Mito-oncology agent: fermented extract suppresses the Warburg effect, restores oxidative mitochondrial activity, and inhibits in vivo tumor growth.

Mitochondrial dysfunction and significant changes in metabolic pathways accompany cancer development and are responsible for maintaining the tumor microenvironment. Normal mitochondria can trigger intrinsic apoptosis by releasing cytochrome c into the cytosol. The survival of malignant cells highly depends on the suppression of this function. We validated that A250, a highly purified fraction of fermented wheat germ extract (FWGE), increases the carbon flux into the mitochondria, the expression of key elements of the Krebs cycle and oxidative phosphorylation (OXPHOS). The increased respiratory chain activity is related to the mitochondria's ability to release cytochrome c into the cytosol, which triggers the apoptotic cascade. The 68% tumor growth inhibitory effect observed in the murine melanoma study is related to this effect, as proteomic analysis validated similar changes in mitochondrial protein levels in the isolated tumor tissue samples. Blood count data indicated that this effect was not accompanied by general toxicity. This study is significant, as it shows that a highly concentrated form of FWGE is an effective agent that increases normal mitochondrial functionality. The lack of hepatotoxic and general toxic effects makes A250 an excellent candidate targeting mitochondria function in cancer therapy.

Heat stress responses in a large set of winter wheat cultivars (Triticum aestivum L.) depend on the timing and duration of stress.

The adverse effects of heat on plant yield strongly depend on its duration and the phenological stage of the crops when the heat occurs. To clarify the effects of these two aspects of heat stress, systematic research was conducted under controlled conditions on 101 wheat cultivars of various geographic origin. Different durations of heat stress (5, 10 and 15 days) were applied starting from three developmental stages (ZD49: booting stage, ZD59: heading, ZD72: 6th day after heading). Various morphological, yield-related traits and physiological parameters were measured to determine the stress response patterns of the wheat genotypes under combinations of the duration and the timing of heat stress. Phenological timing significantly influenced the thousand-kernel weight and reproductive tiller number. The duration of heat stress was the most significant component in determining both seed number and seed weight, as well as the grain yield consequently, explaining 51.6% of its phenotypic variance. Irrespective of the developmental phase, the yield-related traits gradually deteriorated over time, and even a 5-day heat stress was sufficient to cause significant reductions. ZD59 was significantly more sensitive to heat than either ZD49 or ZD72. The photosynthetic activity of the flag leaf was mostly determined by heat stress duration. No significant associations were noted between physiological parameters and heat stress response as measured by grain yield. Significant differences were observed between the wheat genotypes in heat stress responses, which varied greatly with developmental phase. Based on the grain yield across developmental phases and heat stress treatments, eight major response groups of wheat genotypes could be identified, and among them, three clusters were the most heat-tolerant. These cultivars are currently included in crossing schemes, partially for the identification of the genetic determinants of heat stress response and partially for the development of new wheat varieties with better heat tolerance.

Rising atmospheric CO2 concentration may imply higher risk of Fusarium mycotoxin contamination of wheat grains.

Increasing atmospheric CO2 concentration not only has a direct impact on plants but also affects plant-pathogen interactions. Due to economic and health-related problems, special concern was given thus in the present work to the effect of elevated CO2 (750 µmol mol-1) level on the Fusarium culmorum infection and mycotoxin contamination of wheat. Despite the fact that disease severity was found to be not or little affected by elevated CO2 in most varieties, as the spread of Fusarium increased only in one variety, spike grain number and/or grain weight decreased significantly at elevated CO2 in all the varieties, indicating that Fusarium infection generally had a more dramatic impact on the grain yield at elevated CO2 than at the ambient level. Likewise, grain deoxynivalenol (DON) content was usually considerably higher at elevated CO2 than at the ambient level in the single-floret inoculation treatment, suggesting that the toxin content is not in direct relation to the level of Fusarium infection. In the whole-spike inoculation, DON production did not change, decreased or increased depending on the variety × experiment interaction. Cooler (18 °C) conditions delayed rachis penetration while 20 °C maximum temperature caused striking increases in the mycotoxin contents, resulting in extremely high DON values and also in a dramatic triggering of the grain zearalenone contamination at elevated CO2. The results indicate that future environmental conditions, such as rising CO2 levels, may increase the threat of grain mycotoxin contamination.

p53 mutations change phosphatidylinositol acyl chain composition.

Phosphatidylinositol phosphate (PIP) second messengers relay extracellular growth cues through the phosphorylation status of the inositol sugar, a signal transduction system that is deregulated in cancer. In stark contrast to PIP inositol head-group phosphorylation, changes in phosphatidylinositol (PI) lipid acyl chains in cancer have remained ill-defined. Here, we apply a mass-spectrometry-based method capable of unbiased high-throughput identification and quantification of cellular PI acyl chain composition. Using this approach, we find that PI lipid chains represent a cell-specific fingerprint and are unperturbed by serum-mediated signaling in contrast to the inositol head group. We find that mutation of Trp53 results in PIs containing reduced-length fatty acid moieties. Our results suggest that the anchoring tails of lipid second messengers form an additional layer of PIP signaling in cancer that operates independently of PTEN/PI3-kinase activity but is instead linked to p53.