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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Zagoskin AA, Avakova RA, Rezvykh LF, Zakharova MV, Mubarakshina EK, Ivanov RA, Nagornykh MO

The widespread use of antibiotics in medicine and agriculture has significantly accelerated the emergence rate of bacterial infections showing multiple antibiotic resistance. Since resistance to conventional antibiotics is developed rather quickly, designing alternative antimicrobial drugs with other mechanisms underlying their effects on bacteria is a promising. The enzymes possessing bactericidal activity may be one option for such antibacterial agents. The study aimed to produce the combination recombinant protein-based products active against bacteria and their biofilms. Soluble forms of five recombinant proteins were produced using the genetic engineering approaches. Two of these have a bacteriolytic effect (endolysins LysK and PM9 from the Staphylococcus aureus bacteriophages), the other are capable of disrupting extracellular DNA matrix in biofilms (two nonspecific nucleases NucA, as well as the DNA-specific deoxyribonuclease I). It has been shown that natural endolysin PM9 with the truncated catalytic domain shows 4 times lower bacteriolytic efficacy compared to the full-size LysK version. Comparative analysis revealed 1.5–2 timed higher efficacy of nonspecific nucleases in terms of bacterial biofilm disruption compared to the DNA-specific deoxyribonuclease I. It has been shown that simultaneous use of endolysins and nucleases has a synergistic antibacterial effect and disrupts biofilms of the pathogenic bacterium Staphylococcus aureus. The findings show the prospects of developing the recombinant protein-based antibacterial drugs.

Received: 2024-11-25

Published online: 2024-12-23

DOI: 10.24075/brsmu.2024.064

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VIEWS 1267

Osikov MV, Efros LA, Zhuravleva LYu, Fedosov AA

Diabetes mellitus (DM) is one of the major factors contributing to the development and aggravation of chronic kidney disease (CKD). The accurate and convenient markers for early detection, estimation of progression, and adequate control of CKD therapy in individuals with DM are limited to glomerular filtration rate (GFR) and albuminuria. Given the role of chronic inflammation in the pathogenesis of DM and CKD, the study aimed to assess indicators of inflammation and the correlation of those with GFR in patients with type 1 DM (T1D) and early stage CKD. The study involved healthy individuals (n = 14), patients with T1D showing no signs of CKD (n = 30), as well as patients with T1D and stage 1 CKD (n = 60), stage 2 CKD (n = 38), and stage 3 CKD (n = 31). GFR was calculated using the formula СКD-ЕРI (eGFR); serum levels of IL1β and TNFα, C-reactive protein (CRP), and ceruloplasmin (CP) were determined by enzyme immunoassay; the neutrophil-to-lymphocyte index and the leukocyte intoxication index (LII) were calculated. It has been found that serum concentrations of IL1β, TNFα, CRP, and CP are elevated; LII and the neutrophil-to-lymphocyte index are increased. The inflammation and acute phase response severity progresses and reaches its maximum in stage 3b CKD, when the serum concentration of IL1β is increased 2.4-fold (р = 0.042), TNFα concentration by 34% (р = 0.005), CRP concentration 33-fold (р < 0.000), CP concentration by 73% (р = 0.008), LII 8.4-fold (р < 0.000), neutrophil-to-lymphocyte index 5-fold (р = 0.013). The integral kidney function indicator, eGFR, decreases with increasing serum levels of the above indicators. Thus, IL1β, TNFα, CRP, CP, LII, and the neutrophil-to-lymphocyte index can be considered as affordable and informative indicators for estimation of inflammation, the levels of which increase with progression of early stage CKD in patients with T1D.

Received: 2024-10-24

Published online: 2024-12-23

DOI: 10.24075/brsmu.2024.060

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VIEWS 1410

Sinitsyn MV, Voskresenskaya AA, Pozdeyeva NA

Calculation of toric intraocular lenses (tIOLs) in patients after penetrating keratoplasty (PK) is challenging. The study aimed to perform comparative retrospective analysis of various methods for calculation of tIOL during phacoemulsification in patients after PK. We analyzed case reports of 36 eyes (36 patients) after PK, which underwent phacoemulsification with tIOL implantation. All tIOLs were recalculated using four different methods. In group 1, tIOL calculation was performed using keratometry data of the anterior surface of the corneal graft measured using a corneal topographer, and the posterior surface of the corneal graft measured using optical coherence tomography of the cornea or the Scheimpflug keratotopographer. In group 2, keratometry of both corneal graft surfaces was measured using the Scheimpflug keratotopographer, in group 3 — using OCT of the cornea, in group 4 — using the keratotopographer. The online Barrett True — K Toric Calculator was used to calculate tIOLs in groups 1–3, and The Kane Formula was used in group 4. There were significant differences in the values of the spherical and cylindrical components of refraction between the studied groups (p < 0.05). The highest predictability of tIOL calculation was reported for group 1: the ensured postoperative refraction for the spherical component was within ±0.5 D in 58% of eyes, within ±1.0 D in 67% of eyes; postoperative refraction for the cylindrical component was within –0.5 D in 56% of eyes, within ‒1.0 D in 89% of eyes. Thus, the highest predictability of tIOL calculation is observed in patients of group 1.

Received: 2024-11-11

Published online: 2024-12-22

DOI: 10.24075/brsmu.2024.063

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VIEWS 1584

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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VIEWS 1281

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 1223

Takhchidi KhP

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 1334

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 1342

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 1460