Bulletin of RSMU

ISSN Print 2500–1094 ISSN Online 2542–1204

Bulletin of RSMU

BIOMEDICAL JOURNAL OF PIROGOV UNIVERSITY (MOSCOW, RUSSIA)

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Lee YC#, Yang TD#, Chen WC, Dubey NK, Chaturvedi H, Huang AC, Chang CH, Lin CC, Liu MC

Erectile dysfunction (ED), an unusual sexual condition in which the person fails to attain or sustain an erectile penis, severely impacts personal relationships, confidence, and efficiency. To date, low-intensity extracorporeal shock wave therapy (Li-ESWT) is an option to manage ED; however, it is associated with adverse events such as bruising, redness, and pain. Hence, in this study, we applied platelet-rich plasma (PRP), a blood-derived biomaterial containing cargo of growth factors, to enhance the therapeutic efficacy of Li-ESWT on ED. We assessed the synergistic effect of PRP+Li-ESWT, in which Li-ESWT was extracorporeally applied simultaneously with PRP. They were evaluated clinically at 22 ± 2, 50 ± 2 and 78 ± 2 days. Statistical analysis was performed using a non-parametric test, Friedman repeated measures as an alternative non-parametric test of ANOVA test. The international index of erectile function (IIEF-5) and erection hardness score (EHS) were recorded. IIEF-5 score in the pre-treated group was 8.36 ± 1.44. After 22 ± 2 days of synergistic PRP+Li-ESWT treatment, the score was 14.45 ± 2.12 (p < 0.028). This score further increased to 15.45 ± 1.93 (p < 0.008) and 16.18 ± 1.48 (p < 0.001) after 50 ± 2 days and 78 ± 2 days of treatment, respectively. The mean pre-treated EHS was 1.64 ± 0.20 (p < 0.002), which increased to 2.81 ± 0.26 (p < 0.002), 3.09 ± 0.25 (p < 0.0002) and 3.18 ± 0.12 (p < 0.000) on day 22 ± 2, 50 ± 2 and 78 ± 2 days, respectively. Conclusively, our study demonstrated potent synergistic therapy of PRP+Li-ESWT in ED treatment by improving IIEF-5 and EHS scores. However, extensive mechanism-based clinical studies are needed to reach a consensus.

Received: 2024-09-21

Published online: 2024-12-05

DOI: 10.24075/brsmu.2024.054

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VIEWS 93

Osikov MV, Korobkin EA

Reduced bone mineral density (BMD), osteopenia, and osteoporosis are slightly more common in patients with chronic lymphocytic leukemia (CLL). The risk of osteoporotic fractures in individuals with CLL is higher, than in healthy individuals of the same age. The mechanism underlying the CLL-associated BMD reduction can be related to decreased antioxidant protection and oxidative stress (OS). The study aimed to assess the relationship between oxidative stress, antioxidant protection, and osteopenia indicators in patients with CLL. Males aged 50–70 years were examined. Group 1 consisted of 14 healthy men, group 2 consisted of 54 patients with CLL having no BMD alterations, and group 3 consisted of 22 patients with CLL having signs of osteopenia. A densitometer was used to estimate BMD, T- and Z-scores of the lumbar vertebrae, proximal femoral neck (PFN), proximal femoral bone in all groups. At the beginning of the study, the levels of lipid peroxidation (LPO) products were determined in blood serum in all groups and bone tissue homogenate in groups 2 and 3; the total antioxidant status (TAS) was also determined. Bone densitometry indicators, serum LPO and TAS were assessed in all groups after 6 months of follow-up. At the beginning of the study osteopenia in PFN based on bone densitometry data was revealed in 29% of patients, while 6 months later osteopenia of all localizations was observed in 55% of patients. At the beginning of the study patients with CLL and osteopenia showed OS and reduced TAS in both blood serum and bone tissue. After 6 months patients with CLL and osteopenia showed signs of OS progression and TAS reduction. In patients with CLL, serum and bone tissue OS indicators are comparable and can be used to predict the onset of osteopenia within 6 months.

Received: 2024-10-11

Published online: 2024-11-30

DOI: 10.24075/brsmu.2024.053

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VIEWS 125

Kalinina AA, Kubekina MV, Persiyantseva NA, Bruter AV, Khromykh LM, Kazansky DB

T cells, the adaptive immunity effectors, carry an antigen-recognizing T-cell receptor (TCR) that represents an αβ heterodimer. Functional dominance of one chain has been reported for a number of TCRs. This feature is called chain centricity. Today, it is unclear whether chain centricity is an inherent feature of some TCRs, and what mechanism underlies its development. The study aimed to determine the abundance of such receptors in the repertoire of primarily activated effectors and re-stimulated memory cells of mice specific to the allogeneic tumor antigens. The long-lived memory cells formed in the primary immune response in vivo were in vitro re-stimulated with the immunizing tumor cells. Primary effectors were obtained in vitro in the culture by stimulation of T cells of non-immunized mice with cells of the same allogeneic tumor. TCR libraries of effectors involved in the primary and secondary immune response were created by NGS sequencing. To identify chain-centric TCRs, 10 ТCRα variants were selected from each repertoire. T cells of intact mice were modified with individual TCR α-chain variants by transduction, with subsequent assessment of T cell proliferation under exposure to specific allogeneic stimulators. In vitro screening revealed 10% of chain-centric receptors in the primary effector pool, and the proportion of such TCRs in the repertoire of re-activated memory cells was 30%. Thus, chain centricity is an inherent property of some TCRs, but secondary antigenic stimulation can be a factor for selection of clonotypes with such receptors.

Received: 2024-10-09

Published online: 2024-11-30

DOI: 10.24075/brsmu.2024.052

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VIEWS 134

Desyatskova EM, Grechenko VV, Soboleva VV

In case of obstructive disorders, the flow–volume curve has a concave shape, but this feature is not given due attention. Тhe analysis of the velocity indicators of the respiratory function (such as the peak expiratory flow (PEF) and forced expiratory flows (FEFs)) will significantly expand the diagnostic capabilities of the spirometry method. This paper aims to perform a comparative analysis of the diagnostic strength of the methods of the flow-volume curve assessment by the changes in its shape in patients with obstructive airway diseases to determine the most reliable one. The respiratory function of 540 patients was tested (234 are men (57 [36; 67] years) and 306 are women (59 [44; 69] years)), with the ratio of areas under the actual curve and the predicted curve calculated for each one, as well as the angle formed by the curve; the ratio of the actual FEF (henceforth referred to as FEF) to the predicted FEF, cut-off points to differentiate between obstructive diseases and health. On the basis of these results, we concluded whether the patient’s bronchi were blocked. The results were then compared to the Knudson reference equations, with the test’s operational characteristics calculated compared to the standard. The methods of assessing the angle β and the total concavity of the flow-volume curve have high diagnostic sensitivity (87.8% and 95.6% respectively). The assessment of the area under the curve (AEX-FV) has high diagnostic specificity (88.6%). The results obtained show sufficient diagnostic efficiency of the methods of flow-volume curve estimation by the changes in its shape. However, the use of these methods in isolation from the reference equations does not currently seem reasonable for clinical practice. It appears reasonable to use the reference equations and one of the methods of curve shape assessment together.

Received: 2024-10-08

Published online: 2024-11-27

DOI: 10.24075/brsmu.2024.051

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VIEWS 170

Pobozhieva LV, Skvortsov-Igralov GA, Bocharova YuA, Kopetskiy IS, Chebotar IV

The inflammatory periodontal disease pathogenesis is determined by microorganisms of the oral cavity. Along with the well-studied periodontopathogens, microbial agents of unproven clinical significance, including epibiotic bacteria, are found in individuals with gingivitis and periodontitis. The study aimed to determine the association between the Nanosynbacter lyticus epibiont and inflammatory periodontal diseases. Conservative DNA sequences specific for the genera Nanosynbacter, Schaalia and the Bacteria domain were identified using PCR in 47 study participants (31 females and 16 males) aged 18–45 years. The results were expressed as indices determining the quantitative relationships between N. lyticus and Schaalia spp. (NS index), as well as between N. lyticus and representatives of the Bacteria domain (NB index). Schaalia spp. were not found in a large share (11/27, 40.7%) of patients with no periodontitis. All patients with moderate-to-severe periodontitis, as well as 75% of patients with mild periodontitis were carriers of Schaalia spp. All the Schaalia-positive samples from patients with periodontitis showed higher NS indices (p < 0.05) compared to Schaalia-positive samples from patients with no periodontitis: the median NS values were Ме = 0.89 (0.79; 0.93) and Ме = 0.63 (0.00; 0.73), respectively. The patients suffering from chronic generalized periodontitis had significantly higher NB indices (Ме = 0.83 (0.79; 0.85)) (p < 0.05) compared to patients with no periodontitis, Ме = 0.67 (0.00; 0.81).

Received: 2024-10-07

Published online: 2024-11-22

DOI: 10.24075/brsmu.2024.050

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VIEWS 223

Yamgutdinov RR, Mukhamadeev TR, Ahmadeev RR, Mochalov KS

Investigation of the mechanisms underlying retinal photodamage occurring during vitreoretinal interventions is a topical issue of ophtalmology. The study aimed to assess the effect of endoillumination of varying intensity and duration on alteration of oxidative processes in rabbit blood. The experiment involved 16 rabbits, with their retinas exposed to endoillumination of different duration (30 and 60 min) and intensity (8 and 16 cd/m2). Blood samples were collected from the rabbits’ ear vein before and after light exposure. Whole blood and serum biochemiluminescence was measured in order to assess oxidative processes. The data were analyzed using the Mann–Whitney U-test, and the results were considered significant at p ≤ 0.05. A 30-minute light exposure resulted in a significant increase in whole blood biochemiluminescence: 1.5-fold at the intensity of 8 cd/m2 and 2.5-fold at the intensity of 16 cd/m2 relative to control values (p < 0.05), indicating enhanced reactive oxygen species generation by blood cells. In contrast, a significant decrease in serum biochemiluminescence was revealed: 1.2-fold at the intensity of 8 cd/m2 and 2-fold at the intensity of 16 cd/m2 compared to control (p < 0.05) , which likely indicates a compensatory increase in antioxidant activity in response to hyperactivation of free radical processes. With the 60-minute exposure, the changes in biochemiluminescence were more pronounced: 3- and 7-fold increase in whole blood biochemiluminescence and 2- and 3-fold decrease in serum biochemiluminescence, respectively. Thus, intense light exposure resulted in the oxidative process alterations determined by the intensity and duration of exposure.

Received: 2024-09-30

Published online: 2024-11-15

DOI: 10.24075/brsmu.2024.049

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VIEWS 240

Glazunova EV, Kurnosov AS, Zlobovskaya OA

Colorectal cancer (CRC) is one of the most prevalent malignant neoplasms that occupies the leading position in terms of cancer mortality. The main problem of CRC is that the disease is diagnosed at the advanced stages (about 50% of cases identified are stage III and IV CRC), which results in high mortality. Dysbiotic gut microbiota alterations represent one of the key risk factors of CRC. Three hypotheses of CRC emergence were formulated in order to explain the relationship between dysbiosis and carcinogenesis: “alpha-bug”, keystone pathogen, and driver–passenger hypotheses. The driver–passenger model is the most promising, it divides bacteria into “drivers” of cancer triggering inflammation and cell damage and the passenger bacteria modeling tumor microenvironment, accelerating tumor growth, and exacerbating dysbiosis. Drivers and passengers can be markers of various carcinogenesis stages. Colonoscopy involving examination of the surface of the rectum and colon is the most effective method to detect CRC, including the early stage disease. However, the wide use of this procedure is limited by the fact that it is associated with discomfort for patients and the risk of possible sequelae. Non-invasive microbiota assessment based on the driver–passenger model can become a safe and affordable alternative to the invasive diagnostics during preventive screening, since it makes it possible to improve survival rate due to involvement of a larger number of patients.

Received: 2024-10-15

Published online: 2024-10-31

DOI: 10.24075/brsmu.2024.046

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VIEWS 245

Plotnikova MA, Bobkov DE, Klotchenko SA

Human MxA protein induced by type I and III interferons is an important innate immunity mediator, it shows antiviral activity against a broad spectrum of RNA and DNA viruses. According to the latest data, the MxA protein overexpression increases chemotherapy sensitivity and represents one of the favorable prognostic factors in patients with breast cancer. The exogenous mRNA capable of intracellular MxA protein production not only has the potential for treatment of viral respiratory infection, but also can become an important fundamental research tool. The study aimed to construct and produce the exogenous mRNA encoding the functional human cytoplasmic MxA protein by in vitro transcription (IVT); to study its translational properties; to assess and identify the patterns of the expression of some interferon system genes in response to introduction of this exogenous mRNA into cells. As a result of the study, the exogenous mRNAs capable of effective translation (up to 20 ng/mL of protein from 100 ng of mRNA per well of the 96-well plate) in the eukaryotic cell systems were successfully constructed and produced by IVT (in the amount of up to 200 µg); diffuse distribution of the MxA protein in the MDCK cells was confirmed; significant changes in the expression of the interferon-stimulated genes, such as OAS1, PKR (EIF2AK2), MDA5, RIG-I, were revealed. Our further research will be focused on assessing the developed exogenous mRNAs’ therapeutic potential against influenza A and B viruses, respiratory syncytial virus, and coronavirus SARS-CoV-2.

Received: 2024-09-30

Published online: 2024-10-30

DOI: 10.24075/brsmu.2024.048

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VIEWS 229