No abstract

With large-scale production and wide application of nano-titanium oxide (TiO2), its health hazard has attracted extensive attention worldwide. In this study, mouse macrophages (Ana-1 and MH-S cells) were used to evaluate the cytotoxicity of different sized TiO2 nanoparticles. The results showed that TiO2 nanoparticles caused low toxicity, especially in MH-S cells. There was a difference in the cytotoxicity induced by different sized TiO2 particles. The 25 nm anatase particles induced the strongest cytotoxicity and oxidative stress, followed by 5 and 100 nm anatase particles; in contrast, 100 nm rutile particles induced the lowest toxicity. Although TiO2 nanoparticles induced high levels of intracellular reactive oxygen species (ROS), the determination of ROS demonstrated that the inherent oxidative capacity of TiO2 nanoparticles was lower in the absence of photoactivation. Therefore, the generation of intracellular ROS could not completely depend on inherent oxidative capacity of TiO2 nanoparticles. Toxicity of TiO2 nanoparticles could mainly depend on the structural characteristics.

No abstract

Immune thrombocytopenia (ITP) is an acquired autoimmune disease characterized by autoantibody-mediated platelet destruction. Multiple factors have been implicated in ITP pathogenesis, including T-lymphocyte dysfunctions. Increasing studies have indicated that stem cell memory-like T cell (TSCM) plays an important role in the development of multiple autoimmune diseases. This study aimed to explore the clinical correlation between the TSCM subset and ITP. The percentages of peripheral blood naïve T cells (TNs), TSCMs, central memory T cells (TCMs), effector memory T cells (TEMs) and effector T cells (TEs) among CD4 + and CD8 + T cells in 20 ITP patients before and after treatment were detected using flow cytometry. Our results showed that the percentages of peripheral blood CD4 + and CD8 + T cells in ITP patients were imbalanced. The percentage of CD8 + TSCMs in peripheral blood before treatment in ITP patients was significantly higher than that in healthy controls, whereas the percentages of the other T cell subsets did not exhibit significant differences. Our study further analysed the correlation between the change in the percentage of CD8 + TSCMs and the treatment efficacy. The results showed that the percentage of peripheral blood CD8 + TSCMs in ITP patients after glucocorticoid treatment significantly decreased and the changes of the percentages of CD8 + TSCMs before and after treatment in complete response (CR) and response (R) patients were obvious. Our finding showed that the imbalance of the percentage of CD8 + TSCMs might be involved in the development of ITP and might serve as a novel indicator of efficacy.

Although chimeric antigen receptor T (CAR-T) cell therapy has been indicated to be effective in treating relapsed or refractory multiple myeloma (R/R MM), severe hematological toxicity (HT) remains an intractable issue. This study enrolled 54 patients with R/R MM following combined infusion of anti-CD19 and anti-BCMA CAR-T cells. The results showed that the rates of severe cytopenia were high, including severe neutropenia (28/54, 52%), severe anemia (15/54, 28%), and severe thrombocytopenia (18/54, 33%). Moreover, the incidence of prolonged HT (PHT) on Day 28 post-infusion was 52% (28/54), including 46% for severe neutropenia, 30% for severe anemia, and 31% for severe thrombocytopenia. Patients with PHT had a poorer median progression-free survival (PFS) and overall survival (OS) than patients without PHT (P=0.011; P=0.007). Furthermore, Cox regression analyses showed that PHT was an independent risk factor for PFS and OS. Univariate analyses showed that IFNγ (OR: 1.046; 95% CI: 1.002-1.093, P=0.042) and severe HT after lymphodepletion chemotherapy (OR: 0.082; 95% CI: 0.017-0.404; P=0.002) were independent risk factors for PHT. In conclusion, these results indicated that PHT was associated with poor outcomes following CAR-T-cell therapy in MM patients. Early detection and management of PHT would be beneficial for the prevention of life-threatening complications and improvement in the survival of patients after CAR-T-cell therapy.Clinical trial registrationThis trial was registered on 1 May 2017 at http://www.chictr.org.cn as ChiCTR-OIC-17011272.