Carbon nanotubes have mechanical properties that are far in excess of conventional fibrous materials used in engineering polymer composites. Effective reinforcement of polymers using carbon nanotubes is difficult due to poor dispersion and alignment of the nanotubes along the same axis as the applied force during composite loading. This paper reviews the mechanical properties of carbon nanotubes and their polymer composites to highlight how many previously prepared composites do not effectively use the excellent mechanical behaviour of the reinforcement. Nanomechanical tests using atomic force microscopy are carried out on simple uniaxially aligned carbon nanotube-reinforced polyvinyl alcohol (PVA) fibres prepared using electrospinning processes. Dispersion of the carbon nanotubes within the polymer is achieved using a surfactant. Young's modulus of these simple composites is shown to approach theoretically predicted values, indicating that the carbon nanotubes are effective reinforcements. However, the use of dispersant is also shown to lower Young's modulus of the electrospun PVA fibres.
microRNA-34a (miR-34a) and sirtuin 1 (SirT1) have been extensively studied in tumour biology and longevity/aging, but little is known about their functional roles in smooth muscle cell (SMC) differentiation from pluripotent stem cells. Using well-established SMC differentiation models, we have demonstrated that miR-34a has an important role in SMC differentiation from murine and human embryonic stem cells. Surprisingly, deacetylase sirtuin 1 (SirT1), one of the top predicted targets, was positively regulated by miR-34a during SMC differentiation. Mechanistically, we demonstrated that miR-34a promoted differentiating stem cells' arrest at G0/G1 phase and observed a significantly decreased incorporation of miR-34a and SirT1 RNA into Ago2-RISC complex upon SMC differentiation. Importantly, we have identified SirT1 as a transcriptional activator in the regulation of SMC gene programme. Finally, our data showed that SirT1 modulated the enrichment of H3K9 tri-methylation around the SMC gene-promoter regions. Taken together, our data reveal a specific regulatory pathway that miR-34a positively regulates its target gene SirT1 in a cellular context-dependent and sequence-specific manner and suggest a functional role for this pathway in SMC differentiation from stem cells in vitro and in vivo.
In soft tissues, large molecules such as proteoglycans trapped in the extracellular matrix (ECM) generate high levels of osmotic pressure to counter-balance external pressures. The semi-permeable matrix and fixed negative charges on these molecules serve to promote the swelling of tissues when there is an imbalance of molecular concentrations. Structural molecules, such as collagen fibres, form a network of stretch-resistant matrix, which prevents tissue from over-swelling and keeps tissue integrity. However, collagen makes little contribution to load bearing; the osmotic pressure in the ECM is the main contributor balancing external pressures. Although there have been a number of studies on tissue deformation, there is no rigorous analysis focusing on the contribution of the osmotic pressure in the ECM on the viscoelastic behaviour of soft tissues. Furthermore, most previous works were carried out based on the assumption of infinitesimal deformation, whereas tissue deformation is finite under physiological conditions. In the current study, a simplified mathematical model is proposed. Analytic solutions for solute distribution in the ECM and the free-moving boundary were derived by solving integro-differential equations under constant and dynamic loading conditions. Osmotic pressure in the ECM is found to contribute significantly to the viscoelastic characteristics of soft tissues during their deformation.
There is evidence demonstrating the regulation of microRNAs in a myriad of vascular biology events such as cardiogenesis, but the role of miRNA in controlling human embryonic stem cell fate in differentiation towards the endothelial lineage remains to be studied. To study this issue, we designed and developed a differentiation culture model to generate endothelial cells from undifferentiated human embryonic stem cells. We aim to investigate the in vivo therapeutic effects of differentiated endothelial cells derived from human stem cells as well as determining the role of miRNA/s involved in vascular lineage differentiation. Undifferentiated human embryonic stem cells were firstly cultured in differentiation conditions to derive endothelial cells. Differentiated day 9 stem cell-derived endothelial cells expressed specific endothelial markers such as CD31 and CD144. At day 17 of differentiation, flow cytometry analysis showed that 34.1% of the heterogeneous differentiated human stem cells were CD146 positive. This population of cells was sorted for CD146 and expanded in vitro. Expanded CD146 positive cells were capable of ac-LDL uptake, binding to Lectin and formation of vascular structures on Matrigel, suggesting that expanded CD146 positive cell are functional endothelial cells. Determination of potential role of miRNA involved in early endothelial development was next carried out using miRNA array expression profiling in the differentiating human embryonic stem cells. Five potential upregulated miRNA, were selected from the miRNA array analysis and further analysis found that miR-150* and miR-200c were crucial in vascular endothelial lineage differentiation. It was found that the targets of these miRNAs in stem cell differentiation involved several proteins/transcription factors. Thus, we established an effective model to derive endothelial cells in vitro and demonstrated the involvement of miR-150* and miR-200c in human stem cell differentiation, implicating a potential usefulness for stem cell therapy in the future.
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