RESUMO
5-(Hydroxymethyl)-2'-deoxycytidine (5-hmdC), 5-(formyl)-2'-deoxycytidine (5-fodC), and 5-(carboxyl)-2'-deoxycytidine (5-cadC) are crucial intermediate products of the DNA demethylation pathway, which can also act as potential biomarkers reflecting the diagnosis and prognosis in multiple tumors. Detecting 5-hmdC, 5-fodC, and 5-cadC in human urine has various advantages including readily available samples and being noninvasive to patients. However, few works have reported the detection of 5-fodC and 5-cadC due to their trace amounts. Here we developed a novel magnetic hyper-cross-linked microporous polymer (HMP) material based on polyionic liquid (PIL) for the enrichment of 5-hmdC, 5-fodC, and 5-cadC. These magnetic PIL-HMP materials provided specific enrichment superiority for three modified cytidines. After enrichment, the signal intensity of 5-hmdC, 5-fodC, and 5-cadC increased 10-75-fold with lower limits of quantitation (LLOQ) of 0.049, 0.781, and 0.781 ng/mL, respectively. The recoveries were approximately 86.5-95.2% for 5-hmdC, 95.2-107.8% for 5-fodC, and 99.4-102.4% for 5-cadC under the relative standard deviation (RSD) of 0.2-10.3%. Finally, we successfully applied magnetic PIL-HMP materials coupled with high-performance liquid chromatography-electrospray ionization tandem mass spectrometry (HPLC-ESI-MS/MS) in enrichment and quantitative determination of 5-hmdC, 5-fodC, and 5-cadC in human urine of 10 breast cancer patients and 10 healthy people. We found that the level of 5-hmdC decreased in breast cancer patients ( p < 0.05), while the levels of 5-fodC and 5-cadC increased ( p < 0.05, p < 0.01). Our results demonstrated that the levels of metabolic 5-hmdC, 5-fodC, and 5-cadC in human urine are closely related to breast cancer, which could contribute to the clinical diagnosis and investigation of breast cancer and its occurrence and development mechanisms.
Assuntos
Neoplasias da Mama/urina , Desoxicitidina/análogos & derivados , Desoxicitidina/urina , Líquidos Iônicos/química , Nanopartículas de Magnetita/química , Polímeros/química , Adsorção , Cromatografia Líquida de Alta Pressão/métodos , Desoxicitidina/isolamento & purificação , Dissonias , Feminino , Humanos , Extração em Fase Sólida/métodos , Espectrometria de Massas por Ionização por Electrospray/métodos , Espectrometria de Massas em Tandem/métodosRESUMO
Wearable sensors that can precisely detect vital signs are highly desirable for monitoring personal health conditions and medical diagnosis. In this paper, we report an ultrasensitive strain sensor consisting of a 150 nm thick highly conductive dimethylsulfoxide-doped poly(3,4-ethylenedioxythiophene):poly(4-styrenesulfonate) sensing layer and an elastic fluorosilicone rubber substrate. This sensor exhibits a high sensitivity at small strains (e.g., gauge factor at 0.6% strain = 280), low limit of detection (<0.2% strain), and excellent repeatability and cycling stability. Therefore, it is promising for practically detecting vital signs, tiny human motions, and sounds. Furthermore, the semitransparent shallow blue color and the soft rubbery substrate make the strain sensor beautiful and comfortable to the human body.