Vitaliy A. Markelov

The aim of the work is to analyze modern methods of studying the migration of monocytes from blood vessels to tissues. Material and methods.  59 sources were selected in the Pubmed database by key queries related to the migration of monocytes and leukocytes. The selection criterion was the description of the process of the movement of monocytes (transmigration) through the endothelial barrier in vitro or in vivo . Results and discussion.  The mechanisms of monocyte transmigration are summarized. A comparison of in vitro (Boyden chamber, µ-slides, microfluidic systems) methods of studying migration was carried out according to a number of criteria. The Boyden chamber is the simplest and most common method, widely used to test the effect of therapy on monocytes. Real-time transmigration observation is possible using real-time cell assay migration cells and µ-slides with a viewing field, which is widely used to evaluate cell morphological properties. Microfluidic systems have enabled the creation of complex systems capable of mimicking the circulatory system; however, this method is not standardized and is complex to manufacture in laboratory conditions. To assess the representativeness of the experimental models, data on the study of in vivo  migration are presented – fluorescent labeling of cells, nuclear tomography, bioluminescence. Conclusions.  The review combines modern ideas about the mechanisms of monocyte migration and their modeling in vitro and in vivo . The criteria for evaluating model systems, their advantages, disadvantages, and possibilities of application in research and in therapy of diseases are described.

MicroRNAs (miRNAs) are involved in the regulation of glucose metabolism and inflammatory processes associated with type 2 diabetes (T2D) and have potential as biomarkers and therapeutic targets. We analysed the expression of miR-155-5p, miR-141-3p, miR-15b-5p, miR-18a-5p, and miR-379-5p in peripheral blood mononuclear cells (PBMCs) from 79 patients with T2D and 88 non-diabetic controls. Differential expression analysis revealed significant downregulation of miR-15b-5p, miR-155-5p, and miR-18a-5p, and significant upregulation of miR-379-5p in T2D patients. Among the individual miRNAs, miR-15b-5p showed the highest ability to distinguish between T2D and controls (AUC = 0.82, 95% CI 0.76–0.89, p = 0.001). A model combining the four differentially expressed miRNAs (miR-155-5p, miR-15b-5p, miR-18a-5p, and miR-379-5p) with age, sex, and BMI had an AUC of 0.98, compared with 0.93 for age, sex, and BMI alone (p = 0.004, paired DeLong test); the optimism-corrected AUC was 0.97, although the bootstrap procedure did not account for optimism arising from miRNA selection. Functional enrichment analysis identified MAPK, Hippo, FoxO, insulin, AMPK and TGF-β signalling as consistently enriched across analyses based on experimentally supported and predicted miRNA targets.

Aim. To analyze changes in gene expression of S100 calcium-binding protein A8 ( S100A8 ), S100 calcium-binding protein A9 ( S100A9 ), S100 calcium-binding protein A12 ( S100A12 ), chitinase-3-like protein 1 ( YKL40 ), chitinase3-like protein 2 ( YKL39 ), stabilin 1 ( STAB1 ), tumor necrosis factor α ( TNF α), interleukin-1 beta ( IL1B ), interleukin-1 receptor antagonist ( IL1RN ), interleukin-6 ( IL6 ), interleukin-10 ( IL10 ), interleukin-12 subunit A ( IL12A ), C-X-C motif chemokine ligand 8 ( IL8 ), C–C motif chemokine ligand 18 ( CCL18 ), Toll-like receptor 2 ( TLR2 ), Toll-like receptor 4 ( TLR4 ), Toll-like receptor 7 ( TLR7 ), mannose receptor C-type 1 ( MRC1 ), neuropilin-1 ( NRP1 ), transforming growth factor beta-1 ( TGF β 1 ), and colony-stimulating factor 1 ( CSF1 ) in monocytes of prostate cancer (PCa) patients and healthy men. Materials and methods. The study included 35 patients with stage II–IV PCa and 11 healthy men. Monocytes were obtained from peripheral blood by magnetic sorting. Gene expression analysis and ROC analysis were performed, and the Pearson’s correlation was applied. Results. In patients with PCa, decreased expression of the IL8 ( p = 0.0001, q = 0.002) and YKL40 ( p = 0.002, q = 0.017) genes was observed after the Benjamini – Hochberg correction. In contrast, TLR7 ( p = 0.0054, q = 0.031) gene expression was significantly increased two-fold in the PCa group. The ROC analysis demonstrated the ability to statistically significantly differentiate patients with PCa. Conclusion. The study revealed decreased expression of IL8 and YKL40 in monocytes obtained from prostate cancer patients, whereas TLR7 expression was elevated two-fold. The ROC analysis results confirm the diagnostic potential of these markers for differentiating prostate cancer patients.

Background/Objectives: Chronic obstructive pulmonary disease (COPD) is increasingly viewed as a disorder of impaired cellular adaptation to chronic stress, involving oxidative injury, mitochondrial dysfunction, and accelerated cellular senescence. We investigated whether genetic variation in these pathways contributes to disease susceptibility, lung function impairment, and polygenic risk prediction. Methods: Thirty-three single-nucleotide variants were analysed in 747 patients with COPD and 703 controls. Associations with disease susceptibility and lung function parameters were assessed using regression models with correction for multiple testing. Weighted and unweighted polygenic scores were constructed from associated variants and evaluated using receiver operating characteristic and net reclassification improvement analyses. Results: Significant associations were identified in genes involved in antioxidant defence (NFE2L2, HMOX1, GSR), PI3K/AKT/mTOR signalling (PIK3R1, PTEN), mitochondrial function (TOMM40), cellular stress responses (FOXO3A), and long non-coding RNA regulation (MEG3, CDKN2B-AS1). The strongest association was observed for PIK3R1 rs831125 (OR = 2.31, p = 2.53 × 10⁻¹⁰). Variants in NFE2L2, PIK3R1, MEG3, MALAT1, and SIRT3 were additionally associated with pulmonary function parameters. The weighted polygenic score demonstrated good discriminative ability (AUC 68.8%, 95% CI 65.9–71.7%) and substantially improved prediction when combined with age, sex, and smoking exposure (AUC 88.1%, 95% CI 86.3–89.8%; NRI = 0.62, p = 2.21 × 10⁻²⁸). Conclusions: The identified loci converge on interconnected pathways involved in cellular stress adaptation, mitochondrial homeostasis, and senescence, supporting their contribution to chronic obstructive pulmonary disease susceptibility and functional decline.

The centrepiece of this analytical review is the metabolism of hydroxyapatite in its natural, bone, and synthetic forms, where the mitochondria-mediated mechanism may serve as the leading mechanism. The possibility that osteoblast mitochondria play an important role in the initial stages of bone mineralisation is discussed. Furthermore, the paper highlights the key role of mitochondria in the metabolism of synthetic hydroxyapatite. Differences between the results of in vivo and in vitro studies using synthetic hydroxyapatite of different morphologies are also detailed. It is noted that long-term infiltration with immune cells and in vivo studies are necessary to adequately evaluate hydroxyapatite as a bone-plastic material. Particular attention is given to the interaction of hydroxyapatite with immune cells and its ability to affect the ribosomes and mitochondria of cells. Due to its mechanical properties, scalability, and potential use for the treatment of extensive bone defects of tumor origin, hydroxyapatite is a promising material. This study also highlights the importance of further development of in vitro research methods in the context of their biomimeticity. Overall, this work offers a theoretical direction for future studies of hydroxyapatite as a bone grafting material and emphasises the value of in vivo studies.

The poultry industry, a globally fast growing agricultural sector, provides affordable animal protein due to high efficiency. Gallus gallus domesticus are the most common domestic birds. Hybrid chicken breeds (crosses) are widely used to achieve high productivity. Maintaining industry competitiveness requires constant genetic selection of parent stock to improve performance traits. Genetic studies, which are essential in modern breeding programs, help identify genome variants linked to economically important traits and preserve population health. Next-generation sequencing (NGS) has identified millions of single nucleotide polymorphisms (SNPs) and insertions/deletions (INDELs), enabling detection of genome-wide regions associated with selection traits. Recent studies have pinpointed such regions using broiler lines, laying hen lines, or pooled genomic data. This review discusses advances in chicken genomic and transcriptomic research focused on traits enhancing meat breed performance and reproductive abilities. Special attention is given to transcriptome studies revealing regulatory mechanisms and key signaling pathways involved in artificial molting, as well as metagenome studies investigating resistance to infectious diseases and climate adaptation. Finally, a dedicated section highlights CRISPR/Cas genomic editing techniques for targeted genome modification in chicken genomics.

Short bowel syndrome is a life-threatening condition characterized by the intestine’s inability to maintain homeostasis through enteral nutrition. Despite the use of conservative approaches, including parenteral nutrition, most patients fail to achieve complete enteral autonomy or correct electrolyte and nutrient deficiencies. Surgical interventions such as longitudinal intestinal lengthening and tailoring, serial transverse enteroplasty, and intestinal or multivisceral allotransplantation are associated with a high risk of complications owing to technical limitations and the requirement for immunosuppressive therapy. Tissue engineering is a promising alternative. Current strategies use various synthetic and biological extracellular matrices as scaffolds, including silk fibroin, collagen, gelatin, hydrogels, polyglycolic acid, and allogeneic intestinal submucosa. The cellular components of tissue-engineered constructs include embryonic, pluripotent, and mesenchymal stem cell lines, whose regenerative potential is enhanced by various adjuvants and growth factors. Given the biological properties of these cells and specifics of transplantation and post-transplant changes, mesenchymal stem cells are a promising cellular vehicle for morphofunctional restoration of the residual intestine. This study provides a comprehensive review of tissue-engineered constructs developed for intestinal reconstruction in short bowel syndrome.

This review addresses a hypothetical evolutionary scenario based on the self-organization of replicating RNA molecules, and substantiates their link with modern regulatory systems of noncoding RNAs (ncRNAs). We systematize modern scientific data that consider self-organizing RNA molecules as key evolutionary units of the prebiotic stage of life development, and analyze modern models of the formation of chemical RNA precursors in prebiotic conditions, as well as their further polymerization into functional RNAs. The analysis of putative scenarios for the formation of emergent states reveals the regulatory function of early RNA replicators and their role in the development of sophisticated biological systems. The widespread prevalence of regulatory ncRNAs across all groups of living organisms suggests their ancient origin. It is highly likely that modern RNA switches, group II introns, and spliceosomal introns, which are the source of most ncRNAs, originate from a common ancient RNA infrastructure, which may have ensured a coordination of replication, compartmentalization and metabolism during the early stages of evolution. By combining insights from biochemistry, genomics, and evolutionary biology, our analysis offers a comprehensive perspective on the molecular mechanisms underlying the origin and diversification of ncRNAs.

Idiopathic pulmonary fibrosis (IPF) is a rapidly progressive interstitial lung disease of unknown pathogenesis with no effective treatment currently available. Given the regulatory roles of lncRNAs (TP53TG1, LINC00342, H19, MALAT1, DNM3OS, MEG3), miRNAs (miR-218-5p, miR-126-3p, miR-200a-3p, miR-18a-5p, miR-29a-3p), and their target protein-coding genes (PTEN, TGFB2, FOXO3, KEAP1) in the TGF-β/SMAD3, Wnt/β-catenin, focal adhesion, and PI3K/AKT signaling pathways, we investigated the expression levels of selected genes in peripheral blood mononuclear cells (PBMCs) and lung tissue from patients with IPF. Lung tissue and blood samples were collected from 33 newly diagnosed, treatment-naive patients and 70 healthy controls. Gene expression levels were analyzed by RT-qPCR. TaqMan assays and TaqMan MicroRNA assay were employed to quantify the expression of target lncRNAs, mRNAs, and miRNAs. Our study identified significant differential expression in PBMCs from IPF patients compared to healthy controls, including lncRNAs MALAT1 (Fold Change = 3.809, P = 0.0001), TP53TG1 (Fold Change = 0.4261, P = 0.0021), and LINC00342 (Fold Change = 1.837, P = 0.0448); miRNAs miR-126-3p (Fold Change = 0.102, P = 0.0028), miR-200a-3p (Fold Change = 0.442, P = 0.0055), and miR-18a-5p (Fold Change = 0.154, P = 0.0034); and mRNAs FOXO3 (Fold Change = 4.604, P = 0.0032) and PTEN (Fold Change = 2.22, P = 0.0011). In lung tissue from IPF patients, significant expression changes were observed in TP53TG1 (Fold Change = 0.2091, P = 0.0305) and DNM3OS (Fold Change = 4.759, P = 0.05). Combined analysis of PBMCs expression levels for TP53TG1, MALAT1, miRNA miR-126-3p, and PTEN distinguished IPF patients from healthy controls with an AUC = 0.971, sensitivity = 0.80, and specificity = 0.955 (P = 6 × 10^–8). These findings suggest a potential involvement of the identified ncRNAs and mRNAs in IPF pathogenesis. However, additional functional validation studies are needed to elucidate the precise molecular mechanisms by which these lncRNAs, miRNAs, and their targets contribute to PF.

MicroRNAs are key regulators of gene expression controlling components of signaling cascades involved in the pathogenesis of heart failure (HF). The expression profile of microRNAs may serve as a sensitive indicator of different types of HF. The aim of the present study was to compare the gene expression of microRNAs miR-148b-3p, miR-30c-5p, miR-221-3p, miR-328-3p, miR-146a-5p, miR-375-3p, miR-22-3p, miR-15b-3p, miR-148a-3p, miR-590-5p in peripheral blood mononuclear cells (PBMC) and epicardial adipose tissue of coronary heart disease (СHD) patients with and without HF (Non-HF). Among СHD patients with HF, the groups with mildly reduced/reduced and preserved ejection fraction (HFmr/rEF and HFpEF, respectively) were compared. Our study revealed a significant increase in the expression of miR-30c-5p, miR-221-3p and miR-375-3p microRNAs in PBMCs of patients with HFmr/rEF and HFpEF compared with the group of СHD patients without HF. Accordingly, the relative level of miR-30c-5p expression in PBMC of HFF/EFV patients was significantly higher by 1.99 times in comparison with patients without HF (P<0.0001). The expression of this microRNA in PBMC of HFpEF patients relative to patients without HF is significantly higher by 2.94-fold (P<0.0001). The expression level of miR-221-3p in PBMC of HFpEF patients was increased 4.04-fold relative to patients without HF (P<0.0001). A 2.63-fold increase in miR-221-3p expression was detected in PBMC of HFmr/rEF patients (P<0.0001). The expression of miR-375-3p in PBMCs of HFmr/rEF and HFpEF patients compared with Non-HF patients was significantly higher by 2.09- and 1.77-fold (P<0.0001). For all other investigated microRNAs, no significant expression changes were detected in PBMC. Similarly, we did not detect significant expression changes for any of the investigated microRNA genes in the epicardial adipose tissue of CHD patients. Thus, the obtained data can be used to determine the role of the investigated microRNAs in the pathogenesis of HF in СHD patients. The results of the present study can be used for further studies of HF pathogenesis. Accordingly, they can be used for the development of modern clinical strategies to assess the risk of HF development in СHD patients. Keywords. Heart failure, preserved ejection fraction, reduced ejection fraction, microRNA.