Bioresorbable Depot for Sustained Release of Immunostimulatory Resiquimod in Suppressing Both Primary Triple-Negative Breast Tumors and Metastatic Occurrence.

In light of immune facilities trafficking toward the pathological sites along upward gradient of immunostimulatory cytokines, a localized resiquimod (Toll-like receptor 7/8 agonist) release depot was manufactured for pursuit of precision immunostimulation toward intractable triple-negative breast carcinoma. In principle, resiquimod/poly(lactic-co-glycolic acid) microspheres were fabricated and embedded into injectable and biodegradable poly(ethylene glycol) (PEG)-based hydrogel. The subsequent investigations approved persistent retention of immunostimulatory resiquimod in tumors upon peritumoral administration, which consequently led to localized and consistent secretion of immunostimulatory cytokines. Initially, not only innate tumor phagocytosis but also adaptive antitumor immunities were successfully cultivated for in situ suppression of the growth of primary solid tumors, more importantly, capable of inhibiting distant pulmonary metastasis, as evidenced by observation of enormous lymphocytes selectively gathering in the pulmonary artery. Hence, our presented study provided an important clinical indication of using immunostimulatory drugs to activate potent innate and adaptive antitumor immunities for precision antitumor therapy. Further immunomodulatory strategies, such as checkpoint blockage and tumor immunogenicity, could also be complementary for development of advanced antitumor immunotherapeutics in treatment of a number of intractable tumors.

Neuroprotection by Taurine on HBCD-Induced Apoptosis in PC12 Cells.

Hexabromocyclododecane (HBCD) is a widely used brominated flame retardant (BFR). Because of their presence in human issues, including brain tissue, concern has been raised on their possible neurotoxicity. Presently, we explored the neuroprotection of taurine against HBCD-induced apoptotic damages in PC12 cells. Cells were pre-treated with taurine before HBCD exposure and the viability was assayed via the methyl-thiazolyl-tetrazolium (MTT) method. Apoptotic features were observed with Hoechst 33342 staining. Apoptotic ratio was measured using flow cytometry with Annexin V-FITC coupled propidium iodide (PI) double staining. The changes in the levels of Bcl-2 and Bax proteins were quantitated by the western blot. The activity of caspase-3 was tested and the results revealed that presence of HBCD decreased cell survival and led to apoptosis in the tested cells. Further, exposure of HBCD reduced protein expression of Bcl-2, increased expression in Bax protein and activity of caspase-3. Taurine attenuated HBCD-induced cell viability loss and cell apoptosis. Moreover, taurine significantly prevented from reducing Bcl-2 protein expression and elevating Bax protein expression and caspase-3 activity induced by HBCD. These results demonstrated that taurine can alleviate HBCD-induced apoptosis by altering Bcl-2 expression and Bax protein and Caspase-3 activity in PC12.

Taurine Alleviate Hexabromocyclododecane-Induced Cytotoxicity in PC12 Cells via Inhibiting Oxidative Stress.

Hexabromocyclododecane (HBCD) is a widely used brominated flame retardant. Its adverse effects on brain had been observed. Taurine, a sulfur amino acid, take part in many brain physiological functions and exhibits protective effects on a variety of detrimental situations. In this paper, we explored the protections of taurine on cytotoxicity induced by HBCD in PC12 cells. PC12 cells were pretreated with taurine (1 mM, 3 mM and 9 mM) for 30 min before 10 µM HBCD treatment for 24 h. Then, the cell survival was assayed by the lactate dehydrogenase (LDH) release and trypan blue dyeing method. The formation of reactive oxygen species (ROS) and a collapse of mitochondrial membrane potential (MMP) were evaluated with a fluorescence microplate reader using the non-fluorescent probe 2'7'-dichlorofluorescin diacetate (DCFH-DA) and the fluorescent cationic dyestuff Rhodamine 123 (Rh 123), respectively. Further, the activity of many antioxidant enzymes, including superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and the content of glutathione (GSH) were tested by kits. Our results displayed that taurine significantly decreased the cell death induced by HBCD, prevented ROS production and disruption of mitochondrial membrane potential, and reversed the decline of SOD, CAT, GPx activity and GSH content induced by HBCD. These results suggested that taurine could alleviate cytotoxicity induced by HBCD in PC12 cells through inhibition of oxidative stress.