The article is devoted to the construction of lattice endoprosthesis for a long bone. Clinically, the main idea is to design a construction with the ability to improve bone growth. The article presents the algorithm for such a design. The construction should be produced by additive manufacturing. Such an approach allows using not only metallic materials but also ceramics and polymers. The algorithm is based on the influence function as a method to describe the elementary cell geometry. The elementary cell can be described by a number of parameters. The influence function maps the parameters to local stress in construction. Changing the parameters influences the stress distribution in the endoprosthesis. In the paper, a bipyramid was used as an elementary cell. Numerical studies were performed using the finite element method. As a result, manufacturing construction is described. Some problems for different orientations of growth are given. The clinical test was done and histological results were presented.

This study aimed to clarify interactions of the pattern-recognition receptor DC-SIGN with cells from the HIV-infected peripheral blood lymphocyte cultures. Cells from control and HIV-infected peripheral blood lymphocyte cultures were tested for the surface expression of DC-SIGN ligands. The DC-SIGN ligand expressing cells were analyzed for the role of DC-SIGN-ligand interaction in their functionality. In the vast majority of experiments HIV-infected lymphocytes did not express detectable DC-SIGN ligands on their cell surfaces. In contrast, non-infected cells, carrying NK-specific marker CD56, expressed cell surface DC-SIGN ligands. The weakly polysialylated CD56 was identified as a novel DC-SIGN ligand. The treatment of DC-SIGN expressing dendritic cells with anti-DC-SIGN antibodies increased the anti-dendritic cell cytotoxicity of CD56pos cells. The treatment of CD56pos cells with a peptide, blocking the weakly polysialylated CD56-specifc trans-homophilic interactions, inhibited their anti-dendritic cells cytotoxicity. The interaction between DC-SIGN and CD56 inhibits homotypic intercellular interactions of CD56pos cells and protects DC-SIGN expressing dendritic cells against CD56pos cell-mediated cytotoxicity. This finding can have an impact on the development of approaches to HIV infection and cancer therapy as well as in transplantation medicine.

Background/Objectives: Breast cancer remains a major cause of cancer-related mortality among women worldwide, highlighting the need for new therapeutic strategies. Pyrimidine derivatives have shown promise in oncology due to their ability to modulate immune responses and influence tumor growth pathways. Methods: Cytotoxicity of Xymedon was evaluated using MTT and colony formation assays on cancer MCF-7, NCI-H322M, HCT-15 cells, and primary human foreskin fibroblasts. In vivo efficacy was assessed in an orthotopic MCF-7 xenograft model in female Balb/c nude mice. Xymedon was administered orally at 410 mg/kg daily alone or in combination with intraperitoneal doxorubicin (1 mg/kg weekly). Hematological, histological, and immunohistochemical analyses were performed. Results: In vitro, Xymedon (up to 3 mM) showed no cytotoxicity against cancer cell lines or human skin fibroblasts. In vivo, Xymedon significantly increased tumor necrosis (44.1% vs. 28.5%, p < 0.01) and enhanced intratumoral infiltration of CD3+, CD8+, and CD20+ lymphocytes, with peritumoral counts increasing 2.2–5.3-fold. It mitigated Doxorubicin-induced myelosuppression by improving red blood cell counts, hemoglobin, and hematocrit levels, while platelet recovery remained limited. Combination therapy with Xymedon did not affect tumor volume or weight, but resulted in a non-significant trend toward improved survival (80% vs. 30%, p ≈ 0.11; Hazard Ratio [HR] = 0.268, 95% CI: 0.07082 to 1.012) without affecting fibrous capsule formation. Conclusions: These results suggest that Xymedon is a non-cytotoxic immunomodulator with potential as an adjuvant to enhance antitumor immunity and reduce hematologic toxicity associated with chemotherapy. Further studies are needed to elucidate the molecular pathways and confirm clinical efficacy.

Immune dysregulation is one of the main causes of severe coronavirus infection COVID-19. The immune response in COVID-19 is characterized by the activation of innate immune cells and elevated levels of pro-inflammatory cytokines in the blood (tumor necrosis factor alpha, interleukins-1, -6, -8), neutrophils, C-reactive protein and ferritin. Organ dysfunction, including acute respiratory distress syndrome, is associated with cytokine storm. Another important sign of immune dysregulation is lymphopenia, one of the key predictor of the development of severe COVID-19 and poor outcome. One of the main causes of lymphopenia in patients with severe COVID-19 is apoptosis of lymphocytes. The increased proinflammatory cytokines play a critical role in the induction of lymphocytes apoptosis and lymphopenia. The clinical role of lymphocytes apoptosis in COVID-19 is associated with the immunosupression and the opportunistic and secondary infectious diseases. The immunosupression in severe COVID-19 is confirmed by the results of morphological studies demonstrating the depletion of lymphocytes in lymphoid tissue. Next important cause of lymphopenia is lymphocyte sequestration in the lungs. Postmortem studies of the lungs of patients died from COVID-19 show the lymphocytic infiltration. Additionally, lymphopenia may result from impaired lymphopoiesis due to virus-induced damage to lymphocyte precursors in the bone marrow and thymus. In COVID-19 patients, there is a significant reduction in the production of T-cells in the thymus. The decreased thymic function may exacerbate lymphopenia in patients during the acute phase of COVID-19 and prolong the time required for the recovery of circulating T-cell counts.