Browsing by Subject "Drug screening"

Now showing 1 - 4 of 4
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    Drug screening with zebrafish visual behavior identifies carvedilol as a potential treatment for an autosomal dominant form of retinitis pigmentosa
    (Springer Nature, 2021-06-01) Ganzen, Logan; Ko, Mee Jung; Zhang, Mengrui; Xie, Rui; Chen, Yongkai; Zhang, Liyun; James, Rebecca; Mumm, Jeff; van Rijn, Richard M.; Zhong, Wenxuan; Pang, Chi Pui; Zhang, Mingzhi; Tsujikawa, Motokazu; Leung, Yuk Fai; Biochemistry and Molecular Biology, School of Medicine
    Retinitis Pigmentosa (RP) is a mostly incurable inherited retinal degeneration affecting approximately 1 in 4000 individuals globally. The goal of this work was to identify drugs that can help patients suffering from the disease. To accomplish this, we screened drugs on a zebrafish autosomal dominant RP model. This model expresses a truncated human rhodopsin transgene (Q344X) causing significant rod degeneration by 7 days post-fertilization (dpf). Consequently, the larvae displayed a deficit in visual motor response (VMR) under scotopic condition. The diminished VMR was leveraged to screen an ENZO SCREEN-WELL REDOX library since oxidative stress is postulated to play a role in RP progression. Our screening identified a beta-blocker, carvedilol, that ameliorated the deficient VMR of the RP larvae and increased their rod number. Carvedilol may directly on rods as it affected the adrenergic pathway in the photoreceptor-like human Y79 cell line. Since carvedilol is an FDA-approved drug, our findings suggest that carvedilol can potentially be repurposed to treat autosomal dominant RP patients.
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    Microfluidics guided by deep learning for cancer immunotherapy screening
    (National Academy of Science, 2022) Ao, Zheng; Cai, Hongwei; Wu, Zhuhao; Hu, Liya; Nunez, Asael; Zhou, Zhuolong; Liu, Hongcheng; Bondesson, Maria; Lu, Xiongbin; Lu, Xin; Dao, Ming; Guo, Feng; Medical and Molecular Genetics, School of Medicine
    Immune-cell infiltration and cytotoxicity to pathogens and diseased cells are ubiquitous in health and disease. To better understand immune-cell behavior in a 3D environment, we developed an automated high-throughput microfluidic platform that enables real-time imaging of immune-cell infiltration dynamics and killing of the target cancer cells. We trained a deep learning algorithm using clinical data and integrated the algorithm with our microfluidic platform to effectively identify epigenetic drugs that promote T cell tumor infiltration and enhance cancer immunotherapy efficacy both in vitro and in vivo. Our platform provides a unique method to investigate immune-tissue interactions, which can be widely applied to oncology, immunology, neurology, microbiology, tissue engineering, regenerative medicine, translational medicine, and so on.
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    Utilizing Zebrafish Visual Behaviors in Drug Screening for Retinal Degeneration
    (MDPI, 2017-06-02) Ganzen, Logan; Venkatraman, Prahatha; Pang, Chi Pui; Leung, Yuk Fai; Zhang, Mingzhi; Biochemistry and Molecular Biology, School of Medicine
    Zebrafish are a popular vertebrate model in drug discovery. They produce a large number of small and rapidly-developing embryos. These embryos display rich visual-behaviors that can be used to screen drugs for treating retinal degeneration (RD). RD comprises blinding diseases such as Retinitis Pigmentosa, which affects 1 in 4000 people. This disease has no definitive cure, emphasizing an urgency to identify new drugs. In this review, we will discuss advantages, challenges, and research developments in using zebrafish behaviors to screen drugs in vivo. We will specifically discuss a visual-motor response that can potentially expedite discovery of new RD drugs.
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    Who gets screened and who tests positive? Drug screening among justice-involved youth in a midwestern urban county
    (Springer Nature, 2024-04-05) Clifton, Richelle L.; Carson, Ian; Dir, Allyson L.; Tu, Wanzhu; Zapolski, Tamika C. B.; Aalsma, Matthew C.; Psychology, School of Science
    Background: Given high rates of substance use among justice-involved youth, justice systems have attempted to monitor use through drug screening (DS) procedures. However, there is discretion in deciding who is screened for substance use, as not every youth who encounters the system is screened. The aim of the current study was to examine factors associated with selection for and results of oral DS among justice-involved youth assigned to probation to better inform potential DS policy. Electronic court records from 4,668 youth with first-incident records assigned to probation in a midwestern urban county's juvenile justice system between 2011 and 2016 were included in the analytical sample. Race/ethnicity, gender, age, number of charges and charge type for the current incident were included as independent variables. Results: Multivariable hierarchical logistic regression analyses indicated that males were more likely to be assigned to DS (aOR = 0.40, 95%CI [0.34, 0.46]), and more likely to test positive for use (aOR = 0.43, 95% CI [0.34, 0.54]) than females. As age increased, youth were less likely to be assigned to DS (aOR = 0.91, 95% CI [0.87, 0.94]), with non-significant differences in DS results. Greater number of charges were associated with a higher likelihood of being assigned to DS (aOR = 1.55, 95% CI [1.43, 1.68]). Youth with violent offenses were more likely to be assigned to DS than those with other offense types (property offenses, drug offenses, statutory offenses, disorderly conduct, and all other offenses), but less likely to test positive for use. Conclusions: Many factors were associated with differences in DS, but these factors were not always associated with differential DS results. Demographic or charge-based decisions may not be appropriate for DS assignment.