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- W2920468153 abstract "Pleiotropic and evolutionally conserved components of transcription nuclear factor - NF-B play key roles in progression of various diseases by regulating expression of antiapoptotic and cytokine responsive genes [1] [2]. We previously demonstrated that rapidly activating transcription factors (TF) can be detected by using sequence-specific self-quenched reporter probes (oligonucleotide-molecular sensors (ODN-MS), which ideally remain “silent” in the absence of activated TF but emit photons upon specific binding to them [3-5]. Recently we were investigating sensor-based optical imaging of early inflammation in the endocrine pancreas using type 1 diabetes (T1D) model because NF-κB activation is essential for determining the fate of pancreatic β-cells and hence the progression of T1D. Using an immunocompetent SKH1 mouse model of early stage T1D we showed that NF-κB activation was induced by low-dose streptozotocin (LD-STZ). ODNMS probes that carried near-infrared (NIR) fluorophores formed a complex with NF-κB subunits in in vitro assays and in situ after LD-STZ treatment. Imaging studies of pancreas (sections and isolated islets) were corroborated with electrophoresis mobility shift assays (EMSA). A higher specific NIR fluorescence intensity in nuclei and cytoplasm of islets from LD-STZ treated groups compared to non-treated control animals was observed. Our results demonstrate that: 1) the use of ODN-MS probes in non-fixed islets and tissue sections may be used for distinguishing differences in inflammatory pathway activation in animal models of early stage diabetes; 2) early, non-invasive detection of NF-κB in pancreatic islets may serve as a potential strategy for imaging of early T1D-mediated sustained pro-inflammatory changes in the endocrine pancreas." @default.
- W2920468153 created "2019-03-11" @default.
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- W2920468153 date "2019-03-01" @default.
- W2920468153 modified "2023-10-16" @default.
- W2920468153 title "Near-infrared oligonucleotide duplex sensors for imaging rapidly activated transcription factors in vitro and in situ" @default.
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- W2920468153 doi "https://doi.org/10.1117/12.2511124" @default.
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