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Research paper thumbnail of Developmental toxicity of remdesivir, an <scp>anti‐COVID</scp> ‐19 drug, is implicated by in vitro assays using morphogenetic embryoid bodies of mouse and human pluripotent stem cells

Birth Defects Research, Nov 8, 2022

BackgroundRemdesivir is an antiviral drug approved for the treatment of COVID‐19, whose developme... more BackgroundRemdesivir is an antiviral drug approved for the treatment of COVID‐19, whose developmental toxicity remains unclear. More information about the safety of remdesivir is urgently needed for people of childbearing potential, who are affected by the ongoing pandemic. Morphogenetic embryoid bodies (MEBs) are three‐dimensional (3D) aggregates of pluripotent stem cells that recapitulate embryonic body patterning in vitro, and have been used as effective embryo models to detect the developmental toxicity of chemical exposures specifically and sensitively.MethodsMEBs were generated from mouse P19C5 and human H9 pluripotent stem cells, and used to examine the effects of remdesivir. The morphological effects were assessed by analyzing the morphometric parameters of MEBs after exposure to varying concentrations of remdesivir. The molecular impact of remdesivir was evaluated by measuring the transcript levels of developmental regulator genes.ResultsThe mouse MEB morphogenesis was impaired by remdesivir at 1–8 μM. Remdesivir affected MEBs in a manner dependent on metabolic conversion, and its potency was higher than GS‐441524 and GS‐621763, presumptive anti‐COVID‐19 drugs that act similarly to remdesivir. The expressions of developmental regulator genes, particularly those involved in axial and somite patterning, were dysregulated by remdesivir. The early stage of MEB development was more vulnerable to remdesivir exposure than the later stage. The morphogenesis and gene expression profiles of human MEBs were also impaired by remdesivir at 1–8 μM.ConclusionsRemdesivir impaired mouse and human MEBs at concentrations that are comparable to the therapeutic plasma levels in humans, urging further investigation into the potential impact of remdesivir on developing embryos.

Research paper thumbnail of Can We Decipher True vs. False? Psychophysiological Responses to True and False News Headlines Seen on Social Media

Social media has morphed from a form of entertainment used to maintain connections with friends t... more Social media has morphed from a form of entertainment used to maintain connections with friends to a major platform for idea sharing. Almost everyone in our society utilizes at least one form of social media every day, and in 2017, twenty-six percent of

Research paper thumbnail of Developmental toxicity of remdesivir, an anti‐COVID ‐19 drug, is implicated by in vitro assays using morphogenetic embryoid bodies of mouse and human pluripotent stem cells

Research paper thumbnail of Developmental toxicity of remdesivir, an anti‐COVID ‐19 drug, is implicated by in vitro assays using morphogenetic embryoid bodies of mouse and human pluripotent stem cells

Birth Defects Research

Background: Remdesivir is an antiviral drug approved for the treatment of COVID-19, whose develop... more Background: Remdesivir is an antiviral drug approved for the treatment of COVID-19, whose developmental toxicity remains unclear. More information about the safety of remdesivir is urgently needed for people of childbearing potential, who are affected by the ongoing pandemic. Morphogenetic embryoid bodies (MEBs) are three-dimensional (3D) aggregates of pluripotent stem cells that recapitulate embryonic body patterning in vitro, and have been used as effective embryo models to detect the developmental toxicity of chemical exposures specifically and sensitively. Methods: MEBs were generated from mouse P19C5 and human H9 pluripotent stem cells, and used to examine the effects of remdesivir. The morphological effects were assessed by analyzing the morphometric parameters of MEBs after exposure to varying concentrations of remdesivir. The molecular impact of remdesivir was evaluated by measuring the transcript levels of developmental regulator genes. Results: The mouse MEB morphogenesis was impaired by remdesivir at 1-8 μM. Remdesivir affected MEBs in a manner dependent on metabolic conversion, and its potency was higher than GS-441524 and GS-621763, presumptive anti-COVID-19 drugs that act similarly to remdesivir. The expressions of developmental regulator genes, particularly those involved in axial and somite patterning, were dysregulated by remdesivir. The early stage of MEB development was more vulnerable to remdesivir exposure than the later stage. The morphogenesis and gene expression profiles of human MEBs were also impaired by remdesivir at 1-8 μM.

Research paper thumbnail of Dolutegravir Impairs Stem Cell-Based 3D Morphogenesis Models in a Manner Dependent on Dose and Timing of Exposure: An Implication for Its Developmental Toxicity

Toxicological Sciences, 2021

Dolutegravir (DTG) is an antiretroviral drug of the integrase strand transfer inhibitor (INSTI) c... more Dolutegravir (DTG) is an antiretroviral drug of the integrase strand transfer inhibitor (INSTI) class used to treat human immunodeficiency virus infection. It is the recommended first-line regimen for most people, including women of childbearing age. However, some human and animal studies have suggested that DTG causes birth defects, although its developmental toxicity remains controversial. Here, we investigated the adverse effects of DTG using pluripotent stem cell-based in vitro morphogenesis models that have previously been validated as effective tools to assess the developmental toxicity of various chemicals. DTG diminished the growth and axial elongation of the morphogenesis model of mouse pluripotent stem cells at exposures of 2 μM and above in a concentration-dependent manner. Concomitantly, DTG altered the expression profiles of developmental regulator genes involved in embryonic patterning. The adverse effects were observed when the morphogenesis model was exposed to DTG a...

Research paper thumbnail of Approaching Fake News at the Expense of Truth: A Psychophysiological Study of News on Social Media

Proceedings of the 53rd Hawaii International Conference on System Sciences, 2020

In 2018, sixty-eight percent of adults in America obtained their news from social media sites. Du... more In 2018, sixty-eight percent of adults in America obtained their news from social media sites. During the same period, the amount of fake news online has increased substantially, resulting in increased propagation of false information. The research literature is growing on the effects of fake news on social media, but few studies have examined psychophysiological responses to true and fake news on social media. This research utilizes psychophysiological measures, specifically heart rate variability and skin conductance, to compare the perceived believability of news headlines posted on social media. Our findings indicate that individuals exhibit increased levels of approach behavior to true and fake news on social media. Additionally, higher time spent on social media is related to an increase in approach behavior to fake news. These findings have important implications for research and practice.

Research paper thumbnail of Developmental toxicity of remdesivir, an <scp>anti‐COVID</scp> ‐19 drug, is implicated by in vitro assays using morphogenetic embryoid bodies of mouse and human pluripotent stem cells

Birth Defects Research, Nov 8, 2022

BackgroundRemdesivir is an antiviral drug approved for the treatment of COVID‐19, whose developme... more BackgroundRemdesivir is an antiviral drug approved for the treatment of COVID‐19, whose developmental toxicity remains unclear. More information about the safety of remdesivir is urgently needed for people of childbearing potential, who are affected by the ongoing pandemic. Morphogenetic embryoid bodies (MEBs) are three‐dimensional (3D) aggregates of pluripotent stem cells that recapitulate embryonic body patterning in vitro, and have been used as effective embryo models to detect the developmental toxicity of chemical exposures specifically and sensitively.MethodsMEBs were generated from mouse P19C5 and human H9 pluripotent stem cells, and used to examine the effects of remdesivir. The morphological effects were assessed by analyzing the morphometric parameters of MEBs after exposure to varying concentrations of remdesivir. The molecular impact of remdesivir was evaluated by measuring the transcript levels of developmental regulator genes.ResultsThe mouse MEB morphogenesis was impaired by remdesivir at 1–8 μM. Remdesivir affected MEBs in a manner dependent on metabolic conversion, and its potency was higher than GS‐441524 and GS‐621763, presumptive anti‐COVID‐19 drugs that act similarly to remdesivir. The expressions of developmental regulator genes, particularly those involved in axial and somite patterning, were dysregulated by remdesivir. The early stage of MEB development was more vulnerable to remdesivir exposure than the later stage. The morphogenesis and gene expression profiles of human MEBs were also impaired by remdesivir at 1–8 μM.ConclusionsRemdesivir impaired mouse and human MEBs at concentrations that are comparable to the therapeutic plasma levels in humans, urging further investigation into the potential impact of remdesivir on developing embryos.

Research paper thumbnail of Can We Decipher True vs. False? Psychophysiological Responses to True and False News Headlines Seen on Social Media

Social media has morphed from a form of entertainment used to maintain connections with friends t... more Social media has morphed from a form of entertainment used to maintain connections with friends to a major platform for idea sharing. Almost everyone in our society utilizes at least one form of social media every day, and in 2017, twenty-six percent of

Research paper thumbnail of Developmental toxicity of remdesivir, an anti‐COVID ‐19 drug, is implicated by in vitro assays using morphogenetic embryoid bodies of mouse and human pluripotent stem cells

Research paper thumbnail of Developmental toxicity of remdesivir, an anti‐COVID ‐19 drug, is implicated by in vitro assays using morphogenetic embryoid bodies of mouse and human pluripotent stem cells

Birth Defects Research

Background: Remdesivir is an antiviral drug approved for the treatment of COVID-19, whose develop... more Background: Remdesivir is an antiviral drug approved for the treatment of COVID-19, whose developmental toxicity remains unclear. More information about the safety of remdesivir is urgently needed for people of childbearing potential, who are affected by the ongoing pandemic. Morphogenetic embryoid bodies (MEBs) are three-dimensional (3D) aggregates of pluripotent stem cells that recapitulate embryonic body patterning in vitro, and have been used as effective embryo models to detect the developmental toxicity of chemical exposures specifically and sensitively. Methods: MEBs were generated from mouse P19C5 and human H9 pluripotent stem cells, and used to examine the effects of remdesivir. The morphological effects were assessed by analyzing the morphometric parameters of MEBs after exposure to varying concentrations of remdesivir. The molecular impact of remdesivir was evaluated by measuring the transcript levels of developmental regulator genes. Results: The mouse MEB morphogenesis was impaired by remdesivir at 1-8 μM. Remdesivir affected MEBs in a manner dependent on metabolic conversion, and its potency was higher than GS-441524 and GS-621763, presumptive anti-COVID-19 drugs that act similarly to remdesivir. The expressions of developmental regulator genes, particularly those involved in axial and somite patterning, were dysregulated by remdesivir. The early stage of MEB development was more vulnerable to remdesivir exposure than the later stage. The morphogenesis and gene expression profiles of human MEBs were also impaired by remdesivir at 1-8 μM.

Research paper thumbnail of Dolutegravir Impairs Stem Cell-Based 3D Morphogenesis Models in a Manner Dependent on Dose and Timing of Exposure: An Implication for Its Developmental Toxicity

Toxicological Sciences, 2021

Dolutegravir (DTG) is an antiretroviral drug of the integrase strand transfer inhibitor (INSTI) c... more Dolutegravir (DTG) is an antiretroviral drug of the integrase strand transfer inhibitor (INSTI) class used to treat human immunodeficiency virus infection. It is the recommended first-line regimen for most people, including women of childbearing age. However, some human and animal studies have suggested that DTG causes birth defects, although its developmental toxicity remains controversial. Here, we investigated the adverse effects of DTG using pluripotent stem cell-based in vitro morphogenesis models that have previously been validated as effective tools to assess the developmental toxicity of various chemicals. DTG diminished the growth and axial elongation of the morphogenesis model of mouse pluripotent stem cells at exposures of 2 μM and above in a concentration-dependent manner. Concomitantly, DTG altered the expression profiles of developmental regulator genes involved in embryonic patterning. The adverse effects were observed when the morphogenesis model was exposed to DTG a...

Research paper thumbnail of Approaching Fake News at the Expense of Truth: A Psychophysiological Study of News on Social Media

Proceedings of the 53rd Hawaii International Conference on System Sciences, 2020

In 2018, sixty-eight percent of adults in America obtained their news from social media sites. Du... more In 2018, sixty-eight percent of adults in America obtained their news from social media sites. During the same period, the amount of fake news online has increased substantially, resulting in increased propagation of false information. The research literature is growing on the effects of fake news on social media, but few studies have examined psychophysiological responses to true and fake news on social media. This research utilizes psychophysiological measures, specifically heart rate variability and skin conductance, to compare the perceived believability of news headlines posted on social media. Our findings indicate that individuals exhibit increased levels of approach behavior to true and fake news on social media. Additionally, higher time spent on social media is related to an increase in approach behavior to fake news. These findings have important implications for research and practice.