[Effect of Chlorambucil Combined with Ibrutinib on Mantle Cell Lymphoma Cell Line Jeko-1 and Its Related Mechanism].

OBJECTIVE: To investigate the toxic effect of chlorambucil combined with ibrutinib on mantle cell lymphoma (MCL) cell line Jeko-1 and its related mechanism. METHODS: The MCL cell line Jeko-1 was incubated with different concentrations of chlorambucil or ibrutinib or the combination of the two drugs, respectively. CCK-8 assay was used to detect the proliferation of the cells, and Western blot was used to measure the protein expression levels of BCL-2, caspase-3, PI3K, AKT and P-AKT. RESULTS: After Jeko-1 cells were treated with chlorambucil (3.125, 6.25, 12.5, 25, 50 µmol/L) and ibrutinib (3.125, 6.25, 12.5, 25, 50 µmol /L) alone for 24, 48, 72h respectively, the cell proliferation was inhibited in a time- and dose-dependent manner. Moreover, the two drugs were applied in combination at low doses (single drug inhibition rate<50%), and the results showed that the combination of two drugs had a more significant inhibitory effect (all P < 0.05). Compared with the control group, the apoptosis rate of the single drug group of chlorambucil (3.125, 6.25, 12.5, 25, 50 µmol/L) and ibutinib (3.125, 6.25, 12.5, 25, 50 µmol/L) was increased in a dose-dependent manner. The combination of the two drugs at low concentrations (3.125, 6.25, 12.5 µmol/L) could significantly increase the apoptosis rate compared with the corresponding concentration of single drug groups (all P < 0.05). Compared with control group, the protein expression levels of caspase-3 in Jeko-1 cells were upregulated, while the protein expression levels of BCL-2, PI3K, and p-AKT/AKT were downregulated after treatment with chlorambucil or ibrutinib alone. The combination of the two drugs could produce a synergistic effect on the expressions of the above-mentioned proteins, and the differences between the combination group and the single drug groups were statistically significant (all P < 0.05). CONCLUSION: Chlorambucil and ibrutinib can promote the apoptosis of MCL cell line Jeko-1, and combined application of the two drugs shows a synergistic effect, the mechanism may be associated with the AKT-related signaling pathways.

Neural mechanisms underlying the influence of retrieval ability on creating and recalling creative ideas.

Previous studies revealed a close relationship between retrieval ability and creative thinking; however, it is still unclear what processes of creative thinking are influenced by retrieval ability. This study applied a novel task paradigm to distinguish between different processes of creative thinking. We used functional near-infrared spectroscopy (fNIRS) to explore the differences of cortical activation and functional connectivity in the prefrontal cortex (PFC), temporoparietal junction (TPJ) and temporal cortex between high (HRA) and low (LRA) retrieval ability groups during creating original ideas (CO) and recalling original ideas (RO) tasks. The behaviour results revealed that in the CO task, the HRA group performed better than the LRA group on fluency, flexibility, and originality. Importantly, the fNIRS results further indicated that the HRA group exhibited higher activation of the l-TPJ, l-STG, l-MTG, r-FPC, r-DLPFC than the LRA group during the CO task. Moreover, the HRA group exhibited higher activation of the bilateral TPJ, l-STG, l-MTG, r-DLPFC, and r-FPC in the CO task than in the RO task, and the LRA group exhibited higher activation of the l-STG in the CO task than in the RO task. The functional connectivity between the PFC and IFG, TPJ, and MTG of the HRA group was significantly stronger than that of the LRA group in both the CO and RO tasks. The findings suggest that high retrieval ability could facilitate the generation of creative ideas by facilitating the retrieval of novel information and suppression of common information compared to low retrieval ability. This study provides neural evidence for the effect of different levels of retrieval ability on creative thinking.