Ekaterina A. Boeva

The objective was to investigate the nephroprotective effects of dalargin, a synthetic analog of leu-enkephalin, in a rat model of renal ischemia–reperfusion injury, and to evaluate its impact on the expression and phosphorylation of glycogen synthase kinase-3β (GSK-3β). Materials and methods . Acute kidney injury (AKI) was induced in Wistar rats by 60-minute warm renal ischemia combined with contralateral nephrectomy. Dalargin was administered intraperitoneally at doses of 1, 5, and 10 μg/kg. Serum creatinine and urea levels were measured. GSK-3β expression and phosphorylation were assessed by immunoblotting. Morphological changes in renal tissue were evaluated histologically. Results . Dalargin administration resulted in a dose-dependent attenuation of AKI severity, most pronounced at a dose of 10 μg/kg. This effect was associated with a statistically significant improvement in renal function parameters, increased levels of phosphorylated GSK-3β (pGSK-3β), and reduced histological signs of tubular necrosis. In the lowest-dose group (1 μg/kg), a trend toward worsened functional parameters was observed, possibly related to a survivor selection effect. Conclusion . The findings demonstrate a marked dose-dependent nephroprotective effect of dalargin in renal ischemia–reperfusion injury, associated with inhibition of GSK-3β activity. These results support further investigation of dalargin as a component of organ-protective strategies in critical care settings.

Introduction. The early detection of pressure ulcers remains a clinically significant challenge, especially in patients with limited mobility. Visual skin assessment has limited sensitivity to preclinical tissue changes, which drives interest in non-invasive instrumental diagnostic methods. Objective. To evaluate the diagnostic and prognostic significance of non-invasive instrumental methods for detecting early-stage pressure ulcers in adult patients. Material and methods. A systematic review was conducted in accordance with the PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) 2020 guidelines. A literature search was performed in the PubMed/MEDLINE, Cochrane Library, and eLIBRARY.RU databases for the period from 2015 to 2025. The review included diagnostic and prognostic studies involving adult patients that evaluated non-invasive methods. The risk of bias was assessed using the QUADAS-2 (Quality Assessment of Diagnostic Accuracy Studies – 2) and QUIPS (Quality In Prognosis Studies) tools. Results. Seventeen studies were included in the review. Quantitative synthesis (meta-analysis) was not performed due to pronounced clinical and methodological heterogeneity. Most diagnostic studies were characterized by a moderate-to-high risk of bias. All prognostic studies had a high risk of bias. Despite this, a number of studies demonstrated the ability of non-invasive methods to detect tissue changes before the clinical manifestation of a pressure ulcer. Conclusion . Non-invasive instrumental methods have the potential for the early detection of pressure ulcers and risk stratification; however, the existing body of evidence remains limited. Standardized measurement protocols and prospective studies with clearly defined outcomes are necessary for the implementation of these technologies into clinical practice.

Introduction/Objective: Dysfunction of the Neurovascular Unit (NVU) represents a common pathway of injury in ischemia-reperfusion and critical illness. Disruption of blood-brain barrier integrity, microcirculatory reperfusion heterogeneity, and neuroinflammation synergistically amplify secondary neural damage. In this context, attention is increasingly being directed toward interventions that stabilize the NVU as an integrated system rather than targeting neurons alone. This review aimed to summarize and critically appraise the evidence on the beneficial effects of argon in experimental models of ischemia–reperfusion and related critical scenarios, with emphasis on the hierarchy of evidence. Methods: A focused narrative review was conducted by searching major bibliographic databases through December 2025, followed by manual selection of relevant studies and citation tracking. The SANRA checklist was applied for internal quality control of the narrative review. Statements were structured according to level of evidence (“demonstrated,” “indirectly supported,” and “not demonstrated”) and linked to model type, therapeutic time windows, and outcome measures. A total of 110 references were included. Results: The strongest body of evidence concerns the neuroimmune compartment. Argon attenuates microglial activation and suppresses pro-inflammatory cascades, including inflammasomerelated signaling, thereby reducing pyroptotic markers. In the neuronal compartment, argon is associated with pro-survival shifts, including modulation of the Bcl-2 family balance, reduced caspase-3 activity, and partial preservation of mitochondrial membrane potential. By contrast, microcirculatory improvement is documented mainly at the level of integrated outcomes, such as perfusion, cerebral blood flow, and neurological performance. Discussion: However, the underlying cellular mechanisms involving endothelial cells, pericytes, and microthromboinflammation remain insufficiently characterized. Direct evidence regarding tight junction proteins, matrix metalloproteinases, and endothelial nitric oxide signaling under argon exposure is limited, indicating a clear asymmetry in mechanistic resolution across NVU compartments. Conclusion: Current evidence supports argon as a promising NVU-oriented neuroprotective modulator, with the strongest support for neuroimmune mechanisms. Evidence for barrierrelated and microcirculatory mechanisms remains limited and requires direct validation in future studies.

Introduction . Pressure injuries in intensive care unit (ICU) patients remain a significant clinical problem associated with high interobserver variability and substantial time burden for healthcare staff. The objective was to evaluate the accuracy and efficiency of the HosHelper mobile application for objective staging of positional skin injuries in immobile patients. Materials and methods . A prospective single-center study was conducted in 39 ICU patients with pressure injuries. Staging was performed using two approaches: routine visual assessment by medical staff and the HosHelper mobile application. The results were compared with a consensus assessment of three independent experts. Agreement, assessment time, and variability were analyzed. Results . Agreement between the application and expert evaluation reached 97.3%, whereas agreement between subjective assessment and experts was 82.1%. Use of the application significantly reduced assessment time (3.0 ± 1.1 vs 8.0 ± 1.4 min, p < 0.05) and decreased decision variability. Conclusions. Mobile-assisted staging of positional complications improves diagnostic objectivity and reduces staff workload, potentially enhancing prevention and monitoring of pressure injuries in ICU patients.

The relevance of studying the molecular mechanisms of ischemia–reperfusion brain injury is due to the ongoing need to identify therapeutic targets to improve neurologic outcomes following cardiac arrest. This study aims to identify early morphological and molecular changes in the rat brain in the post-resuscitation period after asphyxial cardiac arrest, as well as to assess the relationship of these changes with hemodynamic and acid–base status. Morphological analysis using immunohistochemistry (IHC) revealed an increase in the intensity of the IHC reaction to S-100β protein in astrocytes of the hippocampal CA1 region in rats 3 hours after resuscitation compared to sham-operated controls (p = 0.043). Acid–base disturbances were associated with an increase in the intensity of microglia marker Iba-1 staining in the hippocampal CA4 region (p = 0.015). A correlation was found between the intensity of the IHC reaction to PHD1 in cortical neurons and the values of mean arterial pressure (r = −0.699, p < 0.001), PaO2/FiO2 ratio (r = −0.580, p < 0.005), PaCO2 (r = 0.507, p = 0.014). The results of this hypothesis-generating study suggest a potential association between the oxygen-sensing protein PHD1 in cerebral cortical neurons and clinically relevant indicators of post-resuscitation severity after cardiac arrest. Further studies are needed to clarify the role of oxygen-sensing prolyl hydroxylases in the pathogenesis of brain injury in critical illness accompanied by impaired central hemodynamics and acid–base imbalance.

Background. Despite more than 10-year experience of simulation training In Russia, availability of human resources and equipment, potential of simulation-based educational technologies in training for anesthesiology and critical care residency programs is still unsystematic and insufficiently effective. Objective. To develop a unified practical training program for anesthesiology and critical care residency programs using simulation technologies. Material and methods. A group of experts in simulation training for anesthesiology and critical care conducted a literature review using the Kern methodology to identify problem skills and competencies and evaluate modern simulation training programs. A Delphi consensus assessment was used to identify educational needs. The program sections, topics, and types of lessons, as well as learning outcome assessment system, were developed taking into account existing national and international experience. Results. Analysis of Russian and international lawsuit databases and studies on simulation training in anesthesiology and intensive care allowed us to identify skills and competencies whose poor quality impacts patient safety. Using the Delphi method, we identified practical skills and competencies that should be taught using simulation technologies. These results formed the basis for developing educational needs and formulating learning objectives. The program sections were designed to acquire practical and non-technical skills. For the first time In Russian medical education, the program included introductory simulation course and critical situation training. A system of assessment tools was developed for use in ongoing and final assessment of learning outcomes. This system focuses on skills and competencies. A plan for the pilot implementation of the program for 2026—2028 was developed. Conclusion. For the first time In Russian medical education, a training program involving simulation technologies for residency was developed. Implementation of this program will improve professional training of future anesthesiologists and critical care physicians. Evaluating the implementation of the program is planned in 2027—2028.

Ischemic stroke remains one of the leading causes of mortality and long-term disability worldwide, and existing treatments are bounded by narrow therapeutic windows and low efficacy. Inert gases, particularly argon, have recently emerged as promising neuroprotectors capable of modulating the cellular response to ischemia. However, the analysis of their effects at the systemic, tissue, and cellular levels remains incomplete. The aim of the study was to provide an comprehensive assessment of the neuroprotective properties of argon in vitro and in vivo using the focal cerebral ischemia model in rats . Materials and methods. A two-stage experimental study was conducted, combining in vivo and in vitro approaches. In vivo, focal ischemic stroke was induced in rats using a model of photochemically initiated thrombosis. The animals with induced stroke were divided into two groups based on inhalation mixture composed of N₂ 70% / O₂ 30% (comparison group I + iN₂, n = 10) and Ar 70% / O₂ 30% (main group I + iAr, n = 10). Additionally, 3 groups were included in the experiment: sham-operated animals (SO, n = 6), subjected to sham surgery without stroke induction, and 2 groups of intact animals receiving three inhalations of studied gas mixtures: Int. + iN₂ , n = 7; Int. + iAr, n = 5. Neurological outcomes were studied in a longitudinal mode, followed by a quantitative assessment of the infarction volume based on MRI data, histological and immunohistochemical analyses (GFAP, Iba-1, S100b, caspase-3, von Willebrand factor, etc.), and quantification of marker proteins involved in the regulation of signaling pathways (Akt/GSK-3, Nrf2, NFκB, IL-1α, IL-6, caspase-3) using western blotting. In vitro cultures of neuronal (SH-SY5Y), glial (C6), and endothelial (Ea.Hy926) cells were incubated in an argon-oxygen medium for 24 hours. Functional studies of cultures included assessment of mitochondrial transmembrane potential and lysosomal activity using confocal microscopy. Results. In an in vivo experiment, argon significantly reduced the volume of damage according to MRI data (I + iN2 21.5 ± 5.9 mm³ vs I + iAr 12.5 ± 4.3 mm³, p = 0.0078), improved neurological recovery (I + N₂ and I + iAr group: on the 3[rd] (7.5 (4.2; 10.2) vs 10.0 (10.0; 12.0), p = 0.0015), 7[th] (8.0 (6.7; 9.2) vs 10.0 (9.0; 12.2), p = 0.038) and 14[th] days of the study (4.5 (2.7; 7.2) vs 12.0 (10.7; 12.2), p = 0.0008), It preserved significant neuronal density in the penumbra ( p = 0.001), and downregulated astroglia and microglia activation. In addition to a significant decrease in caspase-3 expression ( p = 0.002) and modulation of pro-inflammatory cytokines (Ila was significantly lower in the I + iAr group, p = 0.002), there was an apparent activation of cytoprotective signaling pathways (Akt ( p = 0.006) and Nrf2 ( p = 0.019)). In vitro , argon exposure increased the proportion of high-potential mitochondria in neuronal ( p = 0.01) and glial cells ( p < 0.0001), and significantly stimulated lysosomal activity in endothelial cells ( p = 0.0006). Conclusion. This comprehensive study demonstrates that argon has a pronounced neuroprotective effect in a model of ischemic brain damage, manifesting by reduction of ischemic lesion volume, improvement in neurological status, and modulation of key molecular and cellular mechanisms of damage. The results demonstrate that argon activates protective mechanisms both in vivo and vitro. Therefore, argon can be considered as a promising and safe candidate for further preclinical and clinical studies in the field of neuroprotective therapy.

Traumatic brain injury (TBI) remains one of the leading causes of disability, and current approaches to neuroprotection have limited efficacy. The inert gas krypton is considered a promising neuroprotective agent; however, data on its effects in TBI and on components of the neurovascular unit (NVU) are limited. Objective. To evaluate the neuroprotective potential of krypton in rats with traumatic brain injury (TBI) in vivo and in NVU cell cultures subjected to oxygen-glucose deprivation (OGD) in vitro . Materials and Methods. The study included 48 Wistar rats divided into 3 groups: SO (sham operated), TBI (N₂/O₂ 70/30 %), and TBI + iKr (Kr/O₂ 70/30 %). A model of controlled open brain contusion injury was used. On day 14, we assessed neurological deficits (limb placing test, LPT), the extent of brain injury (T2-weighted MRI slices), morphological changes (hematoxylin-eosin staining), and the expression of GFAP and Caspase-3 (fluorescent immunohistochemistry, IHC). IL-1β, IL-6, and TNF-α mRNA levels in the injury zone were determined by PCR. In vitro studies investigated the effect of krypton preconditioning (Kr/O₂ 79/21 %, 24 h) on the survival of neuronal (SH-SY5Y), glial (C6), and vascular endothelial (Ea.Hy926) cells during OGD (4–6 h). Results. A significant neurological deficit of 2.5 (2; 5.25) scores was determined by the TBI modeling accompanied by a large volume of brain damage of 33 (28; 39) mm³. Krypton inhalation led to a reduction in the lesion volume to 18 (15; 26) mm³ and accelerated the recovery of sensorimotor functions: starting on day 7, the indicators in the TBI + iKr group were statistically significantly better than in the TBI group, and by day 14, they approached the values of the SO (control) group. In the TBI + iKr group, IL-1β and TNF-α levels in the affected hemisphere were nearly 50% lower than in the TBI group, while remaining higher than in the SO group; changes in IL-6 levels were insignificant. Histologically, less significant cerebral edema, spongiosis, and neuronal degeneration were observed in the TBI + iKr group. Immunohistochemical analysis revealed a trend toward more pronounced reactive gliosis (GFAP) with no differences in Caspase-3. In vitro , krypton preconditioning under OGD conditions did not improve the survival of neuronal, glial, and endothelial cells. Conclusion. Krypton exerted significant neuroprotective effect in experimental TBI in rats, reducing neurological deficits, the extent of structural damage, and the severity of the inflammatory response. The absence of a protective effect in NVU cellular models underscores the essential role of systemic and intercellular interactions in the neuroprotective action of krypton and warrants further research into its mechanisms of action and dosing optimization.

Cardiac arrest remains one of the leading causes of death worldwide. Even with successful resuscitation, patient outcomes are often poor due to post-resuscitation syndrome, which includes cerebral hypoxia, myocardial dysfunction, microcirculatory disorders, coagulation abnormalities, and systemic inflammation. Argon, an inert noble gas, has neuroprotective and cardioprotective properties, making it a promising candidate for early post-resuscitation therapy. The aim of the study was to evaluate the organoprotective properties of an argon-oxygen mixture when inhaled in the early post-resuscitation period for 2 hours after asphyxial circulatory arrest in rats. Materials and methods. A prospective randomized controlled experimental study was conducted on male Wistar rats ( n = 43) using an asphyxial circulatory arrest model. The animals were divided into three groups: sham-operated (SO, n = 12), circulatory arrest with resuscitation (CAR, n = 13), and circulatory arrest with resuscitation and two-hour inhalation of a 70%/30% argon-oxygen mixture in the post-resuscitation period (CAR + iAr, n = 18). Hemodynamics, microcirculation, blood gas composition, coagulation (low-frequency piezothromboelastography), neurological status, and biomarkers of organ damage were evaluated. Beclin-1 and caspase-3 expression was analyzed immunohistochemically. Results. Argon inhalation did not have a significant effect on systemic hemodynamics, but it was accompanied by improved tissue oxygenation and metabolism: a decrease in blood lactate ( p = 0.043), an increase in the p/F oxygenation index ( p = 0.001), and stabilization of microcirculation variability (Kv, σ). Statistically significantly increased expression of the Beclin-1 protein in the lungs, myocardium, and hippocampus reflected activation of autophagy. In the CAR + iAr group, there was an improvement in neurological status compared to CAR ( p = 0.02), a decrease in serum neuron-specific enolase ( p = 0.011), and a decrease in the number of caspase-3-positive cells ( p = 0.011), indicating a reduction in apoptosis and damage to the nervous tissue. Argon had a moderate anticoagulant and antiplatelet effect (coagulation drive intensity — CDI, and maximum clot firmness-MCF reduction), while maintaining normal processes of clot retraction and lysis. The electrophysiological parameters of the heart (QRS, QTc) varied within the physiological range, indicating the absence of pro-arrhythmic effects in argon. Conclusion. Early inhalation of argon-oxygen mixture after circulatory arrest has a multisystem protective effect: improves oxygenation and microcirculation, promotes activation of autophagy mechanisms in vital organs, reduces the severity of neuronal damage, and modulates blood clotting in some measure. Argon can be considered a promising therapeutic agent for post-resuscitation syndrome. Further clarification is needed to assess argon’s molecular mechanisms of action and long-term outcomes after its use.