Search

It has been estimated that one in four stroke patients may have recurrent stroke within five years after they experienced the first stroke. Furthermore, clinical studies have shown that recurrent stroke negatively affects patient outcomes; the risk of disability and the death rate increase with each recurrent stroke. Therefore, it is urgent to find effective methods to prevent recurrent stroke. The gut microbiota has been proven to play an essential role after ischemic stroke, while sudden ischemia disrupts microbial dysbiosis, and the metabolites secreted by the microbiota also reshape the gut microenvironment. In the present study, we established a recurrent ischemic mouse model. Using this experimental model, we compared the survival rate and ischemic infarction between single MCAO and recurrent MCAO, showing that, when two surgeries were performed, the mouse survival rate dramatically decreased, while the infarction size increased. Fecal samples were collected on day 1, day 3 and day 7 after the first MCAO and day 9 (2 days after the second MCAO) for 16S sequencing, which provided a relatively comprehensive picture of the microbiota changes. By further analyzing the potential metabolic pathways, our data also highlighted several important pathways that were significantly altered after the first and recurrent stroke. In the present study, using an experimental mouse model, we showed that acute ischemic stroke, especially recurrent ischemia, significantly decreased the diversity of the gut microbiota.

Although chemotherapy is an important treatment for advanced prostate cancer, its efficacy is relatively limited. Ultrasound-induced cavitation plays an important role in drug delivery and gene transfection. However, whether cavitation can improve the efficacy of chemotherapy for prostate cancer remains unclear. In this study, we treated RM-1 mouse prostate carcinoma cells with a combination of ultrasound-mediated microbubble cavitation and paclitaxel. Our results showed that combination therapy led to a more pronounced inhibition of cell viability and increased cell apoptosis. The enhanced efficacy of chemotherapy was attributed to the increased cell permeability induced by cavitation. Importantly, compared with chemotherapy alone (nab-paclitaxel), chemotherapy combined with ultrasound-mediated microbubble cavitation significantly inhibited tumor growth and prolonged the survival of tumor-bearing mice in an orthotopic mouse model of RM-1 prostate carcinoma, indicating the synergistic effects of combined therapy on tumor reduction. Furthermore, we analyzed tumor-infiltrating lymphocytes and found that during chemotherapy, the proportions of CTLA4+ cells and PD-1+/CTLA4+ cells in CD8+ T cells slightly increased after cavitation treatment.

The luminal-to-basal transition in mammary epithelial cells (MECs) is accompanied by changes in epithelial cell lineage plasticity; however, the underlying mechanism remains elusive. Here, we report that deficiency of Frmd3 inhibits mammary gland lineage development and induces stemness of MECs, subsequently leading to the occurrence of triple-negative breast cancer. Loss of Frmd3 in PyMT mice results in a luminal-to-basal transition phenotype. Single-cell RNA sequencing of MECs indicated that knockout of Frmd3 inhibits the Notch signaling pathway. Mechanistically, FERM domain-containing protein 3 (FRMD3) promotes the degradation of Disheveled-2 by disrupting its interaction with deubiquitinase USP9x. FRMD3 also interrupts the interaction of Disheveled-2 with CK1, FOXK1/2, and NICD and decreases Disheveled-2 phosphorylation and nuclear localization, thereby impairing Notch-dependent luminal epithelial lineage plasticity in MECs. A low level of FRMD3 predicts poor outcomes for breast cancer patients. Together, we demonstrated that FRMD3 is a tumor suppressor that functions as an endogenous activator of the Notch signaling pathway, facilitating the basal-to-luminal transformation in MECs. [ABSTRACT FROM AUTHOR]