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Age-related macular degeneration (AMD) is an age-related disorder that is a global public health problem. The non-enzymatic Maillard reaction results in the formation of advanced glycation end products (AGEs). Accumulation of AGEs in drusen plays a key role in AMD. AGE-reducing drugs may contribute to the prevention and treatment of AGE-related disease. Fructosamine oxidase (FAOD) acts on fructosyl lysine and fructosyl valine. Based upon the published results of fructosamine 3-kinase (FN3K) and FAOD obtained in cataract and presbyopia, we studied ex vivo FAOD treatment as a non-invasive AMD therapy. On glycolaldehyde-treated porcine retinas, FAOD significantly reduced AGE autofluorescence (p = 0.001). FAOD treatment results in a breakdown of AGEs, as evidenced using UV fluorescence, near-infrared microspectroscopy on stained tissue sections of human retina, and gel permeation chromatography. Drusen are accumulations of AGEs that build up between Bruch's membrane and the retinal pigment epithelium. On microscopy slides of human retina affected by AMD, a significant reduction in drusen surface to 45 ± 21% was observed following FAOD treatment. Enzymatic digestion followed by mass spectrometry of fructose- and glucose-based AGEs (produced in vitro) revealed a broader spectrum of substrates for FAOD, as compared to FN3K, including the following: fructosyllysine, carboxymethyllysine, carboxyethyllysine, and imidazolone. In contrast to FN3K digestion, agmatine (4-aminobutyl-guanidine) was formed following FAOD treatment in vitro. The present study highlights the therapeutic potential of FAOD in AMD by repairing glycation-induced damage. [ABSTRACT FROM AUTHOR]

BACKGROUND: Glycation is a green processing technology. Based on our previous studies, glycation with l‐arabinose and xylose was beneficial to enhance the texture properties of silver carp mince (SCM) gels. However, the possible enhancement mechanism remained unclear. Therefore, in this study, SCM gels with different types of reducing sugar (glucose, l‐arabinose, and xylose) were prepared based on our previous study. The possible mechanism of texture enhancement of SCM gels was analyzed by investigating the changes in water distribution, protein structures, and microstructure in the gel system. RESULTS: The glycation of l‐arabinose and xylose enhanced the hardness, cohesiveness, chewiness, and resilience of SCM gels. Hardness increased from 1883.04 (control group) to 3624.54 (l‐arabinose group) and 4348.18 (xylose group). Low‐field nuclear magnetic resonance (LF‐NMR) showed that glycation promoted the tight binding of immobilized water to proteins. Raman spectroscopic analysis showed that glycation increased the surface hydrophobicity and promoted the formation of disulfide bonds. Scanning electron microscopy (SEM) showed that glycation promoted the formation of uniform and dense three‐dimensional network structure in SCM gels. CONCLUSION: In summary, glycation enhanced the binding ability of immobilized water to proteins, improved the surface hydrophobicity, promoted the formation of disulfide bonds, and led to a more uniform and dense gel network structure of proteins, thus enhancing the texture properties of SCM gels. This research provided a theoretical basis for a better understanding of the mechanism of the effect of glycation on the quality of gel products and also provided technical support for the application of l‐arabinose and xylose in new functional gel foods. © 2024 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

This study examined the relationship between dietary intake of advanced glycation end products (dAGEs) and depression and sleep quality in young adults. This study, which included 420 university students (F = 80.2 %; M = 19.8 %), is observational and cross-sectional. Dietary AGEs intakes of individuals were taken with a 24-h food consumption record system. Measuring the depression status of the participants was evaluated with the Beck Depression Inventory (BDI), and the assessment of their sleep quality was evaluated with the Pittsburg Sleep Quality Index (PSQI). Individuals' dAGEs intakes were divided into three equal groups (low, medium, and high). The energy was adjusted in all analyzes of dAGEs intake. Study data were analyzed with the SPSS (27.0 version) and GraphPad program (8.0 version). The BDI and PSQI total score averages of individuals in the high dAGEs intake group were higher than the other groups, and this difference was statistically significant (p < 0.001). There is no significant difference between individuals' dAGEs intakes and energy and macronutrient intakes. Students' dAGEs intake was affected by BDI (β = 0.722, 95 % Cl = 0.639;0.811) and PSQI (β = 0.286, 95 % Cl = 0.179;0.431) scores (p < 0.001). This effect persisted even when various confounding factors were included (age, gender, smoking, body mass index, chronic disease) (p < 0.001). These data are cross-sectional, which limits the generalizability of results and establishing cause-effect relationships. There may be an association between dAGEs intake and the development of depression and sleep quality in young adults. Clinical intervention studies using objective measurement methods should be conducted on this issue in the future. • The BDI score increased as the students' dietary advanced glycation end products increased. • There is a relationship between dietary advanced glycation end products and sleep quality. • The relationship between the feeding pattern and the development of depression is important. • It is important to take a nutritional anamnesis while investigating the secondary causes of the development of depression. [ABSTRACT FROM AUTHOR]

α‐Ketoaldehydes play versatile roles in the ubiquitous natural processes of protein glycation. However, leveraging the reactivity of α‐ketoaldehydes for biomedical applications has been challenging. Previously, the reactivity of α‐ketoaldehydes with guanidine has been harnessed to design probes for labeling Arg residues on proteins in an aqueous medium. Herein, a highly effective, broadly applicable, and operationally simple protocol for stapling native peptides by crosslinking two amino groups through diverse imidazolium linkers with various α‐ketoaldehyde reagents is described. The use of hexafluoroisopropanol as a solvent facilitates rapid and clean reactions under mild conditions and enables unique selectivity for Lys over Arg. The naturally occurring GOLD/MOLD linkers have been expanded to encompass a wide range of modified glyoxal‐lysine dimer (OLD) linkers. In a proof‐of‐concept trial, these modular stapling reactions enabled a convenient two‐round strategy to streamline the structure–activity relationship (SAR) study of the wasp venom peptide anoplin, leading to enhanced biological activities. [ABSTRACT FROM AUTHOR]

Background/Aims: The neurofibrillary tangles consisting of Tau protein are an important pathology in Alzheimer’s disease. The paired helical filaments of Tau form most of the NFTs. These PHFs of Tau are found to carry numerous post-translational modifications, which stabilize them and aid in aggregation. The mechanistic function of Tau is to bind and stabilize the axonal microtubules. Hyperphosphorylation of Tau causes it to compromise its physiological function and accumulate in the neurons in the form of aggregates. Such residue-specific phosphorylation has been studied by employing Tau pseudophosphorylation mutants. But in addition to phosphorylation, several other modifications also aid in stabilizing the Tau PHF. Glycation is one such non-enzymatic PTM caused by sugars and their reactive intermediates. In this study, we employed the pseudophosphorylated Tau double mutants (262/404D, 262/396D, and 231/262) for studying their modification by methyl glyoxal, a reactive intermediate of glucose metabolism. Methods: We studied various biophysical properties like aggregation propensity, Advanced glycation end-product formation, and global conformation of the Tau with dual modifications. Our study includes the use of in vitro techniques e.g., ThS fluorescence assay, electron microscopy, CD spectroscopy, SDS-PAGE. Results: The overall result of the study suggest that the MG-induced Tau aggregation is influenced by the residue-specific Tau phosphorylation. Conclusion: In conclusion, the combinatorial effect of discreet PTMs on Tau function could lead to a better understanding of Tauopathy. [ABSTRACT FROM AUTHOR]

Objectives: Intrapulpal calcifications can occur in the dental pulp of patients with diabetes. We focused on the association between ectopic calcifications in the dental pulp and advanced glycation end products (AGEs) in Spontaneously Diabetic Torii (SDT)‐fatty rats, an obese type 2 diabetic rat model, to determine the mechanism of calcification with pulp stone in the dental pulp. Materials and Methods: Pathologic calcification in the dental pulp of SDT‐fatty rats was observed using electron microscopy and immunohistochemical analysis. Moreover, mechanical analysis of periapical region of molar tooth against occlusal force was performed. Results: In SDT‐fatty rats, pathogenic pulpal calcifications occurred during blood glucose elevation after 6 weeks, and granular calcification was observed in the dental pulp after 11 weeks. Pentosidine, a major AGE, and the receptor for AGEs were strongly expressed in the dental pulp of SDT‐fatty rats. S100A8, TNF‐α, and IL‐6 also showed positive response in the dental pulp of the SDT‐fatty rat, which indicated pulpal inflammation. Blood flow disorder and hypoxic dental pulp cells were also observed. In silico simulation, strain from occlusal force concentrates on the root apex. Conclusions: Glycation makes blood vessels fragile, and occlusal forces damage the vessels mechanically. These are factors for intrapulpal calcification of diabetes. [ABSTRACT FROM AUTHOR]

Advanced glycation end products (AGEs) are a large number of heterogeneous compounds formed by the glycation of proteins, fats or nucleic acids. Endogenous AGEs have been associated with various health problems such as obesity, type 2 diabetes mellitus and cardiovascular disease. Inflammation is thought to be one of the main mechanisms in the development of these disorders. Although AGEs are produced endogenously in the body, exogenous sources such as smoking and diet also contribute to the body pool. Therefore, when the AGE pool in the body rises above physiological levels, different pathological conditions may occur through various mechanisms, especially inflammation. While the effects of endogenous AGEs on the development of inflammation have been studied relatively extensively, and current evidence indicates that dietary AGEs (dAGEs) contribute to the body's AGE pool, it is not yet known whether dAGEs have the same effect on the development of inflammation as endogenous AGEs. Therefore, this review aimed to evaluate the results of cross‐sectional and intervention studies to understand whether dAGEs are associated with inflammation and, if there is an effect on inflammation, through which mechanisms this effect might occur. [ABSTRACT FROM AUTHOR]

Background The growing interest in identifying the mode of action of traditional medicines has strengthened its research. Syzygium jambolanum (Syzyg) is commonly prescribed in homeopathy and is a rich source of phytochemicals. Objective The present study aims to shed light on the anti-glycation molecular mechanism of Syzyg mother tincture (MT), 30c, and 200c on glycated human serum albumin (HSA) by multi-spectroscopic and microscopic approaches. Methods The phytochemicals and antioxidant potential of the Syzyg formulations were estimated by the high-performance liquid chromatography and spectroscopic technique, respectively. Glycation was initiated by incubating HSA with methylglyoxal, three Syzyg formulations, and the known inhibitor aminoguanidine in separate tubes at 37°C for 48 hours. The formation of glycation adducts was assessed by spectrofluorometer and affinity chromatography. The structural modifications were analyzed through circular dichroism, Fourier transform infrared spectroscopy, turbidity, 8-anilinonapthalene-1-sulfonic acid fluorescence, and nuclear magnetic resonance. Further, the formation of the aggregates was examined by thioflavin T, native-polyacrylamide gel electrophoresis, and transmission electron microscopy. Additionally, the functional modifications of glycated HSA were determined by esterase-like activity and antioxidant capacity. The binding analysis of Syzyg formulations with glycated HSA was evaluated by surface plasmon resonance (SPR). Results Syzyg formulations MT, 30c, and 200c contained gallic acid and ellagic acid as major phytochemicals, with concentrations of 16.02, 0.86, and 0.52 µg/mL, and 227.35, 1.35, and 0.84 µg/mL, respectively. Additionally, all three formulations had remarkable radical scavenging ability and could significantly inhibit glycation compared with aminoguanidine. Further, Syzyg formulations inhibited albumin's structural and functional modifications. SPR data showed that Syzyg formulations bind to glycated HSA with an equilibrium dissociation constant of 1.10 nM. Conclusion Syzyg formulations inhibited the glycation process while maintaining the structural and functional integrity of HSA. [ABSTRACT FROM AUTHOR]

Lactobacillus fermentum (L. fermentum) was first evaluated as a potential advanced glycation end-product (AGE) formation inhibitor by establishing a bovine serum albumin (BSA) + glucose (glu) glycation model in the present study. The results showed that the highest inhibition rates of pentosidine and total fluorescent AGEs by L. fermentum were approximately 51.67% and 77.22%, respectively, which were higher than that of aminoguanidine (AG). Mechanistic analysis showed that L. fermentum could capture methylglyoxal and glyoxal, inhibit carbonyl and sulfhydryl oxidation, reduce the binding of glucose and amino groups, increase total phenolic content and antioxidant activity, and release intracellular substances to scavenge free radicals; these abilities were the basis of the antiglycation mechanism of L. fermentum. In addition, L. fermentum significantly prevented conformational changes in proteins during glycation, reduced protein cross-linking by 35.67%, and protected the intrinsic fluorophore. Therefore, the inhibition of L. fermentum on glycation mainly occurs through antioxidation, the capture of dicarbonyl compounds, and the protection of the BSA structure. These findings collectively suggest that Lactobacillus is an inhibitor of protein glycation and AGE formation and has the potential for nutraceutical applications. [ABSTRACT FROM AUTHOR]

The formation of a heterogeneous set of advanced glycation end products (AGEs) is the final outcome of a non-enzymatic process that occurs in vivo on long-life biomolecules. This process, known as glycation, starts with the reaction between reducing sugars, or their autoxidation products, with the amino groups of proteins, DNA, or lipids, thus gaining relevance under hyperglycemic conditions. Once AGEs are formed, they might affect the biological function of the biomacromolecule and, therefore, induce the development of pathophysiological events. In fact, the accumulation of AGEs has been pointed as a triggering factor of obesity, diabetes-related diseases, coronary artery disease, neurological disorders, or chronic renal failure, among others. Given the deleterious consequences of glycation, evolution has designed endogenous mechanisms to undo glycation or to prevent it. In addition, many exogenous molecules have also emerged as powerful glycation inhibitors. This review aims to provide an overview on what glycation is. It starts by explaining the similarities and differences between glycation and glycosylation. Then, it describes in detail the molecular mechanism underlying glycation reactions, and the bio-molecular targets with higher propensity to be glycated. Next, it discusses the precise effects of glycation on protein structure, function, and aggregation, and how computational chemistry has provided insights on these aspects. Finally, it reports the most prevalent diseases induced by glycation, and the endogenous mechanisms and the current therapeutic interventions against it. [ABSTRACT FROM AUTHOR]

When surimi containing nitro blue tetrazolium was heated with vitamin C (AsA), the color intensified. This coloration faded upon the addition of tiron, a scavenger of the superoxide anion radical (O2• - ), indicating that O2• - was generated from AsA in the surimi. In myosin prepared from carp, the generation of thiyl radicals (S•) by O2• - was detected using electron spin resonance spectroscopy. These results illustrate the quality improvement mechanism of AsA in gelatinous protein foods as follows: (1) AsA added to surimi reduces the transition metal, which becomes oxidized, (2) O2 is reduced to O2• - via one-electron reduction, (3) O2• -pulls hydrogen radicals (H•) from the SH group on myosin to form S•, and (4) disulfide (SS) bonds are formed between myosins by radical oxidation, which leads to a denser structure and a quality improvement effect. When cream chicken was prepared using the vacuum cooking method, separation was observed in the sauce. This phenomenon was caused by the dissolution of soluble proteins in the meat during heating. The soluble protein was examined by scanning electron microscopy and was found to consist of spherical particles in a random structure at 75°C heating; upon heating to 90°C, the SS bonds formed a strong structure, resulting in a more uniform material and forming a gel with a wide space and a large surface area. Thus, heating to 90°C is speculated to be the reason for the separation of the source, as the structure at 90°C firmly held the casein micelles and oil droplets. In the functional alteration of chicken myofibrillar proteins (Mfs) through glycation, using the Maillard reaction, the solubility of protein in low-ionic-strength solutions and the antioxidant capacity were determined. The glucosemodified chicken Mfs showed antioxidant capacity in the heated gel. In contrast, the glucose-modified soybean 11S globulin showed high emulsification stability, indicating the possibility of developing an emulsifier that suppresses oil autoxidation. As an antioxidant, soybean 11S globulin was also found to be sufficient to suppress oil oxidation. [ABSTRACT FROM AUTHOR]

The present work elucidates the role of colchicine (COL) on albumin glycation and cellular oxidative stress in diabetic cardiomyopathy (DCM). Human serum albumin (HSA) was glycated with methylglyoxal in the presence of COL (2.5, 3.75, and 5 µM), whereas positive and negative control samples were maintained separately. The effects of COL on HSA glycation, structural and functional modifications in glycated HSA were analyzed using different spectroscopical and fluorescence techniques. Increased fructosamine, carbonyl, and pentosidine formation in glycated HSA samples were inhibited in the presence of COL. Structural conformation of HSA and glycated HSA samples was examined by field emission scanning electron microscopy, circular dichroism, Fourier transform infrared, and proton nuclear magnetic resonance analyses, where COL maintained both secondary and tertiary structures of HSA against glycation. Functional marker assays included ABTS•+ radical scavenging and total antioxidant activities, advanced oxidative protein product formation, and turbidimetry, which showed preserved functional properties of glycated HSA in COL‐containing samples. Afterward, rat cardiomyoblast (H9c2 cell line) was treated with glycated HSA–COL complex (400 μg/mL) for examining various cellular antioxidants (nitric oxide, catalase, superoxide dismutase, and glutathione) and detoxification enzymes (aldose reductase, glyoxalase I, and II) levels. All three concentrations of COL exhibited effective anti‐glycation properties, enhanced cellular antioxidant levels, and detoxification enzyme activities. The report comprehensively analyzes the potential anti‐glycation and properties of COL during its initial assessment. [ABSTRACT FROM AUTHOR]

Context: Chronic kidney disease (CKD) is a worldwide health problem. Recent literature has shown an association of hemoglobin glycation index (HGI) and CKD in patients with dysglycemia. Objective: The aim of this study was to reveal the impact of HGI as a predictor for incident CKD in the general population. Methods: CKD was defined as dipstick proteinuria or estimated glomerular rate (eGFR) < 60 mL/min/1.73 m². Impact of HGI on incident CKD was assessed using the data from CKD-free health examinees (N = 23 467, 4.1% with diabetes) followed for a mean of 5.1 years: Cox proportional hazards model was employed with multivariate adjustment for age, systolic blood pressure, eGFR, fasting plasma glucose, body mass index, log[alanine aminotransferase], log[triglycerides], high-density lipoprotein cholesterol, platelet counts, smoking, and sex. Elevated level of HGI in subjects with CKD was ascertained after propensity score matching of another group of health examinees (N = 2580, 7.6% with diabetes). Results: In the former group, CKD developed in 2540 subjects and HGI was the second most robust predictor for CKD, following low eGFR. With adjustment for the 11 covariates, the hazard ratio of HGI (95% CI) for CKD was 1.293 (1.238 to 1.349) (P < .0001). The population attributable risk of HGI for CKD was 4.2%. In the latter group, among 708 subjects matched 1:1 for 9 covariates, HGI was significantly elevated in subjects with CKD (median [interquartile range] −0.208 [−0.504 to −0.156] vs −0.284 [−0.582 to 0.052], P = .03). Conclusion: HGI was a novel risk factor for CKD in the general population [ABSTRACT FROM AUTHOR]

Fullerenes and their derivatives have great potential for use as materials for medicine and biology. Fullerenes can enter into various reactions due to the presence of double bonds in their structure; it has also been repeatedly noted in the literature that the molecules have antiradical activity, biocompatibility, the ability to pass through biobarriers and immobilize various active molecules. In this work, a water-soluble adduct of C60 fullerene with glycine was synthesized, its physicochemical properties, biocompatibility were studied, and a protective effects toward collagen photodegradation as well as in the model reaction of human serum albumin glycation was shown. [ABSTRACT FROM AUTHOR]

Summary: Sesame has been included in the top eight food allergens, and therefore reduction of sesame allergen potency is of great practical significance. Glycation reactions are extensively researched for their role in regulating the allergic properties of food allergens due to their distinct benefits. This study involved the glycation of sesame proteins with three different reducing sugars to generate reaction products. The structure of the reaction products was characterized by the use of spectroscopic and chromatographic techniques. The impact of glycation on the allergenic properties of sesame proteins was explored by in vitro simulated digestion tests combined with immunological techniques. The study results indicated that all three reducing sugars underwent glycation with sesame proteins, with D‐ribose showing the most significant level of glycation. During the glycation reaction of sesame proteins in this study, the proteins underwent precipitation as well as structural changes, leading to reduced immunoglobulin G (IgG) binding capacity. Glycation alters the digestive stability of sesame proteins and further reduces the ability to bind to IgG. Overall, glycation modification shows promise in decreasing the allergenicity of sesame. [ABSTRACT FROM AUTHOR]

This study aimed to explore the inhibitory effect of pyrogallol on AGE formation in the bovine serum albumin (BSA)/glucose system for 21 days at 37 °C. The AGEs formation was measured in terms of Amadori products, total AGEs, argpyrimidine, and pentosidine. Molecular docking was used to investigate the interaction between pyrogallol and BSA. According to the results, in the presence of pyrogallol, the formation of pentosidine and argpyrimidine AGEs decreased. The molecular interaction studies demonstrated that pyrogallol has a high affinity towards arginine residues of albumin. Finally, results proved pyrogallol is a vigorous antiglycation compound and fruitful for AGE inhibition. [ABSTRACT FROM AUTHOR]

The objective of this study was to investigate a replacement for phosphate in meat products. Protein structural modification was employed in this study, and grafted myofibrillar protein (MP) with palatinose was added to meat emulsion without phosphate. Here, 0.15% of sodium polyphosphate (SPP) was replaced by the same (0.15%) concentration and double (0.3%) the concentration of grafted MP. Although the thermal stability was decreased, the addition of transglutaminase could increase stability. The rheological properties and pH also increased with the addition of grafted MP and transglutaminase. The addition of grafted protein could be perceived by the naked eye by observing a color difference before cooking, but it was not easy to detect after cooking. The cooking loss, emulsion stability, water holding capacity, lipid oxidation, and textural properties improved with the addition of grafted MP. However, the excessive addition of grafted MP and transglutaminase was not recommended to produce a high quality of phosphate replaced meat emulsion, and 0.15% was identified as a suitable addition ratio of grafted MP.

Diabetes and ulcer are the major health problems all over the world. The present study reports synthesis and bio-evaluation of 19 benzimidazole analogs in search of antiglycation, antioxidant and antiulcer agents. The synthetic analogs were characterized using 1H NMR, 13C NMR and HR-EIMS. All compounds were checked for their antiglycation, antiurease and antioxidant activities. The fluorophenyl benzimidazole analogs 12–14 strongly inhibited glycation with IC50 values ranging from 142 µM to 193 µM. The same fluorophenyl analogs (12–14) were also found to exhibit the highest antioxidant activity with IC50 values ranging from 1.2 µM to 6.6 µM which further highlights the significance of these bioactive analogs. The dihydroxyphenyl analogs 6–9 demonstrated the most potent enzyme inhibitory activity with IC50 values ranging from 3.10 µM to 5.90 µM. Molecular docking studies were performed on the active analogs to investigate their interactions with the urease enzyme and provide a plausible explanation for their observed urease inhibitory activity.

Glycosylation is a crucial post-translational modification process where sugar molecules (glycans) are covalently linked to proteins, lipids, or other biomolecules. In this highly regulated and complex process, a series of enzymes are involved in adding, modifying, or removing sugar residues. This process plays a pivotal role in various biological functions, influencing the structure, stability, and functionality of the modified molecules. Glycosylation is essential in numerous biological processes, including cell adhesion, signal transduction, immune response, and biomolecular recognition. Dysregulation of glycosylation is associated with various diseases. Glycation, a post-translational modification characterized by the non-enzymatic attachment of sugar molecules to proteins, has also emerged as a crucial factor in various diseases. This review comprehensively explores the multifaceted role of glycation in disease pathogenesis, with a specific focus on its implications in osteoarthritis (OA). Glycosylation and glycation alterations wield a profound influence on OA pathogenesis, intertwining with disease onset and progression. Diverse studies underscore the multifaceted role of aberrant glycosylation in OA, particularly emphasizing its intricate relationship with joint tissue degradation and inflammatory cascades. Distinct glycosylation patterns, including N-glycans and O-glycans, showcase correlations with inflammatory cytokines, matrix metalloproteinases, and cellular senescence pathways, amplifying the degenerative processes within cartilage. Furthermore, the impact of advanced glycation end-products (AGEs) formation in OA pathophysiology unveils critical insights into glycosylation-driven chondrocyte behavior and extracellular matrix remodeling. These findings illuminate potential therapeutic targets and diagnostic markers, signaling a promising avenue for targeted interventions in OA management. In this comprehensive review, we aim to thoroughly examine the significant impact of glycosylation or AGEs in OA and explore its varied effects on other related conditions, such as liver-related diseases, immune system disorders, and cancers, among others. By emphasizing glycosylation's role beyond OA and its implications in other diseases, we uncover insights that extend beyond the immediate focus on OA, potentially revealing novel perspectives for diagnosing and treating OA.

In this study, we systematically investigated the emulsifying capabilities of myofibrillar protein (MP)- and MP peptide (MPP)-based conjugates synthesized through intensification techniques: water bath (WB), microwave, ultrasound, and the combined ultrasound-microwave (UM) methods. Compared with WB, microwave, and ultrasound treatments, the combined UM treatment greatly promoted the glycation reaction because ultrasound and microwave mutually reinforced modification effects. The resultant conjugate structure tended to unfold with more flexible conformation and homogeneous morphology. Moreover, the emulsifying properties of conjugates developed with single and combined ultrasound-assisted glycation displayed substantial improvement, and pre-hydrolysis further enhanced these performances, as observed in the Principal Component Analysis as well. Remarkably, MPP grafted by maltodextrin with the assistance of a combined UM field produced the smallest and most uniform emulsion system, positioning it as the most efficient emulsifier among all the fabricated glycoconjugates. Our study highlighted the potential of synergistically applying ultrasound and microwave techniques to develop a well-performance glycation with an ideal conjugate structure, in which they would be associated into a strong film that provided the robust physical barrier, creaming stability, heat retention, and oxidation resistance. These findings offered a basis for better utilizing complex ultrasonic technology to develop novel and improved MP-based food products.

Glycated proteins are effective materials for improving the environmental stability and bioavailability of biologically active chemicals. The whey protein concentrate (WPC)-xylose (D) conjugates produced by the Maillard process were used to load and protect purple sweet potato anthocyanins in this study. Response surface optimization was used to determine the best parameters for preparing WPC-D conjugates. Glycation altered the secondary structure of proteins, according to structural studies, which also had an impact on their functional characteristics, which showed better antioxidant activity before and after simulated gastrointestinal (GI) digestion (p

The binding of ubiquitous serum ligands (free fatty acids) to human serum albumin (HSA) or its glycation can affect thiol group reactivity, thus influencing its antioxidant activity. The effects of stearic acid (SA) and glucose binding on HSA structural changes and thiol group content and reactivity were monitored by fluoroscopy and the Ellman method during a 14-day incubation in molar ratios to HSA that mimic pathophysiological conditions. Upon incubation with 5 mM glucose, HSA glycation was the same as HSA without it, in three different HSA:SA molar ratios (HSA:SA-1:1-2-4). The protective effect of SA on the antioxidant property of HSA under different glucose regimes (5-10-20 mM) was significantly affected by molar ratios of HSA:SA. Thiol reactivity was fully restored with 5–20 mM glucose at a 1:1 HSA:SA ratio, while the highest thiol content recovery was in pathological glucose regimes at a 1:1 HSA:SA ratio. The SA affinity for HSA increased significantly (1.5- and 1.3-fold, p < 0.01) with 5 and 10 mM glucose compared to the control. These results deepen the knowledge about the possible regulation of the antioxidant role of HSA in diabetes and other pathophysiological conditions and enable the design of future HSA-drug studies which, in turn, is important for clinicians when designing information-based treatments. [ABSTRACT FROM AUTHOR]

Heparan sulphate (HS) can act as a co-receptor on the cell surface and alterations in this process underpin many pathological conditions. We have previously described the usefulness of mimics of HS (glycomimetics) in protection against β-glycerophosphate-induced vascular calcification and in the restoration of the functional capacity of diabetic endothelial colony-forming cells in vitro. This study aims to investigate whether our novel glycomimetic compounds can attenuate glycated low-density lipoprotein (g-LDL)-induced calcification by inhibiting RAGE signalling within the context of critical limb ischemia (CLI). We used an established osteogenic in vitro vascular smooth muscle cell (VSMC) model. Osteoprotegerin (OPG), sclerostin and glycation levels were all significantly increased in CLI serum compared to healthy controls, while the vascular calcification marker osteocalcin (OCN) was down-regulated in CLI patients vs. controls. Incubation with both CLI serum and g-LDL (10 µg/mL) significantly increased VSMC calcification vs. controls after 21 days, with CLI serum-induced calcification apparent after only 10 days. Glycomimetics (C2 and C3) significantly inhibited g-LDL and CLI serum-induced mineralisation, as shown by a reduction in alizarin red (AR) staining and alkaline phosphatase (ALP) activity. Furthermore, secretion of the osteogenic marker OCN was significantly reduced in VSMCs incubated with CLI serum in the presence of glycomimetics. Phosphorylation of cyclic AMP response element-binding protein (CREB) was significantly increased in g-LDL-treated cells vs. untreated controls, which was attenuated with glycomimetics. Blocking CREB activation with a pharmacological inhibitor 666-15 replicated the protective effects of glycomimetics, evidenced by elevated AR staining. In silico molecular docking simulations revealed the binding affinity of the glycomimetics C2 and C3 with the V domain of RAGE. In conclusion, these findings demonstrate that novel glycomimetics, C2 and C3 have potent anti-calcification properties in vitro, inhibiting both g-LDL and CLI serum-induced VSMC mineralisation via the inhibition of LDLR, RAGE, CREB and subsequent expression of the downstream osteogenic markers, ALP and OCN. [ABSTRACT FROM AUTHOR]

Labels do not disclose the excess-free-fructose/unpaired-fructose content in foods/beverages. Objective was to estimate excess-free-fructose intake using USDA loss-adjusted-food-availability (LAFA) data (1970–2019) for high fructose corn syrup (HFCS) and apple juice, major sources of excess-free-fructose, for comparison with malabsorption dosages (~ 5 g-children/ ~ 10 g-adults). Unlike sucrose and equimolar fructose/glucose, unpaired-fructose triggers fructose malabsorption and its health consequences. Daily intakes were calculated for HFCS that is generally-recognized-as-safe/ (55% fructose/45% glucose), and variants (65/35, 60/40) with higher fructose-to-glucose ratios (1.9:1, 1.5:1), as measured by independent laboratories. Estimations include consumer-level-loss (CLL) allowances used before (20%), and after, subjective, retroactively-applied increases (34%), as recommended by corn-refiners (~ 2012). No contributions from crystalline-fructose or agave syrup were included due to lack of LAFA data. High-excess-free-fructose-fruits (apples/pears/watermelons/mangoes) were not included. Eaten in moderation they are less likely to trigger malabsorption. Another objective was to identify potential parallel trends between excess-free-fructose intake and the "unexplained" US asthma epidemic. The fructose/gut-dysbiosis/lung axis is well documented, case-study evidence and epidemiological research link HFCS/apple juice intake with asthma, and unlike gut-dysbiosis/gut-fructosylation, childhood asthma prevalence data spans > 40 years. Results Excess-free-fructose daily intake for individuals consuming HFCS with an average 1.5:1 fructose-to-glucose ratio, ranged from 0.10 g/d in 1970, to 11.3 g/d in 1999, to 6.5 g/d in 2019, and for those consuming HFCS with an average 1.9:1 ratio, intakes ranged from 0.13 g/d to 16.9 g/d (1999), to 9.7 g/d in 2019, based upon estimates with a 20% CLL allowance. Intake exceeded dosages that trigger malabsorption (~ 5 g) around ~ 1980. By the early 1980's, tripled apple juice intake had added ~ 0.5 g to average-per-capita excess-free-fructose intake. Contributions were higher (~ 3.8 g /4-oz.) for individuals consuming apple juice consistent with a healthy eating pattern (4-oz. children, 8-oz. adults). The "unexplained" childhood asthma epidemic (1980-present) parallels increasing average-per-capita HFCS/apple juice intake trends and reflects epidemiological research findings. Conclusion Displacement of sucrose with HFCS, its ubiquitous presence in the US food-supply, the industry practice of adding more fructose to HFCS than generally-recognized-as-safe, and increased use of apple juice/crystalline fructose/agave syrup in foods/beverages has contributed to unprecedented excess-free-fructose intake levels, fructose malabsorption, gut-dysbiosis and gut-fructosylation (immunogen burden)-gateways to chronic disease. [ABSTRACT FROM AUTHOR]

Glioblastoma (GBM) is a highly aggressive brain tumor that often utilizes aerobic glycolysis for energy production (Warburg effect), resulting in increased methylglyoxal (MGO) production. MGO, a reactive dicarbonyl compound, causes protein alterations and cellular dysfunction via glycation. In this study, we investigated the effect of glycation on sialylation, a common post-translational modification implicated in cancer. Our experiments using glioma cell lines, human astrocytes (hA), and primary glioma samples revealed different gene expressions of sialyltransferases among cells, highlighting the complexity of the system. Glycation has a differential effect on sialyltransferase expression, upregulating ST8SIA4 in the LN229 and U251 cell lines and decreasing the expression in normal hA. Subsequently, polysialylation increased in the LN229 and U251 cell lines and decreased in hA. This increase in polysialylation could lead to a more aggressive phenotype due to its involvement in cancer hallmark processes such as immune evasion, resistance to apoptosis, and enhancing invasion. Our findings provide insights into the mechanisms underlying GBM aggressiveness and suggest that targeting glycation and sialylation could be a potential therapeutic strategy. [ABSTRACT FROM AUTHOR]

Glycation of biomolecules results in the formation of advanced glycation end products (AGEs). Immunoglobulin G (IgG) has been implicated in the progression of various diseases, including diabetes and cancer. This study purified three IgG subclasses (IgG1, IgG2, and IgG3) from Camelus dromedarius colostrum using ammonium sulfate fractionation and chromatographic procedures. SDS‐PAGE was performed to confirm the purity and molecular weight of the IgG subclasses. Several biochemical and biophysical techniques were employed to study the effect of glycation on camel IgG using methylglyoxal (MGO), a dicarbonyl sugar. Early glycation measurement showed an increase in the fructosamine content by ~four‐fold in IgG2, ~two‐fold in IgG3, and a slight rise in IgG1. AGEs were observed in all classes of IgGs with maximum hyperchromicity (96.6%) in IgG2. Furthermore, glycation‐induced oxidation of IgGs led to an increase in carbonyl content and loss of ‐SH groups. Among subclass, IgG2 showed the highest (39.7%) increase in carbonyl content accompanied by 82.5% decrease in ‐SH groups. Far UV‐CD analysis illustrated perturbation of β‐sheet structure during glycation reaction with MGO. Moreover, glycation of IgG proceeds to various conformational states like aggregation and increased hydrophobicity. In addition, the cytotoxicity assay (MTT) illustrated the proliferation of breast cancer cells (MCF‐7) with IgG2 treatment. [ABSTRACT FROM AUTHOR]

The utilization of sesame protein in food products is limited due to the various challenges posed by its functional properties. This study aimed to investigate the Maillard reaction between sesame protein isolate (SPI) and guar gum (GG) under wet-heating conditions (80 °C) and to evaluate the functional and antioxidant properties of prepared conjugates. The functional properties of the samples were analyzed by observing their solubility, emulsion activity, emulsion stability, foam capacity (FC), foam stability, and oil/water-holding capacity. ABTS and DPPH radical scavenging, reducing power, and iron chelating activity were used to analyze the antioxidant properties. FTIR, XRD, and fluorescence spectroscopic studies indicated that the secondary structure of the protein underwent extensive alterations. The functional properties of conjugates were highly improved by the structural changes caused by the Maillard reaction. Emulsion activity (up to1.8-fold), and FC (up to 61.67%) were improved. The antioxidant activity of conjugates was significantly greater than the unmodified protein, DPPH-RS assay (42.83% upper), ABTS-RS assay (up to 74%), reducing power (up to 2.78-fold), and iron chelating (up to 87.55%). This study demonstrates how the Maillard reaction can enhance sesame protein's functional and antioxidant characteristics. [ABSTRACT FROM AUTHOR]

Diabetic kidney disease (DKD) is a leading cause of death in patients with diabetes. An early precursor to DKD is endothelial cell dysfunction (ECD), which often precedes and exacerbates vascular disease progression. We previously discovered that covalent adducts formed on DNA, RNA, and proteins by the reactive metabolic by-product methylglyoxal (MG) predict DKD risk in patients with type 1 diabetes up to 16 years pre-diagnosis. However, the mechanisms by which MG adducts contribute to vascular disease onset and progression remain unclear. Here, we report that the most predominant MG-induced nucleoside adducts, N2-(1-carboxyethyl)-deoxyguanosine (CEdG) and N2-(1-carboxyethyl)-guanosine (CEG), drive endothelial dysfunction. Following CEdG or CEG exposure, primary human umbilical vein endothelial cells (HUVECs) undergo endothelial dysfunction, resulting in enhanced monocyte adhesion, increased reactive oxygen species production, endothelial permeability, impaired endothelial homeostasis, and exhibit a dysfunctional transcriptomic signature. These effects were discovered to be mediated through the receptor for advanced glycation end products (RAGE), as an inhibitor for intracellular RAGE signaling diminished these dysfunctional phenotypes. Therefore, we found that not only are MG adducts biomarkers for DKD, but that they may also have a role as potential drivers of vascular disease onset and progression and a new therapeutic modality. [ABSTRACT FROM AUTHOR]

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Copyright of Food Research & Development is the property of Food Research & Development Editorial Department and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Purpose: Sturgeon notochord, a by-product in the sturgeon aquaculture industry, is a promising yet underutilized source of type II collagen. In this study, functionally enhanced collagen peptides (CPs) were developed from notochordal collagen using optimal glycation via the Maillard reaction, and the potential applications of the by-product and possible contributions to the valorization of the sturgeon aquaculture industry were determined. Methods: CP prepared by papain digestion was mixed with alginate oligosaccharide (AO), glucose (Glu), or glucuronic acid (GluA), lyophilized, and then glycation at 80 °C and 75% relative humidity for up to 8 h. Amino acid analysis was performed to evaluate the formation of glycated CP (CP–sugars). The health-beneficial functions, antioxidative and anti-inflammatory activities of CP–sugars were evaluated by the ABTS radical scavenging assay and by quantification of inflammatory compound (tumor necrosis factor-α and nitric oxide) production in LPS-stimulated macrophages, respectively. Results: During the glycation process, reducing sugars were reacted with lysine and arginine in CP. GluA had a higher reactivity to the reactive amino acids than that of Glu and AO. The antioxidant and anti-inflammatory functions of CP–sugars were increased with the glycation processes, and AO-glycation enhanced the health-beneficial functions of CP without a marked loss of reactive amino acids compared with the Glu- and GluA-glycations. Conclusion: The appropriate glycation via the Maillard reaction is an effective way to simultaneously enhance the antioxidant and anti-inflammatory functions of CP from sturgeon notochord to facilitate its application as a functional food material. [ABSTRACT FROM AUTHOR]

Abstract The brain is a highly metabolically active organ requiring a large amount of glucose. Methylglyoxal (MGO), a by-product of glucose metabolism, is known to be involved in microvascular dysfunction and is associated with reduced cognitive function. Maintenance of the blood-brain barrier (BBB) is essential to maintain optimal brain function and a large amount of evidence indicates negative effects of MGO on BBB integrity. In this review, we summarized the current literature on the effect of MGO on the different cell types forming the BBB. BBB damage by MGO most likely occurs in brain endothelial cells and mural cells, while astrocytes are most resistant to MGO. Microglia on the other hand appear to be not directly influenced by MGO but rather produce MGO upon activation. Although there is clear evidence that MGO affects components of the BBB, the impact of MGO on the BBB as a multicellular system warrants further investigation. Diminishing MGO stress can potentially form the basis for new treatment strategies for maintaining optimal brain function.

From attributing mutations to cancers with the advent of cutting-edge genetic technology in recent decades, to re-searching the age-old theory of intrinsic metabolic shift of cancers (Warburg’s glycolysis), the quest for a precise panacea for mainly the metastatic cancers, remains incessant. This review delineates the advanced glycation end product (AGE)-receptor for AGE (RAGE) pathway driven intricate oncogenic cues, budding from the metabolic (glycolytic) reliance of tumour cells, branching into metastatic emergence of malignancies. Strong AGE-RAGE concomitance in metastasis, chemo-resistance and cancer resurgence adversely incite disease progression and patient mortality. At the conjunction of metabolic and metastatic shift of cancers, are the “glycolytically” generated AGEs and AGE-activated RAGE, instigating aberrant molecular pathways, culminating in aggressive malignancies. AGEs as by-products of metabolic insurgence, modify the metabolome, epigenome and microbiome, besides coercing the inter-, intra- and extra-cellular micro-milieu conducive for oncogenic events like epithelial-mesenchymal transition (EMT). AGE-RAGE synergistically elicit ATP surge for surplus energy, autophagy for apoptotic evasion and chemo-resistance, insulin-like growth factor 1 (IGF-1) for meta-inflammation and angiogenesis, high mobility group box-1 (HMGB1) for immune tolerance, S100 proteins for metastasis, and p53 protein attenuation for tumour suppression. AGEs are pronouncedly reported in invasive forms of breast, prostate, colon and pancreatic cancers, higher in patients with cancer than healthy counterparts, and higher in advanced stage than localized phase. Hence, the investigation of person-specific presence of AGEs, soluble RAGE and AGE-activated RAGE can be advocated as impending bio-markers for diagnostic, prognostic and therapeutic purposes, to predict cancer risk in patients with diabetes, obesity, metabolic syndrome as well as general population, to monitor prognosis and metastasis in patients with cancer, and to reckon complications in cancer survivors. Furthermore, clinical reports of exogenous (dietary) and endogenous (internally formed) AGEs in cancer patients, and contemporary clinical trials involving AGE-RAGE axis in cancer are underlined with theranostic implications.

Diabetic cheiroarthropathy (DCA) is a relatively uncommon and underdiagnosed complication of poorly controlled diabetes. It is caused by non-enzymatic glycation of collagen that ultimately leads to microvascular damage and polyarticular stiffness. If diagnosed early, optimal management of serum glucose levels may lessen joint stiffness and prevent microvascular and macrovascular complications associated with diabetes mellitus. We review the case of a 55-year-old male with type 2 diabetes mellitus who was diagnosed with DCA after complaints of chronic joint stiffness and immobility. [ABSTRACT FROM AUTHOR]

Protein glycation, hyper-inflammatory reactions, and oxidative stress play a crucial role in the pathophysiology of numerous diseases. The current work evaluated the protective ability of ethyl alcohol extract of leaves from holy basil (Ocimum sanctum Linn) against inflammation, oxidative stress, glycation and advanced glycation endproducts formation. Various in vitro assays assessed prementioned properties of holy basil. In addition, molecular docking was conducted. The highest hydrogen peroxide reduction activity (72.7 %) and maximum percentage of DPPH scavenging (71.3 %) depicted its vigorous antioxidant abilities. Furthermore, it showed the most excellent protection against proteinase activity (67.247 %), prevention of denaturation of egg albumin (65.29 %), and BSA (bovine serum albumin) (68.87 %) with 600 µg/ml. Percent aggregation index (57.528 %), browning intensity (56.61 %), and amyloid structure (57.0 %) were all reduced significantly using 600 μg/ml of extract. Additionally, the antimicrobial potential was also confirmed. According to a molecular docking study, active leaf extract ingredients were found to bind with superoxide dismutase, catalase, and carbonic anhydrase. As a conclusion, O. sanctum has a variety of health-promoting properties that may reduce the severity of many diseases in diabetic patients. However, in order to ascertain the mechanisms of action of the components of its leaves in disease prevention, more thorough research based on pharmacological aspects is needed.

The H1 receptor belongs to the family of rhodopsin-like G-protein-coupled receptors activated by the biogenic amine histamine. H1 receptor antagonists are widely used in the treatment of allergies. However, these drugs could have a much broader spectrum of activity, including hypoglycemic effects, which can broaden the spectrum of their use. The aim of the study was to evaluate the antiglycation potential of twelve H1 receptor antagonists (diphenhydramine, antazoline, promethazine, ketotifen, clemastine, pheniramine, cetirizine, levocetirizine, bilastine, fexofenadine, desloratadine, and loratadine). Bovine serum albumin (BSA) was glycated with sugars (glucose, fructose, galactose, and ribose) and aldehydes (glyoxal and methylglyoxal) in the presence of H1 blockers. The tested substances did not induce a significant decrease in the content of albumin glycation end-products, and the inhibition rate of glycoxidation was not influenced by the chemical structure or generation of H1 blockers. None of the tested H1 receptor antagonists exhibited strong antiglycation activity. Antiglycemic potential of H1 blockers could be attributed to their antioxidant and anti-inflammatory activity, as well as their effects on carbohydrate metabolism/metabolic balance at the systemic level.

The differences in maximum Maillard glycation extent of proteins incubated with saccharides of different size/charge might be explained by differences in saccharide reactivity towards each protein modification site. Mixtures of α-lactalbumin-glucose (AG), α-lactalbumin-maltotriose (AMTT) or α-lactalbumin-galacturonic acid (AGalA) were incubated for 10 h, reaching a glycation extent of 42, 19 and 30 %, respectively. Glycated protein samples were enzymatically hydrolyzed followed by UPLC-UV-MS determination and quantification of glycation in individual modification sites. On average, around 80 % of protein glycation was recovered as glycated peptides. For all protein-saccharide mixtures, the N-terminal amino group, K58, K62 and K114 were never glycated, whilst K5 and K122 were always the most glycated sites. The glycated sites R10, K79, K93, K94 and K108 found in AGalA, were absent from AG and AMtt. Differences in glycated/non-glycated sites could not explain the differences in total protein glycation between the various samples.

Poor emulsification of myofibrillar proteins (MPs) limits the production of meat protein emulsion-type products, and it is related to the myosin self-assembles in low-salt settings. The effect of high-intensity ultrasound (HIU) pretreatment combined with non-enzymatic glycation on MP-stabilized emulsions in low-salt settings was investigated in this study, and the potential mechanism was revealed. The results indicated that, compared to using either HIU or glycation treatment alone, HIU pretreatment in combination with glycation significantly improves the physical stability of emulsions while increasing the distribution uniformity and reducing the droplet particle size from 18.05 μm to 2.54 μm (P

The allergic epitopes of α-lactalbumin are the molecular basis for allergenicity. In this paper, the effects of different lengths sugar chains on the structure and allergenicity of allergic epitopes in α-lactalbumin were investigated. The IgE linear epitopes of 13KDLKGYGGVSLPEW26 (13K-W26) were synthesized and glycated with glucose, maltose, maltotriose and maltopentaose. Then the structural changes were analyzed by spectroscopy and chromatography. Cellular assays and ELISA were used to evaluate the histamine, interleukin-4 and interleukin-6 release ability of KU812 cells and the IgE binding ability. The results showed that 13K-W26 was glycated by different lengths sugar chains significantly decreased the free amino content and changed the fluorescence intensity and UV absorption intensity, and decreased the IgE binding ability and the release ability of histamine, interleukin-4 and interleukin-6 in KU812 cells. Therefore, different lengths of sugar chains can change the structure of 13K-W26, and reduce the allergenicity. The order was maltopentaose>maltotriose>maltose>glucose. In conclusion, the sugar chains could mask the linear epitopes 13K-W26 of α-lactalbumin, the sugar chains with longer length had stronger masking effects on epitopes, the better the effect of reducing the allergenicity.

Age-related macular degeneration (AMD) is an age-related disorder that is a global public health problem. The non-enzymatic Maillard reaction results in the formation of advanced glycation end products (AGEs). Accumulation of AGEs in drusen plays a key role in AMD. AGE-reducing drugs may contribute to the prevention and treatment of AGE-related disease. Fructosamine oxidase (FAOD) acts on fructosyl lysine and fructosyl valine. Based upon the published results of fructosamine 3-kinase (FN3K) and FAOD obtained in cataract and presbyopia, we studied ex vivo FAOD treatment as a non-invasive AMD therapy. On glycolaldehyde-treated porcine retinas, FAOD significantly reduced AGE autofluorescence (p = 0.001). FAOD treatment results in a breakdown of AGEs, as evidenced using UV fluorescence, near-infrared microspectroscopy on stained tissue sections of human retina, and gel permeation chromatography. Drusen are accumulations of AGEs that build up between Bruch’s membrane and the retinal pigment epithelium. On microscopy slides of human retina affected by AMD, a significant reduction in drusen surface to 45 ± 21% was observed following FAOD treatment. Enzymatic digestion followed by mass spectrometry of fructose- and glucose-based AGEs (produced in vitro) revealed a broader spectrum of substrates for FAOD, as compared to FN3K, including the following: fructosyllysine, carboxymethyllysine, carboxyethyllysine, and imidazolone. In contrast to FN3K digestion, agmatine (4-aminobutyl-guanidine) was formed following FAOD treatment in vitro. The present study highlights the therapeutic potential of FAOD in AMD by repairing glycation-induced damage.

Lactobacillus fermentum (L. fermentum) was first evaluated as a potential advanced glycation end-product (AGE) formation inhibitor by establishing a bovine serum albumin (BSA) + glucose (glu) glycation model in the present study. The results showed that the highest inhibition rates of pentosidine and total fluorescent AGEs by L. fermentum were approximately 51.67% and 77.22%, respectively, which were higher than that of aminoguanidine (AG). Mechanistic analysis showed that L. fermentum could capture methylglyoxal and glyoxal, inhibit carbonyl and sulfhydryl oxidation, reduce the binding of glucose and amino groups, increase total phenolic content and antioxidant activity, and release intracellular substances to scavenge free radicals; these abilities were the basis of the antiglycation mechanism of L. fermentum. In addition, L. fermentum significantly prevented conformational changes in proteins during glycation, reduced protein cross-linking by 35.67%, and protected the intrinsic fluorophore. Therefore, the inhibition of L. fermentum on glycation mainly occurs through antioxidation, the capture of dicarbonyl compounds, and the protection of the BSA structure. These findings collectively suggest that Lactobacillus is an inhibitor of protein glycation and AGE formation and has the potential for nutraceutical applications.

The diabetic peripheral neuropathy pain model was constructed after 95 Sprague Dawley rats had been randomly divided among blank reference and model groups. Aescin low-dose group (0.5 mg/kg), aescin medium-dose group (1.0 mg/kg), aescin high-dose group (1.5 mg/kg), and positive control group (0.25 mg/ kg mecobalamin) were then randomly assigned to the simulation group following successful modeling. At the conclusion of the study, the mean sciatic nerve conduction velocity was determined, blood glucose in addition to the amount of inflammatory factors tumor necrosis factor-alpha, interleukin-6, and interleukin-1 were determined, and sciatic nerve cells from mice in all groups were collected for Western blot to identify the protein levels of high mobility group box 1 and receptor for advanced glycation end products. The mean sciatic nerve conduction velocity of the medium and high-dose groups of aescin was higher than those of the model control (p<0.05); rat blood glucose content, the contents of inflammatory factors interleukin-1 beta, interleukin-6 and tumor necrosis factor-alpha as well as the protein expression of high mobility group box 1 and receptor for advanced glycation end products in sciatic nerve tissue were lower and the body mass was higher than that of the model control group (p<0.05). Comparing the high-dose aescin group as well as the positive control group, there had been no discernible change in the aforementioned indices (p>0.05). Aescin is able to effectively improve the inflammatory response in the body by regulating high mobility group box 1-receptor for advanced glycation end products levels and slow down diabetic peripheral neuropathy caused by the inflammatory response. [ABSTRACT FROM AUTHOR]

In this study, conjugates were prepared by heating aqueous dispersions of soy protein isolate (SPI) and fructose (F) for 5 and 15 min after ultrasonic treatment (130 W, 20 kHz) and by carrying out a glycation (95 oC, 30 min). Structural and functional properties of the resulting SPI-F conjugates were investigated to determine effect of the ultrasonic pretreatment. The formation of SPI-F conjugates was confirmed by free amino groups, degree of grafting and FT-IR analyses. The glycation reaction was enhanced by ultrasound. Although changes in the structural and physicochemical properties of the conjugates impaired the water- and oil-holding properties of SPI, its emulsifying properties were improved. Therefore, the structure of soy protein glycation conjugates can be modified to control their emulsification properties by using an optimal ultrasonic pretreatment. It can be said that these results are useful for application of glycation-modified protein-saccharide binary systems in food emulsions and other systems. [ABSTRACT FROM AUTHOR]

The current study aims to simulate fatigue microdamage accumulation in glycated cortical bone with increased advanced glycation end-products (AGEs) using a phase field fatigue framework. We link the material degradation in the fracture toughness of cortical bone to the high levels of AGEs in this tissue. We simulate fatigue fracture in 2D models of cortical bone microstructure extracted from human tibias. The results present that the mismatch between the critical energy release rate of microstructural features (e.g., osteons and interstitial tissue) can alter crack initiation and propagation patterns. Moreover, the high AGEs content through the increased mismatch ratio can cause the activation or deactivation of bone toughening mechanisms under cyclic loading. The fatigue fracture simulations also show that the lifetime of diabetic cortical bone samples can be dependent on the geometry of microstructural features and the mismatch ratio between the features. Additionally, the results indicate that the trapped cracks in cement lines in the diabetic cortical microstructure can prevent further crack growth under cyclic loading. The present findings show that alterations in the materials heterogeneity of microstructural features can change the fatigue fracture response, lifetime, and fragility of cortical bone with high AGEs contents. Cortical bone models are created from microscopy images taken from the cortical cross-section of human tibias. Increased glycation contents in the cortical bone sample can change the crack growth trajectories. [ABSTRACT FROM AUTHOR]

Glycation is a non-enzymatic reaction wherein sugars or dicarbonyls such as methylglyoxal (MGO) and glyoxal (GO) react with proteins, leading to protein inactivation. The hydrolysing enzyme human deglycase-1 (hDJ-1) is reported to decrease glycative stress by deglycating the modified proteins, specifically at cysteine, lysine, and arginine sites. This specificity of hDJ-1 is thought to be regulated by its active site cysteine residue (Cys106). Structural analysis of hDJ-1 by molecular docking and simulation studies, however, indicates a possible role of glutamate (Glu18) in determining its substrate specificity. To elucidate this, Glu18 present at the catalytic site of hDJ-1 was modified to aspartate (Asp18) by SDM, and the resultant mutant was termed mutant DJ-1 (mDJ-1). Both hDJ-1 and mDJ-1 were heterologously expressed in Escherichia coli BL21 (DE3) strain and purified to homogeneity. The hDJ-1 showed k cat values of 1.45 × 103 s−1, 3.6 × 102 s−1, and 3.1 × 102 s−1, and K m values 0.181 mM, 18.18 mM, and 12.5 mM for N- acetylcysteine (NacCys), N- acetyllysine (NacLys), and N- acetylarginine (NacArg), respectively. The mDJ-1 showed altered k cat values (8 × 102 s−1, 3.8 × 102 s−1, 4.9 × 102 s−1) and K m values of 0.14 mM, 6.25 mM, 5.88 mM for NacCys, NacLys and NacArg, respectively. A single amino acid change (Glu18 to Asp18) improved the substrate specificity of mDJ-1 toward NacLys and NacArg. Understanding hDJ-1's structure and enhanced functionality will facilitate further exploration of its therapeutic potential for the treatment of glycation-induced diabetic complications. [Display omitted] • Protein human deglycase-1 (hDJ-1) acts on amino acids with different specificities. • The structural analysis of hDJ-1 was performed to understand its substrate specificity. • Docking and MD simulation suggested the role of glutamate-18 in substrate specificity. • Glutamate was replaced with aspartate (E18D) to produce mutant protein mDJ-1. • mDJ-1 showed altered substrate specificity towards N -acetyllysine and N -acetylarginine. [ABSTRACT FROM AUTHOR]

The brain is a highly metabolically active organ requiring a large amount of glucose. Methylglyoxal (MGO), a by-product of glucose metabolism, is known to be involved in microvascular dysfunction and is associated with reduced cognitive function. Maintenance of the blood-brain barrier (BBB) is essential to maintain optimal brain function and a large amount of evidence indicates negative effects of MGO on BBB integrity. In this review, we summarized the current literature on the effect of MGO on the different cell types forming the BBB. BBB damage by MGO most likely occurs in brain endothelial cells and mural cells, while astrocytes are most resistant to MGO. Microglia on the other hand appear to be not directly influenced by MGO but rather produce MGO upon activation. Although there is clear evidence that MGO affects components of the BBB, the impact of MGO on the BBB as a multicellular system warrants further investigation. Diminishing MGO stress can potentially form the basis for new treatment strategies for maintaining optimal brain function. [ABSTRACT FROM AUTHOR]