Objectives: There is growing need for new scaffold constructions for synthetic bone graft substitutes to repair large bone lesions. A very promising and important class of new implants for tissue engineering is based on three‐dimensional scaffolds and bioceramics.Materials and methods: In this study, after investigation of mechanical properties of polyethersulphone (PES) nanofibres, fabricated by electrospinning methodology and coated with bioactive glass (BG), cells of theMG‐63 line were cultured on surfaces of these scaffolds. Their capacity to supportMG‐63 proliferation was also investigatedin vitrobyMTTassay. Osteoconductivity on these scaffolds was investigated by the common osteogenic markers alkaline phosphatase (ALP) activity, calcium mineral deposition and bone‐related gene activation. Next, a bone reconstruction of rat critical‐size defects model was evaluated using radiographic imaging analysis (digital mammography), computed tomography and histological examination.Results: In vitroresults indicated that biocompatibility and osteogenic markers ofMG‐63 cells were significantly enhanced after coatingPESwithBG. Based onin vivoresults, new bone formation in the defect site was enhanced in implanted rats in comparison with a control group. The highest reconstruction was observed in animals implanted withBG‐coated nanofibres.Conclusions: Osteoconductivity ofPESnanofibres was markedly enhanced after coating them withBG, and introduction of this construct as new bone‐graft substitute for bone loss and defects is indicated.

Tumor-associated inflammation plays a vital role in cancer progression. Among the various stromal cells, cancer-associated fibroblasts are promising targets for cancer therapy. Several reports have indicated potent anti-inflammatory effects attributed to Curcumin. This study aimed to investigate whether inhibiting the inflammatory function of cancer-associated fibroblasts (CAFs) with Curcumin can restore anticancer immune responses. CAFs were isolated from breast cancer tissues, treated with Curcumin, and co-cultured with patients' PBMCs to evaluate gene expression and cytokine production alterations. Blood and breast tumor tissue samples were obtained from 12 breast cancer patients with stage II/III invasive ductal carcinoma. Fibroblast Activation Protein (FAP) + CAFs were extracted from tumor tissue, treated with 10 μM Curcumin, and co-cultured with corresponding PBMCs. The expression of smooth muscle actin-alpha (α-SMA), Cyclooxygenase-2(COX-2), production of PGE2, and immune cell cytokines were evaluated using Real-Time PCR and ELISA, respectively. Analyzes showed that treatment with Curcumin decreased the expression of genes α-SMA and COX-2 and the production of PGE2 in CAFs. In PBMCs co-cultured with Curcumin-treated CAFs, the expression of FoxP3 decreased along with the production of TGF-β, IL-10, and IL-4. An increase in IFN-γ production was observed that followed by increased T-bet expression. According to our results, Curcumin could reprogram the pro-tumor phenotype of CAFs and increase the anti-tumor phenotype in PBMCs. Thus, CAFs, as a component of the tumor microenvironment, are a suitable target for combination immunotherapies of breast cancer.

Heat-shock proteins have biochemical and immunological roles in chaperoning/signaling and activation of innate and adaptive immune responses, respectively. Their effect on the immune response is due to a phenomenon known as cross-priming of antigen, in which exogenous antigens are presented via MHC class I by antigen presenting cells. GP96 exerts adjuvant activity with some viral and bacterial antigens when applied in the form of a DNA vaccine. In this study, animals with Her2-expressing tumors were vaccinated by co-administration of GP96+ Her2/neu DNA vaccines. Analyses of the immune response, 2 weeks after the last immunization revealed decreased CD4+ CD25+ Foxp3+ naturally occurring regulatory T cells (Tregs) at the tumor site and increased IFN-γ/IL-4 level. Nevertheless, the graph of tumor size demonstrated a bi-phasic pattern in which partial control of tumor progression initially occurred, but finally its effectiveness was inversely affected by tumor size.