1 January 2005 in Acta Biomaterialia
19 September 2018 in Scientific Reports
Dopamine is a key molecule in neurotransmission and has been known to be responsible for several neurological diseases. Hence, its sensitive and selective detection is important for the early diagnosis of diseases related to abnormal levels of dopamine. In this study, we reported a new cylindrical gold nanoelectrode (CAuNE) platform fabricated via sequential laser interference lithography and electrochemical deposition. Among the fabricated electrodes, CAuNEs with a diameter of 700 nm, 150 s deposited, was found to be the best for electrochemical dopamine detection. According to cyclic voltammetry results, the linear range of the CAuNE-700 nm was 1–100 µM of dopamine with a limit of detection (LOD) of 5.83 µM. Moreover, owing to the homogeneous periodic features of CAuNEs, human neural cells were successfully cultured and maintained for more than 5 daysin vitrowithout the use of any extracellular matrix proteins and dopamine was detectable in the presence of these cells on the electrode. Therefore, we concluded that the developed dopamine sensing platform CAuNE can be used for many applications including early diagnosis of neurological diseases; function tests of dopaminergic neurons derived from various stem cell sources; and toxicity assessments of drugs, chemicals, and nanomaterials on human neuronal cells.
29 May 2019 in BMC Bioinformatics
Drug candidates often cause an unwanted blockage of the potassium ion channel of the human ether-a-go-go-related gene (hERG). The blockage leads to long QT syndrome (LQTS), which is a severe life-threatening cardiac side effect. Therefore, a virtual screening method to predict drug-induced hERG-related cardiotoxicity could facilitate drug discovery by filtering out toxic drug candidates. In this study, we generated a reliable hERG-related cardiotoxicity dataset composed of 2130 compounds, which were carried out under constant conditions. Based on our dataset, we developed a computational hERG-related cardiotoxicity prediction model. The neural network model achieved an area under the receiver operating characteristic curve (AUC) of 0.764, with an accuracy of 90.1%, a Matthews correlation coefficient (MCC) of 0.368, a sensitivity of 0.321, and a specificity of 0.967, when ten-fold cross-validation was performed. The model was further evaluated using ten drug compounds tested on guinea pigs and showed an accuracy of 80.0%, an MCC of 0.655, a sensitivity of 0.600, and a specificity of 1.000, which were better than the performances of existing hERG-toxicity prediction models. The neural network model can predict hERG-related cardiotoxicity of chemical compounds with a high accuracy. Therefore, the model can be applied to virtual high-throughput screening for drug candidates that do not cause cardiotoxicity. The prediction tool is available as a web-tool at http://ssbio.cau.ac.kr/CardPred .