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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Frankevich VE, Novoselova AV, Starodubtseva NL, Patysheva MR, Larionova IV, Rakina MA, Bragina OD, Kzhyshkowska JG

Breast cancer is the leading cause of cancer-related death among women worldwide. Tumor-associated macrophages (TAMs) constitute the primary component of innate immunity in breast cancer tissue. During the development of new approaches for breast cancer treatment aimed at editing the epigenome of TAM, precise methods for the analysis of macrophage metabolome are required to examine the effect on new approaches on macrophage metabolism. Our study aimed to develop an HPLC-MS/MS-based analytical approach to characterize the metabolome of human innate immune cells (TAMs and their precursors, monocytes). Analysis of lipid extracts was conducted on a Dionex UltiMate 3000 liquid chromatograph connected to a Maxis Impact qTOF mass analyzer with an ESI ion source. Quantitative analysis of 38 amino acids in the cells was conducted using the Jasem Amino Acids LC-MS/MS Analysis Kit and an HPLC-MS/MS chromatographic system consisting out of an Agilent 6460 triple quadrupole mass spectrometric detector (Agilent), and an Agilent 1260 II liquid chromatograph (Agilent ) with Amino acids-HPLC Column (Jasem). The modified Folch method with double extraction was found to be the optimal approached for the sample preparation, since it enables to simultaneously isolate the lipid extract and water-soluble substances, in particular, amino acids. The method of reversed-phase chromatography yielded more useful data on the cell lipid composition than the method of hydrophilic interaction liquid chromatography (HILIC). The minimum number of cells required to determine the metabolome of immune system cells (TAM and monocytes) was identified as 2 × 106. Thus, we have developed the approach to determine the lipid and amino acid composition of modelled human TAMs and primary monocytes isolated out of breast cancer patients using minimal amount of clinical material.

Received: 2022-08-22

Published online: 2022-10-13

DOI: 10.24075/brsmu.2022.049

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VIEWS 1969

Okovantsev VS, Ponomarev GYu, Agdzhoyan AT, Agdzhoyan AT, Pylev VYu, Balanovska EV

The peculiarity of the Russian North gene pool has long become scientific fact, but has yet to receive informative explanation. Genetic drift cannot be the only contributing factor in the striking genetic differences between not only northern Russian populations and the southern ones, but among individual northern populations as well. Studying Russian North gene pools previously underrepresented in scientific literature may help understand this phenomenon. The work aimed to perform a subtotal study of the gene pool of the Arkhangelsk Oblast Pomors (Onega Coast, Summer Coast, the western fragment of the Winter Coast; n = 130) using a panel of 60 Y-chromosome SNP markers through multidimensional scaling and mapping of genetic distances. The frequencies of 14 identified haplogroups differ drastically in Pomor populations: haplogroups I1, R1a, and N3 each comprise a quarter of the total Pomor gene pool, I2-P37.2, and R1b each comprise about 8%, and the rest of the haplogroups are rare. The Onega Coast Pomors showed genetic similarity to a wide range of North-Eastern Europe Finnic-speaking populations, as well as to Russian populations with a strong pre-Slavic substratum. The Summer Coast Pomors are close to the Scandinavian gene pools, and the Winter Coast Pomors are similar only to specific Finn and Swede populations. None of the Pomor populations demonstrate genetic similarity with the Novgorod Oblast Russian populations, with which the origin of the Pomors is traditionally associated. The genetic distances between Pomor populations are so great, they are comparable to the general range of variability between the Eastern Slavic, Baltic, and Finno-Ugric peoples of the region. The reasons for such pronounced originality of Pomor populations presumably include, along with genetic drift, the gene pool of each population being underlied by a different pre-Slavic substrate, with later gene flows as an additional factor.

Received: 2022-09-11

Published online: 2022-09-30

DOI: 10.24075/brsmu.2022.046

Comments 1

VIEWS 3449

Gavisova AA, Stenyaeva NN, Gardanova ZR, Nazarenko TA, Dolgushina NV

Androgens play a key role in the physiology of the female body and the reproductive system. Androgen receptor expression in the various tissues points to the importance of androgens in the regulation of the female sexual and social functioning. The study aimed to evaluate sexual functioning in women with infertility and diminished ovarian reserve (DOR) using the Female Sexual Functioning Index questionnaire (FSFI). A cross-sectional study of 496 patients with infertility and DOR assessed the degree of sexual dysfunction in conjunction with the changes in the androgenic profiles as indicated by the androstenedione levels in the blood serum. Women with infertility and DOR were significantly more likely to report changes in sexual functioning, including a decrease in libido and in the quality and frequency of sexual relations. Furthermore, patients with normal androstenedione levels generally significantly outscored patients with decreased androstenedione levels (average questionnaire scores 21.2 ± 7.2 and 15.17 ± 3.0 respectively), indicating a lesser degree of sexual dysfunction in the former group; on the other hand, the latter group reported increased pain and decreased attraction, arousal, lubrication, orgasm, and satisfaction. Hormonal profile changes in patients with DOR, including decreased androstenedione levels, significantly impact sexual functioning, and their detection in clinical practice will allow to objectify complaints at an earlier state in order to assess the severity of sexual dysfunction and determine further personalized management tactics.

Received: 2022-08-26

Published online: 2022-09-23

DOI: 10.24075/brsmu.2022.045

Comments 0

VIEWS 1878

Birulina JG, Voronkova OV, Ivanov VV, Buyko EE, Shcherbakova MM, Chernyshov NA, Motlokhova EA

Chronic systemic inflammation is essential in many chronic non-infectious diseases, including type 2 diabetes, obesity and metabolic syndrome (MS). This study aimed at characterization of systemic inflammatory reaction as a component of diet-induced MS in rat model. Thirty-three male Wistar rats were distributed into two groups designated 'control' (n = 15) and 'experimental (MS)' (n = 18). The groups were fed, respectively, regular and high-fat/high-carbohydrate diets for 12 weeks. The intensity of systemic inflammatory process against the background of metabolic impairments was assessed by total and differential counts of white blood cells and serum levels of total protein, C-reactive protein, cytokines (IL6, IL10 and TNFα), insulin and leptin. We also assessed the production of reactive oxygen species in adipose tissue samples. The experiment revealed signs of systemic inflammation in MS as compared to control, including reactive leukocytosis, hyperproteinemia and increased serum levels of C-reactive protein (2.6-fold; р = 0.001), IL10 (3.7-fold; р = 0.029) and TNFα (4.2-fold; р = 0.035). The observed changes were accompanied by elevated metabolic activity of visceral adipose tissue, indicated by hyperleptinemia and increased free radical oxidation intensity. Pairwise positive correlations of serum levels were revealed for leptin and insulin (r = 0.701; р = 0.001) and leptin and IL10 (r = 0.523; р = 0.012). Thus, high-fat/ high-carbohydrate diet promoted metabolic impairments concomitantly with early signs of systemic inflammation characteristic of MS and obesity.

Received: 2022-08-11

Published online: 2022-08-30

DOI: 10.24075/brsmu.2022.043

Comments 0

VIEWS 1832

Poydasheva AG, Bakulin IS, Sinitsyn DO, Zabirova AH, Suponeva NA, Maslenikov NV, Tsukarzi EE, Mosolov SN, Piradov MA

Stanford neuromodulation therapy (SNT) is the state-of-the-art magnetic stimulation protocol that has been developed for management of treatment-resistant depression (TRD). The study was aimed to assess the possibility of SNT implementation in clinical practice and to define the protocol safety and efficacy in patients with TRD being an episode of the recurrent depressive disorder or bipolar disorder at the independent center. The study involved six patients (among them three women aged 21–66) with TRD associated with recurrent depression and type 1 or 2 bipolar disorder. The patients received intermittent theta-burst stimulation in accordance with the SNT protocol for five days: applying 10 triple blocks of stimulation daily at intervals of 1 hr between the blocks to the selected stimulation site showing maximum negative functional connectivity with subgenual cingulate cortex within the left dorsolateral prefrontal cortex. The Montgomery–Asberg Depression Rating Scale (MADRS) was used for clinical assessment of the effects, the follow-up period was three months. The improvement of depressive symptoms to the levels characteristic of remission immediately after the SNT completion was observed in five patients (MADRS score ≤10). After three months, two patients still had remission, the condition of three patients met the criteria of mild depressive episode, and one female patient withdrew from the study due to logistical difficulties. No serious adverse events were reported. The findings confirm safety and potentially high efficacy of SNT, including in patients with type 1 and 2 bipolar disorders.

Received: 2022-08-08

Published online: 2022-08-30

DOI: 10.24075/brsmu.2022.044

Comments 0

VIEWS 2003

Vagner VD, Sarf EA, Belskaya LV, Korshunov AS, Kuryatnikov KN, Bondar AA, Meloyan AD, Maksimenko KA, Kasiy MN

Oral fluid is a valuable substrate for assessing dental health and other aspects of physical status. New methods for early diagnosis and prognosis of dental diseases on the basis of oral fluid composition are in constant demand. Excessive fluoride concentrations, often oversighted by dental therapists, negatively affect organs and tissues of the oral cavity. This study aimed at development and approbation of a method for reliable measurement of fluoride ions in oral fluid by capillary electrophoresis to be used in patients with dental diseases. The fluoride ion concentrations were measured in health (2.16 ± 0.48 mg/L), in isolated acute pericoronitis (15.2 ± 2.7 mg/L) and in acute pericoronitis combined to multiple caries (18.9 ± 4.2 mg/L). By post-operative day 3, fluoride levels in the group with isolated acute pericoronitis dropped to normal values (2.28 ± 0.52 mg/L), whereas in the group with acute pericoronitis combined to multiple caries fluoride levels remained high (8.7 ± 1.9 mg/L; р < 0.0001). The developed protocol is efficient for studying fluoride ion concentrations in isolated and combined dental diseases.

Received: 2022-08-12

Published online: 2022-08-29

DOI: 10.24075/brsmu.2022.042

Comments 0

VIEWS 1913

Gavisova AA, Shevtsova MA, Kindysheva SV, Starodubtseva NL, Frankevich VE, Nazarenko TA, Dolgushina NV

Androgen concentrations in follicular fluid samples collected from patients undergoing in vitro fertilization (IVF) may provide useful clinical indicators. This study aimed to analyze possible associations of the androgen levels in follicular fluid and blood plasma in patients with diminished ovarian reserve (POR) in IVF programs. Cross-sectional study with a parallel group design, conducted in 2019–2021, enrolled 300 patients with infertility, aged 18–42 years, applying for assisted reproduction involving IVF/intracytoplasmic sperm injection and embryo transfer. The androgen profiles of blood plasma and follicular fluid were determined by liquid chromatography with tandem mass spectrometry (LC-MS/MS). Androgen concentrations in blood plasma and follicular fluid, particularly those of dehydroepiandrosterone (DHEA-S), androstenedione and total testosterone, significantly correlated. The results implicate androgen levels in blood plasma and follicular fluid as early markers of POR in patients with infertility.

Received: 2022-07-29

Published online: 2022-08-19

DOI: 10.24075/brsmu.2022.041

Comments 0

VIEWS 2382

Soldatov VO, Pokrovskiy MV, Puchenkova OA, Zhunusov NS, Krayushkina AM, Grechina AV, Soldatova MO, Lapin KN, Bushueva OYu

Mitochondrial dysfunction is a key driver of neurodegeneration. This study aimed to evaluate the protective potential of EPOR/CD131 (heterodimeric erythropoietin receptor) stimulation in the neurodegeneration caused by rotenone-induced mitochondrial dysfunction. The effects of erythropoietin (EPO) and an EPO mimetic peptide pHBSP were assessed using in vivo and in vitro models. Single injections of 10 µg/kg EPO or 5 µg/kg pHBSP significantly alleviated the degeneration of ganglion cells of the retina in a rotenone-induced retinopathy in rats (p < 0.05). Consistently, in vitro exposure of rotenone-treated murine primary neuroglial cultures to 500 nM EPO or pHBSP significantly rescued the survival of the cells (p < 0.005). The observed enhancement of LC3A, ATG7, Beclin-1, Parkin and BNIP3 mRNA expression by EPOR/CD131 agonists implicates the autophagy and mitophagy activation as a plausible mitoprotective mechanism.

Received: 2022-07-11

Published online: 2022-08-12

DOI: 10.24075/brsmu.2022.040

Comments 0

VIEWS 2215