No abstract

In the last few decades, nanoparticles (NPs) have been recognized as promising candidates for starting a new revolution in science and technology due to their unusual properties, attracting the attention of physicists, chemists, biologists, and engineers. The aim of this study is to evaluate the toxicities (at both cellular and molecular levels) of three forms of superparamagnetic iron oxide nanoparticles (SPIONs) of various surface chemistries (COOH, plain, and NH(2)) through the comparison with gene expression patterns of three cell types (i.e., human heart, brain, and kidney). For this purpose, both an MTT assay and a DNA microarray analysis were applied in three human cell lines--HCM (heart), BE-2-C (brain), and 293T (kidney)--under the exposure to SPIONs-COOH, SPIONs-NH(2), and bare SPIONs. The specific gene alteration and hierarchical clustering revealed that SPIONs-COOH altered genes associated with cell proliferative responses due to their reactive oxygen species (ROS) properties. It was also found that the cell type can have quite a significant role in the definition of suitable pathways for detoxification of NPs, which has deep implications for the safe and high yield design of NPs for biomedical applications and will require serious consideration in the future.

No abstract

Axon growth potential is highest in young neurons but diminishes with age, thus becoming a significant obstacle to axonal regeneration after injury in maturity. The mechanism for the decline is incompletely understood, and no effective clinical treatment is available to rekindle innate growth capability. Here, we show that Smad1-dependent bone morphogenetic protein (BMP) signaling is developmentally regulated and governs axonal growth in dorsal root ganglion (DRG) neurons. Down-regulation of the pathway contributes to the age-related decline of the axon growth potential. Reactivating Smad1 selectively in adult DRG neurons results in sensory axon regeneration in a mouse model of spinal cord injury (SCI). Smad1 signaling can be effectively manipulated by an adenoassociated virus (AAV) vector encoding BMP4 delivered by a clinically applicable and minimally invasive technique, an approach devoid of unwanted abnormalities in mechanosensation or pain perception. Importantly, transected axons are able to regenerate even when the AAV treatment is delivered after SCI, thus mimicking a clinically relevant scenario. Together, our results identify a therapeutic target to promote axonal regeneration after SCI.intrinsic axon growth capacity | intrathecal viral vector delivery S pinal cord injury (SCI) disrupts long-projection axons, with devastating neurological outcomes, yet no effective clinical treatment exists. Neurons fail to regenerate axons because of a growth-inhibiting environment at the injury site (1-4) and because of an age-dependent decline in the intrinsic axon growth potential (5, 6). Nevertheless, blocking extracellular inhibitory molecules (7-10) or alleviating the intracellular negative regulators of axonal growth (5, 6, 11, 12) enables only limited axonal regeneration. Thus, additional molecular pathways that can rekindle innate growth capability must exist but remain unidentified (13).Dorsal root ganglion (DRG) neurons are a favored model system to study axonal regeneration. These neurons have an axon with two branches-a peripheral branch that innervates sensory organs and a central branch that relays information to the CNS. The central branches of adult DRG neurons in the spinal cord are refractory to regeneration unless their peripheral branches are severed first. This so-called "conditioning lesion" paradigm activates a transcription program that enhances the intrinsic axonal growth potential (14). Previously, through gene expression profiling, we have demonstrated that Smad1 is induced after peripheral axotomy and that intraganglionic delivery of bone morphogenetic protein 2 or 4 (BMP2 or -4) activates Smad1 and enhances the axon growth potential of adult DRG neurons in cultures. In contrast, severing the central branches of DRGs fails to activate the Smad1 pathway, which correlates with the absence of regeneration after SCI (15).These results suggested a possible involvement of Smad1 in regulating the growth state of DRG neurons. It is not known, however, whether Smad1 governs the axon growth program ...

No abstract

In this study, we quantitatively analyzed the affinity of cell adhesion to aligned nanofibers composed of composites of poly(glycolic acid) (PGA) and collagen. Electrospun composite fibers were fabricated at various PGA/collagen weight mixing ratio (7, 18, 40, 67, and 86%) to generate fibers that ranged in diameter from 10 mum to 500 nm. Scanning electron microscopy (SEM) observation revealed that the PGA/collagen fibers were long and uniformly aligned, irrespective of the PGA/collagen weight mixing ratio. In addition, it was observed that a significantly higher number of NIH3T3 fibroblasts adhered to nanofibers with smaller diameters in comparison to fibers with larger diameters. The highest affinity of cell adhesion was observed in the PGA/collagen fibers with diameter of 500 nm and PGA/collagen weight mixing ratio of 40%. Furthermore, the adherent cells were more elongated on fibers with smaller diameters. Thus, based on the results here, PGA/collagen composite fibers are suitable for tissue culture studies and provide an attractive material for tissue engineering applications.

No abstract

No abstract