Bacillus Calmette–Guerin (BCG), developed in the early 20th century to protect against tuberculosis, is one of the most widely used vaccines in the world. In addition to protecting against tuberculosis, this vaccine has also been shown to reduce the risk of various other infections. During the COVID-19 pandemic, it was found that BCG-vaccinated healthcare workers had lower detection rates of the SARS-CoV-2 virus compared to unvaccinated individuals. This appears to be due to the generation of trained immunity (TRIM) and non-specific effects (NSE), which are likely a result of the epigenetic and metabolic reprogramming of innate immune cells, known as trained immunity. NSE further holds promise for the development of future therapeutics that can protect against unpredictable pandemics. Additionally, TRIM inducers provide new perspectives on improving the efficacy of standard vaccines by incorporating them into vaccine formulations to enhance both specific and nonspecific immune responses.

BACKGROUND:Anxiety and depressive disorders are the most common mental disorders. Detecting a disorder at an early stage can prevent the development of severe disorders and preserve the patient's functioning ability. Simple and reliable screening tools based on self-completion of questionnaires can be used for this purpose. However, it is not always the case that the scores of the self-questionnaire align with those of the clinician. AIM:To estimate the prevalence of anxiety-depressive disorders using the GAD-7 and HADS self-report questionnaires compared to psychiatrist assessment. METHODS:The study included individuals aged 18 to 65 years, living in Moscow, Russia, without psychiatric disorders, who participated in an online study using the HADS (Hospital Anxiety and Depression Scale, HADS-A and HADS-D) and GAD-7 (Generalized Anxiety Disorder 7-item scale). Anxiety disorder was diagnosed when the total score was ≥10 on the GAD-7 and/or ≥10 on the HADS-A scale, and depression was defined when the total score was ≥9 on the HADS-D scale. Then, 82 randomly selected participants attended an anonymous consultation with a psychiatrist. RESULTS:The study included 1,097 individuals (72% female), median age 29 (23; 37) years. As a result of testing, anxiety disorder was found in 168 (15%); depressive disorder - in 152 (14%) respondents. At medical verification, anxiety was diagnosed in 18 (22%); depression - in 19 (23%) people. The sensitivity of the HADS-D subscale for physician-diagnosed cases of depression was 61%, and specificity was 73%. The sensitivity of the HADS-A and GTR-7 subscale in identifying cases of anxiety disorder was 58%, specificity 59%. Sixteen percent were first diagnosed with a personality disorder or schizotypal disorder. CONCLUSION:The level of anxiety and depression in our sample of the population of Moscow, Russia, was higher than the global level. Self-assessment based on the questionnaire seems to not fully reflect the real state of a patient, as evidenced by the differences with the psychiatrist's assessment.

OBJECTIVES:Current data suggests that Bacille Calmette-Guerin (BCG) vaccination contributes to nonspecific enhancement of resistance to various infections. Thus, BCG vaccination induces both specific immunity against mycobacteria and non-specific "trained immunity" against various pathogens. To understand the fundamental mechanisms of "trained" immunity, studies of transcriptome changes occurring during BCG vaccination in innate immunity cells, as well as in their precursors, are necessary. Furthermore, this data possesses important significance for practical applications associated with the development of recombinant BCG strains aimed to enhance innate immunity against diverse infectious agents. DATA DESCRIPTION:We performed RNA sequencing of innate immune cells derived from murine bone marrow and spleen three days after subcutaneous BCG vaccination. Using fluorescence-activated cell sorting we obtained three cell populations for each mouse from both control and BCG vaccinated groups: bone marrow monocytes and neutrophils and splenic NK-cells. Then double-indexed cDNA libraries for Illumina sequencing from the collected samples were prepared, the resulting cDNA library mix was subjected to NovaSeq 6000 sequencing. This paper describes the collection of 24 RNA sequencing samples comprising 4 sets of immune cell populations obtained from subcutaneously BCG-vaccinated and control mice.

As one of the first live vaccines, Bacillus Calmette-Guérin (BCG) is experiencing a experiencing its second rise. The recent COVID-19 pandemic has spurred interest in BCG due to its ability to provide protection not only against mycobacteria, but also against unrelated pathogens. This ability is based on BCG's ability to non-specifically activate cells of the innate immune system, bringing them into a prepared state where they can be activated more quickly. The process known as trained immunity. This ability of BCG to elicit an immune response gives it the opportunity to become not only a basis for universal or pan-pandemic vaccines, but also a cancer vaccine. We have reviewed the main mechanisms underlying the immunoactivating effect of BCG and proposed ways to enhance this effect. Since the pandemic has greatly altered the research landscape in vaccinology and, to some extent, cancer immunotherapy, we have focused more on studies published during and after the pandemic, minimizing information from the pre-pandemic period where possible. We discuss the recent trend in the use of BCG-based therapies, with particular emphasis on ongoing clinical trials. Based on the data presented, we suggested the most optimal options for further research to develop effective BCG-based vaccines.

Background Anxiety and depression significantly contribute to the overall burden of mental disorders, with depression being one of the leading causes of disability. Despite this, no biochemical test has been implemented for the diagnosis of these mental disorders, while recent studies have highlighted lipids as potential biomarkers. Methods Using a streamlined high-throughput lipidome analysis method, direct-infusion mass spectrometry, we evaluated blood plasma lipid levels in 604 individuals from a general urban population and analysed their association with self-reported anxiety and depression symptoms. We also assessed lipidome profiles in 32 patients with clinical depression, matched to 21 healthy controls. Findings We found a significant correlation between lipid abundances and the severity of self-reported depression symptoms. Moreover, lipid alterations detected in high scoring volunteers mirrored the lipidome profiles identified in patients with clinical depression included in our study. Based on these fi ndings, we developed lipid-based predictive model distinguishing individuals reporting severe depressive symptoms from non-depressed subjects with high accuracy. Interpretation This study demonstrates the possibility of generalizing lipid alterations from a clinical cohort to the general population and underscores the potential of lipid-based biomarkers in assessing depressive states. Funding This study was sponsored by the Moscow Center for Innovative Technologies in Healthcare, N2 2707-2, N2 2102-11. Copyright (c) 2024 The Author(s). Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

52 years have passed since President Nixon launched the "War on Cancer". The goals outlined by the President were not achieved because cancer treatment applied such as chemotherapy, radiotherapy, and targeted therapy have not fully met expectations. We suggest a new chemotherapeutic strategy: disrupting the communication between cancer cells and their microenvironment by chemical means. Immunological synapses that form between cancer cells and immune or other stromal cells provide an attractive target for this approach. Synapses form ligand-receptor clusters within interface of the interacting cells. Despite their differences, synapses share common properties: intercellular protein clusters; the proximity of these proteins; and their cooperative interaction making a synapse an unified functional unit. Synapses provide the limited space for the focused intercellular exchange of signaling molecules and particles. Therefore, destruction of synapses is expected to cause collapse of various tumor types. Additionally, the clustered arrangement of synapse components offers opportunities to increase treatment safety by reducing the concentration of cell impermeable agents used, to enhance its specificity applying cross-linking reagents, thus restricting modifications of surface-exposed molecules. By attaching a cleavable cell permeable toxic agent to a crosslinker should further enhance a killing potential in treating cancer. The proposed approach promises to be simple, universal, and less expensive than existing cancer therapy methods.

BackgroundImmune checkpoint blockade (ICB) is rapidly becoming a standard of care in the treatment of many cancer types. However, the subset of patients who respond to this type of therapy is limited. Another way to promote antitumoral immunity is the use of immunostimulatory molecules, such as cytokines or T cell co-stimulators. The systemic administration of immunotherapeutics leads to significant immune-related adverse events (irAEs), therefore, the localized antitumoral action is needed. One way to achieve this is intratumoral non-viral gene-immune therapy, which allows for prolonged and localized gene expression, and multiple drug administration. In this study, we combined the previously described non-viral gene delivery system, PEG-PEI-TAT copolymer, PPT, with murine OX40L-encoding plasmid DNA.MethodsThe resulting OX40L/PPT nanoparticles were characterized via gel mobility assay, dynamic light scattering analysis and in vitro transfection efficiency evaluation. The antitumoral efficacy of intratumorally (i.t.) administered nanoparticles was estimated using subcutaneously (s.c.) implanted CT26 (colon cancer), B16F0 (melanoma) and 4T1 (breast cancer) tumor models. The dynamics of stromal immune cell populations was analyzed using flow cytometry. Weight loss and cachexia were used as irAE indicators. The effect of combination of i.t. OX40L/PPT with intraperitoneal PD-1 ICB was estimated in s.c. CT26 tumor model.ResultsThe obtained OX40L/PPT nanoparticles had properties applicable for cell transfection and provided OX40L protein expression in vitro in all three investigated cancer models. We observed that OX40L/PPT treatment successfully inhibited tumor growth in B16F0 and CT26 tumor models and showed a tendency to inhibit 4T1 tumor growth. In B16F0 tumor model, OX40L/PPT treatment led to the increase in antitumoral effector NK and T killer cells and to the decrease in pro-tumoral myeloid cells populations within tumor stroma. No irAE signs were observed in all 3 tumor models, which indicates good treatment tolerability in mice. Combining OX40L/PPT with PD-1 ICB significantly improved treatment efficacy in the CT26 subcutaneous colon cancer model, providing protective immunity against CT26 colon cancer cells.ConclusionOverall, the anti-tumor efficacy observed with OX40L non-viral gene therapy, whether administered alone or in combination with ICB, highlights its potential to revolutionize cancer gene therapy, thus paving the way for unprecedented advancements in the cancer therapy field.

Lipids are a crucial component of the human brain, serving important structural and functional roles. They are involved in cell function, myelination of neuronal projections, neurotransmission, neural plasticity, energy metabolism, and neuroinflammation. Despite their significance, the role of lipids in the development of mental disorders has not been well understood. This review focused on the potential use of lipids as blood biomarkers for common mental illnesses, such as major depressive disorder, anxiety disorders, bipolar disorder, and schizophrenia. This review also discussed the impact of commonly used psychiatric medications, such as neuroleptics and antidepressants, on lipid metabolism. The obtained data suggested that lipid biomarkers could be useful for diagnosing psychiatric diseases, but further research is needed to better understand the associations between blood lipids and mental disorders and to identify specific biomarker combinations for each disease.

The problem of biological safety is extremely relevant today for all countries of the world because of the real and potential threats caused by biological agents that are dangerous to public health and the environment. Modern microorganisms are becoming increasingly aggressive towards humans, as clearly demonstrated by the COVID-19 pandemic, which has affected all aspects of people's lives and exposed the vulnerability of the healthcare system. According to the Decree of the President of the Russian Federation «On the Fundamentals of the State policy of the Russian Federation in the field of chemical and biological safety for the period up to 2025 and beyond» and the Federal Law «On Biological Safety in the Russian Federation», the main objectives of state policy are to reduce the risks of negative effects of biological factors on the population and the environment. Antimicrobial resistance, the emergence of new infections and the overcoming of interspecific barriers by microorganisms are of particular concern. Infectious disease agents with epidemic potential, such as Ebola, Zika, Marburg, Lassa, MERS-CoV and SARS-CoV viruses, continue to pose a high threat. To counteract new biological threats, Russia has created a scientific concept of future biosafety, focusing on the development of genomic epidemiological surveillance, digital transformation and mobile technologies. Effective management of epidemic processes requires constant monitoring of genetic changes in infectious agents and prompt response to new threats, which allows the VGARus platform created in Russia to monitor virus mutations. Thus, genomic epidemiological surveillance is becoming a key element of ensuring biological safety and scientific and technological development in Russia.

Fifty-two years have passed since President Nixon launched the “War on Cancer”. Despite unparalleled efforts and funds allocated worldwide, the outlined goals were not achieved because cancer treatment approaches such as chemotherapy, radiation therapy, hormonal and targeted therapies have not fully met the expectations. Based on the recent literature, a new direction in cancer therapy can be proposed which targets connections between cancer cells and their microenvironment by chemical means. Cancer–stromal synapses such as immunological synapses between cancer and immune cells provide an attractive target for this approach. Such synapses form ligand–receptor clusters on the interface of the interacting cells. They share a common property of involving intercellular clusters of spatially proximate and cooperatively acting proteins. Synapses provide the space for the focused intercellular signaling molecules exchange. Thus, the disassembly of cancer–stromal synapses may potentially cause the collapse of various tumors. Additionally, the clustered arrangement of synapse components offers opportunities to enhance treatment safety and precision by using targeted crosslinking chemical agents which may inactivate cancer synapses even in reduced concentrations. Furthermore, attaching a cleavable cell-permeable toxic agent(s) to a crosslinker may further enhance the anti-cancer effect of such therapeutics. The highlighted approach promises to be universal, relatively simple and cost-efficient. We also hope that, unlike chemotherapeutic and immune drugs that interact with a single target, by using supramolecular large clusters that include many different components as a target, the emergence of a resistance characteristic of chemo- and immunotherapy is extremely unlikely.

It is established that BCG vaccination results in the development of both a specific immune response to mycobacterial infections and a nonspecific (heterologous) immune response, designated as trained immunity (TRIM), to other pathogens. We hypothesized that local BCG immunization may induce an early immune response in bone marrow and spleen innate immunity cells. The early transcriptomic response of various populations of innate immune cells, including monocytes, neutrophils, and natural killer (NK) cells, to BCG vaccination was examined. To this end, C57Bl/6J mice were subcutaneously immunized with 106 CFU of BCG. Three days following BCG administration, the three cell populations were collected from the control and BCG-vaccinated groups using FACS. All cell populations obtained were utilized for the preparation and sequencing of RNA-seq libraries. The analysis of FACS data revealed an increase in the proportion of splenic NK cells and monocytes 3 days post-vaccination. Transcriptomic analysis revealed the deregulation of genes associated with the regulation of immune response (according to Gene Ontology terms) in NK cells, monocytes, and unsorted bone marrow cells. Two NK cell-specific immune ligands (Tnfsf14 and S100a8) and two bone marrow-specific immune receptors (C5ar1 and Csf2rb) were identified among differentially expressed genes. No alterations were identified in neutrophils in either their percentage or at the transcriptomic level. Thus, in this study, we demonstrated that BCG vaccination provides an early increase in the proportion of murine bone marrow and spleen immune cell populations, as well as transcriptomic alterations in monocytes, NK cells, and non-sorted bone marrow cells. This early innate immune response may be beneficial for enhancing TRIM.

Normal tissues are essential for studying disease-specific differential gene expression. However, healthy human controls are typically available only in postmortal/autopsy settings. In cancer research, fragments of pathologically normal tissue adjacent to tumor site are frequently used as the controls. However, it is largely underexplored how cancers can systematically influence gene expression of the neighboring tissues. Here we performed a comprehensive pan-cancer comparison of molecular profiles of solid tumor-adjacent and autopsy-derived "healthy" normal tissues. We found a number of systemic molecular differences related to activation of the immune cells, intracellular transport and autophagy, cellular respiration, telomerase activation, p38 signaling, cytoskeleton remodeling, and reorganization of the extracellular matrix. The tumor-adjacent tissues were deficient in apoptotic signaling and negative regulation of cell growth including G2/M cell cycle transition checkpoint. We also detected an extensive rearrangement of the chemical perception network. Molecular targets of 32 and 37 cancer drugs were over- or underexpressed, respectively, in the tumor-adjacent norms. These processes may be driven by molecular events that are correlated between the paired cancer and adjacent normal tissues, that mostly relate to inflammation and regulation of intracellular molecular pathways such as the p38, MAPK, Notch, and IGF1 signaling. However, using a model of macaque postmortal tissues we showed that for the 30 min - 24-hour time frame at 4ºC, an RNA degradation pattern in lung biosamples resulted in an artifact "differential" expression profile for 1140 genes, although no differences could be detected in liver. Thus, such concerns should be addressed in practice.

The inevitability of pandemics outbreaks creates an urgent requirement for emergency action to develop effective technologies to reduce harm to the human population in the period between the onset of an epidemic and the development and production of a vaccine. In this review we discuss the possibility of engineering universal vaccines. Such vaccines exploiting the nonspecific antipathogenic potential of innate immunity, could allow the population to be vaccinated when an unidentified pathogen appears and should reduce disease severity until pathogen-specific vaccines become available. There is strong evidence that bacterial or viral vaccines such as tuberculosis vaccine (BCG), measles and polio provide heterologous protective effects against unrelated pathogens. This is due to the innate immune system’s ability to maintain the memory of past infections and use it to develop immune defenses against new ones. This effect has been called “trained” immunity. The use of trained immunity may also represent an important new approach to improving existing vaccines or to developing new vaccines that combine the induction of classical adaptive immune memory and innate immune memory. Such approaches can be boosted by genetic technologies and could prove extremely useful against future pandemics.

Treatment of metastatic disease remains among the most challenging tasks in oncology. One of the early events that predicts a poor prognosis and precedes the development of metastasis is the occurrence of clusters of cancer cells in the blood flow. Moreover, the presence of heterogeneous clusters of cancerous and noncancerous cells in the circulation is even more dangerous. Review of pathological mechanisms and biological molecules directly involved in the formation and pathogenesis of the heterotypic circulating tumor cell (CTC) clusters revealed their common properties, which include increased adhesiveness, combined epithelial-mesenchymal phenotype, CTC-white blood cell interaction, and polyploidy. Several molecules involved in the heterotypic CTC interactions and their metastatic properties, including IL6R, CXCR4 and EPCAM, are targets of approved or experimental anticancer drugs. Accordingly, analysis of patient survival data from the published literature and public datasets revealed that the expression of several molecules affecting the formation of CTC clusters predicts patient survival in multiple cancer types. Thus, targeting of molecules involved in CTC heterotypic interactions might be a valuable strategy for the treatment of metastatic cancers.

The identification of tissue-specific promoters for gene therapeutic constructs is one of the aims of complex tumor therapy. The genes encoding the fibroblast activation protein (FAP) and the connective tissue growth factor (CTGF) can function in tumor-associated stromal cells but are practically inactive in normal adult cells. Accordingly, the promoters of these genes can be used to develop vectors targeted to the tumor microenvironment. However, the efficiency of these promoters within genetic constructs remains underexplored, particularly, at the organism level. Here, we used the model of Danio rerio embryos to study the efficiency of transient expression of marker genes under the control of promoters of the FAP, CTGF, and immediate early genes of Human cytomegalovirus (CMV). Within 96 h after the injection of vectors, the CTGF and CMV promoters provided similar equal efficiency of reporter protein accumulation. In the case of the FAP promoter, a high level of reporter protein accumulation was observed only in certain zebrafish individuals that were considered developmentally abnormal. Disturbed embryogenesis was the factor of changes in the exogenous FAP promoter function. The data obtained make a significant contribution to understanding the function of the human CTGF and FAP promoters within vectors to assess their potential in gene therapy.

Fibroblast activation protein (FAP) is an integral membrane serine protease that acts as both dipeptidyl peptidase and collagenase. In recent years, FAP has attracted considerable attention due to its specific upregulation in multiple types of tumor cell populations, including cancer cells in various cancer types, making FAP a potential target for therapy. However, relatively few papers pay attention to the mechanisms driving the cell-specific expression of the FAP gene. We found no correlation between the activities of the two FAP promoter variants (short and long) and the endogenous FAP mRNA expression level in several cell lines with different FAP expression levels. This suggested that other mechanisms may be responsible for specific transcriptional regulation of the FAP gene. We analyzed the distribution of known epigenetic and structural chromatin marks in FAP-positive and FAP-negative cell lines and identified two potential enhancer-like elements (E1 and E2) in the FAP gene locus. We confirmed the specific enrichment of H3K27ac in the putative enhancer regions in FAP-expressing cells. Both the elements exhibited enhancer activity independently of each other in the functional test by increasing the activity of the FAP promoter variants to a greater extent in FAP-expressing cell lines than in FAP-negative cell lines. The transcription factors AP-1, CEBPB, and STAT3 may be involved in FAP activation in the tumors. We hypothesized the existence of a positive feedback loop between FAP and STAT3, which may have implications for developing new approaches in cancer therapy.

BACKGROUND:The COVID-19 pandemic had a significant impact on the mental health of medical personnel worldwide, leading to increased levels of anxiety and depression. This study aimed to compare anxiety and depression levels among healthcare workers during the initial wave of the pandemic in April-May 2020 and the post-pandemic period in January-May 2023 in Russia.METHODS:Data from two similar surveys conducted during the respective periods were combined, and a case-control matching approach was used to ensure compatibility between the two samples. The Hospital Anxiety and Depression Scale (HADS) was used to assess anxiety and depression levels.RESULTS:The mean total score for Anxiety subscale in 2020 was 4.126 (SD = 3.042), and in 2023 it increased to 6.632 (SD = 4.132) (F=20.751, df (1, 172), p<0.001, η2p=0.108). Similarly, the mean total score for Depression subscale increased from 3.253 (SD = 2.616) in 2020 to 4.115 (SD = 2.939) in 2023 (F=4.177, df (1, 172), p=0.043, η2p=0.024). The proportion of healthcare workers with higher-than-normal levels of anxiety increased from 16.09% in 2020 to 39.08% in 2023, whereas the effect size for depression remained negligible. The increase in anxiety severity was contrary to previous longitudinal studies showing a decrease in anxiety and depression levels after an initial increase during the pandemic.CONCLUSION:The increase in anxiety and depression levels in healthcare workers in 2023 may be attributed to other factors like "special military operation" in Ukraine, sanctions, and announcement of partial mobilization in September 2022. These factors could be perceived as more serious adverse factors, leading to increased anxiety levels.

The unprecedented non-reproducibility of the results published in the field of cancer research has recently come under the spotlight. In this short review, we try to highlight some general principles in the organization and evolution of cancerous tumors, which objectively lead to their enormous variability and, consequently, the irreproducibility of the results of their investigation. This heterogeneity is also extremely unfavorable for the effective use of molecularly targeted medicine. Against the seemingly comprehensive background of this heterogeneity, we single out two supramolecular characteristics common to all tumors: the clustered nature of tumor interactions with their microenvironment and the formation of biomolecular condensates with tumor-specific distinctive features. We suggest that these features can form the basis of strategies for tumor-specific supramolecular targeted therapies.

e12607 Background: Neoadjuvant therapy (NAT) of TCHP regimen is approved for standard therapy for early and locally advanced HER2-positive breast cancer (eHER2+ BC) based on encourage TRYPHAENA and KRISTINE trials results. There are limited data regarding patients (pts) treatment outcomes after NAT TCHP in the routine clinical practice. Here we presented the 1 st results of ambispective observational program to assess the efficacy and safety of cancer therapy in patients with solid tumors. Early HER2+ breast cancer group: INSIGHT-HER2BC. Methods: We ambispectively reviewed medical records of pts with eHER2+ BC who underwent NAT 6xTCHP (6 docetaxel/carboplatin + trastuzumab/pertuzumab) at three Moscow oncology centers since Jan’2017. This ongoing trial has launched in Feb’22. Here is presented descriptive analyses of pCR (ypT0/is, ypN0) rate for pts who completed NAT and 1-3 yrs. disease-free survival (DFS). Results: At the data cut-off (Jan’2023) 934 pts with HER2+ eBC underwent ≥ 1 cycle of NAТ. The median age is 54.3 y.o. (range: 22-78) where 36% pts were older 60 y.o.; 14% pts - younger than 40 y.o. 75% (571) pts had surgery results. pCR rate is related to KRISTINE trial: 58% (330) pts in the ITT (intention-to-treat) population vs 56% pts, respectively. pCR rate for pts with locally advanced BC is 55% vs 59% for operable BC (114/208 and 215/363 pts, respectively). There is difference in pCR rate achievement according to hormone status (HR+ vs HR-) and HER2 status (3+ vs 2+/ISH +). 1-yr. DFS for pCR group is 97% vs 94% for non-pCR; 2-yr. DFS is 83% vs 83%, respectively, and 3-yr. DFS 64% for pCR group vs 58% for non-pCR. In HR-HER2+ BC the biggest drop between pCR and non-pCR is registered at the 3-yr. DFS: 56% vs 22% while in HR+HER2+ there is almost equal decrease was observed every yr.: 97% vs 93% - 1 st yr.; 90% vs 85% - 2 nd yr.; 72% vs 68% - 3 d yr. Conclusions: NAT TCHP is the effective regimen for HER2+ eBC in the real-world population. The efficiency is observed regardless of disease stage and age. However, there is clear unmet need to find new therapeutic options for HER2 (2+/ISH+) BC. Preliminary results of DFS is markedly lower than in TRYPHAENA and KRISTINE trials but in conjunction with another real-world evidence data. DFS in HR+HER2+ and HR-HER2+ pts likely reflects distinct tumor biology. The mature data for long-term outcomes are awaited. [Table: see text]

The effect of BCG vaccine is known to enhance resistance to another disease, and this effect is associated with the training of innate immune cells. In the framework of this work, the transcriptomes of bone marrow cells of BCG-treated mice were studied. The involvement of differentially expressed genes in multiple immune processes and signaling pathways was demonstrated.