Siberian State Medical University, the Ministry of Healthcare of the Russian Federation
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Effects of metformin on ceramide production in local fat depots in patients with coronary artery disease
Aim. To evaluate the effects of metformin on the expression level of ceramide (Cer) synthesis enzyme genes, and on the total content and spectrum of ceramides in local fat depots in patients with coronary heart disease (CHD). Materials and methods. The study included 41 patients with CHD, who were scheduled to undergo coronary artery bypass graft. Samples of subcutaneous, epicardial, and perivascular adipose tissue (SAT, EAT, and PVAT) were obtained during surgery, adipose tissue adipocytes were isolated and cultured for 24 hours with the addition of metformin (Sigma-Aldrich, USA) at concentrations of 1 and 10 mmol/l. The expression characteristics of de novo ceramide synthesis enzymes were assessed by quantitative polymerase chain reaction on a ViiA 7 amplifier (Applied Biosystems, USA). The total content and spectrum of Cer were determined by high-performance liquid chromatography with mass spectrometry (HPLC-MS/MS). Statistical processing of the results was performed using the STATISTICA 12 software package. Results. Metformin at a concentration of 1 mmol/l statistically significantly decreased the gene expression of the enzymes serine palmitoyltransferase-1 (SPTLC1) in SAT, EAT and PVAT, ceramide synthase-2 (CERS2) in EAT and SAT, ceramide synthase-4 (CERS4) in EAT and PVAT, and increased dihydroceramide desaturase (DEGS1) in EAT and SAT. Metformin at a concentration of 10 mmol/l decreased the level of SPTLC1 and CERS2 mRNA in EAT, CERS4 in EAT and PVAT. A significant decrease in the content of Cer d18:1/16:0 in EAT at a metformin concentration of 1 mmol/l, and Cer d18:1/18:0 in EAT and PVAT, Cer d18:1/20:0 in SAT and EAT at concentrations of 1 and 10 mmol/l was revealed. Conclusion. Thus, the potential ability of metformin to inhibit de novo ceramide synthesis in isolated SAT, EAT and PVAT adipocytes and to reduce the content of ceramides associated with adverse cardiovascular events in fat cells was demonstrated in in vitro experiments.
Morphological changes in cortical neurons and glia of rats in the context of global cerebral ischemia – reperfusion injury and its treatment with p-tyrosol
Aim. To investigate morphological alterations in neurons and glial cells in the cerebral cortex using a rat model of total transient global cerebral ischemia (GCI) and to evaluate the neuroprotective effects of p-tyrosol. Materials and methods. Experiments were performed on Wistar rats (n = 30), randomly divided into three groups: sham-operated, GCI control, and GCI with p-tyrosol treatment. The glioneuronal elements of the cerebral cortex were analyzed by light and transmission electron microscopy combined with a quantitative morphometric assessment. Results. In the GCI group, a significant reduction in neuron density was observed. Surviving neurons showed a marked decrease in the relative volume of membrane-bound organelles, accompanied by an increase in lipofuscin, lysosomes, and vacuoles. Administration of p-tyrosol after GCI enhanced neuronal survival. Conclusion. For the first time in this rat model of GCI, structural and ultrastructural changes of cortical neurons and glial cells in rats were characterized, confirming the validity of the model. Neuroprotective effects of p-tyrosol in the context of GCI were demonstrated at both the light-microscopic and ultrastructural levels.
Mathematical modeling of the intrarenal arterial bed structure using regression models and a graph neural network
The aim was to develop models for numerical modeling of the diameters and lengths of bifurcation segments, structural units of the intrarenal arterial bed (IAB). Materials and methods. The study is based on previously obtained morphometric data on the structure of 9,642 arterial bifurcations (AB) of 60 corrosion casts of the IAB. AB is a section of the IAB consisting of a proximal arterial segment (AS) (D), two distal AS (with a larger (dmax) and smaller (dmin) internal diameter) and a branching point. Regression models were used for numerical modeling of the AS diameters, while a graph attention network (GAT) was used for the lengths of AS. Results. The developed models demonstrate high prediction accuracy: for AS diameters with a larger value (dmax), the training set reached an R2 value of 0.89, for AS with a smaller value (dmin) – R2 = 0.8. For the length of the AS with a larger diameter, the training set reached an R2 value of 0.75, and the test set reached an R2 value of 0.74; for the length of the AS with a smaller diameter, the training set reached an R2 value of 0.77, and the test set reached an R2 value of 0.73. Conclusion. The proposed models can be used for numerical modeling of the IAB structure and assessment of the adequacy of renal blood supply.
Spontaneous neutrophil extracellular trap formation during pollinosis exacerbation
Aim. To study the morphological structure and functional activity of neutrophil extracellular traps in patients with seasonal allergic rhinitis during the exacerbation period. Materials and methods. The study included 12 patients with seasonal allergic rhinitis during the exacerbation period. We studied the morphological structure and functional activity of neutrophil extracellular traps (NET) in pollinosis patients. Fluorescence microscopy with SYBR Green dye was used to visualize NETs. Results. The study of neutrophils from allergic patients during the exacerbation period showed spontaneous NETs formation in the morphological form of neutrophil networks. The number of NETs during 1 hour of incubation is 10 [8.3–14]%, and their size is 28 [17.5–35] μm. Culturing neutrophils from allergic patients for 2 hours does not increase the number of NETs, but the size of NETs doubles, and 10% of NETs form as single threads and fibers. Neutrophil networks have a high functional activity. Conclusion. The results specify that during the exacerbation of seasonal allergic rhinitis, there is an NET formation similar to that observed during infectious inflammation, which is combined with high functional activity of neutrophil networks.
Morphological features of mitochondria isolated from tumor and apparently healthy tissue of the rectum in patients depending on the presence of metastases
Aim. To examine the ultrastructural characteristics of mitochondria isolated from rectal adenocarcinoma tissue and apparently healthy tissue along the tumor resection line in patients of both sexes, depending on the presence or absence of metastases. Materials and methods. The study encompassed the analysis of 28 patients diagnosed with rectal cancer, classified as T2–3N0M0 and T2–3N1–3M1, with tumor differentiation grade G2. Mitochondria were isolated from tumor and intestinal tissue cells via differential centrifugation. The mitochondrial suspension was then placed in a fixative solution containing formaldehyde and glutaraldehyde, followed by immersion in pure Epon-812 resin (SPI Inc., USA). The resin was allowed to cure for a period of 72 hours at a temperature of 70° C. Standard methodologies were employed to prepare the sections, which were then examined using a Jeol JEM-1011 electron microscope (JEOL Inc., Japan). The mitochondrial perimeter on images obtained by electron microscopy was determined using the Fiji program. Results. A comprehensive ultrastructural study and statistical analysis of the perimeter size of mitochondria isolated from rectal adenocarcinoma in patients of both sexes were conducted. The results indicated that there were no statistically significant intergroup differences in mitochondrial size, categorized as conditionally small (0–1 μm), medium (1–2 μm), and large (>2 μm), depending on the presence or absence of metastases. In contrast to the tumor tissue, in apparently healthy tissue along the rectal resection line, the proportion of mitochondria with a perimeter of ˃ 2 μm, characterized by the most pronounced dysfunction, decreased by 3.6 times in women and by 4.8 times in men without metastases compared to the indicators in all patients with metastases (p < 0.05). Conclusion. The significance of differences in the perimeter dimensions of mitochondria isolated from apparently healthy tissue at the resection line of rectal adenocarcinoma, regardless of gender differences in patients, indicated the possibility of a morphofunctional relationship between processes occurring at the ultrastructural mitochondrial level and metastasis of rectal cancer.
The role of systemic inflammatory indices in predicting carotid atherosclerosis in patients with rheumatoid arthritis
Aim. To determine the prognostic significance of systemic inflammatory indices for the development of carotid artery (CA) atherosclerosis in patients with rheumatoid arthritis (RA). Materials and methods. A single-center, observational, cross-sectional study was conducted, which included 52 male and female patients with RA. The average age of the study participants was 59.5 ± 6.7 years. All patients underwent carotid duplex ultrasound. The intima-media thickness was recorded at ≥ 0.9 mm. A hemodynamically significant atherosclerotic plaque (AP) was considered to be a CA thickening of more than 50% compared to adjacent tissues. Based on the general blood test data, the systemic inflammatory response index (SIRI), the aggregate index of systemic inflammation (AISI), the systemic immune-inflammation index (SII), the neutrophil-lymphocyte ratio (NLR), the lymphocyte-monocyte ratio (LMR), the platelet-lymphocyte ratio (PLR), and the Reys leukocyte index of intoxication were calculated. Binary logistic regression was used to develop a prognostic model. Results. Based on the results of the carotid duplex ultrasound, the patients were divided into 2 groups: 32 patients (61.5%) with the presence of AP in the CA and 20 patients (38.5%) without AP. Patients with AP in the CA had higher values of NLR, SII, SIRI, and the Reys leukocyte index of intoxication. During the study, threshold values for these indices were determined, and a prognostic model for the probability of developing atherosclerosis of the CA in patients with RA was developed, in which the predictors were the values of the Reys index, SIRI, low density lipoproteins, and age. Conclusion. In RA, high activity of systemic inflammation is associated with the development of atherosclerotic arterial lesions, which should be taken into account when determining the tactics of managing these patients.
Constitutional and morphological predisposition to suicidal behavior in schizophrenia
Aim. To study the relationship of constitutional and morphological features of patients with schizophrenia with suicidal behavior. Materials and methods. We examined 215 patients with schizophrenia. Information about the age of the patients, the age of manifestation and duration of the disease, and the history of suicide attempts was acquired through structured clinical interviews and examination of medical records. Additionally, the Beck Hopelessness Inventory was used. The anthropometric examination was carried out according to V.V. Bunak’s method, modified by V.P. Chitetsov. Constitutional and morphological body types and somatic sexual differentiation were determined based on the calculation of the Rees – Eysenck index and the Tanner index. Results. The χ2 test revealed significant differences in the distribution frequencies of the main constitutional and morphological types between the groups of patients with and without suicide attempts (p = 0.033). Following a pairwise comparison, significant differences were found only in the frequency of asthenic constitutional and morphological type (p = 0.018). Also, when comparing the frequencies of the distribution of constitutional and morphological types between patients with and without hopelessness, significant differences were found (p = 0.035). In the group of patients with hopelessness, the asthenic constitutional and morphological type prevailed (p = 0.045). The network analysis made it possible to identify two independent suicide risk factors in patients with schizophrenia: clinical and anthropometric. Conclusion. The results of the study clearly confirm the importance of the constitution as an independent risk factor for suicidal behavior in patients with schizophrenia. The data obtained open up prospects for early detection of predisposition to suicidal thoughts and actions in this group of patients.
Content of bone morphogenetic proteins in blood plasma of rats with metabolic syndrome during mandibular defect restoration
The aim was to study the concentration of bone morphogenetic proteins-2 (BMP) and -7 in the blood plasma of rats with metabolic syndrome during reparative osteogenesis in mandibular defect. Materials and methods. The experiments were carried out on male Wistar rats, which were divided into 4 groups: 1) naïve; 2) control (with mandibular defect); 3) metabolic syndrome; 4) experimental (with metabolic syndrome and mandibular defect). Metabolic syndrome was simulated by replacing standard feed with a high-fat and highcarbohydrate diet. The development of metabolic syndrome was confirmed by changes in body weight, glucose and triacylglycerides concentrations in blood plasma. The mandibular defect was formed in rats according to the method proposed by Grigoryan et al. The content of BMP-2 and BMP-7 in blood plasma was determined by the enzyme-linked immunoassay on days 7, 14, 21, and 28 after the surgery. We calculated the median and the interquartile range Me [Q1; Q3] and applied the Mann – Whitney U-test and the Bonferroni correction. Differences in indicators were considered significant at p < 0.025. Results. A significant increase in the content of the studied proteins in the blood plasma was determined in the group metabolic syndrome compared to the naïve group. BMP-2 and BMP-7 concentration in rats of the control group was higher throughout the experiment compared to the naïve group (p < 0.025). In the experimental group, a decrease in the concentration of BMP-2 (on days 7, 14, and 28) and BMP-7 (on days 7–28) was found compared to the control group (p < 0.025). An increase in the concentration of BMP-2 and BMP-7 was detected in the experimental group compared to the metabolic syndrome group (p < 0.025) on day 7 and on days 7–14, respectively. Conclusion. A significant decrease in BMP-2 and BMP-7 concentration in the blood plasma was found in rats with metabolic syndrome during mandibular reparative osteogenesis compared to animals without metabolic disorders.
Efficacy and safety of amino acid-based formulas in the management of infants with cow’s milk protein allergy: an open-label prospective controlled study
Aim. To determine the efficacy and safety of long-term use of an amino acid-based formula in children with cow›s milk protein allergy (CMPA) and moderate to severe atopic dermatitis (AD). Materials and methods. The study included 60 children under 12 months of age with CMPA presenting with cutaneous symptoms (moderate or severe AD according to the oSCORAD) and/or gastrointestinal symptoms. Prior to the study, all patients were prescribed an extensively hydrolyzed formula (EHF) for 4 weeks. Patients with no or incomplete response to EHF (n = 30) were assigned to Group 1, receiving an amino acid-based formula (AAF) for 12 months. The 30 patients who showed a positive response to EHF were assigned to Group 2. Results. Children in Group 1 showed greater gains in weight and height during the first 6 months compared to children in Group 2 (p < 0.001). The resolution of gastrointestinal symptoms in children receiving AAF was observed within 14 days along with an improvement in the clinical picture of AD within 3–5 days. Also, both groups showed a decrease in oSCORAD and EASI scores; however, children receiving AAF had a significantly smaller number of exacerbations (p = 0.041) and a lower impact of dermatosis on daily activities (p = 0.002). After 6 months of therapy, 53.3% of children in Group 1 developed tolerance to cow’s milk proteins, compared to only 23.3% in Group 2 (p = 0.017). After 2 years of follow-up, tolerance was noted in all children who received AAF versus 87.7% of those fed with EHF. Conclusion. The use of AAF in children with CMPA is an effective dietary management method that leads to faster resolution of gastrointestinal symptoms, improvement in the course of atopic dermatitis, and prolongation of its remission. It shortens the period for tolerance development, has a positive effect on the child›s physical development, and contributes to a significant improvement in the quality of life of both patients and their parents.
The influence of preanalytical factors on the algorithm of multiplex spectroscopy of placental samples
Aim. To evaluate the effect of preanalytical processing of placental samples on the results of Raman spectroscopy. Materials and methods. Thirty placental samples were prospectively studied. The samples were examined using the InSpectr M spectrometer at three stages of preanalytical processing of the material: native tissue, after fixation in formalin, after deparaffinization of the section. Statistical analysis included descriptive statistics, the Shapiro – Wilk test, the Friedman test with the post-hoc analysis, and the Spearman’s rank correlation. Results. The analysis of the samples revealed 33 Raman peaks (415–2,915 cm–1), most of which were distributed abnormally (Shapiro – Wilk test, p < 0.05). The Friedman test with the Durbin – Conover post-hoc analysis revealed a group of stable analytes: 19 analytes retained intensity after fixation, 6 – after deparaffinization, and 10 – at all processing stages. The Spearman’s rank correlation revealed selective relationships between processing stages for individual analytes (890; 1,117; 1,204; 753; 830, and 2,225 cm–1). Conclusion. The study revealed a significant effect of preanalytical sample processing on the spectral characteristics of placental tissue, the prospects for the clinical use of Raman spectroscopy, and the need to develop standardized protocols.
The potential application of the random forest method to explore the association between microRNAs and tissue and molecular genetic biomarkers of breast cancer
Aim. Exploring the potential of using a random forest method (RFM) to identify associations between serum levels of microRNAs miR-181a and miR-25 and the expression of the following markers: E-cadherin (CDH1), type II collagen (CII), integrin beta-1 (ITGB1), cyclin D1 (CCND1), and T-lymphocyte costimulator (CD86), as well as their relationship with clinically relevant molecular genetic markers (ER, PR, HER2, Ki-67) in patients with breast cancer (BC). Materials and methods. We recruited 44 BC patients with invasive ductal carcinoma who had not received neoadjuvant treatment. Serum levels of miR-181a and miR-25 were measured using digital droplet PCR, and the expression of CDH1, CII, ITGB1, CCND1, CD86, ER, PR, HER2, and Ki-67 in tumor tissue samples was assessed via immunohistochemistry. Spearman’s correlation analysis and the RFM were applied to assess associations between variables. Results. Spearman’s correlation analysis did not reveal any significant linear relationships between the studied parameters (p > 0.05). However, the RFM identified nonlinear associations: for miR-181a, the optimal predictive model included CDH1 and CCND1 (MAE = 4.267); for miR-25, ITGB1 and CCND1 (MAE = 16.255). Among clinical and pathological characteristics, statistically significant positive correlations were found between CII and ER (r = 0.498; p = 0.001) and PR (r = 0.354; p = 0.018). The RFM models demonstrated the highest accuracy in predicting the HER2 status (82.6%) when using a combination of ITGB1, miR-181a, and CDH1. Conclusion. The RFM revealed complex nonlinear associations between microRNAs and tissue markers of tumor progression that were not detected by conventional statistical methods. These findings are exploratory in nature and provide a foundation for further research aimed at validating these biomarkers and elucidating their role in the pathogenesis of various breast cancer subtypes.
Metabolic reaction of cells to changes in the physical and chemical state of the nitinol surface induced by ultraviolet laser radiation with a wavelength of 266 nm
Aim. MTT (methylthiazolyldiphenyl-tetrazolium bromide) viability assessment of the in vitro cellular response to changes in the physicochemical properties (zeta potential, wettability, topography) of the nitinol surface after treatment with ultraviolet (UV) laser radiation (UV-LR) with a wavelength of 266 nm. Materials and methods. The MCF-7 cell culture was incubated with nitinol-based alloy plates for 24 hours, before and after exposure to UV light (wavelength 266 nm, energy density 0.1 J/cm²) with a Q-smart 850 pulsed Nd:YAG laser. The samples were then analyzed for roughness (Ra) (GOST 2789-73) and surface contact angle with water. Zeta (ζ) potentials were also measured for both nitinol-based alloy substrates (SurPASS 3) and MCF-7 cells (Litesizer DLS 500). Metabolic activity of the cells was assessed using the MTT test, as recommended by GOST ISO 10993-5-2023 for the in vitro assessment of the cytotoxicity of medical materials and devices. Bioinformatics in silico analysis of intracellular signaling and metabolic pathways was conducted using the WikiPathways database. Results. Surface modification caused by UV-LR significantly reduced the toxic response (decrease in metabolic activity) of MCF-7 cells to the nitinol-based alloy substrate. UV-LR did not affect the zeta potential (±10 mV from the isoelectric point), but it significantly decreased the water contact angle (from 75 to 8.7°) and increased the Ra index of surface roughness (from 71.5 nm to 93.9 nm). In silico mechanotransduction analysis revealed that the roughness and hydrophilicity/hydrophobicity of nitinol can independently induce gene expression in MCF-7 cells, as well as through cross-talking molecular mechanisms. At the same time, several signaling pathways (WP5504, WP3680, WP5477, WP3941, WP5046, and WP2435) were found to be close to those involved in the reduction of the MTT reagent, which is used as a marker for the cell death program induced by metabolic imbalance in MCF-7 cells. Conclusion. UV-LR promotes an increase in hydrophilicity and/or nanoroughness of the nitinol-based alloy surface, but it does not affect the zeta potential. This may initiate a cascade of molecular mechanisms regulating cellular and tissue responses to implanted materials. These events can include inflammation, hemostasis activation, angiospasm, vessel regeneration, and metabolic activity of target cells.
Computer simulation of xanthotoxin interaction with caspase 3
Aim. To perform computer modeling and evaluate the interactions between caspase 3 and xanthotoxin. Materials and methods. The structures of caspase 3 and xanthotoxin were extracted from the PDB protein database (ID 2J31) and the PubChem chemical compounds and mixtures database (ID 4114), respectively. PyMOL v. 2.5 was used to prepare the caspase 3 structure for docking, and OpenBabel was used to convert xanthotoxin to .pdb format. Molecular docking was performed in AutoDock Vina. Molecular dynamics was performed using GROMACS 2023.3. The CHARMM 36 force field was used to generate the protein topology, and the CHARMM General Force Field (CGenFF) server was used for the ligand topology. Xmgrace and PyMOL were used to analyze the results. Results. Molecular docking of caspase 3 and xanthotoxin resulted in a stable complex with binding energy of -4.83 kcal/mol. The amino acid residues of caspase 3 involved in intermolecular interaction were identified: tyrosine 195 (TYR195), valine 266 (VAL266), lysine 137 (LYS137). The results of the molecular dynamics simulation confirmed the stability of the complex obtained as a result of docking. Conclusion. The data obtained indicate the possible role of the studied furocoumarin in the implementation of programmed cell death and can be used for further experimental studies.
Assessment of obesity prevalence and associated factors in the russian federation based on the 2024 rosstat sample survey data
Aim. To assess the prevalence of obesity and identify the factors associated with it among the adult population in the Russian Federation in order to determine the main directions for the development of measures for obesity prevention. Materials and methods. We carried out a secondary analysis of the data from the selective monitoring of the population health status by the Federal State Statistics Service for 2024. The study included data from 95,887 respondents from all regions of the Russian Federation. Descriptive statistics, χ2 test, Mann – Whitney test, Kruskal–Wallis test, and multiple logistic regression analysis were used for statistical analysis. Results. The prevalence of obesity among the adult population of the Russian Federation was 23.7% (class 1 – 17.9%, class 2 – 4.7%, and class 3 – 1.6%). Significant regional differences in the prevalence of obesity were revealed: from 6.6% in the Chukotka Autonomous Okrug to 34.3% in the Jewish Autonomous Oblast. The proportion of obese people was significantly higher among women (27.2% vs. 20.4% among men), rural residents (27.9% vs. 22.7% among urban residents), and respondents with low socioeconomic status. Multiple regression analysis revealed the most significant risk factors for obesity: lack of accessible sports infrastructure in the respondents’ area of residence (odds ratio (OR) = 2.71; 95% confidence interval (95% CI): 1.608–4.471), retirement status (OR = 1.63; 95% CI: 1.548–1.707), low income (OR = 1.60; 95% CI: 1.014–2.477), and low awareness of balanced nutrition (OR = 1.44; 95% CI: 1.243–1.659). Conclusion. Based on the results of the study, key areas for the development of measures for the prevention of obesity have been formulated: creating an environment that supports a healthy lifestyle; improving public health literacy; developing preventive healthcare; as well as developing and implementing measures taking into account regional specifics and the needs of various socio-demographic groups.
Cytomegalovirus infection activity as a predictor of adverse clinical events in chronic heart failure
Aim. To evaluate the impact of cytomegalovirus (CMV) infection on the course of chronic heart failure (CHF) over a 24-month prospective follow-up. Material and methods. The study included patients (n = 151) hospitalized due to CHF decompensation. Based on a follow-up, they were divided into groups with favorable and adverse CHF course, underlying pathology, and their complications. The adverse CHF course group included patients who experienced at least one of the following events during the 24-month follow-up period: 1) hospitalization for CHF decompensation; 2) adverse clinical events (cardiovascular death, nonfatal myocardial infarction or acute cerebrovascular accident, and pulmonary embolism); 3) any deterioration in CHF class; 4) a decrease in left ventricular ejection fraction (LVEF) by more than 10% from baseline. Plasma CMV DNA levels were assessed at baseline and after 12 and 24 months of followup. To identify predictors of the development of adverse cardiovascular events, ROC analysis was used with the construction of characteristic curves and the calculation of the area under the curve (AUC). Results. In patients with an adverse CHF course, CMV DNA levels at study inclusion were significantly higher (p < 0.001) compared to those with a favorable CHF course 2,232.0 copies/ml [1,687.0; 2,765.0] and 1,245 copies/ml [991.3; 1,592.0], respectively. The CMV DNA blood plasma level showed a direct correlation with CHF FC (r = 0.66; p = 0.001) and left ventricular end-diastolic dimension (r = 0.53; p = 0.01), while showing a inverse correlation with LVEF (r = –0.49; p = 0.001). The CMV DNA level greater than 1,687 copies/ml predicts adverse cardiovascular events (sensitivity 67%, specificity 81%, AUC = 0.763; p < 0.001) and death (sensitivity 68% and specificity 92%, AUC = 0.844, p < 0.001) in CHF patients over 24 months. Conclusion. To stratify the risk of developing adverse cardiovascular events during a 24-month follow-up period after CHF decompensation, it is advisable to determine the concentration of cytomegalovirus DNA in the blood of patients with coronary artery disease.
Molecular and genetic parameters of prognosis and new strategies for the treatment of peritoneal carcinomatosis in gastric cancer
Despite advances in modern oncology, in Russia, 36% of gastric cancers are detected at an advanced stage, with a one-year mortality rate of 39.6%. One of the most common causes of death from gastric cancer is peritoneal carcinomatosis. Synchronous peritoneal carcinomatosis is diagnosed in 18–26% of cases. Metachronous carcinomatosis occurs in 7–39% of patients 8.5–26 months after the primary tumor is removed. To date, there are no effective treatments for peritoneal carcinomatosis. Tumors accompanied by peritoneal carcinomatosis are often resistant to systemic chemotherapy. Cytoreductive surgeries and intraperitoneal chemotherapy are not always possible or successful for all patients. This review focuses on analyzing the molecular and genetic mechanisms of peritoneal carcinomatosis in gastric cancer and presents an original hypothesis suggesting that peritoneal carcinomatosis occurs when tumor cells acquire the ability to autonomously exist in a matrix-independent state in the ascitic fluid without undergoing apoptosis (anoeucsis). Using the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, 10,025 scientific papers were identified, of which 228 English-language and 323 Russian-language publications met the analysis criteria. Twenty-nine articles (including four Russian-language ones) relevant to the topic of this review were included in the review. It is assumed that the identification of key molecules associated with the matrixindependent existence of tumor cells could serve as the basis for the development of technologies for predicting peritoneal carcinomatosis, as well as for the development of new targeted therapy for metastatic gastric cancer.
Multimodal magnetic resonance imaging of the brain at different stages of rehabilitation after ischemic stroke
Stroke is an important medical and social problem in the world and in the Russian Federation, which is due to high rates of morbidity, mortality, and disability. The basis for the development of innovative approaches to the accelerated rehabilitation of individuals after an ischemic stroke is the study of neuroplasticity using modern neuroimaging methods, such as multimodal magnetic resonance imaging (MRI). The present literature review describes diagnostic capabilities of different multimodal MRI modalities, such as functional MRI (fMRI), ASL MR perfusion, and diffusion tensor MRI, including their advantages and drawbacks in assessing rehabilitation potential of patients after ischemic stroke. These MRI modalities can be successfully utilized to study the mechanisms of neuroplasticity and identify reliable markers of a response to therapy in context of rehabilitation measures in stroke patients. It was shown that broad implementation of multimodal MRI in clinical practice is hindered by a lack of profound knowledge about its diagnostic capabilities in certain clinical settings, complexity of its use, and insufficient evidence base.
Modern aspects of separate mechanisms of sepsis pathogenesis
The objective of the review is to analyze the continuously developing and changing ideas about the numerous interrelated mechanisms of sepsis pathogenesis, new research directions and potential approaches to treatment that are formed on their basis. A search was conducted using keywords in the PubMed database of relevant scientific publications for the period after the Third International Consensus Definition of Sepsis and Septic Shock (Sepsis-3). The review considers modern concepts of the main pathophysiological mechanisms of sepsis development, which remains a pressing health problem. The data accumulated to date on various pathophysiological mechanisms of sepsis reflect the complexity of its pathogenesis, caused by the development and coexistence of a large number of diverse pathological reactions with wide overlap and interaction of various signaling cellular pathways responsible for both cell survival and death. In this case, the outcome of the process is determined by the delicate balance of developing reactions, in particular the balance between activation of the immune response and immunosuppression. New research directions into the pathogenesis of sepsis focus not only on the mechanisms of modulation of the immune system activity, but also on the study of a wide range of pathophysiological processes associated with the development of multiple organ failure syndrome. Accordingly, there is a search for new therapeutic strategies, and with the recognition of sepsis as a heterogeneous syndrome, a transition to more personalized approaches in its treatment.
The role of dyslipidemia and obesity in the pathogenesis of osteonecrosis of the femoral head
The review focuses on current concepts of the role of obesity, the chronic systemic inflammation it induces, and lipid metabolism disorders in the pathogenesis of osteonecrosis of the femoral head (ONFH) in order to substantiate new approaches to its prevention and treatment. This review analyzes modern fundamental and clinical studies focusing on the relationship between metabolic disorders, chronic inflammation, and osteonecrosis. Specifically, we examine research investigating the molecular mechanisms of adipose tissue dysfunction, lipotoxicity, oxidative stress, and their impact on bone tissue homeostasis. The analysis established that obesity acts as a systemic risk factor for ONFH development, functioning not merely as a source of mechanical load but also as an initiator of a pathogenic cascade. Dysfunctional adipose tissue leads to chronic low-grade systemic inflammation and oxidative stress. Together, these factors provoke endothelial dysfunction, impair perfusion of the femoral head bone tissue, and induce lipotoxicity in the bone marrow. Consequently, at the local level, this cascade suppresses osteogenesis, simultaneously enhances bone resorption, and triggers osteocyte apoptosis. Systemic metabolic and inflammatory disruptions initiated by obesity underlie impaired bone remodeling, ischemia, and necrosis of the femoral head subchondral bone. Therefore, the correction of body weight and associated metabolic disorders should be considered an integral part of a comprehensive strategy for treating ONFH and preventing its progression. This integrated approach may improve the outcomes of joint-preserving interventions and delay the need for total hip arthroplasty in young patients.
Chronic kidney disease registries as a tool for monitoring, diagnosis, and quality improvement in medical care
Chronic kidney disease (CKD) is a leading cause of morbidity and mortality worldwide. CKD registries serve as an effective tool for the systematic collection and analysis of data, facilitating early detection, monitoring, and improvement in the quality of medical care. This lectute presents international and Russian experience in using CKD registries, analyzing their structure, variables, and data sources. Particular attention is paid to the organizational and methodological aspects of implementing CKD registries at the regional level. The results of the analysis make it possible to identify key directions for the development and implementation of regional registries. Their maintenance will contribute to increasing the effectiveness of follow-up and, consequently, to improving the epidemiological indicators of socially significant diseases.
Platform Technology Regulation as a Tool for Accelerating Drug Development: Analysis and Prospects for Russia
Objective. The objective of this study is to demonstrate the potential of the platform approach in the regulation of biotechnological drug development, supported by specific examples and case studies from FDA practice. The study examines the Platform Technology Designation Program (PTDD) of the U.S. Food and Drug Administration (FDA), launched in 2024. This program serves as a regulatory mechanism for granting platform technology status and has practical value for accelerating drug development and review through the justified reuse of data. Obtaining platform technology status entitles the developer to partially reuse CMC (Chemistry, Manufacturing, and Controls) data from an already approved drug when submitting applications for subsequent products based on the same “backbone.” The article discusses the mechanisms for granting such status, examples from FDA practice, as well as Russian companies possessing similar technologies and the potential for their development. Based on the analysis, a conclusion is drawn regarding the feasibility of implementing analogous regulatory mechanisms in Russia.