Background: Dysferlinopathy has a high prevalence in relatively isolated ethnic groups where consanguineous marriages are characteristic and/or the founder effect exists. However, the frequency of endemic mutations in most isolates has not been investigated.Methods: The prevalence of the pathological DYSF gene variant (NM_003494.4); c.200_201delinsAT, p. Val67Asp (rs121908957) was investigated in an isolated Avar population in the Republic of Dagestan. Genetic screenings were conducted in a remote mountainous region characterized by a high level of consanguinity among its inhabitants. In total, 746 individuals were included in the screenings.Results: This pathological DYSF gene variant causes two primary phenotypes of dysferlinopathy: limb‐girdle muscular dystrophy (LGMD) type R2 and Miyoshi muscular dystrophy type 1. Results indicated a high prevalence of the allele at 14% (95% confidence interval [CI]: 12–17; 138 out of 1518 alleles), while the allele in the homozygous state was detected in 29 cases—3.8% (CI: 2.6–5.4). The population load for dysferlinopathy was 832.3 ± 153.9 per 100,000 with an average prevalence of limb‐girdle muscular dystrophies ranging from 0.38 ± 0.38 to 5.93 ± 1.44 per 100,000.Conclusion: A significant burden of the allele was due to inbreeding, as evidenced by a deficiency of heterozygotes and the Wright fixation index equal to 0.14 (CI 0.06–0.23).

Management of chronic, non-healing wounds is one of the pressing challenges in surgery. Demonstrating the effectiveness of novel drugs and medical devices is essential for their implementation in clinical practice. For this purpose, many animal models of wound healing have been developed, including in small rodents, which, however, have a specific skin structure and soft tissue regeneration. This review presents comparative characteristics of the main experimental wound models, including chronic ones, and describes their benefits and limitations. Experimental studies most commonly involve mice, rats, and rabbits due to their relatively low cost and ease of maintenance. The most widely used wound modeling method is the creation of an excisional skin defect (with or without modifications) on the back of rodents. This model is technically simple and allows for partial reproduction of various pathological conditions. Although none of the models fully replicates the chronic wound healing process, modeling in small rodents (mice, rats) and rabbits remains the primary approach for studying regeneration and evaluating the efficacy of therapeutic interventions. Excisional and incisional wound models on the back of rodents are popular due to their simplicity and reproducibility. However, a significant limitation of these models is rapid wound closure by contraction, which is uncharacteristic of human healing. Chronic wound models (splinting, tail wounds in mice or ear wounds in rabbits, hyperglycemia, and others) more accurately reproduce the healing process and better reflect clinical situations. The choice of a specific model depends on the study aims and the species-specific features of laboratory animals. Moreover, the short healing period in animals often limits the ability to assess treatment efficacy. Improving and standardizing existing wound models, as well as developing novel experimental approaches, remain important tasks for regenerative medicine and surgery.

Despite modern surgical treatment of idiopathic osteoarthritis, some facts force us to raise the question of revising the concept of aggressive surgical treatment in favor of new therapeutic organ-sparing treatment options for such patients. In particular, these are complexity of redo arthroplasty, insufficient data on genetic, gene-tissue predictors and signs of disease, unsatisfactory quality of life in long-term postoperative period. In addition to clarifying the indications for surgical treatment, searching for new aspects in pathogenesis that can become targets for new drugs, including gene therapy, remains important.

Introduction. Bone grafting is a key approach for overcoming osteogenic insufficiency in the treatment of maxillofacial defects. However, routine clinical methods do not allow for detailed assessment of the histological structure of the newly formed tissues. This study aimed to qualitatively and quantitatively compare the morphological features of bone regenerate formed using conventional and gene-activated osteoplastic materials. Materials and methods. The study included bone regenerate biopsies from 60 patients obtained 6 months after bone grafting prior to dental implantation. Samples were divided into two groups according to the material used during surgery: a conventional xenogenic matrix (n=19) and a synthetic gene-activated material based on octacalcium phosphate with plasmid DNA encoding VEGF (n=41). Histological analysis and histomorphometry were performed using the Parfitt system with Adobe Photoshop and ImageJ software to evaluate tissue components and material contacts. Results. No signs of acute inflammation were observed in either group, and complete material resorption did not occur. The volume of fibroreticular bone tissue was significantly higher with the gene-activated material than with the xenogenic matrix (p=0.043). Furthermore, the synthetic material demonstrated greater contact with newly formed trabeculae and more active vascularization, whereas the xenogenic matrix remained more inert. No differences in the extent of the active osteoblastic surface were revealed between the groups. Conclusion. Both materials demonstrated high biocompatibility and osteoconductivity. However, the gene-activated material ensured more active and prolonged remodeling of the regenerate compared to the conventional xenograft. This was confirmed by a greater volume of newly formed fibroreticular bone tissue and closer integration of the material with bone structures at 6 months. Keywords: reparative regeneration, osteoplastic materials, histomorphometry, gene therapy

BACKGROUND: A high incidence of musculoskeletal injuries and disorders is a major challenge in elite sports. Although the contribution of genetic factors to individual risk is well recognized, the spectrum and frequency of associated genetic variants in a key population—athletes representing national teams of the Russian Federation—remain insufficiently studied, which limits the development of personalized preventive approaches. This work aimed to fill this knowledge gap. AIM: The work aimed to determine the frequency and distribution of gene variants associated with the risk of musculoskeletal injuries and disorders among athletes of the Russian national teams. METHODS: A cross-sectional retrospective study was conducted in athletes of national teams of the Russian Federation aged 18–40 years who provided written informed consent and underwent comprehensive medical examination (CME) in accordance with established procedures. The exclusion criterion was the absence of signed informed consent or incomplete CME data. Study groups were formed based on CME findings: the case group included athletes with a history of at least one musculoskeletal injury or disorder, whereas the control group comprised athletes without any documented musculoskeletal condition. The study was performed at the National Center for Sports Medicine (NCSM) and the Center of Sports Preparation (CSP), both under the Federal Medical-Biological Agency of Russia. Participants were enrolled, and retrospective data were collected from electronic CME databases between 2021 and 2024. RESULTS: Among 152 athletes, 94 (61.8%) had a history of musculoskeletal injuries or disorders. Several genetic associations with outcome were identified for a number of variants. The highest odds ratios (ORs) were observed for the A allele of the IL18RAP gene (rs1420100, OR 31.81; p = 0.003) and the C allele of the FGF10 gene (rs1448037, OR 57.16; p = 0.003). Protective effects were shown for the G allele of the MIR608 gene (rs4919510, OR 0.06; p = 0.006) and the A allele of the MMP3 gene (rs650108, OR 0.10; p = 0.010). Additional significant associations were identified for variants in GDF5 (rs143383, OR 20.36; p = 0.002), VEGFA (rs1570360, OR 28.31; p = 0.003), and COL3A1 (rs1800255, OR 13.22; p = 0.007). CONCLUSION: There were significant differences in the distribution of specific genetic variants between athletes with or without musculoskeletal injuries or disorders. The findings are consistent with the expected biological effects of these genes. The findings can be integrated into the medical and biological support system for athletes.

Introduction. Physical exercise is one of the most powerful environmental factors modulating epigenetic modifications of the genome. The regulation of gene activity via the chemical modification of DNA, histone alterations, and non-coding RNAs serves as a link between training and the developing athletic phenotype. However, published data remain fragmented and often contradictory due to methodological challenges, heterogeneous cohorts, and a lack of protocol standardization. Objective. Systematization and synthesis of current data on the influence of physical exercise on epigenetic modifications of the genome, analysis of their contribution to the processes of adaptation, recovery, and formation of the risk of pathological conditions in athletes, as well as assessment of the prospects for the use of epigenetic markers in sports medicine. Discussion. Physical exercise induces specific changes in the three main components of the epigenome. Acute and chronic loads cause hypomethylation of the promoters of energy metabolism genes ( PPARGC1A , PDK4 , PPARD ), which is accompanied by increased expression and mitochondrial biogenesis. Histone modifications (acetylation, phosphorylation of H3.3-Ser-31, lactylation) alter chromatin packing density. The spectrum of microRNAs depends on the type and duration of training; however, information on individual microRNAs (including miR-1) remains contradictory, largely due to differences in methodology (participant training status, time points, normalization method, sex). Signaling cascades (AMPK, MAPK, IGF-1/Akt, NF-κB, NFE2L2) integrate energetic signals and the epigenetic response. The epigenetic response is tissue-specific and is modulated by sex, age, and ethnicity. Promising directions include the analysis of exerkines, including microRNAs from extracellular vesicles, and nutricepigenetics. Conclusions. Physical exercise consistently induces characteristic epigenetic modifications that participate in adaptation and can be considered as potential biomarkers of an athlete’s functional state. Promising areas of application in sports medicine include monitoring recovery through epigenetic clocks, predicting injury and overtraining, personalizing training, and extending the Athlete Biological Passport with epigenetic markers. Implementation of the results into clinical practice requires overcoming methodological limitations and further prospective research.