Formation Of Advanced Glycation End Products Research Articles

D-mannose promotes diabetic wound healing through inhibiting advanced glycation end products formation in keratinocytes

BackgroundDiabetic chronic foot ulcers pose a significant therapeutic challenge around the world, resulting in adverse effects and complications in patients. D-mannose is enriched in cirtus peel and exerts beneficial effects among various diseases, especially against inflammation-related disorders.MethodsHere, we examined the potential effect of D-mannose during wound healing process in streptozotocin (STZ)-induced diabetes mice in vivo and by culturing keratinocytes under high glucose condition in vitro. The skin lesion healing was recorded in photos and evaluated by histochemical staining. What’s more, the advanced glycation end products (AGEs) concentration in blood and mice skin was quantified. Apoptotic cells were assessed by flow cytometry and Western blotting. Inflammatory cytokines and cellular differential gene expression levels were measured by real-time PCR. The expression of the AMPK/Nrf2/HO-1 signaling-related molecules was determined by Western blotting.ResultsWe first found that topical supplementation of D-mannose remarkably improved skin wound healing in diabetes mice. Furthermore, both in vivo and in vitro experiments demonstrated that D-mannose reduced the AGEs generation. Mechanistically, D-mannose inhibited AGEs, then upregulated AMPK/Nrf2/HO-1 signaling in the context of high glucose to maintain keratinocyte normal functions, which positively influenced macrophage and fibroblast to accelerate diabetic wound healing. Noteworthily, these protective effects of D-mannose were abolished by the pretreatment with inhibitors of AGEs or AMPK.ConclusionAs far as we know, this is the first study exploring the protective role of D-mannose on diabetic wound healing via topical supplementation. We find that D-mannose protects keratinocytes from high glucose stimulation via inhibition of AGEs formation as well as orchestrates inflammatory microenvironment in diabetic wounded skin, suggesting its supplementation as a potential therapy to promote refractory wound healing in diabetic patients.

Assessing the role of Berberine as an inhibitor of advanced glycation end products (AGEs) formation using in vitro and molecular interaction studies.

Glycation and aggregation of proteins have garnered more interest in recent years. Glycation leads to the formation of protein aggregates and advanced glycation ends (AGEs) that play crucial roles within several pathological conditions. The objective of our study is to gain a deeper understanding of the formation of AGEs and aggregates of human serum albumin (HSA) in the presence of methylglyoxal and the protective effects of the phytochemical berberine. HSA was incubated with methylglyoxal and different concentrations of berberine for 7-14 days at 35-37 °C. Methylglyoxal resulted in the formation of AGEs, fibrillar aggregates, and hydrophobic protein patches in HSA, as was evident from AGE fluorescence, ThT and ANS fluorescence studies. It also disrupted the secondary structure of HSA shown by CD spectroscopy. All these parameters were restored towards native HSA in the glycated HSA + berberine samples. Molecular docking was employed to identify the critical HSA residues implicated in the HSA-berberine interaction and also to determine the spontaneous binding of berberine on the HSA sub-domain favoring the thermodynamic binding. The binding energy between HSA-berberine was found to be -9.1 kcal/mol. Various types of forces like hydrophobic interactions, polar forces, hydrogen bonds, etc are were at play between the HSA and berberine interaction. Since MGO level is increased in pathological conditions such as type II diabetes, there is a chance that increased MGO concentration could cause glycation of HSA, leading to decreased levels of HSA, as observed in pathological circumstances. The binding of berberine to lysine and arginine residues might be linked to its antiglycation potential as these amino acids play an important role in the glycation of proteins. Nevertheless, additional inquiries are needed to substantiate this claim. Thus, our study characterizes AGEs and aggregates of clinically important protein HSA.

Inhibition of advanced glycation end-products in frozen-thawed and reheated pork by pigskin gelatin hydrolysates.

This study investigated the effects of pigskin gelatin hydrolysates (PGH, 4 %) as a cryoprotectant on the formation of advanced glycation end-products (AGEs) in pre-heated pork subjected to freeze-thaw cycles and subsequent reheating. During the freeze-thaw process, PGH significantly mitigated the increase in α-dicarbonyl precursors (α-DPs) and AGEs compared to the control group. Specifically, the levels of glyoxal and methylglyoxal decreased by 4.26 % and 6.12 %, respectively, although this inhibition was not statistically significant (P > 0.05). The concentrations of Nε-(carboxymethyl)lysine (CML) and Nε-(carboxyethyl)lysine (CEL) content in the PGH-treated group were 2.86 %-33.19 % and 4.33 %-24.02 % lower than those in the control group, respectively. After reheating (100 °C, 10 min), AGEs levels increased by 1.94 % to 123.21 %, while the levels of glyoxal and methylglyoxal decreased by 17.00 % and 15.24 %, respectively. The addition of PGH significantly reduced AGEs formation after reheating compared to the control (P < 0.01). These results suggest that PGH is effective as a cryoprotectant, inhibiting the formation of harmful AGEs during freeze-thaw cycles and subsequent reheating of pre-heated pork.

Bioactive fraction of Musa balbisiana seed mitigates D-galactose-induced brain aging via SIRT1/PGC-1α/FoxO3a activation and intestinal barrier dysfunction by modulating gut microbiota and core metabolites

Aging is an inevitable biological process, and emerging research has highlighted the potential of dietary and pharmacological interventions to decelerate the trajectory of age-related diseases and prolong the health span. This study evaluates the protective effects of Musa balbisiana seed on healthy aging using D-galactose-induced accelerated aging rats. The results suggested that the bioactive ethyl acetate fraction of Musa balbisiana seed extract (BF) exhibited protective effects against aging-induced oxidative stress by reducing oxidative DNA damage, advanced glycation end-product formation, and malondialdehyde levels while restoring antioxidant and glyoxalase enzyme activities. BF also ameliorated neurodegeneration by decreasing acetylcholinesterase enzyme activity and amyloid beta plaque formation. Histopathological analysis demonstrated the protective effects of BF against brain aging, liver disruption, renal damage, and intestinal barrier dysfunction. BF further restored intestinal permeability by upregulating the tight junctions (zonula occludens 1 and 2, claudin 1,2,3 and 4, and occludin) and mucin (mucin 2 and mucin 5ac) gene expression while downregulating the expression of inflammatory cytokines (IL-1β, IL-6, and TNF-α). BF significantly induced the phosphorylation of FoxO3a proteins and upregulated the gene expression of SIRT1, PGC-1α, and TFAM in the hippocampus. Next-generation sequencing (NGS) of 16s rRNA amplicons of fecal metagenomics DNA and metabolites profiling showed that BF intervention restructured the gut microbiota and altered core metabolites related to cholesterol metabolism. Overall, our findings demonstrated the multifaceted protective effects of Musa balbisiana seed against D-galactose-induced aging.

New Insights into the Role of SGLT-2 Inhibitors in the Prevention of Dementia.

Diabetes mellitus (DM) is a chronic disease associated with numerous complications, including cardiovascular diseases, nephropathy, and neuropathy. Sodium-glucose cotransporter 2 (SGLT-2) inhibitors, a class of novel antidiabetic agents, have demonstrated promising therapeutic effects beyond glycemic control, with potential benefits extending to the cardiovascular and renal systems. Recently, research has increasingly focused on exploring the potential role of SGLT-2 inhibitors in preventing dementia. The aim of this review is to summarize the current research suggesting that SGLT-2 inhibitors, such as empagliflozin and dapagliflozin, may have neuroprotective effects that reduce dementia risk and improve cognitive function in type 2 diabetes patients. These benefits are likely due to better glycemic control, reduced oxidative stress, and less advanced glycation end-product (AGE) formation, all linked to neurodegeneration. Despite these promising findings, existing studies are limited by small sample sizes and short follow-up durations, which may not adequately capture long-term outcomes. To establish more robust evidence, larger-scale, long-term randomized controlled trials (RCTs) involving diverse populations are needed. These studies should involve diverse populations and focus on understanding the mechanisms behind the neuroprotective effects. Addressing these limitations will provide clearer guidelines for using SGLT-2 inhibitors in dementia prevention and management. This will help improve therapeutic strategies for cognitive health in diabetic patients.

Mitigating methylglyoxal-induced glycation stress: the protective role of iron, copper, and manganese coordination compounds in Saccharomyces cerevisiae.

Glycation-induced stress (G-iS) is a physiological phenomenon that leads to the formation of advanced glycation end-products, triggering detrimental effects such as oxidative stress, inflammation, and damage to intracellular structures, tissues, and organs. This process is particularly relevant because it has been associated with various human pathologies, including cancer, neurodegenerative diseases, and diabetes. As therapeutic alternatives, coordination compounds with antioxidant activity show promising potential due to their versatility in attenuating oxidative stress and inflammation. Herein, we investigated the antioxidant-related protective potential of a series of complexes: [Cu(II)(BMPA)Cl2] (1), [Fe(III)(BMPA)Cl3] (2), and [Cl(BMPA)MnII-(μ-Cl)2-MnII(BMPA)-(μ-Cl)- MnII(BMPA)(Cl)2]•5H2O (3), all synthesized with the ligand bis-(2-pyridylmethyl)amine (BMPA) in Saccharomyces cerevisiae exposed to G-iS caused by methylglyoxal (MG). Pre- treatment with complexes 1-3 proved highly effective, increasing yeast tolerance to G-iS and attenuating mitochondrial dysfunction. This observed phenotype appears to result from a reduction in intracellular oxidation, lipid peroxidation levels, and glycation. Additionally, an increase in the activity of the antioxidant enzymes superoxide dismutase and catalase was observed following treatment with complexes 1-3. Notably, although complexes 1-3 provided significant protection against oxidative stress induced by H2O2 and menadione, their protective role was more effective against MG-induced glycation stress. Our results indicate that these complexes possess both antiglycation and antioxidant properties, warranting further investigation as potential interventions for mitigating glycation and oxidative stress-related pathologies.

ANTIOXIDANT, INHIBITION OF ADVANCED GLYCATION END-PRODUCT FORMATION AND ANTIMICROBIAL ACTIVITIES OF OCIMUM GRATISSIMUM (SCENT LEAF) METHANOLIC LEAF EXTRACT AGAINST Escherichia coli AND Bacillus SPP

The study investigates the antioxidant, inhibition of advanced glycation end-product formation and antimicrobial activities of methanolic leaf extract of Ocimum gratissimum. GC-MS, qualitative, antioxidant scavenging and antiglycation activities of the extract of Ocimum gratissimum were determined using standard procedures. The antimicrobial activity was evaluated by agar well diffusion method. Minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) were determined using standard methods. The GC-MS analysis of Ocimum gratissimum leaf revealed the presence of 49 compounds with P –cymene been the most abundant. The phytochemical screening of the extract shows the presence of alkaloids, tannins, phenolic, flavonoids, saponins etc. The in-vitro antioxidant assay of the extract was found to have ?-carotene, lycopene, total phenolic compounds, total flavonoid compounds, reducing power and DPPH scavenging activities. The extract showed significant inhibitory effects on the formation of compounds containing two carbonyl groups and Advanced Glycated End products formation with IC50 of 75.85 ±4.87 µg/mL. Agar well diffusion assay was characterized by inhibition zones of 21.0 ± 0.30, 19.66 ± 0.20, 33.78± 0.30 and 33.25 ± 0.40 mm for Escherichia coli and Bacillus spp respectively at 250 mg/ml for Ocimum gratissimum and 25 mg/ml for tetracycline solution. The MIC values for E.coli and Bacillus spp were 33.33, 66.67, 0.78 and 0.78 for both extract and tetracycline while their MBC values were 66.67, 133.00, 1.56 and 1.56 respectively. MBC/ MIC values showed that Ocimum gratissimum extract and tetracycline had bactericidal effects. These results indicated that Ocimum gratissimum possesses antioxidant, prevents glycation and has antimicrobial activities.

Health Benefits of Olive Leaf: The Focus on Efficacy of Antiglycation Mechanisms.

Olive leaves have been a therapeutic herbal agent for diseases for centuries. Olive leaves contain many health-beneficial nutrients and bioactive components. There is much evidence for the positive effects of the phenolic compounds they contain on health. The main active phenolic component in olive leaves is oleuropein, which can constitute 6%-9% of the leaf's dry matter and has been intensively studied for its promising results/effects on human health. In addition, olive leaf provides health benefits through bioactive components, such as secoiridoids, flavonoids, triterpenes, and lignans. The anti-inflammatory, antioxidant, anticancer, antidiabetic, and antihypertensive properties of bioactive components, especially oleuropein, are well known. In addition, various health benefits, such as neuroprotective effects and microbiota modulation, are also mentioned. In recent years, in vitro studies have shown that olive leaves and bioactive components from olive leaves may have antiglycation effects. Currently, it is thought that the components found in olive leaves have a direct or indirect antiglycation effect. It is thought that, their direct effects include reducing the interaction between sugars and amino acids, nucleic acids, and lipids and sequestering reactive dicarbonyl species, and their indirect effects include preventing the formation of advanced glycation end-products (AGEs) by reducing inflammation and oxidative stress. However, in vivo and clinical studies are needed to prove these mechanisms and understand how their metabolism works in the human body. This review examines the beneficial health effects of olive leaves and their potential antiglycation role.

Comparative assessment of antioxidant and antiglycation properties of Leucas species

Abstract BACKGROUND: The genus Leucas is an aromatic plant and belongs to the Lamiaceae family. They are rich in secondary metabolites. The benefits of Leucas in curing many ailments such as coughs, colds, diarrhea, diabetes, inflammation, and skin diseases have made it an Ayurvedic component. Hence, the present study aims to evaluate the phytochemical, antioxidant, and antiglycation properties of methanol and aqueous extract from three Leucas species, viz, Leucas aspera Link, Leucas zeylanica (L.) W.T.Aiton, and Leucas longifolia Benth. METHODS: Dry powders of the whole part of three species of Leucas were extracted with methanol and aqueous solution. Qualitative analysis of secondary metabolites such as flavonoids, phenolics, alkaloids, glycosides, terpenoids, and tannins was performed by using standard phytochemical procedures. Total phenol, flavonoid, and alkaloid contents were estimated by spectrophotometric methods. The superoxide radical scavenging activity, 1, 1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging activity, hydrogen peroxide radical scavenging activity, and ferric-reducing power methods are in vitro models. Bovine serum albumin glycation assay was used to evaluate the in vitro antiglycation activity of extracts. RESULTS: The highest percentage of extraction yield was observed in the methanolic extract of all Leucas species compared to the aqueous extract. The preliminary phytochemical tests reveal the presence of various bioactive secondary metabolites such as phenols, flavonoids, alkaloids, steroids, terpenoids, and glycosides. These extracts show that L. aspera has high DPPH activity, superoxide radical scavenging activity, hydrogen peroxide radical scavenging activity, and ferric-reducing antioxidant power compared to L. zeylanica and L. longifolia. The methanolic and aqueous extract of L. aspera exhibited more significant inhibitory (96.70 ± 1.78 and 90.33 ± 1.65%) effects on advanced glycation end products formation in bovine serum albumin glycation systems compared to standard aminoguanidine (99.45 ± 1.37%) than L. zeylanica and L. longifolia. The methanol extract of L. aspera is rich in phenols, flavonoids, and alkaloids and has strong antiglycation and antioxidant properties. CONCLUSION: The strong antiglycation and antioxidant activity of all three Leucas species suggests its possible role in combating diseases associated with diabetic complications and oxidative stress.

Increased Levels of Circulating Methylglyoxal Have No Consequence for Cerebral Microvascular Integrity and Cognitive Function in Young Healthy Mice.

Diabetes and other age-related diseases are associated with an increased risk of cognitive impairment, but the underlying mechanisms remain poorly understood. Methylglyoxal (MGO), a by-product of glycolysis and a major precursor in the formation of advanced glycation end-products (AGEs), is increased in individuals with diabetes and other age-related diseases and is associated with microvascular dysfunction. We now investigated whether increased levels of circulating MGO can lead to cerebral microvascular dysfunction, blood-brain barrier (BBB) dysfunction, and cognitive impairment. Mice were supplemented or not with 50mM MGO in drinking water for 13weeks. Plasma and cortical MGO and MGO-derived AGEs were measured with UPLC-MS/MS. Peripheral and cerebral microvascular integrity and inflammation were investigated. Cerebral blood flow and neurovascular coupling were investigated with laser speckle contrast imaging, and cognitive tests were performed. We found a 2-fold increase in plasma MGO and an increase in MGO-derived AGEs in plasma and cortex. Increased plasma MGO did not lead to cerebral microvascular dysfunction, inflammation, or cognitive decline. This study shows that increased concentrations of plasma MGO are not associated with cerebral microvascular dysfunction and cognitive impairment in healthy mice. Future research should focus on the role of endogenously formed MGO in cognitive impairment.

Enrichment of shortcrust pastry cookies with bee products: polyphenol profile, in vitro bioactive potential, heat-induced compounds content, colour parameters and sensory changes

Bee products, including bee pollen (BP) and bee bread (BB) are natural sources that contain a diverse range of bioactive compounds. The objective of this study was to investigate the potential of BP and BB to enhance the functional properties of shortcrust pastry cookies. The impact on BP and BB on the colour parameters, polyphenolic compounds content, heat-induced compounds content (acrylamide, furfural, 5-hydroxymethylfurfural (HMF)), antioxidant properties, and inhibitory effects against advanced glycation end products (AGEs) formation and acetylcholinesterase (AChE) activity was examine by enriching cookies with 3 and 10% of BP or BB. The incorporation of BP or BB resulted in a notable darkening of the cookies. The spectroscopic and chromatographic analyses revealed that the cookies enriched with bee products exhibited an elevated content of phenolic compounds. The antioxidant activity (AA) of the enriched cookies exhibited an average increase of 2- to 3-fold in the ABTS test and 2-fold in the DPPH test. All cookies exhibited inhibitory potential against AGEs formation, witch inhibitory rates ranging from 10.64 to 46.22% in the BSA-GLU model and 1.75–19.33% in BSA-MGO model. The cookies enriched with 10% BP were characterised by to the highest level of AChE activity inhibition (13.72%). The incorporation of BB and BP resulted in elevated concentration of acrylamide, furfural, and HMF. Our findings suggest that bee products may serve as a valuable addition to food ingredients, significantly enhancing the functional properties of shortcrust pastry cookies. However, further investigation is necessary to address the increased level of heat-induced compounds.

Relationship between advanced glycation end-products and advanced oxidation protein products in patients with type 2 diabetes with and without albuminuria: A cross-sectional survey.

Literature suggests that oxidative stress plays a crucial role in the progression of diabetes. Since poor glycemic control enhances the formation of advanced glycation end-products (AGEs) and advanced oxidation protein products (AOPP) in individuals with diabetes, exploring the association between glycation and oxidative states in diabetes could also shed light on potential consequences. This study evaluated the effects of albuminuria on AGEs and AOPP levels and measured their relationship in participants with type 2 diabetes (T2D) with or without albuminuria. A cross-sectional, matched case-control study was designed, including 38 T2D subjects with albuminuria and 38 matched T2D subjects with normoalbuminuria. Patients were matched by their body mass index (BMI), age, and duration of diabetes. The unadjusted and adjusted correlation between AGEs and AOPP in the studied groups were analyzed by multiple logistic regression. Using ggplot2, the ties between these two biochemical factors in cases and controls were plotted. This study elucidated a significant association between AGEs and AOPP in participants with normoalbuminuria (r = 0.331, p-value < 0.05), which continued to be significant after controlling for BMI, age, systolic blood pressure (SBP), and diastolic blood pressure (DBP) (r = 0.355, p-value < 0.05). However, there was no significant association between AGEs and AOPP in those with albuminuria in the unadjusted model (r = 0.034, p-value = 0.841) or after controlling for BMI, age, SBP, and DBP (r = 0.076, p-value = 0.685). Oxidation and glycation molecular biomarkers were correlated in patients without albuminuria; however, this association was not observed in those with albuminuria.

Quantitative NMR Analysis of Marine Macroalgae for AGE Inhibition by Methylglyoxal Scavenging.

Reactive carbonyl species (RCS) induce a fundamental form of biological stress that has driven the evolution of diverse mechanisms for minimizing its impact on organismal health. The complications that accompany uncontrolled hyperglycemia exemplify the health implications when RCS stress exceeds the body's capacity to prevent the excessive formation of advanced glycation end-products. Presented here is a novel quantitative NMR (qNMR) technique for evaluating scavengers of the prominent sugar-derived carbonyl methylglyoxal (MGO). This tool was employed to screen the chemical diversity of marine macroalgae extracts, with a focus on species that have a history of consumption by the World's healthiest populations and are subject to global scale aquacultural production. Fucus vesiculosus demonstrated the highest capacity for inhibiting glycation and scavenging MGO. Additionally, the Chondrus cripsus, Gracilaria vermiculophyla, and Gracilaria tikvahiae extracts had a high capacity for scavenging MGO, representing the first report of this activity. This new qNMR methodology presented is highly applicable for screening extracts and compounds from diverse sources, and the results highlight the potential of macroalgae extracts to be employed as RCS and AGE targeting therapeutics and food additives.

Impact of diabetes mellitus on endodontic treatment outcomes

Diabetes mellitus (DM) is a chronic metabolic disorder that affects various systemic functions, including oral health. Its impact on endodontic treatment outcomes has become a significant concern for dental practitioners. The relationship between DM and endodontic outcomes is complex, involving several pathophysiological mechanisms. Hyperglycemia leads to the formation of advanced glycation end-products, causing vascular dysfunction and impaired blood supply to the pulp, which exacerbates pulpal inflammation and increases the risk of necrosis. Additionally, chronic low-grade inflammation and an impaired immune response in diabetic patients contribute to a higher susceptibility to infections, delayed healing, and compromised tissue repair after endodontic procedures. Diabetic patients often experience lower success rates and prolonged recovery following endodontic treatment due to these systemic challenges. Reduced bone healing, persistent periapical lesions, and altered microbial flora are common complications that can hinder treatment success. Effective management of endodontic treatment in diabetic patients requires a multifaceted approach that includes strict glycemic control, the use of enhanced antimicrobial strategies, and the adoption of minimally invasive techniques to reduce tissue trauma. Additionally, patient education and close monitoring of the healing process are essential for minimizing complications. Understanding the pathophysiological interactions between diabetes and pulpal inflammation, as well as the factors that influence healing and success rates, is crucial for optimizing endodontic care in diabetic patients. By addressing both systemic and local factors, dental practitioners can improve the prognosis of endodontic treatment and ensure better outcomes for patients with diabetes. Ongoing research into the mechanisms underlying these complications will further enhance the ability of clinicians to manage endodontic cases effectively in this growing patient population.

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.

Effects of certain phenolic acids on advanced glycation end products formation in glucose-lysine Maillard reaction models

Effects of certain phenolic acids on advanced glycation end products formation in glucose-lysine Maillard reaction models

GC-MS validation and analysis of targeted plasma metabolites related to carbonyl stress in type 2 diabetes mellitus patients with and without acute coronary syndrome.

Methylglyoxal (MG) is responsible for advanced glycation end-product formation, the mechanisms leading to diabetes pathogenesis and complications like acute coronary syndrome (ACS). Sugar metabolites, amino acids and fatty acids are possible substrates for MG. The study aimed to measure plasma MG substrate levels using a validated gas chromatography-mass spectrometry (GC-MS) method and explore their association with ACS risk in type 2 diabetes mellitus (T2DM). The study included 150 T2DM patients with ACS as cases and 150 T2DM without ACS as controls for the analysis of glucose, fructose, ribulose, sorbitol, glycerol, pyruvate, lactate, glycine, serine, threonine, C16:0, C16:1, C18:0, C18:1, C18:2, C18:3, C20:0 and C22:6 by GC-MS. Validated GC-MS methods were accurate, precise and sensitive. Cases significantly differed in plasma MG and metabolite levels except for lactate, C16:0, C18:0, C18:2, and C18:3 levels compared with controls. On multivariable logistic regression, plasma C20:0, C18:1, glycine and glycerol levels had increased odds of ACS risk. On multivariate receiver operating characteristic analysis, a model containing plasma C20:0, C16:1, C18:1, C18:2, serine, glycerol, lactate and threonine levels had the highest area under the curve value (0.932) for ACS diagnosis. In conclusion, plasma C20:0, C16:1, C18:1, glycine, glycerol and sorbitol levels were associated with ACS risk in T2DM.

Methylglyoxal alters collagen fibril nanostiffness and surface potential

Collagen fibrils are fundamental to the mechanical strength and function of biological tissues. However, they are susceptible to changes from non-enzymatic glycation, resulting in the formation of advanced glycation end-products (AGEs) that are not reversible. AGEs accumulate with aging and disease and can adversely impact tissue mechanics and cell-ECM interactions. AGE-crosslinks have been related, on the one hand, to dysregulation of collagen fibril stiffness and damage and, on the other hand, to altered collagen net surface charge as well as impaired cell recognition sites. While prior studies using Kelvin probe force microscopy (KPFM) have shown the effect glycation has on collagen fibril surface potential (i.e., net charge), the combined effect on individual and isolated collagen fibril mechanics, hydration, and surface potential has not been documented. Here, we explore how methylglyoxal (MGO) treatment affects the mechanics and surface potential of individual and isolated collagen fibrils by utilizing atomic force microscopy (AFM) nanoindentation and KPFM. Our results reveal that MGO treatment significantly increases nanostiffness, alters surface potential, and modifies hydration characteristics at the collagen fibril level. These findings underscore the critical impact of AGEs on collagen fibril physicochemical properties, offering insights into pathophysiological mechanical and biochemical alterations with implications for cell mechanotransduction during aging and in diabetes. Statement of significanceCollagen fibrils are susceptible to glycation, the irreversible reaction of amino acids with sugars. Glycation affects the mechanical properties and surface chemistry of collagen fibrils with adverse alterations in biological tissue mechanics and cell-ECM interactions. Current research on glycation, at the level of individual collagen fibrils, is sparse and has focused either on collagen fibril mechanics, with contradicting evidence, or surface potential. Here, we utilized a multimodal approach combining Kelvin probe force (KPFM) and atomic force microscopy (AFM) to examine how methylglyoxal glycation induces structural, mechanical, and surface potential changes on the same individual and isolated collagen fibrils. This approach helps inform structure-function relationships at the level of individual collagen fibrils.

Arabinoxylan from pearl millet bran: Optimized extraction, structural characterization, and its bioactivities

Arabinoxylan (AX) from cereals and millets have garnered attention due to the myriad of their bioactivities. Pearl millet (Pennisetum glaucum) bran, an underexplored milling by-product was used to extract AX (PMAX) by optimized alkali-assisted extraction using Response Surface Methodology and Central Composite Design, achieving a yield of 15.96 ± 0.39 % (w/w) under optimal conditions (0.57 M NaOH, 1:17 g/mL solid-to-liquid ratio, 60 °C, 4 h). Structural analysis revealed that PMAX was primarily composed of arabinose, xylose, glucose, galactose, and mannose (molar ratio 45.1:36.1:10.4:7.1:1.8), with a highly substituted (1 → 4)-linked β-D-xylopyranose backbone and a molecular weight of 794.88 kDa. PMAX displayed a significant reducing power of 0.617, metal chelating activity of 51.72 %, and DPPH, and ABTS radical scavenging activities (64.43 and 75.4 %, respectively at 5 mg/mL). It also demonstrated anti-glycation effects by inhibiting fructosamine (52.5 %), protein carbonyl (53.6 %), and total advanced glycation end products (77.0 %) formation, and reduced protein oxidation products such as dityrosine (84.7 %), kynurenine (80.2 %), and N′-formyl-kynurenine (50.0 %) at 5 mg/mL. PMAX induced the growth of Lactobacillus spp. in vitro and modulate gut microbiota in male Wistar rats by increasing Bacteroidetes and decreasing Firmicutes. These results provide a basis for further research on pearl millet arabinoxylan and its possible nutraceutical application.

Deciphering the anti-diabetic potential of Dipsacus asperoides root: Identification of active compounds and quality assessment

The plant Dipsacus asperoides C. Y. Cheng et T. M. A., has been traditionally utilized as a medicinal plant in China due to its roots known as “Dipsaci Radix”. It is suggested that Dipsaci Radix exhibits antihyperglycemic, hypolipidemic, and antioxidant properties, along with down-regulating effects on advanced glycation end-products (AGEs) formation. However, there are currently no reliable reports on the effective components derived from Dipsaci Radix for anti-diabetes. In this study, the methanol extract and its corresponding ethyl acetate (EA) fraction of Dipsaci Radix were investigated as potential natural sources of antidiabetic agents and antioxidants by in vivo methods. The existence of phenolic components in extract and fraction enhances their antioxidant and antidiabetic properties. This is evidenced by the fact that all isolated phenolic compounds exhibited such properties, with half of them (Compound 2, 4, 5, 8, 10) displaying multidirectional inhibitory effects. Quality evaluation of these active components using high performance liquid chromatography-ultraviolet (HPLC-UV) technology combined with grey relational analysis provides further information regarding the spectrum-effect relationship between active components and their activities. Among them, the presence of the active ingredient “5-O-caffeoylquinic acid” significantly contributes to the antidiabetic and antioxidant properties of Dipsaci Radix. This holds promising applications in traditional health products and cosmeceuticals.