Xyloketal B Suppresses Glioblastoma Cell Proliferation and Migration in Vitro through Inhibiting TRPM7-Regulated PI3K/Akt and MEK/ERK Signaling Pathways

Glioblastoma, the most common and aggressive type of brain tumors, has devastatingly proliferative and invasive characteristics. The need for finding a novel and specific drug target is urgent as the current approaches have limited therapeutic effects in treating glioblastoma. Xyloketal B is a marine compound obtained from mangrove fungus Xylaria sp. (No. 2508) from the South China Sea, and has displayed antioxidant activity and protective effects on endothelial and neuronal oxidative injuries. In this study, we used a glioblastoma U251 cell line to (1) explore the effects of xyloketal B on cell viability, proliferation, and migration; and (2) investigate the underlying molecular mechanisms and signaling pathways. MTT assay, colony formation, wound healing, western blot, and patch clamp techniques were employed. We found that xyloketal B reduced cell viability, proliferation, and migration of U251 cells. In addition, xyloketal B decreased p-Akt and p-ERK1/2 protein expressions. Furthermore, xyloketal B blocked TRPM7 currents in HEK-293 cells overexpressing TRPM7. These effects were confirmed by using a TRPM7 inhibitor, carvacrol, in a parallel experiment. Our findings indicate that TRPM7-regulated PI3K/Akt and MEK/ERK signaling is involved in anti-proliferation and migration effects of xyloketal B on U251 cells, providing in vitro evidence for the marine compound xyloketal B to be a potential drug for treating glioblastoma.     

Gamma-linolenic Acid from Fifty-seven Ribes Species and Cultivars

Plant Foods for Human Nutrition - γ-linolenic acid (GLA, 18:3n-6) is a bioactive fatty acid (FA) that exerts several healthy actions; however, its occurrence is restricted to a few oils. The...     

A microsatellite and morphological assessment of the Russian National cultivated potato collection

The germplasm collections of the Vavilov Institute of Plant Industry, Russia represent the first germplasm collection made for potatoes, now numbering 8,680 accessions. It has tremendous historical and practical importance and a rich history, having been used to document a polyploid series in the cultivated species, to formulate initial taxonomic hypotheses in potato, for studies of interspecific hybridization, and serving as the germplasm base for Russian breeding efforts. Despite its importance and size, there has never been a study of its molecular diversity, and there were many gaps in its passport data. The purpose of the present study is to obtain morphological, ploidy, and microsatellite (SSR) data needed to set up a useful subset of the collection of cultivated potatoes and closely related wild species, and to use this collection to study cultivated potato taxonomy and phylogeny. Through assessments of viability, passport data, and chromosome counts, we selected a subset of 238 cultivated and 54 wild accessions. A morphological and nuclear SSR study of these collections distinguished only three cultivated species: Solanum curtilobum, S. juzepczukii and S. tuberosum, not the many more cultivated potato species of prior taxonomic treatments. The SSR study supports the ideas of S. acaule as one of the parental species for S. curtilobum and S. juzepczukii. The morphological and SSR results are very similar to other recent studies of cultivated species, and show the need to reclassify the collection of cultivated potatoes by modern taxonomic criteria.     

Regional and temporal differentiation of virulence phenotypes of Puccinia triticina from common wheat in Russia during the period 2001–2018

Leaf rust, caused by the fungus Puccinia triticina, is one of the most damaging rust diseases of wheat in Russia. Populations of P. triticina were monitored in seven regions of Russia from 2001 to 2018, with a total of 5,191 single urediniospore isolates from bread wheat (Triticum aestivum) being analysed. Populations have changed significantly in all regions since 2012, after 2 years of drought (2010–2011). Regional collections of P. triticina were also significantly different between the two periods 2001–2009 and 2012–2018, with changes along two geographic gradients from West Siberia to the north-west and south-west (North Caucasia) of the European part of Russia. All tested isolates were avirulent to resistance gene Lr9 in 2001–2009 but, since 2010, virulence to Lr9 has occurred and annually increased in the Asian part of Russia (Ural and West Siberia) due to deployment of cultivars with the Lr9 gene. Virulence to Lr2a and Lr15 was considerably lower in Dagestan (6%–33%) and all European regions (35%–67%) than in Asian regions (84%–96%). During 2001–2009, virulence on Lr1 was also lower in Dagestan (33%) and the European regions (50%–77%) than in Asia (91%–96%); however, by 2012–2018, nearly all isolates were virulent on Lr1. Remarkable changes were observed in frequencies of P. triticina races defined by their virulence/avirulence to Lr1 and Lr2a genes. We postulate the P. triticina population in Dagestan is specific to that area and pathogen populations in European and Asian parts of Russia are distinct.     

Biological activity of carbonic nano-structures—comparison via enzymatic bioassay

Purpose

The aim of the work is to compare the biological activity of carbonic nano-structures of natural and artificial origination, namely, humic substances (HS) and fullerenols.

Materials and methods

The representative of the fullerenol group, С₆₀О_y(OH)_x where у?+?x?=?20–22, was chosen. Enzyme-based luminescent bioassay was applied to evaluate toxicity and antioxidant properties of HS and fullerenol (F); chemiluminescent luminol method was used to study a content of reactive oxygen species (ROS) in the solutions. Toxicity of the bioactive compounds was evaluated using effective concentrations ЕС₅₀; detoxification coefficients D_OxT were applied to study and compare antioxidant activity of the compounds. Antioxidant activity and ranges of active concentrations of the bioactive compounds were determined in model solutions of organic and inorganic oxidizers—1,4-benzoquinone and potassium ferricianide.

Results and discussion

Values of ЕС₅₀ revealed higher toxicity of HS than F (0.005 and 0.108 g L^?1, respectively); detoxifying concentrations of F were found to be lower. Antioxidant ability of HS was demonstrated to be time-dependent; the 50-min preliminary incubation in oxidizer solutions was suggested as optimal for the detoxification procedure. On the contrary, F’ antioxidant effect demonstrated independency on time. Antioxidant effect of HS did not depend on amphiphilic characteristics of the media (values of D_OxT were 1.3 in the solutions of organic and inorganic oxidizers), while this of F was found to depend: it was maximal (D_OxT?=?2.0) in solutions of organic oxidizer, 1,4-benzoquinone.

Conclusions

Both HS and F demonstrated toxicity and low-concentration antioxidant ability; however, quantitative characteristics of their effects were different. The differences were explained with HS polyfunctionality, higher ability to decrease ROS content, non-rigidity, and diffusion restrictions in their solutions. Antioxidant effect of the bioactive compounds was presumably attributed to catalytic redox activity of their π-fragments. The paper demonstrates a high potential of luminescent enzymatic bioassay to study biological activity of nano-structures of natural and artificial origination.

     

The Biochemical Composition and Antioxidant Properties of Fucus vesiculosus from the Arctic Region

Fucus vesiculosus is one of the most prominent brown algae in the shallow waters of the seas of the Arctic region (Barents (BS), White (WS), Norwegian (NS), and Irminger (IS)). The aim of this study was to determine the biochemical composition of F. vesiculosus from the Arctic at different reproductive phases, and to evaluate the antioxidant properties of F. vesiculosus extracts. The amounts of monosaccharides, phlorotannins, flavonoids, and ash and the mineral composition significantly varied in the algae. A strong correlation was established between monosaccharide, phlorotannin, and flavonoid accumulation and water salinity (Pearson’s correlation coefficients r = −0.58, 0.83, and 0.44, respectively; p < 0.05). We noted a negative correlation between the antioxidant activity and the amount of the structural monosaccharides of fucoidan (r = −0.64). A positive correlation of phlorotannins and flavonoids with antioxidant power was confirmed for all samples. The ash accumulation was relatively lower in the sterile phase for the algae from the BS and WS. The correlation between the Metal Pollution Index (MPI) and the reproductive phases was medium with high fluctuation. Meanwhile, the MPI strongly correlated with the salinity and sampling site. The gradient of the MPI values across the sea was in the following ranking order: BS < WS < NS < IS. Taken together, and based on our data on the elemental contents of F. vesiculosus, we believe that this alga does not accumulate toxic doses of elements. Therefore, the Arctic F. vesiculosus could be safely used in food and drug development as a source of active biochemical compounds and as a source of dietary elements to cover the daily nutritional requirements of humans.     

Genetic diversity and origin of cultivated potatoes based on plastid microsatellite polymorphism

The origin of cultivated potatoes has remaining questions. In this study, 237 accessions of all cultivated species and 155 accessions of wild species closely related to cultivated potatoes, including their putative ancestors, were analyzed using 15 plastid microsatellites (SSRs) to investigate genetic diversity and their relationships with the wild species. We here used polymorphic plastid SSRs we developed from potato plastid genome sequences as well as already known plastid SSR markers. All 15 loci were polymorphic and identified a total of 127 haplotypes. Dramatic decreases in levels of genetic diversity were revealed in landraces in comparison with wild ancestor species. The plastid SSR results showed a decrease in haplotype number and diversity from Peru to both north and south. Phylogenetic analysis revealed two distinct groups. One of them, group A, contained the majority of accessions of cultivated species of the Solanum tuberosum Andigenum group including all accessions of cultivated diploid and triploid cytotypes of this group (S. chaucha, S. phureja, and S. stenotomum by a former taxonomic system) and most of tetraploid accessions of the S. tuberosum Andigenum group (S. tuberosum subsp. andigenum), and the majority of accessions of wild ancestors from the northern members of the S. brevicaule complex. Another group B comprised most of the wild species accessions and almost exclusively hybrid cultivated species which have introgressed plastid genomes from the other wild gene pools. Lack of clustering of traditional cultivated species (as used above) support a revised group classification of S. tuberosum.     

6-Bromohypaphorine from Marine Nudibranch Mollusk Hermissenda crassicornis is an Agonist of Human α7 Nicotinic Acetylcholine Receptor

6-Bromohypaphorine (6-BHP) has been isolated from the marine sponges Pachymatisma johnstoni, Aplysina sp., and the tunicate Aplidium conicum, but data on its biological activity were not available. For the nudibranch mollusk Hermissenda crassicornis no endogenous compounds were known, and here we describe the isolation of 6-BHP from this mollusk and its effects on different nicotinic acetylcholine receptors (nAChR). Two-electrode voltage-clamp experiments on the chimeric α7 nAChR (built of chicken α7 ligand-binding and glycine receptor transmembrane domains) or on rat α4β2 nAChR expressed in Xenopus oocytes revealed no action of 6-BHP. However, in radioligand analysis, 6-BHP competed with radioiodinated α-bungarotoxin for binding to human α7 nAChR expressed in GH₄C₁ cells (IC₅₀ 23 ± 1 μM), but showed no competition on muscle-type nAChR from Torpedo californica. In Ca²⁺-imaging experiments on the human α7 nAChR expressed in the Neuro2a cells, 6-BHP in the presence of PNU120596 behaved as an agonist (EC₅₀ ~80 μM). To the best of our knowledge, 6-BHP is the first low-molecular weight compound from marine source which is an agonist of the nAChR subtype. This may have physiological importance because H. crassicornis, with its simple and tractable nervous system, is a convenient model system for studying the learning and memory processes.