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Abstract Background Coxsackievirus B3 is an important infectious agent of viral myocarditis, pancreatitis and aseptic meningitis, but there are no specific antiviral therapeutic reagents in clinical use. RNA interference-based technology has been developed to prevent the viral infection. Methods To evaluate the impact of RNA interference on viral replication, cytopathogenicity and animal survival, short hairpin RNAs targeting the viral 2B region (shRNA-2B) expressed by a recombinant vector (pGCL-2B) or a recombinant lentivirus (Lenti-2B) were tansfected in HeLa cells or transduced in mice infected with CVB3. Results ShRNA-2B exhibited a significant effect on inhibition of viral production in HeLa cells. Furthermore, shRNA-2B improved mouse survival rate, reduced the viral tissues titers and attenuated tissue damage compared with those of the shRNA-NC treated control group. Lenti-2B displayed more effective role in inhibition of viral replication than pGCL-2B in vivo. Conclusions Coxsackievirus B3 2B is an effective target of gene silencing against coxsackievirus B3 infection, suggesting that shRNA-2B is a potential agent for further development into a treatment for enterviral diseases.

Aims: To evaluate the role of microRNAs (miRNAs) in the pathogenesis of Coxsackievirus B3 (CVB3)-induced viral myocarditis. Methods: We detected miRNA expression pro-filing by microarray utilizing a mouse model on day 4 after CVB3 infection. Then we validated differentially expressed miRNAs using real-time polymerase chain reaction (PCR). We predicted target genes using miRNA target prediction data-bases and assessed them using mRNA microarray and quali-tative reverse transcription PCR measurements. By analyzing the target function of differentially expressed miRNAs, we initially explored the regulating role of miRNAs in viral myo-carditis. Results: We found five differentially expressed miRNAs that are involved in regulating several important innate immune and antiviral pathways such as the Toll-like receptor signaling pathway, RIG-l-like receptor signaling pathway, NOD-like receptor signaling pathway, cytokine-cytokine receptor interaction, MAPK signaling pathway, JAK-STAT signaling pathway, and natural killer cell-mediated cytotoxicity. Conclusion: miRNAs regulate the pathogenesis of viral myocarditis. This study may provide a new perspec-tive and a deeper understanding of the pathogenesis of viral myocarditis that may help with the development of novel therapies against CVB3 infection. [ABSTRACT FROM AUTHOR]

Objectives: The rising threat of antibiotic resistance poses a significant challenge to public health. The research on the new direction of resistance mechanisms is crucial for overcoming this hurdle. This study examines metabolic changes by comparing sensitive and experimentally induced ofloxacin-resistant Escherichia coli (E. coli) strains using multi-omics analyses, aiming to provide novel insights into bacterial resistance., Methods: An ofloxacin-resistant E. coli strain was selected by being exposed to high concentration of ofloxacin. Comparative analyses involving transcriptomics, proteomics, and acetylomics were conducted between the wild-type and the ofloxacin-resistant (Re-OFL) strains. Enrichment pathways of differentially expressed genes, proteins and acetylated proteins between the two strains were analysed using gene ontology and Kyoto Encyclopedia of Genes and Genomes method. In addition, the metabolic network of E. coli was mapped using integrated multi-omics analysis strategies., Results: We identified significant differences in 2775 mRNAs, 1062 proteins, and 1015 acetylated proteins between wild-type and Re-OFL strains. Integrated omics analyses revealed that the common alterations enriched in metabolic processes, particularly the glycolytic pathway. Further analyses demonstrated that 14 metabolic enzymes exhibited upregulated acetylation levels and downregulated transcription and protein levels. Moreover, seven of these metabolic enzymes (fba, tpi, gapA, pykA, sdhA, fumA, and mdh) were components related to the glycolytic pathway., Conclusions: The changes of metabolic enzymes induced by antibiotics seem to be a key factor for E. coli to adapt to the pressure of antibiotics, which shed new light on understanding the adaptation mechanism when responding to ofloxacin pressure., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)