Molekulyarnaya Meditsina (Molecular medicine)

Introduction. Parkinson’s disease (PD) is a chronic, progressive neurodegenerative disorder, the primary pathological feature of which is the death of dopaminergic neurons in the substantia nigra pars compacta and the accumulation of aggregated α-synuclein.

The objective of this review is to systematize current data on the molecular mechanisms of astrocyte involvement in the pathogenesis of PD, including disturbances in metabolic support, neurotransmitter metabolism, Ca²⁺ homeostasis, mitochondrial and lysosomal function, ferroptosis, neuroinflammation, and changes in the blood-brain barrier and glymphatic system, with an emphasis on genetic variants (LRRK2, GBA1, PARK7, SNCA, ATP13A2).

Material and methods. An analysis of original and review publications in PubMed, Scopus, Web of Science, and eLibrary for the period 2015–2025 was performed.

Results. In PD, astrocytes lose the ability to clear glutamate and α-synuclein, acquiring a reactive neurotoxic phenotype. MAO-B-dependent GABA and H₂O₂ synthesis, Ca²⁺ dysregulation, and mitochondrial dysfunction disrupt the neurotrophic support of dopaminergic neurons. Astrocyte-mediated ferroptosis mechanisms promote selective neuronal death. Genetic mutations associated with PD disrupt autophagy and lysosomal proteolysis and enhance the propagation of pathological α-synuclein. Astrocytes initiate and sustain neuroinflammation by influencing blood-brain barrier permeability and glymphatic system function.

Conclusion. Astrocytes are key mediators of non-cell-autonomous neurodegeneration in PD and a promising target for disease-modifying therapy. iPSC-derived astrocytes and midbrain organoids provide the basis for personalized disease modeling and drug screening aimed at correcting astrocytic dysfunction, normalizing intercellular interactions, and slowing PD progression.

Introduction. Obesity can no longer be adequately described by body mass index alone. Similar BMI values may coexist with different fat distribution, inflammatory burden, neuroendocrine dysregulation, psychobehavioral traits, and risks of organ dysfunction.

Objective. To systematize current knowledge on the molecular heterogeneity of obesity and to show why a personalized approach should include not only drug selection, but also diagnostic stratification, phenotyping, assessment of psychobiological drivers, and prediction of treatment response.

Material and methods. An analytical review of publications indexed in PubMed/MEDLINE and peer-reviewed journals from 2021 to 2026 was performed, with emphasis on studies from 2024 to 2026 addressing clinical obesity, adipose tissue heterogeneity, neuroendocrine and immune-inflammatory mechanisms, precision obesity medicine, incretin-based therapy, and clinically meaningful outcomes. The review also integrates the authors’ concept of an integral personalized obesity index and a draft clinical case of a patient who declined GLP-1 receptor agonist therapy.

Results. Molecular heterogeneity of obesity is driven by differences in adipose tissue cellular composition, immune profile, fibrosis, epigenetic memory, central leptin resistance, hypothalamic-pituitary-adrenal axis activation, gut-brain communication, and psychobehavioral phenotypes. The efficacy of anti-obesity therapy is likewise heterogeneous and depends on the complication phenotype, body composition, adherence, risk of lean mass loss, and treatment duration.

Conclusion. Personalized obesity care should rely on multidimensional assessment, including anthropometry, body composition, molecular and inflammatory features, psychobiological factors, organ-specific complications, and expected treatment response. Moving from a BMI-centered model toward phenotype- and endotype-guided care is a key trajectory for molecular medicine of obesity.

Introduction. Primary open-angle glaucoma is considered a multifactorial disease, in the pathogenesis of which low-grade inflammation, cytokine imbalance, extracellular matrix remodeling, and neuroinflammation play a significant role. In comorbid patients with osteoarthritis, these mechanisms may be enhanced by systemic age-associated inflammation.

Objective. To analyze the clinical significance of the pleiotropic effect of diacerein in patients with primary open-angle glaucoma and osteoarthritis from the standpoint of common molecular inflammatory mechanisms of comorbidity and a personalized therapeutic approach.

Material and methods. The study included 42 patients with advanced primary open-angle glaucoma affecting one or both eyes and concomitant osteoarthritis. Group 1 comprised 22 patients treated with diacerein according to the standard regimen in two courses during a 12-month follow-up; Group 2 included 20 patients who did not receive diacerein. The assessment included pain severity according to VAS and WOMAC, the need for nonsteroidal anti-inflammatory drugs, visual acuity, intraocular pressure, ocular hydrodynamic parameters, perimetric indices, and morphometric parameters of the optic nerve disc and retina according to optical coherence tomography data.

Results. In comorbid patients receiving diacerein, a persistent tendency towards stabilization of intraocular pressure, perimetric and morphometric parameters was observed against the backdrop of favorable dynamics of pain syndrome and functional insufficiency in osteoarthritis, as well as a lower need for nonsteroidal anti-inflammatory drugs. In the control group, there was a tendency toward worsening ophthalmic parameters, and some patients required intensification of hypotensive therapy.

Conclusion. The obtained data confirm the significance of low-grade inflammation in the progression of primary open-angle glaucoma in comorbid patients. Diacerein, which possesses anti-inflammatory and structure-modifying effects, can be considered as a component of a personalized approach to managing patients with the combination of glaucoma and osteoarthritis due to its impact on common molecular pathways.

Introduction. Cancer patients have a high risk of developing venous thromboembolic complications, which worsen the outcomes of antitumor treatment and are the second leading cause of death after cancer progression.

Objectives – to assess the effect of modern anticoagulants (LMWH and DOAC) on the hemostasis system and the incidence of thrombotic complications in patients with Hodgkin’s lymphoma.

Material and methods. The hemostasis system and the incidence of thrombotic complications were studied in 90 patients with Hodgkin’s lymphoma receiving antitumor drug therapy. Patients in group I (n=36) did not receive drug prophylaxis of thrombotic complications. Patients in group II (n=44) received DOAC or LMWH The hemostasis system was studied in patients with thrombosis (n=10). Patients received therapeutic doses of anticoagulants.

Results. Patients with Hodgkin’s lymphoma have hypercoagulation with signs of chronic intravascular coagulation even before the start of treatment. The use of anticoagulants in patients with Hodgkin’s lymphoma receiving antitumor drug therapy reduces the activation of intravascular coagulation and the incidence of venous thrombosis. In the group of patients who did not receive drug prophylaxis, the incidence of thrombotic complications was 8 cases, in the group of patients receiving anticoagulants – 2 cases. The use of therapeutic doses of anticoagulants in patients with thrombosis led to a decrease in the concentration of fibrinogen, fibrin monomer and D-dimer. According to ultrasound imaging, venous thrombosis was not detected, or recanalization of the vessel lumen occurred, in no case did PE develop.

Conclusion. Modern anticoagulants reduce the intensity of intravascular blood coagulation and are an effective and safe means for the treatment and prevention of venous thrombosis in patients with Hodgkin’s lymphoma.

The objective of this review is to examine the pathogenetic mechanisms of myocardial injury in coronary artery disease (CAD).

Material and methods. The analysis utilized domestic and international scientific and clinical studies indexed in Scopus, Web of Science, PubMed, and eLibrary, published over the past 5 years. Thirty-five sources were used to write this literature review.

Atherosclerosis is the morphological substrate of CAD. This review describes the mechanisms of its onset and progression.

It has been shown that endothelial-mesenchymal transition is considered a factor in atherogenesis. Cadherins are the main proteins associated with cell transdifferentiation to a mesenchymal phenotype. It is believed that inhibiting the homodimerization of these proteins can prevent myocardial fibrosis. This review examines intracellular pathways associated with the pathogenesis of cardiac disorders influenced by transforming growth factor-β and WNT pathway proteins. Further drug therapy targeting these molecular mechanisms may improve the prognosis of patients with coronary artery disease, which undoubtedly requires more detailed study. The role of gap junction proteins (connexins and pannexins) in the development and progression of coronary artery disease is also discussed. Inhibition of connexin expression is shown to be important for the treatment of atherosclerosis and provides a new therapeutic target for the treatment of atherosclerosis and the subsequent prevention of coronary artery disease.

Conclusion. Investigation of new pathogenetic mechanisms of myocardial injury in coronary artery disease will enable the development of new treatment strategies for this disease.

Relevance. PARP inhibitors (PARPi), have emerged as a significant development in the treatment of high-grade serous ovarian cancer that is associated with mutations in BRCA1/2 and genes of other homologous recombination proteins. These drugs exploit synthetic lethality by disrupting mechanism of repair of single-stranded DNA breaks. In the absence of a functioning homologous recombination system, this leads to the accumulation of double-stranded DNA breaks and the death of tumor cells. Despite the proven effectiveness of PARPi, acquired resistance has been demonstrated to limit the duration of the response. Systematization of the gained knowledge about the molecular mechanisms, clinical and pharmacological properties of PARPi is crucial for the discovery of new approaches to predicting the effectiveness of therapy, overcoming resistance and other breakthroughs in the ovarian cancer targeted therapy.

Objective. A review of the literature is necessary to facilitate a more profound comprehension of the mechanisms of action of PARPi and the development of tumour resistance.

Material and methods. The present paper analyses publications from the past decade, focusing on the molecular mechanisms of PARPi’s action within cells and the processes underlying resistance to these drugs. It provides data on pharmacokinetics and a brief overview of the landmark randomized clinical trials of PARPi. The present literature review drew upon the PubMed (https://pubmed.ncbi.nlm.nih.gov/) and Google Scholar (https://scholar.google.com/) databases. The search was conducted using the following keywords: «PARP», «PARPi», «pharmacodynamics», «pharmacokinetics», «molecular mechanisms of action», «resistance», and «phase III trials». The analysis included experimental studies elaborating on the molecular mechanisms of action of PARP and PARPi, review articles synthesizing the extant data, randomized clinical trials confirming the efficacy of PARPi in treating patients with ovarian cancer and BRCA1/2 mutations or homologous recombination deficiency (HRD), as well as Russian and international guidelines from professional societies current as of March 2026. The analysis did not include case reports on the use of PARPi or studies on the use of PARPi in malignant tumors of other localization.

Results. This literature review presents data regarding the molecular mechanisms of PARP function within the cell. Their role in the repair of single-strand and double-strand DNA breaks is also discussed, as well as the principles of action of PARPi and the effects they induce in malignant tumors. The pharmacodynamic and pharmacokinetic properties of PARPi are discussed, as are the evidence base for the use of these drugs in clinical practice by oncologists and the possible causes of resistance to PARPi.

Conclusion. Further research into the mechanisms of the action of PARPi in cells, as well as the tumor resistance to these drugs, will provide the foundation for the development of combination strategies involving PARPi. These strategies will, in turn, expand the possibilities for personalized treatment of ovarian cancer.

Introduction. An aortic aneurysm is defined as an irreversible progressive enlargement of the aorta with an increasing risk of rupture, often fatal. It is known that the imbalance of inhibitors and activators of cell matrix proteolysis and the death of smooth muscle cells play a key role in the destruction of the aortic wall, impaired elasticity and a pathological diameter increase. The contribution of atherosclerotic changes is not still clear enough.

The purpose of this literature review was to analyze current data on cellular and molecular mechanisms of damage. aortic walls at various stages of aneurysm development.

Material and methods. A search for sources in the PubMed, Google Scholar, and eLibrary databases for the period 2020–2026 was conducted, as well as fundamental research from an earlier period.

The main provisions. The pathogenesis is based on individual genetically determined anatomical and physiological features of the organism. At each of the three stages – initiation, progression, and terminal phase, various elements of pathogenesis play a key role. At an early stage, it is possible to carry out therapeutic correction and suppress inflammation in order to slow down the pace of intimal damage, smooth muscle cell transformation, media destabilization, and extracellular matrix destruction.

Conclusion. Studying the pathogenesis of aortic aneurysm and risk factors for its progression will make it possible to develop therapeutic management methods for patients and reduce the risk of death from sudden rupture or dissection of the aorta.

Introduction. Cerebrovascular diseases are a heterogeneous group of conditions shaped by the interaction of polygenic susceptibility, rare monogenic variants, vascular remodeling, neuroinflammation, dysregulated hemostasis, and epigenetic reprogramming. Recent years have shifted the field from isolated candidate-gene studies toward multi-ancestry GWAS, transcriptomic and proteomic integration, single-cell approaches, and genetic risk scores, enabling a closer link between inherited predisposition and the biology of the neurovascular unit, cerebral small vessel disease, and intracranial aneurysms.

Objective: to assess the role of genetic factors and molecular mechanisms in the development of cerebrovascular diseases in terms of searching for new targets for diagnosis and therapy.

Material and methods. In the course of this study, a review and analysis of the most relevant domestic and foreign literary sources containing information on the problem of cerebrovascular diseases and their genetic aspects was conducted based on search engines in the MEDLINE, PUBMED databases and the scientific electronic libraries CyberLeninka and eLIBRARY.RU over the past 5 years.

Results. Modern research demonstrates that genetic predisposition to stroke and other cerebrovascular diseases is multilayered and complex. Dozens of polygenic loci associated with atherothrombotic mechanisms, cardioembolism, structural changes in the vascular wall, arterial hypertension, inflammatory processes, and endothelial dysfunction are significant for common forms of pathology. Meanwhile, monogenic variants, particularly in the NOTCH3, HTRA1, and COL4A1/COL4A2 genes, play a critical role for certain phenotypes. Furthermore, it has been established that ischemic brain injury is mediated not only by necrotic processes but also by a cascade mechanism of regulated cell death, mitochondrial dysfunction, excitotoxicity, disruption of the blood-brain barrier, cell-specific inflammatory responses, and epigenetic remodeling. In the context of intracranial aneurysms, the importance of genetic loci influencing the state of the endothelium, smooth muscle cells, extracellular matrix, and blood pressure regulation has been demonstrated.

Conclusion. Genetic determinants play a fundamental role in the pathogenesis of cerebrovascular diseases. Modern molecular genetic studies have identified polymorphic loci and mutations associated with an increased risk of developing these pathologies. Genetic predisposition, epigenetic modifications, and variability in regulatory pathways play a key role in the pathophysiological mechanisms of these diseases. Genetic heterogeneity significantly complicates the research process, influencing individual predisposition to cerebrovascular diseases. Pharmacogenetic and ethnogenetic factors also play a significant role in the context of etiology and pathogenesis. Further comprehensive research is needed to better understand all genetic risk factors, which will enable the development of personalized prevention and treatment strategies based on genetic profiling of patients.