Additional file 1: of Computational analysis reveals the coupling between bistability and the sign of a feedback loop in a TGF-β1 activation model

Supplementary Notes. (PDF 107 kb

Additional file 4: Table S3. of Computational analysis reveals the coupling between bistability and the sign of a feedback loop in a TGF-β1 activation model

List of primer sequences for genes probed on quantitative real time PCR. (PDF 26 kb

Mitoxantrone- and Folate-TPGS2k Conjugate Hybrid Micellar Aggregates To Circumvent Toxicity and Enhance Efficiency for Breast Cancer Therapy

Mitoxantrone (MTO) is a potent drug used to treat breast cancer; however, efforts to expand its clinical applicability have been restricted because of its high risk for cardiotoxicity. In this study, we successfully conjugated MTO or folic acid (FA) to a synthesized D-α-tocopheryl polyethylene glycol 2000 succinate (TPGS2k), herein, shortened to MCT and FCT, respectively. The two produced conjugates could self-assemble to form MCT micelles or MCT/FCT mixed micelles (FMCT) aiming to lower systemic toxicity, enhance entrapment efficiency, and provide a platform for targeted delivery. Moreover, these micellar materials showed a significantly low CMC and could be used to load MTO. The diameters of MTO-loaded micelles (MTO-MCT and MTO-FMCT) were less than 100 nm with a negative zeta potential. We further characterized the pH-responsive drug release of MTO-MCT and MTO-FMCT and then assessed their cellular uptake and antitumor efficacy in human breast cancer cell lines (MCF-7) via confocal microscopy, flow cytometry, and cytotoxicity studies. All the results revealed that both MTO-MCT and MTO-FMCT increased drug loading and entrapment efficiency and possessed sufficient pH-sensitive release. Additionally, MTO-FMCT displayed an improved uptake through folate-mediated endocytosis, resulting in a higher cytotoxic effect on MCF-7 cells compared with that of MTO-MCT. Meanwhile, both MTO-MCT and MTO-FMCT exhibited a low toxicity on hCMEC/D3 normal cells. More importantly, pharmacokinetic study demonstrated that, in comparison with free MTO injection, MTO-MCT and MTO-FMCT, respectively, achieved half-lives 11.5 and 13 times longer and a 9.7- and 5.8-fold increase in AUC. In vivo, both MTO-MCT and MTO-FMCT formulations significantly prolonged the survival time of MCF-7 tumor-bearing mice and had a better efficacy/toxicity ratio. Promisingly, MTO-FMCT micelles remarkably increased MTO accumulation in tumors in vivo, induced higher tumor cell apoptosis, and showed lower toxicity toward major organs. These results imply that MTO-FMCT may be used as a potential drug delivery system for breast cancer targeted therapy

Identification of Conserved and Novel microRNAs in Cashmere Goat Skin by Deep Sequencing

<div><p>MicroRNAs (miRNAs) are a class of small RNAs that play significant roles in regulating the expression of the post-transcriptional skin and hair follicle gene. In recent years, extensive studies on these microRNAs have been carried out in mammals such as mice, rats, pigs and cattle. By comparison, the number of microRNAs that have been identified in goats is relatively low; and in particular, the miRNAs associated with the processes of skin and hair follicle development remain largely unknown. In this study, areas of skin where the cashmere grows in anagen were sampled. A total of 10,943,292 reads were obtained using Solexa sequencing, a high-throughput sequencing technology. From 10,644,467 reads, we identified 3,381 distinct reads and after applying the classification statistics we obtained 316 miRNAs. Among them, using conservative identification, we found that 68 miRNAs (55 of these are confirmed to match known sheep and goat miRNAs in miRBase ) are conserved in goat and have been reported in NCBI; the remaining 248 miRNA were conserved in other species but have not been reported in goat. Furthermore, we identified 22 novel miRNAs. Both the known and novel miRNAs were confirmed by a second sequencing using the same method as was used in the first. This study confirmed the authenticity of 316 known miRNAs and the discovery of 22 novel miRNAs in goat. We found that the miRNAs that were co-expressed in goat and sheep were located in the same region of the respective chromosomes and may play an essential role in skin and follicle development. Identificaton of novel miRNAs resulted in significant enrichment of the repertoire of goat miRNAs.</p> </div