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Cardiovascular Molecular Imaging: Overview of Cardiac Reporter Gene Imaging
Published in Robert J. Gropler, David K. Glover, Albert J. Sinusas, Heinrich Taegtmeyer, Cardiovascular Molecular Imaging, 2007
Joseph C. Wu, Sanjiv S. Gambhir
Indirect molecular imaging using reporter genes have only been recently validated. The concept of imaging reporter gene expression is illustrated in Figure 1. A reporter gene is first introduced into target tissues by viral or non-viral vectors. Using molecular biology techniques, the promoter or regulatory regions of genes can be cloned into different vectors to drive the transcription of a reporter gene into mRNA. The promoter activity can be “constitutive” (always on), “inducible” (turned on or off), or “tissue-specific” (expressed only in the heart, liver, or other organs). Translation of the mRNA leads to a reporter protein that can interact with the reporter probe. This interaction may be enzyme-based or receptor-based (discussed in a later section). The signals can then be detected by various imaging modalities such as optical charged coupled device (CCD) camera, PET, or MRI. Clearly, the main advantage of reporter gene system is its flexibility and multiplexing capacity. By altering various components, the reporter gene can provide information about the regulation of DNA by upstream promoter, the fate of intracellular protein trafficking, and the efficiency of vector transduction into cells. Likewise, the reporter probe itself does not have to be changed if one wishes to study a new biological process, which saves valuable time needed to synthesize, test, and validate new radiotracer agents. However, the main disadvantage of indirect imaging is that it is a surrogate marker of the physiologic process of interest rather than a direct measurement of the receptor density, intracellular enzyme, or mRNA copies as discussed above, which are likely to be more clinically relevant.
Genetic variants affecting chemical mediated skin immunotoxicity
Published in Journal of Toxicology and Environmental Health, Part B, 2022
Isisdoris Rodrigues de Souza, Patrícia Savio de Araujo-Souza, Daniela Morais Leme
The human IL31 gene is located on chromosome 12q24.31 (Dillon et al. 2004) and presents polymorphisms with a role in impairing skin immune homeostasis. The SNP IL31-631 T > G (rs10847385) was associated with IL-31 blood levels, IgE levels and severity of extrinsic AD (Hong et al. 2012). The −631 C allele contributed to impaired function of the IL31 promoter and lowered IL-31 serum levels. In addition, −631 C allele downregulates the IL31 expression only under inflammatory conditions suggesting that IL31 – 631 acts as a disease modifier by influencing inflammatory conditions rather than as a disease risk factor. Using the bioinformatics tool TFSER, Hong et al. (2012) found two putative binding sites near IL31 −631, including Cap and Heat shock transcription factor (HSF) that might stimulate promoter activity.
Influence of o,p′-DDT on MUC5AC expression via regulation of NF-κB/AP-1 activation in human lung epithelial cells
Published in Journal of Toxicology and Environmental Health, Part A, 2021
Gi Ho Lee, Sun Woo Jin, Jae Ho Choi, Eun Hee Han, Yong Pil Hwang, Chul Yung Choi, Hye Gwang Jeong
To examine the effects of o,p′-DDT on MUC5AC mRNA levels in A549 cells, cells were treated with o,p′-DDT at different concentrations, and MUC5AC mRNA levels measured using semi-quantitative RT-PCR. o,p′-DDT treatment significantly increased MUC5AC mRNA levels in a concentration- and time-dependent manner (Figures 1A and 1B). The influence of o,p′-DDT on MUC5AC promoter activity was determined using a MUC5AC promoter luciferase construct, transiently transfected into A549 cells incubated with o,p′-DDT for 24 hr. As illustrated in Figure 1C, o,p′-DDT significantly increased luciferase activity of MUC5AC in A549 cells. These results showed that o,p′-DDT induced MUC5AC mRNA levels by promoting its transcription in A549 cells.
Licochalcone A, a licorice flavonoid: antioxidant, cytotoxic, genotoxic, and chemopreventive potential
Published in Journal of Toxicology and Environmental Health, Part A, 2020
Karoline Soares de Freitas, Iara Silva Squarisi, Nathália Oliveira Acésio, Heloiza Diniz Nicolella, Saulo Duarte Ozelin, Matheus Reis Santos de Melo, Ana Paula Prado Guissone, Gabriela Fernandes, Lívia Mara Silva, Ademar Alves da Silva Filho, Denise Crispim Tavares
According to Bhale et al. (2017), chalcones are effective in directly eliminating reactive oxygen and nitrogen species, nitric oxide, and superoxide. Lv et al. (2015) observed that LicoA markedly upregulated the antioxidant enzyme heme oxygenase 1 (HO-1) and nuclear factor erythroid 2-related factor 2 (Nrf2) in mouse macrophages RAW 264.7 cells. This upregulation was associated with induction of Nrf2 nuclear translocation, a decrease in Keap1 protein expression, and elevation in antioxidant response element (ARE) promoter activity. Chen et al. (2017) demonstrated the ability of LicoA to reduce cellular oxidative stress and upregulate expression of antioxidant enzymes superoxide dismutase, catalase, and anti-glutathione peroxidase in human fetal hepatocytes (L-02 cells).