Grain and sweet sorghum (Sorghum bicolor L. Moench) serves as a novel source of bioactive compounds for human health.

Grain sorghum is an important staple food crop grown globally while sweet sorghum is increasingly considered as a promising biofuel feedstock. Biofuels are the major economic products from the processing of large quantities of biomass, which is currently being utilized to make value-added products in the biorefinery approach. To date, these value-added products are typically commodity chemicals and waste materials used in agriculture. However, there are opportunities to generate high-value bioactive compounds from sorghum grain and biomass. Chronic diseases, such as cancers, are the top causes for morbidity and mortality in developed nations and are promoted by inflammation and oxidative stress. Globally, colorectal cancer results in approximately one-half million deaths annually. It is estimated that as much as 80% of colorectal cancer cases can be attributed to environmental and dietary factors. The sorghum grain and ligno-cellulosic biomass generated for biofuel production has been reported to be high in bioactive compounds, including phenolic acids and flavonoids, with antioxidant and anti-inflammatory properties. This review focuses on the bioactive compounds of grain and sweet sorghum (Sorghum bicolor L. Moench), for their anti-inflammatory, antioxidant, anti-colon cancer, and immune modulator functions. The review summarizes previous efforts to identify and quantify bioactive compounds in sorghum and documents their anti-cancer biological activities. Finally, this review discusses bioactive compound extraction methodologies and technologies as well as considerations for incorporating these technologies into current biorefining practices.

Alpha-Synuclein, a Novel Viral Restriction Factor Hiding in Plain Sight.

Alpha-synuclein (α-syn) is a highly conserved protein encoded by the SNCA gene and is expressed uniquely in neurons of both the central and peripheral nervous systems (CNS and PNS). α-Syn is known to cause sporadic and familial forms of Parkinson's disease (PD). However, the role for neuronal expression of α-syn in the first place remains unknown. We review and discuss recently published work that suggests a novel role for α-syn expression in neurons as a restriction factor that inhibits virus transmission from the PNS to the CNS. The potential new role for α-syn expression as a virus inhibitor may provide new approaches to understand the pathogenesis of PD and provide novel approaches to prevent and treat this common neurodegenerative disease.

4EBP-Dependent Signaling Supports West Nile Virus Growth and Protein Expression.

West Nile virus (WNV) is a (+) sense, single-stranded RNA virus in the Flavivirus genus. WNV RNA possesses an m7GpppNm 5' cap with 2'-O-methylation that mimics host mRNAs preventing innate immune detection and allowing the virus to translate its RNA genome through the utilization of cap-dependent translation initiation effectors in a wide variety of host species. Our prior work established the requirement of the host mammalian target of rapamycin complex 1 (mTORC1) for optimal WNV growth and protein expression; yet, the roles of the downstream effectors of mTORC1 in WNV translation are unknown. In this study, we utilize gene deletion mutants in the ribosomal protein kinase called S6 kinase (S6K) and eukaryotic translation initiation factor 4E-binding protein (4EBP) pathways downstream of mTORC1 to define the role of mTOR-dependent translation initiation signals in WNV gene expression and growth. We now show that WNV growth and protein expression are dependent on mTORC1 mediated-regulation of the eukaryotic translation initiation factor 4E-binding protein/eukaryotic translation initiation factor 4E-binding protein (4EBP/eIF4E) interaction and eukaryotic initiation factor 4F (eIF4F) complex formation to support viral growth and viral protein expression. We also show that the canonical signals of mTORC1 activation including ribosomal protein s6 (rpS6) and S6K phosphorylation are not required for WNV growth in these same conditions. Our data suggest that the mTORC1/4EBP/eIF4E signaling axis is activated to support the translation of the WNV genome.

Zika virus produces noncoding RNAs using a multi-pseudoknot structure that confounds a cellular exonuclease.

The outbreak of Zika virus (ZIKV) and associated fetal microcephaly mandates efforts to understand the molecular processes of infection. Related flaviviruses produce noncoding subgenomic flaviviral RNAs (sfRNAs) that are linked to pathogenicity in fetal mice. These viruses make sfRNAs by co-opting a cellular exonuclease via structured RNAs called xrRNAs. We found that ZIKV-infected monkey and human epithelial cells, mouse neurons, and mosquito cells produce sfRNAs. The RNA structure that is responsible for ZIKV sfRNA production forms a complex fold that is likely found in many pathogenic flaviviruses. Mutations that disrupt the structure affect exonuclease resistance in vitro and sfRNA formation during infection. The complete ZIKV xrRNA structure clarifies the mechanism of exonuclease resistance and identifies features that may modulate function in diverse flaviviruses.

The Dermal Layer of Sweet Sorghum (Sorghum bicolor) Stalk, a Byproduct of Biofuel Production and Source of Unique 3-Deoxyanthocyanidins, Has More Antiproliferative and Proapoptotic Activity than the Pith in p53 Variants of HCT116 and Colon Cancer Stem Cells.

There is a growing interest in the utilization of sweet sorghum as a renewable resource for biofuels. During the biofuel production process, large quantities of biomass are generated, creating a rich source of bioactive compounds. However, knowledge of sweet sorghum stalk is lacking. We measured the phenolic content (Folin-Ciocalteu assay), antioxidant activity (2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) assay), and phytochemical composition (LC-MS) in both the pith and dermal layer of the stalk. We further tested the antiproliferative (5-bromo-2'- deoxyuridine assay) and proapoptotic (terminal deoxynucleotidyl transferase dUTP nick end labeling assay) activities of these extracts using HCT116 cells and colon cancer stem cells (CCSCs) with and without the tumor suppressor gene p53. For the first time, we show that the dermal layer extract of sweet sorghum contains more of the 3-deoxyanthocyanidins apigeninidin and luteolinidin than the pith, and this is associated with more anticancer activity. Furthermore, luteolinidin suppressed CCSC proliferation more than apigeninidin. In addition to being renewable biofuel, sweet sorghum may also serve as a source of health-promoting compounds.

Comparison of health-relevant flavonoids in commonly consumed cranberry products.

UNLABELLED: The human health benefits from consumption of cranberry products have been associated with the fruits' unique flavonoid composition, including a complex profile of anthocyanins and proanthocyanidins. However, when processed by techniques such as pressing, canning, concentrating, or drying, a number of these natural components may be compromised or inactivated due to physical separation, thermal degradation, or oxidation. Fresh cranberries were compared to freeze-dried berries and individual fruit tissues (skin and peeled fruit). Products examined included cranberry juices (commercial and prepared from concentrate), cranberry sauces (commercial and homemade), and sweetened-dried cranberries (commercial). Freeze-drying resulted in no detectable losses of anthocyanins or proanthocyanidins from cranberry fruits. Anthocyanins were localized in the skin. Proanthocyanins were higher in the skin than in the flesh, with the exception of procyanidin A-2 dimer which was concentrated in the flesh. Anthocyanins were significantly higher in not-from-concentrate juice than in reconstituted juice from concentrate (8.3 mg and 4.2 mg/100 mL, respectively). Similarly, proanthocyanidins were markedly higher in not-from-concentrate juice compared to juice from concentrate (23.0 mg and 8.9 mg/100 mL, respectively). Homemade sauce contained far higher anthocyanins and proanthocyanidins (15.9 and 87.9 mg/100 g, respectively) than canned sauces processed with whole berries (9.6 and 54.4 mg/100 g, respectively) or jelled-type (1.1 and 16 mg/100 g, respectively). Sweetened-dried cranberries were quite low in anthocyanins (7.9 mg/100 g), but they still retained considerable proanthocyanidins (64.2 mg/100 g). Commercially processed products contained significantly lower levels of polyphenols as compared to fresh and home-processed preparations. Anthocyanins were more sensitive to degradation than proanthocyanidins. PRACTICAL APPLICATION: As cranberry juices and other products are increasingly consumed for their recognized health benefits (including prophylaxis against urinary tract infection), it is relevant to consider how various degrees of commercial and home processing can alter innate levels of the biologically active flavonoids (especially anthocyanins and proanthocyanidins) characteristic to the intact fruits.