Streptococcus mutans has been reported as a primary cariogenic pathogen associated with dental caries. The bacteria can produce glucosyltransferases (Gtfs) to synthesize extracellular polysaccharides (EPSs) that are known as virulence factors for adherence and formation of biofilms. Therefore, an ideal inhibitor for dental caries is one that can inhibit planktonic bacteria growth and prevent biofilm formation. Bergenia crassifolia (L.), widely used as a folk medicine and tea beverage, has been reported to have a variety of bioactivities. The present study aimed to explore the effect of B. crassifolia (L.) leaf extracts on the biofilm of Streptococcus mutans. The B. crassifolia (L.) leaf extracts showed inhibitory effects by decreasing viability of bacteria within the biofilm, as evidenced by the XTT assay, live/dead staining assay and LDH activity assay, and could decrease the adherence property of S. mutans through inhibiting Gtfs to synthesize EPSs. In addition, the reduced quantity of EPSs and the inhibition of Gtfs were positively correlated with concentrations of test samples. Finally, the MTT assay showed that the extracts had no cytotoxicity against normal oral cells. In conclusion, the extracts and sub-extracts of B. crassifolia leaves were found to be antimicrobial and could reduce EPS synthesis by inhibiting activities of Gtfs to prevent bacterial adhesion and biofilm formation. Therefore, B. crassifolia leaves have potential to be developed as a drug to prevent and cure dental caries.

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BackgroundHistone deacetylases (HDACs) are promising therapeutic targets for the treatment of cancer, diabetes and other human diseases. HDAC inhibitors, as a new class of potential therapeutic agents, have attracted a great deal of interest for both research and clinical applications. Increasing efforts have been focused on the discovery of HDAC inhibitors and some HDAC inhibitors have been approved for use in cancer therapy. However, most HDAC inhibitors, including the clinically approved agents, do not selectively inhibit the deacetylase activity of class I and II HDAC isforms, and many suffer from metabolic instability. This study aims to identify new HDAC inhibitors by using a high-throughput virtual screening approach.MethodsAn integration of in silico virtual screening and in vitro experimental validation was used to identify novel HDAC inhibitors from a chemical database.ResultsA virtual screening workflow for HDAC inhibitors were created by integrating ligand- and receptor- based virtual screening methods. Using the virtual screening workflow, 22 hit compounds were selected and further tested via in vitro assays. Enzyme inhibition assays showed that three of the 22 compounds had HDAC inhibitory properties. Among these three compounds, ZINC12555961 significantly inhibited HDAC activity. Further in vitro experiments indicated that ZINC12555961 can selectively inhibit proliferation and promote apoptosis of cancer cells.ConclusionsIn summary, our study presents three new and potent HDAC inhibitors and one of these HDAC inhibitors shows anti-proliferative and apoptosis-inducing activity against various cancer cell lines. These results suggest that the developed virtual screening workflow can provide a useful source of information for the screening and validation of new HDAC inhibitors. The new-found HDAC inhibitors are worthy to further and more comprehensive investigations.Electronic supplementary materialThe online version of this article (doi:10.1186/s40360-016-0075-8) contains supplementary material, which is available to authorized users.

Leaf senescence is a complex and precise regulatory process that is correlated with numerous internal and environmental factors. Leaf senescence is tightly related to the redistribution of nutrients, which significantly affects productivity and quality, especially in crops. Evidence shows that the mediation of transcriptional regulation by WRKY transcription factors is vital for the fine‐tuning of leaf senescence. However, the underlying mechanisms of the involvement of WRKY in leaf senescence are still unclear in wheat. Using RNA sequencing data, we isolated a novel WRKY transcription factor, TaWRKY40‐D, which localizes in the nucleus and is basically induced by the progression of leaf senescence. TaWRKY40‐D is a promoter of natural and dark‐induced leaf senescence in transgenic Arabidopsis thaliana and wheat. We also demonstrated a positive response of TaWRKY40‐D in wheat upon jasmonic acid (JA) and abscisic acid (ABA) treatment. Consistent with this, the detached leaves of TaWRKY40‐D VIGS (virus‐induced gene silencing) wheat plants showed a stay‐green phenotype, while TaWRKY40‐D overexpressing Arabidopsis plants showed premature leaf senescence after JA and ABA treatment. Moreover, our results revealed that TaWRKY40‐D positively regulates leaf senescence, possibly by altering the biosynthesis and signalling of JA and ABA pathway genes. Together, our results suggest a new regulator of JA‐ and ABA‐related leaf senescence, as well as a new candidate gene that can be used for molecular breeding in wheat.

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