Tumor-associated macrophages are a heterogeneous population of immune cells within tumor stroma that play a critical role in tumor development, disease progression, and treatment response. Recent studies of urothelial bladder cancer have highlighted the potential value for investigating these cell populations and their associated target markers. Understanding their biological role is particularly important in patients undergoing bacillary Calmette–Guérin therapy, the most accessible minimally invasive treatment option in Russia. An analysis of international literature on tumor-associated macrophages has identified the most promising target markers and their associations with clinical and prognostic criteria. The markers discussed in this review may contribute to improvement of diagnostic panels for urothelial carcinoma and refine patient selection criteria for various treatment strategies, including minimally invasive methods. This review aimed to highlight the importance of studying the mesenchymal microenvironment of bladder cancer and its components and to identify prognostically significant markers of tumor-associated macrophages based on current literature. Keywords: bladder cancer, urothelial carcinoma, tumor-associated macrophages, tumor-infiltrating lymphocytes, immunohistochemistry, tumor microenvironment, tumor stroma
Introduction. The development of treatment strategies for retinal pigment epithelium diseases, including cell transplantation approaches, requires a rigorous analysis of morphological data. A major limitation for immunohistochemical studies and microscopy is the presence of melanin, which necessitates the identification of an optimal depigmentation method capable of preserving cellular structure. The study aimed to conduct a comparative analysis of depigmentation methods for native preparations and 3D spheroids in order to identify the most effective and least damaging protocol. Materials and methods. The effects of various depigmenting agents on retinal pigment epithelium samples were investigated. The evaluation criteria included the degree of melanin removal, preservation of cellular morphology, autofluorescence levels, and the time required for the procedures. Results. We determined optimal chemical depigmentation protocols for subsequent confocal, light, and phase-contrast microscopy. Conclusion. We developed preferred depigmentation algorithms that ensure preservation of the morphofunctional properties of retinal pigment epithelium and are suitable for detailed microscopic analysis, thereby providing a basis for the standardization of research in this field. Keywords: retinal pigment epithelium, morphological study of retinal pigment epithelium, depigmentation of retinal pigment epithelium, age-related macular degeneration, morphological study of 3D spheroids
Introduction. Bone grafting is a key approach for overcoming osteogenic insufficiency in the treatment of maxillofacial defects. However, routine clinical methods do not allow for detailed assessment of the histological structure of the newly formed tissues. This study aimed to qualitatively and quantitatively compare the morphological features of bone regenerate formed using conventional and gene-activated osteoplastic materials. Materials and methods. The study included bone regenerate biopsies from 60 patients obtained 6 months after bone grafting prior to dental implantation. Samples were divided into two groups according to the material used during surgery: a conventional xenogenic matrix (n=19) and a synthetic gene-activated material based on octacalcium phosphate with plasmid DNA encoding VEGF (n=41). Histological analysis and histomorphometry were performed using the Parfitt system with Adobe Photoshop and ImageJ software to evaluate tissue components and material contacts. Results. No signs of acute inflammation were observed in either group, and complete material resorption did not occur. The volume of fibroreticular bone tissue was significantly higher with the gene-activated material than with the xenogenic matrix (p=0.043). Furthermore, the synthetic material demonstrated greater contact with newly formed trabeculae and more active vascularization, whereas the xenogenic matrix remained more inert. No differences in the extent of the active osteoblastic surface were revealed between the groups. Conclusion. Both materials demonstrated high biocompatibility and osteoconductivity. However, the gene-activated material ensured more active and prolonged remodeling of the regenerate compared to the conventional xenograft. This was confirmed by a greater volume of newly formed fibroreticular bone tissue and closer integration of the material with bone structures at 6 months. Keywords: reparative regeneration, osteoplastic materials, histomorphometry, gene therapy
Introduction. Alzheimer’s disease is the most common neurodegenerative disorder; however, its pathogenesis remains incompletely understood. PGC-1α dysfunction, a key regulator of mitochondrial biogenesis, has been associated with early synapse loss in the brain regions most severely affected by the disease. Nevertheless, current data on neuronal PGC-1α distribution in Alzheimer’s disease remain largely generalized, and its detailed characterization across different cortical and subcortical areas is still scarce. Therefore, we aimed to evaluate PGC-1α distribution in neurons of brain regions critically involved in Alzheimer’s disease, including the anterior cingulate gyrus, middle frontal gyrus, inferior parietal lobule, head of the caudate nucleus, and hippocampus. Materials and methods. Autopsy brain specimens from elderly and young patients with Alzheimer’s disease were subjected to immunohistochemical study of PGC-1α distribution in the abovementioned areas. Results. A marked increase in PGC-1α expression was observed in all examined cortical regions. In contrast, a different pattern of response was found in hippocampal neurons: neurons in the CA1 region showed a tendency toward decreased PGC-1α levels, while neurons in the CA2 region showed a marked decrease in protein expression. Conclusion. Our data indicate that a significant reduction in PGC-1α levels, reflecting impaired mitochondrial biogenesis in the hippocampus may represent a significant factor contributing to neuronal damage in this brain region in Alzheimer’s disease. Keywords: mitochondria, neurodegeneration, Alzheimer’s disease, hippocampus, PGC-1α
Autopsy coverage in OECD countries and globally is steadily declining, with Russia and post-Soviet countries having high autopsy coverage. This is due to different approaches to using autopsy in quality management of medical care. OECD countries perform clinical autopsy mainly in complex cases and for medical education and research. Russia and post-Soviet countries have largely retained the approach developed in the USSR, which implies mandatory autopsy following a patient’s death in a hospital. This includes analysis of the causes of discrepancies between clinical and pathological diagnoses and the development of measures to improve the organization of medical care, resource allocation, and physician training. However, since 2010, the compulsory medical insurance system of Russia has treated discrepancies between clinical and pathologic diagnoses as a medical error, subject to significant fines for healthcare organizations. Thus, by investing resources in autopsies and investigating hospital deaths, organizations penalize themselves, discouraging improvements in care and fostering future errors. The study conducted an OSINT analysis of fines and other economic penalties in OECD, BRICS, and CIS countries. The findings suggest that Russia may be the only country that has transformed discrepancies between clinical and pathological diagnoses from an important quality indicator into an incentive to conceal organizational, resource, and staffing problems. Keywords: autopsy, quality control, discrepancy between clinical and pathological diagnoses, fines
