Background Chemoresistance is one of the main problems in treatment of cancer. Periostin (PN) is a stromal protein which is mostly secreted from cancer associated fibroblasts in the tumor microenvironment and can promote cancer progression including cell survival, metastasis, and chemoresistance. The main objective of this study was to develop an anti-PN peptide from the bacteriophage library to overcome PN effects in breast cancer (BCA) cells. Methods A twelve amino acids bacteriophage display library was used for biopanning against the PN active site. A selected clone was sequenced and analyzed for peptide primary structure. A peptide was synthesized and tested for the binding affinity to PN. PN effects including a proliferation, migration and a drug sensitivity test were performed using PN overexpression BCA cells or PN treatment and inhibited by an anti-PN peptide. An intracellular signaling mechanism of inhibition was studied by western blot analysis. Lastly, PN expressions in BCA patients were analyzed along with clinical data. Results The results showed that a candidate anti-PN peptide was synthesized and showed affinity binding to PN. PN could increase proliferation and migration of BCA cells and these effects could be inhibited by an anti-PN peptide. There was significant resistance to doxorubicin in PN-overexpressed BCA cells and this effect could be reversed by an anti-PN peptide in associations with phosphorylation of AKT and expression of survivin. In BCA patients, serum PN showed a correlation with tissue PN expression but there was no significant correlation with clinical data. Conclusions This finding supports that anti-PN peptide is expected to be used in the development of peptide therapy to reduce PN-induced chemoresistance in BCA.

Objective: This study aimed to develop a wound dressing prepared from the blending of silkworm fibroin and aloe gel extract for use in the treatment of diabetic foot ulcers (DFUs). Methods: Fibroin extracted from silkworm cocoons and aloe gel extract were dissolved in deionised water. pH levels were then adjusted with lactic acid solution. A simple casting technique was used to obtain the fibroin–aloe gel film. The surface morphology, hardness, flexibility and infrared spectrum of the sterilised film were tested. Swelling ratio was measured from changes in weight. The cytocompatibility of the film to human dermal fibroblast was determined using XTT assay. Hard-to-heal DFUs (grade I Wagner score) were treated with the film for four weeks. The application site was assessed for allergic reactions and/or sensitisation. Wound size was measured using standardised digital photography. Results: A total of five hard-to-heal DFUs were treated. The obtained film sterilised with ozonation showed a non-porous structure. The elongation at break and tensile strength of the wet film were 9.00±0.95% and 6.89±1.21N, respectively. Fourier-transform infrared spectroscopy data indicated the presence of amides I, II and III, of peptide linkage, which are the chemical characteristics of the fibroin. Functional groups relating to healing activity of the aloe gel extract were also found. The swelling ratio of the film immersed in water for 24 hours was 0.8±0.01. In three DFUs (40–50mm2 in size), a wound area reduction of 0.4–0.8mm2/day was observed and were healed in 2–3 weeks. The remaining two SFUs (500mm2 in size) showed a wound area reduction of 4mm2/day and were almost closed at four weeks. No allergic reaction or infection was observed in any of the wounds. Conclusion: The obtained film showed a non-porous structure, and its strength and flexibility were adequate for storage and handling. The film tended to increase the proliferation of fibroblasts. The wound dressing showed potential for accelerating the healing rate of DFUs.

Periostin (PN) (also known as osteoblast-specific factor OSF-2) is a protein that in humans is encoded by the POSTN gene and has been correlated with a reduced survival of cholangiocarcinoma (CCA) patients, with the well-known effect of inducing epithelial-to-mesenchymal transition (EMT). The present study investigated the effect of PN, through integrin (ITG)α5β1, in EMT-mediated CCA aggressiveness. The alterations in EMT-related gene and protein expression were investigated by real-time PCR, western blot analysis and zymogram. The effects of PN on migration and the level of TWIST-2 were assessed in CCA cells with and without siITGα5 transfection. PN was found to induce CCA cell migration and EMT features, including increments in Twist-related protein 2 (TWIST-2), zinc finger protein SNAI1 (SNAIL-1), α-smooth muscle actin (ASMA), vimentin (VIM) and matrix metallopeptidase 9 (MMP-9), and a reduction in cytokeratin 19 (CK-19) together with cytoplasmic translocation of E-cadherin (CDH-1). Additionally, PN markedly induced MMP-9 activity. TWIST-2 was significantly induced in PN-treated CCA cells; this effect was attenuated in the ITGα5β1-knockdown cells and corresponded to reduced migration of the cancer cells. These results indicated that PN induced CCA migration through ITGα5β1/TWIST-2-mediated EMT. Moreover, clinical samples from CCA patients showed that higher levels of TWIST-2 were significantly correlated with shorter survival time. In conclusion, the ITGα5β1-mediated TWIST-2 signaling pathway regulates PN-induced EMT in CCA progression, and TWIST-2 is a prognostic marker of poor survival in CCA patients.