RESUMEN
Recently, climate change has had an increasing impact on the world. Innate defense mechanisms operating in plants - such as PAMP-triggered Immunity (PTI) - help to reduce the adverse effects caused by various abiotic and biotic stressors. In this study, the effects of ELICE16INDURES® plant conditioner for organic farming, developed by the Research Institute for Medicinal Plants and Herbs Ltd. Budakalász Hungary, were studied in a soybean population in Northern Hungary. The active compounds and ingredients of this product were selected in such a way as to facilitate the triggering of general plant immunity without the presence and harmful effects of pathogens, thereby strengthening the healthy plant population and preparing it for possible stress effects. In practice, treatments of this agent were applied at two different time points and two concentrations. The conditioning effect was well demonstrated by using agro-drone and ENDVI determination in the soybean field. The genetic background of healthier plants was investigated by NGS sequencing, and by the expression levels of genes encoding enzymes involved in the catalysis of metabolic pathways regulating PTI. The genome-wide transcriptional profiling resulted in 13 contigs related to PAMP-triggered immunity and activated as a result of the treatments. Further analyses showed 16 additional PTI-related contigs whose gene expression changed positively as a result of the treatments. The gene expression values of genes encoded in these contigs were determined by in silico mRNA quantification and validated by RT-qPCR. Both - relatively low and high treatments - showed an increase in gene expression of key genes involving AOC, IFS, MAPK4, MEKK, and GST. Transcriptomic results indicated that the biosyntheses of jasmonic acid (JA), salicylic acid (SA), phenylpropanoid, flavonoid, phytoalexin, and cellular detoxification processes were triggered in the appropriate molecular steps and suggested that plant immune reactions may be activated also artificially, and innate immunity can be enhanced with proper plant biostimulants.
RESUMEN
Crohn's disease (CD) is an inflammatory disorder of the intestines characterized by epithelial barrier dysfunction and mucosal damage. The activity of poly(ADP-ribose) polymerase-1 (PARP-1) is deeply involved in the pathomechanism of inflammation since it leads to energy depletion and mitochondrial failure in cells. Focusing on the epithelial barrier integrity and bioenergetics of epithelial cells, we investigated whether the clinically applied PARP inhibitor olaparib might improve experimental CD. We used the oral PARP inhibitor olaparib in the 2,4,6-trinitrobenzene sulfonic acid- (TNBS-) induced mouse colitis model. Inflammatory scoring, cytokine levels, colon histology, hematological analysis, and intestinal permeability were studied. Caco-2 monolayer culture was utilized as an epithelial barrier model, on which we used qPCR and light microscopy imaging, and measured impedance-based barrier integrity, FITC-dextran permeability, apoptosis, mitochondrial oxygen consumption rate, and extracellular acidification rate. Olaparib reduced the inflammation score, the concentration of IL-1ß and IL-6, enhanced the level of IL-10, and decreased the intestinal permeability in TNBS-colitis. Blood cell ratios, such as lymphocyte to monocyte ratio, platelet to lymphocyte ratio, and neutrophil to lymphocyte ratio were improved. In H2O2-treated Caco-2 monolayer, olaparib decreased morphological changes, barrier permeability, and preserved barrier integrity. In oxidative stress, olaparib enhanced glycolysis (extracellular acidification rate), and it improved mitochondrial function (mitochondrial coupling efficiency, maximal respiration, and spare respiratory capacity) in epithelial cells. Olaparib, a PARP inhibitor used in human cancer therapy, improved experimental CD and protected intestinal barrier integrity by preventing its energetic collapse; therefore, it could be repurposed for the therapy of Crohn's disease.