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Cancer Lett ; 496: 134-143, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-33022290


Glioblastoma multiforme (GBM) is a brain tumor with a high mortality rate. Surgical resection combined with radiotherapy and chemotherapy is the standard treatment for GBM patients, but the 5-year survival rate of patients despite this treatment is low. Immunotherapy has attracted increasing attention in recent years. As the pioneer and the main effector cells of immunotherapy, T cells play a key role in tumor immunotherapy. However, the T cells in GBM microenvironment are inhibited by the highly immunosuppressive environment of GBM, posing huge challenges to T cell-based GBM immunotherapy. This review summarizes the effects of the GBM microenvironment on the infiltration and function of different T-cell subsets and the possible strategies to overcome immunosuppression, and thus enhance the effectiveness of GBM immunotherapy.

Amino Acids ; 2020 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-33245424


As a promising cell therapy, neural crest-derived ectoderm mesenchymal stem cells (EMSCs) secrete high amounts of extracellular matrix (ECM) and neurotrophic factors, promoting neural stem cell (NSC) differentiation into neuronal lineages and aiding tissue regeneration. Additionally, the forced overexpression of secreted proteins can increase the therapeutic efficacy of the secretome. Tissue transglutaminase (TG2) is a ubiquitously expressed member of the transglutaminase family of calcium-dependent crosslinking enzymes, which can stabilize the ECM, inducing smart or living biomaterial to stimulate differentiation and enhance the neurogenesis of NSCs. In this study, we examined the neuronal differentiation of NSCs induced by TG2 gene-modified EMSCs (TG2-EMSCs) in a co-culture model directly. Two weeks after initiating differentiation, levels of the neuronal markers, tubulin beta 3 class III and growth-associated protein 43, were higher in NSCs in the TG2-EMSC co-culture group and those of the astrocytic marker glial fibrillary acidic protein were lower, compared with the control group. These results were confirmed by immunofluorescence, and laminin, fibronectin and sonic hedgehog (Shh) contributed to this effect. The results of western blot analysis and the enzyme-linked immunoassay showed that after TG2-EMSCs were co-cultured for 2 weeks, they expressed much higher levels of Shh than the control group. Moreover, the sustained release of Shh was observed in the TG2-EMSC co-culture group. Overall, our findings indicate that EMSCs can induce the differentiation of NSCs, of which TG2-EMSCs can promote the differentiation of NSCs compared with EMSCs.

J Chem Neuroanat ; 107: 101807, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32474063


Improving the microenvironment of lesioned spinal cord to minimize the secondary injury is one important strategy to treat spinal cord injury (SCI). The ensuing hemorrhage after SCI has tight connection with ferroptosis. This study investigated the effects of proanthocyanidins (PACs) on SCI repair and the underlying mechanisms. Adult female mice were divided into four groups, including sham, SCI, PACs5 and PACs10 (i.p. 5 and 10 mg/kg PACs after SCI respectively). The impacts of SCI and PACs treatment on redox parameters (iron contents, TBARS, GSH, and GPX activities) and ferroptosis essential factors such as ACSL4, LPCAT3, Alox15B, Nrf2, HO-1, GPX4 were investigated. The results demonstrated that PACs treatment significantly decreased the levels of iron, TBARS, ACSL4, and Alox15B, while increased the levels of GSH, GPX4, Nrf2, and HO-1 in traumatic spinal cords. Above all, PACs improved the locomotive function of SCI mice. These results suggest that PACs might be potential therapeutics for SCI repair by inhibiting ferroptosis in SCI.

Acta Histochem ; 119(8): 822-830, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29107325


Ectomesenchymal stem cells (EMSCs), a type of adult stem cells derived from cranial neural crest, can be non-invasively harvested from respiratory mucosa and play vital roles in therapies based on their stemness. However, whether donor age has any impact on the stemness of EMSCs remains elusive and is essential for EMSCs-based therapies. To address this, we first cultivated EMSCs from neonatal mice aged 1 week and adult mice aged 3 months or 6 months, and then compared their morphology, proliferative capacity, and pluripotency through various induced differentiation assays. The results showed that neonatal EMSCs were fibroblast-like, more regular compared to adult EMSCs; the proliferative capacity of neonatal EMSCs was higher than that of adult EMSCs. More importantly, after neural, adipogenic, chondrogenic, and osteogenic differentiation, neonatal EMSCs differentiated into respective cell types significantly better than adult EMSCs. Notably, EMSCs from mice aged 3 months differentiated into mesodermal lineages better than those from 6 months old mice after induction. Collectively, these results suggest donor ages have significant impact on the EMSCs from respiratory mucosa.

Células-Tronco Adultas , Células-Tronco Mesenquimais/citologia , Células-Tronco , Fatores Etários , Animais , Animais Recém-Nascidos , Bioensaio , Diferenciação Celular , Células Cultivadas , Camundongos , Crista Neural/citologia , Mucosa Respiratória/citologia