ISSN Print 2500–1094    ISSN Online 2542–1204
BIOMEDICAL JOURNAL OF PIROGOV UNIVERSITY (MOSCOW, RUSSIA)

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Nonsteroidal anti-inflammatory drugs (NSAIDs), one of which is diclofenac sodium, are widely used in clinical practice. This study aimed to assess the effect of diclofenac sodium on bone marrow cellularity, the population of hematopoietic stem and progenitor cells (Lin−Sca-1+ c-Kit+, LSK), as well as the levels of tumor necrosis factor — (TNFa) and interleukin-1b (IL1b) in laboratory mice with experimental dermatitis. The study was a randomized controlled trial; the experimental phase lasted 96 hours. Male BALB/c mice (n = 6, age 46 weeks, 18–25 g) were randomized into five groups: intact, untreated dermatitis, dermatitis + diclofenac 1.5 mg/kg, dermatitis + diclofenac 3 mg/kg, diclofenac 3 mg/kg without dermatitis. The drug was administered intramuscularly 2 times a day for 96 hours. Dermatitis was modeled using sodium dodecyl sulfate and Dermatophagoides farinae. Bone marrow was collected after 96 hours. The total number of cells was determined by an automatic counter, the LSK cell population by flow cytometry, and cytokine concentrations by ELISA. Statistical analysis was performed using ANOVA (p < 0.05). We observed a decrease in bone marrow cellularity in dermatitis groups (0.95 ± 0.12 versus 1.20 ± 0.15 × 106 ml; p < 0.05). Diclofenac 1.5 mg/kg decreased cellularity moderately (0.80 ± 0.10 × 106 ml) and an increased LSK cells (3.8 ± 0.5% vs. 2.1 ± 0.3%; p < 0.05). Diclofenac 3 mg/kg markedly brought down cellularity (0.60 ± 0.08 × 106/ml) and LSK cells (1.4 ± 0.3%; p < 0.01), and brought up IL1b (15.5 ± 1.2 pg/ml) and TNFa (82.1 ± 4.5 pg/ml). Our findings indicate a dose-dependent effect of diclofenac sodium on hematopoiesis and inflammatory response.
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Intraoperative determination of tumor margins reduces the volume of resected tissue while ensuring complete removal of malignant tissue without increasing the risk of recurrence. The existing approaches, including intraoperative histology or tomography, are highly effective, but they extend the time of the surgery. Therefore, real-time analysis methods are a particularly interesting avenue. One such solution is mass spectrometric profiling based on ambient ionization mass spectrometry. The molecular profile of the examined tissue is compared with a reference database of healthy and pathologically altered tissues. For many human organs, samples for this database can only be obtained from autopsy material. However, due to the unavoidable time delay between the moment of death and sample collection, tissue degradation may change the picture of pathological process. This experimental quantitative study investigated the stability of polar lipid profiles in the liver and brain tissues of healthy BALB/c mice (n = 23) during the early postmortem period (0–72 hours). It has been shown that lysolipids and free fatty acids correlate with the postmortem interval (r > 0.6 overall; r = 0.75 for FA 20:4 and FA 22:6); therefore, they cannot be used as molecular markers in diagnostic models based on autopsy samples. At the same time, the profile of phospholipids in tissue cell membranes remains largely unchanged in the early postmortem period, which preserves their value as biomarkers detectable in both biopsy and autopsy specimens.
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Preeclampsia (PE) is considered as one of the most severe pregnancy complications, an important role in pathogenesis of which is played by immunogenetic factors. The study aimed to assess the contribution of HLA-DR-dependent mechanisms to the immune response regulation in PE associated with the HLA-DRB1*01:01 allele carrier state in an in vitro experimental model. A comparative experimental in vitro study was conducted. Patients with PE (n = 7), who were HLA-DRB1*01:01 carriers, and women with the normal pregnancy course (NP; n = 10), who were not HLA-DRB1*01:01, -DRB1*04:01, -DRB1*10:01 carriers, were enrolled. The CD14+ and CD4+ cells, as well as placental tissue samples, from which the placental conditioned medium (PCM) was derived, were obtained from peripheral blood samples. The CD14+ and CD4+ cells were co-cultured in both groups. PCM was added to the culture to model the effects of placental factors. In the PE group, HLA-DR was blocked with the L243 monoclonal antibody; the IgG2a isotype antibody was used in the NP group. The share of Treg-cells in the cultures was determined by flow cytometry; the IL17, IFNγ, TNFα, IL10, and IL4 cocentrations were determined by ELISA. The direct CD14+ and CD4+ co-culture revealed no intergroup differences in the share of Treg and cytokine concentrations. The PCM supplementation in the PE group resulted in the decreased share of Treg and IL10 levels amid increasing IL17, TNFα, and IFN-γ. In the NP group, on the contrary, the increase in Treg counts, IL10 and IL4 levels, along with the decrease in IFN-γ levels was reported. The HLA-DR blockage in PE was associated with the decrease in IL17 and IFN-γ levels. The findings demonstrate the potential significance of placental factors and maternal immunogenetic features in the immune response regulation in PE.
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Diabetes mellitus (DM) is associated with systemic inflammation and neuroinflammation, but the role of β-arrestin 2 in these processes remains poorly understood. The experimental study aimed to assess the effect of β-arrestin 2 deficiency on the pro-inflammatory state of mice with streptozotocin-induced diabetes. Male C57BL/6J mice and mice with the global β-arrestin 2 gene knockout (Arrb2-/-) were divided into four groups: non-diabetic wild type mice (WT, n = 8), diabetic wild-type mice (WTd, n = 8), non-diabetic knockout mice (KO, n = 8) and diabetic knockout mice (KOd, n = 9). Arrb2 knockout delayed the development of hyperglycemia: on day 39, blood glucose levels were significantly higher in WTd mice than in KOd mice (22.3 ± 8.09 vs. 14.37 ± 7.65 mmol/L, p < 0.05). Arrb2-/- mice also showed increased systemic inflammatory markers: the baseline percentage of neutrophils in KO mice was 2.6-fold higher than in WT mice (p < 0.0001). Starting from day 18 KOd mice had significantly higher neutrophil counts compared to KO and WTd (p < 0.05). β-Arrestin 2 deficiency was associated with increased mRNA expression of the genes encoding pro-inflammatory cytokines and protease-activated receptors. The most pronounced changes included a significant increased Il6 mRNA expression in the hippocampus of KO compared to WT (2.9-fold, p < 0.01), increased Tnf expression in the cerebral cortex (4.3-fold for KO/WT and 2.0-fold for KOd/WTd) and the hippocampus (3.2- and 2.3-fold, respectively) of Arrb2-/- animals compared to appropriate wild type groups (p < 0.05), as well as the increased Par1 and Par4 expression in the cerebral cortex and hippocampus of Arrb2-/- mice (2.4–7.3-fold, p < 0.01). These findings suggest that β-arrestin 2 deficiency is associated with a pro-inflammatory phenotype in the CNS and may contribute to inflammation dysregulation in DM.
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Popular articles

High efficacy of the synthetic Ac-His-Ala-Glu-Glu-NH2 (HAEE) peptide in suppression of the congophilic amyloid plaque formation was earlier shown in the animal model of Alzheimer's disease. The study conducted as part of the pre-clinical trial aimed to determine the optimal therapeutic dose of this peptide when used as an anti-amyloid agent for treatment of this disorder. The APP/PS1 transgenic mice randomized into four experimental groups and one control group (eight males and eight females per group) were used as model animals. Mice of experimental groups 1, 2, 3, and 4 twice a week throughout eight weeks received subcutaneous injections of drugs with the following HAEE dosage: 0.18 mg/kg, 0.30 mg/kg, 1.50 mg/kg, 3.00 mg/kg. Mice of the control group were administered saline. The Congo red stain was used to determine amyloid plaques in the hippocampus of all animals. Quantification of such plaques showed a significant (p < 0.001) decrease in the number of plaques in mice of experimental groups (the average plaque number per brain slice was 7.5 ± 2.1, 3.2 ± 0.9, 3.1 ± 0.6, and 3.3 ± 0.7 in mice of groups 1, 2, 3, and 4, respectively) compared to control mice (15.7 ± 4.6). Since the number of plaques in groups 2, 3, and 4 did not change significantly, the minimal HAEE dose, with which the lowest number of amyloid plaques is observed in the studied mice, is 0.3 mg/kg. This is roughly equivalent to the dose of 1.75 mg in terms of one adult human. Thus, the optimal therapeutic HAEE dose for clinical trials has been experimentally substantiated.
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The study is relevant due to persistent postural control impairment and gait disorder in patients post total knee arthroplasty (TKA), despite pain relief and restoration of the range of motion. The study aimed to assess the effects of kinesiotherapy in suspension on the patients’ stabilometry and gait phase parameters in the long term after TKA. A prospective comparative study was conducted that involved 93 patients (39 males and 54 females; average age 62.3 ± 5.1 years) enrolled 36 months after surgery. The patients were randomized into the index group (standard rehabilitation involving kinesiotherapy in suspension) and comparison group (standard program). The efficacy was assessed using stabilometry and gait phase analysis before and after the 3-week rehabilitation course. In the index group, a significant decrease in the normalized vectorogram area from 320 ± 60 to 190 ± 40 mm2 (p = 0.001) and mean center of pressure movement linear speed from 15.5 ± 2.8 to 8.7 ± 2.1 mm/s (p = 0.002) was revealed. The stance phase duration increased by 18%, and the walking phase symmetry increased from 74 ± 5 to 90 ± 4% (p < 0.01). In the comparison group, the changes were non-significant (p > 0.05). The decrease in WOMAC scores was reported for both groups, there were no intergroup differences. The data obtained confirm the efficacy of using kinesiotherapy in suspension to adjust postural and locomotor disorders after TKA.
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Dear researcher!
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”.
Richard FEYNMAN Cargo cult science
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.
Ivan PAVLOV On the Russian mind
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.