Background: Macrophages are key components of the tumor microenvironment and play a critical role in melanoma progression. However, the dynamics of different macrophage subsets, particularly CD68⁺ and CD163⁺ populations, in relation to tumor thickness and stage remain insufficiently characterized. Objective: This study aimed to quantitatively assess intratumoral and peritumoral CD68⁺ and CD163⁺ macrophages in cutaneous melanoma and to investigate their associations with Breslow thickness, pT stage, and AJCC stage. Methods: We conducted a retrospective cohort study of 126 patients with cutaneous melanoma (AJCC stages IA–IIID). Tumor samples were examined histologically and immunohistochemically for CD68⁺ and CD163⁺ macrophages, and quantitative analysis was performed in intratumoral and peritumoral regions. Results: This study included 126 patients with cutaneous melanoma, ranging in stage from IA to IIID. Histopathological analysis revealed that melanoma tissues were primarily composed of irregular clusters of atypical melanocytic cells infiltrating the dermis and subcutaneous fat. Immunohistochemical staining identified CD68⁺ and CD163⁺ macrophages both within the tumor and in the surrounding stroma. Macrophage infiltration significantly increased with tumor thickness (Breslow) and progression to more advanced stages. Specifically, at Breslow thickness 4.0 mm. CD163⁺ macrophages showed similar trends, with a rise from 15.6 ± 2.8 cells at 4.0 mm in the intratumoral zone. Additionally, macrophage density was higher in tumors with ulceration, and both CD68⁺ and CD163⁺ macrophage numbers increased progressively with tumor stage, particularly in advanced stages. The number of CD68⁺ macrophages at stage IA in the intratumoral zone was 21.6 ± 3.1 cells and increased to 56.4 ± 6.8 cells at stage IIID, while CD163⁺ macrophages rose from 13.8 ± 3.2 cells at stage IA to 36.4 ± 4.6 cells at stage IIID. This suggests that macrophage infiltration, particularly CD163⁺ cells, correlates with melanoma progression. Conclusions: Our findings highlight distinct spatial and phenotypic patterns of macrophage infiltration in melanoma progression. The prominent increase in CD68⁺ and CD163⁺macrophages suggests their important role in tumor-associated immunomodulation. Further studies are warranted to elucidate macrophage polarization states and their prognostic and therapeutic implications in melanoma.

Ionizing radiation at early stages leads to radiation-induced death of Langerhans islet cells and acinar cells, resulting in the development of acute/subacute pancreatitis. Conducting studies on radiation-induced changes in the pancreas following electron beam irradiation appears to be of great interest, and the evaluation of radioprotective agents for safeguarding normal tissues from radiation is equally important. The aim of this study was to preclinically investigate the antioxidant properties of N-Acetylcysteine in an animal model of radiation-induced pancreatitis over a three-month period. In this study, it was proven for the first time that even electrons can lead to characteristic signs of radiation-induced pancreatitis, the degree of which was assessed based on the levels of insulin, glucose, and amylase. Thus, conducting electron therapy also increases the risks of insulin resistance, as well as X-ray and gamma radiation. For the first time, a comprehensive analysis of biochemical, morphological, and immunohistochemical markers in the pancreas of a large cohort of electron-irradiated animals was conducted, including both acute and delayed effects of electron exposure. The crucial role of interleukins in shaping both the cellular and vascular components of the inflammatory response was identified. Additionally, the radioprotective properties of N-Acetylcysteine during electron irradiation of the pancreas were evaluated for the first time, and its effectiveness in reducing both acute and late complications of electron therapy was demonstrated. Thus, it can be concluded that N-Acetylcysteine is capable of effectively suppressing the inflammatory response in the pancreas.

Background: Mast cells, key effectors of the innate immune system, are known to participate in various stages of tumor progression, including inflammation, angiogenesis, and extracellular matrix remodeling. Their role in melanoma, particularly in relation to Breslow thickness, pT stage, and AJCC staging, remains unclear. This study aims to quantitatively and phenotypically assess mast cell infiltration in cutaneous melanoma at different stages of progression, focusing on Tryptase- and Chymase-positive subtypes. Methods: This retrospective multicenter study included 124 patients with cutaneous melanoma (AJCC 8th edition, stages IA–IIIC). Histological sections were stained with hematoxylin and eosin, and mast cells were visualized using toluidine blue and immunohistochemistry with anti-Tryptase and anti-Chymase antibodies. Mast cells were counted manually in intratumoral and peritumoral regions by two independent observers. Quantitative data were analyzed using non-parametric tests and presented as median [Q1–Q3]. Results: Histological examination of 124 melanoma samples confirmed typical features of cutaneous melanoma, with nodular melanoma being the most common subtype (68 cases, 54.8%) and the lower extremities identified as the predominant tumor location (47 cases, 37.9%). Toluidine blue staining verified the presence of mast cells in both intratumoral and peritumoral compartments, with the highest density observed in early-stage melanomas. Immunohistochemical analysis identified both Tryptase+ and Chymase+ mast cells. The intratumoral number of Tryptase+ cells declined from 17 [14–19] per HPF at AJCC stage IA to 6 [5–7] per HPF at stage IIIC, while Chymase+ mast cells decreased from 14 [11–16] per HPF to 2 [1–3] per HPF over the same stages. Peritumoral counts also showed a downward trend, although less pronounced. Overall, the most significant reduction was observed in Chymase+ mast cells, suggesting their potential role as markers of melanoma progression. Conclusions: This study highlights the dynamic changes in mast cell populations in cutaneous melanoma, with a pronounced decrease in Chymase⁺ mast cells as the tumor progresses. Further research is needed to explore the mechanistic role of mast cells and their phenotypic shifts in melanoma progression.

Background/Aim: In surgical dentistry, maxillofacial surgery and traumatology, bone tissue regeneration is one of the most pressing challenges. Aim of this study was assessment of local irritant effects following subcutaneous implantation of polyetheretherketone (PEEK) and polymethyl methacrylate (PMMA)-based devices, with determination of their biocompatibility and safety for intended applications in dental practice. Methods: The study used 30 male Wistar rats (200 g ± 10 g, 9-10 weeks old) to evaluate inflammatory responses to four subcutaneous implants (PEEK, 3DF, Apium, Bonlecule) over 7, 30 and 60 days. Histological analysis assessed cell infiltration, necrosis, neovascularisation, fibrosis and capsule formation using standardised scoring systems. Statistical comparisons were made via one-way ANOVA (p < 0.05) to analyse intergroup differences in tissue reactions. Results: Macroscopic examination showed stable implant integration with no structural changes, while microscopic analysis revealed mild mononuclear infiltration and progressive fibrous tissue replacement, with the strongest response in the Bonlecule group at day 7 and the weakest in PEEK by day 60. Histopathology indicated vascular dilation, reduced fibroblasts and increased immune cells, but no necrosis or fatty infiltration, with PEEK exhibiting the thinnest proliferation zone by day 60. Morphometric data confirmed Bonlecule had the thickest proliferation zone (91.9 µm at day 7), while PEEK showed the most significant reduction (28.34 µm by day 60). Conclusion: The study confirmed high biocompatibility of PEEK and PMMA implants, with PEEK showing optimal integration and minimal tissue reaction, making it suitable for dental applications. The 3DF implant demonstrated the lowest bioresorption, remaining structurally intact over the two-month observation period. These findings support the clinical use of these materials, particularly PEEK, which meets all biocompatibility requirements with moderate immune response and vascularisation.

Cutaneous melanoma remains one of the most aggressive tumors, yet the role innate immunity plays in its progression remains poorly understood. Effector elements with high regulatory potential, capable of both promoting and inhibiting tumor growth—mast cells (MCs), are of particular interest. This includes quantitatively characterizing the interactions between tryptase-positive mast cells (MCs) with atypical Melanin—A⁺ cells and describing their spatial phenotype, in relation to the stage of cutaneous melanoma. A retrospective analysis was carried out on samples retrieved from 128 patients with cutaneous melanoma (AJCC 8th edition: IA–IIID). Histological analysis, histochemistry (toluidine blue, Giemsa), and diplex /multiplex IHC for tryptase and Melan-A were performed; as well as Fluorescence imaging, 3D reconstructions and quantitative mapping in QuPath v 0.6.0. Proximity was assessed by the nucleus-to-nucleus distance: 20 μm (out of interaction). The relative amount of MCs in the intratumoral zone was lower than in the intact dermis, with a simultaneous increase in their absolute density per mm² in the melanoma microenvironment, maximum in the peritumoral area and most pronounced at stage II. Three types of interactions were identified: (i) juxtaposition without secretion, (ii) degranulation of MCs directed to tumor cells, (iii) melanosecretion of Melanin—A⁺ cells directed towards MCs, followed by phagocytosis of melanocores. An inverse intratumoral connection between the number of MCs and the number of Melanin—A⁺ cells was noted; MCs with elongated forms, extensive contacts and polarized tryptase secretion, including granule localization near/at the nuclei of adjacent cells, were frequently observed. The obtained data indicate stage-region-dependent bidirectional cross-talk between melanin and MCs, forming tissue spatial signals, potentially useful as biomarkers and targets for personalized therapy.

BACKGROUND: Melanoma is a malignant neoplasm that arises from melanocytes, which are melanin-producing cells primarily found in the skin. Although rare, melanoma is highly aggressive. In 2023, 13,270 cases of skin melanoma were identified in Russia. The primary risk factor is excessive exposure to ultraviolet radiation. Immunohistochemical studies using markers such as HMB-45 (Human Melanoma Black-45), Melan-A/MART-1 (Melanoma Antigen Recognized by T Cells 1), and S100 are crucial for diagnosing skin melanoma, improving the accuracy of tumor detection, and optimizing treatment. AIM: This study aimed to assess the prognostic significance of melanocytic markers HMB-45, Melan-A/MART-1, and S100 in skin melanoma, taking into account tumor histological subtypes and stages according to the pTNM classification. METHODS: Skin melanoma samples from patients (n = 117) were assessed using immunohistochemistry with antibodies to HMB-45, Melan-A/MART-1, and S100. The results were interpreted based on the histological subtype of the tumor and the Breslow thickness, which was used to determine the disease stage. RESULTS: The count of atypical melanoma cells, considering the histological subtype of the tumor, showed that the S100 marker had the highest sensitivity (91.2%) compared to Melan-A/MART-1 and HMB-45, especially in desmoplastic melanoma. Moreover, S100 and Melan-A/MART-1 demonstrated stable staining regardless of the degree of invasion, whereas the number of HMB-45-positive atypical melanocytes increased as the tumor progressed according to the pTNM classification. CONCLUSION: Immunohistochemical analysis of various histological subtypes of skin melanoma revealed stable expression of S100, Melan-A/MART-1, and HMB-45 proteins in superficial spreading and nodular tumors. In desmoplastic melanoma, the expression of Melan-A/MART-1 and HMB-45 was absent, whereas S100 expression remained. The proportion of S100- and Melan-A/MART-1-positive atypical cells was independent of the degree of tumor invasion (according to pTNM stages). The percentage of HMB-45-positive atypical melanocytes increased proportionally with the thickness of invasion, supporting its prognostic significance.