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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Issue 2, 2025

Topic Salivary gland carcinoma

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Issue 3, 2024

Topic Systemic lupus erythematosus

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Issue 4, 2024

Topic Photopolymerizable materials for biocompatible implantable matrices

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Issue 5, 2024

Topic Gut dysbiosis

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Issue 6, 2024

Topic Crigler-Najjar syndrome: approaches to therapy

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Issue 1, 2025

Topic microRNA

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New articles

Kiseleva VV, Vishnyakova PA, Kosyreva AM, Kananykhina EYu, Emelianov II, Elchaninov AV, Fatkhudinov TH

High fatality rate and the lack of pathophysiological therapy are typical for acute respiratory distress syndrome (ARDS). Intratracheal lipopolysaccharide (LPS) administration is used to model ARDS in animals. The method has the limitation of requiring the use of equipment to perform intubation and control the animal’s state. The study aimed to assess the possibility of using intranasal LPS administration instead of intratracheal and determine the LPS optimal dose. A total of 150 mL of the E. coli O111:B4 LPS (7.5 mg/kg or 15 mg/kg) or 0.9% NaCl was administered to 21 Sprague-Dawley rats. After 48 h blood was collected from the tail vein to determine the white blood cell count and TNFa concentration. The lungs were retrieved to assess dry weight (wet/dry ratio) and to determine the expression of the genes encoding pro- and anti-inflammatory cytokines using real-time PCR. The relative counts of CD68-, CD86-, and MHC II-positive cells in the lung tissue were also evaluated using flow cytometry. The w/d ratio was higher when the dose of 15 mg/kg of body weight was used (p = 0.0228, ordinary one-way Anova). Вlood lymphocyte counts were decreased (p = 0.0019, ordinary one-way Anova), and neutrophil counts were increased (p = 0.0021, ordinary one-way Anova) upon administration of both doses. The counts of CD86- (p = 0.0014, ordinary one-way Anova) and MHC II-positive cells (p = 0.0050, ordinary one-way Anova) increased after LPS administration. The IL10 gene expression was significantly increased upon administration of the dose of 15 mg/kg (p = 0.0024, ordinary oneway Anova), while the IL4 expression (p = 0.0194, ordinary one-way Anova) was decreased upon administration of the dose of 7.5 mg/kg. Thus, intranasal LPS administration can be used to model ARDS in the Sprague-Dawley rats. Administration of the high dose leads to the rapid development of inflammation in the lung.

Received: 2025-04-21

Published online: 2025-05-20

DOI: 10.24075/brsmu.2025.027

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VIEWS 58

Popov NS, Terekhov VM, Baranov MS, Balabanyan VYu, Kaurova DE, Myasnyanko IN, Terekhova EA

Assessment of pharmacologically active molecule biotransformation represents the most important phase of drug development, the results of which make it possible to identify active and toxic metabolites and provide a fundamental basis for the targeted design of new candidate drug molecules. The liver is the main organ involved in biotransformation of drugs. The currently widely used in vitro metabolism assessment methods do not allow one to identify products of extrahepatic drug molecule biotransformation. The study aimed to develop an in vivo approach to determination of the role of the liver in biotransformation of candidate drug molecules. The approach proposed is based on the vascular liver isolation performed surgically in laboratory rats. The organ involvement in biotransformation of pharmacologically active molecules is exemplified by the leader compound of the sydnone imine group possessing vasodilatory activity. It has been shown that elimination of the liver from systemic blood flow does not result in generation of the test compound metabolites identified by chromatography–mass spectrometry. The findings can provide the basis for prediction of drug pharmacokinetics, efficacy, and safety.

Received: 2025-04-16

Published online: 2025-05-15

DOI: 10.24075/brsmu.2025.026

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VIEWS 121

Rebrikov DV, Degtyareva AV, Yanushevich YuG, Gautier MS, Gorodnicheva TV, Bavykin AS, Ushakova LV, Filippova EA, Degtyarev DN, Sukhikh GT

Crigler–Najjar syndrome type I, an orphan UTG1A1 enzyme deficiency, manifests at birth with severe unconjugated hyperbilirubinemia. Here we describe sustained clinical response in a pediatric patient with Crigler–Najjar syndrome type I treated with two consecutive doses of AAV8 delivering the UTG1A1 coding sequence. Infusion I (6 × 1012 vg/kg) afforded sustained decrease in serum bilirubin, allowing substantial relaxation of the phototherapy from 12 h to 4 h daily. Infusion II at a double dose was made in 6 months; the decision was intended at complete elimination of phototherapy. However, the elimination led to a sharp increase in bilirubin levels necessitating resumption of phototherapy. The patient is currently stable on 4 h daily phototherapy for 80 weeks since the resumption and 107 weeks since the AAV8 therapy initiation. No toxic side effects were encountered. A slow incremental dynamics in serum bilirubin opens the issue of clinical advisability for subsequent infusions of the drug.

Received: 2025-04-25

Published online: 2025-04-30

DOI: 10.24075/brsmu.2025.025

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VIEWS 224

Minasov BSh, Yakupov RR, Akbashev VN, Shchekin VS, Vlasova AO, Minasov TB, Karimov KK, Akhmeldinova AA

Morphological subchondral bone tissue alterations associated with knee osteoarthritis represent a key pathogenesis link and can precede articular cartilage destruction. The study aimed to identify typical morphological and morphometric signs of osteosclerosis and osteoporosis in the subchondral zone of the femur and tibia. Analysis of 40 bone tissue fragments collected when performing knee replacement surgery in 20 patients (12 females and 8 males) aged 58–75 years with stage III–IV osteoarthritis was performed. Histological and morphometric assessment involving the use of light microscopy and microfracture index (MFI) calculation revealed significant differences in trabecular thickness, intertrabecular distance, and the degree of microdamage between the sites of sclerosis and osteoporosis. High MFI values in the zones of osteoporosis can reflect reduced subchondral bone strength. The findings confirm the diagnostic value of the subchondral zone morphometry and the prospects of using MFI as a quantitative risk criterion when planning orthopedic treatment.

Received: 2025-04-06

Published online: 2025-04-30

DOI: 10.24075/brsmu.2025.024

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VIEWS 194

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Popular articles

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 1240

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 757

Special Project Author's Work

Secrets of a quality research study and a good manuscript

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”.

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.

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.