MicroRNA miR-26a and long noncoding RNA (lncRNA) MEG3 gene have been independently reported to be tumor suppressor genes in various cancers, but neither has been previously associated with tongue squamous cell carcinoma (TSCC). We report here that miR-26a and lncRNA MEG3 gene expression were both strongly reduced in TSCC compared with levels in matched nonmalignant tissues, and combined low expression levels of both miR-26a and MEG3 emerged as an independent prognostic factor for poor clinical outcome in TSCC patients. Assays in the human TSCC cell lines SCC-15 and CAL27 showed that miR26a targets the DNA methyltransferase 3B transcript and that its inhibition may result in the upregulation of MEG3, providing a plausible link between the observed reduction of miR-26a and MEG3 in TSCC tissue. Furthermore, the overexpression of miR-26a or MEG3 in SCC-15 and CAL27 cells inhibited cell proliferation and cell cycle progression, and promoted cell apoptosis. Considering the poor prognostic outcomes associated with reduced miR-26a and MEG3, our findings imply that these factors likely play important antitumor effects in TSCC pathogenesis. Furthermore, they represent potential prognostic biomarkers for stratification of TSCC patients.Tongue squamous cell carcinoma (TSCC) is the most common type of oral cancer and is well known for its high rate of proliferation and lymph nodal metastasis. 1 In clinical practice, the prediction of prognosis and planning of treatment for patients suffering from oral cancers are predominantly based on the tumor node metastasis (TNM) staging system. 2 However, in many cases of TSCC, these conventional clinical prognostic factors remain inadequate, and are unable to discriminate tumors of the same clinical stage that may have distinct clinical outcomes and different responses to the same treatments. Therefore, the identification and application of additional biomarkers into the prognostic system that better reflect the biologic diversity of TSCC and consequently predict clinical outcomes more accurately is desirable. 3 Differentially expressed genes identified from hundreds of cancer profiling studies over the last several years have yielded numerous biomarkers that have improved the subtyping, classification and diagnosis of tumors for both research and the clinic. However, the human transcriptome comprises not only large numbers of protein-coding messenger RNAs (mRNAs) but also a large set of noncoding RNAs (ncRNAs) that have structural, regulatory or unknown functions. 4 In TSCC many microRNAs (miRNAs), such as miR-195/184/ 138/21, have been shown to be dysregulated and are believed to contribute to its development and progression. [5][6][7][8] In contrast, long noncoding RNAs (lncRNAs), tentatively defined as ncRNAs more than 200 nt in length, 9 are also known to play key roles in cancer development, 10,11 and aberrant expression of lncRNAs has been functionally associated with lung, breast and prostate carcinomas. 12-14 However, whether lncRNA has relevance to TSCC biology had not been p...

Recent studies suggest that transplantation of mesenchymal stem cells might have therapeutic effects in preventing pathogenesis of several neurodegenerative disorders. Adipose-derived mesenchymal stem cells (ADSCs) are a promising new cell source for regenerative therapy. However, whether transplantation of ADSCs could actually ameliorate the neuropathological deficits in Alzheimer's disease (AD) and the mechanisms involved has not yet been established. Here, we evaluated the therapeutic effects of intracerebral ADSC transplantation on AD pathology and spatial learning/memory of APP/PS1 double transgenic AD model mice. Results showed that ADSC transplantation dramatically reduced b-amyloid (Ab) peptide deposition and significantly restored the learning/memory function in APP/PS1 transgenic mice. It was observed that in both regions of the hippocampus and the cortex there were more activated microglia, which preferentially surrounded and infiltrated into plaques after ADSC transplantation. The activated microglia exhibited an alternatively activated phenotype, as indicated by their decreased expression levels of proinflammatory factors and elevated expression levels of alternative activation markers, as well as Ab-degrading enzymes. In conclusion, ADSC transplantation could modulate microglial activation in AD mice, mitigate AD symptoms, and alleviate cognitive decline, all of which suggest ADSC transplantation as a promising choice for AD therapy. This manuscript is published as part of the International Association of Neurorestoratology (IANR) supplement issue of Cell Transplantation.

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Sciatic nerve injury presents an ongoing challenge in reconstructive surgery. Local stem cell application has recently been suggested as a possible novel therapy. In the present study we evaluated the potential of a chitosan/silk fibroin scaffold serving as a delivery vehicle for adipose-derived stem cells and as a structural framework for the injured nerve regeneration. The cell-loaded scaffolds were used to regenerate rat sciatic nerve across a 10 mm surgically-induced sciatic nerve injury. The functional nerve recovery was assessed by both walking track and histology analysis. Results showed that the reconstruction of the injured sciatic nerve had been significantly enhanced with restoration of nerve continuity and function recovery in the cell-loaded scaffold groups, and their target skeletal muscle had been extensively reinnervated. This study raises a potential possibility of using the newly developed nerve grafts as a promising alternative for nerve regeneration.

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In this study, a series of chitosan films with different protonation degrees were prepared by deacidification with NaOH aqueous or ethanol solutions. The films were then used as a model to investigate the effects of the positive charge of chitosan on blood coagulation. The results showed that the positive charge of chitosan acted as a double-edged sword, in that it promoted erythrocyte adhesion, fibrinogen adsorption, and platelet adhesion and activation, but inhibited activation of the contact system. In contrast to prevailing views, we found that the positive charge of chitosan retarded thrombin generation and blood coagulation on these films. At least two reasons were responsible for this phenomenon. First, the positive charge inhibited the contact activation, and second, the positive charge could not significantly promote the activation of non-adherent platelets in the bulk phase during the early stage of coagulation. The present findings improve our understanding of the events leading to blood coagulation on chitosan films, which will be useful for the future development of novel chitosan-based hemostatic devices.

In scaffold based bone tissue engineering, both the pore size and the mechanical properties of the scaffold are of great importance. However, an increase in pore size is generally accompanied by a decrease in mechanical properties. In order to achieve both suitable mechanical properties and porosity, a multilayer scaffold is designed to mimic the structure of cancellous bone and cortical bone. A porous nano-hydroxyapatite-chitosan composite scaffold with a multilayer structure is fabricated and encased in a smooth compact chitosan membrane layer to prevent fibrous tissue ingrowth. The exterior tube is shown to have a small pore size (15-40 microm in diameter) for the enhancement of mechanical properties, while the core of the multilayer scaffold has a large pore size (predominantly 70-150 microm in diameter) for nutrition supply and bone formation. Compared with the uniform porous scaffold, the multilayer scaffold with the same size shows an enhanced mechanical strength and larger pore size in the center. More cells are shown to grow into the center of the multilayer scaffold in vitro than into the uniform porous scaffold under the same seeding condition. Finally, the scaffolds are implanted into a rabbit fibula defect to evaluate the osteoconductivity of the scaffold and the efficacy of the scaffold as a barrier to fibrous tissue ingrowth. At 12 weeks post operation, affluent blood vessels and bone formation are found in the center of the scaffold and little fibrous tissue is noted in the defect site.

Spinal cord injury (SCI) is a common clinical disease that places a heavy burden on families and society. Cellular therapy provides a method of giving a supplement of cells lost in the injury and promoting functional recovery after SCI. Neural stem cells (NSCs) and olfactory ensheathing cells (OECs) are two most promising cell types. NSCs have the potential of differentiating into neurons and glial cells, and OECs could help the axons of neurons pass through the glial scar to promote functional recovery. NSCs were isolated from the cortices of fetal rats on days 12-14 of embryonic development and OECs were isolated from the olfactory bulbs of adult rats. In vitro coculture studies demonstrated OECs could promote NSCs to differentiate into neurons. Four groups of rats that had been 3/4 spinal cord transectioned at T9 were injected with DMEM/F12 solution, NSCs, OECs, and NSCs + OECs, respectively, 7 days post-SCI. Twelve weeks postoperation, the hindlimb locomotor function of rats in the cotransplantation group was significantly improved compared with that in the other three groups. Histological observation and immunohistochemical staining of NF-200 both showed new nerve fibers across the injured region. Cotransplantation of NSCs and OECs might have a synergistic effect on promoting neural regeneration and improving the recovery of locomotion function. Cotransplantation of NSCs and OECs was better than a single graft of either NSCs or OECs. These findings have provided a new way of thinking in the treatment of SCI.