RESUMEN
Nutritional oils (mainly omega-3 fatty acids) are receiving increased attention as critical supplementary compounds for the improvement and maintenance of human health and wellbeing. However, the predominant sources of these oils have historically shown numerous limitations relating to desirability and sustainability; hence the crucial focus is now on developing smarter, greener, and more environmentally favourable alternatives. This study was undertaken to consider and assess the numerous prevailing and emerging techniques implicated across the stages of fatty acid downstream processing. A structured and critical comparison of the major classes of disruption methodology (physical, chemical, thermal, and biological) is presented, with discussion and consideration of the viability of new extraction techniques. Owing to a greater desire for sustainable industrial practices, and a desperate need to make nutritional oils more available; great emphasis has been placed on the discovery and adoption of highly sought-after 'green' alternatives, which demonstrate improved efficiency and reduced toxicity compared to conventional practices. Based on these findings, this review also advocates new forays into application of novel nanomaterials in fatty acid separation to improve the sustainability of nutritional oil downstream processing. In summary, this review provides a detailed overview of the current and developing landscape of nutritional oil; and concludes that adoption and refinement of these sustainable alternatives could promptly allow for development of a more complete 'green' process for nutritional oil extraction; allowing us to better meet worldwide needs without costing the environment.
RESUMEN
Inhibiting the androgen receptor (AR), a ligand-activated transcription factor, with androgen deprivation therapy is a standard-of-care treatment for metastatic prostate cancer. Paradoxically, activation of AR can also inhibit the growth of prostate cancer in some patients and experimental systems, but the mechanisms underlying this phenomenon are poorly understood. This study exploited a potent synthetic androgen, methyltestosterone (MeT), to investigate AR agonist-induced growth inhibition. MeT strongly inhibited growth of prostate cancer cells expressing AR, but not AR-negative models. Genes and pathways regulated by MeT were highly analogous to those regulated by DHT, although MeT induced a quantitatively greater androgenic response in prostate cancer cells. MeT potently downregulated DNA methyltransferases, leading to global DNA hypomethylation. These epigenomic changes were associated with dysregulation of transposable element expression, including upregulation of endogenous retrovirus (ERV) transcripts after sustained MeT treatment. Increased ERV expression led to accumulation of double-stranded RNA and a "viral mimicry" response characterized by activation of IFN signaling, upregulation of MHC class I molecules, and enhanced recognition of murine prostate cancer cells by CD8+ T cells. Positive associations between AR activity and ERVs/antiviral pathways were evident in patient transcriptomic data, supporting the clinical relevance of our findings. Collectively, our study reveals that the potent androgen MeT can increase the immunogenicity of prostate cancer cells via a viral mimicry response, a finding that has potential implications for the development of strategies to sensitize this cancer type to immunotherapies. Significance: Our study demonstrates that potent androgen stimulation of prostate cancer cells can elicit a viral mimicry response, resulting in enhanced IFN signaling. This finding may have implications for the development of strategies to sensitize prostate cancer to immunotherapies.