RESUMEN
Glutathione peroxidase 4 (GPX4) is a promising anticancer therapeutic target; however, the application of GPX4 inhibitors (GPX4i) is limited owing to intrinsic or acquired drug resistance. Hence, understanding the mechanisms underlying drug resistance and discovering molecules that can overcome drug resistance are crucial. Herein, we demonstrated that GPX4i killed bladder cancer cells by inducing lipid reactive oxygen species-mediated ferroptosis and apoptosis, and cisplatin-resistant bladder cancer cells were also resistant to GPX4i, representing a higher half-maximal inhibitory concentration value than that of parent bladder cancer cells. In addition, thioredoxin reductase 1 (TrxR1) overexpression was responsible for GPX4i resistance in cisplatin-resistant bladder cancer cells, and inhibiting TrxR1 restored the sensitivity of these cells to GPX4i. In vitro and in vivo studies revealed that Jolkinolide B (JB), a natural diterpenoid and previously identified as a TrxR1 inhibitor, potentiated the antiproliferative efficacy of GPX4i (RSL3 and ML162) against cisplatin-resistant bladder cancer cells. Furthermore, GPX4 knockdown and inhibition could augment JB-induced paraptosis and apoptosis. Our results suggest that inhibiting TrxR1 can effectively improve GPX4 inhibition-based anticancer therapy. A combination of JB and GPX4i, which is well-tolerated and has several anticancer mechanisms, may serve as a promising therapy for treating bladder cancer.
Asunto(s)
Compuestos de Anilina , Diterpenos , Tiofenos , Neoplasias de la Vejiga Urinaria , Humanos , Cisplatino/farmacología , Tiorredoxina Reductasa 1 , Línea Celular Tumoral , Neoplasias de la Vejiga Urinaria/tratamiento farmacológicoRESUMEN
In this study, the integrated three-in-one (temperature, humidity, and wind speed) microsensor was made through the technology of the Micro-electro-mechanical Systems (MEMS) to measure three important physical quantities of the internal environment of the cold air pipe of the Heating, Ventilation and Air Conditioning (HVAC) in the factory, plan the installation positions of the integrated three-in-one microsensor and commercially available wind speed sensor required by the internal environment of the cold air pipe, and conduct the actual 310-h long term test and comparison. In the experiment, it was also observed that the self-made micro wind speed sensor had higher stability compared to the commercially available wind speed sensor (FS7.0.1L.195). The self-made micro wind speed sensor has a variation range of ±200 mm/s, while the commercially available wind speed sensor a variation range of ±1000 mm/s. The commercially available wind speed sensor (FS7.0.1L.195) can only measure the wind speed; however, the self-made integrated three-in-one microsensor can conduct real-time measurements of temperature and humidity according to the environment at that time, and use different calibration curves to know the wind speed. As a result, it is more accurate and less costly than commercially available wind speed sensors. The material cost of self-made integrated three-in-one microsensor includes chemicals, equipment usage fees, and wires. In the future, factories may install a large number of self-made integrated three-in-one microsensors in place of commercially available wind speed sensors. Through real-time wireless measurements, the self-made integrated three-in-one microsensors can achieve the control optimization of the HVAC cold air pipe's internal environment to improve the quality of manufactured materials.
RESUMEN
A wireless flexible air velocity microsensor was developed by using micro-electro-mechanical systems (MEMS) technology. Polyimide (PI) material was selected for the waterproof and oilproof requirements of the cold air duct environment of heating, ventilation, and air conditioning (HVAC) systems, and then a wireless flexible micro air velocity sensor was completed. To obtain real-time wireless measurements of the air velocity inside the cold air ducts of an HVAC system, and to create a measurements database, the deployment locations and quantity of micro air velocity sensors for the internal environment of the cold air ducts were planned. A field domain verification was performed to optimize the internal environment control of the cold air ducts of ventilation and air conditioning systems and to enhance the quality and reliability of process materials. This study realized real-time monitoring of velocity in the HVAC ducts of a chemical-fiber plant. A commercial velocity sensor (FS7.0.1L.195) was purchased and a micro-electro-mechanical systems (MEMS) approach was also used to develop a home-built micro air velocity sensor, to optimize the provision of the commercial sensors and our home-built micro air velocity sensor. Comparing the specifications of the two commercially available sensors with our home-built micro air velocity sensor, the results show that the home-built micro air velocity sensor has the advantages of fast response time, simultaneous sensing of three important physical quantities, and low cost.