Fluorescent Advanced Glycation End-products Research Articles

Skin senescence-from basic research to clinical practice.

The most recognizable implications of tissue aging manifest themselves on the skin. Skin laxity, roughness, pigmentation disorders, age spots, wrinkles, telangiectasia or hair graying are symptoms of physiological aging. Development of the senescent phenotype depends on the interaction between aging cells and remodeling of the skin's extracellular matrix (ECM) that contains collagen and elastic fiber. Aging changes occur due to the combination of both endogenous (gene mutation, cellular metabolism or hormonal agents) and exogenous factors (ultraviolet light, environmental pollutants, and unsuitable diet). However, overproduction of mitochondrial reactive oxygen species (ROS) is a key factor driving cellular senescence. Aging theories have disclosed a range of diverse molecular mechanisms that are associated with cellular senescence of the body. Theories best supported by evidence include protein glycation, oxidative stress, telomere shortening, cell cycle arrest, and a limited number of cell divisions. Accumulation of the ECM damage is suggested to be a key factor in skin aging. Every cell indicates a functional and morphological change that may be used as a biomarker of senescence. Senescence-associated β-galactosidase (SA-β-gal), cell cycle inhibitors (p16INK4a, p21CIP1, p27, p53), DNA segments with chromatin alterations reinforcing senescence (DNA-SCARS), senescence-associated heterochromatin foci (SAHF), shortening of telomeres or downregulation of lamina B1 constitute just an example of aging biomarkers known so far. Aging may also be assessed non-invasively through measuring the skin fluorescence of advanced glycation end-products (AGEs). This review summarizes the recent knowledge on the pathogenesis and clinical conditions of skin aging as well as biomarkers of skin senescence.

Total body irradiation is associated with long-term deficits in femoral bone structure but not mechanical properties in male rhesus macaques.

Exposure to ionizing radiation for oncological therapy increases the risk for late-onset fractures in survivors. However, the effects of total body irradiation (TBI) on adult bone are not well-characterized. The primary aim of this study was to quantify the long-term effects of TBI on bone microstructure, material composition, and mechanical behavior in skeletally mature rhesus macaque (Macaca mulatta) non-human primates. Femora were obtained post-mortem from animals exposed to an acute dose of TBI (6.0-6.75Gy) nearly a decade earlier, age-matched non-irradiated controls, and non-irradiated young animals. The microstructure of femoral trabecular and cortical bone was assessed via micro-computed tomography. Material composition was evaluated by measuring total fluorescent advanced glycation end products (fAGEs). Cortical bone mechanical behavior was quantified via four-point bending and cyclic reference point indentation (cRPI). Animals exposed to TBI had slightly worse cortical microstructure, including lower cortical thickness (-11%, p = 0.037) and cortical area (-24%, p = 0.049), but similar fAGE content and mechanical properties as age-matched controls. Aging did not influence cortical microstructure, fAGE content, or cRPI measures but diminished femoral cortical post-yield properties, including toughness to fracture (-32%, p = 0.032). Because TBI was administered after the acquisition of peak bone mass, these results suggest that the skeletons of long-term survivors of adulthood TBI may be resilient, retaining or recovering their mechanical integrity during the post-treatment period, despite radiation-induced architectural deficits. Further investigation is necessary to better understand radiation-induced skeletal fragility in mature and immature bone to improve care for radiation patients of all ages.

Chilean papaya (Vasconcellea pubescens A. DC.) residues as a source of bioactive compounds: Chemical composition, antioxidant capacity, and antiglycation effects

The Chilean papaya (Vasconcellea pubescens A.DC.) is a climacteric fruit that grows in the north and center of Chile. During its processing, residues formed mainly by mucilage and seeds are produced and mostly discarded, despite being a potential source of bioactive metabolites. This work aimed to apply untargeted metabolic analysis by HPLC-DAD-QToF to study the chemical composition of ethyl acetate and methanol extracts from Chilean papaya residues and evaluate their antioxidant and antiglycation capacities. Twenty-three metabolites were tentatively identified in papaya residues, including one carboxylic acid, one glycosylated hydroquinone, four flavan-3-ols, three proanthocyanidins, twelve glycosylated flavonols, one carbohydrate, and one alkaloid reported for the first time. The antioxidant capacity measured as the scavenging of DPPH• and ABTS•+ radicals was comparable with that of ascorbic acid. Chilean papaya extracts decreased fluorescent Advanced Glycation End (AGE) products and oxidative modifications in proteins induced by glucose.

Monascus pigments suppress fructose-mediated BSA glycation by trapping methylglyoxal and covalent binding to proteins

In this study, four Monascus pigments (ankaflavin, AK; monascin MS; rubropunctatin, O1; monascorubrin, O2) were proved to exhibit considerable anti-glycation properties in bovine serum albumin (BSA)-fructose model. AK (40.62 %) and MS (48.38 %) were found to exert lower inhibitory effects on the formation of fluorescent advanced glycation end products (AGEs) than aminoguanidine (59.4 %), while O1 (90.64 %) and O2 (93.82 %) displayed much stronger abilities. AK and MS could trap methylglyoxal (MGO) with maximum capture rates of 85.67 % and 84.90 %, respectively, and only mono-MGO adducts of them were detected. LC-Orbitrap MS/MS analysis revealed that four pigments significantly altered the type and reduced the number of the glycated sites and they all covalently bound to BSA, with O1 and O2 possessing high reactivity. Altogether, AK and MS suppressed fluorescent AGEs formation mainly via trapping MGO and covalently interacting with BSA, and blocking free amino groups was the dominant mechanism for O1 and O2. These findings presented new insights into Monascus pigments as dietary supplement for inhibiting protein glycation.

Serum metabolism-transcriptomics investigated into the immunity of whey protein isolate-galacto-oligosaccharide conjugates after dynamic high-pressure microfluidics pretreatment

The objective of this study was to investigate the immunomodulatory effects of whey protein isolate (WPI)-galacto-oligosaccharide conjugates following dynamic high-pressure microfluidics pretreatment (DHPM) in cyclophosphamide-induced immunosuppressed mice. DHPM facilitated the conjugation of WPI and galacto-oligosaccharide, and inhibited the generation of fluorescent advanced glycation end products (AGEs) and pentosidine. The conjugates demonstrated a significant immune recovery effect on CTX-induced immunosuppressed mice, as evidenced by the enhancement of IgG antibody levels (from 3.5 to 4.1) and the reduction of the levels of immunosuppressive effector factors TGF-β (from 148.1 to 111.2) and IFN-γ (from 34.4 to 17.9). Furthermore, the conjugates exhibited a notable ability to repair histological lesion in the spleen of CTX-induced immunosuppressed mice. Spleen transcriptomics revealed that the Marco, Klrc3 and Cd209b genes were associated with the immune enhancement activity of the conjugates. Metabolomic analysis identified arginine biosynthesis, sphingolipid metabolism, alanine, aspartate and glutamate metabolism, and phenylalanine, tyrosine and tryptophan biosynthesis as key pathways in the immune enhancement activity of the conjugates. Metabolomics combined with transcriptomics indicated the importance of macrophage activation in the restoration of immunosuppressed mice’s immunity by the conjugates. Therefore, the improvement in immunity observed with WPI-galacto-oligosaccharide conjugates may be related to the activation of macrophages.

Association between endothelial function and skin advanced glycation end-products (AGEs) accumulation in a sample of predominantly young and healthy adults

BackgroundIn populations with chronic disease, skin autofluorescence (SAF), a measure of long-term fluorescent advanced glycation end-products (AGEs) accumulation in body tissues, has been associated with vascular endothelial function, measured using flow-mediated dilation (FMD). The primary aim of this study was to quantify the relationship between endothelial function and tissue accumulation of AGEs in adults from the general population to determine whether SAF could be used as a marker to predict early impairment of the endothelium.MethodsA cross-sectional study was conducted with 125 participants (median age: 28.5 y, IQR: 24.4–36.0; 54% women). Endothelial function was measured by fasting FMD. Skin AGEs were measured as SAF using an AGE Reader. Participant anthropometry, blood pressure, and blood biomarkers were also measured. Associations were evaluated using multivariable regression analysis and were adjusted for significant covariates.ResultsFMD was inversely correlated with SAF (ρ = -0.50, P < 0.001) and chronological age (ρ = -0.51, P < 0.001). In the multivariable analysis, SAF, chronological age, and male sex were independently associated with reduced FMD (B [95% CI]; -2.60 [-4.40, -0.80]; -0.10 [-0.16, -0.03]; 1.40 [0.14, 2.67], respectively), with the multivariable model adjusted R2 = 0.31, P < 0.001.ConclusionsHigher skin AGE levels, as measured by SAF, were associated with lower FMD values, in a predominantly young, healthy population. Additionally, older age and male participants exhibited significantly lower FMD values, corresponding with compromised endothelial function. These results suggest that SAF, a simple and inexpensive marker, could be used to predict endothelial impairment before the emergence of any structural artery pathophysiology or classic cardiovascular disease risk markers.Trial registrationThe study was prospectively registered with the Australian New Zealand Clinical Trials Registry (ACTRN12621000821897) and concurrently entered into the WHO International Clinical Trials Registry Platform under the same ID number.

Inhibitory effect of chlorogenic acid and vanillic acid on fluorescent advanced glycation end products formation in low-temperature-processed pork meat

This work aimed to investigate the effects of chlorogenic acid (CA) and vanillic acid (VA) on structural changes in myofibrillar protein (MP) and fluorescent advanced glycation end products (fAGEs) formation in low-temperature-processed pork meat. Raw pork was prepared, different concentrations (0, 0.005%, 0.010%, 0.020%, 0.040%) of CA or VA were added, and then heated at 50 °C for 12 h. The results suggested that the degree of lipid oxidation significantly declined with increase in amounts of CA (from 12.166 ± 0.469 to 4.661 ± 0.333) or VA (from 11.771 ± 0.355 to 5.451 ± 0.362), and carbonyls, surface hydrophobicity, tryptophan fluorescence intensity, and protein oxidation products also showed a significant downward trend (p < 0.05). Compared with the control (498.183 ± 10.849), there were marked decrease of fAGEs intensity in samples containing CA (70.958 ± 4.114) or VA (76.667 ± 3.882). Besides, mitigating capacity of CA on fAGEs accumulation was just greater than that of VA. Therefore, CA and VA can impede MP and lipid oxidation of raw pork, which further reduce fAGEs formation in low-temperature-processed pork meat. This study is expected to provide a new strategy to prevent the oxidation of MP and reduce fAGEs contents in the meat industry.

Balancing Maillard reaction products formation and antioxidant activities for improved sensory quality and health benefit properties of pan baked buns

This study investigated the impact of processing temperatures (190 °C, 210 °C, and 230 °C) and durations (7 min, 10 min, and 14 min) on the formation of Maillard reaction products (MRPs) and antioxidant activities in pan baked buns. Key Maillard reaction indicators, including glyoxal (GO), methylglyoxal (MGO), 5-hydroxymethylfurfural (5-HMF), melanoidins, and fluorescent advanced glycation end products (AGEs) were quantified. The results demonstrated significant increases in GO, MGO, 5-HMF contents (p < 0.05), and antioxidant activities (p < 0.05) when the buns were baked at 210 °C for 14 min, 230 °C for 10 min and 14 min. However, the interior MRPs of baked buns were minimally affected by the baking temperature and duration. Prolonged heating temperatures and durations exacerbated MRPs production (43.8 %–1038 %) in the bottom crust. Nonetheless, this process promoted the release of bound phenolic compounds and enhanced the antioxidant activity. Heating induces the thermal degradation of macromolecules in food, such as proteins and polysaccharides, which releases bound phenolic compounds by disrupting their chemical bonds within the food matrix. Appropriate selections of baking parameters can effectively reduce the formation of MRPs while simultaneously improve sensory quality and health benefit of the pan baked buns. Considering the balance between higher antioxidant properties and lower MRPs, the optimal thermal parameters for pan baked buns were 210 °C for 10 min. Furthermore, a normalized analysis revealed a consistent trend for GO, MGO, 5-HMF, fluorescent AGEs, and melanoidins. Moreover, MRPs were positively correlated with total contents of phenolic compounds, ferric-reducing antioxidant power (FRAP), and color, but negatively correlated with moisture contents and reducing sugars. Additionally, the interaction between baking conditions and Maillard reactions probably contributed to enhanced primary flavors in the final product. This study highlights the importance of optimizing baking parameters to achieve desirable MRPs levels, higher antioxidant activity, and optimal sensory attributes in baked buns.

Bone turnover markers in the preoperative assessment of bone quality - A prospective investigation of bone microstructure and advanced glycation endproducts in lumbar fusion patients.

Effective tools to evaluate bone quality preoperatively are scarce and the standard method to determine bone quality requires an invasive biopsy. A non-invasive, and preoperatively available method for bone quality assessment would be of clinical value. The purpose of this study is to investigate the associations of bone formation marker, serum bone alkaline phosphatase (BAP), and bone resorption marker, urine collagen cross-linked N-telopeptide (uNTX) to volumetric bone mineral density (vBMD), fluorescent advanced glycation endproducts (fAGEs) and bone microstructure. A cross-secional analysis using prospective data of patients undergoing lumbar spinal fusion was performed. BAP and uNTX were preoperatively collected. Quantitative computed tomography (QCT) was performed at the lumbar spine (vBMD ≤ 120mg/cm3 osteopenic/osteoporotic). Bone biopsies from the posterior superior iliac spine were obtained and evaluated with multiphoton fluorescence microscopy for fAGEs and microcomputed tomography (µCT) for bone microarchitecture. Correlations between BAP/uNTX to vBMD, fAGEs and µCT parameters were assessed with Spearman's ρ. Receiver operating characteristic (ROC) analysis evaluated BAP and uNTX as predictors for osteopenia/osteoporosis. Multivariable linear regression models adjusting for age, sex, BMI, race and diabetes mellitus determined associations between BAP/uNTX and fAGEs. 127 prospectively enrolled patients (50.4% female, 62.5 years, BMI 28.7kg/m2) were analyzed. uNTX (ρ=-0.331,p < 0.005) and BAP (ρ=-0.245,p < 0.025) decreased with cortical fAGEs, and uNTX (ρ=-0.380,p < 0.001) decreased with trabecular fAGEs. BAP and uNTX revealed no significant correlation with vBMD. ROC analysis for BAP and uNTX discriminated osteopenia/osteoporosis with AUC of 0.477 and 0.561, respectively. In the multivariable analysis, uNTX decreased with increasing trabecular fAGEs after adjusting for covariates (β = 0.923;p = 0.031). This study demonstrated an inverse association of bone turnover markers and fAGEs. Both uNTX and BAP could not predict osteopenia/osteoporosis in the spine. uNTX reflects collagen characteristics and might have a complementary role to vBMD, as a non-invasive tool for bone quality assessment in spine surgery.

Antiglycating Effects of Spirulina platensis Aqueous Extract on Glucose-Induced Glycation of Bovine Serum Albumin.

Glucose, the predominant carbohydrate in the human body, initiates nonenzymatic reactions in hyperglycemia, potentially leading to adverse biochemical interactions. This study investigates the interaction between glucose and Bovine Serum Albumin (BSA), along with the protective effects of Spirulina platensis PCC 7345 aqueous extract. Phycobiliproteins (phycocyanin, phycoerythrin, and allophycocyanin) in the extract were quantified using spectrophotometry. The extract's anti-glycation potential was assessed by analyzing its effects on albumin glycation, fluorescent advanced glycation end products (AGEs), thiol group oxidation, and β-amyloid structure generation. Additionally, its antidiabetic potential was evaluated by measuring α-amylase and α-glucosidase enzyme inhibition. Results indicate that the Spirulina extract significantly mitigated ketoamine levels, fluorescence, and protein-carbonyl production induced by glucose, demonstrating a 67.81 % suppression of AGE formation after 28 days. Moreover, it effectively inhibited amyloid formation in BSA cross-linkages. These findings suggest the potential of S. platensis as an anti-glycation and antidiabetic agent, supporting its consideration for dietary inclusion to manage diabetes and associated complications.

Revealing the Hypoglycemic Effect of Red Yeast Rice: Perspectives from the Inhibition of α-Glucosidase and the Anti-Glycation Capability by Ankaflavin and Monascin

Red yeast rice dietary supplements have been proven to ameliorate hyperglycemia, but the mechanism was unclear. In this work, ankaflavin (AK) and monascin (MS), as typical pigments derived from red yeast rice, were found to exert noteworthy inhibitory ability against α-glucosidase, with an IC50 of 126.5 ± 2.5 and 302.6 ± 2.5 μM, respectively, compared with acarbose (IC50 = 341.3 ± 13.6 μM). They also exhibited mixed-type inhibition of α-glucosidase in vitro and caused fluorescence quenching through the static-quenching process. Molecular-docking studies indicated that AK and MS bind to amino acid residues outside the catalytic center, which induces structural changes in the enzyme, thus influencing its catalytic activity. The anti-glycation ability of Monascus-fermented products was evaluated, and they exhibited a high inhibition rate of 87.1% in fluorescent advanced glycation end-product formation at a concentration of 0.2 mg mL−1, while aminoguanidine showed a rate of 75.7% at the same concentration. These results will be significant in broadening the application scope of Monascus pigments, especially AK and MS, in treating type 2 diabetes.

Quercetin decreases fructose drinking in model of fructose-induced insulin resistance. Unexpected uric acid and TBARS lowering effect of methyl cellulose vehicle and fructose combination.

The aim of this study was to improve insulin sensitivity in fructose-treated animals by ingestion of flavonoid quercetin. Several signs of insulin resistance have been developed in rats by drinking 10% fructose solution for 9 weeks. The effect of 6-week-gavage-administrated quercetin (20 mg/kg/day in 1% methyl cellulose solution) was monitored. Rats of the control groups received methyl cellulose vehicle as well. The most striking result of the quercetin treatment was the normalization of the fructose solution drinking to the level of drinking water intake. In addition, quercetin supplementation considerably decreased the plasma glucose and Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) index in rats consuming fructose. Surprisingly, fructose ingestion did not elevate plasma uric acid, thiobarbituric acid reactive substances, nitrotyrosine, or advanced glycation end products fluorescence. Instead, a reduction of the above parameters was observed. In summary, these results indicate that quercetin supplementation reduces fructose drinking and decreases plasma glucose and the HOMA-IR index. Furthermore, methyl cellulose, in combination with fructose, causes uric acid - lowering, antioxidant and anti-glycation effects. Thus, methyl cellulose possibly shifts fructose metabolism in favor of the utilization of antioxidant features of fructose. Our results call for using methyl cellulose in sweetened beverages and other sweetened food.

Effects of fibrillation combined with glycation by different chain length sugars on structural and functional properties of soybean protein

The key objective of this study was to investigate the effects of fibrillation combined with glycation of soybean protein isolate (SPI) on the protein structure and functional properties. SPI fibrils alone, glycated proteins and glycated fibrils with different chain lengths (glucose–G, maltose–M and dextran–D) were prepared and characterized by spectroscopy and microscopy methods. The results of the O-phthalaldehyde assay, ultraviolet–visible spectroscopy and fluorescent advanced glycation endproducts indicated the degree of glycation. The thioflavin T fluorescence assay, transmission electron microscopy (TEM) and Fourier-transform infrared (FTIR) spectroscopy results demonstrated that the fibril morphology improved, and more flexible and aggregated fibrils were produced after glycation, further improving the protein functional properties. With EAI and ESI values of 37.31 m2/g and 33.80%, respectively, the emulsifying properties of SPI fibrils glycated by dextran were higher than the others. Foam properties and antioxidant activity were highest for the fibrils glycated by glucose. These results are of scientific significance for in-depth understanding and reasonable regulation of protein functional properties for industrial production in a complex food system.

Mentha piperita silver nanoparticle-loaded hydrocolloid film for enhanced diabetic wound healing in rats.

To investigate the role of Mentha piperita silver nanoparticle-loaded carbopol gel for enhanced wound healing in a diabetic rat model. This research further aims to explore bioactive compounds derived from Mentha piperita obtained from high altitude. Methanolic extracts of Mentha piperita (MP), Mentha spicata (MS) and Mentha longifolia (ML) were used to synthesise silver nanoparticles (AgNP). AgNP synthesis was confirmed by ultraviolet-visible (UV-Vis) spectroscopy, X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR) and scanning electron microscopy (SEM). The antioxidant activity was assessed by 2, 2-diphenyl-1-picrylhydrazyl (DDPH) assay. Antiglycation potential was determined by measuring the fluorescent advanced glycation end products. The bioactive compound identified in the Mentha piperita methanolic (MPM) fraction through electrospray ionisation tandem mass spectrometric analysis (ESI-MS) was responsible for the highest antiglycation. The effects of MPM and MPM.AgNP-loaded Carbopol (Sanare Lab, India) on wound healing were compared in male, alloxan-induced, diabetic albino rats (200-250g), divided into control and treated groups. Effects on wound healing were assessed via histopathology. UV-Vis and FTIR confirmed NP synthesis with peaks for flavonoids and polyphenols. SEM and XRD explored the cubical, 30-63nm crystalline NP. The maximum antioxidant and antiglycation potential was observed in order of; MP.AgNP>MS.AgNP>ML.AgNP. The highest antioxidant activity was observed by methanolic and aqueous MP.AgNPs (88.55% and 83.63%, respectively) at 2mg.ml-1, and (75.16% and 69.73%, respectively) at 1mg.ml-1, compared to ascorbic acid (acting as a positive control, 90.01%). MPM.AgNPs demonstrated the best antiglycation potential of 75.2% and 83.3% at 1mg.ml-1 and 2mg.ml-1, respectively, comparable to positive control (rutin: 88.1%) at 14 days post-incubation. A similar trend was observed for antimicrobial activity against Bacillus subtilis, Micrococcus luteus and Escherichia coli with an inhibition zone of 21mm, 21.6mm and 24.6mm. Rosmarinic acid was the active compound present in Mentha piperita, as identified by ESI-MS. MPM.AgNP-loaded Carbopol resulted in 100% wound closure compared with control at 20 days post-wounding. In the treatment group, re-epithelialisation was achieved by day 18, compared with 25 days for the positive control group. MPM.AgNP-loaded Carbopol demonstrated safer and more effective biological properties, hence accelerating the diabetic excision wound healing process in alloxan-induced diabetic rats.

Inhibition of fluorescent advanced glycation end-products by ferulic acid and chlorogenic acid: A fluorescence spectroscopy and molecular docking study

The effects of ferulic acid (FA) and chlorogenic acid (CGA) on fluorescent advanced glycation end-products (fAGEs) were investigated through the Maillard reaction. Model systems were incubated with different concentrations (0, 10, 20, 40, 80, and 160 μg/mL) of FA or CGA at 55 °C for 12 h, and fluorescence intensity of advanced glycation end-products (AGEs) was measured. After adding 160 μg/mL FA and CGA, the fluorescence intensity of AGEs was suppressed by 15.988% ± 0.556% and 16.544% ± 0.275%, respectively (P < 0.05). Compared with control group, free amino groups levels were the highest in model systems containing 160 μg/mL FA (0.096 ± 0.011 mg l-leucine equivalent/mL) and CGA (0.130 ± 0.000 mg l-leucine equivalent/mL) (P < 0.05). Carbonyls content decreased in a dose-dependent fashion with increasing concentrations of FA and CGA (P < 0.05). Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) results demonstrated that FA and CGA could impede the generation of bovine serum albumin (BSA)-glucose cross-linking substances. Spectroscopy results indicated that the binding constant of BSA-CGA was higher than that of BSA-FA. Meanwhile, molecular docking results suggested that the binding affinity of CGA to BSA was greater than to FA. These results suggested that CGA had a stronger inhibitory effect on the fluorescence intensity of AGEs. Therefore, FA and CGA may be potent natural antioxidants in mitigating the accumulation of AGEs during food thermal processing.

Formation of Maillard reaction products in a model bread system of different gluten-free flours.

In this study, we determined the levels of Maillard-type products (furosine, free fluorescent advanced glycation end products, 3-deoxyglucosone, methylglyoxal, and N-ε-carboxymethyllysine) in a model gluten-free bread made of wholegrain white, brown, wild, red, and black rice flour, as well as of yellow and purple corn flour. The total protein, lysine, arginine, and cysteine contents were found to relate directly to the formation of Maillard-type products. The malvidin, ferulic, syringic, sinapic, and p-coumaric acids present in gluten-free breads were effective against the formation of furosine, fluorescent compounds, and dicarbonyls, but were ineffective in mitigating CML. Although the bread formulated with purple corn flour had the lowest levels of furosine and fluorescent compounds, this formulation led to an increase in N-ε-carboxymethyllysine and adversely affected the bread's aroma, on account of the presence of polyphenols responsible for a bitter aroma, which were at their highest concentration (1942.34µg/g) in this bread.

Multiphoton imaging of the monosachharide induced formation of fluorescent advanced glycation end products in tissues.

We studied the in vitro rate of fluorescent advanced glycation end products (fAGEs) formation with multiphoton microscopy in different porcine tissues (aorta, cornea, kidney, dermis, and tendon). These tissues were treated with d-glucose, d-galactose, and d-fructose, three primary monosaccharides found in human diets. We found that the use of d-fructose resulted in the highest glycation rate, followed by d-galactose and then d-glucose. Moreover, compared to non-collagen tissue constituents such as elastic fibers and cells, the rate of tissue glycation was consistently higher in collagen, suggesting that collagen is a more sensitive target for fAGE formation. However, we also found that collagen in different tissues exhibits different rates of fAGE formation, with slower rates observed in tightly packed tissues such as cornea and tendon. Our study suggests that for fAGE to be developed into a long-term glycemic biomarker, loosely organized collagen tissues located in the proximity of vasculature may be the best targets.

Anti-glycation and phytochemical properties of cinnamon stem-bark water extract

The study evaluated the ability of cinnamon stem-bark water extract (CWE) to break established cross-links formed between proteins and advanced glycation end-products (AGEs) as well as its anti-glycation effect. The extract showed a dose-dependent anti-glycation effect against total fluorescent AGEs (FAGEs) derived from both glucose and fructose. CWE recorded a uniform IC50 value of 0.13 mg/mL for both glucose and fructose-derived FAGEs while aminoguanidine, a well-known synthetic anti-glycative agent gave IC50 values of 0.14 mg/mL for the glucose and 0.17 mg/mL for the fructose derived FAGEs. The anti-glycative effect of CWE was also significantly higher than aminoguanidine against total immunogenic AGE (TIAGEs) in both sugar models (p &lt; 0.001). While CWE and aminoguanidine showed weak protein cross-link breaking activity selectively on fructose-derived protein cross-links already formed, none whatsoever was detected exerted on the established glucose-derived protein cross-links. Phytochemical screening revealed the presence of several important secondary metabolites which may have contributed to the anti-glycative effect of CWE. Gas chromatography mass spectrometry enabled the identification of (+)-alpha-tocopherol acetate, a chain breaker, in the methanol fraction of CWE. Although CWE showed great potential for inhibition of formation of major types of AGEs, it appears to be poor in breaking established cross-links formed between proteins and AGEs.

Molecularly imprinted thermosensitive probe based on fluorescent advanced glycation end products to detect α-dicarbonyl compounds and inhibit pyrraline formation.

A thermal-sensitive molecularly imprinted optosensing probe based on fluorescent advanced glycation end products (AGEs) was prepared by one-pot hydrothermal synthesis. Carbon dots (CDs) derived from fluorescent AGEs were used as the luminous centers, while molecularly imprinted polymers (MIPs) were wrapped outside of theCDs to form specific target recognition sites to highly selectively adsorbthe intermediate product of AGEs of 3-deoxyglucosone (3-DG). Thermosensitive N-isopropylacrylamide (NIPAM) was combined with acrylamide (AM) as co-functional monomers, and ethylene glycol dimethacrylate (EGDMA) was chosen as across-linker for targeting identification and detection of 3-DG. Under optimal conditions, the fluorescence of MIPs could be gradually quenched with the adsorption of 3-DG on the surface of MIPs in the linear range of 1-160μg/L, and the detection limit was 0.31μg/L. The spiked recoveries of MIPs ranged from 82.97 to 109.94% in two milk samples, and the relative standard deviations were all less than 1.8%. In addition, the inhibition rate for non-fluorescent AGEs of pyrraline (PRL) was 23% by adsorbing 3-DG in the simulated milk system of casein and D-glucose, indicating that temperature-responsive MIPs not only could detect the dicarbonyl compound 3-DG quickly and sensitively, but also had an excellent inhibitory effect on AGEs.

Germ-Free C57BL/6 Mice Have Increased Bone Mass and Altered Matrix Properties but Not Decreased Bone Fracture Resistance.

The gut microbiome impacts bone mass, which implies a disruption to bone homeostasis. However, it is not yet clear how the gut microbiome affects the regulation of bone mass and bone quality. We hypothesized that germ-free (GF) mice have increased bone mass and decreased bone toughness compared with conventionally housed mice. We tested this hypothesis using adult (20- to 21-week-old) C57BL/6J GF and conventionally raised female and male mice (n = 6-10/group). Trabecular microarchitecture and cortical geometry were measured from micro-CT of the femur distal metaphysis and cortical midshaft. Whole-femur strength and estimated material properties were measured using three-point bending and notched fracture toughness. Bone matrix properties were measured for the cortical femur by quantitative back-scattered electron imaging and nanoindentation, and, for the humerus, by Raman spectroscopy and fluorescent advanced glycation end product (fAGE) assay. Shifts in cortical tissue metabolism were measured from the contralateral humerus. GF mice had reduced bone resorption, increased trabecular bone microarchitecture, increased tissue strength and decreased whole-bone strengththat was not explained by differences in bone size, increased tissue mineralization and fAGEs, and altered collagen structure that did not decrease fracture toughness. We observed several sex differences in GF mice, most notably for bone tissue metabolism. Male GF mice had a greater signature of amino acid metabolism, and female GF mice had a greater signature of lipid metabolism, exceeding the metabolic sex differences of the conventional mice. Together, these data demonstrate that the GF state in C57BL/6J mice alters bone mass and matrix properties but does not decrease bone fracture resistance. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).