Superparamagnetic iron oxide nanoparticles have been widely used in biomedical applications, but understanding of their interactions with the biological immune system is relatively limited. This work is focused on dextran-coated iron oxide nanoparticles and their induced autophagy in human monocytes. We found that these nanoparticles can be taken up by human monocytes, followed by localization within vesicles or free in cytoplasm. Autophagosome formation was observed with increased expression of LC3II protein, the specific marker of autophagy. The autophagy substrate p62 was degraded in a dose-dependent manner, and autophagy was blocked by autophagy (or lysosome) inhibitors alone or along with iron oxide nanoparticles, indicating that autophagosome accumulation was mainly due to autophagy induction, rather than blockade of autophagy flux. Interestingly, iron oxide nanoparticles increased the viability of human monocytes, but the mechanism was not clear. We further found that inhibition of autophagy mostly attenuated the survival of cells, with acceleration of the inflammation induced by these nanoparticles. Taken together, autophagic activation in human monocytes may play a protective role against the cytotoxicity of iron oxide nanoparticles.

In traditional Chinese medicine, shikonin and its derivatives, has been used in East Asia for several years for the prevention and treatment of several diseases, including cancer. We previously identified that β,β-dimethylacrylshikonin (DA) could inhibit hepatocellular carcinoma growth. In the present study, we investigated the inhibitory effects of DA on human colorectal cancer (CRC) cell line HCT-116 in vitro and in vivo. A viability assay showed that DA could inhibit tumor cell growth in a time- and dose-dependent manner. Flow cytometry showed that DA blocks the cell cycle at G₀/G₁ phase. Western blotting results demonstrated that the induction of apoptosis by DA correlated with the induction of pro-apoptotic proteins Bax, and Bid, and a decrease in the expression of anti-apoptotic proteins Bcl-2 and Bcl-xl. Furthermore, treatment of HCT-116 bearing nude mice with DA significantly retarded the growth of xenografts. Consistent with the results in vitro, the DA-mediated suppression of HCT-116 xenografts correlated with Bax and Bcl-2. Taken together, these results suggest that DA could be a novel and promising approach to the treatment of CRC.

With the increase in applications of superparamagnetic iron oxide nanoparticles (SPIONs) in biomedicine, it is essential to investigate the bio‑security of these nanoparticles, especially with respect to the human immune system. In the present study, the biological effects of dextran‑coated superparamagnetic iron oxide nanoparticles (Dex‑SPIONs) on human primary monocyte cells were evaluated. The results of the present study demonstrated that Dex‑SPIONs can be identified in phagosomes or freed in the cytoplasm and did not affect cell viability or induce apoptosis. Notably, there were certain bulky vacuoles and a number of pseudopodia from the cell membrane, suggesting potential activation of human monocyte cells. In addition, the expression levels of pro‑inflammatory cytokines interleukin (IL)‑1β and tumor necrosis factor (TNF)‑α were also increased following treatment with Dex‑SPIONs. Simultaneously, the phosphorylation levels of mitogen‑activated protein kinase (MAPK) p38, c‑Jun N‑terminal kinase 1 and extracellular signal regulated kinase were markedly enhanced following nanoparticle exposure and MAPK inhibitors could abate the production of IL‑1β and TNF‑α. The results of the present study demonstrated that Dex‑SPIONs could activate human monocyte cells and that activation of MAPK pathway may be involved in these effects.

Background: γδ T cells are an important subset of T lymphocytes that play important roles in innate and adaptive immunity via the secretion of various cytokines. Previous studies have found that long noncoding RNAs (lncRNAs) are critical regulators that contribute to the development of immune cells. However, the functions of lncRNAs in the γδ T cells remains poorly studied. Results: Here, we identified the novel function of lncRNA NONHSAT196558.1 in isopentenyl pyrophosphate (IPP)-activated and -expanded γδ T cells using RNA-seq. As it functioned as an activating noncoding RNA of tumor necrosis factor related apoptosis-inducing ligand (TRAIL), an important cytotoxic cytokine that expressed by γδ T cells in responding to various infectious agents, we named this lncRNA as TANCR. Secondly, the expression of TANCR was found to be positively correlated with TRAIL expression in IPP activated γδ T cells. In addition, TANCR was confirmed to localized both in nucleus and cytoplasm. Finally, a loss-of-function was conducted by using siRNA/ASO or CRISPR/Cas9 system to knockdown or knockout TANCR, and confirmed that silencing of TANCR inhibits TRAIL expression in several kinds of cells, including HEK293T cells, Jurkat cells, and primary γδ T cells. Conclusion: These evidences demonstrate that TANCR play important roles in γδ T cell activation. Furthermore, TANCR may be involved in the cytotoxicity of γδ T cells. This study aims to further our understanding of the molecular mechanisms underlying lncRNA-mediated immune responses.