant rat placenta,but has no effect on blood glucose.The expression of TJ-related proteins,including ZO-1,Occludin,and Claudin 5,were downregulated after AGEs treatment.Further,AGEs treatment increased the expression of RAGE and nuclear factor-κB in the placenta of rats and upregulated the levels of vascular endothelial growth factor.The effects of AGEs on the placenta were blocked by RAGE antagonist FPS-ZM1 and sRAGE.This study demonstrates the mechanism underlying AGEs-induced disturbance in placental function in pregnant rats and highlights the potential of AGEs in the treatment of GDM.

Advanced glycation end-product expression is upregulated in the gastrointestinal tract of type 2 diabetic rats

AIM:To investigate changes in advanced glycation end products(AGEs) and their receptor(RAGE) expression in the gastrointestinal(GI) tract in type 2 diabetic rats.METHODS:Eight inherited type 2 diabetic rats GotoKakizak(GK) and ten age-matched normal rats were used in the study.From 18 wk of age,the body weight and blood glucose were measured every week and 2 wk respectively.When the rats reached 32 wk,twocentimeter segments of esophagus,duodenum,jejunum,ileum,and colon were excised and the wet weight was measured.The segments were fixed in 10% formalin,embedded in paraffin and five micron sections were cut.The layer thickness was measured in Hematoxylin and Eosin-stained slides.AGE [N epsilon-(carboxymethyl) lysine and N epsilon-(carboxyethyl)lysine] and RAGE were detected by immunohistochemistry staining and image analysis was done using Sigmascan Pro 4.0 image analysis software.RESULTS:The blood glucose concentration(mmol/L) at 18 wk age was highest in the GK group(8.88 ± 1.87 vs 6.90 ± 0.43,P < 0.001),a difference that continued to exist until the end of the experiment.The wet weight per unit length(mg/cm) increased in esophagus,jejunum and colon from the normal to the GK group(60.64 ± 9.96 vs 68.56 ± 11.69,P < 0.05 for esophagus; 87.01 ± 9.35 vs 105.29 ± 15.45,P < 0.01 for jejunum; 91.37 ± 7.25 vs 97.28 ± 10.90,P < 0.05 for colon).Histologically,the layer thickness of the GItract was higher for esophagus,jejunum and colon in the GK group [full thickness(μm):575.37 ± 69.22 vs 753.20 ± 150.41,P < 0.01 for esophagus; 813.51 ± 44.44 vs 884.81 ± 45.31,P < 0.05 for jejunum; 467.12 ± 65.92 vs 572.26 ± 93.60,P < 0.05 for colon].In esophagus,the AGE and RAGE mainly distributed in striated muscle cells and squamous epithelial cells.The AGE distribution was much stronger in the GK group compared to the normal group both in the striated muscle layer and mucosa layer(immuno-positive area/ total measuring area %:4.52 ± 0.89 vs 10.96 ± 1.34,P < 0.01 for muscle; 8.90 ± 2.62 vs 22.45 ± 1.26,P < 0.01 for mucosa).No visible difference was found for RAGE distribution between the two groups.In the intestine AGE and RAGE distributed in epithelial cells of villi and crypt.RAGE was also found in neurons in the myenteric and submucosal plexus.The intensity of AGE staining in mucosa of all segments and RAGE staining in neurons in all segments were strongest in the diabetes group.Significant difference for AGE was found in the epithelial cells of villi and crypt in duodenum(immunopositive area/total measuring area %:13.37 ± 3.51 vs 37.48 ± 8.43,P < 0.05 for villi; 0.38 ± 0.12 vs 1.87 ± 0.53,P < 0.05 for crypt) and for RAGE in neurons of all segments(e.g.,for jejunum:no staining neurons% 0 vs 0,mild 36.0 ± 5.2 vs 28.7 ± 3.5,moderate 53.2 ± 4.8 vs 55.8 ± 5.4,strong 10.7 ± 1.1 vs 15.4 ± 2.0,P < 0.05).In the colon,RAGE was primarily found in neurons in the myenteric and submucosal plexus.It was stronger in the diabetes group than in the normal group(no staining neurons% 6.2 ± 0.2 vs 0.3 ± 0.04,mild 14.9 ± 2.1 vs 17.6 ± 1.5,moderate 53.1 ± 4.6 vs 44.7 ± 4.4,strong 25.6 ± 18 vs 43.6 ± 4.0,P < 0.05).In the rectum,RAGE was primarily found in the mucosa epithelial cells.CONCLUSION:The AGE and RAGE expression was upregulated in the GI tract of GK diabetic rats and may contribute to GI dysfunction in type 2 diabetic patients.

Fluorescent advanced glycation end-products (ages) detected by spectro-photofluorimetry, as a screening tool to detect diabetic microvascular complications

BACKGROUND: Advanced glycation end-products (AGEs) are one of the mechanisms related to diabetic vascular complications. However, since AGEs are multiple and heterogeneous moieties, there is no universally accepted method to measure them for clinical purposes. The aim of this work was to study the utility of a simple fluorimetric assay as predictor of complications. METHODS: Blood samples from 102 type 2 diabetic patients were obtained to assess glucose, glycosylated haemoglobin, creatinine, lipoproteins and C Reactive Protein (CRP), fluorescent AGES by spectrophotofluorimetry and non-fluorescent AGEs by measurement of N(ε)-carboxymethyl-Lysine (CML) using an ELISA kit in a subsample of 82 patients. Urinary fluorescent AGEs, albumin and creatinine were also measured in a morning urine sample. Microvascular complications were studied by ophthalmologic examination, albuminuria and peripheral nerve conduction velocity. RESULTS: Patients without microvascular complications had significantly lower levels of both serum and urinary AGEs. CML was associated with retinopathy. Multiple regression analysis confirmed that AGEs, length of diabetes and glycosylated haemoglobin were all variables associated with diabetic complications, in this sample. CONCLUSIONS: A simple fluorimetric assay to measure low molecular weight fluorescent AGEs, and CML could be employed as screening tools to predict diabetic complications, at a primary care setting. AGEs should probably be considered as another therapeutic target in diabetes management.

Rosiglitazone inhibits expression of acyl-coenzyme A:cholesterol acyltransferase-1 in THP-1 macrophages induced by advanced glycation end-products

Objective： To investigate the effects of rosiglitazone, a synthetic ligand of peroxisome proliferators-activated receptor gamma （PPARγ）, on the expression of acyl-coenzyme A： cholesterol acyltransferase-1 （ACAT-1） in phorbol myristate acetate （PMA）-pretreated THP-1 cells after the inducement of advanced glycation end products （AGEs）. Methods： After THP-1 cells were cultured in the presence of 0.1 μmol/L PMA for 72 h to induce phagocytic differentiation, the obtained THP-1 macrophages were treated with rosiglitazone for 4 h at different concentrations （1, 5 or 10 μmol/L） and then exposed to AGEs-modified bovine serum albumin （AGEs-BSA） for 24 h at a concentration of 200 mg/L. Reverse transcription polymerase chain reaction （RT-PCR） and Western blot analysis were performed to detect the mRNA and protein expressions of ACAT-1 respectively. Results： Administration of AGEs-BSA （200 mg/L） into the THP-1 macrophages resulted in up-regulation of ACAT-1 at mRNA and protein levels when compared with the expressions in macrophages incubated with serum-free RPMI1640. Pretreatment of rosiglitazone inhibited significantly the increased expression of ACAT-1 induced by AGEs-BSA in a concentration-dependent manner. Conclusion： PPARy activation by rosiglitazone down-regulates ACAT-1 expression induced by AGEs in THP-1 macrophages, which might provide a new way for treating atherogenesis in diabetic patients.

Inhibitory effect of eleven herbal extracts on advanced glycation end-products formation and aldose reductase activity

The formation of advanced glycation end-products （AGEs） and aldose reductase （AR） activity have been implicated in the development of diabetic complications. Our study sought to characterize the capacities of eleven herbal extracts against the formation of AGEs and the AR activity. An ultrahigh performance liquid chromatography and tandem mass spectrometry （UPLC-MS/MS） method was used for the detection of AR activity and the screening of AR inhibitors in this research. The amount of sorbitol from each analyte was directly detected using the multiple reaction monitoring mode and the sorbitol level could be reduced via the addition of an inhibitor. Moreover, the BSA/glucose （fructose） system was applied to investigate their inhibitory activities of AGEs formation in glycation model reactions. Compared with other screened herbs used in our study, Flos Sophorae lrnrnaturus and Radix Scutellariae seemed to be more effective on inhibiting the formation of AGEs and AR activity. The inhibiting capacities of herbal extracts against AR activity and AGEs formation may be correlated with the bioactive components of the herbal extracts. The differences were correlated with the amount of polyphenol and flavonoid components. In the study, we have investigated the potential anti-hyperglycemic bioactivity of eleven herbal extracts in vitro, which could provide a reference for further in vivo research in the prevention and treatment of diabetic complications.

Complications in the spine associated with type 2 diabetes:The role of advanced glycation end-products

Type 2 diabetes mellitus(T2D)is an increasingly prevalent disease with numerous comorbidities including many in the spine.T2D is strongly linked with vertebral fractures,intervertebral disc(IVD)degeneration,and severe chronic spinal pain.Yet the causative mechanism for these musculoskeletal impairments remains unclear.The chronic hyperglycemic state in T2D promotes the formation of advanced glycation end-products(AGEs)in tissues,and the accumulation of AGEs may play a role in musculoskeletal complications by modifying the extracellular matrix,impairing cellular homeostasis,and perpetuating an inflammatory cascade via its receptor(RAGE).The AGE and RAGE associated alterations in extracellular matrix composition and morphological features of the vertebral bodies and IVDs are likely contributors to the incidence and severity of spinal pathologies in T2D.This review will broadly examine the effects of AGEs on tissues in the spine in the context of T2D,with an emphasis on the changes in the vertebrae and the IVD.Along with the clinical and epidemiological findings,we will provide an overview of preclinical rodent models of T2D that exhibit deficits in the IVD and vertebral bone.Elucidating the role of AGEs and RAGE will be crucial for understanding the disease mechanisms and translation therapies of musculoskeletal pathologies in T2D.

Regulatory role of peroxynitrite in advanced glycation end products mediated diabetic cardiovascular complications

The Advanced Glycation End Products(AGE)binding with its receptor can increase reactive oxygen species(ROS)generation through specific signaling mediators.The effect of superoxide(O2-)and O2-mediated ROS and reactive nitrogen species depends on their concentration and location of formation.Nitric oxide(NO)has anti-inflammatory and anticoagulant properties and a vasodilation effect,but NO can be deactivated by reacting with O_(2)^(-).This reaction between NO and O2-produces the potent oxidant ONOO−.Therefore,ONOO-'s regulatory role in AGEs in diabetic cardiovascular complications must considered as a regulator of cardiovascular complications in diabetes.

Advanced glycation end products in gastric cancer:A promising future

In this editorial,we delve into the article and offer valuable insights into a crucial aspect of gastric cancer aetiology.Gastric cancer is a malignancy emanating from the epithelial lining of the gastric mucosa and one of the most prevalent forms of cancer worldwide.The development of gastric cancer is associated with multiple risk factors,including Helicobacter pylori infection,advanced age,a diet rich in salt,and suboptimal eating patterns.Despite notable reductions in morbidity and mortality rates,gastric cancer remains a formidable public health concern,impacting patients’lives.Advanced glycation end products(AGEs)are complex compounds arising from nonenzymatic reactions within living organisms,the accumulation of which is implicated in cellular and tissue damage;thus,the levels are AGEs are correlated with the risk of diverse diseases.The investigation of AGEs is of paramount importance for the treatment of gastric cancer and can provide pivotal insights into disease pathogenesis and preventive and therapeutic strategies.The reduction of AGEs levels and suppression of their accumulation are promising avenues for mitigating the risk of gastric cancer.This approach underscores the need for further research aimed at identifying innovative interventions that can effectively lower the incidence and mortality rates of this malignancy.

Contributions of the receptor for advanced glycation end products axis activation in gastric cancer

Compelling shreds of evidence derived from both clinical and experimental research have demonstrated the crucial contribution of receptor for advanced glycation end products(RAGE)axis activation in the development of neoplasms,including gastric cancer(GC).This new actor in tumor biology plays an important role in the onset of a crucial and long-lasting inflammatory milieu,not only by supporting phenotypic changes favoring growth and dissemination of tumor cells,but also by functioning as a pattern-recognition receptor in the inflammatory response to Helicobacter pylori infection.In the present review,we aim to highlight how the overexpression and activation of the RAGE axis contributes to the proliferation and survival of GC cells as and their acquisition of more invasive phenotypes that promote dissemination and metastasis.Finally,the contribution of some single nucleotide polymorphisms in the RAGE gene as susceptibility or poor prognosis factors is also discussed.

Intra-coronary administration of soluble receptor for advanced glycation end-products attenuates cardiac remodeling with decreased myocardial transforming growth factor-pl expression and fibrosis in minipigs with ischemia-reperfusion injury

Background The cardioprotective effects of soluble receptor for advanced glycation end-products （sRAGE） have not been evaluated in large animals and the underlying mechanisms are not fully understood. This study aimed to evaluate the effects of intra-coronary administration of sRAGE on left ventricular function and myocardial remodeling in a porcine model of ischemia-reperfusion （I/R） injury. Methods Ten male minipigs with I/R injury were randomly allocated to receive intra-coronary administration of sRAGE （sRAGE group, n=5） or saline （control group, n=5）. Echocardiography was performed before and 2 months after infarction. Myocardial expression of transforming growth factor （TGF）-β1 was determined by immunohistochemistry and fibrosis was evaluated by Sirius red staining. Results As compared with the baseline values in the control animals, left ventricular end-diastolic volume （from （19.5±5.1） to （32.3±5.6） ml, P 〈0.05） and end-systolic volume （from （8.3±3.2） to （15.2±4.1） ml, P 〈0.05） were significantly increased, whereas ejection fraction was decreased （from （61.6±13.3）% to （50.2±11.9）%, P 〈0.05）. No obvious change in these parameters was observed in the sRAGE group. Myocardial expression of TGF-β1 was significantly elevated in the infarct and non-infarct regions in the control group, as compared with sRAGE group （both P 〈0.01）. Fibrotic lesions were consistently more prominent in the infarct region of the myocardium in the control animals （P〈0.05）. Conclusion Intra-coronary sRAGE administration attenuates RAGE-mediated myocardial fibrosis and I/R injury through a TGF-β1-dependent mechanism, suggesting a clinical potential in treating RAGE/ligand-associated cardiovascular diseases.

Advanced-glycation end-products axis:A contributor to the risk of severe illness from COVID-19 in diabetes patients

Compelling pieces of evidence derived from both clinical and experimental research has demonstrated the crucial role of the receptor for advanced-glycation end-products(RAGE)in orchestrating a plethora of proinflammatory cellular responses leading to many of the complications and end-organ damages reported in patients with diabetes mellitus(DM).During the coronavirus disease 2019(COVID-19)pandemic,many clinical reports have pointed out that DM increases the risk of COVID-19 complications,hospitalization requirements,as well as the overall severe acute respiratory syndrome coronavirus 2 case-fatality rate.In the present review,we intend to focus on how the basal activation state of the RAGE axis in common preexisting conditions in DM patients such as endothelial dysfunction and hyperglycemia-related prothrombotic phenotype,as well as the contribution of RAGE signaling in lung inflammation,may then lead to the increased mortality risk of COVID-19 in these patients.Additionally,the crosstalk between the RAGE axis with either another severe acute respiratory syndrome coronavirus 2 receptor molecule different of angiotensin-converting enzyme 2 or the renin-angiotensin system imbalance produced by viral infection,as well as the role of this multi-ligand receptor on the obesity-associated lowgrade inflammation in the higher risk for severe illness reported in diabetes patients with COVID-19,are also discussed.

Individual and Combined Effects of Food Components in Attenuating the Formation of Advanced Glycation End Products (AGEs)

Advanced Glycation End Products (AGEs) have been associated as a possible cause in inflammation-mediated chronic diseases such as diabetes, Alzheimer’s and cardiovascular disorders. Thus, inhibition of AGE formation represents a prospective therapeutic target for the prevention and treatment of these complications. This study investigated the individual and combined effects of dietary ingredients, spices, on lowering AGEs formation in meat patties. In the study, Carboxymethyllysine (CML), a well-investigated AGE is used as a marker for AGEs and malondialdehyde (MDA) as an indicator for lipid peroxidation. Nine spices were selected based on their ability to inhibit the formation of AGEs at different stages of Maillard reactions. Individually, all the 9 selected spices significantly inhibited the formation of AGEs. Among the 33 combinations of spices, 26 combinations significantly inhibited the formation of AGEs. The highest reduction (84%) was found by the combination of Black Pepper-Rose-Cumin. The individual spices failed to significantly lower the MDA concentration;however, all 33 combinations were able to significantly reduce MDA concentration. The results of this study showed that spices when supplemented in combinations are more effective in inhibiting the formation of AGEs and in decreasing MDA concentration in meat patties.

Association of advanced glycation endproduct accumulation with overactive bladder in community-dwelling elderly: A cross-sectional Sukagawa study

Objective:This study aimed to evaluate the influence of advanced glycation end-product(AGE)accumulation on the prevalence and severity of overactive bladder(OAB)in community-dwelling elderly adults.Methods:We conducted a cross-sectional study involving 269 Japanese community dwellers aged≥75 years in 2015.AGE accumulation was non-invasively measured via skin autofluorescence(SAF)values using AGE Reader.The primary and secondary outcomes were the presence and severity of OAB evaluated using the Overactive Bladder Symptom Score(OABSS).Individuals with an urgency score of≥2 and sum score of≥3 were considered to have OAB.The associations of SAF with the prevalence and severity of OAB were assessed using logistic and linear regression models,respectively,adjusted for clinically important confounders.Results:The median age of participants was 78 years.Of 269 participants,110(40.9%)were men and 75(27.9%)had OAB.The median SAF was 2.2 arbitrary units(AUs).Increasing median SAF was observed with increasing age.Multivariable analysis revealed that SAF was not associated with either the likelihood of having OAB(odds ratio per AU=0.77,95%confidence interval:0.37-1.62)or the natural log-transformed OABSS(0 per AU=-0.07,95%confidence interval:-0.26-0.12).Conclusions:In this study,AGE accumulation,as assessed by SAF,was not associated with the prevalence and severity of OAB in Japanese community-dwelling elderly people aged≥75 years.

Role of advanced glycation end products in cardiovascular disease

Advanced glycation end products (AGEs) are produced through the non enzymatic glycation and oxidation of proteins, lipids and nucleic acids. Enhanced formation of AGEs occurs particularly in conditions associated with hyperglycaemia such as diabetes mellitus (DM). AGEs are believed to have a key role in the development and progression of cardiovascular disease in patients with DM through the modification of the structure, function and mechanical properties of tissues through crosslinking intracellular as well as extracellular matrix proteins and through modulating cellular processes through binding to cell surface receptors [receptor for AGEs (RAGE)]. A number of studies have shown a correlation between serum AGE levels and the development and severity of heart failure. Moreover, some studies have suggested that therapies targeted against AGEs may have therapeutic potential in patients with heart failure (HF). The purpose of this review is to discuss the role of AGEs in cardiovascular disease and in particular in heart failure, focussing on both cellular mechanisms of action as well as highlighting how targeting AGEs may represent a novel therapeutic strategy in the treatment of HF.