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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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.

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Parkinson disease (PD) is a neurodegenerative disease characterized by selective loss of dopaminergic (DA) neurons in the midbrain. The regulatory role of a variety of microRNAs in PD has been confirmed, and our study is the first to demonstrate that miR-3473b is involved in the regulation of PD. In vitro, an miR-3473b inhibitor can inhibit the secretion of inflammatory factors (TNFα and IL-1β) in moues microglia cell line (BV2) cells induced by lipopolysaccharide (LPS) and promote autophagy in BV2 cells. In vivo, miR-3473b antagomir can inhibit the activation of substantia nigra pars compacta (SNpc) microglia of C57BL/6 mice induced by 1-Methyl-4-phenyl-1, 2,3,6-tetrahydropyridine (MPTP) and promote autophagy. Deletion of TREM2, one of the most highly expressed receptors in microglia, leads to the occurrence and development of PD. ULK1 is a component of the Atg1 complex. Deletion of ULK1 aggravates the pathological reaction of PD. TREM2 and ULK1 are predicted potential targets of miR-3473b by Targetscan. Then, the results of our experiments indicate that transfection with a miR-3473b mimic can inhibit the expression of TREM2 and ULK1. Data from a double luciferase experiment indicate that the 3'-UTR of TREM2, but not ULK1, is the direct target of miR-3473b. Then we aim to investigate the regulation of TREM2 and ULK1 in PD. We found that the expression of p-ULK1 was significantly increased via up-regulation of TREM2. The increased expression of p-ULK1 can promote autophagy and inhibit the expression of inflammatory factors. The regulation of ULK1 by miR-3473b may be accomplished indirectly through TREM2. Thus, miR-3473b may regulate the secretion of proinflammatory mediators by targeting TREM2/ULK1 expression to regulate the role of autophagy in the pathogenesis of inflammation in Parkinson's disease, suggesting that mir-3473b may be a potential therapeutic target to regulate the inflammatory response in PD.