Lineage Plasticity and Stemness Phenotypes in Prostate Cancer: Harnessing the Power of Integrated "Omics" Approaches to Explore Measurable Metrics.

Prostate cancer (PCa), the most frequent and second most lethal cancer type in men in developed countries, is a highly heterogeneous disease. PCa heterogeneity, therapy resistance, stemness, and lethal progression have been attributed to lineage plasticity, which refers to the ability of neoplastic cells to undergo phenotypic changes under microenvironmental pressures by switching between developmental cell states. What remains to be elucidated is how to identify measurements of lineage plasticity, how to implement them to inform preclinical and clinical research, and, further, how to classify patients and inform therapeutic strategies in the clinic. Recent research has highlighted the crucial role of next-generation sequencing technologies in identifying potential biomarkers associated with lineage plasticity. Here, we review the genomic, transcriptomic, and epigenetic events that have been described in PCa and highlight those with significance for lineage plasticity. We further focus on their relevance in PCa research and their benefits in PCa patient classification. Finally, we explore ways in which bioinformatic analyses can be used to determine lineage plasticity based on large omics analyses and algorithms that can shed light on upstream and downstream events. Most importantly, an integrated multiomics approach may soon allow for the identification of a lineage plasticity signature, which would revolutionize the molecular classification of PCa patients.

Edible oils from olive drupes as a source of bioactive pentacyclic triterpenes. Is there a prospect for a health claim authorization?

Virgin olive oil and olive-pomace oil constitute high nutritional value edible oils due to the presence of oleic acid and a variety of bioactives. Among the latter, the group of pentacyclic triterpenes (PcTr) is the least studied. This review provides an insight into the biosynthesis of PcTr in the olive fruit, mainly of oleanane-type, and the factors influencing their transfer to the oil. Particular attention is given to the extraction methods along with the liquid and gas chromatography coupled to mass spectrometry protocols used for the discrimination and determination of PcTr. The in vivo bioactive properties of PcTr through the intake of these oils against cardiovascular diseases, liver dysfunction, obesity and diabetes are presented with a prospect of a future health claim authorization. Gaps in literature are pointed out to support this goal.

Natural ß-Carotene Production by Blakeslea trispora Cultivated in Spanish-Style Green Olive Processing Wastewaters.

In the current research, the potential of Spanish-style green olive processing wastewaters (lye and washing waters) exploitation toward natural ß-carotene production by Blakeslea trispora was tested for the first time. Mating culture generated by the joint cultivation of the heterothallic fungal strains ATCC 14271 and 14272 in the non-sterile lye and washing waters was able to grow, achieving the phytotoxic hydroxytyrosol degradation by 57.3% and 66.8%, respectively. However, the low sugar and nitrogen content of the streams did not favor carotenogenesis. Alternatively, in the nutrient-enriched effluents, a notable quantity of ß-carotene was produced, accounted for 61.2 mg/L (lye) and 64.1 mg/L (washing waters) (82-88% of total carotenoid content). Above all, enriched streams had a noteworthy stimulating effect on the ß-carotene synthesis, because both the maximum ß-carotene yield per volume of enriched effluents and specific ß-carotene production rate were higher when compared with the respective values obtained from trials with synthetic reference medium without added effluents. Hydroxytyrosol and tyrosol showed high stability during the non-sterile process for ß-carotene production by B. trispora grown in the enriched effluents. This finding strengthens the potential toward the generation of multiple high-value products, which could lower the natural ß-carotene production costs.

Processing Wastewaters from Spanish-Style cv. Chalkidiki Green Olives: A Potential Source of Enterococcus Casseliflavus and Hydroxytyrosol.

The purpose of this study was to examine the isolation of indigenous lactic acid bacteria (LAB) with functional properties from Spanish-style cv. Chalkidiki green olive processing wastewaters (GOW). Predominant indigenous LAB could serve as bioaugmentation agents/starter culture for table olives production and protected designation of origin specification. Spontaneous fermentation of fresh GOW over different temperatures (15 °C to 50 °C) and pH values (3.5 to 11.5) for 30 d enabled the isolation/molecular identification of the lactic acid bacterium Enterococcus casseliflavus and the plant-associated bacterium Bacillus amyloliquefaciens subsp. plantarum. E. casseliflavus was found to reduce chemical oxygen demand by 72%. Its resistance to extreme pH values, salinity, and temperature was successfully modeled and the minimum inhibitory concentration of oleuropein against the bacterial growth was determined (0.9 g/L). Furthermore, hydroxytyrosol content was doubled (up to 553 mg/L) after GOW spontaneous fermentation under acidic conditions at 15 °C to 30 °C for 120 d, creating an additional source of input. These results highlight the significance and potential of E. casseliflavus in Spanish-style cv. Chalkidiki green olive processing.

Feasibility of multi-hydrolytic enzymes production from optimized grape pomace residues and wheat bran mixture using Aspergillus niger in an integrated citric acid-enzymes production process.

In this study, the potential of the co-generation of hydrolytic enzymes in the biorefinery plant for citric acid fermentation was investigated. Aspergillus niger B60 mycelium along with the solid residue after the recovery of sugars from white pomace (WP') were recycled from citric acid fermentation. A mixture design was used to determine the optimum ternary feedstock mixture composed of WP' (15%), red grape pomace (15%) and wheat bran (70%) that produced the target enzymes with high activities, which were compared to those from pure feedstocks. Maximum carboxymethyl cellulase, polygalacturonase, amylase, xylanase and acid protease activities obtained through solid-state fermentation (120 h, 30 °C) of the feedstock mixture were 668 IU/g, 3,151 IU/g, 1,099 IU/g, 579 IU/g and 204 IU/g (dry mass basis), respectively. The system was successfully simulated in SuperPro Designer. Results showed that the enzymes production process serves as the main contributor to the profitability of the biorefinery plant.

Citric acid production from the integration of Spanish-style green olive processing wastewaters with white grape pomace by Aspergillus niger.

This study aimed to optimize an integrated simple process for citric acid production using Spanish-style green olive processing wastewaters enriched with sugars from white grape pomace and the robust Aspergillus niger B60. Mild mixing of equal quantities of the above streams governed satisfactory amount of appropriate carbon sources (equimolar mixture of glucose and fructose, 111.5 g/L) in the sugar-enriched wastewater and its neutralization. Various nutrients and fermentation conditions were investigated and maximum citric acid content (85 g/L) and yield (0.56 g/g) were obtained in liquid surface culture after minimum regulation by adding sucrose and NH4NO3 (100 g/L and 1.1 g/L, respectively). Scale-up experiments (5 L-scale) verified findings from small scale (250 mL). The chemical oxygen demand value and phenolic content of the treated wastewater were reduced by 78% and 64%, respectively. Findings support the potential for clustering the respective enterprises in a biorefinery plant for citric acid fermentation.

Changes in Phenolic Compounds and Phytotoxicity of the Spanish-Style Green Olive Processing Wastewaters by Aspergillus niger B60.

This study systematically investigated the degradation kinetics and changes in the composition of phenolic compounds in Spanish-style Chalkidiki green olive processing wastewaters (TOPWs) during treatment using Aspergillus niger B60. The fungal growth and phenol degradation kinetics were described sufficiently by the Logistic and Edward models, respectively. The maximum specific growth rate (2.626 1/d) and the maximum degradation rate (0.690 1/h) were observed at 1500 mg/L of total polar phenols, indicating the applicability of the process in TOPWs with a high concentration of phenolic compounds. Hydroxytyrosol and the other simple phenols were depleted after 3-8 days. The newly formed secoiridoid derivatives identified by HPLC-DAD-FLD and LC-MS are likely produced by oleoside and oleuropein aglycon via the action of fungal ß-glucosidase and esterase. The treated streams were found to be less phytotoxic with reduced chemical oxygen demand by up to 76%. Findings will provide useful information for the subsequent treatment of residual contaminants.