Metformin is a first-line drug for DM2 treatment and prevention, but its complex effect on impaired glucose tolerance (IGT), including its influence on myocardial resistance to ischemia-reperfusion injury, is not completely studied. We aimed to evaluate the influence of metformin on the intestinal microbiota (IM), metabolism, and functional and morphological characteristics of myocardium in rats with IGT. IGT was modelled in SPF Wistar rats with a high-fat diet and streptozotocin and nicotinamide injection. Rats were divided into three groups: IGT (without treatment), IGT MET (metformin therapy), and CRL (without IGT induction and treatment). IGT group was characterized by: higher body weight, increased serum glucose and total cholesterol levels, atherogenic coefficient, impairment in the functional parameters of the isolated heart during perfusion, and larger myocardium infarction (MI) size in comparison with the CRL group. IM of IGT rats differed from that of CRL: an increase of Bacteroides, Acinetobacter, Akkermansia, Roseburia, and a decrease of Lactobacillus genera representation. Metformin therapy led to the diminishing of metabolic syndrome (MS) symptoms, which correlated with IM restoration, especially with the growth of Akkermansia spp. and decline of Roseburia populations and their influence on other members of IM. The obtained results allow us to consider from a new point of view the expediency of probiotic A. muciniphila use for MS treatment.

Despite great advances in the treatment of oncological diseases, the development of medical technologies to prevent or reduce complications of therapy, in particular, those associated with surgery and the introduction of antibiotics, remains relevant. The aim of this study is to evaluate the effectiveness of the use of autoprobiotics based on indigenous non-pathogenic strains of Enterococcus faecium and Enterococcus hirae as a personalized functional food product (PFFP) in the complex therapy of colorectal cancer (CRC) in the early postoperative period. A total of 36 patients diagnosed with CRC were enrolled in the study. Study group A comprised 24 CRC patients who received autoprobiotic therapy in the early postoperative period, while the control group C included 12 CRC patients without autoprobiotic therapy. Prior to surgery and between days 14 and 16 post-surgery, comprehensive evaluations were conducted on all patients, encompassing the following: stool and gastroenterological complaints analysis, examination of the gut microbiota (bacteriological study, quantitative polymerase chain reaction, metagenome analysis), and analysis of interleukins in the serum. Results: The use of autoprobiotics led to a decrease in dyspeptic complaints after surgery. It was also associated with the absence of postoperative complications, did not cause any side effects, and led to a decrease in the level of pro-inflammatory cytokines (IL-6 and IL-18) in the blood serum. The use of autoprobiotics led to positive changes in the structure of escherichia and enterococci populations, the elimination of Parvomonas micra and Fusobacterium nucleatum, and a decrease in the quantitative content of Clostridium perfringens and Akkermansia muciniphila. Metagenomic analysis (16S rRNA) revealed an increase in alpha diversity. Conclusion: The introduction of autoprobiotics in the postoperative period is a highly effective and safe approach in the complex treatment of CRC. Future studies will allow the discovery of additional fine mechanisms of autoprobiotic therapy and its impact on the digestive, immune, endocrine, and neural systems.

BACKGROUND: With the sharp increase in mine-explosive injuries, one of the key tasks of modern histology is to assess the morphogenesis of high-energy limb tissue damage. AIM: This study aimed to characterize striated skeletal muscle tissue in the zone of mine-explosive limb segment avulsion during the early post-traumatic period (days 1–4). METHODS: Histological methods (hematoxylin and eosin staining and Martius Scarlet Blue [MSB] staining for fibrin age determination), immunohistochemical and immunofluorescence techniques (antibodies to CD3, CD20, CD31 [Platelet Endothelial Cell Adhesion Molecule-1], CD68, and NETs [Neutrophil Extracellular Traps]), transmission electron microscopy, and morphometric analyses were applied. RESULTS: Post-traumatic pathological changes affected both muscle tissue (necrosis, fiber fragmentation, traumatic edema) and endomysial and perimysial connective tissue (traumatic edema, fibrin infiltration). Disruption of the cytoskeletal structure (sarcomeres), loss of myosatellite cells, and endothelial cell death in capillaries were observed. Local hemodynamic disturbances manifested as mosaic thrombosis, embolism, and hemorrhage. Within the first 24 hours, arterial and arteriolar spasms led to reduced tissue perfusion. Partial resolution of the spasms by day 4 likely corresponded to the second stage of traumatic shock (the torpid phase). Among leukocytes, CD68+ macrophages were the first to respond, with extravasation beginning on day 2 after injury. A similar trend was observed for CD3+ T cells. CD20+ B cells showed no morphological signs of reactivity during this period. NET formation was observed both intravascularly and in the extravascular compartment. CONCLUSION: Structural and ultrastructural changes in skeletal muscle tissue within the first 4 days after mine-explosive injury have been characterized.

Clarithromycin (CLR) is currently a key antibiotic for Helicobacter pylori infection treatment, however, the data on CLR resistance patterns in Russia are missing. Here, we applied WGS-based approach to H. pylori clinical isolates from Russia to comprehensively investigate sequence variation, identify putative markers of CLR resistance and correlate them with phenotypic susceptibility testing. The phenotypic susceptibility of 44 H. pylori isolates (2014–2022) to CLR was determined by disc diffusion method: 23 isolates were CLR-resistant and 21-CLR-susceptible. All isolates were subjected to WGS and submitted to GenBank. Based on complete sequence analysis, we showed that among all sequence variants, the combination of mutations A2146G/A2147G in the 23S rRNA gene is the most reliable for prediction of phenotypic susceptibility. For the first time, the average number of mutations in 106 virulence-associated genes between resistant and susceptible groups were compared. Moreover, this study presents the first WGS insight into genetic diversity of H. pylori in Russia with a particular focus on the molecular basis of drug resistance: the novel mutations were described as potential markers for the resistance development. Of these, the most prominent was a frameshift deletion (252:CGGGT) in HP0820 coding region, which is a good candidate for further investigation.

The aim of our study was to evaluate the clinical performance of a monotherapy by Enterococcus faecium-based probiotics and indigenous autoprobiotics against H. pylori associated dyspepsia. Materials and methods. There were examined 95 patients with dyspepsia. The entire patient cohort underwent clinical evaluation including filling out the questionnaire to assess dyspepsia symptoms before and after treatment, gastric endoscopy as well as gastric multi-focal biopsy (gastric body and gastric antrum) and verification of H. pylori infection with the three clinical laboratory methods (biochemical, bacteriological and molecular detection). An antagonistic in vitro activity of probiotics against H. pylori was detected by drop plate method for probiotic strains Enterococcus faecium SF68 and Bifidobacterium bifidum (Bifiform), Enterococcus faecium L3 (Laminolact), and autoprobiotic strains combined with indigenous Enterococcus faecium. To examine an antagonistic activity of probiotics and autoprobiotics in clinical trials, we used a starter culture based on the Enterococcus faecium L3 strain and an autoprobiotic based on indigenous Enterococcus faecium. The probiotic or autoprobiotic were administered orally to patients with gastritis twice a day at dose of 50 ml (8.0 lgCFU/ml) for 20 days. H. pylori eradication was assessed by stool antigen test 1.52 months after the end of treatment. Results. Initially the H. pylori infection was confirmed with 49.4% of patients. The sensitivity of H. pylori to the probiotics was detected in 81% of individuals for indigenous Enterococci (the autoprobiotic), 76% for Laminolact, and in 62% for Bifiform. 22 patients with previous history of allergic reactions to antibiotics used in routine H. pylori eradication regimens were divided in two cohorts. One cohort (10 patients) received the autoprobiotic only, another cohort (12 patients) received only probiotic. Monotherapy with autoprobiotic resulted in 100% H. pylori eradication, single-agent therapy with probiotic led to 60% eradication of H. pylori. Dyspepsia symptoms were completely resolved in both groups of patients. Conclusion. Our research demonstrated the sensitivity of examined H. pylori strains to be similar for traditional eradication treatment agents (antibiotics) and the proposed intervention agents (probiotics and autoprobiotics). An autoprobiotic monotherapy with indigenous enterococci led to higher levels of H. pylori eradication than with E. faecium L3-based probiotic agent. Our work demonstrated advantage for application of probiotics in patients with antibiotic allergies or other obstacles for the standard eradication therapy. Nonetheless, further investigation to better understand underlying mechanisms of action, as well as larger observational and randomized studies, are necessary to determine the scope of therapeutic application for probiotics and autoprobitics to eradicate H. pylori infection.

Introduction: Morphofunctional changes of the circulatory system organs detected in athletes may remain without due attention, as clinical (phenotypic) signs of pathological abnormalities are very similar to manifestations of cardiovascular system adaptation to intensive physical loads. The aim of the study is to propose a personalized algorithm for biomedical support of professional athletes with abnormalities and diseases of the circulatory organs based on clinical and genomic data.Materials and methods: The results of in-depth medical examination (2021-2023) of 15,464 athletes who are members of Russian sports teams were analyzed. The structure of circulatory system diseases according to the codes of the International Classification of Diseases, 10th revision (ICD-10), which were included in the summary report of the last examination, was analyzed. Fifty athletes with abnormalities and diseases of the circulatory system organs, experiencing different degrees of intensity of dynamic and static loads in accordance with the Mitchell classification, were selected from the study sample for full genome sequencing and subsequent clinical interpretation of the obtained data.Results: In the study sample the number of people with pathologic conditions of the circulatory system organs amounted to 6 946 people (45 %). Mitchell classification groups had statistically significant differences with respect to the prevalence of 10 diseases of the circulatory system organs. In 50 DNA samples of professional athletes, 5 probably pathogenic variants (10%), 19 variants with uncertain clinical significance (38%), relevant to the phenotype of a monogenic disease with circulatory system organ damage, were detected.Conclusion: Molecular genetic testing is an effective tool for differential diagnostics of pathologic and adaptive changes in the organs of the circulatory system. Carrying causative genes in combination with clinical signs allows to change the tactics of medical and biological support of an athlete according to the proposed algorithm.