A sensitive and selective fluorescent off–on probe is developed for fluoride ion detection, and its applicability has been demonstrated by determining fluoride ions in real-water samples and toothpaste samples.
Bone marrow-derived mesenchymal stem cells (BMMSCs) have the ability to differentiate into osteoblasts and adipocytes, and have been found to promote disease progression of myeloid malignancies like myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). MDS/AML patient-derived BMMSCs often show a shift in the balance between osteoblastogenesis and adipogenesis, indicating that BMMSCs may be reprogrammed or educated. However, the results of reprogrammed differentiation have been inconclusive. In this study, we found that clonal MDS/AML cells promote adipogenic differentiation and inhibit osteogenic differentiation of BMMSCs, which in turn promotes MDS expansion. Mechanistically, highly expressed transcription factor TWIST1 in clonal MDS/AML cells plays a vital role in the MDS/AML cell-mediated BMMSCs reprogramming differentiation. Enhanced TWIST1 expression induces MDS/AML cells to secrete more IFN-γ, which can induce oxidative stress through STAT1-depenent manner, ultimately causing enhanced adipogenic differentiation and inhibited osteogenic differentiation in BMMSCs. Overall, our findings suggest that targeting the driving oncogenes in malignant clonal cells, such as TWIST1, may offer new therapeutic strategies by remodeling the surrounding bone marrow microenvironment in the treatment of MDS/AML and other hematopoietic malignancies.
Cytarabine (Ara-C) has been one of the frontline therapies for clonal hematopoietic stem cell disorders, such as myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML), but Ara-C resistance often occurs and leads to treatment failure. Exosomal microRNAs (miRNAs, miRs) as small noncoding RNA that play important roles in post-transcriptional gene regulation, can be delivered into recipient cells by exosomes and regulate target genes’ expression. miR92a has been reported to be dysregulated in many cancers, including MDS and AML. However, the effects of exosomal miR92a in hematologic malignancies have not been fully investigated. In this study, qualitative analysis showed the significantly enhanced expression of exosomal miR92a in MDS/AML plasma. Subsequent functional assays indicated that exosomal miR92a can be transported and downregulate PTEN in recipient cells and, furthermore, activate the Wnt/β-catenin signaling pathway and interfere with the Ara-C resistance of receipt MDS/AML cells in vitro and in vivo. Altogether, our findings offer novel insights into plasma exosomal miR92a participating in Ara-C resistance in MDS/AML and we propose miR92a as a potential therapeutic target for MDS/AML.
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