Bulletin of RSMU

ISSN Print 2500–1094 ISSN Online 2542–1204

Bulletin of RSMU

BIOMEDICAL JOURNAL OF PIROGOV UNIVERSITY (MOSCOW, RUSSIA)

Scopus

SCImago Journal & Country Rank

Log In Registration RU

Kulinich TM, Kudinova EA, Goncharov SV, Kukoleva EA, Puchkov IA, Chaptykov AA, Dovgan FN, Goncharova OI, Bozhenko VK

Peritoneal carcinomatosis in colorectal and gastric cancer is associated with the extremely poor prognosis and the limited standard therapy efficacy, which suggests the need to develop new targeted drugs. The study aimed to assess the long-term outcomes of the efficacy of the RAS-GTPase peptide inhibitor (“Ing-Ras”) intraperitoneally administered by the PIPAC method to patients with stage III–IV gastric and colorectal tumors. A total of 38 patients (21 with colorectal cancer (CRC), 17 with gastric cancer (GC), including with peritoneal carcinomatosis) were included in the prospective open-label nonrandomized multicenter phase I/IIa trial. The long-term outcomes were assessed after 30 months of follow-up. A significant increase in the overall survival parameters was reported for both disease entities: the one- and two-year overall survival was 95.24 and 80.95% for CRC (historical control: 65–85% and 50–65%), 76.47 and 47.06%, respectively, for GC vs. 40–60% and 20–30%; progression and recurrence rates decreased significantly. Thus, the use of “Ing-Ras” makes it possible to increase the survival rate and reduce the recurrence rate relative to the historical control, which justifies conducting phase III trials.

Received: 2026-08-18

Published online: 2026-09-20

DOI: 10.24075/brsmu.2026.051

Comments 0

VIEWS 101

Rudenok MM, Semenova EI, Rybolovlev IN, Partevian SA, Lukashevich MV, Abaimov DA, Slominsky PA, Shadrina MI, Alieva AKh

Parkinson's disease (PD) is a progressive neurodegenerative disease, the key pathogenetic feature of which is considered to be the degeneration nigrostriatal dopaminergic neurons and the decrease in striatal dopamine (DA) levels. The study aimed to assess the dynamic changes in the levels of DA, serotonin, and their main metabolites in the striatum of C57BL/6 mice with the chronic toxic PD model induced by administration of multiple doses of 1-methyl-4-phenyl-1,2,3,6tetrahydropyridine (MPTP) combined with probenecid. The use of such modeling protocol enables simulation of the long-lasting neurochemical alterations similar to the slow progressive course of the disease in humans. Neurotransmitters and their metabolites were quantified by high-performance liquid chromatography with electrochemical detection. The study results demonstrate the decrease in the total DA metabolism in both axon terminals and the synaptic cleft during early neurodegeneration typical for PD. The most pronounced decrease in the levels of DA and its metabolite DOPAC was observed a week after the course of MPTP/ probenecid injections: it was 36% and 32% of the control level, respectively. It is noteworthy that the DA and DOPAC levels remained decreased throughout 3 months and were restored to the control level as late as 6 months after the end of the course of MPTP/probenecid injections. In general, the model presented makes it possible to extend the window of neurodegenerative alteration manifestation to 3 months. The data obtained once again demonstrate a complex pattern of the effects of neurodegenerative and compensatory processes occurring at the earliest stages of neurodegeneration in PD.

Received: 2026-07-30

Published online: 2026-09-16

DOI: 10.24075/brsmu.2026.049

Comments 0

VIEWS 118

Berezutskaya VP, Mikhailova AA, Shurygina DA, Pavlenko VB

The problem of finding new treatment methods fo r children with autism spectrum disorder (ASD) remains urgent. One of the ways to correct the manifestations of ASD is the Early Start Denver model (ESDM). This article describes a clinical case of a patient (a boy) with ASD. The child began an 8-month ESDM-based psycho-correctional intervention at the age of 4 years and 2 months. Each session lasted 50 minutes; they were held twice a week. One of the parents (the boy's mother) was an active participant in the sessions. Before and after the intervention, the child’s condition was assessed using the ADOS-2 and CARS scales, the E. E. Lyaxo speech development questionnaire, a measure of helping-behavior severity, and EEG. According to the supervising psychiatrist and his parents, the boy’s behavior has improved. Test results indicated a reduction in autism symptom severity (ADOS-2 score: 5 to 4; CARS score: 32 to 24), an increase in the percentage of correctly completed speech tasks from the Lyaxo questionnaire (46.5% to 54.0%), and increases in instrumental (2 to 10), emotional (0 to 5), and altruistic (0 to 9) helping behaviors, as well as in a combined altruistic–emotional helping behavior score (0 to 8). After the ESDM intervention, the child showed stronger µ-rhythm amplitude desynchronization on EEG during observation of another person’s actions. This clinical observation confirms that the ESDM technique can significantly impact the neural circuits underlying social behavior.

Received: 2026-08-03

Published online: 2026-09-17

DOI: 10.24075/brsmu.2026.050

Comments 0

VIEWS 191

Kareem AT

The evolution of multi drug-resistant bacterial diseases enforces the need for new botanical anti-microbiological drugs. Curry leaf (Murraya koenigii L. Spreng) is often used in traditional medicine; however the pharmacognosic effects and extraction efficiency need to be affirmed meticulously. The study aimed at qualitative phytochemical profiling and physicochemical standardization of M. koenigii leaf powder by aqueous, ethanolic and methanolic solvent systems, conducted for the first time. MICs were measured by microdilution to determine antibacterial activities against a panel of clinically relevant pathogens; the disc diffusion method was used for microbiological analysis. Tukey's post-hoc test was used after one-way ANOVA to examine statistical differences. Physicochemical examination showed a total ash value of 15.4% ± 0.3% w/w and a low moisture content of 4.2% ± 0.3% w/w. We detected bioactive secondary metabolites, including as tannins, alkaloids, and, flavonoids were validated by phytochemical screening, with alcoholic solvents showing higher extraction yields than water. The ethanolic extract showed strong antibacterial activity against Proteus mirabilis (21.0 mm) and Staphylococcus aureus (21.0 mm) in disc diffusion experiments, but the aqueous extract was totally inactive (0.0, p < 0.001). Bacillus sp. and Streptococcus mutans showed the lowest MIC values for the ethanolic extract (0.156 mg/mL). These results validate M. koenigii's potential development as a natural therapeutic agent by establishing pharmacognostic quality markers for the plant and showing that its ethanolic extract contains extremely powerful antibacterial agents, especially effective against Gram-positive clinical isolates.

Received: 2026-07-18

Published online: 2026-08-31

DOI: 10.24075/brsmu.2026.047

Comments 0

VIEWS 608

Kerimov KB, Ivanov AS, Tananakina TP, Kashchenko SA, Pogorelova IA

The meniscus degeneration pathogenesis is important for understanding and developing new treatment methods; it includes biochemical, structural, and microcirculatory alterations affecting all joint structures. The study aimed to perform in vitro assessment of the effects of standard and photoactivated platelet-rich plasma (PRP) on the IL6, IL17A concentrations, expression of COL2A1 and CD95 apoptosis marker in human meniscus fibrochondrocytes in the IL1β-induced inflammation. The human knee meniscus cartilage tissue was collected from 12 somatically healthy donors aged 18 to 35 years for the experiment. Cells were divided into four groups: the first was intact (control), the second, third, and fourth ones were exposed to IL1β to induce degenerative alterations; the second one was supplemented with 0.9% NaCl, the third one with donor PRP, and the fourth one with photoactivated PRP. Parameters were determined after 48 h. Statistical analysis was performed in GraphPad Prism 9. The rm-ANOVA was used for related groups. Data were presented as mean ± SD, at p < 0.05. IL6 (79.6 ± 4.3 pg/mL vs. 28.4 ± 2.1 pg/mL), IL17A (42.8 ± 2.5 pg/mL vs. 14.2 ± 1.0 pg/mL), CD95 (28.5 ± 2.2% vs. 6.8 ± 0.7%) levels increased in group II compared to group I; COL2A1 levels decreased from 1.00 ± 0.08 to 0.42 ± 0.0). IL6 levels decreased to 55.1 ± 3.4 pg/mL, IL17A — to 29.4 ± 2.1 pg/mL, CD95 — to 17.2 ± 1.5%, and COL2A1 levels increased to 0.71 ± 0.06 in group III compared to group II. IL6 levels decreased to 38.2 ± 2.6 pg/mL, IL17A — to 18.6 ± 1.7 pg/mL, CD95 — to 9.4 ± 0.8%, and COL2A1 levels increased to 0.94 ± 0.07 (p < 0,05) in group IV compared to group III. Standard PRP has a positive effect on meniscus tissue in vitro after 48 h. The effect is enhanced after the PRP exposure to red light.

Received: 2026-06-27

Published online: 2026-08-26

DOI: 10.24075/brsmu.2026.046

Comments 0

VIEWS 387

Sharko FS, Prokopenko AV, Izotova AO, Toshchakov SV

Genotype imputation makes it possible to considerably reduce the cost of whole-genome data acquisition preserving the information value, but its accuracy depends directly on the availability of a high-quality phased reference panel of haplotypes. The existing panels for Macaca mulatta cover mostly the Indian species lineage and do not reflect the genetic structure of laboratory populations of mixed origin. This retrospective bioinformatics study aimed to produce and validate a phased reference panel based on the consolidation of publicly available whole-genome datasets from 618 M. mulatta individuals of both geographic lineages processed in accordance with the common standardized protocol. The resulting panel includes 33,457,491 SNP markers. Validation on samples of Indian and Chinese origin with ultra-low coverage (0.1x–0.9x) confirmed high imputation accuracy, which was highest for the Indian lineage dominant in the panel. Testing on 10 independent samples with the 0.6x coverage showed a high average imputation reliability score (INFO = 0.898). The created resource opens the prospects for cost-effective genotyping of large M. mulatta cohorts and provides the basis for whole-genome association and population genetic studies in domestic and foreign primate research centers.

Received: 2026-07-14

Published online: 2026-08-21

DOI: 10.24075/brsmu.2026.045

Comments 0

VIEWS 496

Yusef OV, Ibragimov BR, Klimenko MP, Gerasimova AA, Aimetdinova AB, Marnat EG, Abramov DD, Klimenko PA, Kurtser MA

Missed abortion is one of the most prevalent forms of early pregnancy loss that remains a pressing issue of obstetrics and gynecology. Despite advances in reproductive medicine, the molecular mechanisms underlying the embryo development termination in early gestation are poorly understood. A comparative singlecenter study aimed to assess the expression of TGF-β and MMP-9 genes in peripheral blood of women with physiological and missed abortion and assess their potential prognostic value for evaluation of the risk of early pregnancy loss. A total of 40 pregnant women were included in the study: 20 patients with the 9–11 week physiological pregnancy (control group) and 20 women diagnosed with missed abortion (index group). The TGF-β and MMP-9 gene expression was determined by the real-time polymerase chain reaction method after the total RNA isolation from peripheral blood. The Mann‒Whitney U-test and ROC analysis were used for statistical data processing. No significant differences in the TGF-β and MMP-9 gene expression between the studied groups were revealed. At the same time, ROC analysis made it possible to determine the threshold values of the studied indicators having some diagnostic information content. As for MMP-9, the threshold value Ct ≤ 29 ensuring the 80% sensitivity and 60% specificity turned out to be the most informative. As for TGF-β, the threshold value Ct ≤ 27.4 was characterized by the 75% sensitivity and 70% specificity. The findings suggest the potential prognostic value of the studied genes for evaluation of the risk of missed abortion.

Received: 2026-06-24

Published online: 2026-08-18

DOI: 10.24075/brsmu.2026.043

Comments 0

VIEWS 502

Romanovskaya-Romanko EA, Ozhereleva OO, Plotnikova MA, Altuhov AS, Stukova MA

The use of live attenuated influenza vectors requires a balance between decreasing virulence and preserving immunogenicity. One possible approach to enhancing immunogenicity and protective efficacy of such attenuated strains is the integration of transgenes capable of activating the innate and adaptive immunity in the viral genome. The experimental study aimed to construct recombinant attenuated influenza viruses capable of expressing human IL1β and conduct comparative analysis of their replication properties, immunostimulatory activity, and safety profile in vivo. Recombinant strains with different transgene localization were generated by the reverse genetics method; their growth characteristics and transgene expression levels were assessed. Activation of the innate immunity genes in response to infection with recombinant strains was assessed in the А549 cell culture. The attenuated phenotype was confirmed in the mouse model. In the reported study, recombinant attenuated influenza viruses having the NS1 protein truncated to 124 amino acid bases and expressing human IL1β were constructed and produced. It was confirmed that recombinant strains could express the functionally active IL1β; the increase in relative expression of the innate immunity genes (RIG-I, MDA5, OAS1) and pro-inflammatory cytokines (IL6 and TNFα) in response to the infection of cells with recombinant strains compared to the empty vector NS124 was shown. Thus, the IL6 gene expression increased more than 10-fold (p < 0.0001) and that of the TNFα gene increased 3–4-fold (p < 0.0001). The attenuated phenotype of the recombinant strains produced was confirmed in in vivo experiments, which suggests preservation of the safety profile along with the enhanced immunostimulatory activity.

Received: 2026-07-02

Published online: 2026-08-17

DOI: 10.24075/brsmu.2026.044

Comments 0

VIEWS 457