Synephrine and Its Derivative Compound A: Common and Specific Biological Effects.

This review is focused on synephrine, the principal phytochemical found in bitter orange and other medicinal plants and widely used as a dietary supplement for weight loss/body fat reduction. We examine different aspects of synephrine biology, delving into its established and potential molecular targets, as well as its mechanisms of action. We present an overview of the origin, chemical composition, receptors, and pharmacological properties of synephrine, including its anti-inflammatory and anti-cancer activity in various in vitro and animal models. Additionally, we conduct a comparative analysis of the molecular targets and effects of synephrine with those of its metabolite, selective glucocorticoid receptor agonist (SEGRA) Compound A (CpdA), which shares a similar chemical structure with synephrine. SEGRAs, including CpdA, have been extensively studied as glucocorticoid receptor activators that have a better benefit/risk profile than glucocorticoids due to their reduced adverse effects. We discuss the potential of synephrine usage as a template for the synthesis of new generation of non-steroidal SEGRAs. The review also provides insights into the safe pharmacological profile of synephrine.

Influence of the Synthesis Scheme of Nanocrystalline Cerium Oxide and Its Concentration on the Biological Activity of Cells Providing Wound Regeneration.

In the ongoing search for practical uses of rare-earth metal nanoparticles, cerium dioxide nanoparticles (nanoceria) have received special attention. The purpose of this research was to study the biomedical effects of nanocrystalline forms of cerium oxide obtained by different synthesis schemes and to evaluate the effect of different concentrations of nanoceria (from 10-2 to 10-6 M) on cells involved in the regeneration of skin cell structures such as fibroblasts, mesenchymal stem cells, and keratinocytes. Two different methods of nanoceria preparation were investigated: (1) CeO-NPs-1 by precipitation from aqueous solutions of cerium (III) nitrate hexahydrate and citric acid and (2) CeO-NPs-2 by hydrolysis of ammonium hexanitratocerate (IV) under conditions of thermal autoclaving. According to the X-ray diffraction, transmission electron microscopy, and dynamic light scattering data, CeO2-1 consists of individual particles of cerium dioxide (3-5 nm) and their aggregates with diameters of 60-130 nm. CeO2-2 comprises small aggregates of 8-20 nm in diameter, which consist of particles of 2-3 nm in size. Cell cultures of human fibroblasts, human mesenchymal stem cells, and human keratinocytes were cocultured with different concentrations of nanoceria sols (10-2, 10-3, 10-4, 10-5, and 10-6 mol/L). The metabolic activity of all cell types was investigated by MTT test after 48 and 72 h, whereas proliferative activity and cytotoxicity were determined by quantitative cell culture counting and live/dead test. A dependence of biological effects on the method of nanoceria preparation and concentration was revealed. Data were obtained with respect to the optimal concentration of sol to achieve the highest metabolic effect in the used cell cultures. Hypotheses about the mechanisms of the obtained effects and the structure of a fundamentally new medical device for accelerated healing of skin wounds were formulated. The method of nanoceria synthesis and concentration fundamentally and significantly change the biological activity of cell cultures of different types-from suppression to pronounced stimulation. The best biological activity of cell cultures was determined through cocultivation with sols of citrate nanoceria (CeO-NPs-1) at a concentration of 10-3-10-4 M.

The Effects of Rhizophagus irregularis Inoculation on Transcriptome of Medicago lupulina Leaves at Early Vegetative and Flowering Stages of Plant Development.

The study is aimed at revealing the effects of Rhizophagus irregularis inoculation on the transcriptome of Medicago lupulina leaves at the early (second leaf formation) and later (flowering) stages of plant development. A pot experiment was conducted under conditions of low phosphorus (P) level in the substrate. M. lupulina plants were characterized by high mycorrhizal growth response and mycorrhization parameters. Library sequencing was performed on the Illumina HiseqXTen platform. Significant changes in the expression of 4863 (padj < 0.01) genes from 34049 functionally annotated genes were shown by Massive Analysis of cDNA Ends (MACE-Seq). GO enrichment analysis using the Kolmogorov-Smirnov test was performed, and 244 functional GO groups were identified, including genes contributing to the development of effective AM symbiosis. The Mercator online tool was used to assign functional classes of differentially expressed genes (DEGs). The early stage was characterized by the presence of six functional classes that included only upregulated GO groups, such as genes of carbohydrate metabolism, cellular respiration, nutrient uptake, photosynthesis, protein biosynthesis, and solute transport. At the later stage (flowering), the number of stimulated GO groups was reduced to photosynthesis and protein biosynthesis. All DEGs of the GO:0016036 group were downregulated because AM plants had higher resistance to phosphate starvation. For the first time, the upregulation of genes encoding thioredoxin in AM plant leaves was shown. It was supposed to reduce ROS level and thus, consequently, enhance the mechanisms of antioxidant protection in M. lupulina plants under conditions of low phosphorus level. Taken together, the obtained results indicate genes that are the most important for the effective symbiosis with M. lupulina and might be engaged in other plant species.

Diversity of Arbuscular Mycorrhizal Fungi in Distinct Ecosystems of the North Caucasus, a Temperate Biodiversity Hotspot.

BACKGROUND: Investigations that are focused on arbuscular mycorrhizal fungus (AMF) biodiversity is still limited. The analysis of the AMF taxa in the North Caucasus, a temperate biodiversity hotspot, used to be limited to the genus level. This study aimed to define the AMF biodiversity at the species level in the North Caucasus biotopes. METHODS: The molecular genetic identification of fungi was carried out with ITS1 and ITS2 regions as barcodes via sequencing using Illumina MiSeq, the analysis of phylogenetic trees for individual genera, and searches for operational taxonomic units (OTUs) with identification at the species level. Sequences from MaarjAM and NCBI GenBank were used as references. RESULTS: We analyzed >10 million reads in soil samples for three biotopes to estimate fungal biodiversity. Briefly, 50 AMF species belonging to 20 genera were registered. The total number of the AM fungus OTUs for the "Subalpine Meadow" biotope was 171/131, that for "Forest" was 117/60, and that for "River Valley" was 296/221 based on ITS1/ITS2 data. The total number of the AM fungus species (except for virtual taxa) for the "Subalpine Meadow" biotope was 24/19, that for "Forest" was 22/13, and that for "River Valley" was 28/24 based on ITS1/ITS2 data. Greater AMF diversity, as well as number of OTUs and species, in comparison with that of forest biotopes, characterized valley biotopes (disturbed ecosystems; grasslands). The correlation coefficient between "Percentage of annual plants" and "Glomeromycota total reads" r = 0.76 and 0.81 for ITS1 and ITS2, respectively, and the correlation coefficient between "Percentage of annual plants" and "OTUs number (for total species)" was r = 0.67 and 0.77 for ITS1 and ITS2, respectively. CONCLUSION: High AMF biodiversity for the river valley can be associated with a higher percentage of annual plants in these biotopes and the active development of restorative successional processes.

The Role of Medicago lupulina Interaction with Rhizophagus irregularis in the Determination of Root Metabolome at Early Stages of AM Symbiosis.

The nature of plant-fungi interaction at early stages of arbuscular mycorrhiza (AM) development is still a puzzling problem. To investigate the processes behind this interaction, we used the Medicago lupulina MlS-1 line that forms high-efficient AM symbiosis with Rhizophagus irregularis. AM fungus actively colonizes the root system of the host plant and contributes to the formation of effective AM as characterized by a high mycorrhizal growth response (MGR) in the host plant. The present study is aimed at distinguishing the alterations in the M. lupulina root metabolic profile as an indicative marker of effective symbiosis. We examined the root metabolome at the 14th and 24th day after sowing and inoculation (DAS) with low substrate phosphorus levels. A GS-MS analysis detected 316 metabolites. Results indicated that profiles of M. lupulina root metabolites differed from those in leaves previously detected. The roots contained fewer sugars and organic acids. Hence, compounds supporting the growth of mycorrhizal fungus (especially amino acids, specific lipids, and carbohydrates) accumulated, and their presence coincided with intensive development of AM structures. Mycorrhization determined the root metabolite profile to a greater extent than host plant development. The obtained data highlight the importance of active plant-fungi metabolic interaction at early stages of host plant development for the determination of symbiotic efficiency.

Mycorrhiza-Induced Alterations in Metabolome of Medicago lupulina Leaves during Symbiosis Development.

The present study is aimed at disclosing metabolic profile alterations in the leaves of the Medicago lupulina MlS-1 line that result from high-efficiency arbuscular mycorrhiza (AM) symbiosis formed with Rhizophagus irregularis under condition of a low phosphorus level in the substrate. A highly effective AM symbiosis was established in the period from the stooling to the shoot branching initiation stage (the efficiency in stem height exceeded 200%). Mycorrhization led to a more intensive accumulation of phosphates (glycerophosphoglycerol and inorganic phosphate) in M. lupulina leaves. Metabolic spectra were detected with GS-MS analysis. The application of complex mathematical analyses made it possible to identify the clustering of various groups of 320 metabolites and thus demonstrate the central importance of the carbohydrate and carboxylate-amino acid clusters. The results obtained indicate a delay in the metabolic development of mycorrhized plants. Thus, AM not only accelerates the transition between plant developmental stages but delays biochemical "maturation" mainly in the form of a lag of sugar accumulation in comparison with non-mycorrhized plants. Several methods of statistical modeling proved that, at least with respect to determining the metabolic status of host-plant leaves, stages of phenological development have priority over calendar age.