Understanding dose-responses is crucial for determining the utility of biomarkers in ecotoxicity assessment. Nitrofurazone is a broad-spectrum antibiotic that is widely used in the aquaculture industry in China despite its detrimental effects on ecosystems. Potential dose-response models were examined for the effect of nitrofurazone on two antioxidant enzymes, superoxide dismutase (SOD) and glutathione peroxidase (GPx), in the ciliated protozoan Euplotes vannus. This was achieved by measuring enzyme activity and gene expression profiling of SOD and GPx in ciliate cells exposed to nitrofurazone at doses ranging from 0 to 180mgl-1 for 6h, 12h, 18h and 24h. Dose-response dynamics were characterized by mathematical models. Results showed that: 1) dose-response patterns differed significantly among the tested endpoints, nitrofurazone concentrations and durations of exposure; 2) GPx activity was the best candidate biomarker because of its linear dose-response relationship; 3) SOD activity and mRNA relative expression levels of GPx and SOD are also candidate biomarkers but their dose-responses were non-linear and therefore more difficult to interpret; 4) partitioning the dose-response dynamic model by piecewise function can help to clarify the relationships between biological endpoints. This study demonstrates the utility of dynamic model analysis and the potential of antioxidant enzymes, in particular GPx activity, as a candidate biomarkers for environmental monitoring and risk assessment of nitrofurazone in the aquaculture industry.

Aberrant expression of Myc is one of the most common oncogenic events in human cancers. Scores of Myc inhibitors are currently under development for treating Myc-driven cancers. In addition to directly targeting tumor cells, Myc inhibition has been shown to modulate the tumor microenvironment to promote tumor regression. However, the effect of Myc inhibition on immune cells in the tumor microenvironment remains poorly understood. Here, we show that the adaptive immune system plays a vital role in the antitumor effect of pharmacologic inhibition of Myc. Combining genetic and pharmacologic approaches, we found that Myc inhibition enhanced CD8 T cell function by suppressing the homeostasis of regulatory T (Treg) cells and the differentiation of resting Treg (rTreg) cells to activated Treg (aTreg) cells in tumors. Importantly, we demonstrated that different Myc expression levels confer differential sensitivity of T cell subsets to pharmacologic inhibition of Myc. Although ablation of the Myc gene has been shown to suppress CD8 T cell function, Treg cells, which express much less Myc protein than CD8 T cells, are more sensitive to Myc inhibitors. The differential sensitivity of CD8 T and Treg cells to Myc inhibitors resulted in enhanced CD8 T cell function upon Myc inhibition. Our findings revealed that Myc inhibitors can induce an antitumor immune response during tumor progression.

In recent times, co-delivery of therapeutics has emerged as a promising strategy for treating dreadful diseases such as cancer. Materials and methods: In this study, we developed a novel nanocarrier based on bacterial magnetosomes (BMs) that co-loaded with siRNA and doxorubicin (DOX) using polyethyleneimine (PEI) as a cross-linker (BMs/DP/siRNA). The delivery efficiency of siRNA as well as the pH-responsive release of DOX, and synergistic efficacy of these therapeutics in vitro were systematically investigated. Results: The structure of DOX PEI (DP) conjugates that synthesized via hydrazone bond formation was confirmed by nuclear magnetic resonance (NMR). The in vitro release experiments showed that the DP conjugate (DOX-loading efficiency 5.77%+/- 0.08%) exhibited the long-term release behavior. Furthermore, the optimal BMs/DP/siRNA particle size of 107.2 nm and the zeta potential value of 31.1 +/- 1.0 mV facilitated enhanced cellular internalisation efficiency. Moreover, the agarose gel electrophoresis showed that the co-delivery system could protect siRNA from degradation in serum and RNase A. In addition, the cytotoxicity assay showed that BMs/DP/siRNA could achieve an excellent synergistic effect compared to that of siRNA delivery alone. The acridine orange (AO)/ ethidium bromide (EB) double staining assay also showed that BMs/DP/siRNA complex could induce cells in a stage of late apoptosis and nanocomplex located in the proximity of the nucleus. Conclusion: The combination of gene and chemotherapeutic drug using BMs is highly efficient, and the BMs/DP/siRNA would be a promising therapeutic strategy for the future therapeutics.

The Magnetospirillum magneticum AMB-1 species is one of the most widely used magnetotactic bacterial strains for producing magnetosomes under laboratory conditions. Nevertheless, there exist several challenges in expanding and purifying the AMB-1 culture due to the restricted culture conditions. In an attempt to enrich the production of magnetosomes, this study reports the utilization of fermenter culture, which substantially promotes the cell densities at different concentrations of iron content. The experimental results confirmed magnetosomes’ high yield (production rate of 21.1 mg L⁻¹) at the iron content of 0.2 μmol L⁻¹. Moreover, different characterization techniques systematically confirmed the coated lipid membrane, particle size, dispersity, stability, and elemental composition of magnetosomes. Notably, the fermenter culture-based process resulted in highly discrete, dispersed, and stable magnetosomes with an average particle diameter of 50 nm and presented the integrated lipid membrane around the surface. The chemical composition by EDS of magnetosomes represented the presence of various elements, i.e., C, O, Na, P, and Fe, at appropriate proportions. In conclusion, the culture method in our study effectively provides a promising approach towards the culture of the magnetotactic bacterium for the enriched production of magnetosomes.