Search Results (783)

Diabetic retinopathy is a complex, microvascular disease that impacts millions of working adults each year. High blood glucose levels from Diabetes Mellitus lead to the accumulation of advanced glycation end-products (AGEs), which promote inflammation and the breakdown of the inner blood retinal barrier (iBRB), resulting in vision loss. This study used an in vitro model of hyperglycemia to examine how endothelial cells (ECs) and Müller glia (MG) collectively regulate molecular transport. Changes in cell morphology, the expression of junctional proteins, and the reactive oxygen species (ROS) of ECs and MG were examined when exposed to a hyperglycemic medium containing AGEs. Trans-endothelial resistance (TEER) assays were used to measure the changes in cell barrier resistance in response to hyperglycemic and inflammatory conditions, with and without an anti-VEGF compound. Both of the cell types responded to hyperglycemic conditions with significant changes in the cell area and morphology, the ROS, and the expression of the junctional proteins ZO-1, CX-43, and CD40, as well as the receptor for AGEs. The resistivities of the individual and dual ECs and MG barriers decreased within the hyperglycemia model but were restored to that of basal, normoglycemic levels when treated with anti-VEGF. This study illustrated significant phenotypic responses to an in vitro model of hyperglycemia, as well as significant changes in the expression of the key proteins used for cell–cell communication. The results highlight important, synergistic relationships between the ECs and MG and how they contribute to changes in barrier function in combination with conventional treatments. Full article

Advanced glycation end-products (AGEs) play a role in the onset/progression of lifestyle-related diseases (LSRD), suggesting that the suppression of AGE-induced effects can be exploited to prevent and treat LSRD. However, AGEs have a variety of structures with different biological effects. Glyceraldehyde (GA) is an intermediate of glucose, and fructose metabolism and GA-derived AGEs (GA-AGEs) have been associated with LSRD, leading to the concept of toxic AGEs (TAGE). Elevated blood TAGE levels have been implicated in the onset/progression of LSRD; therefore, the measurement of TAGE levels may enable disease prediction at an early stage. Moreover, recent studies have revealed the structures and degradation pathways of TAGE. Herein, we provide an overview of the research on TAGE. The TAGE theory provides novel insights into LSRD and is expected to elucidate new targets for many diseases. Full article

Glucagon-like peptide 1 (GLP-1) receptor agonists are frequently used to treat type 2 diabetes and obesity. Despite the development of several drugs for neuropathic pain management, their poor efficacy, tolerance, addiction potential, and side effects limit their usage. Teneligliptin, a DPP-4 inhibitor, has been shown to reduce spinal astrocyte activation and neuropathic pain caused by partial sciatic nerve transection. Additionally, we showed its capacity to improve the analgesic effects of morphine and reduce analgesic tolerance. Recent studies indicate that GLP-1 synthesized in the brain activates GLP-1 receptor signaling pathways, essential for neuroprotection and anti-inflammatory effects. Multiple in vitro and in vivo studies using preclinical models of neurodegenerative disorders have shown the anti-inflammatory properties associated with glucagon-like peptide-1 receptor (GLP-1R) activation. This study aimed to investigate the mechanism of antinociception and the effects of the GLP-1 agonist semaglutide (SEMA) on diabetic neuropathic pain in diabetic rats. Methods: Male Wistar rats, each weighing between 300 and 350 g, were categorized into four groups: one non-diabetic sham group and three diabetic groups. The diabetic group received a single intraperitoneal injection of streptozotocin (STZ) at a dosage of 60 mg/kg to induce diabetic neuropathy. After 4 weeks of STZ injection, one diabetic group was given saline (vehicle), and the other two were treated with either 1× SEMA (1.44 mg/kg, orally) or 2× SEMA (2.88 mg/kg, orally). Following a 4-week course of oral drug treatment, behavioral, biochemical, and immunohistochemical analyses were carried out. The mechanical allodynia, thermal hyperalgesia, blood glucose, advanced glycation end products (AGEs), plasma HbA1C, and spinal inflammatory markers were evaluated. Results: SEMA treatment significantly reduced both allodynia and hyperalgesia in the diabetic group. SEMA therapy had a limited impact on body weight restoration and blood glucose reduction. In diabetic rats, SEMA lowered the amounts of pro-inflammatory cytokines in the spinal cord and dorsal horn. It also lowered the activation of microglia and astrocytes in the dorsal horn. SEMA significantly reduced HbA1c and AGE levels in diabetic rats compared to the sham control group. Conclusions: These results indicate SEMA’s neuroprotective benefits against diabetic neuropathic pain, most likely by reducing inflammation and oxidative stress by inhibiting astrocyte and microglial activity. Our findings suggest that we can repurpose GLP-1 agonists as potent anti-hyperalgesic and anti-inflammatory drugs to treat neuropathic pain without serious side effects. Full article

It was shown earlier that the use of fast protein and metabolites liquid chromatography (FPMLC) and low-cost deep UV–LED-based optical chromatographic sensors with PD-10 desalting columns as a separation element can facilitate the monitoring of patients on chronic peritoneal dialysis (PD). Previously, we established that the first peak in the FPMLC chromatograms of effluent dialysate is mainly responsible for proteins and could be used for the assessment of peritoneal protein loss in patients on PD, while the origin and clinical significance of the other two peaks still remain unclear. Optical absorption and fluorescence spectroscopy in the UV and visible regions of 240…720 nm were used for the analysis of PD effluent chromatographic fractions collected from a drainpipe of the sensor with photometric detection at 280 nm; chromatograms of twenty dialysate samples were processed. The absorption and fluorescence spectra of the first fraction demonstrated peaks at 270 nm and 330 nm, respectively, which is typical for proteins. The absorption spectra of the third fraction revealed the characteristic maxima of creatinine and uric acid, while the fluorescence spectra showed the characteristic peak of indoxyl sulfate 375 nm at 270 nm excitation. The second fraction had a single, extremely wide absorption band, strong fluorescence was observed at 440–450 nm while excited at 370 nm. Such spectral characteristics are typical for advanced glycation end products (AGE). Thus, it was demonstrated that deep UV–LED-based affordable chromatographic sensors could provide significantly more information about the composition of PD effluent dialysate than just the total protein concentration, including the contents of clinically significant metabolites, e.g., indoxyl sulfate and AGE. Moreover, the introduction of optical fluorescence detection could significantly improve the capabilities of such devices. Full article

Background: Type 2 diabetes (T2DM) affects over 500 million people worldwide, and over 50% of this group experience the most common complication, diabetic peripheral neuropathy (DPN). The presence of advanced glycation end-products (AGEs) has been linked with the development of DPN. The present study assessed AGE levels in participants with type 2 diabetes and explored the hypothesis that there may be increased AGE levels in more severe DPN. Methods: A total of 124 participants with T2DM were consecutively recruited, and they underwent skin autofluorescence, clinical assessment for peripheral neuropathy, peripheral nerve ultrasound, nerve conduction studies, and axonal excitability assessment. Results: AGE accumulation showed weak but significant correlations with neuropathy severity and reduced nerve conduction function. However, after adjusting for confounding variables, a linear regression analysis did not reveal significant associations between the AGE levels and neuropathy outcomes. Conclusions: The present study suggests that the accumulation of AGE is not associated with the clinical, electrophysiological, and morphological measures of neuropathy in T2DM. Full article

Background: Diabetic retinopathy is the most common retinal vascular disease, affecting the retina’s blood vessels and causing chronic inflammation, oxidative stress, and, ultimately, vision loss. Diabetes-induced elevated glucose levels increase glycolysis, the main methylglyoxal (MGO) formation pathway. MGO is a highly reactive dicarbonyl and the most rapid glycation compound to form endogenous advanced glycation end products (AGEs). MGO can act both intra- and extracellularly by glycating molecules and activating the receptor for AGEs (RAGE) pathway. Conclusions: This review summarizes the sources of MGO formation and its actions on various cell pathways in retinal cells such as oxidative stress, glycation, autophagy, ER stress, and mitochondrial dysfunction. Finally, the detoxification of MGO by glyoxalases is discussed. Full article

Background: Controlled non-enzymatic glycation reactions are common under normal physiological conditions. However, during elevated blood glucose conditions, the glycation reactions are accelerated, leading to the formation of toxic compounds such as advanced glycation end products (AGEs). Several natural products are now being investigated as protective agents against glycation to preserve blood protein structure and functions. Methods: Human serum albumin (HSA) was glycated with 0.05 M α-D-glucose alone or in the presence of Zingiber officinale Roscoe (ginger) extract (0.781–100 μg/mL) for 10 weeks, and biochemical, biophysical, and computational analyses were carried out. Results: HSA glycated for 10 weeks (G-HSA-10W) resulted in significant production of ketoamines, carbonyl compounds, and AGE pentosidine. Notable structural alterations were observed in G-HSA-10W, ascertained by ultraviolet (UV), fluorescence, and circular dichroism (CD) studies. Antioxidant, anti-glycating, AGEs inhibitory, and antibacterial effects of ginger extracts were observed and attributed to the presence of various phytochemicals. Molecular docking studies suggested that the compounds 8-shagaol and gingerol exhibited strong and multiple interactions with HSA. Molecular simulation analysis suggests HSA attains a high degree of conformational stability with the compounds gingerol and 8-shogaol. Conclusions: These findings showed that ginger extract has an antioxidant function and can prevent glycation-induced biochemical and biophysical alterations in HSA. Thus, aqueous ginger extract can be utilized to combat glycation and AGE-related health issues, especially diabetes, neurological disorders, inflammatory diseases, etc. Full article

Homeostasis preservation is essential for animal survival, and any event that causes a disturbance in homeostasis is defined as a stressor. Here, we aimed to evaluate the effect of scratch brushes and stages as an environmental enrichment to alleviate stress in dairy goats. Twenty-four mixed-breed goats were divided into two groups according to common physiological conditions in breeding farms: milking and dry (milk-producing and non-milk-producing, respectively). Ten days after exposure to environmental enrichment treatment or not (control), blood was sampled. Following the enrichment, we observed a reduction in reactive oxidative stress metabolites, advanced glycation end products (AGEs), and their binding protein (transferrin) in the dry goats, as determined by an ELISA. In contrast, no change in AGEs, along with an increase in transferrin levels, was observed in the milking goats. Moreover, oxytocin levels decreased in the dry and increased in the milking goats, while serotonin levels increased in the dry and remained unchanged in the milking goats. Additionally, gene expression of the cytokines, IL-6 and IL-1ß, and anti-oxidative proteins, lysozyme and transferrin (in peripheral blood leukocytes), as determined by qPCR, presented the same pattern: down-regulation in the dry or up-regulation in the milking goats. In conclusion, a reliable methodology was developed for measuring husbandry stress in goats and to improve dairy goats’ husbandry practice. Current environmental enrichment produced different responsiveness in goats correlated to their physiological status: beneficial effect in dry goats, detrimental effect in milking goats. Full article

Advanced Glycation End Products (AGEs) are formed through non-enzymatic reactions between reducing sugars and proteins, nucleic acids or lipids (for example through hyperoxidation). In diabetes, elevated glucose levels provide more substrate for AGEs formation. AGEs can also be ingested through the diet from foods cooked at high temperatures, or containing much sugar. The present work aimed to review all published randomized controlled trials (RCT) on low-dietary AGE (L-dAGEs) interventions in patients with diabetes. Pubmed, Scopus and Cochrane databases were searched (until 29 February 2024) with appropriate keywords (inclusion criteria: RCT, patients with diabetes, age > 18 years, outcomes related to inflammation, glucose, and lipids; exclusion criteria: non-RCTs, case-series, case reports and Letter to the Editor, or animal studies). The present review was registered to the Open Science Framework (OSF). From 7091 studies, seven were ultimately included. Bias was assessed with the updated Cochrane Risk of Bias tool. A reduction in circulating AGEs was documented in 3/3 studies. No particular differences were documented in glycemic parameters after a L-dAGEs diet. Reductions in glucose levels were observed in one out of six studies (1/6), while HbA1c and HOMA did not change in any study (0/6 and 0/3, correspondingly). Lipid profile also changed in one out of four studies (1/4). More consistent results were observed for oxidative stress (beneficial effects in 3/3 studies) and inflammatory markers (beneficial effects in 4/4 studies). Other athero-protective effects, such as adiponectin increases, were reported. Limitations included the small sample size and the fact that dietary and physical activity habits were not considered in most studies. In conclusion, a L-dAGEs pattern may minimize AGEs accumulation and have beneficial effects on oxidative stress and inflammation indices, while its effects on glycemic and lipemic parameters are inconsistent and modest in patients with diabetes. Full article

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. Full article

Background: Advanced glycation end products (AGEs), a group of food processing byproducts, have been implicated in the development of various diseases. However, the relationship between circulating AGEs and sleep disorders remains uncertain. Methods: This cross-sectional study elucidated the association of plasma AGEs with sleep disorders among 1732 Chinese adults who participated in the initial visit (2019–2020) of the Tongji–Shenzhen Cohort (TJSZC). Sleep behavior was assessed using self-reported questionnaires and precise accelerometers. Plasma levels of AGEs, including Nε-(Carboxymethyl)lysine (CML), Nε-(Carboxyethyl)lysine (CEL), and Nδ-(5-hydro-5-methyl-4-imidazolone-2-yl)-ornithine (MG-H1), were quantified by ultra-high performance liquid chromatography–tandem mass spectrometry (UPLC-MS/MS). Results: In logistic regression, per IQR increment in individual AGEs was associated with an increased odds ratio of short sleep duration (CML: 1.11 [1.00, 1.23]; CEL: 1.16, [1.04, 1.30]), poor sleep quality (CML: 1.33 [1.10, 1.60]; CEL: 1.53, [1.17, 2.00]; MG-H1: 1.61 [1.25, 2.07]), excessive daytime sleepiness (CML: 1.33 [1.11, 1.60]; MG-H1: 1.39 [1.09, 1.77]), and insomnia (CML: 1.29 [1.05, 1.59]). Furthermore, in weighted quantile sum regression and Bayesian kernel machine regression analyses, elevated overall exposure levels of plasma AGEs were associated with an increased risk of sleep disorders, including short sleep duration, poor sleep quality, excessive daytime sleepiness, and insomnia, with CML being identified as the leading contributor. Insufficient vegetable intake and higher dietary fat intake was associated with an increase in plasma CEL. Conclusions: These findings support a significant association between plasma AGEs and sleep disorders, indicating that AGEs may adversely influence sleep health and reducing the intake of AGEs may facilitate preventing and ameliorating sleep disorders. Full article

Chrysanthemum morifolium cv. Fubaiju (CMF) is regarded as one of the three most renowned varieties of white Chrysanthemum in China, and different extraction methods have significant effects on its composition and activities. Therefore, six extractions were used in this study to assess the effects on extracts. The basic chemical composition showed that hot water extract (Hw) had the highest total phenolic content, alkali water immersion-assisted hot water extract (Al) had the highest content of protein, and enzyme-assisted hot water extract (Enz) had the highest content of carbohydrate. The UPLC-Q-Exactive-MS results evinced the presence of 19 small-molecule compounds, including chlorogenic acid, caffeic acid, tuberonic acid glucoside, luteolin-7-O-rutinoside, and other substances. In addition, the antioxidant test found that the Hw exhibited the best 1,1-diphenyl-2-picrylhydrazyl (DPPH) (82.05 ± 1.59 mM TE/mg) and 2,2’-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) (61.91 ± 0.27 mM TE/mg) scavenging ability. The anti-glycation test demonstrated that Enz possessed the most pronounced inhibitory effect on glycation products, including fructosamine and advanced glycation end products (AGEs). Additionally, the Enz also exhibited the most significant inhibitory effect on the protein oxidation product N’-formylkynurenine. The correlation analysis revealed that there was a close relationship between antioxidant properties and glycation resistance of extracts, and tuberonic acid glucoside, 1,3-di-O-caffeoylquinic acid, 1,4-Dicaffeoylquinic acid, quercetin-7-O-β-D-glucopyranoside, and isochlorogenic acid B were key small molecule components that affected activities. In summary, the extracts of CMF can be regarded as an excellent antioxidant and anti-glycosylation agent. Full article

(1) Background: The non-enzymatic glycation of proteins is a significant contributor to the formation of advanced glycation end products (AGEs) and intermediates that are responsible for diabetic complications. It is imperative to explore effective inhibitors to prevent protein glycation. (2) Methods: This study aimed to investigate the inhibitory potential of various aqueous ethanol extracts of poplar-type propolis on AGEs and oxidative modifications in bovine serum albumin (BSA)-glucose and BSA-methylglyoxal models. (3) Results: The results revealed that these propolis extracts exhibited significant effectiveness in inhibiting the formation of total AGEs, pentosidine, and Nε-carboxymethyllysine (CML). Furthermore, the investigation discovered that these propolis extracts can effectively inhibit oxidative modification, based on measuring the levels of carbonyl and thiol groups and analyzing tryptophan fluorescence quenching. Notably, 75% ethanol extracts of propolis (EEP) exhibited the highest inhibitory activity, surpassing the chemical inhibitor aminoguanidine (AG). (4) Conclusions: The remarkable anti-glycation potency of aqueous ethanol extracts of poplar-type propolis can be attributed to their elevated contents of phenolic compounds, especially abundant flavonoids, which inhibit the formation of AGEs by scavenging free radicals, decreasing the levels of reactive oxygen species (ROS), and capturing reactive carbonyl species (RCS) in the protein glycation process. Our results indicate that poplar-type propolis may be a potential AGE inhibitor and could be used to develop functional foods and nutraceuticals to prevent diabetic complications. Full article

While vitiligo is primarily caused by melanocyte deficiency or dysfunction, recent studies have revealed a notable prevalence of metabolic syndrome (MetS) among patients with vitiligo. This suggests shared pathogenic features between the two conditions. Individuals with vitiligo often exhibit variations in triglyceride levels, cholesterol, and blood pressure, which are also affected in MetS. Given the similarities in their underlying mechanisms, genetic factors, pro-inflammatory signalling pathways, and increased oxidative stress, this study aims to highlight the common traits between vitiligo and metabolic systemic disorders. Serum analyses confirmed increased low-density lipoprotein (LDL) levels in patients with vitiligo, compared to physiological values. In addition, we reported significant decreases in folate and vitamin D (Vit D) levels. Oxidative stress is one of the underlying causes of the development of metabolic syndromes and is related to the advancement of skin diseases. This study found high levels of inflammatory cytokines, such as interleukin-6 (IL-6) and chemokine 10 (CXCL10), which are markers of inflammation and disease progression. The accumulation of insulin growth factor binding proteins 5 (IGFBP5) and advanced glycation end products (AGEs) entailed in atherosclerosis and diabetes onset, respectively, were also disclosed in vitiligo. In addition, the blood-associated activity of the antioxidant enzymes catalase (Cat) and superoxide dismutase (SOD) was impaired. Moreover, the plasma fatty acid (FAs) profile analysis showed an alteration in composition and specific estimated activities of FAs biosynthetic enzymes resembling MetS development, resulting in an imbalance towards pro-inflammatory n6-series FAs. These results revealed a systemic metabolic alteration in vitiligo patients that could be considered a new target for developing a more effective therapeutic approach. Full article

Background: The diagnosis of Alzheimer’s disease (AD) relies on core cerebrospinal fluid (CSF) biomarkers, amyloid beta (Aβ) and tau. As the brain is then already damaged, researchers still strive to discover earlier biomarkers of disease onset and the progression of AD. Glycation, advanced glycation end products (AGEs) and oxidative modifications on proteins in CSF mirror the underlying biological mechanisms that contribute to early AD pathology. However, analyzing free AGEs in the body fluids of AD patients has led to controversial results. Thus, this pilot study aimed to test the feasibility of detecting, identifying and quantifying differentially glycated, AGE or oxidatively modified peptides in CSF proteins of AD patients (n = 5) compared to a control group (n = 5). Methods: To this end, we utilized a data-dependent (DDA) nano liquid chromatography (LC) linear ion trap-Orbitrap tandem mass spectrometry (MS/MS) ) approach and database search that included over 30 glycative and oxidative modifications in four search nodes to analyze endogenous modifications on individual peptides. Furthermore, we quantified candidate peptide abundance using LC Quan. Results: We identified 299 sites of early and advanced glycation and 53 sites of oxidatively modified tryptophan. From those, we identified 17 promising candidates as putative biomarkers (receiver operating curve-area under the curve (ROC-AUC) > 0.8), albeit without statistical significance. Conclusions: The potential candidates with higher discrimination power showed correlations with established diagnostic markers, thus hinting toward the potential of those peptides as biomarkers. Full article