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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Burmenskaya OV, Trofimov DYu, Kometova VV, Rodionova MV, Rodionov VV

Today, preoperative hormone therapy is a standard procedure in the context of treatment of ESR+/HER2-negative early-stage breast cancer. Transcription profiles of genes helps make assessment of effectiveness of this therapy more accurate. This study aimed to investigate the changes in gene expression caused by the preoperative aromatase inhibitor response test in postmenopausal women with ESR+/HER2-negative breast cancer. The participants were 100 breast cancer patients treated at the Department of Breast Pathology of Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology. We did a pathomorphological study of FFPE blocks (trephine biopsied before the hormone response test was prescribed) and intraoperative samples, and immunohistochemical (Ki67, ER, PR, HER2/neu) and molecular genetic studies of 45 target genes (quantitative RT-PCR). Aromatase inhibitors in the preoperative hormone response test caused significant changes in the mRNA expression of 37 genes in breast tumors: for 35 of them (ESR1, PGR, AR, ERBB2, FGFR4, MKI67, MYBL2, CCNB1, AURKA, BIRC5, CCND1, CCNE1, CDKN2A, KIF14, PPP2R2A, PTTG1, TMEM45B, TPX2, ANLN, MMP11, CTSL2, EMSY, PAK1, BCL2, BAG1, PTEN, TYMS, EXO1, UBE2T, NAT1, SCGB2A2, GATA3, FOXA1, ZNF703, CD274/PD-L1) the level was decreased, and for 2 genes it increased (SFRP1, KRT5). The results of this study can be used in the development of a hormone sensitivity test and personification of adjuvant systemic treatment for breast cancer patients.

Received: 2024-11-08

Published online: 2024-12-21

DOI: 10.24075/brsmu.2024.059

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Andreevskaya SN, Smirnova TG, Chernousova LN, Larionova EE, Sevastyanova EV, Ustinova VV, Kiseleva EA, Ergeshov A

As M. tuberculosis strains develop resistance to fluoroquinolones, pools of M. tuberculosis sensitive to drugs of this group and pools of M. tuberculosis with different resistance determinants can simultaneously coexist in the host organism. The goal of this research was to run an in vitro investigation of growth characteristics of M. tuberculosis strains which have different genetic determinants of resistance to fluoroquinolones, in the setting of competition for nutrients. The research used five clinical strains of multidrug-resistant M. tuberculosis differing in gyrA structure. Strains were cultured in pairs and individually under optimal conditions (Middlebrook 7H9 medium) and under conditions of multistress (50% Middlebrook 7H9 medium, 2 mM KNO2, 0.02% H2O2). The experiment took 21 days. The number of cells of each co-cultured strain was estimated from calibration curves. These curves showed the dependence of the threshold cycle of the polymerase chain reaction — respective to the channel targeted by the mutation — on the concentration of M. tuberculosis cells. The competitive fitness value and specific growth rate were calculated from the number of cells of each strain when co-cultured. M. tuberculosis strains with mutations in gyrA were found to be inferior in growth rate to the wild-type gyrA strain, which was particularly pronounced under multistress conditions. The strain with the most common gyrA_D94G mutation had the lowest growth rate of all strains examined. It has been hypothesised that the slow growth of M. tuberculosis with this mutation may lead to tolerance to anti-tuberculosis drugs, and as a result, the strain gains an advantage under chemotherapy conditions compared to other gyrA mutant variants.

Received: 2024-11-05

Published online: 2024-12-19

DOI: 10.24075/brsmu.2024.058

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VIEWS 583

Today, implantation of an intraocular lens (IOL) into the capsular bag is the standard approach to surgical treatment of cataracts and aphakia of various origins. However, there are several reasons and conditions that disallow this operation or increase the risk of instability of the implanted lens, such reasons and conditions including weakness of the lens ligaments; degradation of Zinn's zonule, including dislocation of the IOL‒capsular bag complex post-surgery; damage to or removal of capsular bag during surgery; lack of capsular bag or its destruction during implantation in aphakia cases. To date, problems associated with fixation and centralization of IOL in non-standard cases involving weak or inexistent capsular support remain unresolved. This study aimed to develop techniques allowing to stitch IOL to the iris without compromising its functions in various situations when it is unfeasible or impossible to fix and center lens in the capsular bag. The patients (n = 12; 12 eyes), depending on the clinical situation, were divided into groups: group 1 — dislocations of the IOL–capsular bag complex (6 eyes); group 2 — complete lack of capsular support (3 eyes); group 3 — weakness of capsular support (3 eyes). A special stitching technique was developed for each of these situations. The results of the treatment were good from clinical and functional perspectives: the IOL was fixed securely and centered properly, and the iris's performance and cosmetic aspects were not compromised.

Received: 2024-10-14

Published online: 2024-12-18

DOI: 10.24075/brsmu.2024.057

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VIEWS 640

Krivoshchapova YaV

Residents of the Techa Riverside villages were chronically exposed to the wide range of doses more than 60 years ago. Telomeric regions of metaphase chromosomes in the cultured peripheral blood T-lymphocytes were the subject of the research. The study aimed to assess the impact of chronic exposure on telomere loss in exposed women of the Southern Urals using a fluorescent staining method. Chromatid and chromosome telomere loss was determined in three dose subgroups: comparison group (0–0.01 Gy), group of exposed individuals with the dose of 0.2–0.9 Gy, and group of the exposed individuals with the dose of 1–4.6 Gy. In the sample of female residents of the Southern Urals chronically exposed in the range of absorbed doses to RBM of 0–4.6 Gy, it was shown that there were no differences in telomere loss between the comparison group and the group exposed to the dose exceeding 1 Gy (p > 0.33), while the group of individuals exposed to medium doses of 0.2–0.9 Gy was statistically significantly different (p < 0.05). Statistically significant differences between all groups were reported for chromosome telomere loss (p < 0.05). According to the data obtained, telomere loss was found in 99.85% of donor cells. The loss of telomere region on one of the chromatids occurred statistically significantly more often in all the groups. Thus, in the group exposed to the dose of 0.2–0.9 Gy, the average rate of chromatid telomere loss was higher, it was statistically significantly different from that of the other groups of females of the studied age.

Received: 2024-10-16

Published online: 2024-12-13

DOI: 10.24075/brsmu.2024.055

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VIEWS 710

Luzanova EI, Karpova MI, Abramovskikh OS, Chetvernina EA, Kupriyanov SV, Zotova MA, Bershadskiy AV

Multiple sclerosis (MS) is a chronic disorder of the central nervous system affecting primarily young women. Neurogenic lower urinary tract dysfunction (NLUTD) represents one of the disease manifestations creating the risk of infectious complications and kidney disease. Today, there is insufficient data on the urinary microflora composition obtained by advanced high-tech diagnosis methods. The study aimed to perform clinical assessment of NLUTD associated with MS and its impact on the quality of life (QOL), as well as to clarify the data on the urinary microflora composition. A total of 33 women with MS aged 36 [39.5; 30.5] years were assessed using the customized questionnaires for estimation of the NLUTD prevalence and severity, as well as for QOL evaluation. Qualitative determination and quantification of urinary opportunistic microflora (OM) were performed using the real-time polymerase chain reaction. A total of 19 (57.6%) women with MS had symptoms of NLUTD: symptoms of the storage (15 individuals, 45.5%) and emptying (16 individuals, 48.5%) phases. In almost half of women with MS, the complaints included abnormalities of both bladder functioning phases (12 individuals, 36.4%); moderate abnormalities prevailed (12 individuals, 34.6%). Women with MS and NLUTD were more disabled based on the EDSS score (3.5 [5.0; 3.0] points; p < 0.001) and had longer disease duration (13 [20.0; 5.0] years; p < 0.001). The QOL index of women with NLUTD showed dissatisfaction with bladder function. The study revealed bacteriuria in patients with MS and NLUTD. The data on the urinary microflora composition are provided: OM members (bacteria of the ESKAPE group) have been found in 8 samples obtained from women with MS and NLUTD. Bacteriuria was asymptomatic.

Received: 2024-10-21

Published online: 2024-12-12

DOI: 10.24075/brsmu.2024.056

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VIEWS 667

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 766

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 713

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 687