RESUMEN
Loss of quality in citrus fruit is a common occurrence during postharvest storage due to oxidative stress and energy consumption. In recent years, glycine betaine (GB) has been widely applied to postharvest horticulture fruit. This study aimed to investigate the effect of GB treatment (10 mM and 20 mM) on the quality and antioxidant activity of 'Huangguogan' fruit during postharvest storage at room temperature. Our results indicated that both 10 mM and 20 mM treatments effectively reduced weight and firmness losses and maintained total soluble solid (TSS), titratable acidity (TA), and ascorbic acid contents. Additionally, GB treatment significantly increased the activity of antioxidant enzymes, maintained higher levels of total phenols and total flavonoids, and led to slower accumulation of H2O2. A transcriptome analysis conducted at 28 days after treatment (DAT)identified 391 differentially expressed genes (DEGs) between 20 mM GB (GB-2) and the control (CK) group. These DEGs were enriched in various pathways, particularly related to oxygen oxidoreductase, peroxidase activity, and flavonoid biosynthesis. Overall, the application of GB proved beneficial in enhancing the storability and extending the shelf life of 'Huangguogan' fruit.
RESUMEN
Neutrophil extracellular traps (NETs) have recently been identified to play a crucial role in cancer metastasis. However, the therapeutic target in NETs of melanoma cancer metastasis is still unknown. In this work, we screened a collection of 231 small molecule compounds. We identified ivermectin (IVM), a widely used antiparasitic drug, significantly inhibits neutrophil extracellular traps (NETs) formation after cathepsin B (CTSB) treatment. In vivo, IVM treatment showed no effects of melanoma tumor growth, while the orthotopic melanoma to lung metastasis was significantly suppressed by IVM. Serum level of myeloperoxidase-DNA and neutrophil elastase-DNA were suppressed after IVM treatment. Tumor infiltrated myeloid-derived suppressor cells (MDSCs) were significantly suppressed while tumor infiltrated CD8+T cells in lung was increased after IVM treatment in mouse melanoma model. Mechanistically, IVM targeted a pyroptotic driving factor gasdermin D (GSDMD), and exhibited a Kd of 267.96 nM by microscale thermophoresis (MST) assay. Furthermore, the direct interaction of IVM and GSDMD significantly suppressed GSDMD oligomerization, which are essential for GSDMD-dependent NETs formation. In vitro, treatment with CTSB in bone marrow neutrophils significantly promotes NETs formation, and the release of extracellular DNA was significantly suppressed by IVM pretreatment. Collectively, our results reveal that with the regulation role of IVM in neutrophils and NETs, IVM may potentially be used as a viable therapeutic approach for the treatment of melanoma cancer metastasis.
RESUMEN
Sendai virus strain Tianjin is a novel genotype. Here, we investigate the antitumor and proapoptotic effects of ultraviolet-inactivated Sendai virus strain Tianjin (UV-Tianjin) on human breast cancer MDA-MB-231 cells in vitro, as well as the involvement of the apoptotic pathway in the mechanism of UV-Tianjin-induced antitumor effects. MTT assays showed that treatment with UV-Tianjin dose-dependently inhibited the proliferation of MDA- MB-231 cells but not normal MCF 10A breast epithelium cells. Hoechst staining and flow cytometric analysis revealed that UV-Tianjin induced apoptosis of MDA-MB-231 cells in a dose-dependent manner. Moreover, UV-Tianjin treatment resulted in reduction in the mitochondria membrane potential (MMP) and release of cytochrome complex (cyt c) via regulation of Bax and Bcl-2, as well as activation of caspase-9, caspase-3, Fas, FasL and caspase-8 in MDA-MB-231 cells. In summary, our study suggests that UV-Tianjin exhibits anticancer activity in human breast cancer MDA-MB-231 cells through inducing apoptosis, which may involve both the endogenous mitochondrial and exogenous death receptor pathways.