a b s t r a c tSeveral miRNAs have been implicated in the development and progression of osteosarcoma (OS). In this study, we found that miR-16 is downregulated in OS cell lines and tissues. Overexpression of miR-16 suppresses OS cell proliferation and tumor growth in nude mice. Furthermore, we confirmed that IGF1R is a direct target of miR-16. Mechanistic investigation revealed that miR-16 overexpression inhibits the Raf1-MEK1/2-ERK1/2 pathway. In clinical specimens, IGF1R levels inversely correlate with miR-16 expression. Our results provide significant clues regarding the role of miR-16 as a tumor suppressor by targeting IGF1R in OS.
cWe sequenced pncA and rpsA genes plus flanking regions of 161 Mycobacterium tuberculosis isolates and found 10 new pncA and 3 novel rpsA mutations in pyrazinamide-resistant strains determined by the Bactec MGIT 960 system. The 3= end of rpsA might be added as the target of molecular detection of pyrazinamide susceptibility.
Buruli ulcer (BU) is an emerging infectious disease that causes disfiguring skin ulcers. The causative agent, Mycobacterium ulcerans, secretes toxin called mycolactone that triggers inflammation and immunopathology. Existing treatments are lengthy and consist of drugs developed for tuberculosis. Here, we report that a pyrazolo[1,5-a]pyridine-3-carboxamide, TB47, is highly bactericidal against M. ulcerans both in vitro and in vivo. In the validated mouse model of BU, TB47 alone reduces M. ulcerans burden in mouse footpads by more than 2.5 log10 CFU compared to the standard BU treatment regimen recommended by the WHO. We show that mutations of ubiquinol-cytochrome C reductase cytochrome subunit B confer resistance to TB47 and the dissimilarity of CydABs from different mycobacteria may account for their differences in susceptibility to TB47. TB47 is highly potent against M. ulcerans and possesses desirable pharmacological attributes and low toxicity that warrant further assessment of this agent for treatment of BU.
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