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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Gautier MS, Degtyareva AV, Degtyarev DN, Ushakova LV, Filippova EA, Albegova MB, Bavykin AS, Savilova AM, Zhdanova SI

The review is focused on exploring the etiology, pathogenesis, clinical manifestations, and primarily the contemporary treatment methods for Crigler–Najjar syndrome type 1. It considers relevant data regarding the efficacy and safety of the currently existing therapeutic strategies. Effective management of this condition relies on early diagnosis and prompt initiation of treatment, which are crucial for preventing disabling neurological complications associated with bilirubin encephalopathy in patients with Crigler–Najjar syndrome type 1. Prolonged phototherapy is the key treatment method, while liver transplantation represents a radical approach. Recent advances in gene therapy and the use of mesenchymal multipotent stromal cells present novel opportunities for developing alternative, less invasive treatment modalities aimed at improving the quality of life in such patients and reducing their dependence on long-term phototherapy, along with post-transplantation risk.

Received: 2024-12-06

Published online: 2024-12-30

DOI: 10.24075/brsmu.2024.070

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VIEWS 409

Eldarov CM, Starodubtseva NL, Shevtsova YuA, Goryunov KV, Ionov OV, Silachev DN

Hypoxic ischemic encephalopathy (HIE) is a severe neonatal condition causing various neurological disorders and one of the main causes of mortality among full-term babies. Therapeutic hypothermia (TH), i.e. the newborn’s body temperature decrease that significantly reduces the risk of fatality and contributes to improvement of long-term outcomes in infants with HIE is the key treatment method for moderate-to-severe HIE. However, the timely diagnosis and disease severity determination are crucial for this method to be used, and the method has a number of limitations and requirements. Assessment of the mechanism underlying the effects of TH and the search for the major metabolic pathways and potential targets for HIE therapy are relevant. The study aimed to assess metabolome of dried blood spots by HPLC-MS, since it is the least invasive to patients test for the search for markers and metabolic pathways most active in TH that are likely to mediate its positive effects. As a result, alterations in the class of phosphoglycerolipids were found, which suggests an important role of endocannabinoid metabolism in protection of the body against HIE. Furthermore, metabolic pathways of ubiquinone, certain fatty acids, and bile acids were altered. The targeted quantitative studies of these metabolites will make it possible to optimize HIE diagnosis and treatment based on the potential targets identified.

Received: 2024-12-03

Published online: 2024-12-29

DOI: 10.24075/brsmu.2024.069

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VIEWS 394

Agdzhoyan AT, Adamov DS, Potanina AYu, Voronina MM, Gorin IO, Shtrunov-Shlykov AG, Koshel SM, Balanovska EV, Ponomarev GYu

It has been shown that Y-haplogroup N3a1-B211 is common in the Finnish-speaking peoples of the Ural-Volga region. The study aimed to investigate gene geography and phylogeography of the westernmost variant of this haplogroup: the N3a1-Y23475 branch. Comprehensive genotyping of 395 haplogroup N3a1-B211 carriers from 29 populations of Eastern Europe, Ural-Volga region, and Siberia revealed 78 carriers of its western branch reaching its maximum frequency in Mordovia’s populations (8% in Moksha, 9% in Erzya, 25% in Tengushevsky Erzya-Shoksha). Low N3a1-Y23475 frequencies in the Turkic-speaking and Slavic populations suggest the role of the Finnish-speaking substrate in their gene pools. According to the phylogenetic analysis data, the N3a1-Y23475 branch emerged 2.3–2.7 thousand years ago, but active accumulation of its current diversity took place mainly in the populations of Mordovia during the last millennium. We performed DNA genotyping in 74 haplogoup N3a1-Y23475 carriers using the 37 Y-STR panel. The Y-STR haplotype phylogenetic network created suggests two periods of population growth in ancestors of Mordovia’s indigenous population: about 1000 years ago in the populations of proto-Erzya and proto-Shoksha, about 500 years ago in the populations of Moksha and Shoksha. The fact of finding haplogroup N3a1-Y23475 in the Northern and Southern Altaians requires further research. Position of Northern Altaians-Kumandins in the phylogenetic network presumably reflects migration of Mordovia’s population to Altai in the 19th–20th centuries. The age estimates reported for Southern Altaians-Telengits can indicate the association with the haplogroup N3a1 ancestral homeland in South Siberia before resettlement of its ancient carriers in the Ural-Volga region about 1.7 thousand years ago.

Received: 2024-12-10

Published online: 2024-12-29

DOI: 10.24075/brsmu.2024.066

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VIEWS 554

Roubalsky EO, Abdrakhmanova RA, Baeva GR, Rubalskaya TS, Lazko MV, Poroisky SV, Shcheblyakov DV, Favorskaya IV, Gushchin VA

The solid-phase immunocapture with antibodies is an important tool used in immunology studies, but conventional polystyrene plates are prone to deformation during thermal cycling and cross-contamination of samples, which reduces accuracy and reproducibility, when molecular genetic testing methods are included in the study. The development of alternative solutions, such as modified polystyrene-coated polypropylene tubes, makes it possible to eliminate these limitations. The study aimed to create a new approach to SARS-CoV-2 immunocapture involving the use of modified test tubes and to assess its efficacy. Monoclonal antibodies P2C5 and R107, as well as inactivated strains GК2020/1 (Wuhan) and hCoV-19/Russia/MOW-PMVL-51/2021 (Omicron) were used for analysis. Immobilization of antibodies, sorption of viral particles, and RNA extraction were accomplished using modified test tubes, standard plates, and uncoated test tubes. The key findings showed that the polystyrene-coated modified test tubes ensured better immunocapture compared to the plates (p < 0.0001), especially when using the P2C5 antibody effective against various SARS-CoV-2 lineages, including Omicron. The R107 antibody showed limited specificity, not exceeding that of the control group with bovine serum albumin. The cross-contamination analysis revealed contamination of 14 samples out of 288 in the plates, while no contamination of samples was reported for modified test tubes. Thus, modified test tubes used for high-precision molecular testing have some advantages, since these decrease the risk of cross-contamination and improve immunocapture efficacy.

Received: 2024-11-29

Published online: 2024-12-28

DOI: 10.24075/brsmu.2024.068

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VIEWS 414

Aktanova AA, Bykova MV, Skachkov IP, Denisova VV, Pashkina EA

Today, there is a theory that proliferative potential of hematopoietic stem cells is depleted, and the balance of committed precursor cells shifts towards suppressors during the development of cancer. However, differentiation of hematopoietic stem cells can vary depending on the tumor type, localization, and microenvironment specifics. The study aimed to assess the impact of tumors of various origins on the CD34+ hematopoietic stem cells (n = 10). Assessment of the cell cycle and cell differentiation via both direct contact with the tumor and exchanging humoral factors only in transwells was conducted by flow cytometry. In the co-culture with К562, the number of hematopoietic stem cells being in their synthesis phase was 2.1%, while in the control it was 11.2% (p = 0.01); in the co-culture with SK-mel37, the number of hematopoietic stem cells being in the G2‒M cell cycle phase was reduced to 0.3% (p < 0.05). 1301 and К562 directed the hematopoietic stem cell differentiation towards granulocyte-macrophage precursor cells (p < 0.05), while 1301 and SK-mel37 directed it towards common multipotent progenitor cells. It is interesting that the number of pluripotent hematopoietic stem cells significantly increased (2-fold) compared to control after incubation with К562 in transwells (24.17% and 10.19%, respectively). Thus, properties of hematopoietic stem cells can vary depending on both tumor type and the way of interacting with these cells.

Received: 2024-12-02

Published online: 2024-12-27

DOI: 10.24075/brsmu.2024.065

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VIEWS 1130

Lukash UV, Vlasova AV, Gorev VV, Tiganova OA, Bystrova AA, Kamenev MM, Khasanova KA, Denisenko NP, Sychev DA

The ECMM EQUAL Scores tool was proposed in 2018 as a way to improve the quality of treatment of invasive mycoses and assess compliance with the diagnostic algorithm. Currently, there are no reports of its practical application in pediatrics. This study aimed to assess the prevalence of invasive mycosis in a pediatric hospital, the attributed mortality in children with invasive mycosis, and to analyze the dynamics of consumption of antifungal drugs. By design, the study was multidirectional observational, and spanned two years, with retrospective part over the period from 01.01.2022 to 31.12.2022, and prospective part — from 01.01.2023 to 31.08.2024. We used ECMM EQUAL Scores to evaluate the conformity of the fungal infection prevention measures and the empirical therapy to the established risk tier the patients were allocated to, and calculated the ATC/DDD index to measure the consumption of antifungal drugs. During the 20-month follow-up period, 78 children survived, 20 died; supervision continues. The attributed mortality rate was 25.6%. The weighted average absolute ECMM EQUAL Scores were as follows: for candidiasis — 8.4 (38%), for aspergillosis — 6.6 (24%), and for mucormycosis — 9.85 (31%). With the help of the ATC/DDD index, we assessed the dynamics of consumption of antifungal drugs in 2022 and 2023, the "before" and "after" periods. It was concluded that introduction of the ECMM tool into the invasive mycosis diagnostic routine significantly raised the number of detected cases (from 5 to 98 per year), and pushed down the attributed mortality from 60% to 25.6%. With ECMM EQUAL Scores, the NNT index was 2.9. Before introduction of the ECMM tool, in 2022, antifungal drugs were given for 30.3 DDD per 100 bed-days, after the introduction in 2023 — 54.7 DDD per 100 bed-days.

Received: 2024-11-15

Published online: 2024-12-26

DOI: 10.24075/brsmu.2024.067

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VIEWS 393

Kornienko MA, Kuzin VV, Abdraimova NK, Gorodnichev RB, Shitikov EA

Staphylococcus aureus is the causative agent of a wide range of infections, including severe systemic diseases, which is often multidrug resistant. Given the growing overall antibiotic resistance, a promising approach to treating staphylococcal infections is administration of bacteriophages, especially in combination with antibiotics. This study aimed to evaluate the synergistic effect of linezolid and bacteriophage vB_SauM-515A1 in combating a systemic infection in BALB/c mice. Using 36 animals, we established the optimal way of administration and the infecting dose of the microorganism (5 × 108 CFU/mouse intravenously), and identified the threshold concentrations of antimicrobial agents for monotherapy. The evaluation was based on the revealed contamination of internal organs (kidneys, spleen) and blood. To learn the etiotropic effect of linezolid (10 mg/kg animal weight) combined with the phage (2 × 107 PFU/mouse), we worked with a control group and a test group, 12 mice in each; 2, 8, 18, and 24 hours after infection, the former received the drug only, the latter — the investigated combination. Combined therapy had a more pronounced effect, decreasing the bacterial load in the kidneys by two to three orders of magnitude compared with monotherapy on the first day of treatment. Thus, the combined use of linezolid and bacteriophages is promising for the treatment of infections caused by S. aureus, and may increase the effectiveness of treatment and reduce the risk of side effects of high-dose antibiotics.

Received: 2024-11-06

Published online: 2024-12-25

DOI: 10.24075/brsmu.2024.062

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VIEWS 400

Abdraimova NK, Shitikov EA, Malakhova MV, Gorodnichev RB, Kornienko MA

Staphylococcus aureus causes a broad range of infections and is often characterized by multidrug resistance (MDR). Treatment of staphylococcal infections is further complicated by the ability of bacterium to form biofilms protecting it against antimicrobial agents and the immune system. The use of bacteriophages is one of the promising strategies for combating the bacteria showing MDR and biofilm formation activity. The study aimed to assess the effects of the lytic phages vB_SauM515A1 (genus Kayvirus, family Herelleviridae) and vB_SauP-436A (genus Rosenblumvirus, family Rountreeviridae) on biofilms of the S. aureus clinical strains. The study involved 20 strains of eight sequence types, among which 45% (9/20) belonged to MRSA, and 35% (7/20) showed MDR. All the strains demonstrated the ability to form biofilms, and 65% (13/20) were strong biofilm producers. Genes of the icaADBC operon responsible for synthesis of polysaccharide intercellular adhesin were found in genomes of all samples. The exposure of planktonic bacterial cells to bacteriophages showed that 70% (14/20) of strains were sensitive to phage vB_SauM-515A1 and 50% (10/20) were sensitive to phage vB_SauP-436A. Furthermore, the 24-h treatment of biofilms of sensitive strains with phage vB_SauM-515A1 led to the biofilm biomass increase in 64.3% (9/14) of cases, while phage vB_SauP-436A, on the contrary, significantly reduced the quantity of biofilm in 40% (4/10) of strains. The results obtained highlight the ambiguity of interaction between bacteriophages and S. aureus biofilms and suggest the need for further research aimed at optimizing phage therapy targeting the biofilm-forming strains.

Received: 2024-11-14

Published online: 2024-12-24

DOI: 10.24075/brsmu.2024.061

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VIEWS 397