The relationship between Hashimoto thyroiditis (HT) and papillary thyroid carcinoma (PTC) remains uncertain. We assessed the impact of HT on the tumor immune microenvironment (TIME) in PTC. Thirty patients with PTC (group 1) and 30 patients with PTC and HT (group 2) were enrolled in this pilot study. The distribution and number of CD8+ lymphocytes, plasma cells (CD138+), regulatory T cells (forkhead box P3 [FOXP3+)], mast cell tryptase (MCT+), and M2 macrophages (CD163+) were evaluated. To test the hypothesis that HT impacts PTC development via signal transducer and activator of transcription 6 (STAT6) activation and M2 macrophage polarization, we investigated STAT6 expression in tumor and stromal cells. We also evaluated vascular endothelial growth factor (VEGF) expression by lymph node metastasis (LNM) status. TIME showed significant between-group differences. Group 1 patients demonstrated immune desert or immune-excluded immunophenotypes, while an inflamed phenotype with more CD8+ cells (P<0.001) predominated in group 2. Immune-excluded TIME was associated with the highest LNM rate. In PTC, LNM was associated with more numerous CD163+ cells. Moreover, LNM in group 1 was associated with increased numbers of mast cells peritumorally and FOXP3+ cells intratumorally and peritumorally. Group 2 demonstrated higher STAT6 but not higher VEGF expression in tumor cells. High VEGF expression was associated with LNM regardless of HT status. Concomitant HT impacted PTC signaling via STAT6 and TIME by increasing the number of CD8+ cells. LNM is associated with increases in CD163+ cells and VEGF expression in PTC, whereas HT affected LNM through different mechanisms.

MXenes, a class of two-dimensional transition metal carbides and nitrides, have emerged as promising candidates for biomedical applications due to their electrical conductivity, photothermal response, and rich surface chemistry. However, their biocompatibility is highly sensitive to synthesis conditions, particularly etching and delamination strategies. In this study, we systematically investigated the influence of different synthesis routes─using acidic (concentrated or diluted HF/HCl) etching and Li⁺ versus Na⁺ intercalation─on the surface chemistry, structural integrity, and biological behavior of Ti₃C₂T_x and its carbonitride analog Ti₃C_1.5N_0.5T_x. Detailed physicochemical characterization revealed that water-assisted etching and Na⁺ intercalation enhanced hydroxylation and reduced fluorine terminations. Biological assays using human keratinocytes (HaCaT) demonstrated that Ti₃C_1.5N_0.5T_x exhibited superior biocompatibility compared to Ti₃C₂T_x, with lower cytotoxicity, diminished ROS generation, minimal inflammatory signaling (IL-6 and IL-8 interleukins), and preserved wound healing capacity. Among Ti₃C₂T_x variants, the combination of diluted etchant and Na⁺ intercalation significantly improved biological tolerance, minimizing apoptosis and oxidative stress. These findings underscore the critical role of surface chemistry in MXene-cell interactions and offer a practical guide to engineering safer MXenes for biomedical use.

Although some studies have investigated the clinicopathologic relationships between papillary thyroid carcinoma (PTC) and Hashimoto's thyroiditis (HT), there is still no clear understanding of differences in tumor immune microenvironment for PTC with coexisting HT and HT effect on PTC progression. The aim of this study was to clarify immune-mediated mechanisms of coexisting HT, which might influence PTC progression. 30 patients with histologically confirmed conventional-type PTC and 30 patients with PTC and coexisting HT were enrolled in the study. To analyze the role of immune-mediated links between PTC and HT, immunohistochemical investigation was conducted to count the number of different immune cells including T-cytotoxic cells (CD8), plasma cells (CD138), Treg cells (FOXP3), mast cells (MCT), and M2 macrophages (CD163). It was shown that despite the high number of immune cells in the intact thyroid tissues of PTC patients with coexisting HT there were no significant differences in M2 macrophages, mast cells and Treg counts inside PTC with or without HT. PTC with HT was associated with a higher number of CD8+ cells (P < 0.001) reflecting the ability of immune system to generate and recruit T-cytotoxic cells in tumor area, which can explain the protective effect of HT on PTC progression. Lymph node metastases development was associated with an increased number of mast cells, M2 macrophages and Treg along with a decreased plasma cells count regardless of coexisting HT. However, we did not find significant differences in T-cytotoxic cells quantity in node-positive and node-negative patients with or without HT, which encourages further investigation of immune escape mechanisms in PTC.

BACKGROUND: Osteoarthritis (OA) is a joint affection, defined by articular cartilage demolition, risks of which rise with age. The aim of this study was to compare the efficacy of chondroitin sulfate (CS) course and multistrain live probiotic (LP) administered alone or in combination on the expression of TLR-2, TLR-4, TNF-alpha and NF-kappa B in articular cartilage, subchondral bone and synovial membrane during OA in rats. METHODS: OA was induced in male rats by injecting monoiodoacetate (MIA) in right hind knee. Therapeutic groups received 3 mg/kg of chondroprotector (ChP) CS for 28 days and/or 140 mg/kg of LP diet for 14 days. The expression of TLR-2, TLR-4, TNF-alpha and NF-kappa B in articular cartilage, subchondral bone and synovial membrane were determined with immunohistochemical staining kits (Thermo Fisher Scientific). RESULTS: It was established that MIA injection is associated with long-term structural changes in joint tissues that corresponded to OA-like features and associated with activation of pathogen-recognizing molecules and proinflammatory signaling pathways expression. Separate therapy with ChP and probiotics slightly decreased OA score limiting cell death and subchondral bone resorption. However, these changes were not associated with a significant decrease in TLR-2, TLR-4, NF-kB and TNF-alpha expression. On the other hand, the combination of ChP and LP treatment significantly decreased OA score. This correlated with a decrease in TLR-2, TLR-4, NF-kB and TNF-alpha expression in chondrocytes and synovial cells. CONCLUSIONS: The outcomes of our research prove that ChPs amplify the positive action of LPs in OA attenuation.

Digital pathology (DP) has become a part of the cancer healthcare system, creating additional value for cancer patients. DP implementation in clinical practice provides plenty of benefits but also harbors hidden ethical challenges affecting physician-patient relationships. This paper addresses the ethical obligation to transform the physician-patient relationship for informed and responsible decision-making when using artificial intelligence (AI)-based tools for cancer diagnostics. DP application allows to improve the performance of the Human-AI Team shifting focus from AI challenges towards the Augmented Human Intelligence (AHI) benefits. AHI enhances analytical sensitivity and empowers pathologists to deliver accurate diagnoses and assess predictive biomarkers for further personalized treatment of cancer patients. At the same time, patients’ right to know about using AI tools, their accuracy, strengths and limitations, measures for privacy protection, acceptance of privacy concerns and legal protection defines the duty of physicians to provide the relevant information about AHI-based solutions to patients and the community for building transparency, understanding and trust, respecting patients' autonomy and empowering informed decision-making in oncology.