Project description:Low-intensity pulsed ultrasound (LIPUS) has been applied as a therapeutic adjunct to promote fracture healing. However, the detailed molecular mechanisms by which LIPUS promotes bone fracture healing have not yet been fully elucidated. In the present study, the early response genes elicited by low-intensity pulsed ultrasound (LIPUS) in bone marrow stromal cells (BMSCs) were investigated using GeneChip® oligonucleotide microarrays.
Project description:Here, the effects of non-thermal low intensity pulsed ultrasound (LIPUS) on the gene expression in human lymphoma U937 cells were investigated using by an Affymetrix GeneChip system. Six hours after LIPUS treatment (0.3 W/cm2 for 1 min), apoptosis (14±3.8%, mean±SD) with minimal cell lysis was observed. At 3 h post-treatment, LIPUS down-regulated 193 genes and up-regulated 201 genes by >1.5-fold. Keywords: ultrasound, gene expression, Human lymphoma U937 cell
Project description:Here, the effects of non-thermal low intensity pulsed ultrasound (LIPUS) on the gene expression in human lymphoma U937 cells were investigated using by an Affymetrix GeneChip system. Six hours after LIPUS treatment (0.3 W/cm2 for 1 min), apoptosis (14±3.8%, mean±SD) with minimal cell lysis was observed. At 3 h post-treatment, LIPUS down-regulated 193 genes and up-regulated 201 genes by >1.5-fold. Experiment Overall Design: U937 cells, a human lymphoma cell line, were treated with low intensity pulsed ultrasound (0.3 W/cm2 for 1 min) and followed by incubation for 3 h at 37°C. Non-treated cells were served as control. Total RNA samples were prepared from the cells. Gene expression was analyzed by an Affymetrix GeneChip® system with Human Expression Array U133A which was spotted with 22,283 probe sets. Sample preparation for array hybridization was carried out as described in the manufactureâs instructions.
Project description:Low intensity pulsed ultrasound (LIPUS) is shown to promote osteogenic differentiation and antiinflammation of periodontal mesenchymal stromal cells. We found extracellular vesicles (EVs) derived from LIPUS-induced stem cells from apical papilla (SCAPs) also have stronger anti-inflammatory and osteogenic effects in vitro and in vivo. To obtain clues on whether microRNA (miR) of EVs contribute to stronger anti-inflammatory and osteogenic effects, we analyzed miR expression in EVs from control- and LIPUS-induced SCAPs by deep sequencing. RNA-sequencing suggests that the LIPUS-EVs induce stronger osteogenic differentiation and antiinflammation by using their cargos, including upregulated osteogenic miRNAs to activate the PI3K/Akt and MAPK signaling pathways, and upregulated anti-inflammatory miRNAs to inhibit the TNF-α signaling pathways.
Project description:Therapeutic antibodies targeting immune checkpoints have shown limited efficacy in clinical trials in glioblastoma (GBM) patients. Ultrasound-mediated blood-brain barrier opening (UMBO) using low-intensity pulsed ultrasound improved drug delivery to the brain. We explored the safety and the efficacy of UMBO plus immune checkpoint inhibitors in preclinical models of GBM. A Blood-brain barrier (BBB) opening was performed using a 1 MHz preclinical ultrasound system in combination with 10µl/g microbubbles. Brain penetration of immune checkpoint inhibitors was determined, and immune cell populations were evaluated using flow cytometry.The impact of repeated treatments on survival was determined. In syngeneic GL261-bearing immunocompetent mice, we showed that UMBO safely and repeatedly open the BBB. BBB opening was confirmed visually and microscopically using Evans’s blue dye and magnetic resonance imaging. UMBO plus anti-PDL-1 was associated with a significant improvement of the overall survival compared to anti-PD-L1 alone. Using mass spectroscopy, we showed that the penetration of therapeutic antibodies can be increased when delivered intravenously compared to non-sonicated brains. Furthermore, we observed an enhancement of activated microglia percentage when combined with anti-PD-L1. Here, we report that the combination of UMBO and anti-PD-L1 dramatically increases GL261-bearing mice's survival compared to their counterparts treated with anti-PD-L1 alone. Our study highlights the BBB as a limitation to overcome to increase the efficacy of anti-PD-L1 in GBM and supports clinical trials combining UMBO and in GBM patients.
