Prostate cancer is the most commonly diagnosed malignancy in men and continues to be a leading cause of cancer-related mortality. Accurate and timely diagnosis is essential for distinguishing clinically significant tumors from indolent lesions and for informing treatment decisions. Multiparametric magnetic resonance imaging (mpMRI) has revolutionized prostate cancer detection by enabling precise lesion localization, risk stratification, and improved biopsy targeting. Fusion biopsy, which combines mpMRI findings with real-time transrectal ultrasonography (TRUS), has emerged as a highly effective method for sampling suspicious lesions. This review provides an integrated anatomical, epidemiological, technical, and clinical overview that highlights the evolving role of fusion biopsy in contemporary prostate cancer diagnostics. We also explore emerging strategies such as penumbra-targeted sampling, discuss ongoing clinical challenges, and examine the impact of biopsy underestimation and lack of standardization. Compared to conventional systematic biopsy, mpMRI-TRUS fusion biopsy improves the detection of clinically significant prostate cancer while reducing the overdiagnosis of low-risk tumors. To our knowledge, few recent reviews have comprehensively synthesized current clinical guidelines, emerging biopsy techniques, and future directions within a single narrative. mpMRI-TRUS-guided fusion biopsy represents a major advancement in the prostate cancer diagnostic pathway, promoting precision oncology by reducing overtreatment and facilitating individualized patient care. This review aims to assist clinicians in adopting biopsy innovations that enhance diagnostic accuracy and improve patient outcomes.

The research determined the role of α‐lipoic acid (ALA) in reducing the brain manifestations of insulin resistance. The mechanism of ALA action is mainly based on its ability to “scavenge” oxygen free radicals and stimulate biosynthesis of reduced glutathione (GSH), considered the most critical brain antioxidant. Although the protective effect of ALA is widely documented in various diseases, there are still no studies assessing the influence of ALA on brain metabolism in the context of insulin resistance and type 2 diabetes. The experiment was conducted on male Wistar rats fed a high‐fat diet for ten weeks with intragastric administration of ALA for four weeks. We are the first to demonstrate that ALA improves the function of enzymatic and nonenzymatic brain antioxidant systems, but the protective effects of ALA were mainly observed in the hypothalamus of insulin‐resistant rats. Indeed, ALA caused a significant increase in superoxide dismutase, catalase, peroxidase, and glutathione reductase activities, as well as GSH concentration and redox potential ([GSH]²/[GSSG]) in the hypothalamus of HFD‐fed rats. A consequence of antioxidant barrier enhancement by ALA is the reduction of oxidation, glycation, and nitration of brain proteins, lipids, and DNA. The protective effects of ALA result from hypothalamic activation of the transcription factor Nrf2 and inhibition of NF‐κB. In the hypothalamus of insulin‐resistant rats, we demonstrated reduced levels of oxidation (AOPP) and glycation (AGE) protein products, 4‐hydroxynoneal, 8‐isoprostanes, and 3‐nitrotyrosine and, in the cerebral cortex, lower levels of 8‐hydroxydeoxyguanosine and peroxynitrite. In addition, we demonstrated that ALA decreases levels of proinflammatory TNF‐α but also increases the synthesis of anti‐inflammatory IL‐10 in the hypothalamus of insulin‐resistant rats. ALA also prevents neuronal apoptosis, confirming its multidirectional effects within the brain. Interestingly, we have shown no correlation between brain and serum/plasma oxidative stress biomarkers, indicating the different nature of redox imbalance at the central and systemic levels. To summarize, ALA improves antioxidant balance and diminishes oxidative/glycative stress, protein nitrosative damage, inflammation, and apoptosis, mainly in the hypothalamus of insulin‐resistant rats. Further studies are needed to determine the molecular mechanism of ALA action within the brain.

Background: Aging is inextricably linked to oxidative stress, inflammation, and posttranslational protein modifications. However, no studies evaluate oxidation, glycation, and carbamylation of salivary biomolecules as biomarkers of aging. Saliva collection is non-invasive, painless, and inexpensive, which are advantages over other biofluids. Methods: The study enrolled 180 healthy subjects divided into six groups according to age: 6– 13, 14– 19, 20– 39, 40– 59, 60– 79, and 80– 100 years. The number of individuals was determined a priori based on our previous experiment (power of the test = 0.8; α = 0.05). Non-stimulated saliva and plasma were collected from participants, in which biomarkers of aging were determined by colorimetric, fluorometric, and ELISA methods. Results: The study have demonstrated that modifications of salivary proteins increase with age, as manifested by decreased total thiol levels and increased carbonyl groups, glycation (Nϵ-(carboxymethyl) lysine, advanced glycation end products (AGE)) and carbamylation (carbamyl-lysine) protein products in the saliva of old individuals. Oxidative modifications of lipids (4-hydroxynonenal) and nucleic acids (8-hydroxy-2’-deoxyguanosine (8-OHdG)) also increase with age. Salivary redox biomarkers correlate poorly with their plasma levels; however, salivary AGE and 8-OHdG generally reflect their blood concentrations. In the multivariate regression model, they are a predictor of aging and, in the receiver operating characteristic (ROC) analysis, significantly differentiate children and adolescents (under 15 years old) from the working-age population (15– 64 years) and the older people (65 years and older). Conclusion: Salivary AGE and 8-OHdG have the most excellent diagnostic utility in assessing the aging process. Saliva can be used to evaluate the aging of the body. Graphical Abstract:

Stroke is one of the most common cerebrovascular diseases. Despite significant progress in understanding stroke pathogenesis, cases are still increasing. Thus, laboratory biomarkers of stroke are sought to allow rapid and non-invasive diagnostics. Ischemia-reperfusion injury is an inflammatory process with characteristic cellular changes leading to microvascular disruption. Several studies have shown that hyperactivation of xanthine oxidase (XO) is a major pathogenic factor contributing to brain dysfunction. Given the critical role of XO in stroke complications, this study aimed to evaluate the activity of the enzyme and its metabolic products in the saliva of stroke subjects. Thirty patients in the subacute phase of stroke were included in the study: 15 with hemorrhagic stroke and 15 with ischemic stroke. The control group consisted of 30 healthy subjects similar to the cerebral stroke patients regarding age, gender, and status of the periodontium, dentition, and oral hygiene. The number of individuals was determined a priori based on our previous experiment (power of the test = 0.8; α = 0.05). The study material was mixed non‐stimulated whole saliva (NWS) and stimulated saliva (SWS). We showed that activity, specific activity, and XO output were significantly higher in NWS of ischemic stroke patients than in hemorrhagic stroke and healthy controls. Hydrogen peroxide and uric acid levels were also considerably higher in NWS of ischemic stroke patients. Using receiver operating curve (ROC) analysis, we demonstrated that XO-specific activity in NWS distinguishes ischemic stroke from hemorrhagic stroke (AUC: 0.764) and controls (AUC: 0.973) with very high sensitivity and specificity. Saliva collection is stress-free, requires no specialized medical personnel, and allows continuous monitoring of the patient’s condition through non-invasive sampling multiple times per day. Salivary XO also differentiates with high accuracy (100%) and specificity (93.75%) between stroke patients with mild to moderate cognitive decline (AUC = 0.988). Thus, salivary XO assessment may be a potential screening tool for a comprehensive neuropsychological evaluation. To summarize, our study demonstrates the potential utility of salivary XO in the differential diagnosis of stroke.

An important drug used in the treatment of Parkinson’s disease is amantadine. We are the first to perform a comprehensive study based on various glycation and oxidation factors, determining the impact of amantadine on protein glycoxidation. Sugars (glucose, fructose, galactose) and aldehydes (glyoxal, methylglyoxal) were used as glycation agents, and chloramine T was used as an oxidant. Glycoxidation biomarkers in albumin treated with amantadine were generally not different from the control group (glycation/oxidation factors), indicating that the drug did not affect oxidation and glycation processes. Molecular docking analysis did not reveal strong binding sites of amantadine on the bovine serum albumin structure. Although amantadine poorly scavenged hydroxyl radical and hydrogen peroxide, it had significantly lower antioxidant and antiglycation effect than all protein oxidation and glycation inhibitors. In some cases, amantadine even demonstrated glycoxidant, proglycation, and prooxidant properties. In summary, amantadine exhibited weak antioxidant properties and a lack of antiglycation activity. Graphical Abstract

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.