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https://www.selleckchem.com/products/4u8c.html This bi-functional strategy that uses a single therapeutic molecule can be the basis for novel PCa treatments. It might also be customized to other types of therapies that require the silencing of one gene and the simultaneous expression of a different isoform.Reprogramming scar fibroblasts into new heart muscle cells has the potential to restore function to the injured heart. However, the effectiveness of reprogramming is notably low. We have recently demonstrated that the effectiveness of reprogramming fibroblasts into heart muscle cells (cardiomyocytes) is increased by the addition of RNA-sensing receptor ligands. Clinical use of these ligands is problematic due to their ability to induce adverse inflammatory events. To overcome this issue, we sought to determine whether synthetic analogs of natural RNA-sensing receptor ligands, which avoid generating inflammatory insults and are nuclease resistant, would similarly enhance fibroblast reprogramming into cardiomyocytes. Indeed, one such stabilized RNA, ICR2, increased the expression of cardiomyocyte-specific mRNAs in reprogrammed fibroblasts. Moreover, ICR2 enhanced the ability of reprogramming factors to produce cardiomyocytes with mature sarcomeres. Knockdown assays indicated that the effects of ICR2 were mediated by the RNA-sensing receptors Rig-I and TLR3. In addition, ICR2 reduced the effective dose and number of reprogramming factors needed for efficient reprogramming. In summary, the synthetic RNA oligonucleotide ICR2 is a potential therapeutic agent to enhance cardiac reprogramming efficiency.Colorectal cancer (CRC), ranking as the third commonest cancer, leads to extremely high rates of mortality. Metastasis is the major cause of poor outcome in CRC. When metastasis occurs, 5-year survival rates of patients decrease sharply, and strategies to enhance a patient's lifetime seem limited. MicroRNAs (miRNAs) are evolutionarily conserved small non-coding RNAs that a
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