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Controlled oxidation of methyl‐ketones to aryl glyoxals using Selenium dioxide and iodine is one of the useful transformation. Regardless the availability of many oxidation reagents, Iodine/DMSO system is very efficient and flexible. This system efficiently allows in situ formation of α‐halo ketones and subsequently transforming them directly to useful products. The Iodine/DMSO system allows the selective CI and CO bond formation, substantially useful for converting them to other bond forming reactions and heterocycles useful in the synthetic and medicinal chemistry. Iodine/DMSO system could be an important alternative strategy due to sustainability, metal‐free conditions, allowing multiple/linear domino reactions. This review will focus on heterocyclic systems smartly developed/manipulated by Wu group from methyl‐ketones. The scope and limitations of this method and selected examples of applications for the synthesis of interesting molecules are discussed herein. [ABSTRACT FROM AUTHOR]

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. Collagen 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. [Display omitted] [ABSTRACT FROM AUTHOR]

Glycation is among the underlying mechanisms attributed to ageing and associated morbidities. There is no drug available to combat this deleterious phenomenon. The present study aimed to explore phloroglucinol (PHL) for its anti-glycation potential at preclinical level. The rats were treated with methylglyoxal (MGO, 17.25 mg/kg, i.p. for 14 days) to induce glvcative stress. The treatment groups received additional administration of test drug (PHL; 0.25mg/kg, 0.5mg/kg, and 1mg/kg) or standard aminoguanidine (AG, 50 mg/kg) or saline (control, 5ml/kg). During 14 days, the weight and food intake was noted. Afterwards, the cognitive function was evaluated using Morris Water Maze (MWM) while hepatic and renal functions were assessed through liver function test (bilirubin, alkaline phosphatase, SGPT, and SGOT) and creatinine respectively, using chemical analyzer. The carboxymethyllysine (CML) levels were quantified in the blood using ELISA technique. Histopathological study was performed on the brain, liver, and kidney using H&E staining. Additionally, the qPCR was used to quantify the expression of TNF-α, RAGE and BACE-1 (brain), RAGE, TNF-α, and glyoxalase-I (liver) and RAGE, TNF-α, and VEGF (kidney), while glyceraldehyde-3-phosphate dehydrogenase (GAPDH) was used as a reference housekeeping gene. The data regarding weight and food intake did not reveal significant alterations. In MWM, the MGO treatment caused significant increase in the time to reach target quadrant, while decrease in the time spent in target quadrant and number of crossings through platform position. All these effects were inhibited by both AG and PHL. The navigation maps also exhibit that the retention of spatial memory. Additionally, the MGO-induced alteration in hepatic and renal function indicators was ameliorated by both AG and PHL treatments. The plasma CML levels were found to be elevated following MGO treatment, while the concomitant administration of AG and PHL has resisted this raise. Histopathological assessment revealed no specific pathology in liver kidney and brain tissues. The qPCR data revealed enhanced expression of all genes, especially TNF-α and BACE, which were found to be reduced following both AG and PHL treatments. PHL prevented the brain, hepatic, and renal impairments caused by MGO induced glycative stress. Hence, the PHL, a clinically used anti-spasmodic drug, presents itself as a potential candidate to be repurposed as anti-glycation drug. [ABSTRACT FROM AUTHOR]

Background: Capsicum annuum, a significant agricultural and nutritional crop, faces production challenges due to its sensitivity to various abiotic stresses. Glyoxalase (GLY) and D-lactate dehydrogenase (D-LDH) enzymes play vital roles in mitigating these stresses by detoxifying the stress-induced cytotoxin, methylglyoxal (MG). Methods: A genome-wide study was conducted to identify and characterize glyoxalase I (GLYI), glyoxalase II (GLYII), unique glyoxalase III or DJ-1 (GLYIII), and D-LDH gene candidates in Capsicum annuum. The identified members were evaluated based on their evolutionary relationships with known orthologues, as well as their gene and protein features. Their expression patterns were examined in various tissues, developmental stages, and in response to abiotic stress conditions using RNA-seq data and qRT-PCR. Results: A total of 19 GLYI, 9 GLYII, 3 DJ-1, and 11 D-LDH members were identified, each featuring characteristic domains: glyoxalase, metallo-β-lactamase, DJ-1_PfpI, and FAD_binding_4, respectively. Phylogenetic analysis revealed distinct clades depending on functional diversification. Expression profiling demonstrated significant variability under stress conditions, underscoring their potential roles in stress modulation. Notably, gene-specific responses were observed with CaGLYI-2, CaGLYI-7, CaGLYII-6, CaDJ-1 A, and CaDLDH-1 showed upregulation under salinity, drought, oxidative, heat, and cold stresses, while downregulation were shown for CaGLYI-3, CaGLYII-1, CaDJ-1B, and CaDJ-1 C. Remarkably, CaGLYI-1 presented a unique expression pattern, upregulated against drought and salinity but downregulated under oxidative, heat, and cold stress. Conclusion: The identified GLY and D-LDH gene families in Capsicum annuum exhibited differential expression patterns under different abiotic stresses. Specifically, CaGLYI-2, CaGLYI-7, CaGLYII-6, CaDJ-1 A, and CaDLDH-1 were upregulated in response to all five analyzed abiotic stressors, highlighting their critical role in stress modulation amidst climate change. This study enhances our understanding of plant stress physiology and opens new avenues for developing stress-resilient crop varieties, crucial for sustainable agriculture. [ABSTRACT FROM AUTHOR]

Methylglyoxal (MG), a highly reactive and cytotoxic α-oxoaldehyde compound, can over-accumulate under abiotic stress, consequently injuring plants or even causing death. Glyoxalase I (GLYI), the first enzyme of the glyoxalase pathway, plays multiple roles in the detoxification of MG and in abiotic stress responses. However, the GLY1 gene in maize has been little studied in response to abiotic stress. In this study, we screened a glyoxalase I gene (ZmGLYI-8) and overexpressed in Arabidopsis. This gene was localized in the cytoplasm and can be induced in maize seedlings under multiple stress treatments, including salt, drought, MG, ABA, H2O2 and high temperature stress. Phenotypic analysis revealed that after MG, salt and drought stress treatments, overexpression of ZmGLYI-8 increased the tolerance of transgenic Arabidopsis to MG, salt and drought stress. Furthermore, we demonstrated that the overexpression of ZmGLYI-8 scavenges accumulated reactive oxygen species, detoxifies MG and enhances the activity of antioxidant enzymes to improve the resistance of transgenic Arabidopsis plants to salt and drought stress. In summary, this study preliminarily elucidates the molecular mechanism of the maize ZmGLYI-8 gene in transgenic Arabidopsis and provides new insight into the breeding of salt- and drought-tolerant maize varieties. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Imidazole structures are significant molecular frameworks in pharmaceutical and energetic material research. The synthesis efficiency and yield of their derivatives often vary greatly, making it challenging to establish reaction regularity. In this study, we investigated two types of imidazole derivatives with notably different synthesis efficiencies and yields. Our findings reveal that the catalysis of H2O molecules is crucial for ensuring synthesis efficiency, while side reactions are influenced by the acidity of the solution during the process, thereby affecting the synthesis yield. We observed that the energy barrier for the H2O‐catalyzed ipsilateral H transfer process was reduced to 12.0 from 40.1 kcal/mol, significantly enhancing the reaction efficiency. The synthesis of 34‐dihydroxyimidazolidine‐2‐ketone was found to have a low yield of 19.2% due to competitive side reactions in the reaction system, which have higher energy barriers compared to the desired synthesis pathway. These findings provide a theoretical foundation for future research to optimize the synthesis of imidazole derivatives. Enhancing synthesis conditions could significantly benefit pharmaceutical applications and the development of advanced energetic materials. [ABSTRACT FROM AUTHOR]

Methylglyoxal (MGO) triggers oxidative stress responses in vascular endothelial cells, leading to apoptosis linked to diabetic vascular complications. Total flavonoids of Eucommia ulmoides leaves (TFEL) display antioxidant activity, yet its prevention of MGO‐induced apoptosis and mechanisms are unclear. Our study used western blotting and ELISA to evaluate protein levels and enzyme activities. Cell viability and apoptosis were evaluated using CCK8 assay and PE Annexin V/7‐AAD double staining. Reactive oxygen species (ROS) generation and mitochondrial membrane potential (MMP) were measured using fluorescence probes. Vascular pathological changes and apoptosis were analyzed through H&E and TUNEL staining. In vitro, MGO‐stimulated human umbilical vein endothelial cells (HUVECs) were treated with varying TFEL concentrations. Our results demonstrated that TFEL significantly enhanced cell viability, reduced apoptosis, downregulated caspase‐3 activity, and Bax/Bcl‐2 ratio. Moreover, TFEL markedly suppressed MGO‐induced ROS and malondialdehyde (MDA) production while restoring antioxidant enzyme activity and MMP. TFEL pretreatment promoted the expression of p‐Akt, Nrf2, and HO‐1 proteins. Pharmacological inhibition of p‐Akt significantly suppressed the upregulation of Nrf2 and HO‐1 protein levels mediated by TFEL. Consistently, pharmacological inhibition of Nrf2 or p‐Akt partially abrogated the protective effects of TFEL against MGO‐induced damage in HUVECs. In vivo studies revealed that TFEL (100 and 200 mg/kg) partially restored antioxidant capacity and reduced aortic thickness and apoptosis in MGO‐injured mice. In conclusion, the findings indicate that TFEL mitigates MGO‐induced apoptosis via activation of p‐Akt/Nrf2/HO‐1 and scavenging of oxidative stress, highlighting its potential in diabetic vascular complication management. [ABSTRACT FROM AUTHOR]

Bioconversion of abundant lactose-replete whey permeate to value-added chemicals holds promise for valorization of this expanding food processing waste. Efficient conversion of whey permeate-borne lactose requires adroit microbial engineering to direct carbon to the desired chemical. An engineered strain of Clostridium beijerinckii NCIMB 8052 (C. beijerinckii_mgsA+mgR) that produces 87% more butanol on lactose than the control strain was assessed for global transcriptomic changes. The results revealed broadly contrasting gene expression patterns in C. beijerinckii_mgsA+mgR relative to the control strain. These were characterized by widespread decreases in the abundance of mRNAs of Fe-S proteins in C. beijerinckii_ mgsA+mgR, coupled with increased differential expression of lactose uptake and catabolic genes, iron uptake genes, two-component signal transduction and motility genes, and genes involved in the biosynthesis of vitamins B5 and B12, aromatic amino acids (particularly tryptophan), arginine, and pyrimidines. Conversely, the mRNA patterns suggest that the L-aspartate-dependent de novo biosynthesis of NAD as well as biosynthesis of lysine and asparagine and metabolism of glycine and threonine were likely down-regulated. Furthermore, genes involved in cysteine and methionine biosynthesis and metabolism, including cysteine desulfurase--a central player in Fe-S cluster biosynthesis--equally showed reductions in mRNA abundance. Genes involved in biosynthesis of capsular polysaccharides and stress response also showed reduced mRNA abundance in C. beijerinckii_mgsA+mgR. The results suggest that remodeling of cellular and metabolic networks in C. beijerinckii_mgsA+mgR to counter anticipated effects of methylglyoxal production from heterologous expression of methylglyoxal synthase led to enhanced growth and butanol production in C. beijerinckii_mgsA+mgR. IMPORTANCE Biological production of commodity chemicals from abundant waste streams such as whey permeate represents an opportunity for decarbonizing chemical production. Whey permeate remains a vastly underutilized feedstock for bioproduction purposes. Thus, enhanced understanding of the cellular and metabolic repertoires of lactose-mediated production of chemicals such as butanol promises to identify new targets that can be fine tuned in recombinant and native microbial strains to engender stronger coupling of whey permeate-borne lactose to value-added chemicals. Our results highlight new genetic targets for future engineering of C. beijerinckii for improved butanol production on lactose and ultimately in whey permeate. [ABSTRACT FROM AUTHOR]

This work presents the study results on the acid‐catalyzed cascade condensation of p‐toluenesulfonamide with glyoxal in H2SO4 in order to synthesize aza‐ and oxaazaisowurtzitanes—a platform for promising high‐energy‐density compounds—and explore their formation processes. The effects of the ratio of starting reactants, acidity, reaction medium concentration, and temperature on this process were studied in detail. Five novel compounds were derived, including four oxaazaisowurtzitanes comprising one to three aza groups, and one condensation intermediate. The most favorable conditions for the formation of the resultant caged compounds were established and some new regularities of the process were revealed. For instance, the reaction medium concentration was discovered for the first time to influence the generation process of oxaazaisowurtzitanes via direct condensation. The limiting stage of the cage formation process of oxaazaisowurtzitanes was identified. The formation rate of the oxaazaisowurtzitanes was shown to be dependent on their structure. The factor dramatically reducing the yield of the oxaazaisowurtzitanes at elevated synthesis temperature was also revealed. [ABSTRACT FROM AUTHOR]

Förster resonance energy transfer (FRET) serves as a tool for measuring protein–protein interactions using various sensor molecules. The tension sensor module relies on FRET technology. In our study, this module was inserted within the actinin molecule to measure the surface tension of the cells. Given that the decay curve of FRET efficiency correlates with surface tension increase, precise and accurate efficiency measurement becomes crucial. Among the methods of FRET measurements, FRET efficiency remains the most accurate if sample fixation is successful. However, when cells were fixed with 4% paraformaldehyde (PFA), the actinin-FRET sensor diffused across the cytoplasm; this prompted us to explore fixation method enhancements. Glyoxal fixative has been reported to improve cytoskeletal morphologies compared to PFA. However, it was not known whether glyoxal fits FRET measurements. Glyoxal necessitates an acetic acid solution for fixation; however, acidic conditions could compromise fluorescence stability. We observed that the pH working range of glyoxal fixative aligns closely with MES (methyl-ethylene sulfonic acid) Good's buffer. Initially, we switched the acidic solution for MES buffer and optimized the fixation procedure for in vitro and in vivo FRET imaging. By comparing FRET measurements on hydrogels with known stiffness to tumor nodules in mouse lung, we estimated in vivo stiffness. The estimated stiffness of cancerous tissue was harder than the reported stiffness of smooth muscle. This discovery shed lights on how cancer cells perceive environmental stiffness during metastasis. [ABSTRACT FROM AUTHOR]

BACKGROUND RESULTS CONCLUSION Nε‐carboxymethyllysine (CML), Nε‐carboxyethyllysine (CEL) and α‐aminoadipic acid (AAA) are important foodborne hazards and their intake can cause a variety of diseases in humans. It is extremely important to investigate the formation mechanism of CML, CEL and AAA, as well as their association with each other when aiming to control their production.A multi‐response kinetic model was developed within the glucose‐lysine Maillard reaction model system. The concentrations of glucose, lysine, glyoxal (GO), methylglyoxal (MGO), CML, CEL and AAA were quantified at different temperature (100–160 °C) and at different intervals (0–60 min). The experimental data were fitted to the proposed model to calculate kinetic parameters for the corresponding steps. The results indicated that the production of CML was primarily relied on the direct oxidative cleavage of the Amadori product, rather than the reaction between GO and Lys, whereas CEL and AAA were generated through the reaction of MGO with Lys. Significantly, the reaction between α‐dicarbonyl compounds and Lys preferentially generated CML and CEL, resulting in the lower concentrations of AAA compared to CML and CEL.The multi‐response kinetic model developed in the present study can be applied well to the Maillard reaction. The relationship between the formation mechanisms of CML, CEL and AAA is also explained. © 2024 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

In biomaterials research, using one or two components to prepare materials is common. However, there is a growing interest in developing materials composed of three components, as these can offer enhanced physicochemical properties compared to those consisting of one or two components. The introduction of a third component can significantly improve the mechanical strength, biocompatibility, and functionality of the resulting materials. Cross-linking is often employed to further enhance these properties, with chemical cross-linking agents being the most widely used method. This article provides an overview of the chemical agents utilized in the cross-linking of three-component biomaterials. The literature review focused on cases where the material was composed of three components and a chemical substance was employed as the cross-linking agent. The most commonly used cross-linking agents identified in the literature include glyoxal, glutaraldehyde, dialdehyde starch, dialdehyde chitosan, and the EDC/NHS mixture. Additionally, the review briefly discusses materials cross-linked with the MES/EDC mixture, caffeic acid, tannic acid, and genipin. Through a critical analysis of current research, this work aims to guide the development of more effective and safer biopolymeric materials tailored for biomedical applications, highlighting potential areas for further investigation and optimization. [ABSTRACT FROM AUTHOR]

Toxicological analyses often necessitate the identification of compounds belonging to diverse functional groups. For GC–MS analyses, derivatization of compounds belonging to different functional groups can pose a challenge and requires the development of comprehensive methods of analysis. One example could be ethylene glycol, whose widespread use is related to possible unintentional or suicidal intoxications. This fact clearly indicates the need to develop sensitive methods for the determination of ethylene glycol and its metabolites in biological material, as only such complex analysis allows for proper toxicological expertise. A simultaneous GC–QqQ–MS/MS method for the determination of ethylene glycol together with its metabolites, glyoxal and glycolic acid, as well as the detection of glyoxylic acid and oxalic acid, was developed and fully validated. A novel approach for simultaneous derivatization of substances from different groups (alcohols, aldehydes, and carboxylic acids) was established. Sample preparation included the addition of three internal standards (BHB-d4, ethylene glycol-d4 and methylglyoxal), precipitation with acetonitrile and subsequent derivatization with N-tert-butyldimethylsilyl-N-methyltrifluoroacetamide (MTBSTFA), as well as pentafluorophenylhydrazine (PFPH). Detection was carried out with the use of triple quadrupole mass spectrometer. The ionization method was electron impact, and quantitative analysis was carried out in multiple reaction monitoring mode. The lower limit of quantification was 1 μg/mL, 0.1 μg/mL, and 500 μg/mL for ethylene glycol, glyoxal, and glycolic acid, respectively. The presented method was applied in three authentic postmortem cases of ethylene glycol intoxication. [ABSTRACT FROM AUTHOR]

This study presents new glyoxal (CHOCHO) products from the Ozone Monitoring Instrument (OMI) by utilizing updated level 1B irradiance/radiance data (Collection 4) and an updated glyoxal retrieval algorithm. The adoption of Collection 4 contributes to the reduction of artificial signals in differential glyoxal slant column densities (dSCDs) and improved fitting root mean square, and the updated retrieval settings result in fewer negative values of glyoxal dSCDs over oceans and less noisy dSCDs in the South Atlantic Anomaly. On‐line calculations of air mass factors consider interactive physical processes between input parameters. To address persistent trends in glyoxal SCDs over the Pacific Ocean that remain despite these updates, a trend correction is implemented. We evaluate the updated OMI glyoxal products using inter‐comparisons with GOME‐2A/2B glyoxal products. OMI glyoxal products exhibit good spatial and temporal agreement with GOME‐2A/2B, with correlation coefficients of 0.75–0.78 globally and 0.84–0.85 over source regions. Small biases are observed in OMI glyoxal vertical column densities, ranging from −0.2 ± 5.7% to 9 ± 3% in low and high glyoxal conditions, respectively, against GOME‐2A/2B. These advancements contribute to the reliability and accuracy of OMI glyoxal products, enhancing their utility for atmospheric studies and enabling a 20‐year‐long data record suitable for climate studies. Plain Language Summary: This research introduces new glyoxal (CHOCHO) products obtained from a satellite instrument called the Ozone Monitoring Instrument (OMI). For new glyoxal products, we use the updated OMI irradiance/radiance data and update the way we analyze the radiance data. As a result, new OMI glyoxal products show the reduction of errors caused by the instrument and consider interactive physical processes between the surface and atmosphere. The new data matches well with similar data from other satellite instruments (GOME‐2A/B), showing that the improvements are effective. This better data set helps scientists study the air quality over a long period of time. Key Points: We improve Ozone Monitoring Instrument (OMI) glyoxal column measurements with the new radiance data (Collection 4) and updated retrieval algorithmThe new glyoxal measurements show the stable spectral fitting through OMI's lifetimeCompared to GOME‐2A/B, OMI glyoxal products show good spatial (temporal) correlation coefficients of 0.75–0.78 (0.84–0.85), respectively [ABSTRACT FROM AUTHOR]

The present investigation was carried out to study the leaf composition and methylglyoxal pathway in four barley genotypes on infection with Bipolaris sorokiniana. PL 891 was found to be highly resistant, followed by PL 807 as a resistant cultivar, while PL 426 and RD 2786 depicted susceptible behavior to spot blotch disease. Total soluble sugars increased by more than 1.4 folds in resistant genotypes at the growth stage (GS) 55 (half inflorescence emerged) while declined in the sensitive ones. However, control leaves of the latter had more total soluble sugars and cholorophyll contents at GS 55 but declined after infection. Glyoxalase I activity increased in the lower leaves of PL 807, PL 891 and PL 426 on infection with Bipolaris sorokiniana at GS 87 (hard dough). Glyoxalase II activity increased in the infected leaves of PL 891, PL 807, and PL 426 by 1.3, 1.1 and 1.4 folds respectively at GS 55 stage while declined by more than 1.3 folds in the susceptible genotype RD 2786. Glyoxalase III activity increased in the flag and lower leaves of PL 807 at both stages while declined or remained unaffected in other genotypes indicating the action of glutathione independent pathway in this genotype. Methylglyoxal reductase activity increased by more than 1.3 and 1.9 folds respectively in the flag and lower leaves of both the resistant genotypes. Negative correlation of MG with Gly I (-0.431**) and with methylglyoxal reductase (-0.274*) verified the role of these enzymes in its detoxification in response to leaf blight disease. Analysis of the data shows that the rise in total soluble sugars at initial stages and the activities of Gly III and methylglyoxal reductase at later stages along with the maintenance of redox pool could be responsible for the resistant nature of PL 891 and PL 807. [ABSTRACT FROM AUTHOR]

Bioproduction of industrially relevant chemicals such as 1,2-propanediol (1,2-PD) is central to decarbonization of the economy. Currently, 1,2-PD is produced from fossil-derived feedstocks, contributing to CO 2 emission and generation of hazardous wastes. In this study, Clostridium beijerinckii NCIMB 8052 (Cbei) , C. pasteurianum ATCC 6013 (Cpas), and Clostridium tyrobutyricum ATCC 25755 (Ctyro) were screened for the ability to transform methylglyoxal and acetol—precursors of 1,2-PD—to 1,2-PD in cultures exogenously supplemented with both compounds. Only Cbei transformed methylglyoxal to 1,2-PD (0.08 g/L). Subsequently, multiple recombinant strains of Cbei were engineered to express methylglyoxal-targeting aldo-keto reductases [ mgR , yeaE , yhdN (from Cpas), yqhD , and ydjG (from Enterobacter hormaechei UW0SKVC1), and glycerol dehydrogenase (gldA ; from Ctyro ]. With exogenous supplementation of methylglyoxal, the growth of the control strain of Cbei was impaired. Conversely, Cbei_ydjG , Cbei_yqhD , and Cbei_gldA showed 19.3 %, 130 % and 162 % enhanced growth following methylglyoxal challenge, respectively, whilst producing 0.100, 0.032, and 0.042 g/L 1,2-PD. Wildtype or recombinant strains of Cbei , Cpas , and Ctyro transformed ∼100 % of exogenously supplemented acetol to 1,2-PD. Cbei _ mgsA + mgR co-expressing methylglyoxal synthase (mgsA) and mgR (both from Cpas) produced up to 88 % more butanol on both glucose and lactose than the control strains. [Display omitted] • Clostridium beijerinckii transformed a fraction of exogenously supplemented methylglyoxal to 1,2-propanediol. • Two aldo-keto reductases and a glycerol dehydrogenase that transform cloning and heterologous expression. • YdjG from Enterobacter hormaechei UW0SKVC1 exhibited the highest 1,2-propandiol production from exogenous methylglyoxal. • Heterologous expression of mgR from Clostridium pasteurianum in Clostridium beijerinckii enhanced butanol production. [ABSTRACT FROM AUTHOR]

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. Highlights: MG is a determinant of carbonyl stress in T2DM patients.The substrates of MG were analysed by GC–MS in T2DM with and without ACS.The validated GC–MS methods were sensitive, accurate, precise and reliable.Plasma C20:0, C16:1, C18:1, glycine, glycerol and sorbitol are associated with ACS risk in T2DM. [ABSTRACT FROM AUTHOR]

Abstract Background Capsicum annuum, a significant agricultural and nutritional crop, faces production challenges due to its sensitivity to various abiotic stresses. Glyoxalase (GLY) and D-lactate dehydrogenase (D-LDH) enzymes play vital roles in mitigating these stresses by detoxifying the stress-induced cytotoxin, methylglyoxal (MG). Methods A genome-wide study was conducted to identify and characterize glyoxalase I (GLYI), glyoxalase II (GLYII), unique glyoxalase III or DJ-1 (GLYIII), and D-LDH gene candidates in Capsicum annuum. The identified members were evaluated based on their evolutionary relationships with known orthologues, as well as their gene and protein features. Their expression patterns were examined in various tissues, developmental stages, and in response to abiotic stress conditions using RNA-seq data and qRT-PCR. Results A total of 19 GLYI, 9 GLYII, 3 DJ-1, and 11 D-LDH members were identified, each featuring characteristic domains: glyoxalase, metallo-β-lactamase, DJ-1_PfpI, and FAD_binding_4, respectively. Phylogenetic analysis revealed distinct clades depending on functional diversification. Expression profiling demonstrated significant variability under stress conditions, underscoring their potential roles in stress modulation. Notably, gene-specific responses were observed with CaGLYI-2, CaGLYI-7, CaGLYII-6, CaDJ-1 A, and CaDLDH-1 showed upregulation under salinity, drought, oxidative, heat, and cold stresses, while downregulation were shown for CaGLYI-3, CaGLYII-1, CaDJ-1B, and CaDJ-1 C. Remarkably, CaGLYI-1 presented a unique expression pattern, upregulated against drought and salinity but downregulated under oxidative, heat, and cold stress. Conclusion The identified GLY and D-LDH gene families in Capsicum annuum exhibited differential expression patterns under different abiotic stresses. Specifically, CaGLYI-2, CaGLYI-7, CaGLYII-6, CaDJ-1 A, and CaDLDH-1 were upregulated in response to all five analyzed abiotic stressors, highlighting their critical role in stress modulation amidst climate change. This study enhances our understanding of plant stress physiology and opens new avenues for developing stress-resilient crop varieties, crucial for sustainable agriculture.

Resistance exercise provides significant benefits to skeletal muscle, including hypertrophy and metabolic enhancements, supporting overall health and disease management. However, skeletal muscle responsiveness to resistance exercise is significantly reduced in conditions such as aging and diabetes. Recent reports suggest that glycation stress contributes to muscle atrophy and impaired exercise-induced muscle adaptation; however, its role in the muscle response to resistance exercise remains unclear. Therefore, in this study, we investigated whether methylglyoxal (MGO), a key factor in glycation stress, affects the acute responsiveness of skeletal muscles to resistance exercise, focusing on protein synthesis and the key signaling molecules. This study included 12 8-week-old male Sprague–Dawley rats divided into two groups: one received 0.5% MGO-supplemented drinking water (MGO group) and the other received regular water (control group). After 10 weeks, the left tibialis anterior muscle of each rat was subjected to electrical stimulation (ES) to mimic resistance exercise, with the right muscle serving as a non-stimulated control. Muscle protein-synthesis rates were evaluated with SUnSET, and phosphorylation levels of key signaling molecules (p70S6K and S6rp) were quantified using western blotting. In the control group, stimulated muscles exhibited significantly increased muscle protein synthesis and phosphorylation levels of p70S6K and S6rp. In the MGO group, these increases were attenuated, indicating that MGO treatment suppresses the adaptive response to resistance exercise. MGO diminishes the skeletal muscle's adaptive response to ES-simulated resistance exercise, affecting both muscle protein synthesis and key signaling molecules. The potential influence of glycation stress on the effectiveness of resistance exercise or ES emphasizes the need for individualized interventions in conditions of elevated glycation stress, such as diabetes and aging. [ABSTRACT FROM AUTHOR]

Abstract 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.

Objective: The aim of this study was to investigate the effect on coronavirus disease-2019 (COVID-19) of glyoxal (GO), which is a precursor of advanced glycation end-products, in diabetic and non-diabetic patients, treated in hospital for COVID-19 who were of similar age and disease severity with similar comorbidities. Methods: The study included 57 patients. Measurement of GO was made with the high-performance liquid chromatography method. Results: The GO values were found to be higher in the diabetic group than in the non-diabetic group (p=0.001, p

Background: Advanced glycation end products (AGEs) that accompany many metabolic disorders including diabetes,obesity, and a wide range of dyslipidemia conditions, are strongly associated with adverse effects on cell and tissuehomeostasis. Accordingly, our objective was to investigate the impact of AGE-promoting diets on mouse models,considering both scenarios with and without methylglyoxal (MGO) as a primary precursor of AGEs.Materials and Methods: In this experimental study, 5-week-old C57BL/6 mice were split into four groups as a controlgroup (n=5), AGE (n=5), MGO (n=8), and AGE-MGO-diets (n=8). After five weeks the level of fasting blood sugar (FBS),body weight, food intake, sperm parameters, and functional tests were evaluated. Furthermore, testicular superoxide dismutase(SOD) activity, malondialdehyde, and total antioxidant capacity (TAC) were assessed.Results: After five weeks, AGE, AGE-MGO, and MGO groups showed the highest level of body weight and FBS incomparison to the control group. Mean sperm concentration, sperm malondialdehyde, testicular lipid peroxidation,and TAC did not differ significantly among the study groups. While, AGE, MGO, and AGE-MGO groups showed asignificant reduction in sperm motility and progressive motility compared to the control group (P

Manuka honey (MH) is considered a superfood mainly because of its various health-promoting properties, including its anti-cancer, anti-inflammatory, and clinically proven antibacterial properties. A unique feature of Manuka honey is the high content of methylglyoxal, which has antibacterial potential. Additionally, it contains bioactive and antioxidant substances such as polyphenols that contribute to its protective effects against oxidative stress. In this study, commercially available Manuka honey was tested for its total polyphenol content and DPPH radical scavenging ability. It was then tested in vitro on human fibroblast cells exposed to UV radiation to assess its potential to protect cells against oxidative stress. The results showed that the honey itself significantly interfered with cell metabolism, and its presence only slightly alleviated the effects of UV exposure. This study also suggested that the MGO content has a minor impact on reducing oxidative stress in UV-irradiated cells and efficiency in scavenging the DPPH radical.

Reactive carbonyl species such as methylglyoxal (MGO) act as potent glycating agents that are implicated in several oxidative stress-induced diseases, including, but not limited to, cancer, diabetes and neurodegenerative diseases such as Alzheimer’s and Parkinson’s diseases. In the present study, a combined approach of initial computational studies and in vitro analysis was utilized to investigate the therapeutic benefit of L-cysteine (CYS), a thiol-containing compound. Based on the reactive analysis using global and local density functional theory (DFT) descriptors, the data reported here has revealed that CYS matches its electron-donating capacity with the electron acceptor, methylglyoxal, making the former a good candidate sequestering agent for the latter. Furthermore, in vitro analysis shows that CYS exhibits significant inhibitory effects towards damaging protein structural alteration and formation of advanced glycation end products (AGEs). Such assessment came about through Congo red binding Assay and Antiglycation Assay using BSA-MGO and BSA-glucose model systems. Additionally, CYS also demonstrates a significant protective effect towards MGO-induced oxidative stress in mouse C2C12 myotubes. Therefore, this thiol-containing compound is a promising therapeutic tool for several glycation or AGEs-induced pathological conditions. The use of more relevant cellular and animal models of desired disease studies is recommended to better understand the mechanistic basis of CYS’s potential therapeutic effect. This study utilizing the combined approach of computational and in-vitro analysis, provides helpful data to maximize the potential impact of CYS by designing related molecules that could serve as novel treatment strategies that are effective, safe, and accessible to all in the future.

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. [ABSTRACT FROM AUTHOR]

The damage caused by oxidative and glycative stress to cells accumulates on a daily basis and accelerates aging. Glutathione (GSH), a major antioxidant molecule in living organisms, plays a crucial role in detoxifying the stress-causing substances inherent in cells, such as H2O2 and methylglyoxal (MG), an important intermediate of advanced glycation end-products (AGEs). In this study, we focused on the enhanced antioxidant capacity of the selenium analog of GSH, i.e., selenoglutathione (GSeH), compared to GSH, and examined its effects on the detoxification of stress-causing substances and improvement in cell viability. In cell-free systems, GSeH (1 mM) generated in situ from GSeSeG in the presence of NADPH and glutathione reductase (GR) rapidly reduced more than 80% of 0.1 mM H2O2, indicating the significant glutathione peroxidase (GPx)-like antioxidant activity of GSeSeG. Similarly, around 50% of 0.5 mM MG was degraded by 0.5 mM GSeH within 30 min through a non-enzymatic mechanism. It was also found that GSeSeG (0.05–0.5 mM) showed glutathione S-transferase (GST)-like activity against 1-chloro-2,4-dinitrobenzene (CDNB), a model substance of oxidative stress-causing toxic materials in cells. Meanwhile, HeLa cells that had been pre-treated with GSeSeG exhibited increased viability against 1.2 mM H2O2 (at [GSeSeG] = 0.5–50 μM) and 4 mM MG (at [GSeSeG] = 3 μM), and the latter effect was maintained for two days. Thus, GSeSeG is a potential antioxidant and antiglycative stress agent for cells. [ABSTRACT FROM AUTHOR]

Aminoacetaldehyde (glycinal, NH2CH2CHO) is a first-generation oxidation product of monoethanolamine (MEA, NH2CH2CH2OH), a solvent widely used for CO2 gas separation, which is proposed as the basis for a range of carbon capture technologies. A complete oxidation mechanism for MEA is required to understand the atmospheric transformation of carbon capture plant emissions, as well as the degradation of this solvent during its use and the oxidative destruction of waste solvent. In this study, we have investigated the •OH radical-initiated oxidation chemistry of aminoacetaldehyde using quantum chemical calculations and RRKM theory/master equation kinetic modeling. This work predicts that aminoacetaldehyde has a tropospheric lifetime of around 6 h and that the reaction predominantly produces the NH2CH2C•O radical intermediate at room temperature, along with minor contributions from NH2•CHCHO and •NHCH2CHO. The dominant radical intermediate NH2CH2C•O is predicted to promptly dissociate to NH2•CH2 and CO, where NH2•CH2 is known to react with O2 under tropospheric conditions to form the imine NH = CH2 + HO2. The NH2•CHCHO radical experiences captodative stabilization and is found to form a weakly bound peroxyl radical upon reaction with O2. Instead, the major oxidation product of NH2•CHCHO and the aminyl radical •NHCH2CHO is the imine NH = CHCHO (+HO2). In the atmosphere, the dominant fate of imine compounds is thought to be hydrolysis, where NH = CH2 will form ammonia and formaldehyde, and NH = CHCHO will produce ammonia and glyoxal. Efficient conversion of the dominant first-generation oxidation products of MEA to ammonia is consistent with field observations and supports the important role of imine intermediates in MEA oxidation. [ABSTRACT FROM AUTHOR]

Context: Carbonyl compounds, especially aldehydes, emitted to the atmosphere, may suffer hydration in aerosols or water droplets in clouds. At the same time, they can react with hydroxyl radicals which may add or abstract hydrogen atoms from these species. The interplay between hydration and hydrogen abstraction is studied using density functional and quantum composite theoretical methods, both in the gas phase and in simulated bulk water. The H-abstraction from the aldehydic and geminal diol forms of formaldehyde, acetaldehyde, glycolaldehyde, glyoxal, methylglyoxal, and acrolein is studied to determine whether the substituent has any noticeable effect in the preference for the abstraction of one form or another. It is found that abstraction of the H-atom adjacent to the carbonyl group gives a more stable radical than same abstraction from the geminal diol in the case of formaldehyde, acetaldehyde, and glycolaldehyde. The presence of a delocalizing group in the Cα (a carbonyl group in glyoxal and methylglyoxal, and a vinyl group in acrolein), reverts this trend, and now the abstraction of the H-atom from the geminal diol gives more stable radicals. A further study was conducted abstracting hydrogen atoms from the other different positions in the species considered, both in the aldehydic and geminal diol forms. Only in the case of glycolaldehyde, the radical formed by H-abstraction from the –CH2OH group is more stable than any of the other radical species. Abstraction of the hydrogen atom in one of the hydroxyl groups in the geminal diol is equivalent to the addition of the •OH radical to the aldehyde. It leads, in some cases, to decomposition into a smaller radical and a neutral molecule. In these cases, some interesting theoretical differences are observed between the results in gas phase and (simulated) bulk solvent, as well as with respect to the method of calculation chosen. Methods: DFT (M06-2X, B2PLYP, PW6B95), CCSD(T), and composite (CBS-QB3, jun-ChS, SCVECV-f12) methods using Dunning basis sets and extrapolation to the CBS limit were used to study the energetics of closed shell aldehydes in their keto and geminal-diol forms, as well as the radical derived from them by hydrogen abstraction. Both gas phase and simulated bulk solvent calculations were performed, in the last case using the Polarizable Continuum Model. [ABSTRACT FROM AUTHOR]

This review summarises the data from long-term experimental studies and literature data on the role of oxidatively modified low-density lipoproteins (LDL) in atherogenesis and diabetogenesis. It was shown that not “oxidized” (lipoperoxide-containing) LDL, but dicarbonylmodified LDL are atherogenic (actively captured by cultured macrophages with the help of scavenger receptors), and also cause expression of lectin like oxidized low density lipoprotein receptor 1 (LOX-1) and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 1 (NOX-1) genes in endotheliocytes, which stimulate apoptosis and endothelial dysfunction. The obtained data allowed us to justify new approaches to pharmacotherapy of atherosclerosis and diabetes mellitus. [ABSTRACT FROM AUTHOR]

We report an efficient synthetic route for the synthesis of tetrahydro indole-2,4-diones from readily available β-enaminones and glyoxal and subsequent I2/DMSO-mediated oxidation/aromatization of tetrahydro indole-2,4-dione to produce 4-hydroxyisatin derivatives. The key aspect of this protocol includes the dual catalytic activity of molecular iodine in the presence of DMSO. Mechanistic study suggested that this reaction is substrate selective as corresponding aromatization and sp3 C–H oxidation stops in the presence of 6,6-disubstituted tetrahydro indole-2,4-dione. Additionally, a thorough investigation into the synthesis of tetrahydro indole-2,4-dione follows acid-catalyzed cyclization/dehydration/enol–keto tautomerism from β-enaminones and glyoxal. [ABSTRACT FROM AUTHOR]

This document provides information on the use of photoacid generators (PAGs) in catalysis, specifically in the Friedel-Crafts alkylation of indoles with aldehydes/ketones. The study focuses on diarylethenes and terarylenes as PAGs, which have advantages such as high quantum yields and autonomy. The researchers developed an environmentally friendly method for synthesizing diindolylmethane derivatives with potential antibacterial, antitumor, and antifungal activities. The document also provides detailed information on the synthesis and characterization of various compounds, including their physical properties and spectroscopic data. This information can be useful for researchers studying these compounds and their properties. [Extracted from the article]

A tandem Cu‐catalyzed oxidation‐intramolecular Cannizzaro reaction leading to bioactive α‐hydroxyesters from α‐hydroxyketones is reported. The process uses oxygen as a sole oxidant to achieve the formation of glyoxals, which are efficiently converted in situ to important α‐hydroxyesters. The mechanistic insights are provided by isotopic labeling and supported by DFT calculations. The transformation proved a robust synthetic tool to achieve the synthesis of human metabolites and hydroxyl esters of various biologically active steroid derivatives. [ABSTRACT FROM AUTHOR]

Diabetes is commonly associated with an elevated level of reactive carbonyl species due to alteration of glucose and fatty acid metabolism. These metabolic changes cause an abnormality in cardiac Ca2+ regulation that can lead to cardiomyopathies. In this study, we explored how the reactive α-dicarbonyl methylglyoxal (MGO) affects Ca2+ regulation in mouse ventricular myocytes. Analysis of intracellular Ca2+ dynamics revealed that MGO (200 μM) increases action potential (AP)-induced Ca2+ transients and sarcoplasmic reticulum (SR) Ca2+ load, with a limited effect on L-type Ca2+ channel-mediated Ca2+ transients and SERCA-mediated Ca2+ uptake. At the same time, MGO significantly slowed down cytosolic Ca2+ extrusion by Na+/Ca2+ exchanger (NCX). MGO also increased the frequency of Ca2+ waves during rest and these Ca2+ release events were abolished by an external solution with zero [Na+] and [Ca2+]. Adrenergic receptor activation with isoproterenol (10 nM) increased Ca2+ transients and SR Ca2+ load, but it also triggered spontaneous Ca2+ waves in 27% of studied cells. Pretreatment of myocytes with MGO increased the fraction of cells with Ca2+ waves during adrenergic receptor stimulation by 163%. Measurements of intracellular [Na+] revealed that MGO increases cytosolic [Na+] by 57% from the maximal effect produced by the Na+-K+ ATPase inhibitor ouabain (20 μM). This increase in cytosolic [Na+] was a result of activation of a tetrodotoxin-sensitive Na+ influx, but not an inhibition of Na+-K+ ATPase. An increase in cytosolic [Na+] after treating cells with ouabain produced similar effects on Ca2+ regulation as MGO. These results suggest that protein carbonylation can affect cardiac Ca2+ regulation by increasing cytosolic [Na+] via a tetrodotoxin-sensitive pathway. This, in turn, reduces Ca2+ extrusion by NCX, causing SR Ca2+ overload and spontaneous Ca2+ waves. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to investigate the effect on coronavirus disease-2019 (COVID-19) of glyoxal (GO), which is a precursor of advanced glycation end-products, in diabetic and non-diabetic patients, treated in hospital for COVID-19 who were of similar age and disease severity with similar comorbidities. Methods: The study included 57 patients. Measurement of GO was made with the high-performance liquid chromatography method. Results: The GO values were found to be higher in the diabetic group than in the non-diabetic group (p=0.001, p<0.01). The length of stay in hospital was longer in the diabetic group (p=0.017, p<0.05). The white blood cell, neutrophil, neutrophil/lymphocyte ratio, procalcitonin, and ferritin values were determined to be higher in the diabetic group than in the non-diabetic group (p=0.006; p=0.005, p=0.017, p=0.011, p=0.030). Although the mortality and intensive care unit admission rates were similar in the diabetic and non-diabetic patients of similar age with similar comorbidities and COVID-19 severity, the total length of stay in hospital was determined to be longer in the diabetic patients. Together with other inflammation markers, GO, was determined to be higher in the diabetic group. Conclusion: The results of this study showed that elevated GO could be associated with a prolonged recovery time in COVID-19. [ABSTRACT FROM AUTHOR]

Methylglyoxal (MG) is considered a classical biomarker of diabetes mellitus and its comorbidities. However, a role for this compound in exacerbated immune responses, such as septicemia, is being increasingly observed and requires clarification, particularly in the context of neuroinflammatory responses. Herein, we used two different approaches (in vivo and acute hippocampal slice models) to investigate MG as a biomarker of neuroinflammation and the neuroimmunometabolic shift to glycolysis in lipopolysaccharide (LPS) inflammation models. Our data reinforce the hypothesis that LPS-induced neuroinflammation stimulates the cerebral innate immune response by increasing IL-1β, a classical pro-inflammatory cytokine, and the astrocyte reactive response, via elevating S100B secretion and GFAP levels. Acute neuroinflammation promotes an early neuroimmunometabolic shift to glycolysis by elevating glucose uptake, lactate release, PFK1, and PK activities. We observed high serum and cerebral MG levels, in association with a reduction in glyoxalase 1 detoxification activity, and a close correlation between serum and hippocampus MG levels with the systemic and neuroinflammatory responses to LPS. Findings strongly suggest a role for MG in immune responses. [ABSTRACT FROM AUTHOR]

Background: Advanced glycation end products (AGEs) that accompany many metabolic disorders including diabetes, obesity, and a wide range of dyslipidemia conditions, are strongly associated with adverse effects on cell and tissue homeostasis. Accordingly, our objective was to investigate the impact of AGE-promoting diets on mouse models, considering both scenarios with and without methylglyoxal (MGO) as a primary precursor of AGEs. Materials and Methods: In this experimental study, 5-week-old C57BL/6 mice were split into four groups as a control group (n=5), AGE (n=5), MGO (n=8), and AGE-MGO-diets (n=8). After five weeks the level of fasting blood sugar (FBS), body weight, food intake, sperm parameters, and functional tests were evaluated. Furthermore, testicular superoxide dismutase (SOD) activity, malondialdehyde, and total antioxidant capacity (TAC) were assessed. Results: After five weeks, AGE, AGE-MGO, and MGO groups showed the highest level of body weight and FBS in comparison to the control group. Mean sperm concentration, sperm malondialdehyde, testicular lipid peroxidation, and TAC did not differ significantly among the study groups. While, AGE, MGO, and AGE-MGO groups showed a significant reduction in sperm motility and progressive motility compared to the control group (P<0.05). The greatest increases in abnormal sperm morphology and intracytoplasmic reactive oxygen species (ROS) were observed in the MGO and AGE-MGO groups than in the control group (P<0.05). Sperm protamine deficiency and residual histone were significantly increased in the three treatment groups compared to the control group (P<0.05). Regarding the DNA damage, the AGE and AGE-MGO groups showed the most severe damage. The lowest amount of testicular superoxide dismutases (SOD, P<0.001) was observed in the AGE-MGO group. Conclusion: AGEs and MGO have a negative influence on sperm function and reproductive potential. These effects could be possibly attributed to both increased oxidative stress (OS) and inflammation. [ABSTRACT FROM AUTHOR]

The 1,2‐dicarbonyl compound methylglyoxal (MGO) can react with and thereby impair the function of proteins and DNA, leading to pathophysiological pathways in vivo. However, studies on the bioavailability of dietary MGO and its reactions during digestion have diverging results. Therefore, simulated digestion experiments of MGO, protein, and creatine were performed in the dynamic, in vitro model of the upper gastrointestinal tract (TIM‐1). This multicompartment model continuously adjusts pH values and has realistic gastrointestinal transit times while also removing water and metabolites by dialysis. Samples were analyzed with HPLC‐UV for MGO and HPLC–MS/MS for creatine and glycated amino compounds. MGO reacted with creatine during simulated digestion in TIM‐1 to form the hydroimidazolone MG‐HCr in similar amounts as in a human intervention study. 28%–69% of MGO from the meal were passively absorbed in TIM‐1, depending on the addition of creatine and protein. Simultaneous digestion of MGO with ovalbumin led to the formation of the lysine adduct Nε‐carboxyethyllysine (CEL) and the methylglyoxal‐derived hydroimidazolone of arginine (MG‐H1). The formation of both compounds decreased with added creatine. Hence, glycation compounds are formed during digestion and significantly contribute to other ingested dietary glycation compounds, whose physiological consequences are critically discussed. [ABSTRACT FROM AUTHOR]

BACKGROUND: Preeclampsia is a multifaceted syndrome that includes maternal vascular dysfunction. We hypothesize that increased placental glycolysis and hypoxia in preeclampsia lead to increased levels of methylglyoxal (MGO), consequently causing vascular dysfunction. METHODS: Plasma samples and placentas were collected from uncomplicated and preeclampsia pregnancies. Uncomplicated placentas and trophoblast cells (BeWo) were exposed to hypoxia. The reactive dicarbonyl MGO and advanced glycation end products (Nε-(carboxymethyl)lysine [CML], Nε-(carboxyethyl)lysine [CEL], and MGO-derived hydroimidazolone [MG-H]) were quantified using liquid chromatography-tandem mass spectrometry. The activity of GLO1 (glyoxalase-1), that is, the enzyme detoxifying MGO, was measured. The impact of MGO on vascular function was evaluated using wire/pressure myography. The therapeutic potential of the MGO-quencher quercetin and mitochondrial-specific antioxidant mitoquinone mesylate (MitoQ) was explored. RESULTS: MGO, CML, CEL, and MG-H2 levels were elevated in preeclampsia-placentas (+36%, +36%, +25%, and +22%, respectively). Reduced GLO1 activity was observed in preeclampsia-placentas (−12%) and hypoxia-exposed placentas (−16%). Hypoxia-induced MGO accumulation in placentas was mitigated by the MGO-quencher quercetin. Trophoblast cells were identified as the primary source of MGO. Reduced GLO1 activity was also observed in hypoxia-exposed BeWo cells (−26%). Maternal plasma concentrations of CML and the MGO-derived MG-H1 increased as early as 12 weeks of gestation (+16% and +17%, respectively). MGO impaired endothelial barrier function, an effect mitigated by MitoQ, and heightened vascular responsiveness to thromboxane A2. CONCLUSIONS: This study reveals the accumulation of placental MGO in preeclampsia and upon exposure to hypoxia, demonstrates how MGO can contribute to vascular impairment, and highlights plasma CML and MG-H1 levels as promising early biomarkers for preeclampsia. [ABSTRACT FROM AUTHOR]

More than a century after its initial synthesis, urea-formaldehyde (UF) resins still have dominant applications as adhesives, paints, and coatings. However, formaldehyde in this industry produces formaldehyde emissions that are dangerous to health. Scientists have spent the last decade replacing formaldehyde and phenol with environmentally friendly substances such as glyoxal and tannin to create bio-based adhesives. This review covers recent advances in synthesizing glyoxal tannin-based resins, especially those made from sustainable raw material substitutes and changes made to synthetic processes to improve mechanical properties. The efficacy of using tannin-glyoxal adhesives in producing wood-based composites has been proven. The glyoxylate reaction forms cross-linked bridges between the aromatic sites of the tannin and glyoxal molecular structures. Glyoxal tannin adhesive with a greater percentage of glyoxal than tannin will produce an adhesive with better characteristics. The gel time reduces as the hardener concentration rises from 7.5% to 15% when glyoxal is used in adhesives. However, excessive amounts of glyoxal will result in a decrease in viscosity values. Glyoxal exhibits faster delivery degradation when it reaches a maximum temperature of approximately 130°C, although it initiates the curing process slightly slower at 110°C. Adding glyoxal to tannin-based adhesives can improve the mechanical properties of composite boards. The wet shear strength of the resulting plywood is increased by 105.4% with the addition of 5-weight percent tannin-based resin with glyoxal as a cross-linker in Soy Protein Adhesive. With glyoxal as a hardener, the panels produced showed good internal bond strengths (>0.35 MPa) and met the international standard specifications for interior-grade panels. [ABSTRACT FROM AUTHOR]

Background: Though maternal diabetes effects are well described in the literature, the effects of maternal diabetes in postnatal phases are often overlooked. Diabetic individuals have higher levels of circulating glycotoxins, and there is a positive correlation between maternal-derived glycotoxins and circulating glycotoxins in their progeny. Previous studies evaluated the metabolic effects of high glycotoxin exposure during lactation in adult animals. However, here we focus on the cardiovascular system of juvenile rats. Methods: For this, we used two experimental models: 1. High Methylglyoxal (MG) environment: pregnant Wistar rats were injected with PBS (VEH group) or Methylglyoxal (MG group; 60 mg/kg/day; orally, postnatal day (PND) 3 to PND14). 2. GLO-1 inhibition: pregnant Wistar rats were injected with dimethyl sulfoxide (VEH group) or a GLO-1 inhibitor (BBGC group; 5 mg/kg/day; subcutaneously, PND1–PND5). The offspring were evaluated at PND45. Results: MG offspring presented cardiac dysfunction and subtly worsened vasomotor responses in the presence of perivascular adipose tissue, without morphological alterations. In addition, an endogenous increase in maternal glycotoxins impacts offspring vasomotricity due to impaired redox status. Conclusions: Our data suggest that early glycotoxin exposure led to cardiac and vascular impairments, which may increase the risk for developing cardiovascular diseases later in life. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to investigate the antibacterial activity of two types of Manuka honey with varying concentrations of methylglyoxal (MGO), 70 and 1050 mg/kg against S. aureus in vitro. Methods: Two types of Manuka honey were purchased and tested for their antimicrobial activities. The Minimum Inhibitory Concentration (MIC) and Minimum Bactericidal Concentration (MBC) were determined using the broth tube dilution method. Results: The results revealed that both concentrations of Manuka honey exhibited antibacterial activity against S. aureus, with the higher concentration (1050 mg/kg) exhibiting enhanced antibacterial activity. The MIC was determined to be 100% v/v (undiluted) for the initial concentration and 1:2 (50% v/v) for the higher concentration. The MBC was not reached at the dilution level used in this experiment for the initial concentration, but it was inferred to be at a dilution of 1:2 for the higher concentration. Conclusion: These findings suggest that Manuka honey with a higher concentration of MGO may be more effective in inhibiting the growth of S. aureus and potentially killing bacteria present. The results of this study highlight the potential use of a high concentration of Manuka honey as an alternative antimicrobial agent against S. aureus. Further investigation into its efficacy in various clinical settings is required. [ABSTRACT FROM AUTHOR]

It is well‐known that people suffering from hyperglycemia have a higher propensity to develop Parkinson's disease (PD). One of the most plausible mechanisms linking these two pathologies is the glycation of neuronal proteins and the pathological consequences of it. α‐Synuclein, a key component in PD, can be glycated at its fifteen lysine. In fact, the end products of this process have been detected on aggregated α‐synuclein isolated from in vivo. However, the consequences of glycation are not entirely clear, which are of crucial importance to understand the mechanism underlying the connection between diabetes and PD. To better clarify this, we have here examined how methylglyoxal (the most important carbonyl compound found in the cytoplasm) affects the conformation and aggregation propensity of α‐synuclein, as well as its ability to cluster and fuse synaptic‐like vesicles. The obtained data prove that methylglyoxal induces the Lys‐Lys crosslinking through the formation of MOLD. However, this does not have a remarkable effect on the averaged conformational ensemble of α‐synuclein, although it completely depletes its native propensity to form soluble oligomers and insoluble amyloid fibrils. Moreover, methylglyoxal has a disrupting effect on the ability of α‐synuclein to bind, cluster and fusion synaptic‐like vesicles. [ABSTRACT FROM AUTHOR]

Modern crops exhibit diverse sensitivities to ammonium as the primary nitrogen source, influenced by environmental factors such as external pH and nutrient availability. Despite its significance, there is currently no systematic classification of plant species based on their ammonium sensitivity. We conducted a meta-analysis of 50 plant species and present a new classification method based on the comparison of fresh biomass obtained under ammonium and nitrate nutrition. The classification uses the natural logarithm of the biomass ratio as the size effect indicator of ammonium sensitivity. This numerical parameter is associated with critical factors for nitrogen demand and form preference, such as Ellenberg indicators and the repertoire of nitrogen transporters for ammonium and nitrate uptake. Finally, a comparative analysis of the developmental and metabolic responses, including hormonal balance, is conducted in two species with divergent ammonium sensitivity values in the classification. Results indicate that nitrate has a key role in counteracting ammonium toxicity in species with a higher abundance of genes encoding NRT2-type proteins and fewer of those encoding the AMT2-type proteins. Additionally, the study demonstrates the reliability of the phytohormone balance and methylglyoxal content as indicators for anticipating ammonium toxicity. [ABSTRACT FROM AUTHOR]

Background: Type 2 diabetes mellitus (T2DM) is often associated with metabolic disorders. Statin drugs are potent inhibitors of cholesterol biosynthesis. Objective: The aim of this study was to evaluate the effect of atorvastatin on the concentrations of methylglyoxal (MGO), glyoxalase 1 (GLO-1), and aldo–keto reductase family 1 member B10 (AKR1B10) in patients with T2DM and prediabetes. Methods: This study was conducted on 80 subjects with and without T2DM and prediabetics divided into 5 groups: patients with T2DM receiving statins (group A, n = 17), patients with T2DM not receiving statins (group B, n = 17), patients with prediabetes receiving statins (group C, n = 12), patients with prediabetes not receiving statins (group D, n = 17), and healthy controls without T2DM (control group, n = 17). Patients with T2DM and prediabetes received atorvastatin 20 mg/day for 3 months. The measurement of MGO and AKR1B10 was performed with a non-competitive sandwich-type enzyme-linked immunosorbent assay (ELISA) at 450 nm. The measurement of GLO-1 was performed by an enzymatic method at 240 nm. Results: The serum level of MGO was significantly higher in patients with T2DM and prediabetes than that of healthy controls (p = 0.001). In patients with T2DM, statins decreased the serum level of MGO, but in patients with prediabetes, statins increased the serum level of MGO (p = 0.001). The level of GLO-1 activity was significantly higher in healthy controls than that of patients with T2DM and prediabetes (p = 0.001). Furthermore, the level of GLO-1 activity was significantly higher in patients with T2DM and prediabetes receiving statins than that of patients with T2DM and prediabetes not receiving statins (p = 0.002). The serum level of AKR1B10 was significantly higher in groups C and D than that of the other groups (p = 0.001). Conclusion: Atorvastatin can improve the level of GLO-1 activity and thereby prevent diabetic complications. [ABSTRACT FROM AUTHOR]

Introduction: Systemic lupus erythematosus (SLE) is a chronic, autoimmune disease, often characterised by severe course and unclear etiopathogenesis. The reaction of protein glycoxidation, also known as glycation, may be linked to etiopathogenesis of SLE. Advanced glycation end-products (AGEs) exhibit cytotoxic properties, affect cellular signalling, impair functions of extracellular proteins, and may act as neoepitopes. Glucosone (GS), glyoxal (GO), and methylglyoxal (MGO) are examples of α-dicarbonyl compounds (α-DCs) partaking in glycoxidation. The study aimed to evaluate concentrations of these three compounds in blood serum of SLE patients, and to compare the results with healthy individuals. Material and methods: 31 women suffering from SLE and 26 healthy individuals were included in the study. High-performance liquid chromatography with fluorescence detection was applied to evaluate concentrations of α-DCs in their serum samples. Correlations between the results and parameters such as disease duration time, age, glomerular filtration rate (GFR), Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K), and creatinine were analysed. Results: The SLE patients exhibited lower concentrations of glucosone, glyoxal, and methylglyoxal than the control group. Analysis of correlations showed a difference between the examined groups. Conclusions: In women suffering from SLE the course of α-DCs metabolism is altered. SLE patients are characterised by low serum levels of α-DCs. We hypothesise that either hindered proteasomal degradation or fast consumption of α-DCs in oxidative conditions may cause the observed low concentration of these compounds. [ABSTRACT FROM AUTHOR]

Excessive accumulation of advanced glycation end products (AGEs) in the body is associated with diabetes and its complications. In this study, we aimed to explore the potential and mechanism of coffee leaf extract (CLE) in inhibiting the generation of AGEs and their precursors in an in vitro glycation model using bovine serum albumin and glucose (BSA–Glu) for the first time. High‐performance liquid chromatography analysis revealed that CLE prepared with ultrasound pretreatment (CLE‐U) contained higher levels of trigonelline, mangiferin, 3,5‐dicaffeoylquinic acid, and γ‐aminobutyric acid than CLE without ultrasound pretreatment (CLE‐NU). The concentrations of these components, along with caffeine and rutin, were dramatically decreased when CLE‐U or CLE‐NU was incubated with BSA–Glu reaction mixture. Both CLE‐U and CLE‐NU exhibited a dose‐dependent inhibition of fluorescent AGEs, carboxymethyllysine, fructosamine, 5‐hydroxymethylfurfural, 3‐deoxyglucosone, glyoxal, as well as protein oxidation products. Notably, CLE‐U exhibited a higher inhibitory capacity compared to CLE‐NU. CLE‐U effectively quenched fluorescence intensity and increased the α‐helix structure of the BSA–Glu complex. Molecular docking results suggested that the key bioactive compounds present in CLE‐U interacted with the arginine residues of BSA, thereby preventing its glycation. Overall, this research sheds light on the possible application of CLE as a functional ingredient in combating diabetes by inhibiting the generation of AGEs. [ABSTRACT FROM AUTHOR]

Enols—tautomers of ketones or aldehydes—are considered key intermediates in the formation of prebiotic sugars and sugar acids. Although laboratory simulation experiments suggest that enols should be ubiquitous in the interstellar medium, the underlying formation mechanisms of enols in interstellar environments are largely elusive. Here, we present the laboratory experiments on the formation of glyoxal (HCOCHO) along with its ynol tautomer acetylenediol (HOCCOH) in interstellar ice analogs composed of carbon monoxide (CO) and water (H2O) upon exposure to energetic electrons as a proxy for secondary electrons generated from Galactic cosmic rays. Utilizing tunable vacuum ultraviolet photoionization reflectron time-of-flight mass spectrometry, glyoxal and acetylenediol were detected in the gas phase during temperature-programmed desorption. Our results reveal the formation pathways of glyoxal via radical–radical recombination of two formyl (HĊO) radicals, and that of acetylenediol via keto-enol-ynol tautomerization. Due to the abundance of carbon monoxide and water in interstellar ices, glyoxal and acetylenediol are suitable candidates for future astronomical searches. Furthermore, the detection of acetylenediol in astrophysically relevant ices advances our understanding for the formation pathways of high-energy tautomers such as enols in deep space. [ABSTRACT FROM AUTHOR]

Obesity is a complex condition associated with disruptions in carbohydrate, protein, and fat metabolism, linked to increased insulin resistance and glucose intolerance. High levels of Advanced Glycation End-products (AGEs) are associated with a range of chronic diseases, including kidney diseases, diabetic complications, cardiovascular diseases, and neurodegenerative diseases. Our study aims to investigate the accumulation of AGEs in the liver, renal and adipose tissues of mice fed a high-fat diet, contributing to a deeper understanding of obesity and its related metabolic disorders. Our study consists of three different groups fed with diets containing 60% and 10% fat. The Experiment 1 group was maintained on their diet for 12 weeks, while the obese 2 and control groups continued their diets for 24 weeks. AGEs in the liver and kidney tissues obtained were measured using the High-performance liquid chromatography grade (HPLC) method. Higher accumulation of AGEs has been observed in kidney tissue compared to adipose and liver tissues (p < 0.05). Moreover, the GO levels were notably higher in liver tissue than in adipose tissue of the D1 and D2 groups (p < 0.0001). Our results suggest that particularly in kidney tissue, increased filtration burden, functional impairment, and receptor interaction due to obesity may be effective. The lower levels of AGEs detected, especially in the obese groups compared to the control, can be attributed to the inability to metabolize AGEs due to tissue damage caused by obesity. [ABSTRACT FROM AUTHOR]

Metformin, a biguanide compound (N-1,1-dimethylbiguanide), is widely prescribed for diabetes mellitus type 2 (T2D) treatment. It also presents a plethora of properties, such as anti-oxidant, anti-inflammatory, anti-apoptosis, anti-tumorigenic, and anti-AGE formation activity. However, the precise mechanism of action of metformin in the central nervous system (CNS) needs to be clarified. Herein, we investigated the neuroprotective role of metformin in acute hippocampal slices exposed to methylglyoxal (MG), a highly reactive dicarbonyl compound and a key molecule in T2D developmental pathophysiology. Metformin protected acute hippocampal slices from MG-induced glutamatergic neurotoxicity and neuroinflammation by reducing IL-1β synthesis and secretion and RAGE protein expression. The drug also improved astrocyte function, particularly with regard to the glutamatergic system, increasing glutamate uptake. Moreover, we observed a direct effect of metformin on glutamate transporters, where the compound prevented glycation, by facilitating enzymatic phosphorylation close to Lys residues, suggesting a new neuroprotective role of metformin via PKC ζ in preventing dysfunction in glutamatergic system induced by MG. Proposed neuroprotection role of metformin in acute hippocampal slices against impairment in glutamatergic system induced in a model of methylglyoxal glycotoxicity. Metformin reversed methylglyoxal (MG)-induced neuroinflammation by reducing pro-inflammatory IL-1β synthesis and secretion and RAGE protein expression. Metformin did not alter the effect of MG on S100B secretion (1). Both MG and metformin also influenced astrocyte function in hippocampal slices. Metformin did not reverse the elevation in GLO1 activity induced by glycotoxicity; however, it abrogated the high GSH level and the expression of the co-factor of GLO1 (2). Both treatments per se changed bioenergetic metabolism and increased glucose uptake, extracellular lactate content, and pyruvate kinase (PK) activity. The increment in glucose uptake and lactate levels ceased during the co-incubation of MG with metformin. Metformin reversed the elevation of hexokinase activity by MG (3). We suggest a new role of metformin in the glutamate system, whereby it protects the hippocampus against the derangements of the glutamatergic system induced by MG, possibly by phosphorylation via PKC ζ (4). The neuroprotective action of metformin may be mediated by the phosphorylation of specific amino acid residues (Lysine) of the glutamate transporters (GLAST and GLT-1), since metformin activated the PKC ζ signaling and promoted cascades of phosphorylation in p38 MAPK and Akt proteins. The transporter protein phosphorylation prevented the Lys-glycation and the impairment of glutamate uptake induced by MG (5). [ABSTRACT FROM AUTHOR]