ABSTRACT
Ferroptosis is a newly discovered iron-dependent form of regulated cell death associated with high levels of hydroxyl radical (ËOH) production. Meanwhile, lysosome dysfunction has been shown to be one of the causes of ferroptosis. Although a variety of ËOH-responsive fluorescent probes have been developed for detecting intracellular ËOH in living cells, there are still only few lysosome-targeted probes to monitor the variation in lysosomal ËOH levels during ferroptosis. Herein, we report a novel ËOH-specific fluorescent probe HCy-Lyso, which is composed of the hydrocyanine and morpholine moiety. Upon treatment with ËOH, its hydrocyanine unit was converted to the corresponding cyanine group, thus leading to a large π-conjugation extension of HCy-Lyso, accompanied by a significant fluorescence off-on response. Moreover, after reacting with ËOH in an acidic environment, the protonation product of HCy-Lyso exhibits a higher fluorescence enhancement, which is suitable for detecting lysosomal ËOH variation. HCy-Lyso has been utilized for imaging endogenous ËOH in living cells under phorbol myristate acetate (PMA) stimuli and monitoring the changes in lysosomal ËOH levels during ferroptosis. Thus, our study proposes a new strategy to design lysosome-targeted and ËOH-responsive fluorescent probes to investigate the relationship between lysosomes and ferroptosis.
ABSTRACT
Noble metal catalysts exhibit high catalytic activity in lean CH4 combustion at low temperatures. However, the high surface energy of noble metal nanoparticles makes them susceptible to deactivation due to migratory-aggregation during the catalytic process. Herein, a core-shell structure with a Pd/CeO2 core and a SiO2 shell (denoted as Pd/CeO2@SiO2) was designed and prepared to enhance the thermal stability for catalytic lean CH4 combustion. A series of characterization methods demonstrated the successful encapsulation of SiO2 and the modified thermal stability. The results of activity tests indicated that Pd/CeO2@SiO2 exhibited the optimal catalytic performance. After seven runs, Pd/CeO2@SiO2 achieved 90% conversion of CH4 at 385 °C compared to Pd/CeO2 at 440 °C. The remarkable catalytic performance was attributed to the synergistic effect of strengthened metal-support interactions and the core-shell structure. On the one hand, the migration and aggregation of Pd nanoparticles were limited due to the protection of the SiO2 shell layer. On the other hand, the SiO2 shell layer further enhanced the interactions between the Pd nanoparticles and CeO2, thus promoting the formation of PdxCe1-xO2-δ solid solutions and active oxygen species, which were beneficial for the improvement of the stability and redox capacity of the catalyst.
ABSTRACT
@#Objective:To investigate the role of cyclo-oxygenase-2 (COX-2) in breast cancer metastasis and its possible mechanism. Methods: A total of 45 cases of primary breast cancer tissues and brain metastatic breast cancer tissues were collected from patients, who underwent mastectomy in Yunnan Cancer Hospital from October 2015 to April 2018, including 30 cases of primary lesions and 15 cases of brain metastasis. qPCR was used to detect the expression of COX-2 in breast cancer tissues and brain metastatic breast cancer tissues. Recombinant viruses with COX-2 over-expression (LV6-COX2) or COX-2 knockdown (LV3-COX2 shRNA1, LV3-COX2 shRNA2) were transfected into human breast cancer MDA-MB-231 cells; After obtaining the stable expression cell lines, the effect of COX-2 expression on the proliferation of MDA-MB-231 cells was detected by CCK-8, and the effects of COX-2 expression on the migration and invasion of MDA-MB-231 cells were detected by scratch test and Transwell assay, respectively. The mRNAand protein expressions of COX-2 in each group were examined by qPCR and WB, respectively. The effect of COX-2 expression on the expression of EMT-related genes in MDA-MB-231 cells was analyzed by qPCR. Results: The expression of COX-2 in tissues of patients with brain metastases was significantly higher than that in patients with primary breast cancer tissues (P<0.01), and it was correlated with tumor TMN stage in breast cancer patients. MDA-MB-231 cell lines with stable COX-2 over-expression/knockout were successfully constructed. Over-expression of COX-2 promoted the migration and invasion of MDA-MB-231 cells (all P<0.01), and significantly increased the expressions of MMP2, MMP1, N-cadherin and vimentin (all P<0.01), but exerted insignificant effect on cell proliferation. The effect of COX-2 silence exerted the opposite effect and promoted cell proliferation (P<0.05). Conclusion: COX-2 is highly expressed in brain metastatic breast cancer tissues, which may promote the migration and invasion of breast cancer MDA-MB-231 cells by regulating EMT processes.
