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Glycation is a non-enzymatic process involving the reaction of reducing sugars or reactive oxoaldehyde with proteins, lipids or nucleic acids, which results in the formation of advanced glycation end products (AGEs). The presented work discusses the glycation process in people with advanced stage of type 1 or type 2 diabetes. The concentration of different AGEs and their receptors for 58 serum samples was determined by ELISA and by spectrofluorimetric methods. In addition to fluorescent low molecular weight and protein-bound AGEs, we have also marked a new class of AGEs: melibiose-derived glycation product (MAGE). Our attention was also focused on the two groups of AGEs receptors: scavenger receptors (SR-A and SR-B) and RAGE. The correlation between the SR-AI scavenging receptors concentration and the fluorescence of AGEs as well as diabetes biological markers: GFR, creatinine contentration and HbA1c was demonstrated. A relationship between the concentration of AGEs and their receptors was also found in serum sample of patients treated with the metformin and aspirin. Furthermore, the concentration of SR-AI scavenger and the fluorescence of total AGEs was significantly lower in treated patients than in non treated patients. AGEs have also been found to contribute to the development of cardiovascular disease, atherosclerosis and diabetic complications, what could be deduced from the correlation of AGEs level and HDL cholesterol or uric acid level. Thus, it was confirmed that AGEs are involved in the pathomechanism of diabetes and other degenerative diseases. Nowadays, it is believed that AGEs due to the long time remaining in the body may be an important diagnostic marker. Their determination may allow monitoring the progression of the disease and the effectiveness of the therapy.

Elucidating the biochemical mechanisms associated with the progression of alcoholic liver disease (ALD) to more advanced stages such as alcoholic hepatitis (AH) remains an important clinical and scientific challenge. Several hypotheses point to the involvement of advanced glycation end-products (AGEs) in alcohol-associated liver injuries. Recently, we determined the structure of a synthetic, melibiose-derived AGE (MAGE), which was an analog of the novel AGE subgroup AGE10. The primary objective of our study was to determine whether AGE10 was associated with alcoholic hepatitis. The secondary objective was to provide a diagnostic accuracy of AGE10 in AH. To achieve this objective, we examined the plasma levels of AGE10 in 65 healthy individuals and 65 patients with AH. The AGE10 level was measured using a competitive ELISA. Our study confirmed that patients with AH had significantly higher plasma concentrations of AGE10 compared with healthy controls (184.5 ± 71.1 μg/mL and 123.5 ± 44.9 μg/mL, respectively; p < 0.001). In addition, AGE10 showed an acceptable performance as a diagnostic marker of AH, with an AUC of 0.78. In conclusion, AH was associated with elevated levels of novel advanced glycation end-product AGE10.

Despite the restrictive legal regulations related to the reduction of dioxins emission, their concentration in the environment is still too high. Mainly, this is related to the illegal utilisation of electronic equipment and combustion of wastes, and also to intensified activity and maintenance of ships, especially in developing countries. The most important remaining source in Europe is the metal industry. Studies on the mechanism of impact of dioxins are still being carried out. This review points at new possibilities for limiting the molecular mechanisms of dioxins activity, inter alia, through the application of high doses of tocopherol and acetylsalicylic acid while treating dioxins intoxication. BRIEF DESCRIPTION OF THE STATE OF KNOWLEDGE: Apart from the knowledge of dioxins affinity to the aryl hydrocarbon receptor (AhR), the multi-stage radical-form actions and the pro-inflammatory mechanism associated with cyclooxygenase-II enzyme (COX-2) are under intense investigation at the moment. Due to the high affinity of dioxins to animals adipose tissue and their ability to accumulate in it, they can enter the food chain. Furthermore, high dioxin doses can cause poisoning manifested as advanced clinical symptoms, whereas in smaller doses, when cumulated, can cause metabolic changes which are often difficult to associate with their presence. Recently, some serious food contaminations by dioxins have been demonstrated. Sea fish and products from contaminated aqueducts still constitute potential sources of dioxins pollution. According to recent studies, dioxins are present in different concentrations in the environment and cause specific and long-time effects. These effects could be limited by the use of tocopherol and acetylsalicylic acid.

Reactive carbonyls such as 4-hydroxy-2-nonenal (4-HNE), trans-2-nonenal (T2 N), acrolein (ACR) can react readily with nucleophilic protein sites forming of advanced glycation end-products (AGE). In this study, the human and pig muscle-specific enolase was used as a protein model for in vitro modification by 4-HNE, T2 N and ACR. While the human enolase interaction with reactive α-oxoaldehyde methylglyoxal (MOG) was demonstrated previously, the effect of 4-HNE, T2 N and ACR has not been identified yet. Altering in catalytic function were observed after the enzyme incubation with these active compounds for 1–24 h at 25, 37 and 45 °C. The inhibition degree of enolase activity occurred in following order: 4-HNE > ACR > MOG > T2 N and inactivation of pig muscle-specific enolase was more effective relatively to human enzyme. The efficiency of AGE formation depends on time and incubation temperature with glycating agent. More amounts of insoluble AGE were formed at 45 °C. We found that pirydoxamine and natural dipeptide carnosine counteracted AGE formation and protected enolase against the total loss of catalytic activity. Moreover, we demonstrated for the first time that phosphatidylserine may significantly protect enolase against decrease of catalytic activity in spite of AGE production.

Advanced glycation end-products (AGEs) contribute to vascular complications and organ damage in diabetes. The unique AGE epitope (AGE10) has recently been identified in human serum using synthetic melibiose-derived AGE (MAGE). We aimed at developing ELISA for AGE10 quantification, determining whether AGE10 is present in diabetic patients (n = 82), and evaluating its association with diabetic complications. In a competitive ELISA developed, the reaction of synthetic MAGE with anti-MAGE was inhibited by physiological AGE10 present in serum. In this assay, new murine IgE anti-MAGE monoclonal antibodies, which do not recognize conventional AGEs, a synthetic MAGE used to coat the plate, and LMW-MAGE (low molecular mass MAGE) necessary to plot a standard curve were used. AGE10 was significantly higher in patients with microangiopathy, in whom it depended on treatment, being lower in patients treated with aspirin. AGE10 levels were positively correlated with estimated glomerular filtration rate (eGFR) and negatively with creatinine. As a marker of stage ≥3 chronic kidney disease or microangiopathy, AGE10 displayed moderate overall accuracy (respectively, 69% and 71%) and good sensitivity (82.6% and 83.3%) but poor specificity (58.1% and 57.8%). In conclusion, newly developed immunoassay allows for AGE10 quantification. AGE10 elevation is associated with microangiopathy while its decrease accompanies stage ≥3 chronic kidney disease.

To date, thyroid cancers (TCs) remain a clinical challenge owing to their heterogeneous nature. The etiopathology of TCs is associated not only with genetic mutations or chromosomal rearrangements, but also non-genetic factors, such as oxidative-, nitrosative-, and carbonyl stress-related alterations in tumor environment. These factors, through leading to the activation of intracellular signaling pathways, induce tumor tissue proliferation. Interestingly, the incidence of TCs is often coexistent with various simultaneous mutations. Advanced glycation end-products (AGEs), their precursors and receptors (RAGEs), and other ligands for RAGEs are reported to have significant influence on carcinogenesis and TCs progression, inducing gene mutations, disturbances in histone methylation, and disorders in important carcinogenesis-related pathways, such as PI3K/AKT/NF-kB, p21/MEK/MPAK, or JAK/STAT, RAS/ERK/p53, which induce synthesis of interleukins, growth factors, and cytokines, thus influencing metastasis, angiogenesis, and cancer proliferation. Precursors of AGE (such as methylglyoxal (MG)) and selected ligands for RAGEs: AS1004, AS1008, and HMGB1 may, in the future, become potential targets for TCs treatment, as low MG concentration is associated with less aggressive anaplastic thyroid cancer, whereas the administration of anti-RAGE antibodies inhibits the progression of papillary thyroid cancer and anaplastic thyroid cancer. This review is aimed at collecting the information on the role of compounds, engaged in glycation process, in the pathogenesis of TCs. Moreover, the utility of these compounds in the diagnosis and treatment of TCs is thoroughly discussed. Understanding the mechanism of action of these compounds on TCs pathogenesis and progression may potentially be the grounds for the development of new treatment strategies, aiming at quality-of-life improvements.

Non-enzymatic modification of proteins by carbohydrates, known as glycation, leads to generation of advanced glycation end-products (AGEs). In our study we used in vitro generated AGEs to model glycation in vivo. We discovered in vivo analogs of unusual melibiose-adducts designated MAGEs (mel-derived AGEs) synthesized in vitro under anhydrous conditions with bovine serum albumin and myoglobin. Using nuclear magnetic resonance spectroscopy we have identified MAGEs as a set of isomers, with open-chain and cyclic structures, of the fructosamine moiety. We generated a mouse anti-MAGE monoclonal antibody and show for the first time that the native and previously undescribed analogous glycation product exists in living organisms and is naturally present in tissues of both invertebrates and vertebrates, including humans. We also report MAGE cross-reactive auto-antibodies in patients with diabetes. We anticipate our approach for modeling glycation in vivo will be a foundational methodology in cell biology. Further studies relevant to the discovery of MAGE may contribute to clarifying disease mechanisms and to the development of novel therapeutic options for diabetic complications, neuropathology, and cancer.

Modern medicine requires effective, continuous, and safe therapies, which largely depend on the targeted delivery and activity of the drug. This goal can be achieved by designing drug delivery systems with improved pharmacokinetic properties and enhanced drug transport to the affected tissue. Human serum albumin (HSA) is an attractive carrier for the synthesis of therapeutic nanoparticles, several of which have already been approved by the United States Food and Drug Administration (FDA). The success of Abraxane as an effective treatment for metastatic breast cancer and non-small cell lung carcinoma, the application of Optison in ultrasound imaging, and the use of Nanocoll as an agent for SPECT diagnostics in sentinel node localisation confirm the strong potential of albumin-based systems. Further benefits are expected in patients with soft tissue cancers, as LadRx is seeking FDA marketing approval for Aldoxorubicin. The future of oncology lies in theranostics, which combines a tumour-localising factor on one platform with a drug targeting cancer cells and a factor that activates the cytotoxicity of the drug after it reaches the target tissue. This article presents recent advancements in albumin-based nanoparticles for drug delivery, targeting, and imaging. It also briefly discusses methods of synthesis and surface modification of albumin nanocarriers to enable targeted delivery to pathological sites. Finally, it outlines the latest approaches in multimodal theranostic platforms, highlighting albumin’s potential to improve cancer therapy.

The COVID-19 pandemic has revealed that viruses can have multiple receptor properties, penetrating various tissues and causing mutations in various genes, thus promoting a range of metabolic disorders. The purpose of this study was to investigate the connection between three factors: diabetic status, pre-hospitalization oxygen therapy, and saturation levels, to the values of morphological, inflammatory, and biochemical parameters in the blood serum of COVID-19 patients. The study group consisted of 2139 patients, 1076 women (50.30%) and 1063 men (49.70%), with an average age of 63.73 ± 15.69 years. The population was divided into three groups based on a three-stage scale, taking into account patients with either type 2 diabetes/prediabetes (473 patients), those who received oxygen therapy before hospitalization, and those with a saturation value of below 95% (cut-off value). Among patients who did not receive pre-hospitalization oxygen therapy, those with diabetes and a SpO2 level < 95% had significantly higher levels of D-dimers, procalcitonin, albumin, lymphocytes, RDW-SD ≥ 47, potassium, creatinine, and troponin T when compared to diabetic patients with a SpO2 level ≥ 95%. Similarly, in the same group of patients without pre-hospitalization oxygen therapy, those without diabetes but with a SpO2 level < 95% showed significantly increased levels of IL-6, CRP, albumin, lymphocytes, RDW-SD ≥ 47, glucose, potassium, sodium, creatinine, and ALT, compared to patients without diabetes and with a SpO2 level ≥ 95%. The findings suggest that lower saturation levels may result in increased potassium and glucose levels in patients who did not receive any oxygen therapy before hospitalization due to COVID-19. It is hypothesized that this may be caused by damage to pancreatic β-cells by SARS-CoV-2, and disturbances in the potassium channel, leading to cell membrane depolarization and insulin secretion.

Background: Sleep bruxism (SB), a sleep behavior, is one of the most common sleep pathologies. Tenascin-C (TnC) and thrombospondin-1 (TSP-1) are involved in the pathogenesis of cardiovascular disease. The aim of our study was to assess the relationship between SB and TSP-1 and TnC. Methods: A total of 80 participants, who were hospitalized in the Sleep Laboratory of the Department of Internal Medicine, Occupational Diseases, Hypertension, and Clinical Oncology at Wroclaw Medical University, were enrolled in the study. Polysomnographic examination was conducted following the standard sleep evaluation criteria set by the American Academy of Sleep Medicine, utilizing the Nox-A1 device. Serum TnC and TSP-1 concentrations were determined using Elisa Kits. Results: The study showed an increased concentration of TnC in the group of patients with a BEI (bruxism episode index) >10.3, compared to <10.3 (6786.79 ± 5655.62 vs. 1585.16 ± 2526.56). In regression analysis, higher values of phasic bruxism, smoking, and older age were independently associated with increased concentrations of TnC in the serum. Moreover, higher values of tonic bruxism, as well as smoking, were independently associated with TSP-1. Conclusions: Since tenascin-C and thrombospondin-1 levels are associated with sleep bruxism, atherosclerosis may be a potential consequence of SB. This relationship is especially noticeable in severe bruxism. Therefore, monitoring for clinical signs of atherosclerosis should be considered in patients with severe bruxism.