@article { ISI:000300871600018, title = {Antagonism of microRNA function in zebrafish embryos by using locked nucleic acid enzymes (LNAzymes)}, journal = {Chembiochem}, volume = {13}, number = {4}, year = {2012}, month = {MAR}, pages = {584-589}, publisher = {WILEY-V C H VERLAG GMBH}, address = {PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY}, abstract = {

MicroRNAs (miRNAs) have crucial functions in many cellular processes, such as differentiation, proliferation and apoptosis; aberrant expression of miRNAs has been linked to human diseases, including cancer. Tools that allow specific and efficient knockdown of miRNAs would be of immense importance for exploring miRNA function. Zebrafish serves as an excellent vertebrate model system to understand the functions of miRNAs involved in a variety of biological processes. We designed and employed a strategy based on locked nucleic acid enzymes (LNAzymes) for in vivo knockdown of miRNA in zebrafish embryos. We demonstrate that LNAzyme can efficiently knockdown miRNAs with minimal toxicity to the zebrafish embryos.

}, keywords = {enzymes, locked nucleic acids, microRNA, morpholino, zebrafish}, issn = {1439-4227}, doi = {10.1002/cbic.201100789}, author = {Suryawanshi, Hemant and Lalwani, Mukesh Kumar and Ramasamy, Soundhar and Rana, Rajiv and Scaria, Vinod and Sivasubbu, Sridhar and Maiti, Souvik} } @article {47373, title = {Chronic systemic exposure to IL6 leads to deregulation of glycolysis and fat accumulation in the zebrafish liver}, journal = {Biochimica ET Biophysica Acta-Molecular and Cell Biology of Lipids}, volume = {1866}, year = {2021}, month = {MAY}, pages = {158905}, type = {Article}, abstract = {

Inflammation is a constant in Non-Alcoholic Fatty Liver Disease (NAFLD), although their relationship is unclear. In a transgenic zebrafish system with chronic systemic overexpression of human IL6 (IL6-OE) we show that inflammation can cause intra-hepatic accumulation of triglycerides. Transcriptomics and proteomics analysis of the IL6-OE liver revealed a deregulation of glycolysis/gluconeogenesis pathway, especially a striking down regulation of the glycolytic enzyme aldolase b. Metabolomics analysis by mass spectrometry showed accumulation of hexose monophosphates and their derivatives, which can act as precursors for triglyceride synthesis. Our results suggest that IL6-driven repression of glycolysis/gluconeogenesis, specifically aldolase b, may be a novel mechanism for fatty liver. This mechanism may be relevant for NAFLD in lean individuals, an emerging class of NAFLD prevalent more in Asian Indian populations.

}, keywords = {Aldolase b, DHAP, Inflammation, Interleukin 6, Lean NAFLD, Non-alcoholic fatty liver}, issn = {1388-1981}, doi = {10.1016/j.bbalip.2021.158905}, author = {Singh, Manoj K. and Jayarajan, Rijith and Varshney, Swati and Upadrasta, Sindhuri and Singh, Archana and Yadav, Rajni and Scaria, Vinod and Sengupta, Shantanu and Shanmugam, Dhanasekaran and Shalimar and Sivasubbu, Sridhar and Gandotra, Sheetal and Sachidanandan, Chetana} } @article {48338, title = {G4-binding drugs, chlorpromazine and prochlorperazine, repurposed against COVID-19 infection in hamsters}, journal = {Frontiers in Molecular Biosciences}, volume = {10}, year = {2023}, month = {MAR }, pages = {1133123}, type = {Article}, abstract = {

The COVID-19 pandemic caused by SARS-CoV-2 has caused millions of infections and deaths worldwide. Limited treatment options and the threat from emerging variants underline the need for novel and widely accessible therapeutics. G-quadruplexes (G4s) are nucleic acid secondary structures known to affect many cellular processes including viral replication and transcription. We identified heretofore not reported G4s with remarkably low mutation frequency across \>5 million SARS-CoV-2 genomes. The G4 structure was targeted using FDA-approved drugs that can bind G4s - Chlorpromazine (CPZ) and Prochlorperazine (PCZ). We found significant inhibition in lung pathology and lung viral load of SARS-CoV-2 challenged hamsters when treated with CPZ or PCZ that was comparable to the widely used antiviral drug Remdesivir. In support, in vitro G4 binding, inhibition of reverse transcription from RNA isolated from COVID-infected humans, and attenuated viral replication and infectivity in Vero cell cultures were clear in case of both CPZ and PCZ. Apart from the wide accessibility of CPZ/PCZ, targeting relatively invariant nucleic acid structures poses an attractive strategy against viruses like SARS-CoV-2, which spread fast and accumulate mutations quickly.

}, keywords = {Conserved motif, FDA-approved drugs, G-quadruplex binding drugs, hamster model of COVID-19, RNA G-quadruplex}, doi = {10.3389/fmolb.2023.1133123}, author = {Roy, Shuvra Shekhar and Sharma, Shalu and Rizvi, Zaigham Abbas and Sinha, Dipanjali and Gupta, Divya and Rophina, Mercy and Sehgal, Paras and Sadhu, Srikanth and Tripathy, Manas Ranjan and Samal, Sweety and Maiti, Souvik and Scaria, Vinod and Sivasubbu, Sridhar and Awasthi, Amit and Harshan, Krishnan H. and Jain, Sanjeev and Chowdhury, Shantanu} }