Search for: drug-development
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    Combined effects of electric stimulation and microgrooves in cardiac tissue-on-a-chip for drug screening

    , Article Small Methods ; Volume 4, Issue 10 , 2020 Ren, L ; Zhou, X ; Nasiri, R ; Fang, J ; Jiang, X ; Wang, C ; Qu, M ; Ling, H ; Chen, Y ; Xue, Y ; Hartel, M.C ; Tebon, P ; Zhang, S ; Kim, H.-J ; Yuan, X ; Shamloo, A ; Dokmeci, M. R ; Li, S ; Khademhosseini, A ; Ahadian, S ; Sun, W ; Sharif University of Technology
    John Wiley and Sons Inc  2020
    Animal models and traditional cell cultures are essential tools for drug development. However, these platforms can show striking discrepancies in efficacy and side effects when compared to human trials. These differences can lengthen the drug development process and even lead to drug withdrawal from the market. The establishment of preclinical drug screening platforms that have higher relevancy to physiological conditions is desirable to facilitate drug development. Here, a heart-on-a-chip platform, incorporating microgrooves and electrical pulse stimulations to recapitulate the well-aligned structure and synchronous beating of cardiomyocytes (CMs) for drug screening, is reported. Each chip... 

    Capturing single-cell heterogeneity via data fusion improves image-based profiling

    , Article Nature Communications ; Volume 10, Issue 1 , 2019 ; 20411723 (ISSN) Rohban, M. H ; Abbasi, H. S ; Singh, S ; Carpenter, A. E ; Sharif University of Technology
    Nature Publishing Group  2019
    Single-cell resolution technologies warrant computational methods that capture cell heterogeneity while allowing efficient comparisons of populations. Here, we summarize cell populations by adding features’ dispersion and covariances to population averages, in the context of image-based profiling. We find that data fusion is critical for these metrics to improve results over the prior alternatives, providing at least ~20% better performance in predicting a compound’s mechanism of action (MoA) and a gene’s pathway. © 2019, The Author(s)  

    Mining the potential of label-free biosensors for in vitro antipsychotic drug screening

    , Article Biosensors ; Volume 8, Issue 1 , 2018 ; 20796374 (ISSN) Kilic, T ; Soler, M ; Fahimi Kashani, N ; Altug, H ; Carrara, S ; Sharif University of Technology
    MDPI AG  2018
    The pharmaceutical industry is facing enormous challenges due to high drug attribution rates. For the past decades, novel methods have been developed for safety and efficacy testing, as well as for improving early development stages. In vitro screening methods for drug-receptor binding are considered to be good alternatives for decreasing costs in the identification of drug candidates. However, these methods require lengthy and troublesome labeling steps. Biosensors hold great promise due to the fact that label-free detection schemes can be designed in an easy and low-cost manner. In this paper, for the first time in the literature, we aimed to compare the potential of label-free optical and... 

    Discovery of a tetracyclic indole alkaloid that postpones fibrillation of hen egg white lysozyme protein

    , Article International Journal of Biological Macromolecules ; Volume 183 , 2021 , Pages 1939-1947 ; 01418130 (ISSN) Ashrafian, H ; Zadeh, E.H ; Tajbakhsh, M ; Majid, N ; Srivastava, G.N ; Khan, R.H ; Sharif University of Technology
    Elsevier B.V  2021
    Protein aggregation, such as amyloid fibril formation, is molecular hallmark of many neurodegenerative disorders including Alzheimer's, Parkinson's, and Prion disease. Indole alkaloids are well-known as the compounds having the ability to inhibit protein fibrillation. In this study, we experimentally and computationally have investigated the anti-amyloid property of a derivative of a synthesized tetracyclic indole alkaloid (TCIA), possessing capable functional groups. The fibrillation reaction of Hen White Egg Lysozyme (HEWL) was performed in absence and presence of the indole alkaloid. For quantitative analysis, we used Thioflovin T binding assay which showed ~50% reduction in fibril...