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‐1β 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.

Macrophage polarization is highly involved in autoimmunity. M1 polarized macrophages drive inflammation and undergo metabolic reprogramming, involving downregulation of mitochondrial energy production and acceleration of glycolysis. Macrophage migration inhibitory factor (MIF), an enigmatic tautomerase (ketonase and enolase), was discovered to regulate M1 polarization. Here, we reveal that KRP-6, a potent and highly selective MIF ketonase inhibitor, reduces MIF-induced human blood eosinophil and neutrophil migration similarly to ISO-1, the most investigated tautomerase inhibitor. We equally discovered that KRP-6 prevents M1 macrophage polarization and reduces ROS production in IFN-γ-treated cells. During metabolic reprogramming, KRP-6 improved mitochondrial bioenergetics by ameliorating basal respiration, ATP production, coupling efficiency and maximal respiration in LPS+IFN-γ-treated cells. KRP-6 also reduced glycolytic flux in M1 macrophages. Moreover, the selective MIF ketonase inhibitor attenuated LPS+IFN-γ-induced downregulation of PARP-1 and PARP-2 mRNA expression. We conclude that KRP-6 represents a promising novel therapeutic compound for autoimmune diseases, which strongly involves M1 macrophage polarization.

Background: The spread of herbicide-resistance Ambrosia artemisiifolia threatens not only the production of agricultural crops, but also the composition of weed communities. The reduction of their spread would positively affect the biodiversity and beneficial weed communities in the arable habitats. Detection of resistant populations would help to reduce herbicide exposure which may contribute to the development of sustainable agroecosystems. Methods: This study focuses on the application of target-site resistance (TSR) diagnostic of A. artemisiifolia caused by different herbicides. We used targeted amplicon sequencing (TAS) on Illumina Miseq platform to detect amino acid changes in herbicide target enzymes of resistant and wild-type plants. Results: 16 mutation points of four enzymes targeted by four herbicide groups, such as Photosystem II (PSII), Acetohydroxyacid synthase (AHAS), 5-enolpyruvylshikimate 3-phosphate synthase (EPSPS) and protoporphyrinogen IX oxidase (PPO) inhibitors have been identified in common ragweed populations, so far. All the 16 mutation points were analyzed and identified. Out of these, two mutations were detected in resistant biotypes. Conclusions: The applied next-generation sequencing-targeted amplicon sequencing (NGS-TAS) method on A. artemisiifolia resistant and wild-type populations enable TSR detection of large sample numbers in a single reaction. The NGS-TAS provides information about the evolved herbicide resistance that supports the integrated weed control through the reduction of herbicide exposure which may preserve ecological properties in agroecosystems.

Recently, environmentally friendly crop improvements using next-generation plant biostimulants (PBs) come to the forefront in agriculture, regardless of whether they are used by scientists, farmers, or industries. Various organic and inorganic solutions have been investigated by researchers and producers, focusing on tolerance to abiotic and biotic stresses, crop quality, or nutritional deficiency. Garlic has been considered a universal remedy ever since antiquity. A supercritical carbon dioxide garlic extract encapsulated in nanoscale liposomes composed of plant-derived lipids was examined as a possible PB agent. The present study focused on the characterization of the genes associated with the pathways involved in defense response triggered by the liposome nanoparticles that were loaded with supercritical garlic extracts. This material was applied to Triticum aestivum in greenhouse experiments using foliar spraying. The effects were examined in a large-scale genome-wide transcriptional profiling experiment by collecting the samples four times (0 min, used as a control, and 15 min, 24 h, and 48 h after spraying). Based on a time-course expression analysis, the dynamics of the cellular response were determined by examining differentially expressed genes and applying a cluster analysis. The results suggested an enhanced expression of abscisic acid (ABA) pathway and pathogenesis-related (PR) genes, of which positive regulation was found for the AP2-, C2H2-, HD-ZIP-, and MYB-related transcription factor families.

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.

Heart failure (HF) is a complex chronic clinical disease characterized by among others the damage of the mitochondrial network. The disruption of the mitochondrial quality control and the imbalance in fusion‐fission processes lead to a lack of energy supply and, finally, to cell death. BGP‐15 (O‐[3‐piperidino‐2‐hydroxy‐1‐propyl]‐nicotinic acid amidoxime dihydrochloride) is an insulin sensitizer molecule and has a cytoprotective effect in a wide variety of experimental models. In our recent work, we aimed to clarify the mitochondrial protective effects of BGP‐15 in a hypertension‐induced heart failure model and “in vitro.” Spontaneously hypertensive rats (SHRs) received BGP‐15 or placebo for 18 weeks. BGP‐15 treatment preserved the normal mitochondrial ultrastructure and enhanced the mitochondrial fusion. Neonatal rat cardiomyocytes (NRCMs) were stressed by hydrogen‐peroxide. BGP‐15 treatment inhibited the mitochondrial fission processes, promoted mitochondrial fusion, maintained the integrity of the mitochondrial genome, and moreover enhanced the de novo biogenesis of the mitochondria. As a result of these effects, BGP‐15 treatment also supports the maintenance of mitochondrial function through the preservation of the mitochondrial structure during hydrogen peroxide‐induced oxidative stress as well as in an “in vivo” heart failure model. It offers the possibility, which pharmacological modulation of mitochondrial quality control under oxidative stress could be a novel therapeutic approach in heart failure.