ACKGROUND The hemoglobin glycation index(HGI)represents the discrepancy between the glucose management indicator(GMI)based on mean blood glucose levels and laboratory values of glycated hemoglobin(HbA1c).The HGI is a ...ACKGROUND The hemoglobin glycation index(HGI)represents the discrepancy between the glucose management indicator(GMI)based on mean blood glucose levels and laboratory values of glycated hemoglobin(HbA1c).The HGI is a promising indicator for identifying individuals with excessive glycosylation,facilitating personalized evaluation and prediction of diabetic complications.However,the factors influencing the HGI in patients with type 1 diabetes(T1D)remain unclear.Autoimmune destruction of pancreaticβcells is central in T1D pathogenesis,yet insulin resistance can also be a feature of patients with T1D and their coexistence is called“double diabetes”(DD).However,knowledge regarding the relationship between DD features and the HGI in T1D is limited.AIM To assess the association between the HGI and DD features in adults with T1D.METHODS A total of 83 patients with T1D were recruited for this cross-sectional study.Laboratory HbA1c and GMI from continuous glucose monitoring data were collected to calculate the HGI.DD features included a family history of type 2 diabetes,overweight/obesity/central adiposity,hypertension,atherogenic dyslipidemia,an abnormal percentage of body fat(PBF)and/or visceral fat area(VFA)and decreased estimated insulin sensitivity.Skin autofluorescence of advanced glycation end products(SAF-AGEs),diabetic complications,and DD features were assessed,and their association with the HGI was analyzed.RESULTS A discrepancy was observed between HbA1c and GMI among patients with T1D and DD.A higher HGI was associated with an increased number of SAF-AGEs and a higher prevalence of diabetic microangiopathy(P=0.030),particularly retinopathy(P=0.031).Patients with three or more DD features exhibited an eight-fold increased risk of having a high HGI,compared with those without DD features(adjusted odds ratio=8.12;95%confidence interval:1.52-43.47).Specifically,an elevated PBF and/or VFA and decreased estimated insulin sensitivity were associated with high HGI.Regression analysis identified estimated insulin sensitivity and VFA as factors independently associated with HGI.CONCLUSION In patients with T1D,DD features are associated with a higher HGI,which represents a trend toward excessive glycosylation and is associated with a higher prevalence of chronic diabetic complications.展开更多
OBJECTIVE:To evaluate the therapeutic effects of Xiahuo Pingwei San(夏藿平胃散,XHPWS)on ulcerative colitis(UC)in mice and to explore the underlying mechanisms through a network pharmacology approach.METHODS:Ultra-perf...OBJECTIVE:To evaluate the therapeutic effects of Xiahuo Pingwei San(夏藿平胃散,XHPWS)on ulcerative colitis(UC)in mice and to explore the underlying mechanisms through a network pharmacology approach.METHODS:Ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF/MS)was utilized to identify the chemical composition and authenticate the active constituents of XHPWS,ensuring rigorous quality control across batches.A dextran sulfate sodium(DSS)-induced UC model was established in C57BL/6 mice,which were treated with XHPWS in vivo.The efficacy against UC was assessed by measuring parameters such as body weight,disease activity index(DAI)scores,and colon length.Levels of inflammatory cytokines,including interleukin-6(IL-6),interleukin-1β(IL-1β),and tumor necrosis factor-alpha(TNF-α),in colonic tissue were evaluated using enzymelinked immunosorbent assay(ELISA).Histological analysis of colon sections was conducted using hematoxylin and eosin staining.A network pharmacology approach was employed to explore the mechanisms of XHPWS and to predict its potential targets in UC treatment.Predicted protein expressions in colonic tissue were validated using immune-ohistochemistry(IHC)and Western blotting techniques.RESULTS:XHPWS effectively alle via ted DSS-induced UC symptoms in mice,as evidenced by restored body weight,reduced colon shortening,and decreased DAI scores.Histopathological examination revealed that XHPWS significantly reduced intestinal inflammatory infiltration,restored intestinal epithelial permeability,and increased goblet cell count.Network pharmacology analysis identified 63 active compounds in XHPWS and suggested that it might target 35 potential proteins associated with UC treatment.Functional enrichment analysis indicated that the protective mechanism of XHPWS could be related to the advanced glycation end products-receptor for advanced glycation end products(AGE-RAGE)signaling pathway.Notably,quercetin,kaempferol,wogonin,and nobiletin,the main components of XHPWS,showed strong correlations with the core targets.Additionally,experimental validation demonstrated that XHPWS significantly decreased levels of inflammatory cytokines interleukin 6(IL-6),interleukin 1 beta(IL-1β),and tumor necrosis factor alpha(TNF-α)in UC mice,while downregulating the expression of proteins related to the AGE-RAGE pathway.CONCLUSION:Our study demonstrated that XHPWS effectively alle via tes colitis symptoms and inflammation in UC mice,potentially through the regulation of the AGE-RAGE pathway.These findings provide strong evidence for the therapeutic potential of XHPWS in UC treatment,thereby broadening its clinical applications.展开更多
BACKGROUND Gestational diabetes mellitus(GDM)is one of the most prevalent metabolic disorders of pregnancy.Advanced glycation end-products(AGEs)are a complex and highly heterogeneous group of compounds formed from ami...BACKGROUND Gestational diabetes mellitus(GDM)is one of the most prevalent metabolic disorders of pregnancy.Advanced glycation end-products(AGEs)are a complex and highly heterogeneous group of compounds formed from amino acids and reducing sugars.High-AGE diet exposure during pregnancy may cause adverse effects.AIM To investigate the expression levels of AGE and AGE receptor(RAGE)in the serum and placenta of pregnant women with GDM and to assess the association of their mediated oxidative stress response with perinatal outcomes.METHODS This study retrospectively analyzed the clinical data of 126 pregnant women with GDM who gave birth in the Obstetrics Department of Obstetrics and Gynecology Hospital of Fudan University from January 2023 to January 2024.A total of 85 pregnant women of similar age without GDM during the same period were selected as the control group.Fasting blood glucose,glycated hemoglobin,AGEs,soluble RAGE(sRAGE),and oxidative stress were compared in both groups.Postpartum placental tissue was collected to identify RAGE protein expression.Participants with GDM were categorized based on perinatal outcomes into normal(n=89)and adverse perinatal outcome groups(n=37),and differences in serum AGE–RAGE levels and oxidative stress were analyzed.The influencing factors of adverse perinatal outcomes were analyzed using logistic regression.RESULTS The GDM group demonstrated notably higher serum AGE(t=8.955)and malondialdehyde(MDA)levels(t=14.14)and lower sRAGE(t=16.37)and superoxide dismutase(SOD)levels(t=18.50)than the control group at 24-28 weeks of gestation and before delivery(P<0.0001).Serum AGE levels were positively correlated with MDA and negatively related to SOD at 24-28 weeks of pregnancy(SOD:r=0.393,MDA:r=0.424,P<0.0001)and before delivery(SOD:r=0.443,MDA:r=0.492,P<0.0001),whereas AGE was inversely associated with sRAGE in the GDM group(r=-0.495,P<0.0001).Serum AGE levels were significantly higher(t=9.225,P<0.0001)and the sRAGE level(r=3.563,P<0.0001)was significantly lower in participants with adverse perinatal outcomes than those with normal perinatal outcomes in the GDM group.Logistic regression analysis revealed AGE level as a risk factor(OR=1.056,P<0.0001)and sRAGE level(OR=0.949,P<0.0001)as a protective factor for adverse perinatal outcomes in GDM.CONCLUSION High serum AGE level is a risk factor for adverse perinatal outcomes in GDM,whereas high sRAGE levels are protective.AGEs and RAGE may be associated with oxidative stress in pregnant women with GDM.展开更多
BACKGROUND Colorectal cancer(CRC)ranks among the most prevalent malignancies in elderly populations,and chemotherapy resistance remains a critical clinical challenge.Emerging evidence highlights the interplay between ...BACKGROUND Colorectal cancer(CRC)ranks among the most prevalent malignancies in elderly populations,and chemotherapy resistance remains a critical clinical challenge.Emerging evidence highlights the interplay between chronic inflammation,gut microbiome dysbiosis,and CRC progression.Proinflammatory cytokines[e.g.,interleukin(IL)-6,tumor necrosis factor-alpha(TNF-α)]and mediators like S100 calcium-binding protein A12(S100A12)/soluble receptor for advanced glycation end products(sRAGE)are implicated in tumorigenesis,while gut microbial imbalances may exacerbate inflammatory microenvironments conducive to che-motherapy resistance.However,the triad relationship between S100A12/sRAGE,gut microbiota profiles,and chemotherapy efficacy in elderly patients with CRC remains unexplored,limiting biomarker-driven therapeutic strategies.AIM To analyze the correlation between serum levels of S100A12,sRAGE,gut microbiome dysbiosis,and systemic inflammation in elderly patients with CRC and to assess their predictive value for chemotherapy efficacy.METHODS A retrospective analysis was conducted on the clinical data of 120 elderly patients with advanced-stage CRC who visited our hospital from August 2023 to May 2024.These patients were enrolled in the study group.Additionally,120 healthy individuals undergoing routine health check-ups during the same period were selected as the control group.Serum S100A12,sRAGE,IL-6,and TNF-αlevels were measured by ELISA,and fresh stool samples were collected before chemotherapy to analyze gut microbiome composition in the study group.Follow-up observations were conducted after chemotherapy.Pearson correlation analysis was used to explore the relationship between serum S100A12,sRAGE levels,and gut microbiome dysbiosis in patients with CRC.The predictive diagnostic value of pre-chemotherapy serum S100A12 and sRAGE levels for chemotherapy efficacy was assessed using receiver operating characteristic curves.RESULTS Pre-chemotherapy serum S100A12,sRAGE,IL-6,and TNF-αlevels were significantly elevated in patients with CRC vs controls(all P<0.05).These biomarkers progressively increased with microbiota dysbiosis severity(severe vs mild dysbiosis:S100A12:340.26±52.39μg/L vs 302.53±56.97μg/L;sRAGE:525.64±37.32 ng/L vs 441.38±48.73 ng/L,P<0.05)and correlated strongly with IL-6(r=0.712)and TNF-α(r=0.698).Post-chemotherapy,biomarker levels decreased(P<0.05),coinciding with beneficial microbiota recovery(Bifidobacterium 176%,Lactobacillus 153%)and pathogenic taxa reduction(Escherichia coli 62%).The combined S100A12/sRAGE model predicted chemotherapy resistance with an area under the curve of 0.914(sensitivity=86.07%,specificity=88.89%),outper-forming individual biomarkers.CONCLUSION Elevated serum S100A12 and sRAGE in elderly patients with CRC reflected gut microbiome dysbiosis and systemic inflammation,driven by IL-6/TNF-αsignaling.Their post-chemotherapy decline parallels microbiota restoration,supporting a microbiome-inflammation-biomarker axis.The combined biomarker model offers robust clinical utility for chemotherapy efficacy prediction and personalized therapeutic strategies.展开更多
Advanced glycation end products(AGEs)are complex compounds formed through interaction of carbonyl groups from saccharides with amino groups in amino acids,proteins,lipids and nucleic acids,mainly via Maillard reaction...Advanced glycation end products(AGEs)are complex compounds formed through interaction of carbonyl groups from saccharides with amino groups in amino acids,proteins,lipids and nucleic acids,mainly via Maillard reaction.Studies have shown that AGEs can accumulate in the body and lead to neurodegenerative diseases,cardiovascular diseases,inflammatory responses,diabetes,and other diseases.This comment will provide a review of the inhibitory mechanism of flavonoids on dietary AGEs formation in food models and aims to provide a theoretical basis for the development of new therapeutic strategies and drugs.展开更多
Type 2 diabetes markedly elevates fracture risk despite normal or high bone mineral density,a paradox reflecting qualitative skeletal deficits rather than loss of mass.Chronic hyperglycemia fosters the accumulation of...Type 2 diabetes markedly elevates fracture risk despite normal or high bone mineral density,a paradox reflecting qualitative skeletal deficits rather than loss of mass.Chronic hyperglycemia fosters the accumulation of advanced glycation end products in bone;their nonenzymatic crosslinks stiffen type I collagen,impair mineralization,and erode mechanical strength.By engaging the receptor for advanced glycation end products,these adducts activate nuclear factorκB and mitogen-activated protein kinase cascades,amplifying oxidative stress,inflammation,osteoblast dysfunction,and osteoclastogenesis.This review synthesizes epidemiological data from type 1 and type 2 diabetes,highlights the limits of densitybased skeletal assessment,and details the molecular pathology of the glycation-collagen axis.It also appraises antiglycation therapies,including formation inhibitors,crosslink breakers and receptor antagonists,with a particular focus on sodium-glucose cotransporter 2 inhibitors that couple glycemic control with modulation of the glycation pathway.By integrating recent basic and clinical advances,we propose a mechanistic framework for diabetic bone disease and outline strategies to mitigate glycationdriven skeletal fragility.展开更多
Effect of ellagitannins gut microbiota metabolites ellagic acid(EA)and urolithin A-urolithin D(UroA-UroD)on human serum albumin(HSA)glycation were firstly evaluated in this research.The inhibition mechanisms were inve...Effect of ellagitannins gut microbiota metabolites ellagic acid(EA)and urolithin A-urolithin D(UroA-UroD)on human serum albumin(HSA)glycation were firstly evaluated in this research.The inhibition mechanisms were investigated by methylglyoxal(MGO)trapping and radical scavenging ability assays,docking studies and nano LC-orbitrap-MS/MS technology.Results indicated that the inhibition of urolithins on HSA glycation was highly positive correlated with the number of phenolic hydroxy groups.Addition of UroD and EA could effectively enhance the content of free amino group,suppress dicarbonyl compounds and advanced glycation end-products(AGEs)formation,alleviated tryptophan and protein oxidation,inhibited HSA amyloid-like aggregation.They could also trap MGO and scavenge 1,1-diphenyl-2-picrylhydrazyl free radical(DPPH·)and2,2'-azino-bis-3-ethylbenzthiazoline-6-sulphonic acid free radical(ABTS^(+)·).Molecular docking indicated that EA and UroA-UroD interact with HSA mainly through hydrogen bound and hydrophobic interaction,among which 2 or 3 hydrogen bonds were formed.The number of glycation sites were reduced from 11 to10,10,7,and 10,respectively,when 90μmol/L of EA,UroA,UroC and UroD were added.However,weak inhibition was observed on UroA and UroB.These findings can provide scientific evidence for the application of ellagitannins-rich foods in alleviating diabetic complications.展开更多
The incidence of type 2 diabetes mellitus is growing in epidemic proportions and has become one of the most critical public health concerns.Cardiovascular complications associated with diabetes are the leading cause o...The incidence of type 2 diabetes mellitus is growing in epidemic proportions and has become one of the most critical public health concerns.Cardiovascular complications associated with diabetes are the leading cause of morbidity and mortality.The cardiovascular diseases that accompany diabetes include angina,myocardial infarction,stroke,peripheral artery disease,and congestive heart failure.Among the various risk factors generated secondary to hyperglycemic situations,advanced glycation end products(AGEs)are one of the important targets for future diagnosis and prevention of diabetes.In the last decade,AGEs have drawn a lot of attention due to their involvement in diabetic pathophysiology.AGEs can be derived exogenously and endogenously through various pathways.These are a nonhomogeneous,chemically diverse group of compounds formed nonenzymatically by condensation between carbonyl groups of reducing sugars and free amino groups of protein,lipids,and nucleic acid.AGEs mediate their pathological effects at the cellular and extracellular levels by multiple pathways.At the cellular level,they activate signaling cascades via the receptor for AGEs and initiate a complex series of intracellular signaling resulting in reactive oxygen species generation,inflammation,cellular proliferation,and fibrosis that may possibly exacerbate the damaging effects on cardiac functions in diabetics.AGEs also cause covalent modifications and cross-linking of serum and extracellular matrix proteins;altering their structure,stability,and functions.Early diagnosis of diabetes may prevent its progression to complications and decrease its associated comorbidities.In the present review,we recapitulate the role of AGEs as a crucial mediator of hyperglycemia-mediated detrimental effects in diabetes-associated complications.Furthermore,this review presents an overview of future perspectives for new therapeutic interventions to ameliorate cardiovascular complications in diabetes.展开更多
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...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.展开更多
The presence of excess glucose in blood is regarded as a sweet hurt for patients with diabetes.Human serum albumin(HSA)is the most abundant protein in human plasma,which undergoes severe non-enzymatic glycation with g...The presence of excess glucose in blood is regarded as a sweet hurt for patients with diabetes.Human serum albumin(HSA)is the most abundant protein in human plasma,which undergoes severe non-enzymatic glycation with glucose in patients with diabetes;this modifies the structure and function of HSA.Furthermore,the advanced glycation end products produced by glycated HSA can cause pathological damage to the human body through various signaling pathways,eventually leading to complications of diabetes.Many potential glycation sites on HSA have different degrees of sensitivity to glucose concentration.This review provides a comprehensive assessment of the in vivo glycation sites of HSA;it also discusses the effects of glycation on the structure and function of HSA.Moreover,it addresses the relationship between HSA glycation and diabetes complications.Finally,it focuses on the value of non-enzymatic glycation of HSA in diabetes-related clinical applications.展开更多
Obesity and type 2 diabetes mellitus(T2DM)are chronic pathologies with a high incidence worldwide.They share some pathological mechanisms,including hyperinsulinemia,the production and release of hormones,and hyperglyc...Obesity and type 2 diabetes mellitus(T2DM)are chronic pathologies with a high incidence worldwide.They share some pathological mechanisms,including hyperinsulinemia,the production and release of hormones,and hyperglycemia.The above,over time,affects other systems of the human body by causing tissue hypoxia,low-grade inflammation,and oxidative stress,which lay the pathophysiological groundwork for cancer.The leading causes of death globally are T2DM and cancer.Other main alterations of this pathological triad include the accumulation of advanced glycation end products and the release of endogenous alarmins due to cell death(i.e.,damage-associated molecular patterns)such as the intracellular proteins high-mobility group box protein 1 and protein S100 that bind to the receptor for advanced glycation products(RAGE)-a multiligand receptor involved in inflammatory and metabolic and neoplastic processes.This review analyzes the latest advanced reports on the role of RAGE in the development of obesity,T2DM,and cancer,with an aim to understand the intracellular signaling mechanisms linked with cancer initiation.This review also explores inflammation,oxidative stress,hypoxia,cellular senescence,RAGE ligands,tumor microenvironment changes,and the“cancer hallmarks”of the leading tumors associated with T2DM.The assimilation of this information could aid in the development of diagnostic and therapeutic approaches to lower the morbidity and mortality associated with these diseases.展开更多
[ Objective] In order to study the anti-oxidation and inhibitory effect on nonenzymatic glycation reaction of EGB fermentation extraction biotransformed by Hericium erinaceus. [ Method ] The free radical scavenging ab...[ Objective] In order to study the anti-oxidation and inhibitory effect on nonenzymatic glycation reaction of EGB fermentation extraction biotransformed by Hericium erinaceus. [ Method ] The free radical scavenging ability and reducing capacity of DPPH as well as inhibitory rate of nonenzymatic glycation reaction were measured targets for comparing changes of anti-oxidation and inhibitory effect on nonenzymatic glycation reaction of fermentation lyophilizer and fermentation extraction before and after EGB fermention adsorbed by AB-8 macroporous resin. The EGB fermention was biotransformed by Hericium erinaceus. [ Result ] After adsorbed by AB-8 macroporous resin, the bioactive matters were concentrated and separated. The free radical scavenging rate, reducing capacity and inhibitory rate of nonenzymatic glycation reaction were increased significantly after adsorbed by AB-8 macroporous resin. [ Conclusion] AB-8 macroporous resin could be used for preliminary concentration of EGB fermentation which was biotransformed by Hericium erinaceus.展开更多
AIM： To study the role of advanced glycation end products （AGE） and their specific receptor （RAGE） in the pathogenesis of liver fibrogenesis. METHODS： In vitro RAGE expression and extracellular matrix-related ge...AIM： To study the role of advanced glycation end products （AGE） and their specific receptor （RAGE） in the pathogenesis of liver fibrogenesis. METHODS： In vitro RAGE expression and extracellular matrix-related gene expression in both rat and human hepatic stellate cells （HSC） were measured after stimulation with the two RAGE ligands, advanced glycation end product-bovine serum albumin （AGE- BSA） and N＇-（carboxymethyl） lysine （CML）-BSA, or with tumor necrosis factor-α （TNF-α）. In vivo RAGE expression was examined in models of hepatic fibrosis induced by bile duct ligation or thioacetamide. The effects of AGE-BSA and CML-BSA on HSC proliferation, signal transduction and profibrogenic gene expression were studied in vitro. RESULTS： In hepatic fibrosis, RAGE expression was enhanced in activated HSC, and also in endothelial cells, inflammatory cells and activated bile duct epithelia. HSC expressed RAGE which was upregulated after stimulation with AGE-BSA, CML-BSA, and TNF-α.RAGE stimulation with AGE-BSA and CML-BSA did not alter HSC proliferation, apoptosis, fibrogenic signal transduction and fibrosis- or fibrolysis-related gene expression, except for marginal upregulation of procollagen α1（ I ） mRNA by AGE-BSA. CONCLUSION： Despite upregulation of RAGE in activated HSC, RAGE stimulation by AGE does not alter their fibrogenic activation. Therefore, RAGE does not contribute directly to hepatic fibrogenesis.展开更多
Advanced glycation end products lead to cell apoptosis, and cause cell death by increasing endoplasmic reticulum stress. Advanced glycation end products alone may also directly cause damage to tissues and cells, but t...Advanced glycation end products lead to cell apoptosis, and cause cell death by increasing endoplasmic reticulum stress. Advanced glycation end products alone may also directly cause damage to tissues and cells, but the precise mechanism remains unknown. This study used primary cultures of rat cerebral cortex neurons, and treated cells with different concentrations of glycation end products （50, 100, 200, 400 mg/L）, and with an antibody for the receptor of advanced glycation end products before and after treatment with advanced glycation end products. The results showed that with increasing concentrations of glycation end products, free radical content increased in neurons, and the number of apoptotic cells increased in a dose-dependent manner. Before and after treatment of advanced glycation end products, the addition of the antibody against advanced glycation end-products markedly reduced hydroxyl free radicals, malondialdehyde levels, and inhibited cell apoptosis. This result indicated that the antibody for receptor of advanced glycation end-products in neurons from the rat cerebral cortex can reduce glycation end product-induced oxidative stress damage by suppressing glycation end product receptors. Overall, our study confirms that the advanced glycation end products-advanced glycation end products receptor pathway may be the main signaling pathway leading to neuronal damage.展开更多
Advanced glycation end products(AGEs)are a heterogeneous collection of compounds formed during industrial processing and home cooking through a sequence of nonenzymatic glycation reactions.The modern western diet is f...Advanced glycation end products(AGEs)are a heterogeneous collection of compounds formed during industrial processing and home cooking through a sequence of nonenzymatic glycation reactions.The modern western diet is full of heat-treated foods that contribute to AGE intake.Foods high in AGEs in the contemporary diet include processed cereal products.Due to industrialization and marketing strategies,restaurant meals are modified rather than being traditionally or conventionally cooked.Fried,grilled,baked,and boiled foods have the greatest AGE levels.Higher AGE-content foods include dry nuts,roasted walnuts,sunflower seeds,fried chicken,bacon,and beef.Animal proteins and processed plant foods contain furosine,acrylamide,heterocyclic amines,and 5-hydroxymethylfurfural.Furosine(2-furoil-methyl-lysine)is an amino acid found in cooked meat products and other processed foods.High concentrations of carboxymethyl-lysine,carboxyethyl-lysine,and methylglyoxal-O are found in heat-treated nonvegetarian foods,peanut butter,and cereal items.Increased plasma levels of AGEs,which are harmful chemicals that lead to age-related diseases and physiological aging,diabetes,and autoimmune/inflammatory rheumatic diseases such as systemic lupus erythematosus and rheumatoid arthritis.AGEs in the pathophysiology of metabolic diseases have been linked to individuals with diabetes mellitus who have peripheral nerves with high amounts of AGEs and diabetes has been linked to increased myelin glycation.Insulin resistance and hyperglycemia can impact numerous human tissues and organs,leading to long-term difficulties in a number of systems and organs,including the cardiovascular system.Plasma AGE levels are linked to all-cause mortality in individuals with diabetes who have fatal or nonfatal coronary artery disease,such as ventricular dysfunction.High levels of tissue AGEs are independently associated with cardiac systolic dysfunction in diabetic patients with heart failure compared with diabetic patients without heart failure.It is widely recognized that AGEs and oxidative stress play a key role in the cardiovascular complications of diabetes because they both influence and are impacted by oxidative stress.All chronic illnesses involve protein,lipid,or nucleic acid modifications including crosslinked and nondegradable aggregates known as AGEs.Endogenous AGE formation or dietary AGE uptake can result in additional protein modifications and stimulation of several inflammatory signaling pathways.Many of these systems,however,require additional explanation because they are not entirely obvious.This review summarizes the current evidence regarding dietary sources of AGEs and metabolism-related complications associated with AGEs.展开更多
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 ...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.展开更多
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 de...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.展开更多
OBJECTIVE: To investigate the inhibitive efficacy of Nymphoides Indica(L.) Kuntze rhizome extract onα-glucosidase and on cross-link formation of advanced glycation end products(AGEs).METHODS: The plant extracts were ...OBJECTIVE: To investigate the inhibitive efficacy of Nymphoides Indica(L.) Kuntze rhizome extract onα-glucosidase and on cross-link formation of advanced glycation end products(AGEs).METHODS: The plant extracts were prepared by cold maceration and fractionated in solvents of diverse polarity. The in vitro α-glucosidase inhibition assay, fluorescence spectrometry and SDS-PAGE analysis was performed for antiglycation assays.RESULTS: During α-glucosidase inhibition assay significant inhibition by chloroform(0.43 mg/mL)and methanol fractions(0.66 mg/mL) was noticed.During the AGEs inhibition assay, both oxidative(BSA-MGO) and non-oxidative(BSA-glucose)modes were employed. The inhibition of AGEs by total extract was considered moderate(IC_(50)0.10 mg/mL) as a result of non-oxidative mode, whereas in case of oxidative mode(BASA-MGO) no activity was recorded. Among fractions the methanolic fraction presented significant results both in oxidative(IC_(50)0.01 mg/mL) and non-oxidative modes(IC_(50) 0.3 mg/mL). Likewise the ethyl acetate fraction was more active in non-oxidative mode(IC_(50)0.04 mg/mL) compared to oxidative mode(IC_(50)0.32 mg/mL).During assay for inhibition of cross-link formation,the chloroform fraction significantly inhibited cross-link formation in a dose dependent mode.CONCLUSION: It was finally concluded that N. Indica rhizome extract possesses significant properties that inhibit α-glucosidase, and AGEs cross-link formation.展开更多
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 proinflammat...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.展开更多
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 o...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.展开更多
基金Supported by the National Key R D Program of China,No.2022YFC2010102Natural Science Foundation of Hunan Province,No.2021JC0003+1 种基金National Natural Science Foundation of China,No.82070812the Sinocare Diabetes Foundation,No.LYF2022039.
文摘ACKGROUND The hemoglobin glycation index(HGI)represents the discrepancy between the glucose management indicator(GMI)based on mean blood glucose levels and laboratory values of glycated hemoglobin(HbA1c).The HGI is a promising indicator for identifying individuals with excessive glycosylation,facilitating personalized evaluation and prediction of diabetic complications.However,the factors influencing the HGI in patients with type 1 diabetes(T1D)remain unclear.Autoimmune destruction of pancreaticβcells is central in T1D pathogenesis,yet insulin resistance can also be a feature of patients with T1D and their coexistence is called“double diabetes”(DD).However,knowledge regarding the relationship between DD features and the HGI in T1D is limited.AIM To assess the association between the HGI and DD features in adults with T1D.METHODS A total of 83 patients with T1D were recruited for this cross-sectional study.Laboratory HbA1c and GMI from continuous glucose monitoring data were collected to calculate the HGI.DD features included a family history of type 2 diabetes,overweight/obesity/central adiposity,hypertension,atherogenic dyslipidemia,an abnormal percentage of body fat(PBF)and/or visceral fat area(VFA)and decreased estimated insulin sensitivity.Skin autofluorescence of advanced glycation end products(SAF-AGEs),diabetic complications,and DD features were assessed,and their association with the HGI was analyzed.RESULTS A discrepancy was observed between HbA1c and GMI among patients with T1D and DD.A higher HGI was associated with an increased number of SAF-AGEs and a higher prevalence of diabetic microangiopathy(P=0.030),particularly retinopathy(P=0.031).Patients with three or more DD features exhibited an eight-fold increased risk of having a high HGI,compared with those without DD features(adjusted odds ratio=8.12;95%confidence interval:1.52-43.47).Specifically,an elevated PBF and/or VFA and decreased estimated insulin sensitivity were associated with high HGI.Regression analysis identified estimated insulin sensitivity and VFA as factors independently associated with HGI.CONCLUSION In patients with T1D,DD features are associated with a higher HGI,which represents a trend toward excessive glycosylation and is associated with a higher prevalence of chronic diabetic complications.
基金the Guangdong Provincial Basic and Applied Basic Research Project:Mechanistic Study on the Regulation of Inflammatory Microenvironment and Improvement of Ulcerative Colitis by Lingnan Traditional Medicine Ficus Pandurata Hance through Wilms'Tumor 1-associating Protein-Mediated RNA Methyltransferase Promoting Toll Like Receptor 4 m6A Modification(2023A1515011699)the Zhongshan Medical Research Project:Mechanistic Study on the Action of Xiahuo Pingwei San in the Treatment of Ulcerative Colitis(2022A020446)。
文摘OBJECTIVE:To evaluate the therapeutic effects of Xiahuo Pingwei San(夏藿平胃散,XHPWS)on ulcerative colitis(UC)in mice and to explore the underlying mechanisms through a network pharmacology approach.METHODS:Ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF/MS)was utilized to identify the chemical composition and authenticate the active constituents of XHPWS,ensuring rigorous quality control across batches.A dextran sulfate sodium(DSS)-induced UC model was established in C57BL/6 mice,which were treated with XHPWS in vivo.The efficacy against UC was assessed by measuring parameters such as body weight,disease activity index(DAI)scores,and colon length.Levels of inflammatory cytokines,including interleukin-6(IL-6),interleukin-1β(IL-1β),and tumor necrosis factor-alpha(TNF-α),in colonic tissue were evaluated using enzymelinked immunosorbent assay(ELISA).Histological analysis of colon sections was conducted using hematoxylin and eosin staining.A network pharmacology approach was employed to explore the mechanisms of XHPWS and to predict its potential targets in UC treatment.Predicted protein expressions in colonic tissue were validated using immune-ohistochemistry(IHC)and Western blotting techniques.RESULTS:XHPWS effectively alle via ted DSS-induced UC symptoms in mice,as evidenced by restored body weight,reduced colon shortening,and decreased DAI scores.Histopathological examination revealed that XHPWS significantly reduced intestinal inflammatory infiltration,restored intestinal epithelial permeability,and increased goblet cell count.Network pharmacology analysis identified 63 active compounds in XHPWS and suggested that it might target 35 potential proteins associated with UC treatment.Functional enrichment analysis indicated that the protective mechanism of XHPWS could be related to the advanced glycation end products-receptor for advanced glycation end products(AGE-RAGE)signaling pathway.Notably,quercetin,kaempferol,wogonin,and nobiletin,the main components of XHPWS,showed strong correlations with the core targets.Additionally,experimental validation demonstrated that XHPWS significantly decreased levels of inflammatory cytokines interleukin 6(IL-6),interleukin 1 beta(IL-1β),and tumor necrosis factor alpha(TNF-α)in UC mice,while downregulating the expression of proteins related to the AGE-RAGE pathway.CONCLUSION:Our study demonstrated that XHPWS effectively alle via tes colitis symptoms and inflammation in UC mice,potentially through the regulation of the AGE-RAGE pathway.These findings provide strong evidence for the therapeutic potential of XHPWS in UC treatment,thereby broadening its clinical applications.
文摘BACKGROUND Gestational diabetes mellitus(GDM)is one of the most prevalent metabolic disorders of pregnancy.Advanced glycation end-products(AGEs)are a complex and highly heterogeneous group of compounds formed from amino acids and reducing sugars.High-AGE diet exposure during pregnancy may cause adverse effects.AIM To investigate the expression levels of AGE and AGE receptor(RAGE)in the serum and placenta of pregnant women with GDM and to assess the association of their mediated oxidative stress response with perinatal outcomes.METHODS This study retrospectively analyzed the clinical data of 126 pregnant women with GDM who gave birth in the Obstetrics Department of Obstetrics and Gynecology Hospital of Fudan University from January 2023 to January 2024.A total of 85 pregnant women of similar age without GDM during the same period were selected as the control group.Fasting blood glucose,glycated hemoglobin,AGEs,soluble RAGE(sRAGE),and oxidative stress were compared in both groups.Postpartum placental tissue was collected to identify RAGE protein expression.Participants with GDM were categorized based on perinatal outcomes into normal(n=89)and adverse perinatal outcome groups(n=37),and differences in serum AGE–RAGE levels and oxidative stress were analyzed.The influencing factors of adverse perinatal outcomes were analyzed using logistic regression.RESULTS The GDM group demonstrated notably higher serum AGE(t=8.955)and malondialdehyde(MDA)levels(t=14.14)and lower sRAGE(t=16.37)and superoxide dismutase(SOD)levels(t=18.50)than the control group at 24-28 weeks of gestation and before delivery(P<0.0001).Serum AGE levels were positively correlated with MDA and negatively related to SOD at 24-28 weeks of pregnancy(SOD:r=0.393,MDA:r=0.424,P<0.0001)and before delivery(SOD:r=0.443,MDA:r=0.492,P<0.0001),whereas AGE was inversely associated with sRAGE in the GDM group(r=-0.495,P<0.0001).Serum AGE levels were significantly higher(t=9.225,P<0.0001)and the sRAGE level(r=3.563,P<0.0001)was significantly lower in participants with adverse perinatal outcomes than those with normal perinatal outcomes in the GDM group.Logistic regression analysis revealed AGE level as a risk factor(OR=1.056,P<0.0001)and sRAGE level(OR=0.949,P<0.0001)as a protective factor for adverse perinatal outcomes in GDM.CONCLUSION High serum AGE level is a risk factor for adverse perinatal outcomes in GDM,whereas high sRAGE levels are protective.AGEs and RAGE may be associated with oxidative stress in pregnant women with GDM.
文摘BACKGROUND Colorectal cancer(CRC)ranks among the most prevalent malignancies in elderly populations,and chemotherapy resistance remains a critical clinical challenge.Emerging evidence highlights the interplay between chronic inflammation,gut microbiome dysbiosis,and CRC progression.Proinflammatory cytokines[e.g.,interleukin(IL)-6,tumor necrosis factor-alpha(TNF-α)]and mediators like S100 calcium-binding protein A12(S100A12)/soluble receptor for advanced glycation end products(sRAGE)are implicated in tumorigenesis,while gut microbial imbalances may exacerbate inflammatory microenvironments conducive to che-motherapy resistance.However,the triad relationship between S100A12/sRAGE,gut microbiota profiles,and chemotherapy efficacy in elderly patients with CRC remains unexplored,limiting biomarker-driven therapeutic strategies.AIM To analyze the correlation between serum levels of S100A12,sRAGE,gut microbiome dysbiosis,and systemic inflammation in elderly patients with CRC and to assess their predictive value for chemotherapy efficacy.METHODS A retrospective analysis was conducted on the clinical data of 120 elderly patients with advanced-stage CRC who visited our hospital from August 2023 to May 2024.These patients were enrolled in the study group.Additionally,120 healthy individuals undergoing routine health check-ups during the same period were selected as the control group.Serum S100A12,sRAGE,IL-6,and TNF-αlevels were measured by ELISA,and fresh stool samples were collected before chemotherapy to analyze gut microbiome composition in the study group.Follow-up observations were conducted after chemotherapy.Pearson correlation analysis was used to explore the relationship between serum S100A12,sRAGE levels,and gut microbiome dysbiosis in patients with CRC.The predictive diagnostic value of pre-chemotherapy serum S100A12 and sRAGE levels for chemotherapy efficacy was assessed using receiver operating characteristic curves.RESULTS Pre-chemotherapy serum S100A12,sRAGE,IL-6,and TNF-αlevels were significantly elevated in patients with CRC vs controls(all P<0.05).These biomarkers progressively increased with microbiota dysbiosis severity(severe vs mild dysbiosis:S100A12:340.26±52.39μg/L vs 302.53±56.97μg/L;sRAGE:525.64±37.32 ng/L vs 441.38±48.73 ng/L,P<0.05)and correlated strongly with IL-6(r=0.712)and TNF-α(r=0.698).Post-chemotherapy,biomarker levels decreased(P<0.05),coinciding with beneficial microbiota recovery(Bifidobacterium 176%,Lactobacillus 153%)and pathogenic taxa reduction(Escherichia coli 62%).The combined S100A12/sRAGE model predicted chemotherapy resistance with an area under the curve of 0.914(sensitivity=86.07%,specificity=88.89%),outper-forming individual biomarkers.CONCLUSION Elevated serum S100A12 and sRAGE in elderly patients with CRC reflected gut microbiome dysbiosis and systemic inflammation,driven by IL-6/TNF-αsignaling.Their post-chemotherapy decline parallels microbiota restoration,supporting a microbiome-inflammation-biomarker axis.The combined biomarker model offers robust clinical utility for chemotherapy efficacy prediction and personalized therapeutic strategies.
基金financially supported by the National Natural Science Foundation of China(Grant No.32472468 and No.32001817)the Fundamental Research Program of Shanxi Province(202303021221123).
文摘Advanced glycation end products(AGEs)are complex compounds formed through interaction of carbonyl groups from saccharides with amino groups in amino acids,proteins,lipids and nucleic acids,mainly via Maillard reaction.Studies have shown that AGEs can accumulate in the body and lead to neurodegenerative diseases,cardiovascular diseases,inflammatory responses,diabetes,and other diseases.This comment will provide a review of the inhibitory mechanism of flavonoids on dietary AGEs formation in food models and aims to provide a theoretical basis for the development of new therapeutic strategies and drugs.
基金Supported by Clinical Medical Research Fund of the Zhejiang Medical Association,No.2025ZYC-Z32Henan Provincial Key Research and Development Program,No.231111311000+1 种基金Henan Provincial Science and Technology Research Project,No.232102310411Clinical Medical Research Fund of the Zhejiang Medical Association,2024ZYC-Z30.
文摘Type 2 diabetes markedly elevates fracture risk despite normal or high bone mineral density,a paradox reflecting qualitative skeletal deficits rather than loss of mass.Chronic hyperglycemia fosters the accumulation of advanced glycation end products in bone;their nonenzymatic crosslinks stiffen type I collagen,impair mineralization,and erode mechanical strength.By engaging the receptor for advanced glycation end products,these adducts activate nuclear factorκB and mitogen-activated protein kinase cascades,amplifying oxidative stress,inflammation,osteoblast dysfunction,and osteoclastogenesis.This review synthesizes epidemiological data from type 1 and type 2 diabetes,highlights the limits of densitybased skeletal assessment,and details the molecular pathology of the glycation-collagen axis.It also appraises antiglycation therapies,including formation inhibitors,crosslink breakers and receptor antagonists,with a particular focus on sodium-glucose cotransporter 2 inhibitors that couple glycemic control with modulation of the glycation pathway.By integrating recent basic and clinical advances,we propose a mechanistic framework for diabetic bone disease and outline strategies to mitigate glycationdriven skeletal fragility.
基金supported by the Natural Science Foundation of Jiangxi Province(20212BAB205017,20192ACB21011)National Science and Technology Award Reserve Cultivation Program Project of Jiangxi(20212AEI91001)。
文摘Effect of ellagitannins gut microbiota metabolites ellagic acid(EA)and urolithin A-urolithin D(UroA-UroD)on human serum albumin(HSA)glycation were firstly evaluated in this research.The inhibition mechanisms were investigated by methylglyoxal(MGO)trapping and radical scavenging ability assays,docking studies and nano LC-orbitrap-MS/MS technology.Results indicated that the inhibition of urolithins on HSA glycation was highly positive correlated with the number of phenolic hydroxy groups.Addition of UroD and EA could effectively enhance the content of free amino group,suppress dicarbonyl compounds and advanced glycation end-products(AGEs)formation,alleviated tryptophan and protein oxidation,inhibited HSA amyloid-like aggregation.They could also trap MGO and scavenge 1,1-diphenyl-2-picrylhydrazyl free radical(DPPH·)and2,2'-azino-bis-3-ethylbenzthiazoline-6-sulphonic acid free radical(ABTS^(+)·).Molecular docking indicated that EA and UroA-UroD interact with HSA mainly through hydrogen bound and hydrophobic interaction,among which 2 or 3 hydrogen bonds were formed.The number of glycation sites were reduced from 11 to10,10,7,and 10,respectively,when 90μmol/L of EA,UroA,UroC and UroD were added.However,weak inhibition was observed on UroA and UroB.These findings can provide scientific evidence for the application of ellagitannins-rich foods in alleviating diabetic complications.
文摘The incidence of type 2 diabetes mellitus is growing in epidemic proportions and has become one of the most critical public health concerns.Cardiovascular complications associated with diabetes are the leading cause of morbidity and mortality.The cardiovascular diseases that accompany diabetes include angina,myocardial infarction,stroke,peripheral artery disease,and congestive heart failure.Among the various risk factors generated secondary to hyperglycemic situations,advanced glycation end products(AGEs)are one of the important targets for future diagnosis and prevention of diabetes.In the last decade,AGEs have drawn a lot of attention due to their involvement in diabetic pathophysiology.AGEs can be derived exogenously and endogenously through various pathways.These are a nonhomogeneous,chemically diverse group of compounds formed nonenzymatically by condensation between carbonyl groups of reducing sugars and free amino groups of protein,lipids,and nucleic acid.AGEs mediate their pathological effects at the cellular and extracellular levels by multiple pathways.At the cellular level,they activate signaling cascades via the receptor for AGEs and initiate a complex series of intracellular signaling resulting in reactive oxygen species generation,inflammation,cellular proliferation,and fibrosis that may possibly exacerbate the damaging effects on cardiac functions in diabetics.AGEs also cause covalent modifications and cross-linking of serum and extracellular matrix proteins;altering their structure,stability,and functions.Early diagnosis of diabetes may prevent its progression to complications and decrease its associated comorbidities.In the present review,we recapitulate the role of AGEs as a crucial mediator of hyperglycemia-mediated detrimental effects in diabetes-associated complications.Furthermore,this review presents an overview of future perspectives for new therapeutic interventions to ameliorate cardiovascular complications in diabetes.
文摘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.
基金Supported by the National Natural Science Foundation of China,No.81870593Natural Science Foundation of Shandong Province of China,No.ZR2020MH106and Medical Health Science and Technology Project of Shandong Province,No.202003060400.
文摘The presence of excess glucose in blood is regarded as a sweet hurt for patients with diabetes.Human serum albumin(HSA)is the most abundant protein in human plasma,which undergoes severe non-enzymatic glycation with glucose in patients with diabetes;this modifies the structure and function of HSA.Furthermore,the advanced glycation end products produced by glycated HSA can cause pathological damage to the human body through various signaling pathways,eventually leading to complications of diabetes.Many potential glycation sites on HSA have different degrees of sensitivity to glucose concentration.This review provides a comprehensive assessment of the in vivo glycation sites of HSA;it also discusses the effects of glycation on the structure and function of HSA.Moreover,it addresses the relationship between HSA glycation and diabetes complications.Finally,it focuses on the value of non-enzymatic glycation of HSA in diabetes-related clinical applications.
基金Supported by the Founding Proyectos de Impulso a la Investigación to Hernandez-Nazara ZH from Universidad de Guadalajara,Mexico,No.PIN 2020-I.
文摘Obesity and type 2 diabetes mellitus(T2DM)are chronic pathologies with a high incidence worldwide.They share some pathological mechanisms,including hyperinsulinemia,the production and release of hormones,and hyperglycemia.The above,over time,affects other systems of the human body by causing tissue hypoxia,low-grade inflammation,and oxidative stress,which lay the pathophysiological groundwork for cancer.The leading causes of death globally are T2DM and cancer.Other main alterations of this pathological triad include the accumulation of advanced glycation end products and the release of endogenous alarmins due to cell death(i.e.,damage-associated molecular patterns)such as the intracellular proteins high-mobility group box protein 1 and protein S100 that bind to the receptor for advanced glycation products(RAGE)-a multiligand receptor involved in inflammatory and metabolic and neoplastic processes.This review analyzes the latest advanced reports on the role of RAGE in the development of obesity,T2DM,and cancer,with an aim to understand the intracellular signaling mechanisms linked with cancer initiation.This review also explores inflammation,oxidative stress,hypoxia,cellular senescence,RAGE ligands,tumor microenvironment changes,and the“cancer hallmarks”of the leading tumors associated with T2DM.The assimilation of this information could aid in the development of diagnostic and therapeutic approaches to lower the morbidity and mortality associated with these diseases.
基金the Natural Science Foundation of Jiangsu Province (BK2003047)~~
文摘[ Objective] In order to study the anti-oxidation and inhibitory effect on nonenzymatic glycation reaction of EGB fermentation extraction biotransformed by Hericium erinaceus. [ Method ] The free radical scavenging ability and reducing capacity of DPPH as well as inhibitory rate of nonenzymatic glycation reaction were measured targets for comparing changes of anti-oxidation and inhibitory effect on nonenzymatic glycation reaction of fermentation lyophilizer and fermentation extraction before and after EGB fermention adsorbed by AB-8 macroporous resin. The EGB fermention was biotransformed by Hericium erinaceus. [ Result ] After adsorbed by AB-8 macroporous resin, the bioactive matters were concentrated and separated. The free radical scavenging rate, reducing capacity and inhibitory rate of nonenzymatic glycation reaction were increased significantly after adsorbed by AB-8 macroporous resin. [ Conclusion] AB-8 macroporous resin could be used for preliminary concentration of EGB fermentation which was biotransformed by Hericium erinaceus.
基金Supported by Grants from the Interdisciplinary Center for Clinical Research(IZKF,Project B39)the Johannes and Frieda Marohn Foundation of the University of Erlangen-Nuremberg,Germany
文摘AIM： To study the role of advanced glycation end products （AGE） and their specific receptor （RAGE） in the pathogenesis of liver fibrogenesis. METHODS： In vitro RAGE expression and extracellular matrix-related gene expression in both rat and human hepatic stellate cells （HSC） were measured after stimulation with the two RAGE ligands, advanced glycation end product-bovine serum albumin （AGE- BSA） and N＇-（carboxymethyl） lysine （CML）-BSA, or with tumor necrosis factor-α （TNF-α）. In vivo RAGE expression was examined in models of hepatic fibrosis induced by bile duct ligation or thioacetamide. The effects of AGE-BSA and CML-BSA on HSC proliferation, signal transduction and profibrogenic gene expression were studied in vitro. RESULTS： In hepatic fibrosis, RAGE expression was enhanced in activated HSC, and also in endothelial cells, inflammatory cells and activated bile duct epithelia. HSC expressed RAGE which was upregulated after stimulation with AGE-BSA, CML-BSA, and TNF-α.RAGE stimulation with AGE-BSA and CML-BSA did not alter HSC proliferation, apoptosis, fibrogenic signal transduction and fibrosis- or fibrolysis-related gene expression, except for marginal upregulation of procollagen α1（ I ） mRNA by AGE-BSA. CONCLUSION： Despite upregulation of RAGE in activated HSC, RAGE stimulation by AGE does not alter their fibrogenic activation. Therefore, RAGE does not contribute directly to hepatic fibrogenesis.
文摘Advanced glycation end products lead to cell apoptosis, and cause cell death by increasing endoplasmic reticulum stress. Advanced glycation end products alone may also directly cause damage to tissues and cells, but the precise mechanism remains unknown. This study used primary cultures of rat cerebral cortex neurons, and treated cells with different concentrations of glycation end products （50, 100, 200, 400 mg/L）, and with an antibody for the receptor of advanced glycation end products before and after treatment with advanced glycation end products. The results showed that with increasing concentrations of glycation end products, free radical content increased in neurons, and the number of apoptotic cells increased in a dose-dependent manner. Before and after treatment of advanced glycation end products, the addition of the antibody against advanced glycation end-products markedly reduced hydroxyl free radicals, malondialdehyde levels, and inhibited cell apoptosis. This result indicated that the antibody for receptor of advanced glycation end-products in neurons from the rat cerebral cortex can reduce glycation end product-induced oxidative stress damage by suppressing glycation end product receptors. Overall, our study confirms that the advanced glycation end products-advanced glycation end products receptor pathway may be the main signaling pathway leading to neuronal damage.
基金Supported by the Deputyship for Research and Innovation,Ministry of Education and Qassim University,Saudi Arabia(Project No.QUIF-2-2-1-27012).
文摘Advanced glycation end products(AGEs)are a heterogeneous collection of compounds formed during industrial processing and home cooking through a sequence of nonenzymatic glycation reactions.The modern western diet is full of heat-treated foods that contribute to AGE intake.Foods high in AGEs in the contemporary diet include processed cereal products.Due to industrialization and marketing strategies,restaurant meals are modified rather than being traditionally or conventionally cooked.Fried,grilled,baked,and boiled foods have the greatest AGE levels.Higher AGE-content foods include dry nuts,roasted walnuts,sunflower seeds,fried chicken,bacon,and beef.Animal proteins and processed plant foods contain furosine,acrylamide,heterocyclic amines,and 5-hydroxymethylfurfural.Furosine(2-furoil-methyl-lysine)is an amino acid found in cooked meat products and other processed foods.High concentrations of carboxymethyl-lysine,carboxyethyl-lysine,and methylglyoxal-O are found in heat-treated nonvegetarian foods,peanut butter,and cereal items.Increased plasma levels of AGEs,which are harmful chemicals that lead to age-related diseases and physiological aging,diabetes,and autoimmune/inflammatory rheumatic diseases such as systemic lupus erythematosus and rheumatoid arthritis.AGEs in the pathophysiology of metabolic diseases have been linked to individuals with diabetes mellitus who have peripheral nerves with high amounts of AGEs and diabetes has been linked to increased myelin glycation.Insulin resistance and hyperglycemia can impact numerous human tissues and organs,leading to long-term difficulties in a number of systems and organs,including the cardiovascular system.Plasma AGE levels are linked to all-cause mortality in individuals with diabetes who have fatal or nonfatal coronary artery disease,such as ventricular dysfunction.High levels of tissue AGEs are independently associated with cardiac systolic dysfunction in diabetic patients with heart failure compared with diabetic patients without heart failure.It is widely recognized that AGEs and oxidative stress play a key role in the cardiovascular complications of diabetes because they both influence and are impacted by oxidative stress.All chronic illnesses involve protein,lipid,or nucleic acid modifications including crosslinked and nondegradable aggregates known as AGEs.Endogenous AGE formation or dietary AGE uptake can result in additional protein modifications and stimulation of several inflammatory signaling pathways.Many of these systems,however,require additional explanation because they are not entirely obvious.This review summarizes the current evidence regarding dietary sources of AGEs and metabolism-related complications associated with AGEs.
文摘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.
文摘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.
文摘OBJECTIVE: To investigate the inhibitive efficacy of Nymphoides Indica(L.) Kuntze rhizome extract onα-glucosidase and on cross-link formation of advanced glycation end products(AGEs).METHODS: The plant extracts were prepared by cold maceration and fractionated in solvents of diverse polarity. The in vitro α-glucosidase inhibition assay, fluorescence spectrometry and SDS-PAGE analysis was performed for antiglycation assays.RESULTS: During α-glucosidase inhibition assay significant inhibition by chloroform(0.43 mg/mL)and methanol fractions(0.66 mg/mL) was noticed.During the AGEs inhibition assay, both oxidative(BSA-MGO) and non-oxidative(BSA-glucose)modes were employed. The inhibition of AGEs by total extract was considered moderate(IC_(50)0.10 mg/mL) as a result of non-oxidative mode, whereas in case of oxidative mode(BASA-MGO) no activity was recorded. Among fractions the methanolic fraction presented significant results both in oxidative(IC_(50)0.01 mg/mL) and non-oxidative modes(IC_(50) 0.3 mg/mL). Likewise the ethyl acetate fraction was more active in non-oxidative mode(IC_(50)0.04 mg/mL) compared to oxidative mode(IC_(50)0.32 mg/mL).During assay for inhibition of cross-link formation,the chloroform fraction significantly inhibited cross-link formation in a dose dependent mode.CONCLUSION: It was finally concluded that N. Indica rhizome extract possesses significant properties that inhibit α-glucosidase, and AGEs cross-link formation.
文摘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.
基金Supported by The National Natural Science Foundation of China,No.82100599 and No.81960112The Jiangxi Provincial Department of Science and Technology,No.20212ACB216003+1 种基金The Science and Technology Plan of Jiangxi Provincial Administration of Traditional Chinese Medicine,No.2023Z021The Young Talents Project of Jiangxi Provincial Academic and Technical Leaders Training Program for Major Disciplines,No.20204BCJ23022.
文摘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.
