Accumulation Of AGEs Research Articles

Relationship Between Advanced Glycation End Products Tissue Accumulation and Frailty in Patients Undergoing Cardiac Rehabilitation.

The advanced glycation end products (AGEs), which can be assessed through skin autofluorescence (SAF), have been linked to chronic kidney disease (CKD), diabetes mellitus (DM), and aging. However, it is unknown how frailty and SAF levels are associated with cardiovascular disease (CVD). We enrolled 1,000 consecutive CVD patients who participated in phase II cardiac rehabilitation (CR) and underwent assessment of SAF between November 2015 and September 2017 at Juntendo University Hospital. Of these, 48 patients were excluded as duplicate cases, and a deficiency in SAF data led to the exclusion of an additional 146 patients. The final analysis included 806 patients. Seventy percent of patients were male, and the mean age was 67.0 ± 12.9 years. In this study, the patients were divided into two groups (high SAF group and low SAF group) based on the median SAF level (2.9 a.u.), which is known as a cutoff value to increase the risk of CVD in previous studies. Compared with the low SAF group (n = 368, 45.7%), the high SAF group (n = 438; 54.3%) was older, and the Kihon Checklist (KCL) total score and prevalence of DM and CKD were significantly higher (all, P < 0.05). Multivariate regression analyses demonstrated that age was the only independent associated factor (P < 0.05) in the low SAF group. Conversely, in the high SAF group, creatinine, hemoglobin A1c (HbA1c) and the sub-total KCL score (1 - 20) were independently associated with SAF levels (all, P < 0.05). Frailty assessed by KCL is one of the factors significantly correlated with the accumulation of AGEs as well as creatinine, HbA1c and brain natriuretic peptide (BNP) levels in the high SAF group of patients with CVD undergoing phase II CR, who have the higher risk of the onset of CVD and all-cause mortality.

L-Theanine Extends the Lifespan of Caenorhabditis elegans by Reducing the End Products of Advanced Glycosylation.

L-theanine, a non-protein amino acid naturally occurring in tea leaves, is recognized for its antioxidant, anti-inflammatory, and neuroprotective properties. Despite its known benefits, the mechanisms by which L-theanine influences lifespan extension remain poorly understood. This study investigated the effects of L-theanine on the lifespan of Caenorhabditis elegans and explored the underlying mechanisms. Our findings indicate that L-theanine significantly diminishes the accumulation of advanced glycation end products (AGEs), which are biomarkers closely linked to aging and age-related diseases. Through an AGE-level analysis, we observed that L-theanine, when administered during early adulthood, notably extended the lifespan of Caenorhabditis elegans under both normal and high-glucose-induced stress conditions. L-theanine enhanced the lifespan under typical conditions and provided protective effects against high-glucose-induced stress. A further analysis demonstrated that L-theanine extends the lifespan of Caenorhabditis elegans by modulating the DAF-2/DAF-16 insulin-like signaling pathway and reducing the accumulation of advanced glycation end products (AGEs). In summary, this study identified L-theanine as a potential anti-aging intervention that extends the lifespan by reducing AGE accumulation and regulating insulin-like signaling pathways. These findings provide new insights for developing anti-aging strategies and lay the groundwork for further research on the potential benefits of L-theanine in mammals. Future studies could explore the molecular mechanisms, test L-theanine in mammalian models, and assess the long-term side effects.

Investigating the association between cholinergic integrity and amyloid burden using cholinergic anatomy and [18F]‐FEOBV PET in individuals with Down Syndrome from the ABC‐DS and TRC‐DS cohorts

AbstractBackgroundAdults with Down Syndrome (DS) have the highest risk of developing Alzheimer’s disease (AD) worldwide. Triplication of the amyloid precursor protein gene on chromosome 21 results in early amyloid accumulation and Alzheimer’s pathology. The cholinergic system is known to decline early in the development of AD and plays a fundamental role in observed cognitive deficits. In the present work, we assess the association between amyloid accumulation and cholinergic integrity.Method188 individuals from the ABC‐DS cohort (U01AG051406; U01AG051412; U19AG068054) were assessed cross‐sectionally. Basal forebrain volumes were calculated using the ScLimbic FreeSurfer pipeline for the basal forebrain (Ch1‐Ch4) and the DnSeg pipeline for Ch4 volumes. Linear regressions were performed between centiloid values, age, and basal forebrain volumes. Nine individuals recruited for a TRC‐DS sub‐study underwent a multimodal imaging assessment, including [11C]‐PiB PET and [18F]‐FEOBV PET imaging. Global centiloid values were calculated using PMOD, with regional SUVRs calculated using PetSurfer with GTM for partial volume corrections. Linear regressions were performed between global centiloid, regional [11C]‐PiB SUVR, and regional [18F]‐FEOBV SUVR.ResultIn ABC‐DS and the TRC‐DS sub‐study, global amyloid accumulation was positively associated with age (p&lt;0.0001 and p=0.041). Age and global amyloid accumulation were negatively associated with Ch1‐Ch4 (p&lt;0.005) and Ch4 (p&lt;0.05) cholinergic basal forebrain volumes. In the TRC‐DS sub‐study, global amyloid accumulation negatively associated with [18F]‐FEOBV uptake in the amygdala (p&lt;0.05), statistical trends were observed in the thalamus and left entorhinal cortex (p&lt;0.08). Regional [11C]‐PiB uptake was negatively associated with [18F]‐FEOBV uptake in the left inferior temporal and right pericalcarine cortices (p&lt;0.05), with statistical trends observed in the right amygdala, left pericalcarine, and left fusiform cortices (p&lt;0.08).ConclusionMeasures of cholinergic integrity were found to decline with increasing amyloid in individuals with DS across two cohorts, utilizing different methodologies. In the ABC‐DS cohort, we observed a reduction in basal forebrain nuclei volume with increasing age and amyloid accumulation. The basal forebrain contains cholinergic and noncholinergic neurons. To understand whether this volume reduction was from cholinergic loss, we assessed the integrity of cholinergic terminals using [18F]‐FEOBV PET and found regional cholinergic integrity negatively associated with both global and regional amyloid accumulation.

Measurement of Advanced Glycation End Products (AGEs) Accumulated in Dentin Collagen.

In the Maillard reaction, reducing sugars bind to proteins in a non-enzymatic manner, and the final products are collectively named, advanced glycation end products (AGEs). AGEs accumulate in the human body with age and cause various disorders in tissues and cells. In this study, pentosidine, an AGE that can be stably measured, was used to investigate the differences in pentosidine accumulation within dentin, and whether the results can indicate age. High-performance liquid chromatography was used to measure pentosidine, an AGE that accumulates in dentin collagen, in extracted teeth with no caries and a clear history. The dentin pentosidine concentration increased with age, with a higher pentosidine concentration observed at the enamel-dentin junction aspect than at the pulp cavity aspect. A close correlation was observed between the dentin pentosidine level and age. These findings suggest the utility of measuring accumulation of AGEs in dentin collagen as an indicator of age.

Long-duration type 1 diabetes is associated with deficient cortical bone mechanical behavior and altered matrix composition in human femoral bone.

Type 1 diabetes (T1D) is associated with an increased risk of hip fracture beyond what can be explained by reduced bone mineral density, possibly due to changes in bone material from accumulation of advanced glycation end products (AGEs) and altered matrix composition, though data from human cortical bone in T1D are limited. The objective of this study was to evaluate cortical bone material behavior in T1D by examining specimens from cadaveric femora from older adults with long-duration T1D (≥50years; n= 20) and age- and sex-matched non-diabetic controls (n= 14). Cortical bone was assessed by mechanical testing (4-point bending, cyclic reference point indentation, impact microindentation), AGE quantification (total fluorescent AGEs, pentosidine, carboxymethyl-lysine (CML)), and matrix composition via Raman spectroscopy. Cortical bone from older adults with T1D had diminished post-yield toughness to fracture (-30%, P=.036), elevated levels of AGEs (pentosidine, +17%, P=.039), lower mineral crystallinity (-1.4%, P=.010), greater proline hydroxylation (+1.9%, P=.009), and reduced glycosaminoglycan (GAG) content (-1.3%, P<.03) compared to non-diabetics. In multiple regression models to predict cortical bone toughness, cortical tissue mineral density (Ct.TMD), CML, and Raman spectroscopic measures of enzymatic collagen crosslinks and GAG content remained highly significant predictors of toughness, while diabetic status was no longer significant (adjusted R2> 0.60, P<.001). Thus, impairment of cortical bone to absorb energy following long-duration T1D is well explained by AGE accumulation and modifications to the bone matrix. These results provide novel insight into the pathogenesis of skeletal fragility in individuals with T1D.

The Discrete Grey Power Model Based on Aging Accumulation and its Application

Abstract Accumulation generation is one of the key methods to reduce the randomness of data series, which significantly enhances the predictive performance of the grey prediction model. By integrating a degenerate operator, a novel accumulating discrete grey power model is introduced, capable of substantially enhancing the accuracy of predictions. This method allows for the flexible adjustment of the accumulation coefficient in the modeling data, mitigating the fluctuations in model parameters due to data perturbations, and effectively minimizing the loss of differential information. The outcomes of practical numerical examples demonstrate that the proposed aging accumulation discrete grey power model exhibits superior performance.

Modeling aging and retinal degeneration with mitochondrial DNA mutation burden.

Somatic mitochondrial DNA (mtDNA) mutation accumulation has been observed in individuals with retinal degenerative disorders. To study the effects of aging and mtDNA mutation accumulation in the retina, a polymerase gamma (POLG) exonuclease-deficient model, the PolgD257A mutator mice (D257A), was used. POLG is an enzyme responsible for regulating mtDNA replication and repair. Retinas of young and older mice with this mutation were analyzed invivo and exvivo to provide new insights into the contribution of age-related mitochondrial (mt) dysfunction due to mtDNA damage. Optical coherence tomography (OCT) image analysis revealed a decrease in retinal and photoreceptor thickness starting at 6 months of age in mice with the D257A mutation compared to wild-type (WT) mice. Electroretinography (ERG) testing showed a significant decrease in all recorded responses at 6 months of age. Sections labeled with markers of different types of retinal cells, including cones, rods, and bipolar cells, exhibited decreased labeling starting at 6 months. However, electron microscopy analysis revealed differences in retinal pigment epithelium (RPE) mt morphology beginning at 3 months. Interestingly, there was no increase in oxidative stress and parkin-mediated mitophagy in the ages analyzed in the retina or RPE of D257A mice. Additionally, D257A RPE exhibited an accelerated rate of autofluorescence cytoplasmic granule formation and accumulation. Mt markers displayed different abundance in protein lysates obtained from retina and RPE samples. These findings suggest that the accumulation of mtDNA mutations leads to impaired mt function and accelerated aging, resulting in retinal degeneration.

Effects of age, elastin density, and glycosaminoglycan accumulation on the delamination strength of human thoracic and abdominal aortas

Aortic dissection is a life-threatening condition caused by layer separation. Despite extensive research, the relationship between the aortic wall's structural integrity and dissection risk remains unclear. Glycosaminoglycan (GAG) accumulation and elastin loss are suspected to play significant roles. We investigated how age-related changes in aortic structure affect dissection susceptibility. Peeling tests were performed on longitudinal and circumferential thoracic (TA) and abdominal aortic (AA) strips from 35 donors aged 13–76 years (mean 38 ± 15 years, 34 % female). GAG, elastin, collagen, and smooth muscle cell (SMC) contents were assessed using bidirectional histology. Young TAs resisted longitudinal peeling better than circumferential, with delamination strengths of 65.4 mN/mm and 44.2 mN/mm, respectively. Delamination strength decreased with age in both directions, more rapidly longitudinally, equalizing at ∼20–25 mN/mm in older TAs. Delamination strength in AAs was 22 % higher than in TAs. No sex differences were observed. GAG density increased, while elastin density decreased by 2.5 % and 4 % per decade, respectively. Collagen density did not change with age, while SMC density decreased circumferentially. GAGs partially mediated the reduction in longitudinal delamination strength due to aging, while circumferential strength reduction was not mediated by changes in either GAG or elastin densities. This study explains why aortic dissections are more common in TAs, especially in older individuals, and why they typically propagate spirally. TAs exhibit lower delamination strength compared to AAs and experience strength reduction with age, a phenomenon linked to increased GAG accumulation and elastin loss. These findings enhance our understanding of the pathophysiological mechanisms behind aortic dissection. Statement of significanceThis work explores the age-dependent relationships between delamination strength in human aortas and wall structural content. We investigated 35 human aortas from donors aged 13 to 76 years, providing new insights into the biomechanical and histological factors that influence aortic dissection risk. Our findings elucidate how variations in elastin, glycosaminoglycan, collagen, and smooth muscle cell densities impact the structural integrity of the aorta, contributing significantly to the understanding of aortic dissection mechanisms.

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

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

European bilberry extract reduces high-temperature baked food-induced accumulation of Nε-carboxymethyllysine and Nε-carboxyethyllysine in vivo

This study aimed to investigate the effect of European bilberry extract (EBE) on the accumulation of Nε-carboxymethyllysine (CML) and Nε-carboxyethyllysine (CEL) in rats exposed to a high advanced glycation end products (AGEs) diet. We found that EBE reduced high AGEs diet-induced accumulation of free-CML, bound-CML, free-CEL, and bound-CEL in the serum, kidney, skin, and brain. EBE also inhibited high AGEs diet-induced accumulation of bound-CML and bound-CEL in the uterus, ovary, stomach, duodenum, and colon. Meanwhile, EBE attenuated high AGEs diet-induced accumulation of free-CML and free-CEL in the muscle, bone, joint, and eyes. In addition, EBE ameliorated high AGEs diet-induced accumulation of free-CML and bound-CML in the liver, free-CML in the ovary, and bound-CML in the thyroid gland. EBE had no effect on the accumulation of free-CML, bound-CML, free-CEL, and bound-CEL in the adrenal gland and free-CML and free-CEL in the heart caused by a high AGEs diet. We did not observe AGEs accumulation in the pancreas, aorta, lung, spleen, and adipose tissues. This study revealed the in vivo distribution of CML and CEL exposed to a high AGEs diet and the effect of EBE on reducing the accumulation of CML and CEL in the specific target tissues.

Leukocyte Extracellular Vesicles Predict Progression of Systolic Dysfunction in Heart Failure with Mildly Reduced Ejection Fraction (LYCHEE) - A Prospective, Multicentre Cohort Study.

Risk stratification in heart failure with mildly-reduced ejection fraction (HFmrEF) remains challenging. We evaluated the predictive value of advanced glycation end products (AGEs) and plasma concentrations of extracellular vesicles (EVs) for the systolic and diastolic dysfunction progression in HFmrEF patients. Skin AGE accumulation was measured using AGE Reader. Plasma EV concentrations were measured using flow cytometry. Among 74 patients enrolled, 13 (18%) had systolic dysfunction progression and 5 (7%) had diastolic dysfunction progression during 6.5months follow-up. Leukocyte EVs concentrations were higher in patients with systolic dysfunction progression (p = 0.002) and predicted the progression with 75.0% sensitivity and 58.3% specificity, independent of other clinical variables (OR 4.72, 95% CI 0.99-22.31). Skin AGE levels and concentrations of other EV subtypes were not associated with systolic or diastolic dysfunction progression. Increased leukocyte EVs concentrations are associated with 4.7-fold higher odds of systolic dysfunction progression in HFmrEF patients.

Navigating the Intersection of Glycemic Control and Fertility: A Network Perspective.

The rising incidence of metabolic diseases is linked to elevated blood glucose levels, contributing to conditions such as diabetes and promoting the accumulation of advanced glycation end products (AGEs). AGEs, formed by non-enzymatic reactions between sugars and proteins, build up in tissues and are implicated in various diseases. This article explores the relationship between glycemic control and AGE accumulation, focusing on fertility implications. A computational model using network theory was developed, featuring a molecular database and a network with 145 nodes and 262 links, categorized as a Barabasi-Albert scale-free network. Three main subsets of nodes emerged, centered on glycemic control, fertility, and immunity, with AGEs playing a critical role. The transient receptor potential vanilloid 1 (TRPV1), a receptor expressed in several tissues including sperm, was identified as a key hub, suggesting that the modulation of TRPV1 in sperm by AGEs may influence fertility. Additionally, a novel link between glycemic control and immunity was found, indicating that immune cells may play a role in endocytosing specific AGEs. This discovery underscores the complex interplay between glycemic control and immune function, with significant implications for metabolic, immune health, and fertility.

Advanced glycation end products impair the repair of injured tendon: a study in rats

BackgroundThe AGEs levels in tissues of diabetics and elderly tend to be higher than in normal individuals. This study aims to determine the effects of AGEs on Achilles tendon repair.Materials and methodsThirty-six male eight-week-old Sprague Dawley rats were selected in this study. The rats were randomly divided into two experimental groups and a control group after the transection of the Achilles tendon. During the tendon repair, the experimental groups were injected around the Achilles tendon with 350mmol/L (low dose group) and 1000mmol/L (high dose group) D-ribose 0.2 ml respectively to increase the AGEs level, while in the control group were given the same amount of PBS. The injections were given twice a week for six weeks. Collagen-I, TNF-α, and IL-6 expression in the healed Achilles tendon was assessed. Additionally, macroscopic, pathological, and biomechanical evaluations of Achilles tendon repair were conducted.ResultsThe repaired Achilles tendons in the high dose group showed severe swelling and distinctive adhesions. The histological score went up with the increase of the AGEs in the Achilles tendon (p<0.001). TNF- α and IL-6 in the Achilles tendon increased (p<0.001, p<0.001), and the production of collagen-I decreased with the accumulation of AGEs in the repaired Achilles tendon (p<0.001). The tensile strength of Achilles tendon in the high dose group was impaired significantly.ConclusionIn current study, the compromised tendon repair model induced by AGEs was successfully established in rat. The study demonstrated that AGEs significantly impair Achilles tendon repair.

Cosmic‐ray exposure age accumulated in near‐Earth space: A carbonaceous chondrite case study

AbstractThis study investigates the expected cosmic‐ray exposure (CRE) of meteorites if they were to be ejected by a near‐Earth object, that is, from an object already transferred to an Earth‐crossing orbit by an orbital resonance. Specifically, we examine the CRE ages of CI and CM carbonaceous chondrites (CCs), which have some of the shortest measured CRE ages of any meteorite type. A steady‐state near‐Earth carbonaceous meteoroid probability density function is estimated based on the low‐albedo near‐Earth asteroid population, including parameters such as the near‐Earth dynamic lifetime, the impact probability with the Earth, and the orbital parameters. This model was then compared to the orbits and CRE ages of the five CC falls with precisely measured orbits: Tagish Lake, Maribo, Sutter's Mill, Flensburg, and Winchcombe. The study examined two meteoroid ejection scenarios for CI/CM meteoroids: Main Belt collisions and ejections in near‐Earth space. The results indicated that applying a maximum physical lifetime in near‐Earth space of 2–10 Myr to meteoroids and eliminating events evolving onto orbits entirely detached from the Main Belt (Q &lt; 1.78 au) significantly improved the agreement with the observed orbits of carbonaceous falls. Additionally, the CRE ages of three of the five carbonaceous falls have measured CRE ages one to three orders of magnitude shorter than expected for an object originating from the Main Belt with the corresponding semi‐major axis value. This discrepancy between the expected CRE ages from the model and the measured ages of three of the carbonaceous falls indicates that some CI/CM meteoroids are being ejected in near‐Earth space. This study proposes a nuanced hypothesis involving meteoroid impacts and tidal disruptions as significant contributors to the ejection and subsequent CRE age accumulation of CI/CM chondrites in near‐Earth space.

Advanced glycation end products promote the progression of endometrial cancer via activating the RAGE/CHKA/PI3K/AKT signaling pathway.

Endometrial cancer (EC) is a common malignant tumor that is closely associated with metabolic disorders such as diabetes and obesity. Advanced glycation end products (AGEs) are complex polymers formed by the reaction of reducing sugars with the amino groups of biomacromolecules, mediating the occurrence and development of many chronic metabolic diseases. Recent research has demonstrated that the accumulation of AGEs can affect the tumor microenvironment, metabolism, and signaling pathways, thereby affecting the malignant progression of tumors. However, the mechanism by which AGEs affect EC is unclear. Our research aimed to investigate how AGEs promote the development of EC through metabolic pathways and to explore their potential underlying mechanisms. Our experimental results demonstrated that AGEs upregulated the choline metabolism mediated by choline kinase alpha (CHKA) through the receptor for advanced glycation end products (RAGE), activating the PI3K/AKT pathway and enhancing the malignant biological behavior of EC cells. Virtual screening and molecular dynamics simulation revealed that timosaponin A3 (timo A3) could target CHKA to inhibit AGE-induced progression of EC and that a newly discovered CHKA inhibitor could be a novel targeted inhibitor for the treatment of EC. This study provides new therapeutic strategies and contributes to the treatment of EC.

Exploring Natural Products to Control Type 2 Diabetes Mellitus through Targeting Advanced Glycation End Products

Objective: Cardiovascular disease (CVD) and diabetes mellitus (DM) are the pressing global health issue, with advanced glycation end products (AGEs) playing a crucial role in its development. AGEs are harmful compounds formed through chronic exposure to elevated blood glucose levels and oxidative stress, both of which are prevalent in diabetes mellitus. These molecules have detrimental effects on vascular function, inflammation, and oxidative stress, exacerbating CVD progression. Conventional strategies for managing AGEs are often limited by side effects and insufficient efficacy, driving the need for alternative approaches. This review investigates the intricate relationship between AGEs, diabetes mellitus, and CVD, with a focus on the therapeutic potential of natural products-particularly phenolic compounds. The review explores how AGEs contribute to the pathogenesis of diabetes-related complications and their impact on cardiovascular health. It examines the molecular mechanisms underlying AGE formation and the inhibitory effects of various natural compounds on this process. Additionally, the review assesses preclinical and clinical evidence supporting the efficacy of these natural agents in mitigating AGE-induced damage. By highlighting the significant role of AGEs in diabetes and CVD, the study underscores the potential of natural products to counteract AGE accumulation. It provides an in-depth analysis of AGE biochemistry, their sources, and the effects of different natural products on AGE formation. The review concludes by emphasizing the promise of natural compounds in reducing oxidative stress and inflammation, and thereby lowering the risk of cardiovascular complications associated with diabetes. This comprehensive overview advocates for the integration of natural products into therapeutic strategies for managing AGE-mediated cardiovascular and diabetic conditions

Taurine, alpha lipoic acid and vitamin B6 ameliorate the reduced developmental competence of immature mouse oocytes exposed to methylglyoxal

Advanced glycation end products (AGEs) are the final products of the Maillard reaction, formed through the interaction of carbohydrates and proteins. Reactive dicarbonyl compounds such as methylglyoxal (MGO) serve as precursors for AGEs formation. Elevated levels of MGO/AGEs are observed in conditions like obesity, polycystic ovarian syndrome (PCOS), and diabetes, negatively impacting oocyte development. Previous studies have shown that hydrogen sulfide, a gasotransmitter with anti-AGEs effects, is produced in a process influenced by vitamin B6. R-α-lipoic acid (ALA) inhibits protein glycation and AGEs formation while stimulating glutathione (GSH) production. Taurine mitigates oxidative stress and acts as an anti-glycation compound, preventing in vitro glycation and AGEs accumulation. This study aimed to explore the ameliorative effects of a micronutrient support (Taurine, ALA and B6: TAB) on mouse oocytes challenged with MGO. Our results indicate that MGO reduces oocyte developmental competence, while TAB supplementation improves maturation, fertilization, and blastocyst formation rates. TAB also restores cell lineage allocation, redox balance and mitigates mitochondrial dysfunction in MGO-challenged oocytes. Furthermore, cumulus cells express key enzymes in the transsulfuration pathway, and TAB enhances their mRNA expression. However, TAB does not rescue MGO-induced damage in denuded oocytes, emphasizing the supportive role of cumulus cells. Overall, these findings suggest that TAB interventions may have significant implications for addressing reproductive dysfunctions associated with elevated MGO/AGEs levels. This study highlights the potential of TAB supplementation in preserving the developmental competence of COCs exposed to MGO stress, providing insights into mitigating the impact of dicarbonyl stress on oocyte quality and reproductive outcomes.

Association between Mediterranean Diet and Advanced Glycation End Products in University Students: A Cross-Sectional Study.

The aim of this study was to evaluate the association between the Mediterranean diet (MD) and the accumulation of advanced glycation end products (AGEs) measured by skin autofluorescence. This cross-sectional study included 1016 healthy students from the University of Split, Croatia. Participants completed a self-administered questionnaire. Adherence to the MD was assessed using the Mediterranean Diet Serving Score (MDSS), and tissue AGEs accumulation was measured using the AGE Reader mu (DiagnOptics). Multivariate linear regression was used in the analysis. Students' age and female gender were associated with higher levels of AGEs, which was likewise found for greater coffee intake, adequate olive oil consumption, smoking, and lower levels of physical activity. Higher consummation of vegetables and eating breakfast regularly were associated with lower AGEs levels. The overall MD adherence was not associated with AGEs, possibly due to very low overall compliance to the MD principles among students (8.3% in women and 3.8% in men). Health perception was positively associated with the MD and nonsmoking and negatively with the perceived stress level, while AGEs did not show significant association with self-rated students' health. These results indicate that various lifestyle habits are associated with AGEs accumulation even in young and generally healthy people. Hence, health promotion and preventive measures are necessary from an early age.

Enhancement of Waterlogging Tolerance and Improvement of Grain Quality in Waxy Maize With Exogenous EDAH: A Mixture of Ethephon and Diethyl Aminoethyl Hexanoate

ABSTRACTGlobal warming has led to more frequent extreme weather events, such as heavy summer rains, in the Huang‐Huai‐Hai region. These events significantly impede the growth and development of waxy maize in the area and disrupt the stable progression of the industry. However, there is a lack of effective agricultural measures to mitigate the impact of waterlogging, and the underlying regulation mechanisms remain unclear. To fill this knowledge gap, we conducted a two‐year experiment to assess whether exogenous EDAH (a mixture of ethephon and diethyl aminoethyl hexanoate (DA‐6), ethephon: DA‐6 = 27%: 3%) application during the waxy maize V6 stage, combined with 10 days of waterlogging treatment at the V6, VT and R2 growth stages. The results indicate that exogenous EDAH mitigates the adverse effects of waterlogging stress to a certain extent. It is noteworthy that exogenous EDAH increases the leaf area index and photosynthetic parameters of waxy maize, enhances the activity of catalase in ear leaves at the R3 stage, inhibits the accumulation of malondialdehyde and delays premature aging of plants. Furthermore, exogenous EDAH delays premature ripening of grains caused by waterlogging, increases the moisture content of fresh waxy maize grains during the fresh edible period, but does not effectively mitigate the yield losses caused by waterlogging. However, exogenous EDAH effectively improves grain quality under waterlogging stress, increasing the soluble sugar content and total protein content while reducing starch content, ultimately enhancing the edibility of fresh ears. Through TOPSIS comprehensive evaluation, it can be inferred that exogenous EDAH effectively mitigates the overall impact of waterlogging on waxy maize at both the V6 and VT stages. This research sheds light on potential strategies to mitigate the adverse effects of waterlogging on agricultural productivity and grain quality.

Accumulation of Intracellular Protein Advanced Glycation End Products Alters Cellular Homeostasis for Protein Clearance in Pancreatic Ductal Epithelial Cells.

Protein advanced glycation end products (AGEs) can be formed via nonenzymatic glycation and accumulated intracellularly to disrupt cellular homeostasis for protein clearance. Here, we investigated the formation particulars of intracellular protein AGEs and sought to elucidate the molecular events implicated in the impact of cellular clearance systems. The formation and accumulation of intracellular protein AGEs increased protein aggregation and protease resistance, potentially overwhelming the ubiquitin-proteasome system (UPS). At high levels of protein AGEs, the abundance of many E3 ligases decreased and the overall ubiquitination level was reduced, all of which indicated decreased UPS activity. On the other hand, autophagy activity was stimulated, as evidenced by the upregulation of autophagy marker LC3II and important proteins in autophagosome and autolysosome formation, as well as downregulation of mTOR. Understanding the functional impacts of intracellular protein AGEs on the UPS and autophagy could pave the way for the future development of pharmaceutical agents targeting AGE-related diseases.