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Background: Neural stem/progenitor cells (NSPCs)-based treatment is a potential therapeutic approach for stroke. MicroRNAs (miRNAs) have been recently verified as promoters or suppressors in the regulation of NSPCs. However, the underlying mechanisms regulating cell biological behaviors of NSPCs remain largely unknown., Methods: we retrieved papers focusing on potential roles and mechanisms of miRNAs in the regulation of NSPCs, and paid a special attention to clinical therapeutic potentials of miRNAs in stroke patients. This narrative review provides a comprehensive and critical landscape of this issue., Results: We summarize the most recent studies on the roles and mechanisms of miRNAs in regulating the proliferation, differentiation and migration of NSPCs and fully discuss the potential clinical implications of miRNAs interacting with NSPCs in stroke patients., Conclusion: Promising but full of hurdles, miRNAs have been confirmed to play a critical role in regulating NSPCs. Clinical potentials of miRNAs are huge in treating stroke patients receiving NSPCs-based therapy, which can be used as biomarkers for the diagnosis and prognosis, and as targets for controlling the proliferation, differentiation and migration of NSPCs., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

Ligustilide is widely thought to be the most potent bioactive constituent of Angelica sinensis. We have previously reported the role of ligustilide in preventing TNF-α-induced apoptosis and identified the presence of autophagosome clusters. Then, we hypothesised that autophagy may contribute to muscle loss and that ligustilide could protect cell fibres by regulating the autophagic process. The aim of this study was to identify the effects of ligustilide on autophagy regulation during cell differentiation in the presence of TNF-α. We then observed intracellular morphologic changes and autophagosome formation using transmission electron microscopy. LC3B expression was assessed by immunofluorescence and Atg-7, Atg-5, Atg-12 and LC3B expression levels were detected by western blot. The results revealed a reduction in the number of TNF-α-induced autophagosomes after ligustilide treatment accompanied by a decrease in Atg-7, Atg-5, Atg-12 and LC3B expression, as well as a reduction of the LC3BII/I ratio in a concentration-dependent manner. Our findings provide evidence supporting a protective effect of ligustilide against TNF-α-induced autophagy during myotubes formation., (Copyright © 2014 Elsevier Masson SAS. All rights reserved.)

Although the mammalian target of rapamycin complex 1 (mTORC1) functions as an important signaling complex in many cellular processes, the role of mTORC1 in neurons derived from embryonic stem cells (ESCs) has been less explored. Here, using a modified protocol to differentiate mouse ESCs (mESCs) into almost uniform glutamatergic neurons, we explored the importance of raptor/mTORC1 in the differentiation of mESCs. Raptor gene-trap mESCs, and raptor-knockdown mESCs formed smaller-sized embryonic bodies than the wild type and failed to undergo neuronal differentiation. Treatment with 1μM rapamycin starting at the point when neuronal precursors began to differentiate from mESCs caused the gradual loss of neurites, shrinkage of soma, and a decreased ratio of neurite length to cell number over 48 to 72h of treatment. This change was accompanied by activation of caspase-3 and S6 kinase (S6K), but not 4E-binding protein 1 (4EBP1). Knockdown of raptor during neuronal differentiation from mESCs also resulted in gradual loss of neurites and shrinkage of cell bodies. Loss of neurite density resulting from rapamycin treatment could be reversed by overexpression of S6K T389E. Taken together, these data demonstrate that raptor/mTORC1/S6K plays a critical role in the differentiation and survival of neurons derived from mESCs., (© 2013.)

Multiple tumor-derived factors are responsible for the accumulation and expansion of immune-suppressing myeloid-derived suppressor cells (MDSC) and M2-like tumor-associated macrophages (TAM) in tumors. Here, we show that treatment of tumor-bearing mice with docetaxel in combination with the phosphatidylserine-targeting antibody 2aG4 potently suppressed the growth and progression of prostate tumors, depleted M2-like TAMs, and MDSCs, and increased the presence of M1-like TAMs and mature dendritic cells in the tumors. In addition, the antibody markedly altered the cytokine balance in the tumor microenvironment from immunosuppressive to immunostimulatory. In vitro studies confirmed that 2aG4 repolarized TAMs from an M2- to an M1-like phenotype and drove the differentiation of MDSCs into M1-like TAMs and functional dendritic cells. These data suggest that phosphatidylserine is responsible for the expansion of MDSCs and M2-like TAMs in tumors, and that bavituximab, a phosphatidylserine-targeting antibody currently in clinical trials for cancer, could reverse this process and reactivate antitumor immunity., (©2013 AACR.)

Objective: To observe and evaluate the effect of transdifferentiation of bone marrow derived stroma cells (BMSCs) into nerve cells by ultrafiltration membrane extract mixture from Angelica sinensis and Hedysarum polybotrys., Methods: The BMSCs in vitro cultured after treated by ultrafiltration membrane extract mixture from Angelica sinensis and Hedysarum polybotrys were divided into 5 groups, i.e., the blank group, the low dose group (6 g/L mixture), the high dose group (12 g/L mixture), the combination group (3 g/L mixture + 0.5 mmol/Lbeta-mercaptoethanol), and the positive control group (13-mercaptoethanol). The effects of transdifferentiation of nerve cells were observed using toluidine blue staining in each group. The differences of 5 specific neuroproteins, i.e. neuron-specific enolase (NSE), nestin, neurofilament protein (NFP), microtubule associated protein 2 (MAP2), and glial fibrillary acidic protein (GFAP) were detected using immunohistochemical technique and immunofluorescent technique respectively. The changes of the cell cycle were detected using flow cytometry (FCM)., Results: After induction BMSCs changed morphologically. The morphological features were weaker in the high and low dose groups than in the combination group and the positive group. Except the blank group, the aforesaid 5 proteins expressed positively in the rest groups. Their expression levels were highest in the positive control group (P <0.05), followed by the combination group (P <0.05). As for the cell proliferation rate detected by FCM, it was the lowest in the positive control group, followed by high dose group, low dose group, and then the combination group (all P <0.05)., Conclusions: The ultrafiltration membrane extract mixture from Angelica sinensis and Hedysarum polybotrys could effectively induce the transdifferentiation of BMSCs into nerve cells. Its inducing capacities were weaker in the positive control group, but it showed marked proliferation effects on differentiated cells. Therefore, the mixture might be a more ideal medication pathway for effectively inducing BMSCs' transdifferentiation into nerve cells, which might have higher proliferation and be used for clinical research.

Much effort is being marshaled to generate uniform neuronal populations from embryonic stem (ES) cells, but a completely reliable method has yet to be developed. Here we modified and established a method that brings us closer to this goal. By examining many parameters, we found that the optimal timing of applying a freshly made trypsin/EDTA (ethylenediaminetetraacetic acid) solution to dissociate embryoid bodies determines the success of the outcome. Analyses demonstrated that with this approach, more than 87% of cells differentiated into glutamatergic neurons. Hence, these uniform neurons that were differentiated from ES cells provide an ideal cellular model for many aspects of research., (2010 Elsevier Inc. All rights reserved.)

Objective: To investigate the molecular mechanism underlying the differentiation of human umbilical cord-derived mesenchymal stem cells (hUCMSCs) into myocardial cells induced by 5-azacytidine (5-aza), and to explore the expression and significance of DLL4-Notch signaling in this process., Materials and Methods: hUCMSCs were isolated and purified from the umbilical cords of normal or cesarean term deliveries under sterile conditions. After treatment with 5-aza for 24 h, hUCMSCs was continued to culture, the expression of GATA4 and NKx2.5 at 4 weeks after induction, DLL4 and Notch1 mRNA at 1d, 3d, 5d, 7d after induction were detected. The expression of cardiac troponin I (cTnI) after 4 weeks was determined by immunocytochemistry., Results: hUCMSCs treated with 5-aza were stained positively for cTnI 4 weeks after induction. The expression of Notch1 and DLL4 mRNA in the 5-aza-induced group was stable and significantly higher than that in the control group (mean Ct value for the Notch1 gene: 0.51 ± 0.21 in the 5-aza-induced group vs. 7.85 ± 0.35 in the control group; mean Ct value for the DLL4 gene: 1.60 ± 0.49 in the 5-aza-induced group vs. 12.42 ± 0.73 in the control group). Similar results were observed for Nkx2.5 and GATA4 genes. The expressions of Nkx2.5 and GATA4 mRNA in the 5-aza group were 4.72 ± 0.58 and 3.76 ± 0.06 times higher than that in the control group, respectively, with statistical significance., Conclusions: hUCMSCs can be differentiated into myocardial cells by 5-aza induction in vitro. 5-Aza may affect this process by regulating the expression of GATA4 and Nkx2.5 genes. The DLL4-Notch signal pathway may be involved in this process.

Abstract: Ligustilide, the major component of Angelica sinensis, is also thought to be the most potent bioactive constituent of this plant. Ligustilide has been reported to markedly protect neural tissue against apoptosis. However, little is known regarding ligustilide's anti-apoptosis effect in muscle tissue. The aim of the study was to investigate the anti-apoptosis effects of ligustilide on TNF-α-induced C2C12 cells during differentiation. It was revealed that ligustilide at various concentrations significantly prevented the apoptosis of C2C12 cells incubated in TNF-α as assessed by apoptosis index and DNA fragmentation. Moreover, ligustilide-treated groups exhibited a significant increase in the bcl-2/bax ratio, pro-caspase 3 and pro-caspase 8 compared with the TNF-α-control group in a dose-dependent manner. Meanwhile, ligustilide-treated groups presented a significantly increased level of phosphorylated Akt and suppressed expression of the myogenin protein. Therefore, the findings derived suggested that ligustilide protected C2C12 cells from TNF-α-induced apoptosis during differentiation by reducing apoptosis and inducing cell proliferation. [Copyright &y& Elsevier]