The presented controversial hypothesis is an attempt to reflect on the role of the adaptive immune response in carcinogenesis. It is a well-known fact that the most of the signaling pathways which are participating in embryogenesis and regeneration are also active in tumor growth. Considering their presence in different evolutionary groups, there's such a contradiction that with same mechanisms of proliferation, animals with high regenerative potential are less predisposed to malignancy than mammals. Comparing these two groups, it's being discovered that despite the importance of immune control as a factor impeding carcinogenesis, the animals' immune system with high regenerative potential is less developed. The above is a reading of the complete or partial absence of the adaptive link of immunity. These described distinctions have formed the basis of the hypothesis of the procarcino-genic role of the adaptive immune response.

BACKGROUND: Intestinal metaplasia of the gastric mucosa epithelium in chronic atrophic gastritis is considered a precancerous condition; however, it is potentially reversible. The study of the regulation mechanisms of metaplastic epithelial changes may help in understanding carcinogenesis and cancer prevention. AIM: To determine whether the microenvironment is related to the development of gastric mucosa epithelium metaplasia in patients with chronic atrophic gastritis by assessing gene expression and cellular composition of immune infiltrates. MATERIALS AND METHODS: In this retrospective cohort study, the alternative hypothesis was that the composition of the immune microenvironment of the gastric mucosa differed between cases with and without metaplastic changes in the epithelium. Biopsy specimens of the mucosa (n=38) obtained during endoscopic examination from five stomach sites (2 from the antrum, 2 from the body, and 1 from the corner) in patients with chronic atrophic gastritis of unspecified etiology and results of RNA sequencing of biopsy specimens of patients with chronic gastritis registered in the NCBI open database (n=12) were analyzed. Histological analysis, histochemical staining methods, and immunohistochemical study and morphometric, statistical, and bioinformatic analyses were performed. RESULTS: The proportion of macrophages, T-cytotoxic lymphocytes, and plasmocytes increased in the samples with metaplastic changes of the gastric mucosa epithelium. A correlation was found between T-cytotoxic lymphocytes and risk for metaplasia. It was found that changes in the number of B cells, macrophages M2, T-regulatory cells and NK-cells are associated with increase in the expression of six genes most specific for intestinal-type epithelium. CONCLUSION: The significant difference in the composition of the immune microenvironment between samples with and without metaplastic changes in the mucosal epithelium indicates the potential influence of immune cells on the development of metaplasia and progression of the pathological process along the Correa cascade. One of the mechanisms of regulation of metaplasia development by the microenvironment may be their influence on gene expression as an epigenetic factor.

Introduction: Intracerebral hemorrhage (ICH) is among the most severe forms of stroke. Whereas traditional hemorrhagic stroke models reproduce hemorrhage within the striatum (specifically the putamen), localization of the hematoma with involvement of the internal capsule and globus pallidus may better recapitulate clinically relevant sensorimotor deficits due to more extensive basal ganglia involvement and damage to dense clusters of white matter tracts. Materials and Methods: Male CD1 mice (3–4 months, 30–35 g) were assigned to intact control (n=15) or ICH (n=15) groups. ICH was induced by stereotaxic injection of 30 μL autologous blood into the right cerebral hemisphere (2.3 mm lateral, 0.2 mm caudal to bregma, depths 3.0 and 3.5 mm). Neurological status was assessed using the modified Garcia scale, limb placement tests, horizontal and vertical pole tests, inverted grid test, corner test, and open field test at baseline and on days 1, 3, 7, 14, 21, and 28. Results and Discussion: The model showed high reproducibility with 33–40% acute mortality. All ICH mice developed contralateral sensorimotor-pyramidal deficits with predominant forelimb involvement. Garcia scores declined from 21 to 14.83±1.72 on day 1 with gradual but incomplete recovery by day 28 (18 [18;18.5]). Forelimb placement showed >50% acute deficit with a nonlinear recovery pattern, whereas hindlimb deficits appeared later (days 3–7) and persisted to day 21. The modified Garcia scale, forelimb placement, modified horizontal bar, and open field tests were most sensitive to functional impairment and recovery. Conclusion: Stereotaxic autologous blood injection into the basal ganglia (putamen and globus pallidus) with involvement of the internal capsule in mice reproduces clinically relevant, reproducible sensorimotor deficits with persistent functional impairment, making this model suitable for preclinical testing of neuroprotective strategies.

Reduced early mortality in sepsis and severe injuries led to the formation of a cohort of patients with chronic critical conditions (diseases). One of the mechanisms of chronization of acute critical conditions is the development of persistent inflammation, immunosuppression and catabolism syndrome (PICS). Diagnosis of PICS is currently based on clinical and laboratory markers, whereas morphological changes insufficiently studied. Lack of pathogenesis and morphogenesis understanding makes it difficult to stratify patients with prolonged critical conditions and develop new treatment approaches, and also leads to the absence of PICS in clinical and anatomical diagnoses. The article systematized current understanding of PICS mechanisms of development and morphological manifestations. Examples of clinical cases are presented.

Background/Objectives: Comprehensive genomic profiling (CGP) is a cornerstone of personalized oncology. However, large-scale, systematic data on the somatic mutation spectrum in Russian cancer patients are scarce. This study aimed to characterize the genomic landscape and assess the potential for matched therapy in a Russian cohort of patients with solid tumors. Methods: This retrospective study included 204 patients with various solid tumors. CGP was performed using the FoundationOne^®CDx (FFPE tissue) and FoundationOne^®Liquid CDx (cfDNA) platforms. The analysis assessed single-nucleotide variants, indels, copy number alterations, gene fusions, tumor mutational burden (TMB), microsatellite instability (MSI), and PD-L1 expression. Results: The most frequently mutated genes were TP53 (61.5%) and KRAS. The median TMB was 4.0 mut/Mb and was significantly lower in stage IV tumors. Significant co-occurrence was observed between KRAS and TP53 mutations, as well as between APC and KRAS mutations, which were particularly characteristic of colorectal cancer. KRAS mutations were associated with higher combined positive score (CPS) values in cases with lung cancer. Based on the CGP results, 44% of patients had findings that supported the use of an approved matched targeted therapy or immunotherapy for their tumor type. An additional 36% of patients had alterations indicating potential benefit from off-label targeted therapy. Conclusions: This study reveals the distinct genomic characteristics of solid tumors in a Russian cohort and confirms the high clinical utility of CGP for identifying actionable targets. Implementing CGP early in the diagnostic process is a necessary step towards realizing personalized treatment strategies for cancer patients.

Background: Although drug-induced liver injury (DILI) remains a concern in polypharmacy, especially in older cardiovascular patients, pharmacogenetic markers are not routinely used for DILI risk prediction. Genome-wide polygenic scores aggregate thousands of variants but remain costly for routine care. In this study, we developed and preliminarily evaluated a PCR-based pharmacogenetic panel targeting key drug metabolism and transport genes for hepatotoxicity risk stratification in polypharmacy patients. Methods: A real-time PCR panel covering 12 polymorphisms in NAT2, CYP2C9, UGT2B7, ABCB1, and SLCO1B1 was developed using fluorescent probe melting. Autopsy liver samples and clinical data were obtained from 47 patients over 50 years old who had taken five or more cardiovascular drugs for at least six months. Liver morphology was assessed histomorphometrically using METAVIR fibrosis/activity scores and a composite Hepatic Lesion Index (HLI), while an integrated pharmacogenetic (PGx) score combined CYP2C9 metabolizer status, NAT2 acetylation, and SLCO1B1/OATP1B1 transport function. Results: Significant fibrosis (METAVIR F ≥ 2) was found in 36.2% of patients, and no liver was entirely histologically normal. Carriage of the NAT2 rs1799931 minor allele was strongly associated with a higher HLI (median 7.0 vs. 4.0; adjusted p = 0.00013) and was the only independent predictor of fibrosis stage in multivariable regression (OR = 16.36; p = 0.00268). Conclusions: A limited, accessible five-gene panel identified clinically relevant variability in hepatotoxicity-associated genetic profiles among polypharmacy patients, with NAT2 status showing the strongest association with liver injury severity. These preliminary findings support further validation of targeted pharmacogenetic screening as a potentially scalable and cost-effective alternative to genome-wide approaches for assessing hepatotoxicity susceptibility in vulnerable populations.