Double-stranded RNA (dsRNA) is produced in host cells during viral replication. The effects of DNA demethylation on gene expression in dsRNA transfected swine cells are unclear. The study aims to profile the transcriptome changes which are induced by DNA methyltransferase inhibitor (Aza-CdR) in porcine PK15 cells transfected with viral-like dsRNA (Poly(I:C)). A total of 44, 76 and 952 differentially expressed genes (DEGs) were detected in the cells treated by Poly(I:C) plus Aza-CdR (P+A), Poly(I:C) (P) or Aza-CdR (A) alone compared to the controls (C). Immune response-related pathways are observed in the comparison of A vs. C and P vs. C, and the genes in the pathways were recovered in the comparison of (P+A) vs. C. GO analysis indicated that Aza-CdR has negative regulatory effects on viral reproduction. The results suggest that the stimulant of Poly(I:C) could be regressed by Aza-CdR. These observations provide new insights into the epigenetic regulatory effects on viral replication.
A facile electrochemical sulfonylative cycloetherification of linear unsaturated alcohols with sulfonyl hydrazides under mild conditions has been accomplished. This catalyst-and oxidant-free protocol proceeds via electro-oxidation, followed by radical addition, as well as an intramolecular oxygen nucleophilic process. This methodology is compatible with a broad substrate scope and good functional group compatibility, which provides a valuable and convenient synthetic tool for the synthesis of saturated five-, six-, seven-, and eight-membered ring oxygen heterocycles. Furthermore, sulfonylative cycloesterification of linear unsaturated acids toward the lactone products has also been established under this electrochemical system. In addition, control experiments indicated that the N−H bonds of the sulfonyl hydrazide molecule are non-essential.
A direct and efficient method for constructing N,Ndisubstituted hydrazines via a palladium-catalyzed allylic substitution of allyl acetates with arylhydrazines as nucleophiles has been developed. This method is highly selective in terms of both chemoand regio-selectivity and is carried out under an open-air system with the use of the DPPPy phosphine ligand. Additionally, this reaction is compatible with a wide variety of substrates, including those bearing reactive groups such as Cl, Br, and I, to afford various N 1 -allylation products in moderate to good yields under simple and mild reaction conditions. N,N-Disubstituted hydrazines are a class of important scaffolds, which have been widely found in biologically active natural products and pharmaceutical molecules 1 and are also useful building blocks for the synthesis of N-substituted indoles in organic synthesis. 2 Therefore, tremendous effort has been dedicated to constructing N,N-disubstituted hydrazine frameworks. 3 Classical synthesis methods for access to these scaffolds could be classified into two categories, N−N bond formation reactions of secondary amines and direct N 1functionalization of monosubstituted hydrazines. The former mainly focused on reduction of N-nitrosamines, formed by nitrosation of secondary amines in presence of nitrous acid. 4 The later involved reductive amination of carbonyl compounds 5 and nucleophilic substitution of halides. 6 Despite significant advances, these methods still existed with some limitations, including harsh and complex conditions, multistep reaction processes, and narrow substrate scope.Recently, transition-metal catalyzed direct N-functionalization of hydrazines has been considered a powerful method for the synthesis of substituted hydrazines. 7 For example, Pd-and Cu-catalyzed coupling reactions of N-Boc hydrazine or hydrazine with aryl halides have been reported for the construction of polysubstituted hydrazines. 8 However, to our knowledge, transition-metal catalyzed N 1 -functionalization of arylhydrazines remains challenging, because arylhydrazines are prone to undergoing dehydrazination reactions under transition-metal catalytic conditions. 9 To address this issue, phosphine ligands have been employed to lower the rate of carbon−nitrogen bond cleavage of arylhydrazines. In this field, the Breit group developed a N 1 -allylation reaction of arylhydrazines with allenes using [Rh(COD)Cl] 2 with a chiral phosphine ligand (L1 or L2) in 2015 (Scheme 1, eq 1), 10 and the Kwong group reported a N 1 -arylation reaction of arylhydrazines with aryl tosylates using Pd(TFA) 2 and a phosphine ligand (L3) in 2020 (Scheme 1, eq 2). 11 By employing this approach, we herein present a novel Pd-
An efficient palladium-catalyzed oxidative nonclassical Heck reaction of arylhydrazines with allylic alcohols via C–N bond cleavage has been successfully developed. This method provides a series of β-arylated carbonyl compounds with broad functional group tolerance under base-free, simple, and mild open air reaction conditions. In the reaction, arylhydrazines with the smaller molecular weight of the leaving group were employed as the “green” arylation reagent, which released N2 and water as the byproducts under air. Mechanistic studies suggested that an aryl radical process and Pd–H complex migration reinsertion were involved. Moreover, the synthesis of the antiarrhythmic drug propafenone was completed with this transformation as the key step.
A B S T R A C TDuring RNA viruses's replication, double-stranded RNA (dsRNA) is normally produced and induce host innate immune response. Most of gene activation due cytokine mediated but which are due to methylation mediated is still unknown. In the study, DNA methylome was integrated with our previous transcriptome data to investigate the differentially methylated regions and genes using MeDIP-chip technology. We found that the transcriptional expressions of 15, 37 and 18 genes were negatively related with their promoter DNA methylation levels in the cells treated by PolyI:C, Aza-CdR, as well as PolyI:C plus Aza-CdR, respectively, compared with the untreated cells. GO analysis revealed hypo-methylated genes (BNIP3L and CDK9) and a hyper-methylated gene (ZC3HAV1) involved in the host response to viral replication. Our results suggest that these novel genes targeted by DNA methylation can be potential markers relevant to virus replication and host innate immune response to set up a medical model of infectious diseases. PolyI:C treated cells (P < 0.05) [2]. Out of these DEGs, eighteen are Abbreviations: PK15, porcine kidney epithelial cell line; dsRNA, double-stranded RNA; PolyI:C, a synthetic viral-like dsRNA analogplolyinosinic: polycyticdylic acid; Aza-CdR, DNA methyltransferases inhibitor 5-aza-2′-deoxycytidine; P, PK15 cells extracellular treatment with PolyI:C; A, PK15 cells treated with Aza-CdR; P+A, PK15 cells treated with PolyI:C followed by the addition of Aza-
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.