Guangxi University of Chinese Medicine

Total flavonoids from Litchi chinensis Sonn. (Sapindaceae) seeds (TFLS) effectively attenuate stem cell-like properties in breast cancer cells. However, their pharmacological effects and mechanisms in suppressing breast cancer metastasis remain unclear.

This study aimed to elucidate the inhibitory effects and underlying mechanisms of TFLS on breast cancer metastasis.

The antiproliferative, migratory, and invasive activities of breast cancer cells following TFLS treatment were evaluated using CCK-8, wound-healing, and transwell assays. The epithelial-mesenchymal transition (EMT) biomarkers were evaluated via Western blot analysis. The anti-metastatic effects of TFLS were further validated in vivo using zebrafish and mouse models. Network pharmacology methodology was utilized to predict potential targets and signaling pathways, which were subsequently corroborated by Western blot. Potential active compounds were identified through molecular docking, and the chemical constituents of TFLS were analyzed and characterized using UPLC-QTOF/MS.

TFLS suppressed the proliferation of MDA-MB-231 and MDA-MB-468 cells, with IC₅₀ values of 44.47 μg/mL and 37.35 μg/mL at 72 h, respectively. It effectively suppressed breast cancer metastasis in vitro, demonstrated by a marked reduction in cellular motility and invasiveness, alongside the reversal of EMT. Consistent with pathway enrichment analysis, network pharmacology revealed that TFLS reduced the phosphorylation levels of PI3K, AKT, mTOR, JNK, ERK, and p38 in breast cancer cells. Molecular docking identified seven potential active ingredients, and UPLC-MS/MS confirmed the presence of key compounds, including procyanidin A2.

TFLS effectively inhibits breast cancer cell proliferation, migration, and invasion in vitro by reversing the EMT phenotype, while suppressing metastasis in vivo. These effects are likely mediated via the attenuation of the PI3K/AKT/mTOR and MAPK signaling pathways.

The mitochondrial potassium channel Kv1.3 is a critical therapeutic target, as its blockade induces cancer cell apoptosis, highlighting its therapeutic potential. PAP-1, a potent and selective membrane-permeant Kv1.3 inhibitor, faces solubility challenges affecting its bioavailability and antitumor efficacy. To circumvent these challenges, we developed a tumor-targeting drug delivery system by encapsulating PAP-1 within pH-responsive mPEG-PAE polymeric micelles. These self-assembled micelles exhibited high entrapment efficiency (91.35%) and drug loading level (8.30%). As pH decreased, the micelles exhibited a significant increase in particle size and zeta potential, accompanied by a surge in PAP-1 release. Molecular simulations revealed that PAE's tertiary amine protonation affected the self-assembly process, modifying hydrophobicity and resulting in larger, loosely packed particles. Furthermore, compared to free PAP-1 or PAP-1 combined with MDR inhibitors, PAP-1-loaded micelles significantly enhanced cytotoxicity and apoptosis induction in Jurkat and B16F10 cells, through mechanisms involving decreased mitochondrial membrane potential and elevated caspase-3 activity. In vivo, while free PAP-1 failed to reduce tumor size in a B16F10 melanoma mouse model, PAP-1-loaded micelles substantially suppressed tumors, reducing volume by up to 94.26%. Fluorescent-marked micelles effectively accumulated in mouse tumors, confirming their targeting efficiency. This strategy holds promise for significantly improving PAP-1's antitumor efficacy in tumor therapy.

Objective. In this study, we investigated the different effects of roller and centrifugal pumps on blood and myocardial tissue structure in a normothermic machine-perfused ex vivo porcine heart model. Methods. We selected 16 healthy Guangxi Bama miniature pigs weighing 25-30 kg and randomly divided them into two groups, one perfused by a roller pump and the other perfused by a centrifugal pump. We recorded hemodynamic parameters, measured blood gases to test for erythrocyte destruction, coagulation, myocardial injury markers, and inflammatory factors, and observed pathological and ultrastructural changes in the left ventricular wall myocardial tissue. Results. There were no differences in perfusion, heart rate, blood gases, hemolysis, or cardiac enzyme levels between the two groups (p > .05). The centrifugal pump group had a higher platelet count, fibrinogen level, and prothrombin time and lower levels of D-dimer (p < .05). In the centrifugal pump group, compared to the roller pump group, the pro-inflammatory factor levels were significantly higher and interleukin-10 levels were significantly lower (p < .05). Hematoxylin-eosin staining and transmission electron microscopy results showed no difference in the degree of myocardial tissue damage between the two groups. Conclusion. The results of this study suggested that the centrifugal pump model reduced platelet destruction, prolonged prothrombin time, avoided excessive fibrinogen activation, and attenuated elevated D-dimer levels. However, the centrifugal pump induced a greater inflammatory response compared to roller pump.