Russian Journal of Infection and Immunity
ISSN (print): 2220-7619, ISSN (online): 2313-7398 Founders: Russian Association of Allergologists and Clinical Immunologists Saint-Petersburg Regional Branch, Saint-Petersburg Pasteur Institute, North-Western Department of Medical Sciences Editor-in-Chief: Areg A. Totolyan, academician of RAS, Doctor of Sc., Professor Frequency / Access: 6 issues per year / Open Included in: White List (3rd level), Higher Attestation Commission List, RISC, Scopus, Web of Science Core Collection
Authors who publish with this journal agree to the following terms: Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal. Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal. Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (See The Effect of Open Access).
Modeling respiratory viral infections actual in the first quarter of the XXI century: from primary epithelial cultures to organoids
Respiratory viral infections pose a serious public health issue resulting in high morbidity and mortality, as well as profound socioeconomic losses. Therefore, it accounts for a need to research respiratory viral infections immunopathogenesis, development of effective vaccines and antiviral drugs, as well as measures to monitor viral infections. The aim of the review is to analyze current methods for modeling respiratory viral infections ex vivo. Material and methods. There were analyzed current data regarding development and application of models based on primary epithelial cells (PECs) derived from various anatomical sites of the human respiratory tract (RT) and 3D cell cultures. For this, there were assessed 158 publications retrieved from the main databases (Web of Science, PubMed, Scopus, Elsevier, Google Scholar and RSCI until January 2025) by querying the keywords: respiratory viruses; primary airway epithelium cultures; organoids; immunopathogenesis; tropism; cellular receptors; cytokines. Results and discussion. The analysis showed that models based on PECC are widely used in virological studies of respiratory viral infections, which, however, is coupled to certain disadvantages. More advanced are RT 3D models (organoids or mini-organs, spheroids, “organs on a chip”), which allow not only to reproduce infectious processes, but also to study immunopathogenesis taking into account the immunometabolic and immunoneurological status. Using RT PECs and 3D models, the properties of a number of respiratory viruses actual in the first quarter of the XXI century (influenza and parainfluenza, pneumoviruses, coronaviruses, rhinoviruses, bocaviruses, adenoviruses) such as tissue tropism, receptor interactions and innate immune response were assessed. Moreover, we also present information on promising models for respiratory viral infections that reproduce essential aspects of RT physiology. Conclusion. The primary biotechnological aim for virological studies of respiratory viral infections is to generate a multiparameter, reproducible and cost-effective RT modeling system that imitates its morphological and functional structure.
Copyright (c) 2025 Kuznetsova T.A., Mikhalko A.A., Shchelkanov E.M., Kryzhanovsky S.P., Shchelkanov M.Y. https://creativecommons.org/licenses/by/4.0
Immunopathogenesis of neurosyphilis: clinical management perspectives
This review provides a comprehensive analysis on the immunopathogenesis of neurosyphilis and discusses the related clinical perspectives. Neurosyphilis remains one of the most complex and variable forms of syphilitic infection, driven by the interaction between T. pallidum and host innate and adaptive immune cells leading to chronic inflammation and damage to the nervous system. The article highlights three major relevant areas. 1) Cellular and molecular mechanisms. The role of different T-lymphocyte subsets, cytokine cascades, macrophages, and microglia in shaping persistent inflammation, disrupting immune control, and contributing to neurodegenerative processes is examined. In particular, it emphasizes the imbalance between pro- and anti-inflammatory cytokines, as well as the strategies by which the pathogen evades immune surveillance. 2) Clinical manifestations and diagnostic approaches. Current knowledge of the wide clinical spectrum of neurosyphilis is summarized, ranging from asymptomatic forms to severe progressive neurological involvement. Special attention is given to biomarkers, including cerebrospinal fluid indices and immunological tests, as well as instrumental methods such as MRI, serological, and molecular assays, which help refine disease staging and assess activity. 3) Therapeutic opportunities and prospective targets. Existing antibiotic regimens are discussed, along with the challenges of limited efficacy and potential antibiotic resistance. The review further explores the potential of immunotherapy and combined strategies aimed at restoring immune control and reducing central nervous system inflammation. Overall, the review integrates fundamental aspects of immunopathogenesis with practical clinical considerations. By linking cellular and molecular insights with diagnostic and therapeutic perspectives, it provides a relevant resource for both clinicians and researchers primarily engaged in the search for innovative therapeutic strategies against neurosyphilis.
Copyright (c) 2025 Bekhalo V.A., Loseva O.K. https://creativecommons.org/licenses/by/4.0
Preparation and characterization of the recombinant norovirus VP1 surface protein S domain
Introduction. In the structure of the norovirus surface VP1, it consists of the S domain which N-terminal sequence is responsible for capsid formation, and P domain that extends beyond the capsid. Possibility of using S domain for preparing chimeric virus-like particles is shown. The aim of the work is to obtain a recombinant VP1 protein S domain and to characterize its immunogenic and antigenic properties. Materials and methods. Cloning of the sequence encoding VP1 protein S domain, modeling the structure of proteins, microbiological methods for working with E. coli cells producing recombinant proteins, polymerase chain reaction, electrophoresis of nucleic acids in an agarose gel and proteins in a polyacrylamide gel, affinity chromatography, enzyme immunoassay, electron microscopy were applied during the study. Results. A genetic construct encoding the recombinant VP1 norovirus genotype GII.4 protein S domain optimized for highly efficient expression in E. coli is obtained. E. coli Rosetta 2 cells were transformed with the genetic construct. Conditions for protein production and purification were optimized. A soluble recombinant protein reproducing norovirus VP1 protein S domain and forming virus-like particles with a diameter of 30 nm is obtained. Immunization of mice with the obtained protein caused specific antibody production including low-avidity IgM antibodies. When assessing antigenic properties, it was shown that antibodies interacting with the recombinant S domain are found in the blood samples collected from volunteers. Antibody titers, but of lower avidity, specific to the latter corresponded to those against full-length VP1. Likely, it was due to the localization of the S domain inside the viral particle. Conclusion. Antigenic and immunogenic properties of recombinant protein reproducing structure of norovirus VP1 S domain are characterized, and its ability to form virus-like particles is shown.
Copyright (c) 2025 Lapin V.A., Novikov D.V., Mokhonova E.V., Melentyev D.A., Tsyganova M.I., Manakova E.A., Novikov V.V. https://creativecommons.org/licenses/by/4.0
Immunochemical detection specificity and molecular properties of Staphylococcus aureus-derived cytokine-like substances
Cytokines are main interaction regulators between cells of different origin in higher organisms and human. However similar molecules called cytokine-like substances (CLS) have been also found in more primitive organisms. Using immunochemical methods, CLS mimicking some human cytokines were detected in supernatants obtained after cultivation of different bacterial strains, including Staphylococcus aureus. This article was aimed at assessing immunochemical detection specificity and molecular properties of CLS derived from Staphylococcus aureus АТСС 25923 supernatants. Maximal CLS concentrations were detected using antibodies against human interleukin-1 receptor antagonist (IL-1rа), therefore justifying use of this cytokine for immunochemical specificity studies. According to the obtained data Staphylococcus aureus АТСС 25923 supernatants contained unspecific substance different from IL-1ra because it interacted not only with specific anti IL-1ra antibodies, but also with antibodies recognizing other proteins (for example, human enzyme superoxide dismutase). Upon this, Staphylococcus aureus АТСС 25923 supernatant had no competitive effect on interaction with immobilized IL-1rа, evidencing about the lack of specific antigen in the test material. For CLS identification they were purified from S. aureus АТСС 25923 supernatant using immunoaffinity chromatography on Sepharose column containing anti-human IL-1ra antibodies. In the eluate studied with SDS PAGE electrophoresis we have found heterogenous material characterized by four major bands with Mr = 50–60 kDa and 35 kDa. Importantly, it lacked 20 kDa signal specific for human IL-1ra. Each of four study electrophoretic components were extracted from the gel, digested with trypsin, and analyzed using mass-spectrometry that allowed to identify tryptic peptides highly homologous to that of staphylococcal protein A (SpA). Thus, the data obtained allowed to reveal SpA as a major eluate component. Highly likely it may be assumed that immunoglobulins used in enzyme immunoassay test kits for cytokine detection can react with secretory derivatives of staphylococcal immunoglobulin-binding proteins identified as CLS. Consequently, the so-called CLS detected by ELISA in supernatants derived after staphylococcus cultivation differ from true human cytokines, and their interaction with antibodies may be “non-specific”.
Copyright (c) 2025 Gorbunov N.P., Ischenko A.M., Afinogenova A.G., Zhakhov A.V., Trofimov A.V., Eliseev I.Y., Zurochka A.V., Fomina L.O., Fayzullina A.I., Gritsenko V.A., Simbirtsev A.S. https://creativecommons.org/licenses/by/4.0
Regulation of Clostridiodes difficile CRISPR-Cas system by biofilm-associated factors and glucose
Clostridioides difficile is a spore-forming enteropathogenic anaerobic bacterium and one of the most common opportunistic human pathogens. Its pathogenicity relies on the production of toxins, sporulation, biofilm formation, and the ability to withstand numerous stresses encountered in the host environment. In addition to these well-known mechanisms, C. difficile possesses a remarkably complex CRISPR-Cas system characterized by two cas operons and multiple CRISPR arrays. While CRISPR-Cas systems are primarily studied as adaptive immune mechanisms against bacteriophages and mobile genetic elements, accumulating evidence suggests they may also be integrated into broader regulatory networks that contribute to bacterial physiology, adaptation, and virulence. However, the regulation and functional dynamics of this system in C. difficile remain largely unexplored. In this study, we investigated the regulation of the C. difficile CRISPR-Cas system under biofilm-inducing factors. Quantitative PCR analysis revealed the induction of several CRISPR arrays and the partial cas operon under high intracellular levels of the secondary messenger cyclic di-guanosine monophosphate, a key regulator of bacterial phenotypic shifts. These results were partially confirmed by interference efficiency assays. A secondary bile salt, sodium deoxycholate, known to trigger biofilm formation, also increased both cas operons and one CRISPR array expression, suggesting its role for CRISPR-Cas system regulation during host-associated stress Moreover we identified glucose as a regulatory factor for C. difficile CRISPR-Cas system. Elevated glucose concentration in the medium induced the expression of the partial cas operon and CRISPR 3–4 arrays. However, at the same time it functionally suppressed the interference efficiency of the system. Together, our findings demonstrate that the C. difficile CRISPR-Cas system is responsive to biofilm-inducing signals and nutrient availability, linking its regulation to key aspects of bacterial physiology and adaptation to the host. This work also highlights the potential for non-canonical regulatory roles of CRISPR-Cas in C. difficile survival and pathogenesis.
Copyright (c) 2025 Maikova A.S., Polev D.E., Khodorkovskii M.A. https://creativecommons.org/licenses/by/4.0
Exploring the impact of gut microbiota on epilepsy pathogenesis in Krushinsky–Molodkina rats
The gut–brain axis represents a bidirectional communication network that integrates neural, endocrine, and immune pathways with intestinal microbiota-derived signals. Disruption of this system, often resulting from gut microbiota dysbiosis, has been increasingly associated with neurological and psychiatric disorders, including depression, Alzheimer’s disease, and Parkinson’s disease. Understanding a crosstalk between host genetics, microbiota composition, and neuroinflammatory processes is therefore crucial for elucidating the mechanisms underlying brain health and disease. In the present study, we investigated gut microbiota composition in two genetically distinct rat Wistar and Krushinsky–Molodkina (KM) strains, and further assessed the effects of kindling-induced epileptogenesis and associated neuroinflammation on the KM microbiota. Our analyses revealed notable inter-group alterations in microbial composition. In particular, Enterococcus hirae abundance differed significantly between Wistar and KM control rats, while Streptococcus hyointestinalis exhibited changes between the KM control and KM kindling groups. Furthermore, we observed a reduced relative abundance of Lactobacillus murinus and Lactobacillus reuteri in KM control rats compared with both Wistar and KM kindling animals. In parallel, we observed altered expression of NF-κB p65 in the temporal lobe white matter. Specifically, Wistar vs KM control rats displayed lower NF-κB p65 expression, whereas KM kindling rats showed reduced expression compared to the KM control group. Such alterations in NF-kB p65 expression correlate with observed shifts in abundance of Lactobacillus murinus and Lactobacillus reuteri, suggesting a link between microbiota composition and neuroinflammatory processes. These findings provide deeper insight into the multifaceted interplay between host genetic background, neuroinflammation, and gut microbial composition. The results suggest that differences in bacterial taxa, particularly within Lactobacillus species, may be linked to NF-κB-mediated processes in the brain, thereby shaping the pathophysiological landscape of neurological disorders. Further investigations are required to better understand the complex crosstalk between host genetics, brain and gut microbiota, and their implication for health and disease.
Copyright (c) 2025 Bidzhiev A.Z., Kraeva L.A., Ivlev A.P., Goncharova A.R., Bazhanova E.D. https://creativecommons.org/licenses/by/4.0
Development and validation for intra-species classification of HHV6A and HHV6B molecular genetic diversity
Human herpesvirus 6A (HHV6A) and human herpesvirus 6B (HHV6B) are ubiquitous viruses that infect more than 95% of the population. Clinical manifestations of HHV6 infection and associated diseases are diverse, which may depend on virus molecular genetic characteristics (genovariants). Estimating the significance of the molecular genetic diversity is complicated due to the lack of proper classification. The aim of the study was to develop an intraspecies HHV6A and HHV6B classification. Using 50 and 207 HHV6A and HHV6B full-genome sequences retrieved from the NCBI Nucleotide database, various fragments of virus genome were analyzed. Multiple sequence alignment was performed using MAFFT L-INS-i algorithm; F81 nucleotide substitution model and maximum likelihood method were used to construct dendrograms. Nucleotide substitutions were determined relative to reference sequences X83413 (HHV6A) and AF157706 (HHV6B). Genovariants were defined based on the nucleotide substitutions in variable positions of the genomic fragment. The results were confirmed by constructing dendrograms. An opportunity of using fragments of HHV6A and HHV6B genomes to construct an intraspecies classification was assessed. Fragments U90(part206) and U90В(part431) were selected as optimal. Based on the nucleotide sequences of the fragments, the intraspecies classification for HHV6A and HHV6B was constructed, including seven genovariants of each virus. The genovariants were characterized by unique nucleotide composition in the signature positions. A minimum (0.001 or less for both viruses) nucleotide diversity within the isolated genovariants was established. The classification reflects the phylogenetic relationships of circulating and inherited chromosomally integrated forms of HHV6A and HHV6B: divergence of HHV6A genovariants depending on its persistence form and integration site and coevolution of two HHV6B forms within several genovariants. Further studies on virus molecular genetic diversity in different regions of Russia and abroad may supplement the classification. The method of HHV6A and HHV6B classification is characterized by simplicity, technological accessibility and can be implemented in laboratories of different levels of technical equipment. The classification can be used to analyze an effect of virus molecular genetic diversity on the clinical characteristics of associated diseases, optimize the epidemiological surveillance system and develop new approaches for diagnostics, prevention, and treatment of HHV6 infection.
Copyright (c) 2025 Filatova E.N., Utkin O.V., Khrulev A.E., Zaitseva N.N. https://creativecommons.org/licenses/by/4.0
The effect of active and latent Herpes Simplex Virus-1,2 (HSV-1,2) infections on peripheral blood lymphocyte subpopulation composition in patients with inflammatory diseases of the anterior eye segment
Herpes simplex virus-1 (HSV-1), Herpes simplex virus-2 (HSV-2) cause lifelong infections with two-phase cycle: productive lytic and latent phase. The aim of this research work was to study the effect of HSV-1, HSV-2 on immune status of patients in latent and lytic phases of infection. Materials and methods. 99 people with anterior uveitis, corneal ulcers, episcleritis, scleritis. IgG-antibodies to late and early antigens (IE antibodies — markers of latent infection reactivation) of HSV-1, HSV-2, and CMV (comparison virus) were determined in blood serum by ELISA. Immune status was assessed in whole blood by flow cytometry (BD FACS Canto II, USA): percentage and absolute count of lymphocytes (CD45+), T lymphocytes (CD3+), cytotoxic T lymphocytes (CD3+CD8+), T helper cells (CD3+CD4+), double-positive lymphocytes (CD3+CD4+CD8+), natural killer cells (CD3–CD16+CD56+), B lymphocytes (CD19+), CD4+/CD8+ ratio. Statistical analysis: StatTech v.4.7.2 (Russia). Results. 86 out of 99 patients were infected with HSV-1,2, 84 out of 98 — with CMV. Reactivation of HSV-1 detected in 47 patients, HSV-2 — 13, CMV — 17. 13 patients were seronegative for HSV-1,2, and 14 — for CMV. Group 1 included infected with HSV-1,2 and/or CMV patients; group 2 included not infected patients. In group 1, subgroups with latent and lytic phases were identified. Immune status in patients with latent HSV-1,2 infection was mainly the same as in lytic phase. During HSV-1 reactivation, proportion of CD3+CD8+ decreased, while proportion of CD3+CD4+, CD3–CD16+CD56+ absolute count, CD4+/CD8+ ratio increased (p < 0.05). In HSV-2 reactivation and latent HSV-1,2 infection, in contrast to HSV-1 reactivation, there was an additional increase in CD3+CD4+ (%) and CD45+. Unlike HSV-1 and HSV-2, in comparison group patients proportion of CD3+CD8+ (497.95±118.01) decreased significantly compared to latent CMV infection (620.38±326.38; p = 0.026). Conclusion. Unidirectional changes in immune status of patients with latent and lytic phases of HSV-1,2 infection are likely associated with low levels of viral reactivation and weak humoral response in some. Therefore, patients with “false-negative” results of early antibody testing could have been included in the group with latent HSV-1,2 infection. Apparently, a single test for HSV-1,2 reactivation markers is insufficient to rule out subclinical infection activity. Undiagnosed HHV reactivation in patients with inflammatory ophthalmopathology may be prognostically unfavorable.
Copyright (c) 2025 Krichevskaya G.I., Balatskaya N.V., Sorozhkina E.S., Kovaleva L.A., Kulikova I.G. https://creativecommons.org/licenses/by/4.0
Predictive utility of monocyte chemoattractant Protein-1 (MCP-1) and D-dimer in risk stratification of sepsis: a prospective cohort study
Background. Sepsis is a severe and life-threatening clinical syndrome characterized by a dysregulated host immune response to infection. This maladaptive response promotes widespread endothelial injury and abnormalities in coagulation, often progressing to multi-organ dysfunction and death. Mortality rates remain high, highlighting the urgent need for reliable biomarkers to enable early identification of patients at high risk. Such tools are particularly valuable in low- and middle-income countries (LMICs), where access to advanced diagnostic and therapeutic resources is limited. Monocyte Chemoattractant Protein-1 (MCP-1) is a chemokine that reflects hyperactivation of the innate immune system, while D-dimer indicates activation of coagulation and fibrinolysis. Although both pathways are central to the pathophysiology of sepsis, data evaluating their combined prognostic value in LMIC settings remain scarce. This study aimed to assess the prognostic significance of MCP-1 and D-dimer, both individually and in combination, for predicting 28-day mortality in patients with sepsis. Materials and methods. We conducted a prospective cohort study involving 83 adult patients with newly diagnosed sepsis at Dr. Saiful Anwar General Hospital, Malang, Indonesia. Serum MCP-1 levels were measured using enzyme-linked immunosorbent assay (ELISA), and plasma D-dimer levels were determined by immunoturbidimetry at the time of diagnosis. Patients were followed for 28 days, and survival outcomes were evaluated using Kaplan–Meier survival analysis and Cox proportional hazards regression models. Results. Among the 83 participants, 58 patients (70%) died within 28 days. Non-survivors demonstrated significantly higher MCP-1 and D-dimer levels compared with survivors. An MCP-1 concentration ≥ 123.03 pg/mL was strongly associated with increased mortality (HR 2.664, p = 0.005). Elevated D-dimer (≥ 43.5 mg/L FEU) showed a weaker individual association, but when combined with MCP-1, predictive accuracy for mortality was significantly enhanced (HR 3.986, p = 0.037). Conclusion. The concurrent elevation of MCP-1 and D-dimer identifies patients with sepsis who are at markedly increased risk of death. These findings support the potential utility of integrating inflammatory and coagulation biomarkers for early risk stratification. Moreover, they highlight the central role of the inflammation–coagulation axis in sepsis pathophysiology, with particular relevance for clinical practice in resource-limited settings.
Copyright (c) 2025 Iskandar A., Fathonah S., Soraya M., Lova N.N. https://creativecommons.org/licenses/by/4.0
Cytokine levels and FOXP3 gene expression in the blood of patients with various stage of pulmonary sarcoidosis
The cytokine concentration may be related to the level of inflammation and clinical features of diseases. The study was aimed to evaluate blood plasma level for TNFα, sTNFRII, IL-1β, IL-10 and FOXP3 gene expression in patients with different clinical forms of pulmonary sarcoidosis. Materials and methods. Patients with pulmonary sarcoidosis (PS) enrolled in the study were characterized by chronic, progressive and active forms at PS stage 2. Control group was formed by conditionally healthy individuals. The cytokine (TNFα, sTNFRII, IL-1β, IL-10) concentration was examined by enzyme-linked immunosorbent assay (ELISA). Real-time polymerase chain reaction (RT-PCR) was used to analyze FOXP3 gene expression in peripheral blood leukocytes (PBL). Results. The high levels of plasma TNFα and sTNFRII were detected in patients with progressive and active PS vs chronic PS (p = 0.0263, p = 0.0321 and p = 0.0012, p = 0.0009, respectively). Concentration of IL-1β was higher in active PS rather than in chronic and progressive PS (p = 0.0002 and p = 0.0020, respectively). The IL-10 plasma level in patients from all studied groups was lower compare to healthy individuals (p = 0.0009, p = 0.00009, p = 0.0004, respectively). A decreased number of PBL FOXP3 gene transcripts was found in patients with progressive and active PS (p = 0.0008 compared with healthy individuals and patients with chronic PS). Conclusion. The level of cytokines in patients with PS is determined by disease clinical features. Upregulated proinflammatory factor (TNFα, sTNFRII, IL-1β) level as well as downregulated FOXP3 gene expression and the IL-10 concentration may suggest about potentiated inflammatory reactions in patients with progressive and active PS. To clarify disease clinical presentation, it is crucial to gain more information about the molecular biomarker dynamics mirroring magnitude of inflammation in PS. In addition, it is also required to propose proper therapy and its refinement. Moreover, the data obtained can be used to assess pathogenetic mechanisms underlying disease development and progression.
Copyright (c) 2025 Malysheva I.E., Topchieva L.V., Balan O.V., Kurbatova I.V., Tikhonovich E.L. https://creativecommons.org/licenses/by/4.0
Expression levels of miR-146a and miR-155 and their association with Interleukin-6 in type 1 diabetes
Background. Type 1 diabetes mellitus (T1DM) is a chronic autoimmune disease characterized by the immune-mediated destruction of pancreatic beta cells, leading to insulin deficiency. Inflammatory cytokines, particularly interleukin-6 (IL-6), play a central role in this pathological process by promoting pro-inflammatory immune responses. Recent evidence highlights the involvement of microRNAs, especially miR-146a and miR-155, in regulating immune cell activation and cytokine signaling pathways. Dysregulation of these microRNAs may disrupt immune homeostasis and contribute to the progression of T1DM. This study aimed to investigate the expression levels of miR-146a and miR-155 in patients with T1DM and to examine their association with serum IL-6 concentrations. Materials and methods. This case-control study included 150 participants, comprising 100 individuals diagnosed with T1DM and 50 healthy controls. Peripheral blood samples were collected to evaluate fasting blood glucose, glycated hemoglobin, and IL-6 levels using an enzyme-linked immunosorbent assay. Quantitative real-time polymerase chain reaction was used to assess the expression of miR-146a and miR-155, normalized to miR-16 as the internal control. Results. The results revealed significantly elevated levels of fasting blood glucose, glycated hemoglobin, and IL-6 in patients compared to controls (p < 0.0001). Additionally, miR-146a expression was increased by a 3.1-fold change, and miR-155 showed a 1.58-fold increase in patients with T1DM compared to healthy individuals. Conclusions. The significant overexpression of microRNAs miR-146a and miR-155, in parallel with elevated serum levels of the pro-inflammatory cytokine IL-6, highlights their crucial role in the immunopathogenesis of T1DM. These findings suggest that miR-146a and miR-155 may act as key regulators in modulating immune responses, contributing to the autoimmune destruction of pancreatic beta cells. Moreover, the combined assessment of these microRNAs and IL-6 may serve as valuable molecular biomarkers for early diagnosis, disease prognosis, and the development of novel immunomodulatory therapeutic strategies in T1DM management.
Copyright (c) 2025 Natiq Z.A., Nader M.I. https://creativecommons.org/licenses/by/4.0
Hematological parameters in hepatocellular carcinoma AND microRNA-223 gene associated with Hepatitis virus in local area
Background. Hepatocyte function may be altered by chronic HBV and HCV infections through similar mechanisms that influence the onset of hepatocellular cancer. This current work points to examine the function of microRNA-223 in Iraqi hepatocellular carcinoma (HCC) patients induced by hepatitis virus. MicroRNA-223 served as calibrator to explores its evaluate disease progression and diagnosis. Materials and methods. Blood samples were then drawn from 20 people (males and females and different ages), some of them were latterly diagnosed with HCC. these blood samples were used later for molecular study to find target gene expression. Results. The importance of HCV, HBV, and liver cancer was examined in this study, along with the drop in research and studies conducted in Iraq. Those who got treatment had somewhat higher levels of microRNA-223 countenance, whereas those who were diagnosed early and did not get treatment had lower levels. MicroRNA-223 appearance stages were meaningfully lower in the first phase of hepatitis samples than in standard samples (p < 0.0001), which may indicate that microRNA-223 can be used as a biomarker to monitor conduct effectiveness. It is recommended that more research done in this area to help in diagnosis. Conclusion. MicroRNAs are an essential tool for early diagnosis and for monitoring the onset and progression of disease due to their great specificity and reliability. all results hat HCC patients with HBV and HCV expressed miR-223 at lower levels than healthy controls. Some hematological and parameters differed significantly from those in the control group.
Copyright (c) 2025 Al-Janaby M.S., Abdujaleel R.H., Najm M.A., Mohsen R.T., Alalwani A.K. https://creativecommons.org/licenses/by/4.0
Methamphetamine use and HSV-1 coinfection synergistically alter IFNα, IFNγ, and IL-29 expression in gingival crevicular fluid: implications for gingivitis pathogenesis
Background. Methamphetamine use compromises both innate and adaptive immune responses, substantially reducing the body’s ability to combat pathogens and preserve mucosal integrity. This immunosuppression heightens susceptibility to opportunistic infections such as herpes simplex virus type 1 (HSV-1), promotes viral reactivation, disrupts the balance and diversity of the oral microbiota, and accelerates inflammatory processes within oral tissues. As a result, it exacerbates a wide range of oral health problems, including gingivitis, periodontal disease, dental caries, oral mucosal lesions, and delayed wound healing within the oral cavity. The aim of the study was to investigate the levels of interferon-alpha (IFNα), interferon-gamma (IFNγ), and interleukin-29 (IL-29) in methamphetamine users with or without HSV-1 infection, and to examine their association with the development of gingivitis. Materials and methods. This case-control study included 88 male participants aged 20–35 years, categorized into four groups: healthy controls, methamphetamine users, methamphetamine users with HSV-1 infection, and patients with gingivitis. Gingival crevicular fluid (GCF) samples were collected from all participants, and the concentrations of IFNα, IFNγ, and IL-29 were measured using enzyme-linked immunosorbent assay (ELISA). Results. IFNα and IFNγ levels were highest in the healthy control group and were significantly reduced in the methamphetamine, methamphetamine with HSV-1, and gingivitis groups (p < 0.05). In contrast, IL-29 levels were significantly elevated in gingivitis patients compared to all other groups. Furthermore, methamphetamine users with HSV-1 infection exhibited markedly higher IL-29 concentrations than methamphetamine users without HSV-1 infection. Conclusion. Methamphetamine use and HSV-1 infection significantly impair immune cytokine responses, reflected by marked reductions in IFNα and IFNγ levels, alongside elevated IL-29. The pronounced increase in IL-29 was most evident in gingivitis patients, suggesting a potential role for this cytokine in amplifying local inflammatory processes and contributing to periodontal tissue breakdown.
Copyright (c) 2025 Alsattar N.A., Taha G.I. https://creativecommons.org/licenses/by/4.0
Epidemiological patterns of salmonellosis incidence among the population of Armenia in 2009–2024
Salmonella infection remains one of the most significant global public health challenges, characterized by high prevalence, antimicrobial resistance, substantial socio-economic burden, and wide variability of clinical manifestations, which underscores the need for continuous epidemiological surveillance, improvement of laboratory diagnostics, and the development of effective prevention strategies at the international level. The aim of the study was to analyze the data and determine the burden of salmonellosis among people in Armenia. Materials and methods. The study was conducted during the period spanning from 2009 to 2024 based on statistical reporting data received by the National Center for Disease Control and Prevention of the Ministry of Health of the Republic of Armenia. Descriptive epidemiology was used in the study. Statistical data analysis was performed using MS Excel and R software packages. Results: During the analyzed period, the incidence of salmonellosis among the population of Armenia increased from 15.2 per 100 000 habitants in 2009 to 22.5 in 2024. The percentage of salmonellosis among all cases of acute intestinal infections increased from 2.8–4.5% in the period from 2012 to 2018 to 6.0–7.1% in the period from 2019 to 2024 (p < 0.001). Analyzing the dynamics of morbidity by month shows that the peak of morbidity among people occurs in the summer months. Analysis of the dynamics of salmonellosis incidence over the past 13 years by age groups shows that the incidence among the child population has always been higher (4.8–8.5 times, p < 0.001). The incidence among children in the period from 2016 to 2024 increased by 1.6 times, and among adults — by 2.3 times. Analysis by individual pediatric age groups showed that the incidence of salmonellosis declines with increasing age. Conclusion. As a result of our study, salmonellosis burden in Armenia was found to be at high level. The high incidence among pediatric population with rise in indicator levels over the past 5 years are comparable to trends recorded in European countries. Based on the results obtained, the authors developed a number of recommendations for improving salmonellosis epidemiological surveillance system in Armenia.
Copyright (c) 2025 Palozyan G.H., Hovhannisyan A.S., Grigoryan N.A., Abovyan R.A., Tsakanyan A.V., Margaryan A.V., Khachatryan T.S., Melik-Andreasyan G.G., Atoyan S.A. https://creativecommons.org/licenses/by/4.0
Measles, rubella, mumps and diphtheria нerd immunity in the population of the some Kherson’s region districts
Introduction. Specific prevention of vaccine-preventable infections (VPIs) has been the main prerequisite to radically lower their incidence in the Russian Federation. Since the Kherson Region joined the Russian Federation in 2024–2025, no VPI cases have been recorded, likely due to the level of herd immunity. The actual number of individuals immune to VPIs can only be estimated through serologically monitored herd immunity. Study objective was to assess herd immunity to measles, mumps, rubella, and diphtheria in specific Kherson Region districts. Materials and methods. The study involved 2.807 volunteers in seven municipal districts, aged 1 to 70+ years. A volunteer cohort, stratified by age (1–5, 6–11, 12–17, 18–29, 30–39, 40–49, 50–59, 60–69, ≥ 70), was randomized using the Web application. During the study, participants completed a questionnaire, IgG antibodies to specific agents (measles, mumps, rubella, diphtheria toxin) were measured in venous blood samples using ELISA test kits (Russia). Results. The average cohort seroprevalence for measles, rubella, mumps, and diphtheria among volunteers in the region were 83.4%, 95.1%, 65.7%, and 83.4%, respectively. Adults aged 18–29 years were the least protected against measles, rubella, and mumps, with the seropositivity: < 70% for measles; 84.5% for rubella; and 44.6% for mumps. The most protected were people aged ≥ 50 years: 91.5–99.4% for measles; > 98% for rubella; and 74.5–87.1% for mumps. People over 60 were the least protected against diphtheria (63.8–76.5%). In children’s groups, maximum seroprevalence was noted in the group aged 6–11 years: 90.8% for measles; > 96.9% for rubella; 64.6% for mumps; and 90.4% for diphtheria. Most volunteers had low to moderate anti-measles and anti-diphtheria toxin IgG levels; and high anti-rubella IgG levels. The seropositivity of “naive” volunteers (those denying infection or vaccination) indicates insufficient laboratory VPI diagnostics in the Kherson Region. Conclusion. The level of herd immunity in the surveyed areas (Kherson Region) met the criterion for epidemiological well-being only with regard to rubella. Specifically, the percentage of seronegative individuals was below 10%. Insufficient seroprevalence for the measles and mumps viruses, as well as the C. diphtheriae, reflects conditions conducive for the spread of these infections among the population.
Copyright (c) 2025 Popova A.Y., Smirnov V.S., Egorova S.A., Milichkina A.M., Turov V.M., Drozd I.V., Vasilyeva Z.V., Zhimbaeva O.B., Gubanova A.V., Buts L.V., Zotkin N.N., Arbuzova T.V., Demidyuk O.I., Ivanov V.A., Dymchenko G.B., Totolian A.A. https://creativecommons.org/licenses/by/4.0
Tuberculoma caseous necrosis-derived bacteria (Corynebacterium and Staphylococcus) enhance granuloma formation in vitro and stimulate mycobacterial biofilm development
Granuloma formation represents one of the key stages in tuberculosis pathogenesis, characterized by the development of specialized cellular structures surrounding Mycobacterium tuberculosis within foci. These structures are presented by complex, multicomponent assemblies that both detain the pathogen and simultaneously serve as a niche for its persistence. It has been firmly established that the mycobacterial cord factor is an important driver of granuloma induction, being involved in intercellular interactions and the organization of granuloma three-dimensional scaffold. However, the influence of the resident microbiota on this process, as well as its contribution to the formation of mycobacterial biofilms, remains understudied. This work investigates an effect of Corynebacterium kefirresidentii and Staphylococcus epidermidis lysates (isolated from tuberculoma-related caseous necrosis) on in vitro granuloma formation using C57BL/6 mouse peritoneal macrophages and splenocytes. Additionally, an influence of C. kefirresidentii on vaccine strain M. bovis BCG growth and biofilm development was examined. The study demonstrates that C. kefirresidentii induces the formation of a rapidly growing M. bovis BCG biofilm with characteristic cord-like architecture and a prominent extracellular matrix. This effect was accompanied by a statistically significantly expanded area under the growth curve compared to the control (p < 0.0001). Co-cultivation experiments with the clinical strain M. tuberculosis Beijing B0/W148 and bacterial lysates revealed limited antimycobacterial activity but demonstrated a pronounced stimulatory effect on the formation of granuloma-like structures in the M. tuberculosis-induced in vitro granulemogenesis model. C. kefirresidentii and S. epidermidis lysates significantly propagated granuloma formation as evidenced by markedly increased both cellular aggregate number and size (p < 0.01), including the formation of large clusters containing more than 50 cells. Taken together, these findings suggest that satellite pathobiota derived from caseous necrosis of tuberculous foci might be involved in modulating key mechanisms of infection pathogenesis and point at its potential contribution to unfavorable outcomes in pulmonary tuberculosis.
Copyright (c) 2025 Orlova E.A., Ogarkov O.B., Schwartz Y.S., Lykov A.P., Nemkova E.K. https://creativecommons.org/licenses/by/4.0
A diagnostic algorithm for Helicobacter pylori detection and identification in gastric mucosal biopsies
Helicobacter pylori is a major etiological agent in gastritis, peptic ulcer disease, gastric adenocarcinoma, and MALT lymphoma. While gastric mucosal biopsies are the primary material for invasive diagnosis, a comprehensive diagnostic approach is needed. This study presents a diagnostic algorithm that facilitates not only H. pylori detection and identification but also, when necessary, the subsequent analysis of isolated microbial strains, e.g., virulence gene determinants or antibiotic resistance mutations. Having applied this algorithm from 2013 to 2024, we examined gastric biopsies from 610 patients (57% female, 43% male) aged 19–73 years with various gastrointestinal pathologies using culture and molecular methods. In our study, H. pylori detection rate by PCR vs culture examination (48.20% vs 32.3% respectively) in gastric biopsies was significantly higher. In gastric cancer, H. pylori DNA detection rate was minimal and amounted to 35.7%, which correlated with the lowest culture-based isolation rate (9.5%). Since vacA virulence gene is presented in all H. pylori strains, it was used as a marker for H. pylori detection in our study. Thus, the vacA gene was detected in 48.0% (258/537) biopsy samples. The cagA gene is not presented in all H. pylori strains and considered to be a high virulence marker. In addition, it was found out that the cagA gene was present in 47.3% H. pylori-positive cases. Notably, the proportion of cagA-positive isolates turned out to be minimal in chronic gastritis — 39.4%, in contrast to its level in peptic ulcer and gastric cancer comprising 77.3% (p < 0.001) and 72.7% (p = 0.029), respectively. Conclusion. The proposed diagnostic algorithm is applicable in microbiological practice for diagnosis, epidemiological monitoring, and research in H. pylori infections.
Copyright (c) 2025 Svarval A.V., Starkova D.A., Kaftyreva L.A. https://creativecommons.org/licenses/by/4.0
The impact of COVID-19 on respiratory tract microbiota pattern in patients with severe pneumonia
COVID-19 weakens the body’s immune system and predisposes to bacterial infections. It has been increasingly evident about changes in the etiological pattern of pneumonia pathogens due to altered lung microbiota after viral pneumonia, the effect of SARS-CoV-2 on the immune system, and antibiotics taking as part of preventing secondary bacterial infection. Our study was aimed to analyze the dynamic change in the pattern of the respiratory tract microbiota in patients with severe pneumonia in the years from 2019 to 2023. There were enrolled 304 patients with pneumonia diagnosed after X-ray examination assessed from January 2019 to December 2023 inclusive. During the pandemic, all the investigated patients had a positive SARS-CoV-2 PCR result, and in the period after the pandemic all the examined patients were negative. Sputum samples delivered to the laboratory, where we performed microbiological culture with identification by MALDI-ToF mass spectrometry. In the pre-COVID-19 pandemic, 62 sputum samples were analyzed, among which Klebsiella pneumoniae and Stenotrophomonas maltophilia were the most common found in 21% and 17.7%, respectively. Both Acinetobacter baumanii and Staphylococcus aureus were isolated in 14.5% cases. Streptococcus pneumoniae was found in 8.1% cases. During the COVID-19 pandemic, 122 samples were evaluated allowing to observe that K. pneumoniae accounted for half of all isolated microorganisms. The second most common was A. baumannii (23.8%). In the post-pandemic period, 120 samples were analyzed, from which K. pneumoniae was mainly identified (31.7%). The next most frequent among pathogens were S. aureus and A. baumannii — 23.3% and 18.3%, respectively. In this way, there was a statistically significant change in the frequency of detection of Gram-positive and Gram-negative microorganisms in ICU patients during the study periods. Before the COVID-19 pandemic, the proportion of Gram-negative microorganisms in the pattern of pathogens was 67.7%, during the pandemic — 91.0%, in the post-pandemic period — approached the values of 2019–2020 and amounted to 70.0% (p < 0.001). K. pneumoniae and A. baumannii were the most frequently found, however, the statistical significance of the changes was observed only for K. pneumoniae (p < 0.005). An insignificant decline in the detection rate of pneumococcus was established as well. The frequency of staphylococcal discharge after coronavirus infection exceeded the pre-pandemic magnitude (p < 0.001).
Copyright (c) 2025 Zolotov M.O., Kozlov A.V., Shafigullina L.R., Lyamin A.V. https://creativecommons.org/licenses/by/4.0