Mechanical and biological properties of photocurable oligolactide-HA composites investigated under accelerated degradation

The major concern related to biodegradable bone substitute materials is the loss of mechanical strength which can be undesirable when occurring too quickly before new bone formation. In this study, the multifunctional lactide oligomers having 2, 3, and 4 arms end capped with methacrylate groups were synthesized with the aim of improving the degradation properties. Their composites with hydroxyapatite (HA) were photopolymerized and subjected to accelerated degradation at 60 °C. The results showed that increasing number of arms significantly improved thermal and mechanical properties as well as biocompatibility of the composites. All composites although varying in number of arms had similar levels of bone-specific gene expression and calcification indicating their equal bioactivity in supporting bone formation. The high HA content in the composites was proposed to be responsible for enhanced osteoblast response, and this tended to suppress the effects of polymeric structure.     

A bibenzyl from <Emphasis Type="Italic">Dendrobium ellipsophyllum</Emphasis> induces apoptosis in human lung cancer cells

Failure of current chemotherapeutic drugs leads to the recurrence of tumor pathology and mortality in lung cancer patients. This study aimed to evaluate the anticancer activity and related mechanisms of 4,5,4′-trihydroxy-3,3′-dimethoxybibenzyl (TDB), a bibenzyl extracted from Dendrobium ellipsophyllum Tang and Wang, in human lung cancer cells. Cytotoxicity of TDB (0–300 µM) in different types of human lung cancer cells (H460, H292 and H23) and human dermal papilla cells (DPCs) was evaluated via MTT viability assay. Selective anticancer activity of TDB against human lung cancer cells was demonstrated with a high IC₅₀ (approximately > 300 µM) in DPCs, while IC₅₀ in human lung cancer H460, H292 and H23 cells was approximately 100 ± 5.18, 100 ± 8.73 and 188.89 ± 8.30 µM, respectively. After treatment with 50 µM of TDB for 24 h, flow cytometry analysis revealed the significant increase of early and late apoptosis with absence of necrosis cell death in human lung cancer cells. The up-regulation of p53, a tumor-suppressor protein, was elucidated in human lung cancer cells treated with 10–50 µM of TDB. Alteration to down-stream signaling of p53 including activation of pro-apoptosis protein (Bcl-2-associated X protein; Bax), reduction of anti-apoptosis (B cell lymphoma 2; Bcl-2 and myeloid cell leukemia 1; Mcl-1) and suppression on protein kinase B (Akt) survival pathway were notified in TDB-treated lung cancer cells. The information obtained from this study strengthens the potential development of TDB as an anticancer compound with a favorable human safety profile and high efficacy.     

Synthesis of GTMAC modified chitin-PAA gel and evaluation of its biological properties

The dressing prepared from GTMAC modified chitin-PAA was introduced with the aim of facilitating wound healing, particularly those effectively absorbing exudates, maintaining a moist wound environment and controlling bacterial proliferation. Chitin was chemically modified with acrylic acid to encourage a moist wound healing environment. The highly water-absorbable resulting product (chitin-PAA) was further reacted with glycidyltrimethylammonium chloride (GTMAC) to impart antibacterial activities. The final product, chitin-PAA-GTMAC was characterized by the techniques of Fourier Transform Infrared (FTIR), solid state (15) N NMR, and elemental analysis. Their cytotoxicity and antibacterial activities against S. epidermidis and E. coli were evaluated which found increasing effects in those properties with increasing degree substitution of GTMAC. All materials also showed good blood-clotting ability. The collagen gel contraction assay was used to analyze the behavior of fibroblasts after contact with the gels. The extent of the gel contraction as well as the examination of the secreted interleukin-8 (IL-8) and transforming growth factor-β1 (TGF-β1) were investigated. The results showed that chitin-PAA modified with GTMAC could stimulate the production of IL-8, but TGF-β1. Fibroblasts presented normal spreading and formation of cellular processes in the collagen gels with all of the modifications. Furthermore, all modified gels except for the highest GTMAC content gel [chitin-PAA-GTMAC (1:20)] were found a greater extent in gel contraction than the unmodified chitin-PAA. It suggested the promoting effect of GTMAC on cell proliferation if the GTMAC content in the gel was not too high, that is, the mole ratio of glucosamine to GTMAC of the gel should not greater than 1:10.     

Peptides extracted from edible mushroom: Lentinus squarrosulus induces apoptosis in human lung cancer cells

Context: Lentinus squarrosulus Mont. (Polyporaceae) is an interesting source of diverse bioactive compounds.

Objective: This is the first study of the anticancer activity and underlying mechanism of peptides extracted from Lentinus squarrosuls.

Materials and methods: Peptides were isolated from the aqueous extract of L. squarrosulus by employing solid ammonium sulphate precipitation. They were further purified by ion-exchange chromatography on diethylaminoethanol (DEAE)-cellulose and gel filtration chromatography on Sephadex G25. Anticancer activity was investigated in human lung cancer H460, H292 and H23 cells cultured with 0–40?μg/mL of peptide extracts for 24?h. Cell viability and mode of cell death were evaluated by MTT and nuclear staining assay, respectively. Western blotting was used to investigate the alteration of apoptosis-regulating proteins in lung cancer cells treated with peptide extracts (0–20?μg/mL) for 24?h.

Results: The cytotoxicity of partially-purified peptide extracts from L. squarrosulus was indicated with IC₅₀ of ～26.84?±?2.84, 2.80?±?2.14 and 18.84?±?0.30?μg/mL in lung cancer H460, H292 and H23 cells, respectively. The extracts at 20?μg/mL induced apoptosis through the reduction of anti-apoptotic Bcl-2 protein (～0.5-fold reduction) and up-regulation of BAX (～4.5-fold induction), a pro-apoptotic protein. Furthermore, L. squarrosulus peptide extracts (20?μg/mL) also decreased the cellular level of death receptor inhibitor c-FLIP (～0.6-fold reduction).

Conclusions and discussion: This study provides the novel anticancer activity and mechanism of L. squarrosulus peptide extracts, which encourage further investigation and development of the extracts for anticancer use.