Yanina R. Timasheva

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.

Genetic variation in the genes involved in the maintenance of cellular homeostasis may influence susceptibility to type 2 diabetes (T2D). However, the nature of the interplay among these loci and their prognostic value remains unclear. In this study, we analyzed variants in the FOXO3A, FOXO3, FOXO1, HMOX1, and SIRT1 genes. The HMOX1 rs2071746*T/T genotype was associated with an increased risk of T2D (OR = 1.36, PFDR = 0.030), whereas the FOXO1 rs9549240 (OR = 0.52, PFDR = 0.002) and SIRT1 rs3758391 (OR = 0.80, PFDR = 0.015) genotypes exhibited a protective effect. We detected nonlinear interactions, including FOXO1 rs9549240*G + SIRT1 rs3758391*T + SIRT1 rs7895833*A and HMOX1 rs2071746*A + SIRT1 rs3758391*T + SIRT1 rs7895833*A, with significant synergistic effects (SF = 3.19 and 2.56, P 0.03). Models incorporating these interactions achieved an AUC of 69.8%, which increased to 86.2% when combined with age, sex, and the body mass index. These findings suggest that interactions between the pathways regulating oxidative stress and metabolism may contribute to the genetic predisposition to T2D.

Prostate cancer (PrC) is one of the most common malignancies among men worldwide. However, the contribution of genetic variation in microRNA (miRNA) biogenesis pathway genes to PrC susceptibility remains poorly characterized in many ethnically diverse populations. We conducted a case–control study involving 532 PrC patients and 550 controls from the Volga-Ural region of Eurasia to evaluate the association of twenty-one single nucleotide polymorphisms (SNPs) with PrC risk using single-variant and polygenic approaches. Association analyses identified rs595055 in the AGO1 gene as significantly associated with PrC risk after correction for multiple testing. To evaluate the cumulative effect of genetic variation, weighted and unweighted polygenic risk scores (PRSs) were constructed. The weighted PRS was significantly associated with PrC risk (odds ratio per standard deviation increase = 1.63, 95% CI [1.43–1.85], P = 1.37 × 10⁻¹³), and demonstrated moderate discriminatory performance (AUC = 63.1%), outperforming the unweighted model. Individuals in the highest PRS quartile had approximately threefold higher odds of PrC than those in the lowest quartile. Combining the weighted PRS with prostate-specific antigen improved discrimination (AUC = 68.1%). These findings support the contribution of miRNA biogenesis pathway genes to PrC susceptibility and highlight the potential value of pathway-based polygenic risk stratification in understudied populations.

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.

Egg production in Gallus gallus domesticus represents a complex, economically critical trait shaped by multiple interrelated phenotypes, including age at first egg, total egg number, egg weight, and clutch characteristics. These traits are governed by polygenic inheritance and modulated by environmental factors, making the dissection of their genetic architecture essential for improving breeding efficiency, particularly under the emerging “long-life layers” production model. This systematic review aimed to integrate current knowledge on the genetic and molecular basis of egg production traits through analysis of genome-wide association studies and related genomic approaches. A structured literature search identified 27 eligible studies, which were evaluated following PRISMA guidelines. Data extraction and meta-analysis were conducted using standardized genome annotations and computational pipelines. The synthesis of available evidence demonstrates moderate to high heritability for key reproductive traits and highlights consistent genomic signals across multiple chromosomes. Importantly, the findings reveal a shift toward a systems-level understanding of egg production, involving conserved biological pathways related to neuroendocrine regulation, folliculogenesis, and energy metabolism. The integration of diverse genomic approaches enables the development of more precise, breed-specific selection strategies. Overall, these advances support a transition from traditional selection toward molecularly informed breeding frameworks, with significant implications for productivity, sustainability, and global food security.

Abdominal fat deposition in chickens significantly impacts production efficiency and is influenced by complex genetic and molecular mechanisms. This review summarizes current genomic and transcriptomic research on the regulation of adipogenesis and fat accumulation in chickens, highlighting key genes and loci identified through genome-wide association studies as well as other candidates involved in lipogenesis, lipolysis, and transcriptional regulation. Major metabolic pathways, including MAPK, AMPK, PI3K/AKT/mTOR, TGFβ1/Smad3, FoxO, JAK–STAT, Wnt/β-catenin, and Sonic Hedgehog signaling, are examined for their roles in fat deposition. The regulatory functions of non-coding RNAs, including microRNAs, long non-coding RNAs, and circular RNAs, are discussed, focusing on their interactions with target mRNAs and signaling networks that control lipid metabolism, adipocyte differentiation, and energy balance. Integrating insights from both avian and human studies, this review emphasizes the molecular mechanisms underlying adipogenesis and highlights potential strategies for genetic selection aimed at reducing excessive abdominal fat and improving poultry productivity.

Heart failure (HF) remains a leading cause of morbidity and mortality worldwide, affecting over 30 million individuals, with its prevalence steadily increasing due to population aging. Among its forms, heart failure with preserved ejection fraction (HFpEF) has emerged as a major clinical and public health concern, now accounting for more than half of all HF cases and closely associated with comorbidities such as hypertension, obesity, and diabetes. MicroRNAs (miRNAs) have gained recognition as key regulators of the molecular mechanisms underlying HF, particularly HFpEF, where they modulate interconnected pathways of inflammation, fibrosis, and endothelial dysfunction. This review discusses the mechanisms by which miRNAs contribute to the pathogenesis of HF and examines their potential as both biomarkers and therapeutic targets. By integrating current evidence, it aims to clarify the prognostic significance and clinical applicability of these molecular markers, highlighting their role in advancing personalized strategies for the diagnosis and management of HF.

Objective. To identify informative predictors of the development and progression of multiple sclerosis (MS) based on polygenic analysis of associations of polymorphic variants in the IL1R1, IL10, IL12B, IL2, IL2RA, and IL7R genes. Material and methods. The study included 247 patients with MS and 1271 control subjects. Associations of development and progression of MS with polymorphic variants of the IL1R1, IL10, IL12B, IL2, IL2RA, IL7, and IL7R genes were analyzed. The combinations of allelic variants associated with the disease were searched using the APSampler software, and predictive models of the development and progression of MS were developed using multifactorial logistic regression with step-by-step inclusion of variables. Results. The increased probability of MS was associated with the IL1R1 rs2287047 (recessive model, OR=2.2, pFDR=0.022), IL7R rs1494558 polymorphic variants (log additive model, OR=1.49, pFDR=0.003), and IL2RA rs12722580 *I/D genotype (codominant model, OR=1.67, pFDR=0.03). Reduced MS risk was associated with IL10 rs1800872 (recessive model, OR=0.38, pFDR=0.044), IL7R rs10624573 (dominant model, OR=0.67, pFDR=0.022), IL7R rs6897932 variants (recessive model, OR=0.21, pFDR=0.008), and IL2RA rs12722580 * D/D genotype (codominant model, OR=0.78, pFDR=0.03). Combinations (IL7R rs1494558*T+IL7R rs6897932*T, IL1R1 rs2287047*C+IL12B rs3212227*C and IL7R rs1494558*T/C+IL12B rs3212227*A) with a synergistic effect were identified, and predictive models of MS development and progression risk with a sufficiently high prognostic value were created. Conclusion. The results of the study emphasize the importance of polymorphic variants of IL7R, IL1R1, IL2RA, and IL10 in the genetic predisposition to MS. The obtained models require validation and can be supplemented with other predictors to improve accuracy; nevertheless, they demonstrate important pathogenetic patterns and directions for further study.