Igor Moiseyevich Kvetnoy

Maintaining healthy longevity requires slowing down age-related changes and supporting the body's ability to recover function after stress. With age, the adaptive response becomes increasingly compromised: inflammation and metabolic mobilization persist, the reserve decreases, and allostatic load accumulates. This article reviews data on age-related changes through the concept of the redox code — the spatiotemporal organization of electron transfer, reduction fluxes, and reversible protein modifications. This approach enables us to correlate molecular mechanisms of aging with the disruption of effective feedback loops, mitochondrial maintenance, and cellular turnover. Based on advances in redox biology and the results of studying precursor drugs, we proposed a concept of the pharmacological modulation of the redox code in the context of adaptive response development — signal perception, matching needs with resources, and timely restoration of regulatory circuits. The proposed approach has been shown to complement risk mitigation, physical adaptation, interference with cellular renewal, and epigenetic reprogramming. Organ-specific ageotypes and the circadian phases determine the individual context of modulation. This approach distinguishes the reductive capacity as an independent level of healthy longevity pharmacology. Its practical results include the completion of adaptation, decreased residual chronic stress, and preserving readiness for subsequent impacts.

The review evaluates current clinical and epidemiological evidence regarding the use of plant-derived compounds in pediatric practice. Data from randomized controlled trials indicate symptomatic efficacy of selected agents—particularly in acute respiratory infections—alongside generally favorable safety profiles when standardized preparations are used. Emerging research also explores applications in neurodevelopmental disorders, gastrointestinal conditions, and dermatology, and as supportive therapy in pediatric oncology. However, variability in product quality, limited pediatric-specific trials, potential toxicity, and regulatory inconsistencies remain significant challenges. The integration of phytotherapy into pediatric care therefore requires rigorous study design, careful safety monitoring, and clear quality standards to ensure an evidence-based risk–benefit balance.

Diabetes mellitus (DM) is a group of metabolic diseases characterized by chronic hyperglycemia resulting from defects in insulin secretion, insulin action, or both. The most common types—type 1 and type 2 diabetes—have different etiologies and pathophysiological mechanisms. Type 1 diabetes (T1DM) results from autoimmune destruction of the insulin-producing pancreatic β-cells, leading to the development of absolute insulin deficiency, whereas in type 2 diabetes (T2DM), impaired carbohydrate metabolism is primarily caused by insulin resistance and relative insulin deficiency. Current diagnostic criteria do not allow for the detection of the disease at the preclinical stage. MicroRNA (miRNA) influences post-translational regulation of gene expression by inhibiting mRNA translation and also promotes mRNA degradation. The aim of this review is to summarize current evidence on the role of microRNAs in the pathogenesis of T1DM and T2DM and to evaluate their potential as early diagnostic biomarkers and therapeutic targets. It is demonstrated that T1DM and T2DM exhibit altered expression of specific microRNAs involved in β-cell apoptosis, autoimmune inflammation, and insulin signaling. In T1DM, key miRNAs include miR-21, miR-25, miR-146a, and miR-375, which reflect β-cell destruction and the autoimmune process. In T2DM, critical roles are played by miR-9, miR-29, miR-34a, miR-103/107, miR-126, miR-143, and miR-375, which regulate insulin secretion, lipid metabolism, and tissue insulin sensitivity. Particular attention is given to microRNAs whose expression changes several years before clinical disease onset (miR-15a, miR-126, miR-375), offering opportunities for early diagnosis. Data are presented on circulating miRNAs in stable biological fluids (blood, urine). It should be emphasized, however, that the proposed microRNA panel currently represents only a potential diagnostic tool. This panel requires further validation and confirmation by clinicians in large-scale prospective studies and does not yet claim to be ready for routine clinical use. Nevertheless, the development of such a universal microRNA panel, followed by thorough clinical evaluation, has promising biomedical potential, which will not only allow for the diagnosis of diabetes at an early stage but also identify new therapeutic targets for personalized medicine.

Redox (reduction–oxidation) processes underlie all forms of life and are a universal regulatory mechanism that maintains homeostasis and adapts the organism to changes in the internal and external environments. From capturing solar energy in photosynthesis and oxygen generation to fine-tuning cellular metabolism, redox reactions are key determinants of life activity. Proteins containing sulfur- and selenium-containing amino acid residues play a crucial role in redox regulation. Their reversible oxidation by physiological oxidants, such as hydrogen peroxide (H₂O₂), plays the role of molecular switches that control enzymatic activity, protein structure, and signaling cascades. This enables rapid and flexible cellular responses to a wide range of stimuli—from growth factors and nutrient signals to toxins and stressors. Mitochondria, the main energy organelles and also the major sources of reactive oxygen species (ROS), play a special role in redox balance. On the one hand, mitochondrial ROS function as signaling molecules, regulating cellular processes, including proliferation, apoptosis, and immune response, while, on the other hand, their excessive accumulation leads to oxidative stress, damage to biomolecules, and the development of pathological processes. So, mitochondria act not only as a “generator” of redox signals but also as a central link in maintaining cellular and systemic redox homeostasis. Redox signaling forms a multi-layered cybernetic system, which includes signal perception, activation of signaling pathways, the initiation of physiological responses, and feedback regulatory mechanisms. At the molecular level, this is manifested by changes in the activity of redox-regulated proteins of which the redox proteome consists, thereby affecting the epigenetic landscape and gene expression. Physiological processes at all levels of biological organization—from subcellular to systemic—are controlled by redox mechanisms. Studying these processes opens a way to understanding the universal principles of life activity and identifying the biochemical mechanisms whose disruption causes the occurrence and development of pathological reactions. It is important to emphasize that new approaches to redox balance modulation are now actively developed, ranging from antioxidant therapy and targeted intervention on mitochondria to pharmacological and nutraceutical regulation of signaling pathways. This article analyzes the pivotal role of redox balance and its regulation at various levels of living organisms—from molecular and cellular to tissue, organ, and organismal levels—with a special emphasis on the role of mitochondria and modern strategies for influencing redox homeostasis.

Cognitive disorders present significant medical and social challenges nowadays, due to their high prevalence, progressive course and a lack of effective methods for treatment of neurodegenerative diseases and comorbid pathologies. An important area of research is the identification of molecular biomarkers that reflect early pathophysiological changes and facilitate a more accurate biological characterization of cognitive impairment. This study provides an overview of the most relevant signaling molecules for diagnosing cognitive disorders. It presents data on the effectiveness of using comprehensive panels of molecular biomarkers in clinical practice, including β-amyloid, CD34, claudin, DRP1, endothelin-1, NF-kB, PINK1, RAGE, S100, α-synuclein, and tau protein, in patients with Alzheimer’s disease (AD) and vascular dementia (VD). The study results demonstrate that cumulative changes in the expression of signaling molecules reflect various neurodegenerative and vascular-associated biological processes. The data obtained are comparative in nature and require further validation before potential clinical application.

Redox (reduction-oxidation) processes underlie all forms of life and are a universal regulatory mechanism that maintains homeostasis and adapts the organism to changes in the internal and external environments. From capturing solar energy in photosynthesis and oxygen generation to fine-tuning cellular metabolism, redox reactions are key determinants of life activity. Proteins containing sulfur- and selenium-containing amino acid residues play a crucial role in redox regulation. Their reversible oxidation by physiological oxidants, such as hydrogen peroxide (H₂O₂), plays the role of molecular switches that control enzymatic activity, protein structure, and signaling cascades. This enables rapid and flexible cellular responses to a wide range of stimuli—from growth factors and nutrient signals to toxins and stressors. Mitochondria, the main energy organelles and also the major sources of reactive oxygen species (ROS), play a special role in redox balance. On the one hand, mitochondrial ROS function as signaling molecules, regulating cellular processes, including proliferation, apoptosis, and immune response, while, on the other hand, their excessive accumulation leads to oxidative stress, damage to biomolecules, and the development of pathological processes. So, mitochondria act not only as a "generator" of redox signals but also as a central link in maintaining cellular and systemic redox homeostasis. Redox signaling forms a multi-layered cybernetic system, which includes signal perception, activation of signaling pathways, the initiation of physiological responses, and feedback regulatory mechanisms. At the molecular level, this is manifested by changes in the activity of redox-regulated proteins of which the redox proteome consists, thereby affecting the epigenetic landscape and gene expression. Physiological processes at all levels of biological organization—from subcellular to systemic—are controlled by redox mechanisms. Studying these processes opens a way to understanding the universal principles of life activity and identifying the biochemical mechanisms whose disruption causes the occurrence and development of pathological reactions. It is important to emphasize that new approaches to redox balance modulation are now actively developed, ranging from antioxidant therapy and targeted intervention on mitochondria to pharmacological and nutraceutical regulation of signaling pathways. This article analyzes the pivotal role of redox balance and its regulation at various levels of living organisms—from molecular and cellular to tissue, organ, and organismal levels—with a special emphasis on the role of mitochondria and modern strategies for influencing redox homeostasis.

Cognitive disorders present significant medical and social challenges nowadays, due to their high prevalence, progressive course and a lack of effective methods for treatment of neurodegenerative diseases and comorbid pathologies. An important path for solving this problem is the search for reliable biomarkers that allow for early and differential diagnosis, especially in view of the similarity between clinical manifestations of different forms of dementia. This study provides an overview of the most relevant signaling molecules for diagnosing cognitive disorders. It presents data on the effectiveness of using comprehensive panels of molecular biomarkers in clinical practice, including β-amyloid, CD34, claudin, DRP1, endothelin-1, NF-kB, PINK1, RAGE, S100, α-synuclein, and tau protein, in patients with Alzheimer's disease (AD) and vascular dementia (VD). The study results demonstrate a high diagnostic relevance of the combined use of signaling molecules as a biomarker panel for screening and differentiating neurodegenerative diseases.

Introduction . The mechanisms of interaction between lung cancer and tuberculosis (TB) are not fully understood. The aim of the study is to study the effect of pulmonary tuberculosis on the lung cancer. Materials and methods . The study utilized a model (Patent RU 2800964 C1) of isolated Lewis lung carcinoma (LLC) and generalized TB (H37Rv and 5582 strains) in C57BL/6 mice. Five groups of laboratory animals were formed: isolated tuberculosis (different M. tuberculosis susceptibility), isolated LLC, and 2 groups with combined pathology. An immunohistochemical analysis for TNF-α, PCNA, and MMP-9 was completed. Results . The relative expression of MMP-9 in the groups with combined pathology was significantly lower than in the isolated tumor group: LLC + H37Rv — 2.60; LLC + 5582–3.00; LLC — 8.90 ( p = 0.043). The relative expression of TNF-α showed no statistically significant differences between the combined pathology groups and the isolated tumor group: LLC + H37Rv — 1.35; LLC + 5582–3.70; LLC — 1.70. A statistically significant increase in TNF-α expression was observed in mice infected with the drug-resistant M. tuberculosis strain (5582). The relative expression of PCNA was significantly lower in the combined pathology groups compared to the isolated tumor group: LLC + H37Rv — 8.50; LLC + 5582 — 14.30; LLC — 36.45 ( p = 0.012). Discussion . Data demonstrated that TB led to the suppression of tumor-induced MMP-9 expression, reduction in PCNA expression. This may indicate the suppression of metastasisе, cell proliferation. The TNF-α expression level didn`t differ significantly between the groups. Conclusion . The obtained data may suggest an oncosuppressive effect of tuberculosis on the lung tumors.

Cognitive impairment screening is an important issue in modern biomedicine. Neuropsychological tests have their limitations and, in some cases, fail to ensure an objective assessment of the dementia presence in individuals, especially in early stages of the disease development. In this study, we have investigated the expression of signaling molecules in the buccal epithelium, which are involved in the biochemical mechanisms of cognitive impairment caused by neurovascular pathology, in order to develop a diagnostic panel of molecular markers for dementia. Buccal epithelial samples from 146 participants, including 100 patients with vascular dementia (VD) and 46 healthy volunteers, were analyzed using immunocytochemistry. Based on the obtained results, a diagnostic panel for vascular dementia screening was developed, including such markers as β-amyloid, NF-κB, tau protein, claudin, and S100 protein. The buccal epithelium has been found to provide a convenient source of biomaterial for non-invasive diagnosis of cognitive disorders caused by neurovascular pathologies.

Sirtuins (SIRT1–SIRT7) are NAD⁺-dependent deacetylases that link cellular energy status to chromatin maintenance, mitochondrial function and inflammatory signaling. While modulation of SIRT1, SIRT3 and SIRT6 extends lifespan in model organisms, evidence in extreme-age humans is scarce. We quantified protein and mRNA levels, and protein-to-mRNA ratios for SIRT1, SIRT3 and SIRT6 in buccal epithelial cells obtained from healthy young adults, middle/late-aged individuals and nonagenarians/centenarians residing in a longevity-enriched region of south-eastern Azerbaijan. The cohort comprised 23 participants, stratified by sex and cardiovascular disease (CVD) status (5 per sex/CVD subgroup). This design allows us to: (1) define a baseline “sirtuin profile” of healthy longevity, (2) evaluate the impact of CVD as a prevalent age-related pathology, and (3) explore potential sex-specific modulation. These findings establish an initial human framework linking sirtuin translational control to healthy ageing and cardiovascular health.