Background: Lone atrial fibrillation (AF) is characterized by the absence of discernible risk factors, yet its long-term prognostic implications remain unclear. We evaluated genetic predisposition to lone AF and conducted a Mendelian randomization (MR) study to assess its causal effect on cardiovascular outcomes. Methods: A genome-wide association study (GWAS) for lone AF, along with common AF was conducted using UK Biobank data. Lone AF was defined as AF occurring without clinical risk factors. Summary-level data for cardiovascular phenotypes were obtained from publicly available GWAS datasets and the causal effects were estimated using MR. Results: We identified 36 single-nucleotide polymorphisms associated with lone AF, including two novel loci. In MR analyses, lone AF was significantly associated with an increased risk of stroke (odds ratio [OR] 2.62, 95% confidence interval [CI] 2.14-3.22) and heart failure (HF) (OR 2.55, 95% CI 2.14-3.04). The associations with coronary artery disease (CAD) (OR 0.90, 95% CI 0.73-1.10) and cardiac death (OR 1.32, 95% CI 0.99-1.77) were not significant. MR analyses of common AF also demonstrated significant associations with stroke (OR 1.86, 95% CI 1.69-2.04) and HF (OR 1.71, 95% CI 1.59-1.84), though the effect sizes were smaller compared to those of lone AF. Conclusions: Genetic predisposition to lone AF is associated with more than a twofold increase in the risk of stroke and HF. However, no clear association was observed between lone AF and CAD or cardiac death.

Cellular senescence is a permanent cell cycle arrest that plays a critical role in the development and pathogenesis of age-related diseases. This paper aims to present the biological mechanisms of cellular senescence and the role of the senescence-associated secretory phenotype (SASP) in the pathogenesis of atherosclerosis, as well as to discuss therapeutic strategies targeting senescent cells in cardiovascular diseases. Different types of cellular senescence are described, including replicative, stress-induced, and oncogene-induced senescence, along with the composition and regulation of SASP and its impact on chronic inflammation, endothelial dysfunction, vascular remodeling, and plaque destabilization. The involvement of senescent endothelial cells, vascular smooth muscle cells, and macrophages in the initiation and progression of atherosclerosis is also discussed. The paper reviews current research on senolytic and senomorphic therapies and highlights emerging approaches such as immunosenolytic and epigenetic interventions. The therapeutic potential of these strategies in reducing chronic vascular inflammation and improving plaque stability, as well as their limitations and challenges in clinical application, is emphasized.

Personalized anesthesia has emerged as a key direction in modern perioperative medicine, driven by advances in molecular biology, analytical technologies, and digital monitoring. Traditional physiological parameters often fail to detect early stages of organ dysfunction, whereas molecular biomarkers provide earlier and more sensitive insight into inflammation, oxidative stress, neurotoxicity, and renal or hepatic injury. Inflammatory markers such as IL-6, CRP, and PCT indicate early immune activation, while oxidative stress biomarkers, including 8-isoprostanes and malondialdehyde, quantify metabolic imbalance and ischemia-reperfusion injury. Neurotoxicity biomarkers such as S100β, NSE, and GFAP allow early detection of subclinical cerebral injury, whereas kynurenine-pathway metabolites reflect neuroinflammation and the risk of postoperative cognitive dysfunction. Renal biomarkers such as NGAL, KIM-1, and cystatin C detect acute kidney injury significantly earlier than creatinine, and miR-122 holds strong potential as an early marker of hepatocellular injury. Genetic and epigenetic biomarkers-including polymorphisms in CYP2D6, CYP3A4/5, RYR1, OPRM1, and COMT, as well as microRNA-based signatures-enable individualized drug dosing and optimization of anesthetic strategies. Meanwhile, digital biomarkers such as EEG-derived indices, HRV, and NIRS provide continuous real-time physiological monitoring and can integrate with AI-based algorithms for predictive, adaptive anesthesia management. Although no single biomarker meets all criteria for an ideal clinical indicator, combining molecular, genetic, and digital biomarkers represents the most promising pathway toward fully personalized, safe, and outcome-optimized perioperative care.

Background: This study aimed to assess the effects of postbiotic derived from Bacillus subtilis natto (Szendi2020) on endothelial responses under LPS-induced inflammatory stress. Methods: In human umbilical vein endothelial cells (HUVECs), inflammation was induced with 200 ng/mL LPS. Cell viability, apoptosis, and mitochondrial integrity were assessed using MTT assay, DiIC, and Sytox Green permeability assays. Intracellular ROS levels, heat shock proteins (HSPB1/Hsp27, HSPA1L/Hsp70), adhesion molecules (ICAM-1, VCAM-1), tight junction protein (Occludin), transcription regulators (NF-κB, TNFα), and proinflammatory cytokines (IL-1β, IL-6, IL-8) were quantified using qPCR and ELISA. Results: LPS exposure significantly induced apoptosis in HUVECs, as reflected by decreased metabolic activity, decreased mitochondrial membrane potential, and increased cell death (p < 0.05). Concurrent postbiotic administration completely abolished LPS-induced cytotoxicity in all assay platforms, demonstrating a potent cytoprotective effect. Postbiotic treatment significantly reduced LPS-induced ROS accumulation (p < 0.05). LPS significantly increased Hsp27 and Hsp70 mRNA expression. However, combined LPS and postbiotic exposure mitigated Hsp27 and Hsp70 mRNA expression compared with LPS treatment alone (p < 0.001, p < 0.005). Postbiotic treatment also decreased the upregulation of adhesion molecules induced by LPS. Although this effect decreased after 24 h (p < 0.001). LPS strongly increased NF-κB, IL-1β and TNFα mRNA levels and was suppressed by postbiotics at early time points but not maintained over 24 h. Importantly, postbiotics significantly reduced IL-6, and IL-8 expression at both the mRNA and protein levels, highlighting the attenuation of endothelial inflammatory features (p < 0.05, p < 0.005, p < 0.001). Conclusions: Our results are the first to demonstrate that postbiotics derived from Bacillus subtilis natto (Szendi2020) exert potent cytoprotective and anti-inflammatory effects in LPS-induced endothelial inflammation. By reducing ROS accumulation, preventing apoptosis, stabilizing mitochondrial and barrier integrity, modulating HSP, NF-κB, and cytokine responses. Postbiotics may be promising therapeutic candidates for alleviating endothelial inflammation and the resulting endothelial dysfunction.

Cardiovascular disease is a major cause of death worldwide and a global socio-economic problem. To date, there are numerous studies focused on finding new biomarkers of cardiovascular diseases. High-technological methods such as mass spectrometry (MS), high-performance liquid chromatography (HPLC), and nuclear magnetic resonance (NMR) spectroscopy enable us to record thousands of metabolites of organs and tissues. Studying organisms at a molecular level contributes to an in-depth understanding of preclinical conditions of various diseases. Metabolomics reflects the dynamics of metabolism distribution, including environmental influences, allowing us to create a metabolic profile of the patient. The aim of this review was to analyze current data on metabolomic and proteomic biomarkers in the diagnosis of cardiovascular diseases. The search databases were used to select studies on the potential clinical and diagnostic application of proteomic and metabolomic markers in cardiology. The selected sources were subjected to qualitative and thematic analysis. All biomarkers were grouped according to the pathophysiological process (inflammation, blood coagulation and lipid metabolism disorders, myocardial necrosis, etc.). The association of changes in metabolomic and proteomic profiles with the activation of pathogenic processes in the cardiovascular system was demonstrated. The use of these multivariate markers, individually or in combination, will increase the accuracy of early diagnosis and the effectiveness of treatment. This article also highlights the limitations of the method and possible ways to solve them.

Oxidative stress and redox (REDOX) imbalance play a key role in the development of many chronic and degenerative disorders, including cardiovascular diseases, neurodegenerative conditions, cancer, and age-related illnesses. Beyond causing direct damage to macromolecules, disrupted REDOX signaling affects cellular homeostasis, alters inflammatory responses, and modifies metabolic control, leading to disease onset and progression. Therefore, targeting oxidative pathways offers a promising therapeutic approach for managing chronic diseases. Naturally derived antioxidants, especially phytochemicals such as polyphenols, flavonoids, and carotenoids, have been identified as novel REDOX modulators with diverse biological effects that extend beyond simple free-radical scavenging. This review provides a detailed overview of the molecular mechanisms through which these phytochemicals influence oxidative pathways and exert protective effects on cells. We discuss their relevance in oxidative stress-related diseases, evaluate current clinical evidence regarding their efficacy, and highlight key challenges that limit their clinical application. Special attention is given to the roles of bioavailability, metabolism, and gut microbiota in shaping health outcomes associated with phytochemical consumption. Additionally, we outline emerging strategies to enhance phytochemical efficacy, including synergistic combinations and advanced delivery systems. Overall, this article underscores the potential of phytochemicals as active modulators of REDOX biology, supporting their role in precision nutrition and modern therapeutic approaches.

Reactive oxygen species (ROS) have traditionally been viewed as pathological by-products of metabolism that drive tissue damage through oxidative stress. However, accumulating evidence across chronic diseases, including metabolic, cardiovascular, neurodegenerative disorders, and cancer, indicates that ROS also function as tightly regulated signaling molecules essential for cellular adaptation and survival. This paradigm shift from oxidative stress to redox signaling necessitates a fundamental re-evaluation of how redox imbalance contributes to chronic disease pathogenesis. In this review, we propose that chronic diseases should be understood as disorders of maladaptive redox homeostasis rather than simple consequences of excessive oxidative damage. We delineate the distinction between oxidative stress and redox signaling, emphasizing how chronic redox remodeling stabilizes pathological cellular states through coordinated regulation of key redox-sensitive transcriptional nodes, including KEAP1-NRF2, FOXO, HIFs, and NF-κB. Using cancer as a representative model, we illustrate how elevated but buffered ROS levels support oncogenic signaling, metabolic rewiring, and therapeutic resistance through redox addiction. We further discuss why non-specific antioxidant strategies have largely failed and argue that effective intervention requires context-dependent redox modulation rather than global ROS suppression. Finally, we introduce therapeutic redox reprogramming and outline future directions for precision redox medicine based on biomarker-guided stratification and disease stage-specific targeting strategies.

Cardiovascular diseases (CVDs) remain the leading cause of mortality worldwide. CVDs are associated with multiple factors, including oxidative stress, mediated endothelial dysfunction, vascular inflammation, and atherothrombosis. Although traditional antioxidant supplementation (such as vitamins C, E, and β-carotene) has shown promising results in rigorous animal model studies, it has consistently failed to demonstrate clinical benefit in most human trials. Consequently, there is a substantial unmet need for novel paradigms involving mechanistically and biologically relevant pharmaceutical-grade antioxidant therapies ("next-generation antioxidants"). Rapid advancements in redox biology, nanotechnology, genetic modulation of redox processes, and metabolic regulation have enabled the development of new antioxidant therapeutics, including mitochondrial-targeted agents, NADPH oxidase (NOX) inhibitors, selenoprotein and Nrf2 activators, engineered nanoparticles, catalytic antioxidants, and RNA-based and gene-editing strategies. These interventions have the potential to modulate specific oxidative pathways that contribute to CVD pathogenesis. This review provides a comprehensive assessment of current oxidative stress-modulating modalities and their potential to inform personalized cardiovascular prevention and treatment strategies.

Recent advances in single-cell RNA sequencing (scRNA-seq) have substantially deepened our understanding of adult hippocampal neurogenesis (AHN), enabling the detection of neural stem cells, progenitors, and immature neurons in postmortem human brain tissue and revealing how these populations are altered in neurological disease. Additionally, scRNA-seq enables the identification of disease-specific cell subtypes and distinct gene expression signatures associated with neurological disorders, many of which are linked to alterations in AHN and cognitive function. Such cellular- and molecular-level insights into neurological disease mechanisms provide a strong foundation for the development of targeted therapeutic strategies. Indeed, scRNA-seq has also emerged as a powerful tool in drug discovery and development across multiple disease areas, including cancer, cardiovascular disorders, and neurological conditions. In this review, we offer a comprehensive and integrative perspective on the cellular and molecular landscape of human hippocampal neurogenesis, the pathological mechanisms underlying neurological disorders, and their implications for therapeutic development.

In carbon monoxide (CO) therapy, CO is administered at low concentrations as a controlled solution; this approach enables the drug to achieve its cytoprotective properties, including anti-inflammatory, anti-apoptotic, and vasodilatory effects. CO therapy, initially reported to benefit cardiovascular and pulmonary conditions, is now used to treat ocular diseases in preclinical models. Carbon monoxide, a compound most famously known for its deleterious effects, is receiving more attention as a potential therapeutic candidate in ocular medicine. In a few studies, controlled low-dose CO therapy has shown anti-inflammatory and anti-apoptotic effects in various models of retinal disease (such as retinal ischemia-reperfusion injury, optic nerve crush, ocular hypertension, and autoimmune uveitis). We have summarized the clinical and preclinical findings, along with the potential therapeutic value of CO, in this review. In this context, the current and emerging CO delivery methods are also described, with a focus on exploring their safety, efficacy, and applicability in retinal disorders. Although a strong preclinical paradigm exists, clinical translation is limited at best. While some trials indicate acceptable safety levels for inhaled CO or CORM-based interventions, these results have not been robust or reproducible. Bridging this efficacy gap will rely on enhanced delivery strategies, stringent PK/PD-informed dosing, and mechanism-specific endpoint-based trials.