Breast cancer is one of the leading causes of death in cancer categories, followed by lung, colorectal, and ovarian among the female gender across the world. 10H-3,6-diazaphenothiazine (PTZ) is a thiazine derivative compound that exhibits many pharmacological activities. Herein, we proceed to investigate the pharmacological activities of PTZ toward breast cancer MCF-7 cells as a representative in vitro breast cancer cell model. The PTZ exhibited a proliferation inhibition (IC50 = 0.895 µM) toward MCF-7 cells. Further, cell cycle analysis illustrated that the S-phase checkpoint was activated to achieve proliferation inhibition. In vitro cytotoxicity test on three normal cell lines (HEK293 normal kidney cells, MCF-10A normal breast cells, and H9C2 normal heart cells) demonstrated that PTZ was more potent toward cancer cells. Increase in the levels of reactive oxygen species results in polarization of mitochondrial membrane potential (ΔΨm), together with suppression of mitochondrial thioredoxin reductase enzymatic activity suggested that PTZ induced oxidative damages toward mitochondria and contributed to improved drug efficacy toward treatment. The RT2 PCR Profiler Array (human apoptosis pathways) proved that PTZ induced cell death via mitochondria-dependent and cell death receptor-dependent pathways, through a series of modulation of caspases, and the respective morphology of apoptosis was observed. Mechanistic studies of apoptosis suggested that PTZ inhibited AKT1 pathways resulting in enhanced drug efficacy despite it preventing invasion of cancer cells. These results showed the effectiveness of PTZ in initiation of apoptosis, programmed cell death, toward highly chemoresistant MCF-7 cells, thus suggesting its potential as a chemotherapeutic drug.
Although starch has been intensively studied as a raw material for 3D printing, the relationship between several important process parameters in the preparation of starch gels and the printing results is unclear. In this study, the relationship between different processing conditions and the gel printing performance of corn starch was evaluated by printing tests, rheological tests and low-field nuclear magnetic resonance (LF-NMR) tests, and a back-propagation artificial neural network (BP-ANN) model for predicting gel printing performance was developed. The results revealed that starch gels exhibited favorable printing performance when the gelatinization temperature ranged from 75 °C to 85 °C, and the starch content was maintained between 15 % and 20 %. The R2adj of the BP-ANN models were all reached 0.894, which indicated good predictive ability. The results of the study not only provide theoretical support for the application of corn starch gels in 3D food printing, but also present a novel approach for predicting the printing performance of related materials. This method contributes to the optimization of printing parameters, thereby enhancing printing efficiency and quality.
Porcine reproductive and respiratory syndrome virus (PRRSV) causes a highly transmissible disease of significant concern in the pig industry. Previous studies have demonstrated that the XM-2020 strain (a lineage 1.8 PRRSV IA/2012/NADC30) can induce special hemorrhagic injury in the small intestines. However, the specific mechanism underlying this injurious effect remains incompletely understood. In this study, we examined the pathogenic properties of XM-2020 and YC-2020 strains (a lineage 1.5 PRRSV IA/2014/NADC34) in piglets. Animal pathogenic tests revealed that with either Lineage 1 PRRSVs strains XM-2020 or YC-2020 demonstrated pronounced intestinal hemorrhage and suppression of peripheral immunological organs, comparing to JXA1 infection. Transcriptome analysis of diseased small intestines unveiled that PRRSV infection stimulated oxidative and inflammatory reactions. Remarkably, we also observed activation of the complement system alongside a notable down-regulation of complement and coagulation cascade pathways in the Lineage 1 PRRSVs infection group. Based on these findings, we propose that the primary mechanism driving the hemorrhagic injury of the small intestine caused by Lineage 1 PRRSVs is the suppression of complement and coagulation cascades resulting from immunosuppression. This discovery deepens our understanding of the pathogenicity of PRRSV in the small intestine and provides promising ways out for the development of innovative strategies aimed at controlling PRRSV.