ABSTRACT
OBJECTIVE: Acute lymphoblastic leukemia (ALL) is a highly heterogeneous leukemia. Despite the current improvement in conventional chemotherapy and high survival rates, the outcomes remain challenging. Sesquiterpen extracted from the Tanacetum parthenium, parthenolide, is a potential anticancer agent that can modulate the expression of miRNAs and induce apoptosis. The objective of this study was to investigate the effect of parthenolide in combination with vincristine and alone on the apoptosis rate and expression of miR-125b-5p, miR-181b-5p, and miR-17-5p in the NALM6 cell line. MATERIALS AND METHODS: In this experimental study, cell viability and metabolic activity were determined through MTT assay and PI staining. Flow cytometry was applied to evaluate the rate of apoptosis. The expression of miRNAs was assessed using real-time polymerase chain reaction. Bioinformatic analyses, including Cytoscape, RNAhybrid, and signaling pathway analysis were employed to investigate the association of miR-17-5p, miR-181b-5p and miR-125b- 5p with apoptosis. Further, molecular docking served to validate the modulation of these miRNAs by parthenolide and vincristine treatment. RESULTS: The MTT assay indicated that 7.7 µM of parthenolide decreased the metabolic activity to 50% after 48 hours. PI staining analysis indicated that at concentrations below the half maximal inhibitory concentration, parthenolide caused 50% cell death. Flow cytometric analysis indicated that parthenolide (1.925 µM) in combination with vincristine (1.2 nM) induced apoptosis in 83.2% of the cells. Real-time quantitative reverse transcription polymerase chain reaction (qRTPCR) analysis showed significant changes in the expression levels of miR-17-5p, miR-125b-5p, and miR-181b-5p. Moreover, the combination therapy downregulated the expression of miRNAs significantly. This was consistent with our bioinformatic analysis demonstrating that the studied miRNAs are regulators of apoptosis. Finally, molecular docking validated the modulation of the miRNAs by parthenolide and vincristine. CONCLUSION: Parthenolide in combination with vincristine triggers apoptosis at a high rate in the NALM6 cell line. Moreover, this combination therapy can decrease the expression of miR-17-5p, miR-181b-5p, and miR-125b-5p.
ABSTRACT
BACKGROUND: Peripheral blood film morphology in neonates is significantly different from the adults as neonatal erythrocytes show a marked heterogeneity. Moreover, there seem to be a more significant numbers of irregular shaped red blood cells such as stomatocytes, keratocytes, schistocytes, and acantocytes in newborns, particularly in preterm infants. This review study focused on the red blood cell morphology in term and preterm neonates to detect clues to distinguish between the peripheral blood film of newborns under physiological and pathological conditions. METHODS: The peripheral blood findings and blood cell counts in preterm and term neonates were studied and compared to each other using available scientific databases and indexing systems such as PubMed and Google Scholar. RESULTS: This approach is a simple, cost-effective, quick, and informative method to distinguish between physiological and pathological conditions in neonates and detect hematological disorders. CONCLUSIONS: Peripheral blood film plays a crucial role in diagnosing anemia and blood-related diseases, determining the type of anemia, and identifying specific morphological abnormalities of red cell membrane disorders.
