Effect of Hypoxia on Siglec-7 and Siglec-9 Receptors and Sialoglycan Ligands and Impact of Their Targeting on NK Cell Cytotoxicity.

Background/objectives: Tumor microenvironmental hypoxia is an established hallmark of solid tumors. It significantly contributes to tumor aggressiveness and therapy resistance and has been reported to affect the balance of activating/inhibitory surface receptors' expression and activity on NK cells. In the current study, we investigated the impact of hypoxia on the surface expression of Siglec-7 and Siglec-9 (Sig-7/9) and their ligands in NK cells and tumor target cells.

Comprehensive Ocular and Systemic Safety Evaluation of Polysialic Acid-Decorated Immune Modulating Therapeutic Nanoparticles (PolySia-NPs) to Support Entry into First-in-Human Clinical Trials.

An inflammation-resolving polysialic acid-decorated PLGA nanoparticle (PolySia-NP) has been developed to treat geographic atrophy/age-related macular degeneration and other conditions caused by macrophage and complement over-activation. While PolySia-NPs have demonstrated pre-clinical efficacy, this study evaluated its systemic and intraocular safety. PolySia-NPs were evaluated in vitro for mutagenic activity using strains and , with and without metabolic activation; cytotoxicity was evaluated based on its interference with normal mitosis.

Harnessing Innate Immunity to Treat Infections: Heat-Killed as a Novel Biotherapeutic.

Tuberculosis, caused by (), is a serious and devastating infectious disease worldwide. Approximately a quarter of the world population harbors latent infection without pathological consequences. Exposure of immunocompetent healthy individuals with does not result in active disease in more than 90% individuals, suggesting a defining role of host immunity to prevent and/or clear early infection.

Anti-Mycobacterial Activity of Flavonoid and Pyrimidine Compounds.

We evaluated the anti-mycobacterial effect of a flavonoid 5,7-dihydroxy-2-(4-hydroxyphenyl) 4-chromen-4-one () and two pyrimidines, 4-hydroxy-2-dimethylamino-5-nitroso-6-aminopyrimidine () and 2-chloro-5--nonylpyrimidine () in vitro against (, H37Ra) and , using a Microplate Alamar Blue Assay (MABA). The effects of the compounds - in combination with first- and second-line anti-TB drugs isoniazid, rifampicin, cycloserine, and clarithromycin on the growth of and were also evaluated in in vitro assays. As a single agent, compounds and exhibited modest activity while compound was the most effective against and .