The rat has been used extensively as a model for evaluating chemical toxicities and for understanding drug mechanisms. However, its transcriptome across multiple organs, or developmental stages, has not yet been reported. Here we show, as part of the SEQC consortium efforts, a comprehensive rat transcriptomic BodyMap created by performing RNA-Seq on 320 samples from 11 organs of both sexes of juvenile, adolescent, adult and aged Fischer 344 rats. We catalogue the expression profiles of 40,064 genes, 65,167 transcripts, 31,909 alternatively spliced transcript variants and 2,367 non-coding genes/non-coding RNAs (ncRNAs) annotated in AceView. We find that organ-enriched, differentially expressed genes reflect the known organ-specific biological activities. A large number of transcripts show organ-specific, age-dependent or sex-specific differential expression patterns. We create a web-based, open-access rat BodyMap database of expression profiles with crosslinks to other widely used databases, anticipating that it will serve as a primary resource for biomedical research using the rat model.

The pandemic of novel coronavirus disease 2019 (COVID-19) has rampaged the world, with more than 58.4 million confirmed cases and over 1.38 million deaths across the world by 23 November 2020. There is an urgent need to identify effective drugs and vaccines to fight against the virus. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) belongs to the family of coronaviruses consisting of four structural and 16 non-structural proteins (NSP). Three non-structural proteins, main protease (Mpro), papain-like protease (PLpro), and RNA-dependent RNA polymerase (RdRp), are believed to have a crucial role in replication of the virus. We applied computational ligand-receptor binding modeling and performed comprehensive virtual screening on FDA-approved drugs against these three SARS-CoV-2 proteins using AutoDock Vina, Glide, and rDock. Our computational studies identified six novel ligands as potential inhibitors against SARS-CoV-2, including antiemetics rolapitant and ondansetron for Mpro; labetalol and levomefolic acid for PLpro; and leucal and antifungal natamycin for RdRp. Molecular dynamics simulation confirmed the stability of the ligand-protein complexes. The results of our analysis with some other suggested drugs indicated that chloroquine and hydroxychloroquine had high binding energy (low inhibitory effect) with all three proteins—Mpro, PLpro, and RdRp. In summary, our computational molecular docking approach and virtual screening identified some promising candidate SARS-CoV-2 inhibitors that may be considered for further clinical studies.

Systemic hypertension, which eventually results in heart failure, renal failure or stroke, is a common chronic human disorder that particularly affects elders. Although many signaling pathways involved in the development of hypertension have been reported over the past decades, which has led to the implementation of a wide variety of anti-hypertensive therapies, one half of all hypertensive patients still do not have their blood pressure controlled. The frontier in understanding the molecular mechanisms underlying hypertension has now advanced to the level of epigenomics. Particularly, increasing evidence is emerging that DNA methylation and histone modifications play an important role in gene regulation and are involved in alteration of the phenotype and function of vascular cells in response to environmental stresses. This review seeks to highlight the recent advances in our knowledge of the epigenetic regulations and mechanisms of hypertension, focusing on the role of DNA methylation and histone modification in the vascular wall. A better understanding of the epigenomic regulation in the hypertensive vessel may lead to the identification of novel target molecules that, in turn, may lead to novel drug discoveries for the treatment of hypertension.