Integrated transcriptome and metabolome profiling of Camellia reticulata reveal mechanisms of flower color differentiation.

Camellia reticulata (Lindl.) is an important ornamental plant in China. Long-term natural or artificial selections have resulted in diverse phenotypes, especially for flower colors. Modulating flower colors can enhance the visual appeal and economic value in ornamental plants. In this study, we investigated the molecular mechanisms underlying flower color differentiation in C. reticulata. We performed a combined transcriptome and metabolome analysis of the petals of a popular variety C. reticulata (HHYC) (red), and its two cultivars "Xuejiao" (XJ) (pink) and "Tongzimian" (TZM) (white). Targeted metabolome profiling identified 310 flavonoid compounds of which 18 anthocyanins were differentially accumulated among the three samples with an accumulation pattern of HHYC > XJ > TZM. Likewise, transcriptome analysis showed that carotenoid and anthocyanin biosynthetic structural genes were mostly expressed in order of HHYC > XJ > TZM. Two genes (gene-LOC114287745765 and gene-LOC114289234) encoding for anthocyanidin 3-O-glucosyltransferase are predicted to be responsible for red coloration in HHYC and XJ. We also detected 42 MYB and 29 bHLH transcription factors as key regulators of anthocyanin-structural genes. Overall, this work showed that flavonoids, particularly anthocyanins contents are the major determinants of flower color differentiation among the 3 C. reticulata samples. In addition, the main regulatory and structural genes modulating anthocyanin contents in C. reticulata have been unveiled. Our results will help in the development of Camellia varieties with specific flower color and quality.

Arsenic trioxide at conventional dosage does not aggravate hemorrhage in the first-line treatment of adult acute promyelocytic leukemia.

OBJECTIVES: The arsenic trioxide (ATO) plus all-trans retinoic acid (ATRA) therapy has demonstrated a tremendous success in the first-line treatment of acute promyelocytic leukemia (APL). Actually, early death (ED) is currently thought as a major challenge in APL. ATO has been reported to inhibit platelet function in vitro, and whether it increases the ED rate by exacerbating the hemorrhagic symptoms remains to be investigated. METHODS: Effects of ATO on platelet aggregation and adhesion were evaluated in vitro and in thirty-two complete remission (CR) and four newly diagnosed APL patients. Furthermore, concentrations of plasma total arsenic were monitored in APL patients via ICP-MS. RESULTS: The inhibition of platelet function, either aggregation or adhesion, did occur in vitro when the concentration of ATO reached 2 µmol/L. However, in CR APL patients receiving ATO with normal platelet count, the platelets responded normally when being activated and so did those in the newly diagnosed patients with thrombocytopenia. Our data further showed that the conventional dosage of ATO reached a plasma concentration substantially below the required concentration to inhibit platelets. CONCLUSIONS: In the first-line treatment of APL, the use of ATO is safe and effective and does not compromise the hemostatic potential that may eventually increase ED rate.

[A new artemisinin derivative SM1044 induces apoptosis of Kasumi-1 cells and its mechanism].

The aim of this study was to investigate the apoptosis-inducing effect of artemisinin derivative SM1044 on Kasumi-1 cells and its possible mechanism. Kasumi-1 cells were treated with different concentrations of SM1044, the cell viability was evaluated by MTT assay. Cell apoptosis and cell cycle progression were assessed by using flow cytometry with Annexin-V/PI double staining and flow cytometry with PI staining respectively. The expression of apoptosis-related proteins caspase 3, PARP and the fusion protein AML1-ETO were detected by Western blot. The results indicated that SM1044 inhibited cell growth of Kasumi-1 cells in time- and dose-dependent manners. After exposure of Kasumi-1 cells to 1 µmol/L SM1044 for 24 hours, the cell viability was decreased to 50%. IC(50) of SM1044 to Kasumi-1 cells at 48 hours was 0.17 ± 0.067 µmol/L. SM1044 induced cell apoptosis in a caspase-dependent manner, and the apoptotic rate of Kasumi-1 cells increased as SM1044 concentration increased. Flow cytometry with PI staining revealed that SM1044 induced cell cycle arrest, and the proportion of cells in G(0)/G(1) phase increased from 58.33 ± 4.46% to 71.75 ± 2.24% after exposure to 5 µmol/L SM1044 for 24 hours. Western blot showed that SM1044 increased the expression of apoptosis-related proteins cPARP and cleaved caspase 3 and also degraded the AML1-ETO fusion protein. It is concluded that SM1044 can inhibit the proliferation of Kasumi-1 cells, induce cell apoptosis which may be related to the increased level of cleaved PARP and cleaved caspase 3. SM1044 can also induce cell arrest in G(0)/G(1) phase. As the fusion protein AML1-ETO degrades obviously, it can be the potential target of SM1044 in Kasumi-1 cells.