Novel human STING activation by hydrated-prenylated xanthones from Garcinia cowa.

OBJECTIVES: We investigate the anticancer activity and human stimulator of interferon genes pathway activation by a new hydrated-prenylated tetraoxygenated xanthone, garcicowanone I (1) and two known xanthones (2 and 3) that were isolated from the root bark of Garcinia cowa Roxb. ex Choisy. METHODS: The anticancer activity of each compound was evaluated by sulforhodamine B assay in immortalized cancer cell lines. Stimulator of interferon genes pathway activation was assessed by western blot analysis using human THP-1-derived macrophages. The production of pro-inflammatory cytokines from these macrophages was also evaluated via enzyme-linked immunosorbent assay. KEY FINDINGS: Both compounds 1 and 3 displayed moderate inhibitory effects on the cancer cells, including a cisplatin-resistant cell line, with IC50 values in the range of 10-20 µM. All three xanthones activated the stimulator of interferon genes, as evidenced by phosphorylation of tank-binding kinase 1, the stimulator of interferon genes protein and interferon regulatory factor 3. Furthermore, treatment of these macrophages with compounds 1-3 led to the production of pro-inflammatory cytokines, including interleukin 6, tumour necrosis factor α and interleukin 1ß. CONCLUSIONS: In conclusion, the isolated xanthones, including the novel garcicowanone I, displayed promising anticancer and immunomodulatory activity that warrants further research.

Isolation, Characterization, and Genome Analysis of a Novel Bacteriophage, Escherichia Phage vB_EcoM-4HA13, Representing a New Phage Genus in the Novel Phage Family Chaseviridae.

Shiga toxin-producing Escherichia coli (STEC) is one of the leading causes of foodborne illnesses in North America and can lead to severe symptoms, with increased fatality risk for young children. While E. coli O157:H7 remains the dominant STEC serotype associated with foodborne outbreaks, there has been an increasing number of non-O157 STEC outbreaks in recent years. For the food industry, lytic bacteriophages offer an organic, self-limiting alternative to pathogen reduction-one that could replace or reduce the use of chemical and physical food processing methods. From EHEC-enriched sewage, we isolated a novel bacteriophage, vB_EcoM-4HA13 (4HA13). Phenotypic characterizations revealed 4HA13 to possess a myoviral morphotype, with a high specificity to non-motile O111 serotype, and a long latent period (90 min). Through genomic analyses, this 52,401-bp dsDNA phage was found to contain 81 CDS, but no detectable presence of antibiotic resistance, integrase, or virulence genes. A BLASTn search for each of the identified 81 CDS yielded homologues with low levels of similarity. Comparison of RNA polymerase and terminase large subunit amino acid sequences led to the proposal and acceptance of a new bacteriophage family, Chaseviridae, with 4HA13 representing a new species and genus. The discovery of this phage has broadened our current knowledge of bacteriophage diversity.