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Metastasis accounts for 90% of cancer-related deaths and, currently, there are no effective clinical therapies to block the metastatic cascade. A need to develop novel therapies specifically targeting fundamental metastasis processes remains urgent. Here, we demonstrate that Salmonella YB1, an engineered oxygen-sensitive strain, potently inhibits metastasis of a broad range of cancers. This process requires both IFN-γ and NK cells, as the absence of IFN-γ greatly reduces, whilst depletion of NK cells in vivo completely abolishes, the anti-metastatic ability of Salmonella. Mechanistically, we find that IFN-γ is mainly produced by NK cells during early Salmonella infection, and in turn, IFN-γ promotes the accumulation, activation, and cytotoxicity of NK cells, which kill the metastatic cancer cells thus achieving an anti-metastatic effect. Our findings highlight the significance of a self-regulatory feedback loop of NK cells in inhibiting metastasis, pointing a possible approach to develop anti-metastatic therapies by harnessing the power of NK cells. Cancer metastasis is one of the major causes of cancer related deaths and there is an urgent need to find more clinically effective metastasis targeting agents. Here, the authors show that Salmonella YB1 inhibits metastasis in multiple mouse models of cancer through a mechanism dependent on IFN-γ and NK cells. [ABSTRACT FROM AUTHOR]

Aim: To identify the potential metabolite markers in diabetic retinopathy (DR) by using gas chromatography coupled with time-of-flight mass spectrometry (GC-TOFMS). Methods: GC-TOFMS spectra were acquired from vitreous and aqueous humor (AH) samples of patients with DR and non-diabetic participants. Comparative analysis was used to elucidate the distinct metabolites of DR. Metabolic pathway was employed to explicate the metabolic reprogramming pathways involved in DR. Logistic regression and receiver-operating characteristic analyses were carried out to select and validate the biomarker metabolites and establish a therapeutic model. Results: Comparative analysis showed a clear separation between disease and control groups. Eight differentiating metabolites from AH and 15 differentiating metabolites from vitreous were highlighted. Out of these 23 metabolites, 11 novel metabolites have not been detected previously. Pathway analysis identified nine pathways (three in AH and six in vitreous) as the major disturbed pathways associated with DR. The abnormal of gluconeogenesis, ascorbate–aldarate metabolism, valine–leucine–isoleucine biosynthesis, and arginine–proline metabolism might weigh the most in the development of DR. The AUC of the logistic regression model established by d-2,3-Dihydroxypropanoic acid, isocitric acid, fructose 6-phosphate, and l-Lactic acid in AH was 0.965. The AUC established by pyroglutamic acid and pyruvic acid in vitreous was 0.951. Conclusions: These findings have expanded our understanding of identified metabolites and revealed for the first time some novel metabolites in DR. These results may provide useful information to explore the mechanism and may eventually allow the development of metabolic biomarkers for prognosis and novel therapeutic strategies for the management of DR. [ABSTRACT FROM AUTHOR]