Cancer cells mechanically interact with the tumor microenvironment during cancer development. Mechano-reciprocity has emerged as a crucial factor affecting anti-cancer drug resistance during adjuvant therapy. Here, we investigated the focal adhesion kinase (FAK)/Yes-associated protein (YAP) signaling axis as a prospective strategy for circumventing cisplatin resistance in ovarian cancer (OC). The Cancer Genome Atlas (TCGA) data analysis revealed that FAK overexpression significantly correlated with unfavorable clinical outcomes in patients with ovarian cancer. AFM indentation experiments showed that cell elasticity depends on FAK activity. Notably, the combination of FAK inhibition and cisplatin treatment led to a 69 % reduction in the IC₅₀ of cisplatin. This combined treatment also increased apoptosis compared to the individual treatments, along with the upregulation of the pro-apoptotic factor BAX and cleaved PARP. Suppressing FAK expression sequestered YAP in the cytosol, potentially reducing cellular proliferation and promoting apoptosis. Moreover, reduced FAK expression sensitized drug-resistant OC cells to cisplatin treatment owing to a decrease in nuclear tension, allowing the relocation of YAP to the cytosol. In a mouse model, the co-administration of an FAK inhibitor and cisplatin significantly suppressed tumor growth and increased apoptotic events and DNA fragmentation. Our findings suggest that drug resistance can be attributed to the perturbation of mechanosensing signaling pathways, which drive the mechanical reinforcement of cancer cells. OC cells can restore their sensitivity to cisplatin treatment by strategically reducing YAP localization in the nucleus through FAK downregulation.

Plumbagin (PL; 5-hydroxy-2-methyl-1,4-naphthoquinone) is an analogue of juglone (JG) with additional methylation on carbon 2. It has been found in fungi, insects, and plants, especially Malaysian persimmons, and plants containing PL are globally used as folk medicines. Among 1,4-naphthoquinones tested in this study, PL and JG exhibited high lethality towards zebrafish (Danio rerio) embryos and reduced their hatchability, and induced morphological changes. In addition, zebrafish embryos exposed to 0.13 µM of PL at 4 h post-fertilization exhibited severely reduced brain differentiation in a PL concentration-dependent manner, resulting in severe cyclopia symptoms, with individuals experiencing cyclopia ultimately dying. The cyclopia induced by PL was more severe than that of the positive controls, ethanol, forskolin, and cyclopamine. Increased apoptosis and reactive oxygen species (ROS) generation were associated with PL-induced cyclopia, and concurrent treatments with ROS-quenching curcuminoids decreased cyclopia. Metabolomic activity in PL-treated embryos was also severely disrupted, and even surviving individuals would likely not retain proper function. Thus, plants should be monitored for the presence of PL, given its strong cyclopia-inducing effects on animals. Due to the high frequency and severity of symptomatic zebrafish embryos in this study, PL's association with holoprosencephaly, specifically cyclopia, is undeniable.

In this study, we evaluated the physiological effects of fermented metabolites derived from puffed grains (z), fermented using Bacillus amyloliquefaciens NPKE6, a strain isolated from Korean water kimchi. In vitro assays showed that NPKE6-FM significantly increased antioxidant enzyme activities (SOD, CAT, GPx) and digestive enzyme activities (α-amylase, protease), suggesting its strong biofunctional potential. To confirm its in vivo efficacy, we established two inflammatory disease models—ulcerative colitis and liver injury—in male C57BL/6 mice. Colitis was induced by oral administration of 1% dextran sodium sulfate (DSS, 1 mL), while liver injury was induced by intraperitoneal injection of acetaminophen (APAP, 300 mg/kg) three times per week for 4 weeks. In disease-induced control groups, elevated serum biomarkers (AST, ALT, ALP) and reduced antioxidant activity were observed. Experimental groups received 10 or 50 mg/kg/day of NPKE6-FM for 4 weeks. Treatment significantly restored antioxidant enzyme levels and reduced inflammatory markers such as TNF-α and IL-6. In the colitis model, NPKE6-FM alleviated DSS-induced tissue damage, evidenced by improved colon length, weight, and histological scores. Gene expression analysis showed downregulation of iNOS and COX-2 in colon tissues and Akt and MCP-1 in liver, indicating molecular anti-inflammatory effects. Although liver histopathology did not show marked improvement, biochemical and gene expression results supported its protective role. In summary, NPKE6-FM demonstrated potent antioxidant and anti-inflammatory activities in vitro and in vivo, indicating its potential as a functional food additive to prevent or alleviate inflammatory conditions such as colitis and liver injury.