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.

This study aimed to explore the association between weekend catch-up sleep (WCS) and chronic kidney disease (CKD) in American adults.

Utilizing data from the National Health and Nutrition Examination Survey (NHANES) spanning 2017 to 2020, this study encompassed 4,934 individuals aged 20 years and above. We assessed the risk of CKD in relation to WCS. To evaluate CKD risk across various WCS durations, participants were categorized into four groups based on WCS length: < 1 h (reference group), ≥ 1 h and < 2 h, ≥ 2 h and < 3 h, and ≥ 3 h.

In the fully adjusted multivariate logistic regression model, the odds ratio (OR) of CKD to WCS response was 0.86 (95% CI = 0.61-1.22; p = 0.31). In addition, only CKD was significantly associated with WCS duration between 2-3 h (OR = 0.44, 95% CI = 0.21-0.88, p = 0.03). Subgroup analyses showed stronger negative associations (p < 0.05) for men and women with a WCS of 2-3 h, adults under 60 years of age with a WCS of 2-3 h, those with less than 1 h of catch-up sleep on weekends and a body mass index (BMI) of 25-29.9, those with a BMI of less than 25 or greater than or equal to 30 with a WCS of 2-3 h, and those with less than 7 h of sleep on weekdays and 2-3 h of catch-up sleep on weekends.

Our findings suggest that when weekday sleep duration is < 7 h, WCS in 2-3 h is strongly associated with a lower prevalence of CKD.