ISSN Print 2500–1094    ISSN Online 2542–1204
BIOMEDICAL JOURNAL OF PIROGOV UNIVERSITY (MOSCOW, RUSSIA)

New articles

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.
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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.
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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.
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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.
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Popular articles

The PI3K/AKT/mTOR signaling pathway is a key regulator of cell growth, and its dysregulation is involved in oncogenesis. Existing methods for assessing mTOR activity have design flaws. The aim of this work was to develop and validate a novel multiplex RT-qPCR assay for relative quantification of mTOR gene expression normalized to RPLP0 and TBP. Primers and probes were designed in silico. Validation was performed using the human SCP-1 cell line. Specificity was assessed in 10 separate and 10 multiplex runs. Analytical sensitivity and efficiency were determined from 27 technical replicates using a protocol without an elongation step. Specificity of amplification was assessed by agarose gel electrophoresis, and quantitative analysis was performed in real-time PCR using FAM (mTOR), HEX (RPLP0), and ROX (TBP) fluorescence channels. The assay showed 100% specificity. Stable detection was achieved at 125,000 cells/mL. Amplification efficiencies were 73–81%. The variation of mTOR expression normalized to RPLP0 ranged from –21.5% to 26.4%, and normalized to TBP from –14.3% to 19.2%. Normalization to the geometric mean of both reference genes provided the best reproducibility, with an interquartile range from –9% to 23.4%. The developed assay demonstrates high specificity, sensitivity, and reproducibility, making it a reliable tool for subsequent clinical research.
VIEWS 1078
For several decades, Wilson’s disease (WD) has remained the focus of attention for a wide range of specialists, including hepatologists, general practitioners, neurologists, geneticists, etc. However, despite significant advances in understanding its molecular basis, establishing clear correlations between the genotype and clinical phenotype of the disease remains a key unresolved issue. The study aimed to identify patterns between genetic variants in the ATP7B gene and the WD clinical manifestations using next-generation sequencing. The data from 81 WD patients, who were followed up between 2015 and 2019, were used in the study. Molecular genetic testing of biomaterial (blood) samples was performed by NGS. The analysis of the molecular genetic testing results using targeted NGS revealed 31 pathogenic variants. The following variants were the most frequent: c.3207C>A (p.His1069Gln) — 51.85% alleles, c.3190G>A (p.Glu1064Lys) — 8.64% alleles, and c.3402delC (p.Ala1135fs) — 6.17% alleles. A moderate correlation between genotype and phenotype was established: pathogenic variants (nonsense, frameshift, splicing) in the homo- or compound heterozygous state are associated with severe liver damage, severe degree of cirrhosis, and lower cholinesterase levels. The data obtained emphasize the importance of molecular genetic diagnosis for clarifying the diagnosis of WD and predicting the disease severity.
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Dear researcher!
At the end of 2015, Bulletin of RSMU saw an important change in its typographic design and content. We formulated new editorial policies and established strict ethical standards for submitted manuscripts in accordance with the guidelines of reputable international bodies. As a result, about a quarter of the submitted works have been rejected, the primary reason being the author trying to submit a previously published article. Sometimes authors believe that by making slight changes to the introduction, excluding a few people from the study, performing a new statistical analysis, and thus obtaining totally new results they will turn their old manuscript into a novel work. That is why we would like to talk about scientific integrity, honesty, plagiarism, and self-plagiarism in our special project “Author’s work”.
Richard FEYNMAN Cargo cult science
American physicist Richard P. Feynman, a Nobel laureate, was always very scrupulous about the quality of a research study. During his commencement address at the California Institute of Technology in 1974, he talked about scientific integrity and honesty and warned young researchers “not to fool” themselves. A must-read for anyone who believes he/she is a true scientist.
Ivan PAVLOV On the Russian mind
In 1918, Russian physiologist Ivan Pavlov, a Nobel laureate, delivered two lectures: on the mind in general and the Russian mind in particular; on those mind qualities that determine the success of a research work and on how these qualities are present in the Russian mind. Pavlov's thoughts are an effective vaccine against poor intellectual work.