Vol 32, No 11 (2025)
REVIEWS
Modern trends in the development of antifungal agents
Abstract
Mycoses pose an increasing threat to public health, resulting in millions of invasive infections and a high mortality rate each year. The limited arsenal of antifungal agents, their toxicity, and the rapid spread of resistance underscore the urgent need for new therapeutic strategies. This review systematizes current trends in the development of antimycotic agents intended for the treatment of invasive mycoses. The primary focus is on drugs with novel mechanisms of action targeting key structures and metabolic pathways of the fungal cell. The emphasis is on publications from the past decade; however, significant fundamental research from earlier times has also been taken into account. The search was conducted in the electronic databases eLibrary.ru, PubMed, Google Scholar, and Wally. Promising approaches include inhibition of cell wall component synthesis, disruption of cell membrane function through effects on ergosterol, phospholipids, and sphingolipids, as well as effects on intracellular targets: fungal intracellular proteins and signaling pathways, protein biosynthesis processes, and nucleic acid replication and transcription. Agents inhibiting the synthesis of major cell wall components such as β-1,3-glucan (echinocandins, ibrexafungerpY), β-1,6-glucan, chitin (nikkomycin ZY), and GPI anchors (fosmanogepixY), are reviewed. Agents acting on ergosterol (oteseconazoleY, opelconazoleY), sphingolipids (IPC-synthase inhibitorsY), and phospholipids (mandimycinY) are analyzed. Fungal kinase inhibitors, Hsp90, calcineurin, N-myristoyltransferase, elongation factor EF-2, and nucleic acids (olorofimY) are described. Several of these compounds (olorofimY, fosmanogepixY, VT-1598Y, BSG005) are currently in clinical trials. The importance of identifying selective targets and developing combination therapy to overcome resistance and improve treatment effectiveness is emphasized.
Y Hereafter, it means that the medicinal product is not registered in the Russian Federation.
763-774
ORIGINAL STUDY ARTICLES
Hair mineralograms in children with autism spectrum disorders
Abstract
BACKGROUND: Autism spectrum disorders are often accompanied by comorbid somatic conditions, which necessitates the development of reliable methods of predictive diagnostics. The analysis of hair elemental composition, which reflects long-term metabolic status, can identify individual micronutrient imbalances and enable the development of personalized correction plans to prevent related health disorders.
AIM: This work aimed to evaluate the potential of hair mineralograms as a predictive biomarker for the risk of comorbid somatic disorders in children with autism spectrum disorders, thereby facilitating the development of personalized correction plans.
METHODS: In 36 children diagnosed with conditions classified as “Pervasive developmental disorders” (group 1) and 64 children of the control group (group 2) living in Magadan, the concentrations of 25 macro- and microelements in hair were determined using spectrometric methods. We performed a step-by-step analysis of the absolute bioelement content, an intergroup comparison of deviation frequencies from reference values, a correlation analysis, and constructed an elemental imbalance formula for group 1.
RESULTS: In group 1, potassium and cobalt levels were statistically significantly higher than in group 2, whereas the concentrations of iron, selenium, manganese, chromium, silicon, and arsenic were lower (p < 0.05). The frequency analysis of deviations revealed manganese deficiency (44% in group 1 and 23% in group 2), zinc deficiency (25% and 50% in group 1 and group 2, respectively), phosphorus deficiency (86% and 42% in group 1 and group 2, respectively), and sodium deficiency (39% and 17% in group 1 and group 2, respectively). Silicon deficiency was identified for the first time in group 1 (42%), which is not typical for Magadan residents in general. In the center of the correlation cluster of group 1 lies manganese, forming strong statistically significant correlations with iron and zinc (r > 0.7; p < 0.05).
CONCLUSION: The elemental imbalance formula for autism spectrum disorders incorporates an excess of vanadium and a deficiency of sodium, silicon, manganese, and phosphorus. This pattern is identified against the characteristic “northern” deficiency of calcium, magnesium, cobalt, and iodine in these children. Iron and selenium deficiency in the hair of children with autism spectrum disorders was not detected, which may indicate sufficient intake but impaired absorption in a leaky gut, preventing adequate metabolism. The findings provide insight into the fundamental organization of the bioelemental system in autism spectrum disorders, suggesting possible variations depending on regional biogeochemistry, sex, age, and diagnosis characteristics.
775-786
Chemical composition of drinking water in Murmansk and Kola, element migration forms in waters and the human body, and comparison with the waters in Kirovsk
Abstract
BACKGROUND: This study is a logical continuation of earlier work examining the chemical composition of drinking water in various areas of the Murmansk Region and assessing its potential impact on human health. The relevance of such research is underscored by the fact that several cities and districts of the Murmansk Region exhibit disease incidence rates exceeding national averages. Thermodynamic modeling enables the application of new approaches to examining potential migration forms of chemical elements in natural waters and the formation of secondary phases, depending on various parameters (water chemistry, pH, Eh, temperature, conditions of water formation, etc.). Investigating the transformation of element species upon entry into the human body makes it possible to predict pathological conditions and, consequently, to shift toward disease prevention. Among the analyzed chemical elements, special attention was given to rare and rare earth elements, whose biological properties have attracted increasing scientific interest both in Russia and internationally.
AIM: This work aimed to assess the complete chemical composition of drinking water from centralized water supply systems in the administrative districts of Murmansk and to compare it with the chemical composition of water from the Central water intake facility in Kirovsk with respect to maximum permissible concentrations, biologically significant concentrations, and the assessment of their potential health relevance.
METHODS: Inductively coupled plasma mass spectrometry, potentiometry, and titrimetry were employed. Thermodynamic calculations were performed using physico-chemical (thermodynamic) modeling implemented in the Selector software package.
RESULTS: Significant differences in chemical composition were identified among the three districts of Murmansk and Kola. The chemical composition of water from the Pervomaysky district was characterized by comparatively higher concentrations of Y, Zr, La, Ce, and U. Comparison of drinking water from Murmansk districts with water from the Central intake (Kirovsk) showed higher levels of Ca, Mg, Sr, Ba, La, and Ce, and lower levels of F-, Al, NO3-, Na+, HCO3-, U, and pH. Changes in the migration forms of elements and the formation of newly formed phases were demonstrated both in tap water and under gastric conditions.
CONCLUSION: Drinking water distributed across Murmansk districts is low-mineralized. Except for silicon, the concentrations of macroelements and essential elements do not reach the lower limits of biologically significant concentrations. The water contains rare and rare earth elements for which biologically significant concentration thresholds have not yet been established. Thermodynamic modeling showed that, upon entering the gastrointestinal tract, these elements change their migration forms and become more mobile. The work presents preliminary data on the migration forms of lanthanides under varying gastric conditions, whose chlorides may influence blood coagulation.
787-798
Use of certain natural polymers to reduce the toxic effects of lead ions on biological objects
Abstract
BACKGROUND: The wide use of lead compounds in electrical engineering, dye production, insecticides, and in the manufacture and use of ammunition has led to its negative impact on the environment and the human body. Lead levels increase as a result of military operations, which is relevant today, because of its use in ammunition. During explosions or shots, ammunition releases lead as particles and vapor that can contaminate water, soil, and air, entering the upper respiratory tract of humans. Although there are currently a significant number of eco- and enterosorbents, most of the latter are based primarily on silicon dioxide, lignin, smectites, etc. These materials are not always specifically effective against heavy metals. Consequently, there is an urgent need to address two key challenges: immobilizing pollutants to remove them from geochemical flows, and developing preventive and therapeutic measures to detoxify individuals living or working in areas with adverse industrial exposure.
AIM: This work aimed to analyze and comparatively evaluate the sorption activity of humic acids and ground reindeer antlers with known enterosorbents against lead ions at pH 3.
METHODS: Biopolymer samples (humic acids and reindeer antler tissue) were selected as study objects. Colloidal silicon dioxide (Polysorbâ) and hydrolyzed lignin (Filtrum-STIâ) were used as standard reference enterosorbents. Direct potentiometry and infrared spectroscopy were used in the study.
RESULTS: Sorbents derived from natural raw materials (humic acids and reindeer antler tissue) demonstrated sufficiently high sorption activity toward lead ions and strength of binding according to the calculated sorption capacity constant and binding capacity coefficient, respectively. The bone tissue of reindeer antlers exhibited higher values of sorbent–sorbate affinity coefficients and Pb2+ absorption rate compared with other sorbents. The recorded infrared spectra of biopolymer samples had qualitatively similar absorption peaks; however, the quantitative content of functional groups within their molecules differed.
CONCLUSION: The studied biopolymers (humic acids and reindeer antler tissue) exhibit high sorption properties toward lead ions, significantly exceeding those of enterosorbents already available on the pharmaceutical market. The implementation of high sorption characteristics of the examined natural biopolymers and their ability to participate in heavy metal ion binding through chelation likely relates to the features of their structural-functional organization.
799-810
Health risk assessment associated with indoor air pollution by metals and metalloids in PM2.5: a cross-sectional study
Abstract
BACKGROUND: Fine particulate matter with an aerodynamic diameter <2.5 μm (PM2.5) is among the most hazardous atmospheric pollutants for human health. In Russia, no prior studies have assessed population health risks associated with indoor air contamination by PM2.5 containing potentially toxic metals and metalloids.
AIM: This work aimed to examine indoor air PM2.5 concentrations, investigate the content of metals and metalloids within PM2.5, and assess the associated inhalation health risks in Chelyabinsk.
METHODS: Samples were collected in university classrooms (n = 3), laboratories (n = 3), dormitory rooms (n = 4), and residential apartments (n = 14) in Chelyabinsk during seasons of low PM2.5 pollution (November–March) and high pollution (April–October) in 2024–2025. PM2.5 samples were obtained using cascade impactors on polycarbonate filters. Air PM2.5 concentrations were calculated from the mass increment of filters relative to the volume of sampled air. Concentrations of metals and metalloids (Al, As, Cd, Co, Cr, Cu, Fe, Mn, Ni, Pb, Zn) were measured using inductively coupled plasma mass spectrometry. These data were used to calculate carcinogenic and non-carcinogenic risks.
RESULTS: No statistically significant differences were observed between the indoor environments during either the low-pollution (p = 0.287) or high-pollution (p = 0.966) season. However, concentrations differed significantly between the two seasons (p < 0.001). In the low-pollution season, PM2.5 levels ranged 5–31 μg/m3 (median, 16 μg/m3). In the high-pollution season, PM2.5 concentrations ranged 13–59 μg/m3 (median, 32 μg/m3). Non-carcinogenic risk assessment showed that respiratory effects (HIresp) exceeded neurological effects (HIneuro). In adults, non-carcinogenic risk was minimal or within acceptable ranges; in children, depending on exposure scenario, risks ranged from high (HIresp = 6.42) and moderate (HIresp 3.10–3.75; HIneuro 3.17–5.19) to acceptable. Carcinogenic risks for both adults and children across exposure scenarios remained within acceptable limits (total risk, 5.71 × 10–6 to 4.66 × 10–5).
CONCLUSION: The identified high and moderate levels of non-carcinogenic health risk for children necessitate the development of targeted intervention measures.
811-821
Implementing digital technologies in microbiological monitoring and antimicrobial resistance assessment in intensive care units
Abstract
BACKGROUND: Healthcare-associated infections remain a major challenge of modern medical practice, with multidrug-resistant strains representing the most clinically significant pathogens. A central problem is the widespread dissemination of Klebsiella pneumoniae in intensive care units. This prevalence is associated with the severe condition of patients, for whom infection with multidrug-resistant strains exacerbates the underlying disease, extends the duration of therapy, and results in a significant economic burden. Systematic microbiological monitoring and evaluation of the antimicrobial resistance of strains isolated from patient biological specimens are key elements of healthcare-associated infection control in inpatient healthcare settings.
AIM: This work aimed to perform a comparative analysis of the microbiological landscape and antimicrobial resistance patterns of multidrug-resistant isolates using modern digital technologies in the intensive care and cardiac intensive care units of two multidisciplinary hospitals in Saint Petersburg.
METHODS: A retrospective analysis was conducted using microbiological surveillance data from the intensive care units and cardiac intensive care units of two multidisciplinary hospitals in Saint Petersburg for 2024. The obtained data were processed using the analytical software WHONET and the online platform AMRCloud.
RESULTS: ESCAPE pathogens were the predominant microorganisms isolated from sputum and bronchoalveolar lavage in both intensive care units and cardiac intensive care units. A statistically significant higher level of resistance among these isolates was observed in intensive care units compared with cardiac intensive care units. To analyze the prevalence of ventilator-associated pneumonia, we calculated stratified epidemiological indicators. The results were consistent with the published data.
CONCLUSION: Regular microbiological monitoring is a key tool for controlling healthcare-associated pathogens and tracking their antimicrobial resistance in a hospital setting. This monitoring enables a timely response to shifts in the epidemiological situation, including changes in microbial profile, the emergence of new strain associations, and their resistance to antibacterial agents. Such work is inherently linked to the rapid analysis of large datasets, which necessitates the development of new digital technologies for integration into hospital information systems.
822-831