Yulia S. Sotnikova

Immunotherapy with the use of induced CAR-T cells is an effective method of cancer suppression in close to in vivo conditions. The question of the nature of metabolism of CAR-T cells in the conditions of fighting not against single cancer cells, but against tumor cells, remains relevant. Our studies have shown the metabolomic profile of mouse GD2-specific CAR-T cells upon contact with B78-21 melanoma tumor cells and upon exposure to B-21 melanoma 3D spheroid structures.

Despite ongoing efforts, limited understanding of the fundamental causes of atrial fibrillation (AF) continues to hinder progress in its diagnosis and treatment. Pathogenetic processes that determine the development of AF are closely related to cellular metabolism, in this regard, metabolomics is a promising direction for the search for new biomarkers, studying the metabolic mechanisms of AF, and identifying potential therapeutic targets. Material and methods. The open, crosssectional, retrospective, non-randomized parallel group study included data from 34 female and male patients diagnosed with coronary artery disease (CAD). The patients were divided into two groups: the first group consisted of patients with CAD and AF ( n = 17), the second ‒ of patients with CAD without AF ( n = 17). Metabolomic profiling was performed by high-performance liquid chromatography with tandem mass spectrometric detection on a triple quadrupole mass spectrometer. Results and discussion . In total, 56 metabolites were identified, the content of which in the blood plasma of the groups of patients with and without AF differed statistically significantly. Conclusions . The presented data indicate the involvement of a number of metabolites in energy, amino acid and lipid metabolism, as well as in the mechanisms of inflammation and fibrosis. These compounds play a significant role in the pathogenesis of AF and can be considered as potential biomarkers for the diagnosis and monitoring of the disease.

Microplastics, defined as particles up to 5 mm in size, present a significant environmental and health concern due to their ubiquity, capacity to accumulate in organisms, and potential to cause toxic effects, inflammation, and endocrine disruption. A major challenge in addressing this issue is the lack of a universal method for sample preparation and analysis across different environmental matrices. This study addresses this gap by applying a custom-developed method for isolating microplastics from freshwater, followed by a comparative analysis of their abundance using three techniques: spectral (μ-FTIR) and thermal (TGA and pyro-GC-MS). The study was conducted on water samples from the Ob River near Novosibirsk, a major industrial center in Siberia. Field processing entailed filtering 20 L water volumes through a polyamide fabric with a nominal 100 µm pore size. Subsequent characterization established that the entire population of detected particles fell within the 100 to 500 µm interval. The results revealed microplastic concentrations of 0–10,000 particles/m³ (μ-FTIR), 6–19 mg/m³ (TGA), and 0.47–2.96 mg/m³ (pyro-GC-MS). Critically, the data showed spatially variable contamination, with higher microplastic levels identified near industrial wastewater discharge stations and urban recreational areas.

Lung surfactant is a lipid–protein complex essential for maintaining alveolar stability by reducing surface tension. In surfactant‐deficient states such as pneumonia or acute respiratory distress syndrome, alveolar collapse and impaired gas exchange may occur. Exogenous supplementation of surfactant phospholipids has been proposed to improve lung function. In this work, we performed LC–MS/MS analysis of phosphatidylcholines from a commercially available Essentiale phospholipid preparation in bronchoalveolar lavage (BAL) fluid. The dynamics of BAL phosphatidylcholine levels in mice following intravenous and aerosol administration of Essentiale were investigated for the first time, revealing the time course and extent of pulmonary accumulation for each route. A 20‐min aerosol inhalation of Essentiale (≈3 mg/kg phospholipids) achieved BAL phosphatidylcholine concentrations comparable to those obtained with a 500 mg/kg intravenous dose. Repeated daily intravenous dosing caused a gradual increase in BAL phosphatidylcholine over 3–4 days, whereas prolonged aerosol exposure beyond 20 min did not further elevate BAL levels, likely due to uptake by alveolar cells. These findings highlight aerosol inhalation as a more efficient delivery method for surfactant phospholipids and suggest an optimal dosing regimen (≈ 3 mg/kg, 20 min) for adjunctive therapy in conditions associated with surfactant deficiency.

T Background. Lung cancer (LC) is still one of the leading problems of modern medicine. Currently, lung cancer diagnostic methods are mainly based on physical, biochemical and histopathologic examinations. Late diagnosis, high cost and unsuitability of traditional, though proven methods for screening in the population actualize the problem of developing a new method for early detection and improving the prognosis of lung cancer treatment. The results of our own study of metabolite content in the plasma of patients with non-small cell lung cancer (NSCLC) in comparison with patients without NSCLC are analyzed. Purpose of the study. To conduct a pilot study to search for potential metabolomic predictors of non-small cell lung cancer. Characterization of patients and methods of the study. The prospective non-randomized parallel-group method study included 8 patients with NSCLC (mean age 63.142 years) and 8 patients with long cardiovascular history (mean age 64.156 years) in routine clinical practice setting. The study was approved by the local ethical committee of SCB No. 1. All patients underwent a full range of investigations according to the current clinical recommendations. Additionally, we performed mass spectrometric detection of metabolites in MRM (multiple reaction monitoring) mode in the form of positive and negative ions using API 6500 QTRAP mass spectrometer (AB SCIEX, USA) equipped with electrospray ionization source. Statistical analysis methods. Chromatograms were processed using the Skyline program (Skyline version v23.1, https://skyline.gs.washington.edu). Results and Conclusion. In this work, 31 metabolites were identified in which the studied groups differed significantly according to the Mann-Whitney U-criterion (p-value<0.05); they are associated with energy and lipid metabolism, inflammation, angiogenesis and regulation of cell growth, and play a key role in the pathogenesis of lung cancer. In the future, the mentioned metabolites may serve as important biomarkers for the diagnosis and monitoring of the disease.

Increasing evidence on the adverse health impacts of microplastics (MPs) is available, but their associated risks to the well-being of humans and long-term impacts are poorly understood. An indicator of the remote effects of MPs may be their influence on the rate of aging. To assess the effects of MPs on the aging process, we used accelerated senescence OXYS rats that develop a complex of geriatric diseases. We prepared the polyethylene terephthalate MPs (2–6 microns in size) and in OXYS and Wistar (maternal strain) rats assessed the influence of chronic administration of MPs (10 or 100 mg/kg per day from age 1.5 to 3.5 months,) on the hematological and biochemical blood parameters, spatial learning, and memory. In addition, the effects of MPs on the development of cataracts and retinopathy, similar to age-related macular degeneration (AMD), in OXYS rats were assessed. We found that in the absence of significant changes in standard clinical blood parameters, chronic MP administration negatively affected the cognitive functions of both Wistar rats and OXYS rats. Additionally, a dose of 100 mg/kg MPs contributed to cataract and AMD progression in OXYS rats. Our results suggest that MPs may increase the rate of aging and, in the long term, lifespan.

The time spent on this new procedure is no more than 3 hours, which is 6 to 12 times faster than the most widely used methods. This approach makes it possible to obtain samples suitable for subsequent analysis by any analytical instrumental method.

Microplastics (MPs) in aquatic environments can be associated with various substances, including persistent organic pollutants, which add to the problem of plastic ecotoxicity. The abundance of 1–5 mm microplastics and concentrations of particle-adsorbed organochlorine pesticides (OCPs) and polychlorinated biphenyls (PCBs) in sandy sediments from three beaches in recreational areas along the upper Ob River in Western Siberia were assessed. MP pollution levels in the Ob River beach sands ranged from 24 ± 20.7 to 104 ± 46.2 items m⁻² or, in terms of mass concentration, from 0.26 ± 0.21 to 1.22 ± 0.39 mg m⁻². The average abundance of MP particles reached 0.67 ± 0.58 items kg⁻¹ or 8.22 ± 6.13 μg kg⁻¹ in the studied sediments. MP concentrations were significantly higher in number (p < 0.05) and mass (p < 0.01) at the riverbank site downstream of the Novosibirsk wastewater treatment plant (WWTP) outfall compared to these at the upstream and more distant beaches. Most MPs (70–100%) were represented by irregularly shaped fragments. The polymer composition of MPs varied between sites, with a general predominance of polyethylene (PE). The study revealed associations of MPs with PCBs and OCPs not previously detected in the riverbed and beach sediments, suggesting that these substances are circulating in the Ob River basin. Although MP concentrations were higher downstream of the WWTP, the maximum levels of particle-associated OCPs were observed in the beach sands of the site farthest from the urban agglomeration. The pesticides γ-HCH, 4,4-DDT, and 4,4-DDE were detected on MPs at relatively low concentrations. PCBs were more abundant in the studied samples, including 118 dioxin-like congener. The results obtained indicate that the Ob River is susceptible to plastic and persistent organic pollutant (POP) contamination and serve as a starting point for further studies and practical solutions to the problem.

An acute coronary event in the presence of SARS-CoV-2 infection has its own characteristics that affect the course of the disease and the choice of treatment methods. Due to the lack of data on this category of patients, it is necessary to look for ways to determine the risk of adverse outcomes of this condition, including the difficulties of risk stratification.   Aim: assessment of clinical and laboratory parameters and features of the clinical course in patients with ACS in combination with SARS-CoV-2 infection at the hospital stage. Construction of a prognostic model for the risk of death.  Materials and methods. The study included 225 patients admitted to the regional vascular center with a diagnosis of ACS and a verified diagnosis of SARS-CoV-2 infection. Initially, 120 general clinical, biochemical and instrumental parameters were assessed. The second stage involved analysis of plasma metabolites in 73 patients.   Results. A predictive model was constructed highlighting the eight most significant variables that correlate with in-hospital mortality in patients with ACS in combination with SARS-CoV-2: age, the presence of atrial fibrillation (except for that first detected in ACS), acute kidney injury, CKD above stage 2, severe and extremely severe course of SARS-CoV-2 infection, levels of ferritin, albumin and glycemia in the blood serum upon admission to the hospital. The present study identified new markers of mortality risk, such as C18 ceramide (d18:1/22:0) and ceramide (d18:1/24:0) levels.   Conclusions. The proposed approach to assessing the risk of nosocomial death in acute coronary syndrome in combination with SARS-CoV-2 infection has good prognostic accuracy and is easy to use.

Postoperative delirium (POD) is considered one of the most severe complications, resulting in impaired cognitive function, extended hospitalization, and higher treatment costs. The challenge of early POD diagnosis becomes particularly significant in cardiac surgery cases, as the incidence of this complication exceeds 50 % in certain patient categories. While it is known that neuroinflammation, neurotransmitter imbalances, disruptions in neuroendocrine regulation, and interneuronal connections contribute significantly to the development of POD, the molecular, genetic mechanisms of POD in cardiac surgery patients, along with potential metabolomic diagnostic markers, remain in adequately understood. In this study, blood plasma was collected from a group of patients over 65 years old after cardiac surgery involving artificial circulation. The collected samples were analyzed for sphingomyelin content and quantity using high-performance liquid chromatography coupled with mass spectrometry (HPLC-MS/MS) me thods. The analysis revealed four significantly different sphingomyelin contents in patients with POD compared to those who did not develop POD (control group). Employing gene network reconstruction, we perceived a set of 82 regulatory enzymes affiliated with the genetic coordination of the sphingolipid metabolism pathway. Within this set, 47 are assumed to be regulators of gene expression, governing the transcription of enzymes pivotal to the metabolic cascade. Complementing this, an additional assembly of 35 regulators are considered to be regulators of activity, degradation, and translocation dynamics of enzymes integral to the aforementioned pathway. Analysis of the overrepresentation of diseases with which these regulatory proteins are associated showed that the regulators can be categorized into two groups, associated with cardiovascular pathologies (CVP) and neuropsychiatric diseases (NPD), respectively. The regulators associated with CVP are expectedly related to the effects on myocardial tissue during surgery. It is hypothesized that dysfunction of NPD-associated regulators may specifically account for the development of POD after cardiac surgery. Thus, the identified regulatory genes may provide a basis for planning further experiments, in order to study disorders at the level of expression of these genes, as well as impaired function of proteins encoded by them in patients with POD. The identified significant sphingolipids can be considered as potential markers of POD.