Vol 30, No 3 (2026): CELL BIOLOGY

Relevance. Understanding the fundamental mechanisms of immunothrombosis is essential for developing effective treatments and prevention of thrombotic disorders. This review aims to summarize the current knowledge on the role of programmed neutrophil death in the molecular and cellular mechanisms underlying immunothrombosis, as well as to demonstrate how dysregulation of hemostasis initiated by neutrophil death is associated with various pathological conditions. Based on a search of the electronic scientific databases Google Scholar, PubMed (MEDLINE), Scopus, and Web of Science using keywords and their combinations, with the methodological quality assessed using the AMSTAR 2 software, the role of neutrophil death in the development of immunothrombosis is presented. The review describes the types of programmed neutrophil cell death, namely apoptosis, pyroptosis, necroptosis, ferroptosis, and neutrophil extracellular traps (NETs), along with their molecular triggers and mechanisms. A modern concept of immunothrombosis pathogenesis is presented, demonstrating the involvement of hemostatic proteins, platelets, and proinflammatory cells in its pathogenesis and taking into account the complex relationship between hemostasis and inflammation. Each type of programmed neutrophil death is shown to be involved in the development of immunothrombosis. In addition, the review presents data on therapeutic strategies employing immunometabolic regulators and NET inhibitors, which potentially can attenuate immunothrombotic activity without affecting hemostasis. Such treatment approaches offer advantages for managing patients with various thrombo-inflammatory conditions. Conclusion. Overall, the data demonstrate that neutrophil apoptosis has an antithrombotic effect, whereas other types of programmed cell death promote thrombus formation and vascular events. The latter differ in that they require specific triggers: a cytokine storm for pyroptosis, the release of death-associated molecular patterns (DAMPs) for necroptosis, and oxidative stress for ferroptosis. These types of cell death are unified by their capacity to initiate NET formation, thereby providing a trigger framework for the development of severe thrombotic complications.

Relevance. Single-cell sequencing technologies (scRNA-seq) provide unique opportunities for studying the heterogeneity of immune populations, enabling the analysis of expression profiles, ligand-receptor interactions, and differentiation trajectories at the single-cell level. However, the quality of cell typing significantly depends on the accuracy of data annotation. Marker ambiguity, variability in their expression depending on physiological context, limitations of automated tools such as CellTypist, Azimuth, and SingleR, and the incompleteness of databases like PanglaoDB and CellMarker, including insufficient information on the functional roles of markers, substantially hinder the identification of cell populations and require additional efforts to achieve meaningful results. Aim. To systematize markers of T- and B-cells of the adaptive immune response to facilitate scRNA-seq data annotation. Materials and Methods. An analysis of 30 scientific publications from PubMed, Scopus, and Web of Science (2008-2024) and marker data from PanglaoDB and CellMarker was conducted. Results and discussion. Key and additional T-cell (CD3D, CD3E, CD3G, CD4, CD8A, CD8B, FOXP3, GZMA, TBX21) and B-cell (CD19, MS4A1, CD27, IGHM, IGHD) markers, their roles in immune processes, including activation, cytotoxicity, and regulation, were examined. Subpopulations such as Th1 cells (T-bet, IFN-γ), follicular helper cells (CXCR5, BCL-6), and regulatory B-cells (CD24, IL-10) and their functions in health and disease were described. Conclusion. The systematization of T- and B-cell markers was developed to improve the quality of single-cell sequencing data annotation and is applicable for enhanced typing of cell functional states in health and pathological conditions, including infectious, autoimmune, and oncological diseases. This opens opportunities for a deeper understanding of immune processes and the development of immunotherapy approaches, such as CAR-T therapy. However, the limited specificity of markers and the lack of standardized annotation algorithms highlight the need for further research to refine typing methods.

Relevance. Intronic enhancers are cis-regulatory DNA elements located within introns of protein-coding or non-coding genes. Although introns were historically regarded mainly as non-coding interruptions removed during pre-mRNA splicing, contemporary functional genomics has shown that they are repositories of regulatory information. Intronic enhancers can control the expression of their host genes, neighboring genes, or even distant genes. Their activity is usually cell-type-specific and is associated with open chromatin, transcription-factor binding, enhancer-associated histone modifications such as H3K4me1 and H3K27ac, recruitment of coactivators, enhancer-promoter looping, and in many cases transcription of enhancer RNAs. Results and discussion. This article reviews the biological significance of intronic enhancers with particular attention to two areas: tissue differentiation and disease. During differentiation, intronic enhancers integrate lineage-determining transcription factors, developmental signals and determine tissue specificity. They contribute to hematopoietic, endothelial, muscle, adipocyte, neuronal, and immune-cell identity by controlling the timing, intensity, and specificity of gene expression. In disease, intronic enhancers are vulnerable sites for pathogenic single-nucleotide variants, insertions, deletions, copy-number changes, epigenetic disruption, and aberrant enhancer hijacking. Examples include GATA2 enhancer mutations in immunodeficiency and myeloid malignancy predisposition, FTO intronic variants affecting IRX3/IRX5 regulation in obesity, and oncogenic enhancer activation near TAL1 in T-cell acute lymphoblastic leukemia. Conclusion. Thus intronic enhancers should not be treated as secondary regulatory elements merely because they lie inside genes. Instead, they represent a major layer of genome regulation, connecting non-coding variation to developmental biology, complex traits, and disease mechanisms. Their study is increasingly important for precision medicine, functional interpretation of genome-wide association studies, and future enhancer-targeted therapeutic strategies.

Relevance. Obstructive sleep apnea (OSA) is the most common medical cause of excessive daytime sleepiness and is recognised worldwide as a significant risk factor for road traffic accidents when undiagnosed or untreated. OSA presents a critical occupational health concern in the transportation industry, affecting a substantial proportion of today's transport operators, especially in the trucking sector. Aim of the study was to estimate the risk of OSA among commercial drivers in North India and investigate its association with vehicle accidents. Materials and methods. A cross-sectional study was conducted involving 153 commercial drivers aged between 24 and 65 years, each with at least 5 years of driving experience. Participants were selected through simple random sampling after giving their consent. The collected data included demographic information, driving history (total years of driving, vehicular collisions due to sleepiness, and vehicular incidents), anthropometric measurements (height, weight, and neck circumference), and health history. Sleep quality, particularly difficulty in falling asleep or maintaining restful sleep, was assessed using the Pittsburgh Sleep Quality Index (PSQI). The risk of OSA and excessive daytime sleepiness was evaluated using the STOP-BANG questionnaire and the Epworth Sleepiness Scale, respectively. Results and discussion. Among participants, 21.56% were at risk of OSA, while 28.10% exhibited poor sleep quality as per the PSQI, and 15.16% of high-risk OSA drivers experienced excessive daytime sleepiness. A significant association was observed between the high-risk OSA group and vehicle collisions (p < 0.05). Conclusion. The prevalence of OSA risk is notably high among commercial drivers, who also display poor sleep quality. In a country with a population of 1.4 billion, studies on OSA among commercial drivers are limited. Currently, there are no guidelines for OSA detection in Indian commercial drivers, despite its recognised prevalence in studies from other countries and related hazards such as an increased risk of motor vehicle collisions.

Relevance. Growing resistance of bacterial pathogens to antibiotics is a fundamental threat to healthcare worldwide. Many antibiotics currently used in clinical practice were developed decades ago, and their efficiency has been declining over time. Research efforts focusing on identification and optimization of new promising antibacterial compounds and new molecular targets in bacterial cells establish the foundation for developing new potent antibiotics relevant to modern day clinical needs. The bacterial RNA polymerase is a validated target for a number of natural, semisynthetic, and synthetic antibacterial compounds. This essential enzyme maintains a high potential for developing a new generation of antibiotics. Materials and methods. We prepared a complex of recombinant Escherichia coli RNA polymerase with a new small-molecule transcription inhibitor, and studied it using cryoelectron microscopy to determine the mechanism of inhibition. Results and discussion. The current work establishes the molecular basis of RNA polymerase inhibition by the compound N-(9H-fluoren-9-yl)-3-(2-methylpropyl)-[1,2,4]triazolo[4,3-a]pyridine-8-carboxamide (compound A) that blocks transcription through binding to a previously unknown binding site. We describe interactions of the compound A with RNA polymerase and reveal its mechanism of action that involves steric restriction of template DNA binding in the enzyme active site. We demonstrate that the compound A targets only certain types of transcription complexes since its binding site is formed in part by a dissociable subunit of RNA polymerase. Conclusion. The results of the study may be used for development of conjugates of rifamycins with the compound A to obtain a new class of bacterial RNA polymerase inhibitors with a new mechanism of action.