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BACKGROUND: In this study, we manufactured a complex of human nasal septal cartilage (hNC) with polycaprolactone (PCL) for transplantation into cartilaginous skeletal defects and evaluated their characteristics. METHODS: Nasal septum tissue was obtained from five patients aged ≥ 20 years who were undergoing septoplasty. hNCs were isolated and subcultured for three passages in vitro. To formulate the cell–PCL complex, we used type I collagen as an adhesive between chondrocyte and PCL. Immunofluorescence staining, cell viability and growth in the hNC–PCL complex, and mycoplasma contamination were assessed. RESULTS: hNCs in PCL showed viability ≥ 70% and remained at these levels for 9 h of incubation at 4 °C. Immunostaining of the hNC–PCL complex also showed high expression levels of chondrocyte-specific protein, COL2A1, SOX9, and aggrecan during 24 h of clinically applicable conditions. CONCLUSION: The hNC–PCL complex may be a valuable therapeutic agent for implantation into injured cartilage tissue, and can be used clinically to repair cartilaginous skeletal defects. From a clinical perspective, it is important to set the short duration of the implantation process to achieve effective functional implantation.

The present study aimed to analyze the compensatory signaling pathways induced by forkhead domain inhibitor‑6 (FDI‑6), which is a forkhead box protein M1 (FOXM1) inhibitor, in ovarian cancer cells and evaluate the effectiveness of simultaneous inhibition of FOXM1 and the compensatory signaling pathway in decreasing the survival of ovarian cancer cells. The present study identified the proteins involved in the compensatory mechanism activated by FDI‑6 in HeyA8 ovarian cancer cells using western blot analysis and a reverse‑phase protein array. In addition, a cell viability assay was performed to determine the effects of FDI‑6 and the compensatory signaling pathway on cancer cell viability. All experiments were performed in three‑dimensional cell cultures. The present study observed that FDI‑6 stimulated the upregulation of N‑Ras, phosphoprotein kinase Cδ (p‑PKCδ) (S664) and HER3 in HeyA8 cells. Tipifarnib as an N‑Ras inhibitor, rottlerin as a p‑PKCδ (S664) inhibitor and sapitinib as a HER3 inhibitor were selected. The combination of FDI‑6 with tipifarnib attenuated the upregulation of N‑Ras induced by FDI‑6 and the combination of FDI‑6 with sapitinib also attenuated HER3 downstream signaling pathway in HeyA8 cells, as shown by on western blot analysis. Rottlerin downregulated p‑PKCδ (S664) by inhibiting the activity of a Src‑related tyrosine kinase that transfers a phosphate group to PKCδ. Compared with FDI‑6 alone, the addition of tipifarnib or rottlerin to FDI‑6 was significantly more effective in reducing the growth of HeyA8 cells. However, the combination of FDI‑6 and sapitinib did not induce a significant decrease in survival of HeyA8 cells. In conclusion, the addition of tipifarnib or rottlerin to inhibit N‑Ras or p‑PKCδ (S664), respectively, inhibited the compensatory signaling pathway response induced by FDI‑6 in HeyA8 cells. These inhibitors increased the efficacy of FDI‑6, which inhibits FOXM1, in reducing ovarian cancer cell viability.

The characteristics of mesenchymal stem cells (MSCs) derived from human turbinates (hTMSCs) have not been investigated in allergic rhinitis. We evaluated the influence of allergic state of the donor on the characteristics, proliferation, and differentiation potential of hTMSCs, compared with hTMSCs derived from non-allergic patients. hTMSCs were isolated from five non-allergic and five allergic patients. The expression of toll-like receptors (TLRs) in hTMSCs was measured by FACS, and cell proliferation was measured using a cell counting kit. Cytokine secretion was analyzed using multiplex immunoassays. The osteogenic, chondrogenic, and adipogenic differentiation potentials of hTMSCs were evaluated by histology and gene expression analysis. In allergic patients, FACS analysis showed that TLR3 and TLR4 were more highly expressed on the surface of hTMSCs than TLR2 and TLR5. The proliferation of hTMSCs was not influenced by the presence of TLR priming. The expression of IL-6, IL-8, IL-12, IP-10, and RANTES was upregulated after the TLR4 priming. The differentiation potential of hTMSCs was not influenced by TLR priming. These characteristics of hTMSCs were similar to those of hTMSCs from non-allergic patients. We conclude that the allergic condition of the donor does not influence TLR expression, proliferation, or immunomodulatory potential of hTMSCs.