Hypertension has earned the “silent killer” nickname since it may lead to a number of comorbidities, including diabetes and cardiovascular diseases. Oxidative stress and protein glycation play vital roles in the pathogenesis of hypertension. Several studies have shown that they profoundly account for vascular dysfunction, endothelial damage, and disruption of blood pressure regulatory mechanisms. Of particular note are advanced glycation end products (AGEs). AGEs alter vascular tissues’ functional and mechanical properties by binding to receptors for advanced glycation end products (RAGE), stimulating inflammation and free radical-mediated pathways. Propranolol, a nonselective beta-adrenergic receptor antagonist, is one of the most commonly used drugs to treat hypertension and cardiovascular diseases. Our study is the first to analyze propranolol’s effects on protein glycoxidation through in vitro and in silico approaches. Bovine serum albumin (BSA) was utilized to evaluate glycoxidation inhibition by propranolol. Propranolol (1 mM) and BSA (0.09 mM) were incubated with different glycating (0.5 M glucose, fructose, and galactose for 6 days and 2.5 mM glyoxal and methylglyoxal for 12 h) or oxidizing agents (chloramine T for 1 h). Biomarkers of protein glycation (Amadori products (APs), β-amyloid (βA), and advanced glycation end products (AGEs)), protein glycoxidation (dityrosine (DT), kynurenine (KYN), and N-formylkynurenine (NFK)), protein oxidation (protein carbonyls (PCs), and advanced oxidation protein products (AOPPs)) were measured by means of colorimetric and fluorimetric methods. The scavenging of reactive oxygen species (hydrogen peroxide, hydroxyl radical, and nitric oxide) and the antioxidant capacity (2,2-diphenyl-1-picrylhydrazyl radical and ferrous ion chelating (FIC) assays)) of propranolol were also evaluated. Additionally, in silico docking was performed to showcase propranolol’s interaction with BSA, glycosides, and AGE/RAGE pathway proteins. The products of protein glycation (↓APs, ↓βA, ↓AGEs), glycoxidation (↓DT, ↓KYN, ↓NFK), and oxidation (↓PCs, ↓AOPPs) prominently decreased in the BSA samples with both glycating/oxidizing factors and propranolol. The antiglycoxidant properties of propranolol were similar to those of aminoguanidine, a known protein oxidation inhibitor, and captopril, which is an established antioxidant. Propranolol showed a potent antioxidant activity in the FIC and H2O2 scavenging assays, comparable to aminoguanidine and captopril. In silico analysis indicated propranolol’s antiglycative properties during its interaction with BSA, glycosidases, and AGE/RAGE pathway proteins. Our results confirm that propranolol may decrease protein oxidation and glycoxidation in vitro. Additional studies on human and animal models are vital for in vivo verification of propranolol’s antiglycation activity, as this discovery might hold the key to the prevention of diabetic complications among cardiology-burdened patients.

Ovarian cancer (OC) has emerged as the leading cause of death due to gynecological malignancies among women. Oxidative stress and metalloproteinases (MMPs) have been shown to influence signaling pathways and afflict the progression of carcinogenesis. Therefore, the assessment of matrix-remodeling and oxidative stress intensity can determine the degree of cellular injury and often the severity of redox-mediated chemoresistance. The study group comprised 27 patients with serous OC of which 18% were classified as Federation of Gynecology and Obstetrics (FIGO) stages I/II, while the rest were diagnosed grades III/IV. The control group comprised of 15 ovarian tissue samples. The results were compared with genetic data from The Cancer Genome Atlas. Nitro-oxidative stress, inflammation and apoptosis biomarkers were measured colorimetrically/fluorometrically or via real-time PCR in the primary ovarian tumor and healthy tissue. Stratification of patients according to FIGO stages revealed that high-grade carcinoma exhibited substantial alterations in redox balance, including the accumulation of protein glycoxidation and lipid peroxidation products. TCGA data demonstrated only limited prognostic usefulness of the studied genes. In conclusion, high-grade serous OC is associated with enhanced tissue oxidative/nitrosative stress and macromolecule damage that could not be overridden by the simultaneously augmented measures of antioxidant defense. Therefore, it can be assumed that tumor cells acquire adaptive mechanisms that enable them to withstand the potential toxic effects of elevated reactive oxygen species.

Introduction: Agomelatine is an atypical antidepressant drug enhancing norepinephrine and dopamine liberation; nevertheless, additional mechanisms are considered for the drug's pharmacological action. Since protein glycoxidation plays a crucial role in depression pathogenesis, agomelatine's impact on carbonyl/oxidative stress was the research purpose.Methods: Reactive oxygen species scavenging (hydroxyl radical, hydrogen peroxide, and nitrogen oxide) and antioxidant capacity (2,2-diphenyl-1-picrylhydrazyl radical and ferrous ion chelating assays) of agomelatine were marked. Agomelatine's antiglycoxidation properties were assayed in sugars (glucose, fructose, and galactose) and aldehydes- (glyoxal and methylglyoxal) glycated bovine serum albumin (BSA). Aminoguanidine and α-lipoic acid were used as standard glycation/oxidation inhibitors.Results: Agomelatine did not show meaningful scavenging/antioxidant capacity vs. standards. Sugars/aldehydes increased glycation (↑kynurenine, ↑N-formylkynurenine, ↑dityrosine, ↑advanced glycation end products, and ↑β-amyloid) and oxidation (↑protein carbonyls and ↑advanced oxidation protein products) parameters in addition to BSA. Standards restored BSA baselines of glycation and oxidation markers, unlike agomelatine which sometimes even intensifies glycation above BSA + glycators levels. Molecular docking analysis of agomelatine in BSA demonstrated its very weak binding affinity.Discussion: Agomelatine's very low affinity to the BSA could proclaim non-specific bonding and simplify attachment of glycation factors. Thereby, the drug may stimulate brain adaptation to carbonyl/oxidative stress as the systematic review indicates. Moreover, the drug's active metabolites could exert an antiglycoxidative effect.

Introduction: Glycoxidative stress is essential for linking glucose disturbances and cardiovascular diseases. Unfortunately, contemporary antidiabetic drugs do not have an antiglycative effect but only lower blood glucose levels. Therefore, there is an intense search for substances that could inhibit protein glycation and prevent diabetic complications. A potential antioxidant activity has been demonstrated with verapamil, a phenylalkylamine derivative belonging to selective calcium channel blockers. Verapamil has a well-established position in cardiology due to its wide range of indications and good safety profile. Nevertheless, the antidiabetic activity of verapamil is still unclear. We are the first to comprehensively evaluate the verapamil’s effect on protein glycoxidation using various in vitro and in silico models.Methods: Bovine serum albumin (BSA) was used to assess the rate of glycoxidation inhibition by verapamil. As glycating factors, sugars (glucose, fructose, and ribose) and aldehyde (glyoxal) were used. Chloramine T was used as an oxidizing agent. Aminoguanidine (protein glycation inhibitor) and Trolox (antioxidant) were used as control substances. The biomarkers of oxidation (total thiols, protein carbonyls, advanced oxidation protein products), glycation (Amadori products, β-amyloid, advanced glycation end products [AGEs]), and glycoxidation (tryptophan, kynurenine, N-formylkynurenine, dityrosine) were evaluated using colorimetric and fluorimetric methods. The mechanism of antiglycative activity of verapamil was assessed using in silico docking to study its interaction with BSA, glycosidases, and seventeen AGE pathway proteins.Results: In all in vitro models, biomarkers of protein glycation, oxidation, and glycoxidation were significantly ameliorated under the influence of verapamil. The glycoxidation inhibition rate by verapamil is comparable to that of potent antiglycating agents and antioxidants. The molecular docking simulations showed that verapamil bound preferentially to amino acids prone to glycoxidative damage out of an α-glucosidase’s active center. Among all AGE pathway proteins, verapamil was best docked with the Janus kinase 2 (JAK2) and nuclear factor-κB (NF-κB).Discussion: The results of our study confirm the antiglycoxidant properties of verapamil. The drug’s action is comparable to recognized substances protecting against oxidative and glycation modifications. Verapamil may be particularly helpful in patients with cardiovascular disease and concomitant diabetes. Studies in animal models and humans are needed to confirm verapamil’s antiglycative/antidiabetic activity.

Introduction: Idiopathic intracranial hypertension (IIH) is a rare neurological condition characterized by elevated intracranial pressure in the absence of a detectable cause. It predominantly affects obese women of childbearing age. The underlying pathophysiological mechanisms remain unclear, but increasing evidence suggests a significant role of obesity-related metabolic and hormonal disturbances. Materials and methods: A review of selected literature in the PubMed database was conducted, using the following keywords: “idiopathic intracranial hypertension”, “pseudotumor cerebri”, “obesity” Summary: The development of IIH appears to be multifactorial, involving impaired cerebrospinal fluid dynamics, venous outflow obstruction, and endocrine dysfunction. Obesity contributes through increased intra-abdominal and intracranial pressure, altered secretion of adipokines (such as leptin), and chronic low-grade inflammation. The review highlights the role of obesity as a modifiable risk factor and the impact of weight loss on symptom relief and disease progression. Conclusions: Understanding the link between obesity and IIH is crucial for effective prevention and treatment. Multidisciplinary care, including neurologists, ophthalmologists, and nutritionists, should focus on weight management and early detection of visual complications. Further research is needed to clarify the molecular mechanisms involved and to develop more targeted therapeutic strategies.

Introduction: Prader-Willi syndrome (PWS) is a rare genetic disorder whose most characteristic and dangerous symptom is massive obesity. It develops as a result of neurohormonal abnormalities, abnormal appetite regulation and reduced energy expenditure. Due to its multifactorial nature, the treatment of obesity in PWS presents particular clinical challenges. Materials and methods: A review of selected literature in the PubMed database was conducted, using the following keywords: “Prader Willie Syndrom”, “Phisical excercise”, “Obesity”,”Treatment” Summary: This paper discusses the main mechanisms leading to the development of obesity in PWS, such as hypothalamic dysfunction, endocrine disruption (ghrelin, leptin, GH) and changes in body composition. Current therapeutic strategies - nutritional therapy adapted to the developmental stage of the patient, growth hormone treatment and the potential use of anti-obesity drugs - were analysed. Special attention was given to the role of physical activity, which, despite its limited effect on body weight, significantly improves fitness, muscle strength, body composition and quality of life in patients. Conclusions: The management of obesity in PWS requires an individualised, multidirectional approach based on collaboration between the specialist team and the family. Given the limited efficacy of available therapies, further research is needed into new treatments - both pharmacological and non-pharmacological - that are better adapted to the metabolic and behavioural specificities of this patient group.