Recombinant Spidroin Films Attenuate Individual Markers of Glucose Induced Aging in NIH 3T3 Fibroblasts.

The effect of bioresorbable materials on aging in cultured mouse NIH 3T3 fibroblasts treated with elevated glucose concentration was investigated. The cells were grown on films produced from the silkworm fibroin and rS1/9, a recombinant analog of Nephila clavipes spidroin 1. Exposure to 50 mM glucose of the cells grown on uncoated glass support resulted in the cell growth retardation. The average areas of the cells and nuclei and the percentage of apoptotic cells increased, whereas the amount of soluble collagen decreased. In contrast, on the fibroin and spidroin films, the cell density and the percentage of 5-bromo-2'-deoxyuridine (BrdU)-positive cells were higher vs. the cells grown on the glass support. The films protected NIH 3T3 fibroblasts from the glucose-induced death. The most prominent effects on the cell density, BrdU incorporation, and apoptosis prevention were observed in the cells cultured on spidroin films. Unlike the cells grown on glass support (decrease in the soluble collagen production) or fibroin (no effect), production of soluble collagen by the cells grown on spidroin films increased after cell exposure to 50 mM glucose. Molecular analysis demonstrated that 50 mM glucose upregulated phosphorylation of the NFκB heterodimer p65 subunit in the cells grown on the glass support. The treatment of cells grown on fibroin films with 5.5 mM or 50 mM glucose had no effect on p65 phosphorylation. The same treatment decreased p65 phosphorylation in the cells on the spidroin films. These results demonstrate the anti-aging efficacy of biomaterials derived from the silk proteins and suggest that spidroin is more advantageous for tissue engineering and therapy than fibroin.

Snail-Family Proteins: Role in Carcinogenesis and Prospects for Antitumor Therapy.

The review analyzes Snail family proteins, which are transcription factors involved in the regulation of the epithelial-mesenchymal transition (EMT) of tumor cells. We describe the structure of these proteins, their post-translational modification, and the mechanisms of Snail-dependent regulation of genes. The role of Snail proteins in carcinogenesis, invasion, and metastasis is analyzed. Furthermore, we focus on EMT signaling mechanisms involving Snail proteins. Next, we dissect Snail signaling in hypoxia, a condition that complicates anticancer treatment. Finally, we offer classes of chemical compounds capable of down-regulating the transcriptional activity of Snails. Given the important role of Snail proteins in cancer biology and the potential for pharmacological inhibition, Snail family proteins may be considered promising as therapeutic targets.

A Unique Prototypic Device for Radiation Therapy: The p53-Independent Antiproliferative Effect of Neutron Radiation.

Radiation therapy with heavy particles including neutrons, an otherwise therapeutically perspective because of its high tissue penetration and efficient tumor damage, is currently limited by the lack of adequate equipment. An NG-24 generator (140 kg, 42 × 110 cm, ~1011 particles/s, > 14 MeV) has been designed and engineered to replace the huge and environmentally harmful neutron reactors, cyclotrons, and accelerators with a compact, portable, safe, and potent source of high-energy neutrons. We demonstrate that the neutron beam produced by NG-24 causes a significant antiproliferative effect on human tumor cell lines regardless of the status of the anti-apoptotic p53 protein. Phosphorylation of histone 2A and increased amounts of p21, cyclin D, and phospho-p53 were detectable in HCT116 colon carcinoma cells (wild-type p53) irradiated with 4 Gy several days post-treatment, accompanied by G2/M phase arrest. These treatments dramatically reduced the ability of single cells to form colonies. In the HCT116p53KO subline (p53 -/-), the G2/M arrest was independent of the aforementioned mechanisms. Hence, the NG-24 generator is a source of a powerful, therapeutically relevant neutron flux that triggers a p53-independent antiproliferative response in tumor cells.