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When glucose and Amadori products are auto-oxidized, glycation occurs, resulting in the formation of early (Amadori) and late advanced glycation end products (AGEs), as well as free radicals. Glycation and an increase in free radical activity induce diabetic complications. Antioxidant and antiglycation compounds may aid in the prevention of oxidation and glycation. The goal of this study was to assess the antiglycation and antioxidant capacity of C-phycocyanin (C-PC) derived from Plectonema sp. The DPPH (1, 1-diphenyl-2-picrylhydrazyl), nitric oxide, hydroxyl radical scavenging activities and ferric ions reducing antioxidant power (FRAP) assays were used to assess antioxidant activity, while an in vitro bovine serum albumin-methyl glyoxal glycation (BSA-MG) model was used to assess glycation inhibitory potential. Glycation inhibition was measured using a variety of spectroscopic and biochemical parameters, including UV-visible & fluorescence spectroscopy, ketoamine, carbonyl and hydroxymethyl furfural content, as well as free lysine & free arginine estimations. In vitro, C-PC exhibited dose-dependent potent antioxidant activity, but lacked significant antiglycation potential. As a result, it is recommended that further studies be conducted to evaluate the antiglycation potential of C-PC.

Hyperglycemia is a poorly controlled diabetic condition, affects about 70% of people all round the world. In the year 2015, about 41.5 crore people were diabetic and is expected to reach around 64.3 crore by the year 2040. Cardiovascular diseases (CVDs) are considered as one of the major risk factors that cause more than half of the death of diabetic patients and promote related comorbidities. Atherosclerosis and amyloidosis are the prime factors linked with CVDs. Apolipoprotein A-I (ApoA-I) of HDL has protective action against CVDs, participates in reverse cholesterol transport mechanism and lipid metabolism, but gets easily glycated under prolonged hyperglycemic aura, i.e. glycation. ApoA-I has a potent role in maintenance of glucose level, providing a compelling link between diabetes and CVDs. Increased protein glycation in people with diabetes promotes atherosclerosis, which might play possible role in promotion of protein aggregation by altering the protein structure and its conformation. Here, we intend to investigate the mechanistic behavior of ApoA-I under the menace of glycation and its impact on ApoA-I structure and function that possibly link with aggregation or amyloidosis. [ABSTRACT FROM AUTHOR]

Glycation refers to carbonyl group condensation of the reducing sugar with the free amino group of protein, which forms Amadori products and advanced glycation end products (AGEs). These AGEs alter protein structure and function by configuring a negative charge on the positively charged arginine and lysine residues. Glycation plays a vital role in the pathogenesis of metabolic diseases, brain disorders, aging, and gut microbiome dysregulation with the aid of 3 mechanisms: (i) formation of highly reactive metabolic pathway-derived intermediates, which directly affect protein function in cells, (ii) the interaction of AGEs with its associated receptors to create oxidative stress causing the activation of transcription factor NF-κB, and (iii) production of extracellular AGEs hinders interactions between cellular and matrix molecules affecting vascular and neural genesis. Therapeutic strategies are thus required to inhibit glycation at different steps, such as blocking amino and carbonyl groups, Amadori products, AGEs-RAGE interactions, chelating transition metals, scavenging free radicals, and breaking crosslinks formed by AGEs. The present review focused on explicitly elaborating the impact of glycation-influenced molecular mechanisms in developing and treating noncommunicable diseases. [ABSTRACT FROM AUTHOR]

Biosynthetic procedure is one of the best alternatives, inexpensive and ecologically sound for the synthesis of titanium dioxide (TiO2) nanoparticles using a methanolic extract of medicinal plant. The main prospect of this study was to investigate the antiglycation activity of the TiO2 nanoparticles (TNP) prepared by ethanolic leaf extract of the Coleus scutellarioides. In this study, biosynthesized TNP characterized with UV‐Visible spectroscopy, X‐ray diffraction, Fourier transform infrared spectroscopy and scanning electron microscope. These TNP were further investigated with respect to their antiglycation property and it was checked in the mixture of d‐ribose glycated bovine serum albumin (BSA) by measuring ketoamine, carbonyl content, Advanced glycation end products (AGEs) and aggregation of protein instigated by glycation process. The inhibitory effect of TNP to restore the structure of BSA in presence of d‐ribose were also characterize by biophysical techniques mentioned above. Therefore, the findings of this study suggest repurposing of TNP for its antiglycation property that could be helpful in prevention of glycation instigated AGEs formation and structural loss of proteins. Significance statement: Provide a low cost green synthesis method for the synthesis of biologically active titanium dioxide (TiO2) nanoparticles.Provide the structural characterization of green synthesized TiO2 nanoparticles (TNP).An insight to identify the TNP as significant glycation inhibitor.Study suggest antiglycation potential detection of plant based TNP as possible therapeutic invention for hyperglycemia assisted diabetes and associated diseases. [ABSTRACT FROM AUTHOR]

Glycation is vital in terms of its damaging effect on macromolecules resulting in the formation of end products, which are highly reactive and cross‐linked irreversible structures, known as advanced glycation end products (AGEs). The continuous accumulation of AGEs is associated with severe diabetes and its associated ailments. Saccharides with their reducing ends can glycate amino acid side chains of proteins, among them glucose is well‐known for its potent glycating capability. However, other reducing sugars can be more reactive glycating agents than glucose. The D‐ribose is a pentose sugar‐containing an active aldehyde group in its open form and is responsible for affecting the biological processes of the cellular system. D‐ribose, a key component of many biological molecules, is more reactive than most reducing sugars. Protein glycation by reducing monosaccharides such as D‐ribose promotes the accelerated formation of AGEs that could lead to cellular impairments and dysfunctions. Also, under a physiological cellular state, the bioavailability rate of D‐ribose is much higher than that of glucose in diabetes, which makes this species much more active in protein glycation as compared with D‐glucose. Due to the abnormal level of D‐ribose in the biological system, the glycation of proteins with D‐ribose needs to be analyzed and addressed carefully. In the present study, human immunoglobulin G (IgG) was isolated and purified via affinity column chromatography. D‐ribose at 10 and 100 mM concentrations was used as glycating agent, for 1–12 days of incubation at 37°C. The postglycation changes in IgG molecule were characterized by UV‐visible and fluorescence spectroscopy, nitroblue tetrazolium assay, and various other physicochemical analyses for the confirmation of D‐ribose mediated IgG glycation. Significance statement: 1.D‐ribose‐induced glycation leads to structural perturbations in immunoglobulin G (IgG), the formation of IgG‐advanced glycation end products, and the generation of oxidative stress. 2.UV‐visible spectroscopy revealed the hyperchromicity of glycated IgG increases with the increase in the concentration of D‐ribose and time interval. 3.The early glycation products that is, Amadori products or ketoamines formed during D‐ribose mediated glycation of IgG were assessed by nitroblue tetrazolium assay and found to be increased initially in the first 5 days. 4.Hydroxymethylfurfural, carbonyl content, thiobarbituric acid reactive substances, and fluorescence intensity were found to be increased in glycated IgG as compared to the native analog. 5.Free lysine and arginine were found to be decreased in glycated IgG in comparison to the native conformer of the protein. [ABSTRACT FROM AUTHOR]

Non-enzymatic glycosylation is glycation between protein and reducing sugar transforming into the formation of advanced glycation end products (AGEs). Many of the epidemiological studies have demonstrated a strong correlation between the formation of AGEs with the pathogenesis of several chronic complications like inflammation, diabetes, nephropathy, retinopathy, neuropathy, atherosclerosis, and cancer. Besides, considering AGEs as lethal components, there are still very fragmentary research on the discovery and development of AGEs inhibitors. One of the causes may be the lack of awareness about the importance of anti-AGEs in the said disorders. The discovery and investigation of compounds with an AGEs inhibitor activity may offer a potential therapeutic approach for the prevention of such several pathogenic complications. The present review summarizes research on anti-AGEs products in chronic complications like inflammation, atherosclerosis, diabetes, cancer and several other disorders. [ABSTRACT FROM AUTHOR]

The Reactive carbonyl species (RCS) like, 3-deoxyglucosone (3-DG) is a highly reactive intermediate of the glycation reaction which may result into the formation of protein advanced glycation end-products (AGEs), like myoglobin-AGEs (Mb-AGEs) which further lead to the structural perturbations. In the present work, we studied the glycation of myoglobin (Mb) by physico-chemical techniques and the resulting immunogenicity by ELISA techniques. The level of free lysine and arginine determined was found to be significantly decreased indicating the establishment of the glycation reaction. The glycated myoglobin (G-Mb) shows the increased absorbance at 280 nm and enhanced fluorescence emission at 350 nm excitation wavelengths. The levels of ketoamine and hydroxymethylfurfural (HMF) were recorded to be enhanced in G-Mb when compared to its native conformer. Furthermore, the New-Zealand white female rabbits immunized with native and its glycated analogue 'G-Mb' induced high titer antibodies as compared to the native one. [ABSTRACT FROM AUTHOR]

Glycation of biological macromolecules, due to hyperglycemia, promotes the formation of advanced glycation end products (AGEs). It is accelerated in diabetic patients and is responsible for the pathophysiology and progression of diabetes. Previous reports have shown that amount of AGEs formation and glycation-induced structural damage is higher in hemoglobin (Hb) than other proteins present in blood. In our previous study, we have shown structural changes in Hb by D-ribose which may result into the generation of immunogenic neo-epitopes. Thus, we hypothesized that D-ribose induced structural perturbations in Hb, could result in the formation of neo-epitopes which may provoke an auto-immune response and may also be involved in the immuno-pathogenesis of diabetes type-2 associated complications. Therefore, in the current study, we analyzed the prevalence of autoantibodies in diabetic patient's sera against D-ribose glycated-Hb by direct binding and competitive ELISA. Direct binding ELISA confirmed that autoantibodies in diabetic patients exhibit significantly high binding with D-ribose glycated-Hb as compared to its native form. The antigen binding specificity of these antibodies was also screened by competitive inhibition ELISA. We also used D-glucose glycated-Hb as a positive control to detect the presence of auto-antibodies by direct binding and inhibiton ELISA. We found that D-glucose glycated-Hb binds with T2DM samples but the affinity to binding is lower than D-ribose glycated-Hb. The overall findings of this study suggest the prevalence of circulating autoantibodies against D-ribose glycated-Hb in diabetic patients and thus, the level of these autoantibodies may be used as biomarker for progression of diabetes. [ABSTRACT FROM AUTHOR]

Abstract: The glycation reaction is the addition of free carbonyl group of reducing sugar to the free amino groups of proteins, lipoproteins and nucleic acids which results in the formation of an Amadori product which may ultimately lead to the generation of advanced glycation products (AGEs). The impact of AGEs on proteins consequently generates free radicals, “a key player” for the pathogenesis of diabetes mellitus. Gel electrophoresis was carried out to see the visual changes taking place as a result of the glycation reaction. In this study, the anti‐glycation and anti‐diabetic effect of wedelolactone (WED) was seen both in vitro and in vivo. WED reverted various biochemical markers in streptozotocin‐induced diabetic rats along‐with the improvements in the oxidative stress markers. It also decreased the levels of the glycated serum protein and fasting blood glucose. Broadly, WED not only inhibited glycation in vitro but also proved to be an effective in vivo anti‐glycating agent. © 2018 IUBMB Life, 70(6):547–552, 2018 [ABSTRACT FROM AUTHOR]

Advanced glycation end products (AGEs) are a cohort of heterogeneous compounds that are formed after the nonenzymatic glycation of proteins, lipids and nucleic acids. Accumulation of AGEs in the body is implicated in various pathophysiological conditions like diabetes, cardiovascular diseases and atherosclerosis. Numerous studies have reported the connecting link between AGEs and the various complications associated with diseases. Hence, detection and measurement of AGEs becomes centrally important to understand and manage the menace created by AGEs inside the body. In recent years, an increasing number of immunotechniques as well as bioanalytical techniques have been developed to efficiently measure the levels of AGEs, but most of them are still far away from being clinically consistent, as relative disparity and ambiguity masks their standardization. This article is designed to critically review the recent advances and the emerging techniques for detection of AGEs. It is an attempt to summarize the major techniques that exist currently for the detection of AGEs both qualitatively and quantitatively. This review primarily focuses on the detection and quantification of AGEs which are formed in vivo. Immunochemical approach though costly but most effective and accurate method to measure the level of AGEs. Literature review suggests that detection of autoantibody targeting AGEs is a promising way that can be utilized for detection of AGEs. Future research efforts should be dedicated to develop this method in order to push forward the clinical applications of detection of AGEs. [ABSTRACT FROM AUTHOR]

Advanced glycation end-products comprise a complex and heterogeneous group of compounds that have been implicated in diabetes-related complications. The importance of the Maillard reaction is depicted by the formation of reactive intermediate products known as α-oxoaldehydes, such as 3-deoxyglucosone (3-DG). This product has been found to be involved in accelerated vascular damage in diabetes. In the present study, calf thymus histone H2A was reacted with 3-DG, and the generation of advanced glycation end products was investigated by determining the degree of side chain modifications (lysine and arginine residues), Amadori products, carbonyl content, Nε-carboxymethyl lysine, and pentosidine using various physicochemical techniques. Moreover, fluorescence, absorbance as well as structural characteristics of glycated-H2A were comprehensively investigated. Overall, this study demonstrates structural perturbation, formation of different intermediates, and AGEs that are believed to hamper the normal functioning of H2A histone, compromising the integrity of chromatin structures and function in secondary complications of diabetes. © 2014 IUBMB Life, 66(10):686-693, 2014 [ABSTRACT FROM AUTHOR]

Advanced glycation end-products (AGEs) are known to be mutagenic, diabetogenic and vascular disease risk factors. Methylglyoxal (MG) is a dicarbonyl species that reacts with biological macromolecule (proteins, DNA and lipids) to give AGEs. Nonenzymatic glycation of MG with lysine (Lys) in the presence of copper (Cu2+) is reported to generate reactive oxygen species (ROS) capable of causing DNA damage. We show that DNA modification in MG–Lys–Cu2+ system results in the generation of strand breaks, base modification, hyperchromicity and increased fluorescence intensity. Superoxide generation in the MG–Lys system was found to be significantly higher when compared with that in the MG and Lys alone. Moreover, d-penicillamine and pyridoxal phosphate significantly inhibited the formation of glycation products. The presence of a major DNA glycation adduct, N2-carboxyethyl-2′-deoxyguanosine (CEdG), was detected by high performance liquid chromatography (HPLC) and confirmed by nuclear magnetic resonance (NMR). As reported earlier, modified DNA (MG–Lys-Cu2+-DNA) was highly immunogenic in experimental animals. Furthermore, induced anti-MG–Lys–Cu2+–DNA antibodies were effective probe for detecting glycoxidative lesions in human genomic DNA of type I diabetes patients. Our results clearly imply that interaction of MG–Lys and Cu2+ leads to the formation of AGEs and also the production of potent ROS, capable of causing DNA damage, thereby playing an important role in diabetes mellitus. [ABSTRACT FROM AUTHOR]

Abstract: Glycation of biomolecules leads to the establishment of advanced glycation end products (AGEs), which have significant role in the pathophysiology of diabetes leading to disorders, such as atherosclerosis. Ribose appears to be the most reactive among the naturally occurring sugars and contribute significantly to the glycation reactions in vivo, however, no report has been published to discuss d-ribose induced glycation of low density lipoprotein (LDL). The present study initially focuses on the glycation of commercially available LDL using different concentrations of d-ribose for varied incubation time intervals. The structural perturbations induced in LDL were analyzed by UV–vis, fluorescence & circular dichroism spectroscopy, and thermal denaturation studies. The ketoamine moieties, carbonyl content and HMF content were also quantitated in native and glycated LDL. We report structural perturbations, increased carbonyl content, ketoamine moieties and HMF content in d-ribose induced glycated LDL (LDL-AGEs) as compared to native analogue. These results provide evidence that LDL-AGEs could interfere in normal physiological functions and might contribute in the initiation of diabetes induced atherosclerosis and other secondary cardiovascular problems in diabetic patients. Though ours is a preliminary study, we are sure it would open the topic for further studies. [Copyright &y& Elsevier]

Abstract: Aims: Glycation of proteins and DNA, results in the generation of free radicals causing structural modification of biomacromolecule. This leads to the generation of neo-antigenic epitopes having implication in diabetes mellitus. In this study, human placental DNA was glycated with fructose and its binding was probed with the serum antibodies from type 1 and 2 diabetes patients. Methods: Glycation was carried out by incubating DNA (10μg/ml) with fructose (25mM) for 5 days at 37°C. The induced structural changes in DNA were studied by spectroscopic techniques, thermal denaturation studies and agarose gel electrophoresis. Furthermore, binding characteristics of autoantibodies in diabetes (type 1 and 2) patients were assessed by direct binding and competitive ELISA. Results: DNA glycation with fructose resulted in single strand breaks, hyperchromicity in UV spectrum and increased fluorescence intensity. Thermal denaturation studies demonstrated the unstacking of bases and early onset of duplex unwinding. Type 1 diabetes patients exhibited enhanced binding with glycated DNA as compared to native form, while for type 2 diabetes only those with secondary complications (Nephropathy) showed higher binding. Conclusions: Glycation of DNA has resulted in structural perturbation causing generation of neo-antigenic epitopes that are better antigens for antibodies in diabetes patients. [Copyright &y& Elsevier]

Glycation of proteins results in structural alteration, functional deprivation, and generation of advanced glycation end products (AGEs). Reactive oxygen species (ROS) that are generated during in vivo autoxidation of glucose induces glycoxidation of intermediate glycation-adducts, which in turn give rise to aldehyde and/or ketone groups containing dicarbonyls or reactive carbonyl species (RCS). RCS further reacts non-enzymatically and starts the glycation-oxidation vicious cycle, thus exacerbating oxidative, carbonyl, and glycative stress in the physiological system. Glyoxal (GO), a reactive dicarbonyl that generates during glycoxidation and lipid peroxidation, contributes to glycation. This in vitro physicochemical characterization study focuses on GO-induced glycoxidative damage suffered by immunoglobulin G (IgG) and fibrinogen proteins. The structural alterations were analyzed by UV–vis, fluorescence, circular dichroism, and Fourier transform infrared (FT-IR) spectroscopy. Ketoamines, protein carbonyls, hydroxymethylfurfural (HMF), free lysine, free arginine, carboxymethyllysine (CML), and protein aggregation were also quantified. Structural perturbations, increased concentration of ketoamines, protein carbonyls, HMF, and malondialdehyde (MDA) were reported in glycated proteins. The experiment results also validate increased oxidative stress and AGEs formation i.e. IgG-AGEs and Fib-AGEs. Thus, we can conclude that AGEs formation during GO-mediated glycation of IgG and fibrinogen could hamper normal physiology and might play a significant role in the pathogenesis of diabetes-associated secondary complications. [ABSTRACT FROM AUTHOR]

The process of glycation, characterized by the non-enzymatic reaction between sugars and free amino groups on biomolecules, is a key contributor to the development and progression of both microvascular and macrovascular complications associated with diabetes, particularly due to persistent hyperglycemia. This glycation process gives rise to advanced glycation end products (AGEs), which play a central role in the pathophysiology of diabetes complications, including nephropathy. The d -ribose-mediated glycation of fibrinogen plays a central role in the pathogenesis of diabetes nephropathy (DN) and retinopathy (DR) by the generation and accumulation of advanced glycation end products (AGEs). Glycated fibrinogen with d -ribose (Rb-gly-Fb) induces structural changes that trigger an autoimmune response by generating and exposing neoepitopes on fibrinogen molecules. The present research is designed to investigate the prevalence of autoantibodies against Rb-gly-Fb in individuals with type 2 diabetes mellitus (T2DM), DN & DR. Direct binding ELISA was used to test the binding affinity of autoantibodies from patients' sera against Rb-gly-Fb and competitive ELISA was used to confirm the direct binding findings by checking the bindings of isolated IgG against Rb-gly-Fb and its native conformer. In comparison to healthy subjects, 32% of T2DM, 67% of DN and 57.85% of DR patients' samples demonstrated a strong binding affinity towards Rb-gly-Fb. Both native and Rb-gly-Fb binding by healthy subjects (HS) sera were non-significant (p > 0.05). Furthermore, the early, intermediate, and end products of glycation have been assessed through biochemical and physicochemical analysis. The biochemical markers in the patient groups were also significant (p < 0.05) in comparison to the HS group. This study not only establishes the prevalence of autoantibodies against d -ribose glycated fibrinogen in DN but also highlights the potential of glycated fibrinogen as a biomarker for the detection of DN and/or DR. These insights may open new avenues for research into novel therapeutic strategies and the prevention of diabetes-related nephropathy and retinopathy. [Display omitted] • Prevalence of autoantibodies against d -ribose glycated fibrinogen in type 2 diabetes mellitus (T2DM). • Glycation plays a critical role in generating an autoimmune response. • Ketoamines, protein carbonyls, TBARS, HMF, AGEs, and CML concentrations in patient sera were high. • Glycated fibrinogen might act as a biomarker for the early detection of diabetes-related diseases. [ABSTRACT FROM AUTHOR]

Abstract Advanced glycation end-products (AGEs) can aggregate amid incessant inflammation, as may be available in patients with rheumatoid arthritis. d -Ribose reacts more promptly than glucose monosaccharide to the proteins and forms heterogeneous group of products known as AGEs. Obesity includes persons with provocative joint inflammation with increased lipid profile. Immunogenic evidences recommend a cross-sectional relationship between glycated LDL-Apo B100 and inflammation. The point of this examination was to look at the connection between d -ribose glycated ApoB100 (ApoB100-AGE) with obesity and rheumatoid arthritis. The binding specificity of auto-antibodies against ApoB100-AGE antigen present in obesity and rheumatoid arthritis patient's serum were inspected by direct binding and was further established by competitive inhibition ELISA. In the present study, hydroxyl radical, superoxide radical, ketoamine moieties, hydroxyl-methyl furfural (HMF) and carbonyl substances were evaluated in the patients' serum via respective specific methods. The prevalence of auto-antibodies against ApoB100-AGE antigen was recorded to be 58% and 52.86% from obese and rheumatoid arthritis patient respectively in contrast to its native analogue (P < 0.001). Moreover, the autoantibodies present in obese and arthritis patients were found to be highly specific towards ApoB100-AGE as confirmed by inhibition ELISA. Highlights • The keto-amine moieties, HMF and carbonyl substance were higher in obese and Arthritic patient sera. • High degree of specificity in 80% obese and 73% rheumatoid sera against Apo-B100-AGE-IgG was obtained. • In obese and Rheumatoid sera, inhibition with glycated ApB 100 was 87% and 64% respectively. [ABSTRACT FROM AUTHOR]

Glycation of biological macromolecule leads to the establishment of advanced glycation end products (AGEs) having implications in metabolic disorders. d ‑ribose appears to be the most reactive among the naturally occurring sugars and contribute significantly to the glycation reactions in vivo , however, no report have been published yet to discuss d ‑ribose induced glycation of hemoglobin (Hb). Therefore, the present study was designed to investigate d ‑ribose induced glycoxidative damage to Hb protein. Briefly, the commercially available Hb was glycated with d ‑ribose for varying time intervals. The structural perturbation induced in glycated Hb (GHb) was confirmed by biophysical techniques viz. , UV–visible, fluorescence spectroscopy, circular dichroism, Fourier transform infra-red spectroscopy, dynamic light scattering, MALDIthermal denaturation by UV–visible spectrophotometer and DSC. Biophysical techniques confirm the secondary and tertiary structural perturbation in GHb as compared to native Hb. The values of carbonyl content, hydroxy methyl furfural, thiobarbituric acid reactive substance and nitro blue tetrazolium were found to be increased and free lysine and free arginine content were decreased in the GHb due to structural change. Thus, results of this study have established that glycation with d ‑ribose lead to the structural changes in the native Hb which might play an important role in pathophysiology metabolic diseases. [ABSTRACT FROM AUTHOR]

A nonenzymatic reaction between reducing sugars and amino groups of proteins results in the formation of advanced glycation end products, which are linked to a number of chronic progressive diseases with macro- and microvascular complications. In this research, we sought to ascertain the immunological response to d -ibose-glycated fibrinogen. New Zealand White female rabbits were immunized with native and d -ribose-glycated (Rb-gly-Fb) fibrinogen and used for studying the immunological response. Serum from these rabbits analyzed using direct binding and competitive inhibition ELISA was found to contain a high titer of antibodies against Rb-gly-Fb; Rb-gly-Fb was much more immunogenic than its native form. The IgG against Rb-gly-Fb (Rb-gly-Fb-IgG) was highly specific against the immunogenic protein. Moreover, histopathology and immunofluorescence studies revealed the deposition of the Rb-gly-Fb-IgG immune complex in the glomerular basement membrane of the kidneys of immunized rabbits. Furthermore, immunization with Rb-gly-Fb increased the expression of genes encoding proinflammatory cytokines, tumour necrosis factor α, interleukin-6, interleukin-1β, and interferon-gamma, which is indicative of increased inflammation and the antigenic role of Rb-gly-Fb in provoking an immune response. • Fibrinogen because of glycation results in the structural perturbations. • Fibrinogen protein becomes highly immunogenic after the glycation reaction. • Immunogenicity of the Fibrinogen is due to the formation of neo-epitopes in its structure. [ABSTRACT FROM AUTHOR]

Glyoxal, methylglyoxal and 3-deoxyglucosones are reactive dicarbonyl compounds, which transform free amino groups of proteins and lipoproteins macromolecule into advanced glycation end-products (AGEs). AGEs play a significant role in the pathophysiology of aging and diabetic complications because of their genotoxic effect. Glyoxal also reacts with free amino group of nucleic acids resulting in the formation of DNA–AGEs. The present study reports the genotoxicity and immunogenicity of AGEs formed by Glyoxal–Arginine–Fe 3+ (G–Arg–Fe 3+ ) system as a glycating agent. Immunogenicity of native and G–Arg–Fe 3+ –DNA was probed in female rabbits. Immunofluorescence suggests the presence of immune complex deposition in the kidney section of immunized rabbits. Spectroscopic analysis and melting temperature indicates the structural modification in the human DNA. The modified human DNA is found to be highly immunogenic, whereas unmodified form was simply non-immunogenic. This study shows the presence of auto-antibodies against G–Arg–Fe 3+ modified human DNA in the sera of diabetes type 1 and in few cases type 2 patients due to secondary complications of nephropathy. The glyco-oxidative lesions have also been detected in the lymphocyte DNA isolated from patients having type 1 and type 2 diabetes. The results show structural perturbations generating new epitopes in G–Arg–Fe 3+ –DNA rendering it pretty immunogenic. [ABSTRACT FROM AUTHOR]

Highlights: [•] This is the first ever report of the synthesis of GNps using glycation reaction. [•] These particles were proved effective against the bone cancer cell line (Saos-2). [•] These particles were found nontoxic on normal cell line (L-132). [Copyright &y& Elsevier]

Non-enzymatic protein glycation results in the formation of advanced glycation end products (AGEs) leads to the pathogenesis of long-term diabetic complications. Iridin (ID), an antioxidant, plays an important role in protecting against oxidative stress and could therefore be an efficacious anti-glycating regimen. Herein, we assessed the anti-glycating potential of ID against d -ribose induced glycation of bovine serum albumin (BSA) by various biophysical and biochemical techniques. Our results from several physicochemical assays advocated that ID was able to evidently prevent the AGEs generation via reducing hyperchromicity, early glycation products (EGPs), carbonyl content (CC), hydroxymethyl furfural (HMF) content, production of fluorescent AGEs, protection against loss of secondary structure (i.e. α-helix and β-sheets) of proteins, increasing the free lysine and free arginine content, reduced binding of congo red (CR), and reduced thioflavin T (ThT) and 8-aninilo-1-napthalene sulphonate (ANS)-specific fuorescence in glycated-BSA (Gly-BSA). On the basis of these findings, we concluded that ID possesses the significant anti-glycation potential and may be established as a remarkable anti-AGEs therapeutic agent. Further in-vivo and clinical studies are still warranted to uncover the therapeutic effects of ID against age-related as well as metabolic diseases. [ABSTRACT FROM AUTHOR]