Glioblastoma (GBM) is the most common and malignant intracranial tumor in adults. Despite continuous improvements in diagnosis and therapeutic method, the prognosis is still far away from expectations. The invasive phenotype of GBM is the main reason for the poor prognosis. Epithelial-mesenchymal transition (EMT) is recognized as a participator in this invasive phenotype. Resveratrol, a natural plant-derived compound, is reported to be able to regulate EMT. In the present study, we used TGF-β1 to induce EMT and aimed to evaluate the effect of resveratrol on EMT and to explore the underline mechanism in GBM. Western blotting was used to detect the expression of EMT-related markers, stemness markers, and Smad-dependent signaling. Wound healing assay and transwell invasion assay were performed to evaluate the migratory and invasive ability of GBM cells. Gliosphere formation assay was used to investigate the effect of resveratrol on the ability of self-renewal. Xenograft experiment was conducted to examine the effect of resveratrol on EMT and Smad-dependent signaling in vivo. Our data validated that resveratrol suppressed EMT and EMT-associated migratory and invasive ability via Smad-dependent signaling in GBM cells. We also confirmed that resveratrol obviously inhibited EMT-induced self-renewal ability of glioma stem cells (GSCs) and inhibited EMT-induced cancer stem cell markers Bmi1 and Sox2, suggesting that resveratrol is able to suppress EMT-generated stem cell-like properties in GBM cells. Furthermore, we also showed the inhibitory effect of resveratrol on EMT in xenograft experiments in vivo. Overall, our study reveals that resveratrol suppresses EMT and EMT-generated stem cell-like properties in GBM by regulating Smad-dependent signaling and provides experimental evidence of resveratrol for GBM treatment.

No abstract

The ability to precisely deliver molecules into single cells while maintaining good cell viability is of great importance to applications in therapeutics, diagnostics, and drug delivery as it is an advancement toward the promise of personalized medicine. This paper reports a single-cell individualized electroporation method with real-time impedance monitoring to improve cell perforation efficiency and cell viability using a microelectrode array chip. The microchip contains a plurality of sextupole-electrode units patterned in an array, which are used to perform in situ electroporation and real-time impedance monitoring on single cells. The dynamic recovery processes of single cells under electroporation are tracked in real time via impedance measurement, which provide detailed transient cell states and facilitate understanding the whole recovery process at the level of single cells. We define single-cell impedance indicators to characterize cell perforation efficiency and cell viability, which are used to optimize electroporation. By applying the proposed electroporation method to different cell lines, including human cancer cell lines and normal human cell lines individually, optimum stimuli are determined for these cells, by which high transfection levels of enhanced green fluorescent protein (EGFP) plasmid into cells are achieved. The results validate the effectiveness of the proposed single-cell individualized electroporation/transfection method and demonstrate promising potential in applications of cell reprogramming, induced pluripotent stem cells, adoptive cell therapy, and intracellular drug delivery technology.

No abstract

As a crucial kind of pervasive gene, long noncoding RNAs (lncRNAs) are abundant and key players in brain function as well as numerous neurological disorders, especially ischemic stroke. The mechanisms underlying ischemic stroke include angiogenesis, autophagy, apoptosis, cell death, and neuroinflammation. Inflammation plays a vital role in the pathological process of ischemic stroke, and systemic inflammation affects the patient's prognosis. Although a great deal of research has illustrated that various lncRNAs are closely relevant to regulate neuroinflammation and microglial activation in ischemic stroke, the specific interactional relationships and mechanisms between lncRNAs and neuroinflammation have not been described clearly. This review aimed to summarize the therapeutic effects and action mechanisms of lncRNAs on ischemia by regulating inflammation and microglial activation. In addition, we emphasize that lncRNAs have the potential to modulate inflammation by inhibiting and activating various signaling pathways, such as microRNAs, NF-κB and ERK.