Transcriptome reprogramming of resistant and susceptible peach genotypes during <i>Xanthomonas arboricola</i> pv. <i>pruni</i> early leaf infection

<div><p>Bacterial spot caused by <i>Xanthomonas arboricola</i> pv. <i>pruni</i> (Xap) is a major threat to <i>Prunus</i> species worldwide. The molecular mechanisms of peach resistance to Xap during early leaf infection were investigated by RNA-Seq analysis of two <i>Prunus persica</i> cultivars, ‘Redkist’ (resistant), and ‘JH Hale’ (susceptible) at 30 minutes, 1 and 3 hours-post-infection (hpi). Both cultivars exhibited extensive modulation of gene expression at 30 mpi, which reduced significantly at 1 hpi, increasing again at 3 hpi. Overall, 714 differentially expressed genes (DEGs) were detected in ‘Redkist’ (12% at 30 mpi and 1 hpi and 88% at 3 hpi). In ‘JH Hale’, 821 DEGs were identified (47% at 30 mpi and 1 hpi and 53% at 3 hpi). Highly up-regulated genes (fold change > 100) at 3 hpi exhibited higher fold change values in ‘Redkist’ than in ‘JH Hale’. RNA-Seq bioinformatics analyses were validated by RT-qPCR. In both cultivars, DEGs included genes with putative roles in perception, signal transduction, secondary metabolism, and transcription regulation, and there were defense responses in both cultivars, with enrichment for the gene ontology terms, ‘immune system process’, ‘defense response’, and ‘cell death’. There were particular differences between the cultivars in the intensity and kinetics of modulation of expression of genes with putative roles in transcriptional activity, secondary metabolism, photosynthesis, and receptor and signaling processes. Analysis of differential exon usage (DEU) revealed that both cultivars initiated remodeling their transcriptomes at 30 mpi; however, ‘Redkist’ exhibited alternative exon usage for a greater number of genes at every time point compared with ‘JH Hale’. Candidate resistance genes (<i>WRKY</i>-like, <i>CRK</i>-like, <i>Copper amine oxidase</i>-like, and <i>TIR-NBS-LRR</i>-like) are of interest for further functional characterization with the aim of elucidating their role in <i>Prunus</i> spp. resistance to Xap.</p></div

Distribution of frequency classes of gene expression levels (RPKM) after Xap inoculation on leaves of ‘JH Hale’ (susceptible) and ‘Redkist’ (resistant) peach cultivars.

<p>Distribution of frequency classes of gene expression levels (RPKM) after Xap inoculation on leaves of ‘JH Hale’ (susceptible) and ‘Redkist’ (resistant) peach cultivars.</p

Significantly enriched GO terms (Biological processes) in the susceptible cultivar ‘JH Hale’ at 30 mpi with Xap.

<p>Significantly enriched GO terms (Biological processes) in the susceptible cultivar ‘JH Hale’ at 30 mpi with Xap.</p

RNA-Seq statistics for reads mapped to the peach genome.

<p>Data are presented as averages of two biological replicates.</p

Transcriptome remodeling in terms of numbers of regulated genes in ‘Redkist’ (resistant) and ‘JH Hale’ (susceptible) cultivars during a time course (30 mpi, 1, and 3 hpi) after Xap infection.

<p>Transcriptome remodeling in terms of numbers of regulated genes in ‘Redkist’ (resistant) and ‘JH Hale’ (susceptible) cultivars during a time course (30 mpi, 1, and 3 hpi) after Xap infection.</p

Relative fold change (FC) of expression levels of genes regulated in both ‘Redkist’ (resistant) and in ‘JH Hale’ (susceptible) peach cultivars after Xap infection; max FC = 2216, min FC = -49.

<p>Relative fold change (FC) of expression levels of genes regulated in both ‘Redkist’ (resistant) and in ‘JH Hale’ (susceptible) peach cultivars after Xap infection; max FC = 2216, min FC = -49.</p

Highly up-regulated genes (fold change > 100) at 3 hpi with Xap in ‘Redkist’ (resistant) and ‘JH Hale’ (susceptible) peach cultivars.

<p>Highly up-regulated genes (fold change > 100) at 3 hpi with Xap in ‘Redkist’ (resistant) and ‘JH Hale’ (susceptible) peach cultivars.</p

RNA-Seq read statistics before mapping and after quality selection and trimming.

<p>RNA-Seq read statistics before mapping and after quality selection and trimming.</p

MA plot of genes differentially expressed (red dots) by two peach varieties during a time course after Xap infection.

<p>DEGs were selected by filtering based on log₂ (FC) > 2, or log₂ (FC) < -2, and FDR < 0.05.</p

Table1_Casticin as potential anticancer agent: recent advancements in multi-mechanistic approaches.docx

Plants, with their range of pharmacologically active molecules, represent the most promising source for the production of new anticancer drugs and for the formulation of adjuvants in chemotherapy treatments to reduce drug content and/or counteract the side effects of chemotherapy. Casticin is a major bioactive flavonoid isolated from several plants, mainly from the Vitex species. This compound is well known for its anti-inflammatory and antioxidant properties, which are mainly exploited in traditional medicine. Recently, the antineoplastic potential of casticin has attracted the attention of the scientific community for its ability to target multiple cancer pathways. The purpose of this review is, therefore, to present and critically analyze the antineoplastic potential of casticin, highlighting the molecular pathways underlying its antitumor effects. Bibliometric data were extracted from the Scopus database using the search strings “casticin” and “cancer” and analyzed using VOSviewer software to generate network maps to visualize the results. Overall, more than 50% of the articles were published since 2018 and even more recent studies have expanded the knowledge of casticin’s antitumor activity by adding interesting new mechanisms of action as a topoisomerase IIα inhibitor, DNA methylase 1 inhibitor, and an upregulator of the onco-suppressive miR-338-3p. Casticin counteracts cancer progression through the induction of apoptosis, cell cycle arrest, and metastasis arrest, acting on several pathways that are generally dysregulated in different types of cancer. In addition, they highlight that casticin can be considered as a promising epigenetic drug candidate to target not only cancer cells but also cancer stem-like cells.</p