Positive regulation of ataxia-telangiectasia-mutated protein (ATM) by E2F transcription Factor 1 (E2F-1) in cisplatin-resistant nasopharyngeal carcinoma cells.

OBJECTIVE: To explore the mechanism of E2F transcription Factor 1 (E2F-1)-mediated ataxia-telangiectasia-mutated protein (ATM) in cisplatin (DDP)-resistant nasopharyngeal carcinoma (NPC). METHODS: E2F-1 and ATM expression was assessed in DDP-resistant NPC cell lines (CNE2/DDP and HNE1/DDP) and parental cells. Then, DDP-resistant NPC cells were transfected with control shRNA (short hairpin RNA) or E2F-1 shRNAs with or without ATM lentiviral activation particles. The half maximal inhibitory concentration (IC50) was evaluated by 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assay, and the cell cycle and cell proliferation were measured by flow cytometry and EdU staining, respectively. In addition, the expression of genes and proteins was quantified by quantitative reverse-transcription polymerase chain reaction (qRT-PCR) and western blotting, respectively. RESULTS: Both E2F-1 and ATM expression in DDP-resistant NPC cells was much higher than that in parental cells. E2F-1 shRNA reduced ATM expression in DDP-resistant NPC cells, but ATM overexpression had no significant effect on E2F-1. ATM overexpression enhanced DDP resistance in DDP-resistant NPC cells with increased IC50 values, which was reversed by E2F-1 inhibition. Meanwhile, ATM overexpression resulted in upregulation of ABCA2 and ABCA5 in DDP-resistant NPC cells, induced elevations in the transition of the cells into S-phase, and increased cell proliferation with enhanced expression of cyclin E1, CDK2, and Ki67, which was reversed by E2F-1 shRNAs. CONCLUSION: Downregulation of E2F-1, possibly by regulating ATM, could block the cell cycle in the G1 phase and reduce the proliferation of CNE2/DDP cells, thereby reversing the resistance of human NPC cells to DDP.

Wireless Multimodality Sensing System-on-a-Chip With Time-Based Resolution Scaling Technique and Analog Waveform Generator in 0.18 µm CMOS for Chronic Wound Care.

Multimodal sensing can provide a comprehensive and accurate diagnosis of biological information. This paper presents a fully integrated wireless multimodal sensing chip with voltammetric electrochemical sensing at a scanning rate range of 0.08-400 V/s, temperature monitoring, and bi-phasic electrical stimulation for wound healing progress monitoring. The time-based readout circuitry can achieve a 1-20X scalable resolution through dynamic threshold voltage adjustment. A low-noise analog waveform generator is designed using current reducer techniques to eliminate the large passive components. The chip is fabricated via a 0.18 µm CMOS process. The design achieves R2 linearity of 0.995 over a wide current detection range (2 pA-12 µA) while consuming 49 µW at 1.2 V supply. The temperature sensing circuit achieves a 43 mK resolution from 20 to 80 degrees. The current stimulator provides an output current ranging from 8 µA to 1 mA in an impedance range of up to 3 kΩ. A wakeup receiver with data correlators is used to control the operation modes. The sensing data are wirelessly transmitted to the external readers. The proposed sensing IC is verified for measuring critical biomarkers, including C-reactive protein, uric acid, and temperature.