Free Amino Groups Of Proteins Research Articles

Elucidating the Antiglycation Effect of Creatine on Methylglyoxal-Induced Carbonyl Stress In Vitro.

Advanced glycation end products (AGEs) with multiple structures are formed at the sites where carbonyl groups of reducing sugars bind to free amino groups of proteins through the Maillard reaction. In recent years, it has been highlighted that the accumulation of AGEs, which are generated when carbonyl compounds produced in the process of sugar metabolism react with proteins, is involved in various diseases. Creatine is a biocomponent that is homeostatically present throughout the body and is known to react nonenzymatically with α-dicarbonyl compounds. This study evaluated the antiglycation potential of creatine against methylglyoxal (MGO), a glucose metabolite that induces carbonyl stress with formation of AGEs in vitro. Further, to elucidate the mechanism of the cytoprotective action of creatine, its effect on the accumulation of carbonyl proteins in the cells and the MGO-induced cellular damage were investigated using neuroblastoma cells. The results revealed that creatine significantly inhibits protein carbonylation by directly reacting with MGO, and creatine added to the culture medium suppressed MGO-derived carbonylation of intracellular proteins and exerted a protective effect on MGO-induced cytotoxicity. These findings suggest that endogenous and supplemented creatine may contribute to the attenuation of carbonyl stress in vivo.

Comprehensive characterization of differential glycation in hepatocellular carcinoma using tissue proteomics with stable isotopic labeling.

Glycation is anon-enzymatic posttranslational modification coming from the reaction between reducing sugars and free amino groups in proteins, where early glycation products (fructosyl-lysine, FL) and advanced glycation end products (AGEs) are formed. The occurrence of glycation and accumulation of AGEs have been closely associated with hepatocellular carcinoma (HCC). Here, we reported the characterization of differential glycation in HCC using tissue proteomics with stable isotopic labeling; early glycation-modified peptides were enriched with boronate affinity chromatography (BAC), and AGEs-modified peptides were fractionated with basic reversed-phase separation. By this integrated approach, 3717 and 1137 early and advanced glycated peptides corresponding to 4007 sites on 1484 proteins were identified with afalse discovery rate (FDR) ofno more than 1%. One hundred fifty-five sites were modified with both early and advanced end glycation products. Five early and 7 advanced glycated peptides were quantified to be differentially expressed in HCC tissues relative to paired adjacent tissues. Most (8 out of 10) of the proteins corresponding to the differential glycated peptides have previously been reported with dysregulation in HCC. The results together may deepen our knowledge of glycation as well as provide insights for therapeutics.

Non-enzymatic glycation and diabetic kidney disease.

Chronic diabetes leads to various complications including diabetic kidney disease (DKD). DKD is a major microvascular complication and the leading cause of morbidity and mortality in diabetic patients. Varying degrees of proteinuria and reduced glomerular filtration rate are the cardinal clinical manifestations of DKD that eventually progress into end-stage renal disease. Histopathologically, DKD is characterized by renal hypertrophy, mesangial expansion, podocyte injury, glomerulosclerosis, and tubulointerstitial fibrosis, ultimately leading to renal replacement therapy. Amongst the many mechanisms, hyperglycemia contributes to the pathogenesis of DKD via a mechanism known as non-enzymatic glycation (NEG). NEG is the irreversible conjugation of reducing sugars onto a free amino group of proteins by a series of events, resulting in the formation of initial Schiff's base and an Amadori product and to a variety of advanced glycation end products (AGEs). AGEs interact with cognate receptors and evoke aberrant signaling cascades that execute adverse events such as oxidative stress, inflammation, phenotypic switch, complement activation, and cell death in different kidney cells. Elevated levels of AGEs and their receptors were associated with clinical and morphological manifestations of DKD. In this chapter, we discussed the mechanism of AGEs accumulation, AGEs-induced cellular and molecular events in the kidney and their impact on the pathogenesis of DKD. We have also reflected upon the possible options to curtail the AGEs accumulation and approaches to prevent AGEs mediated adverse renal outcomes.

Novel Fluorometric Assay of Antiglycation Activity Based on Methylglyoxal-Induced Protein Carbonylation.

Advanced glycation end products (AGEs), which can have multiple structures, are formed at the sites where the carbonyl groups of reducing sugars bind to the free amino groups of proteins through the Maillard reaction. Some AGE structures exhibit fluorescence, and this fluorescence has been used to measure the formation and quantitative changes in carbonylated proteins. Recently, fluorescent AGEs have also been used as an index for the evaluation of compounds that inhibit protein glycation. However, the systems used to generate fluorescent AGEs from the reaction of reducing sugars and proteins used for the evaluation of antiglycation activity have not been determined through appropriate research; thus, problems remain regarding sensitivity, quantification, and precision. In the present study, using methylglyoxal (MGO), a reactive carbonyl compound to induce glycation, a comparative analysis of the mechanisms of formation of fluorescent substances from several types of proteins was conducted. The analysis identified hen egg lysozyme (HEL) as a protein that produces stronger fluorescent AGEs faster in the Maillard reaction with MGO. It was also found that the AGE structure produced in MGO-induced in HEL was argpyrimidine. By optimizing the reaction system, we developed a new evaluation method for compounds with antiglycation activity and established an efficient evaluation method (HEL-MGO assay) with greater sensitivity and accuracy than the conventional method, which requires high concentrations of bovine serum albumin and glucose. Furthermore, when compounds known to inhibit glycation were evaluated using this method, their antiglycation activities were clearly and significantly measured, demonstrating the practicality of this method.

Advanced glycation end products: Key mediator and therapeutic target of cardiovascular complications in diabetes.

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 patho-physiology. AGEs can be derived exogenously and endogenously through various pathways. These are a non-homogeneous, chemically diverse group of compounds formed non-enzymatically 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.

RESTRICTED PROTEOLIS AND OXIDIZING MODIFICATION OF PROTEINS IN HEPATOCYATES OF PATIENTS WITH DIABETES AND TUBERCULOSIS

Objective: The objective of the work is to investigate the oxidative modification of proteins and limited proteolysis in hepatocytes in patients with diabetes and pulmonary tuberculosis. Design and method: A prospective pathomorphological study of 60 cases of death of patients who died of various causes, in which in the final clinical and pathologoanatomical diagnosis as the main disease appeared pulmonary tuberculosis. Depending on clinical forms and variants of tuberculosis, the main group was divided into three subgroups. Results: An important role in the pathogenesis of the formation of both diabetes mellitus and tuberculosis play an impairment of immune homeostasis, especially in patients with expressive symptoms of exacerbation of the disease and prolonged relapse. Oxidative stress leads to an increase in the production of active forms of oxygen and as a consequence - oxidation modification of proteins (OMB): their aggregation and fragmentation, which is accompanied by irreversible changes in the physical, chemical and biological properties of the protein molecule. Taking into account the different functional activity of hepatocytes of different zones of the acinus (according to Rappoport) according to their own research, the R / B coefficient (specific coloration on acid and main proteins for Michel Calvo) and average values of relative units of optical density of a specific color on the free amino group of proteins for A. Yasuma and T. Ichikava were determined separately in the hepatocytes of the first, second and third zones and established the linear nature of the increase in the intensity of the oxidative modification of proteins and limited proteolysis from the 1st to the 3rd zone (from peripartal to centrolobular branches of acinus) in patients with resistant forms of tuberculosis. Conclusions: Diabetes mellitus in patients with lung tuberculosis leads to increased processes of free radical oxidation of proteins with characteristic effects - increased proteolysis and oxidation of amino groups of proteins – in hepatocytes of the liver.

THE FEATURES OF LIMITED PROTEOLYSIS IN PLACENTAL FIBRINOID IN COMBINATION WITH INFLAMMATION AND IRON DEFICIENCY ANEMIA OF PREGNANT WOMEN.

The aim: To establish the features of limited proteolysis in fibrinoid of the chorionic and basal plates of the placenta in acute and chronic chorioamnionitis, as well as basal deciduitis on the background of iron deficiency anemia in pregnant women. Materials and methods: The histochemical procedure was performed using the ninhydrin-Schiff response to free amino groups of proteins by the method of A. Yasuma and T. Ichikava, and Bonheg bromophenol blue. Results: With iron deficiency anemia of pregnant women, the relative units of optical density in the chorionic plate were 0.312±0.0026, and with basal one - 0.310±0.0024 (with indicators of physiological pregnancy 0.285±0.0024 and 0.289±0.002.1). In the observations of acute chorioamnionitis, the quantitative indicators were 0.311±0.0024, chronic one - 0.311±0.0024, and with inflammation on the background of anemia of pregnant women - 0.315±0.0031 and 0.339±0.0036, respectively. With acute basal deciduitis - 0.316±0.0027, chronic one - 0.326±0.0034, and with inflammation of the basal plate of the placenta on the background of anemia of pregnant women - 0.320±0.0031 and 0.341±0.0038, respectively. Conclusions: With anemia of pregnant women, the processes of limited proteolysis are intensified in accordance with the indicators of optical density of histochemical staining in the fibrinoid of the chorionic and basal plates of the placenta compared with physiological pregnancy. In case of acute and chronic forms of chorioamnionitis and basal deciduitis, quantitative indicators of optic density of histochemical staining increase compared with physiological preg¬nancy. Comorbid anemia of pregnant women activates the processes of limited proteolysis only in the chronic form of chorioamnionitis and basal deciduitis.

Inhibitory effect of LSOPC on AGEs formation and sensory quality in cookies.

At the conclusion of the Maillard reaction (MR), free amino groups of proteins, amino acids, or lipids with the carboxyl groups of reducing sugars to form stable molecules known as advanced glycation end products (AGEs), which hasten aging and may potentially be the root cause of a number of chronic degenerative diseases. According to researches, lotus seedpod oligomeric procyanidins (LSOPC), a premium natural antioxidant produced from lotus waste, can be included in cookies to improve flavor and lower the risk of illnesses linked to AGEs. In this work, we used cookies without LSOPC as a control to examine the effects of adding various concentrations of LSOPC (0, 0.05, 0.1, 0.2, and 0.4%) on the AGEs formation and the sensory quality in cookies. The amounts of AGEs and N-ε-carboxymethyl lysine (CML) decreased with the increase of LSOPC concentration, indicating that the concentration of LSOPC was positively correlated with the ability to inhibit AGEs formation. It was also demonstrated that the amount of antioxidant capacity of the cookies increased significantly with the increase of LSOPC concentration. On the other hand, the chromaticity, texture, electronic nose, and other aspects of the cookies' sensory attributes were also evaluated. The color of the cookies deepened and the flavor varied as LSOPC added content increased. The sensory quality of the cookies was examined, and the findings indicated that LSOPC would somewhat improve that quality. These findings implied that AGEs formation could be decreased in cookies while also enhancing their sensory quality by adding LSOPC.

A highly active esterase from Lactobacillus helveticus hydrolyzes chlorogenic acid in sunflower meal to prevent chlorogenic acid induced greening in sunflower protein isolates

Chlorogenic acid (CGA) is an ester between caffeic and quinic acid. It is found in many foods and reacts with free amino groups in proteins at alkaline pH, leading to the formation of an undesirable green pigment in sunflower seed-derived ingredients. This paper presents the biochemical characterization and application of a highly active chlorogenic acid esterase from Lactobacillus helveticus. The enzyme is one of the most active CGA esterases known to date with a Km of 0.090 mM and a kcat of 82.1 s−1. The CGA esterase is easily expressed recombinantly in E. coli in large yields and is stable over a wide range of pH and temperatures. We characterized CGA esterase’s kinetic properties in sunflower meal and demonstrated that the enzyme completely hydrolyzes CGA in the meal. Finally, we showed that CGA esterase treatment of sunflower seed meal enables the production of pale brown sunflower protein isolates using alkaline extraction. This work will allow for more widespread use of sunflower-derived products in applications where neutrally-colored food products are desired.

The OSE complotype and its clinical potential.

Cellular death, aging, and tissue damage trigger inflammation that leads to enzymatic and non-enzymatic lipid peroxidation of polyunsaturated fatty acids present on cellular membranes and lipoproteins. This results in the generation of highly reactive degradation products, such as malondialdehyde (MDA) and 4-hydroxynonenal (4-HNE), that covalently modify free amino groups of proteins and lipids in their vicinity. These newly generated neoepitopes represent a unique set of damage-associated molecular patterns (DAMPs) associated with oxidative stress termed oxidation-specific epitopes (OSEs). OSEs are enriched on oxidized lipoproteins, microvesicles, and dying cells, and can trigger sterile inflammation. Therefore, prompt recognition and removal of OSEs is required to maintain the homeostatic balance. This is partially achieved by various humoral components of the innate immune system, such as natural IgM antibodies, pentraxins and complement components that not only bind OSEs but in some cases modulate their pro-inflammatory potential. Natural IgM antibodies are potent complement activators, and 30% of them recognize OSEs such as oxidized phosphocholine (OxPC-), 4-HNE-, and MDA-epitopes. Furthermore, OxPC-epitopes can bind the complement-activating pentraxin C-reactive protein, while MDA-epitopes are bound by C1q, C3a, complement factor H (CFH), and complement factor H-related proteins 1, 3, 5 (FHR-1, FHR-3, FHR-5). In addition, CFH and FHR-3 are recruited to 2-(ω-carboxyethyl)pyrrole (CEP), and full-length CFH also possesses the ability to attenuate 4-HNE-induced oxidative stress. Consequently, alterations in the innate humoral defense against OSEs predispose to the development of diseases associated with oxidative stress, as shown for the prototypical OSE, MDA-epitopes. In this mini-review, we focus on the mechanisms of the accumulation of OSEs, the pathophysiological consequences, and the interactions between different OSEs and complement components. Additionally, we will discuss the clinical potential of genetic variants in OSE-recognizing complement proteins – the OSE complotype - in the risk estimation of diseases associated with oxidative stress.

Dietary Advanced Glycation End-Products and Mortality after Breast Cancer in the Women's Health Initiative.

Advanced glycation end-products (AGE) are formed through nonenzymatic glycation of free amino groups in proteins or lipid. They are associated with inflammation and oxidative stress, and their accumulation in the body is implicated in chronic disease morbidity and mortality. We examined the association between postdiagnosis dietary Nε-carboxymethyl-lysine (CML)-AGE intake and mortality among women diagnosed with breast cancer. Postmenopausal women aged 50 to 79 years were enrolled in the Women's Health Initiative (WHI) between 1993 and 1998 and followed up until death or censoring through March 2018. We included 2,023 women diagnosed with first primary invasive breast cancer during follow-up who completed a food frequency questionnaire (FFQ) after diagnosis. Cox proportional hazards (PH) regression models estimated adjusted hazard ratios (HR) and 95% confidence intervals (CI) of association between tertiles of postdiagnosis CML-AGE intake and mortality risk from all causes, breast cancer, and cardiovascular disease. After a median 15.1 years of follow-up, 630 deaths from all causes were reported (193 were breast cancer-related, and 129 were cardiovascular disease-related). Postdiagnosis CML-AGE intake was associated with all-cause (HRT3vsT1, 1.37; 95% CI, 1.09-1.74), breast cancer (HRT3vsT1, 1.49; 95% CI, 0.98-2.24), and cardiovascular disease (HRT3vsT1, 1.91; 95% CI, 1.09-3.32) mortality. Higher intake of AGEs was associated with higher risk of major causes of mortality among postmenopausal women diagnosed with breast cancer. Our findings suggest that dietary AGEs may contribute to the risk of mortality after breast cancer diagnosis. Further prospective studies examining dietary AGEs in breast cancer outcomes and intervention studies targeting dietary AGE reduction are needed to confirm our findings.

Гістохімічне дослідження процесів окиснювальної модифікації білків та обмеженого протеолізу в ендотелії судин міометрію у проекції плацентарного ложа матки при залізодефіцитній анемії вагітних

Utero-placental bed is the cumulation of gestationally altered endometrium at the place of ovum attachment to the uterine wall. As far as the protein oxidative modification and limited proteolysis in iron deficiency anemia are due to the fact that in conditions of hypoxia, free radical processes in the blood and tissues are enhanced, and iron deficiency is additionally able to cause hemodynamic disorders because of endothelial dysfunction in the vessels of the utero-placental area. The purpose of the study was to establish histochemical features of protein oxidative modification and limited proteolysis in the endotheliocytes of myometrial vessels in the projection of the utero-placental area depending on the degree of iron deficiency anemia in pregnant women. Materials and methods. By histochemical methods of Mikel Calvo, using reactions with bromophenol blue on "acidic" and "basic" proteins, and the method of A. Yasumа and T. Ichikawa, ninhydrin-Schiff reaction to free amino groups of proteins to assess the degree of limited proteolysis, in combination with computer microspectrophotometry and microdensitometry, quantitative characteristics of oxidative modification of proteins and limited proteolysis in endotheliocytes of myometrial segments of the utero-placental vessels in iron deficiency anemia of pregnant women were established. 74 biopsies of the observed uterine-placental area in physiological pregnancy and gestation based on iron deficiency anemia of I, II and III degrees of severity were investigated. Results and discussion. In physiological pregnancy, the intensity of oxidative modification of proteins and limited proteolysis is the lowest in endotheliocytes of myometrial segments of the spiral arteries and the highest one is in the endothelium of the vessels of the microcirculatory tract of the utero-placental area. In gestations based on iron deficiency anemia, intensification of proteins oxidative modification and limited proteolysis in the endothelium of all types of myometrial vessels of the projection of the utero-placental bed correlates with the severity of anemia. Iron deficiency anemia greatly affects the modification of proteins in the endothelial cells mostly of myometrial segments of spiral arteries of the placental bed. Conclusion. Intensification of protein oxidative modification and limited proteolysis in endotheliocytes of all type vessels of myometrium of the uterine-placental area formed by iron deficiency can be considered as a significant factor of endothelial dysfunction and a predictor of hemodynamic disorders of the placental bed

Role of saturated and unsaturated fatty acids on dicarbonyl-albumin derived advanced glycation end products in vitro.

Glycation is a non-enzymatic reaction that occurs between the free amino group of proteins and reducing sugars and/or lipids, leading to the formation of advanced glycation end products (AGEs). The reaction also produces reactive oxygen species that have detrimental effects on cellular and extracellular proteins. Aminoguanidine is a known inhibitor of AGEs, and some fatty acids are known to have a beneficial role in vivo by reducing inflammation and oxidative stress. However, the role of fatty acids on AGE formation has not been thoroughly reported. We investigated the role of a range of fatty acids in the formation of AGEs and their reactive intermediates using an in vitro BSA-dicarbonyl model. The model assessed a time-dependent (0-72h) and dicarbonyl concentration (0-2mM) -dependent studies for the optimal formation of AGEs. A 72h time point was found to be optimal for the reaction of BSA with either methylglyoxal (MGO) or glyoxal (GO) to generate AGE-BSA complexes. When arachidonic, eicosapentaenoic or docosahexaenoic acids were included in the reaction, a significant decrease in protein-bound fluorescent AGEs was seen compared totherespective controls. In contrast, saturated and 18 carbon polyunsaturated fatty acids showed no significant activity. Liquid chromatography-mass spectrometry (LC-MS/MS) analysis showed saturated fatty acids significantly decreased the production of Nε-carboxymethyllysine (CML) and Nε-carboxyethyllysine (CEL) from GO and MGO models, respectively, whilst increasing methylglyoxal-derived hydroimidazolone (MG-H1). In contrast, arachidonic, eicosapentaenoic and docosahexaenoic acids did not significantly change either CEL or MG-H1 compared to no treatment controls whilst significantly reducing CML levels.

The Effect of formetanate hydrochloride on the glycated human hemoglobin

ABSTRACTGlycation refers to the nonenzymatic glycosylation of the free amino groups of proteins and sugars. Advanced glycation end products (AGEs) is the final stage in glycation process. AGEs cause many complications in diabetic’s patients. Formetanate hydrochloride is a highly effective pesticide widely used in agriculture. Hence, all human beings, both healthy and diabetics affected patients, can be exposed to this toxin. Therefore, the purpose the present research is to study, the effect of Formetanate hydrochloride upon the glycated human hemoglobin (GHb). To form glycated hemoglobin, Hb was incubated with glucose for 35 days under physiological conditions (dark, 37Ċ and pH 7.4). The effect of the toxin on GHb was investigated via docking studies, flurometry, and UV-Vis and circular dichroism spectroscopy. Incubating Hb with glucose could degrade the structure the protein. Samples contained GHb and formetanate hydrochloride showed remarkable changes in structure; Heme-group degradation and an increase in β-sheet structures was also observed. The results of docking studies were consistent with these results. As diabetes is rapidly expanding in today's world and formetanate hydrochloride is widely used in agriculture, the impact of this toxin on these patients will be very important. According to the results obtained, this toxin can have more destructive effect on the glycated Hb in these patients.

Роль конечных продуктов гликирования в развитии и прогрессировании диабетической нейроостеоартропатии

Diabetic neuroarthropathy (DNOAP, Charcot’s foot) is a serious complication of diabetes mellitus, the genesis of which is not fully understood. In most cases, this pathology is diagnosed late, which leads to the development of severe deformities of the foot, up to the loss of support ability of the limb. There is no single hypothesis for the formation of Charcot’s foot, but there are factors predisposing to its development, as well as a few likely provoking events. Excessive formation and accumulation of end products of glycation may play an important role in the pathogenesis of this complication of diabetes. End products of glycation (AGE) are a variety of compounds formed as a result of a non-enzymatic reaction between carbohydrates and free amino groups of proteins, lipids and nucleic acids. There are various factors that lead to the accumulation of AGE in the human body. Allocate endogenous and exogenous factors. The former include certain diseases, such as diabetes mellitus, renal failure, which accelerate glycation processes. Exogenous factors leading to the formation of lipo-oxidation and glyco-oxidation products include tobacco smoke and prolonged heat treatment of food. This review provides information on the role of glycation end products in the development and progression of complications in patients with diabetes mellitus.

Correlation between serum carnitine level and Soluble Receptors for Advance Glycation End Products(sRAGE) in Clomiphene Citrate Resistant- PCOS Women

The most frequently diagnosed condition in women at the age of reproduction is the polycystic ovarian syndrome (PCOS).it could be related to a complex endocrine condition, due to its heterogeneity and uncertainty about its etiology, as the clinical highlights of PCOS incorporate those related to reproductive signs such as decreased frequency of ovulation, irregular menstrual cycles, decreased fertility. Carnitine plays a substantial role in weight loss, glucose tolerance, insulin function and fatty acid metabolism. Thus carnitine plays a crucial role in controlling obesity, insulin resistance, oxidative stress that are associated with PCOS .While, AGEs are a diverse group of reactive molecules that are formed endogenously by non-enzymatic reactions of carbonyl group of carbohydrates with free amino groups of proteins, nucleic acids or lipids. The soluble form of receptors of AGE (sRAGE) could play an important role in management obesity, insulin resistance, hyperandrogenism, oxidative stress which could be related to PCOS. This study was aimed to investigate serum levels of carnitine & soluble receptors for advanced glycation end products (sRAGE) in clomiphene resistant PCOS .Besides assessing the correlation between serum levels of carnitine ,as well as, soluble receptors of AGE with hormonal ( LH, FSH& Testosterone) and metabolic ( serum glucose , serum insulin & HOMA-IR) markers in these patients .
 The study included thirty women with clomiphene resistant PCOS and thirty apparently healthy women, as a control .In order to measure serum total carnitine and serum soluble receptor of advance glycation end product (sRAGE in PCOS and control groups.
 The results of our study have shown a decreased serum levels of total carnitine in PCOS group in comparison with control group (48.05 and 59.73 nmol/ml, respectively), but there was no significant elevation in serum levels of sRAGE in patients group as compared with control group .In addition to a significant correlation between serum total carnitine and serum sRAGE levels (r=0.45, P-value=0.03). 
 In conclusion serum total carnitine level was low in Clomiphene resistant-PCOS patients in comparison with control group. Although, sRAGE levels in clomiphene resistant- PCOS patients were not significantly different from the age and BMI-matching controls, but a significant correlation between serum total carnitine and sRAGE was detected.
 Key words: Poly cystic ovarian syndrome, soluble receptor of advance glycation end products (sRAGE) , SerumTotal Carnitine

Comparative evaluation of Salivary-Soluble Receptor for Advanced Glycation End Product (sRAGE) levels among betel chewers and chronic periodontitis patients

Background: Advanced glycation end products (AGE) are heterogeneous groups of molecules formed from the nonenzymatic reaction of reducing sugars with free amino groups of proteins, lipids, and nucleic acids. Activation of receptor for advanced glycation end products (RAGE) by ligands in a variety of cell types and tissues may play a role in oral-systemic associations. The aim of the study is to estimate the salivary-soluble RAGE (sRAGE) levels in betel chewers and compare with salivary sRAGE levels of chronic periodontitis and normal healthy controls. Methods: Detailed case history and clinical examination was done for the study participants based on the inclusion and exclusion criteria. Study participants were grouped as Group I (chewers), Group II (chronic periodontitis), and Group III (normal controls). Unstimulated saliva samples were collected and salivary sRAGE levels were calculated using the sandwich ELISA technique. Results: Individuals with pan chewing habits have demonstrated increase in salivary sRAGE compared to chronic periodontitis and normal controls. Conclusions: Understanding AGE formation and biochemistry, cellular receptors for AGE, and AGE-induced effects on extracellular and intracellular functions will serve to expedite the process of finding effective therapies that block the excessive accumulation of these species and their interaction with the signal transduction receptor RAGE.

The cardiovascular complications of diabetes: a striking link through protein glycation.

Diabetes mellitus is a predominant cause of mortality and morbidity worldwide. One of its serious health problems is cardiovascular complications. Advanced glycation end products (AGEs) are a group of heterogeneous toxic oxidant compounds that are formed after a non-enzymatic reaction between monosaccharides and free amino groups of proteins, compound lipids, and nucleic acids. AGE interacts with various types of cells through a receptor for AGE (RAGE). The interaction between AGE and RAGE is responsible for a cascade of inflammation, oxidative stress, and disruption of calcium homeostasis in cardiac cells of diabetic patients. There is striking evidence that the AGE/RAGE axis with its consequences on inflammation and oxidative stress plays a major role in the development of cardiovascular complications. Therefore, considering AGE as a therapeutic target with foreseeable results would be a wise direction for future research. Interestingly, several studies on nutraceutical, pharmaceutical, and natural products have begun to reveal promising therapeutic results, and this could lead to better health outcomes for many diabetic patients worldwide. This article discusses the current literature addressing the connection between protein glycation and diabetes cardiovascular complications and suggests future avenues of research.

An in vitro approach to unveil the structural alterations in d-ribose induced glycated fibrinogen

Plasma proteins persistently bear non-enzymatic post-translational modifications (NEPTM) that proceeds with nucleophilic addition between free amino groups of proteins, and carbonyl group of reducing sugars. Glycation, a prevalent NEPTM rush by the high availability of reducing sugars results in the generation of advanced glycation end products (AGEs). Plasma proteins are more vulnerable to glycation because of the presence of multiple glycation sites and are widely studied. However, fibrinogen glycation is less studied. Therefore, it was designed as an in vitro study to elucidate d-ribose mediated glycative damage suffered by fibrinogen protein at secondary and tertiary structure level. The glycation induced structural alterations were analyzed by UV-vis, fluorescence, circular dichroism, scanning electron microcopy and Fourier transform infrared spectroscopy. Glycation induced protein aggregation and fibrils formation was confirmed by thioflavin T and congo red assay. Moreover, molecular docking study was performed to further validate physicochemical characterization. Structural alterations, increased ketoamines, protein carbonyls and HMF contents were reported in d-ribose glycated fibrinogen against their native analogues. The results validate structural perturbations, increased glycoxidative stress and AGEs formation, which might influence normal function of fibrinogen especially blood coagulation cascade. Thus, we can conclude that under diabetes induced hyperglycemic state in physiological systems, d-ribose induced fibrinogen glycation might play a crucial role in the onset of micro- and macro-vascular complications, thereby worsen the diabetes associated secondary disorders. Moreover, this in vitro study might pave a path to choose fibrinogen as a future biomarker for the early detection of diabetes mediated vascular complications. Communicated by Ramaswamy H. Sarma

The Role of Dietary Advanced Glycation End Products in Metabolic Dysfunction.

Advanced glycation end products (AGEs) are a heterogeneous group of molecules produced, non-enzymatically, from the interaction between reducing sugars and the free amino groups of proteins, nucleic acids, and lipids. AGEs are formed as a normal consequence of metabolism but can also be absorbed from the diet. They have been widely implicated in the complications of diabetes affecting cardiovascular health, the nervous system, eyes, and kidneys. Increased levels of AGEs are also detrimental to metabolic health and may contribute to the metabolic abnormalities induced by the Western diet, which is high in processed foods and represents a significant source of AGEs. While increased AGE levels are a consequence of diabetic hyperglycaemia, AGEs themselves activate signaling pathways, which compromise insulin signaling and pancreatic β-cell function, thus, contributing to the development of type 2 diabetes mellitus (T2DM). Furthermore, AGEs may also contribute to the obesogenic effects of the Western diet by promoting hypothalamic inflammation and disrupting the central control of energy balance. Here, the role of dietary AGEs in metabolic dysfunction is reviewed with a focus on the mechanisms underpinning their detrimental role in insulin resistance, pancreatic β-cell dysfunction, hypothalamic control of energy balance, and the pathogenesis of T2DM and obesity.