ABSTRACT
Di(1-adamantyl)phosphine oxide (SPO-Ad: Ad2P(V)(=O)H), a stable tautomer of di(1-adamantyl)phosphinous acid (PA-Ad: Ad2P(III)-OH), was employed to synthesize two new PA-Ad-coordinated complexes, POPd-Ad and POPd2-Ad. POPd-Ad was easily transformed from POPd2-Ad in acetonitrile, and the [M - H]- ion of the deprotonated POPd-Ad was observed in the electrospray ionization-mass spectrum of POPd2-Ad. Both complexes are effective precatalysts for the Suzuki reaction of aryl chlorides. The reduction of Pd(II) in POPd-Ad and POPd2-Ad by arylboronic acid was examined, and the ideal Pd-to-PA ratio in the Suzuki reaction was found to be 1:1. The effect of temperature on the catalytic yields was studied to examine the possible ligation state of the active species and the dimer-to-monomer process of POPd2-Ad. Mononuclear and mono-ligated Pd species was assumed to be catalytically active. The electronic and steric effects of PA-Ad were slightly better than those reported for PA-tBu ( t Bu2P(III)-OH). Density functional theory calculations were performed to evaluate the formation of mono-ligated and mononuclear Pd species from POPd-Ad and POPd2-Ad. Furthermore, the reaction time and catalyst loading could be reduced for the reported POPd1-tBu precatalyst using the optimized reaction conditions for POPd-Ad. The complexes synthesized in this extensive study will complement the existing SPO-coordinated POPd series of precatalysts.
ABSTRACT
BACKGROUND: To explore the expression level of coagulation and fibrinolysis-related indexes in the plasma of breast cancer patients after surgery, and explore their predictive value for deep venous thrombosis (DVT). METHODS: From May 2016 to May 2019, 63 patients with lower extremity DVT after radical mastectomy in our hospital were selected as the thrombus group, and 69 patients without venous thrombosis after radical mastectomy were selected as the control group. The levels of D-dimer (D-D) and fibrinolytic product (FDP) were measured by latex enhanced immunoturbidimetry, Fibrinogen (FIB) levels were measured using the von Clauss method, thrombin antithrombin complex (TAT) and thrombomodulin (TM) levels were measured by enzyme-linked immunosorbent assay (ELISA), and the evaluation value of coagulation markers on tumor thrombosis was analyzed by receiver operating characteristic curve (ROC) curve analysis. RESULTS: There were significant differences in blood pressure, platelet count (PLT) level, diabetes history, and tumor metastasis between the two groups (P<0.05). The levels of PT, D-D, FDP, TAT, and TM in the thrombus group were significantly higher than those in control group (P<0.05). The area under the curve (AUC) of D-D, FDP, and TAT were 0.790, 0.881, and 0.672, respectively and there was a marked difference among the indexes (P<0.05). The AUC of FDP was the largest, and the sensitivity and diagnostic value of FDP were the highest. CONCLUSIONS: The plasma levels of FDP, D-D, TAT, and TM in breast cancer patients with DVT after radical mastectomy were significantly increased, which is related to imbalanced coagulation and fibrinolysis functioning in patients. FDP had the highest predictive value for DVT after radical mastectomy.
ABSTRACT
Transcription factor nuclear factor-erythroid 2-like 2 (NRF2) mainly regulates cellular antioxidant response, redox homeostasis and metabolic balance. Our previous study illustrated the translational significance of NRF2-mediated transcriptional repression, and the transcription of FOCAD gene might be negatively regulated by NRF2. However, the detailed mechanism and the related significance remain unclear. In this study, we mainly explored the effect of NRF2-FOCAD signaling pathway on ferroptosis regulation in human non-small-cell lung carcinoma (NSCLC) model. Our results confirmed the negative regulation relationship between NRF2 and FOCAD, which was dependent on NRF2-Replication Protein A1 (RPA1)-Antioxidant Response Elements (ARE) complex. In addition, FOCAD promoted the activity of focal adhesion kinase (FAK), which further enhanced the sensitivity of NSCLC cells to cysteine deprivation-induced ferroptosis via promoting the tricarboxylic acid (TCA) cycle and the activity of Complex I in mitochondrial electron transport chain (ETC). However, FOCAD didn't affect GPX4 inhibition-induced ferroptosis. Moreover, the treatment with the combination of NRF2 inhibitor (brusatol) and erastin showed better therapeutic action against NSCLC in vitro and in vivo than single treatment, and the improved therapeutic function partially depended on the activation of FOCAD-FAK signal. Taken together, our study indicates the close association of NRF2-FOCAD-FAK signaling pathway with cysteine deprivation-induced ferroptosis, and elucidates a novel insight into the ferroptosis-based therapeutic approach for the patients with NSCLC.
