Soluble Advanced Glycation End Research Articles

Correlation Analysis of CML, sRAGE, and esRAGE and the Measure of Atherosclerosis of Coronary Heart Disease.

Objective To investigate the correlation between CML, sRAGE, and esRAGE and the measure of atherosclerosis of coronary heart disease. Methods From June 2019 to December 2021, there were 100 patients in all suffering from coronary heart disease (CHD) selected as the observation group. On the basis of Gensini score, they were divided into mild group (Gensini score < 12 points), moderate group (12 points ≤ Gensini score ≤60 points), and severe group (Gensini score > 60). Apart from that, 50 normal people staying in our hospital for physical examination were chosen as the control group in the meantime. N in each group was detected and compared ε-Carboxymethyl lysine (CML), soluble advanced glycation end product receptor (sRAGE), and endogenous secretory advanced glycation end product receptor (esRAGE). Pearson correlation coefficient was adapted to assay the relevance between CML, sRAGE, and esRAGE, as well as the degree of atherosclerosis in CHD. Receiver operator characteristic (ROC) curve was applied to during the evaluation of the diagnosis of CML, sRAGE, and esRAGE, as well as their combined detection of severe atherosclerosis in CHD. Results In contrast with the control group, the level of serum CML together with sRAGE in the observation group was considerably elevated, while the level of esRAGE appeared in a downward trend (P < 0.05). The level of serum CML and sRAGE was directly proportional to the measure of atherosclerosis in CHD, while the level of esRAGE was inversely proportional to the measure of atherosclerosis in CHD (P < 0.05). That is to say that serum CML and sRAGE were positive in matter of the measure of atherosclerosis in CHD, while esRAGE negatively appertains to the measure of atherosclerosis in CHD (P < 0.05). Serum CML, sRAGE, and esRAGE could effectively diagnose severe atherosclerosis in CHD, and the combined detection sensitivity (89.79%), specificity (77.16%), accuracy (86.12%), positive predictive value (86.63%), negative predictive value (88.59%), and area under ROC curve (AUC) (0.924) were higher (P < 0.05). Conclusion CML and sRAGE, as well as esRAGE, are bound up with the degree of atherosclerosis in CHD, which is conducive to clinical diagnosis and treatment.

Antihyperglycemic, Endothelial protection and Toxicity study of Basil Leaves Extract on Diabetic Rats

BACKGROUND: Diabetes Mellitus (DM) remains a serious debilitating global health problem in low- and middle-income countries with rising incidence of DM-related complications due to ineffective Diabetic control. Herbs of the Ocimum family, especially Ocimum basilicum or basil leaves, have been investigated for their antihyperglycemic properties. AIM: This study aimed to demonstrate the antihyperglycemic effect, endothelial protection, and toxicity of basil leaves on Diabetes-induced Wistar rats in vivo. METHODS: Streptozosin injections were used to induced diabetes in male Wistar rats. Basil leaves extracts 100, 300, and 1000 mg/kg BW were introduced to diabetic rats. Blood glucose levels (BGL), soluble Advanced Glycation End, tumor necrosis factor-α, interleukin (IL)-6, IL-2 were measured using enzyme-linked immunosorbent assay. Kidney and liver functions together with the histopathology reports were reported for acute, subacute, and chronic toxicity studies. RESULTS: Basil leaves exposure significantly lowers BGL (p &lt; 0.00), but yielded no statistically significant difference between extract doses. Hemostatic parametersshowed significantly reduced endothelial dysfunction markers for all doses compared to control. Toxicity study yielded no differences between control and any doses of basil leaves in all acute, subacute, and chronic toxicity studies. Histopathological findings exhibited no evidence of tissue damage on the liver, kidney, heart, pancreas, lung, and lymph tissues in either control or experiment rats. CONCLUSIONS: Basil leaves exposure were positively associated with lower glucose level, lower endothelial activation markers on Diabetic rats. The toxicity and histopathological results of the extract are on par with control.

GW28-e0060 Changes of high mobility protein B1 and soluble advanced glycation end product receptor in elderly patients with congestive heart failure at high altitude

Heart failure is considered to be a chronic inflammatory disease. High mobility protein B1(HMGB1) is a sensitive marker of the body, s nonspecific inflammation. Soluble advanced glycation end product receptor(sRAGE) can competitively combine with HMGB1 to reduce and inhibit inflammation, thus

Generation of Soluble Advanced Glycation End Products Receptor (sRAGE)-Binding Ligands during Extensive Heat Treatment of Whey Protein/Lactose Mixtures Is Dependent on Glycation and Aggregation.

Heating of protein- and sugar-containing materials is considered the primary factor affecting the formation of advanced glycation end products (AGEs). This study aimed to investigate the influence of heating conditions, digestion, and aggregation on the binding capacity of AGEs to the soluble AGE receptor (sRAGE). Samples consisting of mixtures of whey protein and lactose were heated at 130 °C. An in vitro infant digestion model was used to study the influence of heat treatment on the digestibility of whey proteins. The amount of sRAGE-binding ligands before and after digestion was measured by an ELISA-based sRAGE-binding assay. Water activity did not significantly affect the extent of digestibility of whey proteins dry heated at pH 5 (ranging from 3.3 ± 0.2 to 3.6 ± 0.1% for gastric digestion and from 53.5 ± 1.5 to 64.7 ± 1.1% for duodenal digestion), but there were differences in cleavage patterns of peptides among the samples heated at different pH values. Formation of sRAGE-binding ligands depended on the formation of aggregates and was limited in the samples heated at pH 5. Moreover, the sRAGE-binding activity of digested sample was changed by protease degradation and correlated with the digestibility of samples. In conclusion, generation of sRAGE-binding ligands during extensive heat treatment of whey protein/lactose mixtures is limited in acidic heating condition and dependent on glycation and aggregation.

Circulating soluble advanced glycation end product is inversely associated with the significant risk of developing cancer: evidence from a meta-analysis.

Currently, advanced glycation end product (RAGE) is receiving much attention in carcinogenesis research due to its involvement in cancer progression and metastasis. We therefore sought to examine the association of circulating soluble RAGE (sRAGE) with all types of cancer by a meta-analysis. The PubMed and EMBASE databases were searched before March 1, 2014. Data and study quality were assessed in duplicate. Effect estimates were expressed as weighted mean difference (WMD) and its 95 % confidence interval (CI). Altogether, nine eligible articles including 1,337 cancer patients and 1,839 controls were analyzed. The overall analysis indicated that circulating sRAGE was remarkably reduced by 222.07 pg/ml in cancer patients compared with controls (95 % CI: -373.77 to -70.37; P = 0.004), with heterogeneity and without publication bias. In subgroup analyses, this reduction was weakened yet still significant in prospective studies (WMD = -87.62; 95 % CI: -138.60 to -36.63; P = 0.001) with improved heterogeneity (I (2) = 56.5 %; P = 0.056). Restricting analyses to the large studies (total number of subjects ≥200) identified significant reduction of circulating sRAGE in cancer patients relative to controls (WMD = -231.34; 95 % CI: -450.10 to -12.58; P = 0.038). Further meta-regression analysis showed that smoking status explained some part of heterogeneity for the association of circulating sRAGE with cancer risk (regression coefficient: -67.02; P = 0.046). Our findings demonstrate a protective role of circulating sRAGE in the development of cancer, especially in patients without diabetes mellitus or with normal renal function.

Effects of enalapril/lercanidipine combination on some emerging biomarkers in cardiovascular risk stratification in hypertensive patients

There is considerable interest in pharmacogenetic and molecular biomarkers. Our aim was to evaluate the effects of enalapril/lercanidipine combination on some emerging biomarkers for cardiovascular risk stratification of hypertensive patients, such as lipoprotein(a) [Lp(a)], soluble advanced glycation end products (sRAGE), soluble CD40 ligand (sCD40L) and serum myeloperoxidase (MPO). Three hundred and forty-five patients were enrolled in this randomized, double-blind, clinical trial: 120 hypertensive patients were randomized to enalapril 20 mg, 110 to lercanidipine 10 mg and 115 to enalapril/lercanidipine 20/10 mg fixed combination. We measures the following markers at baseline and after 6, 12, 18 and 24 months: blood pressure, fasting plasma glucose (FPG), lipid profile, Lp(a), sRAGE, sCD40L and MPO. There was a decrease in blood pressure in all groups compared with baseline, even if, as expected, enalapril/lercanidipine combination was more effective in reducing blood pressure compared with the monotherapies. No variations in lipid profile or FPG were recorded in any of the groups. Lercanidipine, but not enalapril, improved Lp(a) levels compared with baseline. The combination enalapril/lercanidipine improved it more than the single therapies. All treatments increased sRAGE levels, and decreased sCD40L and MPO, with a better effect seen with the enalapril/lercanidipine combination compared with single monotherapies. The combination enalapril/lercanidipine seems to be better than the single monotherapies in reducing not only blood pressure, but also the levels of some emerging biomarkers, potentially useful for cardiovascular risk stratification of hypertensive patients.

Studying the association of plasma S100A12 and noninfectious pulmonary complication in infants and young children following cardiopulmonary bypass

Objective To examine the kinetics of plasma S100A12 and soluble receptor for advanced glycation end products (sRAGE) in infants and young children undergoing cardiopulmonary bypass ( CPB),and to investigate whether they could protective the occurrence of noninfectious pulmonary complication (NPC) after cardiac surgery.Methods This was a case-control study.The subjects included all children aged ＜3 years old who underwent cardiac surgery with CPB during the period from June 1st to July 31st 2011.The patient who showed pulmonary inflammation or had abnormal liver or renal function before surgery was excluded.The remain patients were divided into 2 groups according to whether they had developed NPC postoperatively.Twenty patients were grouped into NPC because they developed the complications of pleural effusion,chylothorax,partial lung collapse,pulmonary hypertensive crisis,airway disorders,pneumothorax,pneumomediastinum,or phrenic nerve palsy.Forty patients were categorized into the no-NPC group.Plasma concentrations of S100A12 and sRAGE were measured using ELISA at baseline,before CPB,immediately after CPB,1 h,12 h and 24 h after operation.Differences concentrations between two groups were analyzed with t test.A stepwise logistic regression analysis was used to indentify the independent risk factor for NPC.A P value ＜0.05 was considered statistically significant.Results Plasma levels of S100A12 and sRAGE dramatically increased immediately after CPB ( P ＜ 0.01 ).The levels of sRAGE dropped to lower than baseline level (P ＜0.05),while S100A12 was still at high level 24h after operation (P ＜0.01 ).Levels of S100A12 and sRAGE immediately after CPB in NPC group were significantly higher than the no-NPC group (P ＜ 0.05).Twenty-four hours after operation,levels of S100A12 were still higher in NPC group than no-NPC (P ＜ 0.01 ),while levels of sRAGE were similar in the two groups ( P ＞ 0.05 ).In the stepwise logistic regression analysis,plasma S100A12 level immediately after CPB remained as a independently predictor for postoperative NPC (OR =1.042,95％ CI:1.010 ～ 1.076,P =0.011 ).Levels of S100A12 immediately after CPB were positively associated with mechanical ventilation time ( r =0.47,P ＜ 0.01 ),duration of surgical Intensive Care Unit ( r =0.407,P =0.002) and hospital stay ( r =0.421,P =0.01 ).Conclusions Plasma levels of S100A12 and sRAGE were significantly increased immediately after CPB and the elevated plasma S100A12 immediately after CPB served as an early reliable biomarker of the occurrence and the prognosis of NPC after CPB in infants and young children. Key words: S100A12; Soluble advanced glycation end products (sRAGE); Noninfectious pulmonary complication (NPC) ; Cardiopulmonary bypass; cardiac surgery; Congenital heart disease; Infant and young children ; Case-control; Correlation.

Evaluation of emerging biomarkers in cardiovascular risk stratification of hypertensive patients: a 2-year study

Objective:To evaluate if there is a correlation between some new emerging biomarkers, such as lipoprotein(a) (Lp[a]), apo(a) isoform phenotyping, soluble advanced glycation end products (sRAGE), soluble CD40 ligand (sCD40L), serum myeloperoxidase (MPO), and cardiovascular risk stratification.Research design and methods:Three hundred patients were enrolled in this open-label, case–control design trial: 156 hypertensive patients and 144 healthy subjects as control group. Hypertensive patients were treated according to the latest ESH/ESC guidelines, until the desirable goal of systolic blood pressure (SBP) <140 mmHg, and diastolic blood pressure (DBP) <90 mmHg was reached. We evaluated at baseline and after 6, 12, 18, and 24 months: SBP, DBP, lipid profile, Lp(a), apo(a) isoform phenotyping, sRAGE, sCD40L, and MPO.Results:Hypertensive patients presented higher levels of blood pressure, Lp(a), sCD40L, and MPO and lower levels of sRAGE compared with controls. We observed a decrease of blood pressure, Lp(a), sCD40L, and MPO and an increase of sRAGE after anti-hypertensive treatment. Moreover we observed moderate, but statistically significant, correlations between blood pressure decrease and Lp(a), MPO, and sCD40L decrease and between blood pressure decrease and sRAGE increase. There was also a modest, positive correlation between low molecular weight apo(a) isoforms and hypertension. A limitation of this study is that we cannot exclude a role for lifestyle measures. Furthermore the studied markers seem to improve with blood pressure lowering treatment, but we do not have enough statistical power to definitely state which drug used has a specific action on the various variables measured.Conclusion:Lp(a), sRAGE, MPO, sCD40L, and low molecular weight apo(a) isoforms are associated with hypertension and may represent an increased cardiovascular risk. Longer studies are needed to see if these parameters can be also used to predict specific complications linked to hypertension.

Levels of Soluble Advanced Glycation End Product-Receptors and Other Soluble Serum Markers as Indicators of Diabetic Neuropathy in the Foot

ObjectiveAdvanced glycation end products (AGEs) and the interaction with their receptors (RAGE) play an important role in the pathogenesis of diabetic foot (DF) associated with diabetic neuropathy. Our study examined...

CCN-2 is up-regulated by and mediates effects of matrix bound advanced glycated end-products in human renal mesangial cells

CCN-2, also known as connective tissue growth factor (CCN-2/CTGF) is a cysteine rich, extracellular matrix protein that acts as a pro-fibrotic cytokine in tissues in many diseases, including in diabetic nephropathy. We have published that soluble advanced glycation end products (AGEs), that are present in increased amounts in diabetes, induce CCN-2. However in vivo AGEs are known to be heavily tissue bound and whether matrix bound AGEs regulate CCN-2 has not been investigated. In this study we determined in human renal mesangial cells if CCN-2 is induced by matrix associated AGEs and if CCN-2 may then secondarily mediate effects of matrix AGEs on extracellular matrix expansion. Data generated show that CCN-2 mRNA and protein expression are induced by matrix bound AGEs, and in contrast, this was not the case for TGF-β1 mRNA regulation. Using CCN-2 adenoviral anti-sense it was found that CCN-2 mediated the up-regulation of fibronectin and the tissue inhibitor of matrix metalloproteinase, TIMP-1, that was caused by matrix bound AGEs. In conclusion, CCN-2 is induced by non-enzymatically glycated matrix and it mediates downstream fibronectin and TIMP-1 increases, thus through this mechanism potentially contributing to ECM accumulation in the renal glomerulus in diabetes.

Plasma sRAGE is independently associated with high sensitivity C-reactive protein in type 2 diabetes without coronary artery disease

Our studies suggest that plasma soluble advanced glycation end products (sRAGEs) has significantly negative association with high sensitivity C-reactive protein (hs-CRP) in 245 type 2 diabetes patients without diagnosed coronary artery disease (CAD). sRAGE maybe act as a novel biomarker for predicting the atherosclerosis in diabetes at the early stage.