ABSTRACT
Currently the main treatment of acute myeloid leukemia (AML) is chemotherapy combining hematopoietic stem cell transplantation. However, the unbearable side effect of chemotherapy and the high risk of life-threatening infections and disease relapse following hematopoietic stem cell transplantation restrict its application in clinical practice. Thus, there is an urgent need to develop alternative therapeutic tactics with significant efficacy and attenuated adverse effects. Here, we revealed that umbilical cord-derived mesenchymal stem cells (UC-MSC) efficiently induced AML cell differentiation by shuttling the neutrophil elastase (NE)-packaged extracellular vesicles (EVs) into AML cells. Interestingly, the generation and release of NE-packaged EVs could be dramatically increased by vitamin D receptor (VDR) activation in UC-MSC. Chemical activation of VDR by using its agonist 1α,25-dihydroxyvitamin D3 efficiently enhanced the pro-differentiation capacity of UC-MSC and then alleviated malignant burden in AML mouse model. Based on these discoveries, to evade the risk of hypercalcemia, we synthetized and identified sw-22, a novel non-steroidal VDR agonist, which exerted a synergistic pro-differentiation function with UC-MSC on mitigating the progress of AML. Collectively, our findings provided a non-gene editing MSC-based therapeutic regimen to overcome the differentiation blockade in AML.
ABSTRACT
A case of IgG4-related hypertrophic pachymeningitis was reported. The patient was an elderly female, with the course of disease more than 8 years. Clinical manifestations included recurrent headache, vision and hearing loss, exophthalmos and thyroid dysfunction. Finally, she was diagnosed as IgG4-related disease and IgG4-related hypertrophic pachymeningitis by PET-CT and dural biopsy. After treatment with methylprednisolone and mycophenolate mofetil, the patient′s clinical symptoms improved.
ABSTRACT
This study was to investigate the inhibitory effects of artemether in combination with etoposide on the proliferation and invasion ability of human small cell lung cancer cell line H446.H446 cells were treated with different concentrations of artemether or etoposide alone or their combination.The inhibitory effects on proliferation were detected by MTT assay,while cell cycle and apoptosis of H446 cells in each group were analyzed by flow cytometry using PI and Annexin V/PI-staining,respectively.The invasion capability of H446 cells in different groups was tested with matrigel-coated transwell.The results implicated that artemether or etoposide or their combination does inhibit proliferation of H446 cells dose-dependently.Artemether alone had little effect on the apoptosis of H446 cells while its combination with etoposide resulted in significantly apoptosis of H446 cells comparing with other groups (P ＜ 0.05).Etoposide blocked H446 progression markedly by arresting cell cycle in G2 phase with percentage of cells in G1 phase decreasing significantly while artemether alone or in combination with etoposide had little synergetic effect on cell cycle.Artemether or etoposite alone or their combination could dramatically inhibit the invasion ability of H446 cells.