Baicalin induces apoptosis in human osteosarcoma cell through ROS-mediated mitochondrial pathway

<p>Baicalin is extracted from a traditional Chinese herb, <i>Scutellaria baicalensis</i>. In this study, the anticancer activity and underlying mechanisms of baicalin towards human osteosarcoma cell (HOS) were investigated. Baicalin could inhibit HOS cell proliferation in a concentration-dependent manner. Mitochondrial membrane potential decreased obviously after treated with different concentration of baicalin by flow cytometry assay and revealed that baicalin triggered a significant generation of reactive oxygen species (ROS). Western blotting assay further revealed that baicalin-induced cell apoptosis by suppressing Bcl-2 level, then activating caspase-9 and caspase-3. In vivo experiment, baicalin significantly suppressed tumour growth in female BALB/C nude mice bearing HOS tumours. In addition, baicalin did show toxicity to treated animal by comparing the body weight increase and mortality. In general, the present results demonstrated that baicalin-induced apoptosis in human osteosarcoma cell via a ROS-mediated mitochondrial pathway. The paper indicated that baicalin is a promising candidate for the treatment of HOS.</p

DataSheet1_Screening for MicroRNA combination with engineered exosomes as a new tool against osteosarcoma in elderly patients.docx

The most common primary malignant bone sarcoma is Osteogenic sarcoma (OS) which has a bimodal age distribution. Unfortunately, the treatment of OS was less effective for elderly patients than for younger ones. The study aimed to explore a new microRNA (miRNA) which can bind to combining engineered exosomes for treatment of older OS patients. Based on GSE65071 and miRNet 2.0, two up-regulated miRNAs (miR-328, miR-107) and seven down-regulated miRNAs (miR-133b, miR-206, miR-1-3p, miR-133a, miR-449a, miR-181daysay, miR-134) were selected. Next, we used FunRich software to predict the up-stream transcription factors (TFs) of differentially expressed miRNAs (DE-miRNAs). By comparing target genes predicted from DE-miRNAs with differentially expressed genes, we identified 12 down-regulated and 310 up-regulated mRNAs. For KEGG analysis, the most enriched KEGG pathway was Cell cycle, Spliceosome, and Protein digestion and absorption. By using protein-protein interactions network, topological analysis algorithm and GEPIA database, miR-449a /CCNB1 axis was identified. Experiments in vitro were conducted to confirm the results too. MiRNA-449a is down-regulated in osteosarcoma and suppresses cell proliferation by targeting CCNB1. Our findings not only reveal a novel mechanism of miR-449a /CCNB1 in OS but also had laid the groundwork for further investigation and analysis in the field of exosome engineering.</p

Multimodal Nanoprobe Based on Upconversion Nanoparticles for Monitoring Implanted Stem Cells in Bone Defect of Big Animal

Monitoring implanted stem cells in bone regeneration and other cell therapies is of great importance to reveal the mechanism of tissue repair and to optimize clinical treatments. However, big challenge still remained in lacking an imaging nanoprobe. Herein, we designed surface modified upconversion nanoparticles (UCNs) with multimodal imaging capabilities of fluorescence, magnetic resonance imaging (MRI) and dual-energy computed tomography (CT). It was found that the UCNs can label stem cells in an efficient (over 200 pg/cell) and long-term (at least 14 days) manner, with almost no influence on the viability, cell cycle, apoptosis, and multilineage differentiation. Thus, clinical dual-energy CT and MRI were successfully applied to observe the migration of labeled cells on a bone-defect model of rabbit for at least 14 days. The results visualized the gathering of stem cells at the defect site of cortical bone, and the in vivo images were well-correlated with the in vitro fluorescence observation without extra staining. Therefore, a potentially translatable nanoprobe was developed for noninvasive and real-time tracking of cells, which may be meaningful for understanding the bone regeneration in clinic and shed light on the visualization of cells in other cell therapies