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Impairment of genome instability drives the development of cancer by disrupting anti-cancer barriers. Upon genotoxic insults, DNA damage responsive factors, notably ATM kinase, is crucial to protect genomic integrity while promoting cell death. Meanwhile, cytotoxic therapy-inducing DNA lesions is double-edged sword by causing cancer metastasis based on animal models and clinical observations. The underlying mechanisms for the procancer effect of cytotoxic therapies are poorly understood. Here, we report that cancer cells subjected to cytotoxic treatments elicit dramatic alteration of gene expression controlling the potential of epithelium-mesenchyme transition (EMT). Resultantly, EMT-dependent cell mobility is potently induced upon DNA damage. This stimulation of EMT is mainly Ataxia-Telangiectasia-mutated (ATM)-dependent, as the chemical inhibitor specifically inhibiting ATM kinase activity can suppress the EMT gene expression and thus cell mobility. At last, we show that cancer cells with ATM activation display increased metastatic potential in ovarian cancer tissues. Taken together, we reveal a novel role of ATM in promoting metastatic potential of cancer cells by favoring EMT gene expression.

The incidence of COVID-19 in children and teenagers is only about 2% in China. Children had mild symptoms and hardly infected other children or adults. It is worth considering that children are the most vulnerable to respiratory pathogens, but fatal SARS-like virus had not caused severe cases among them. According to the pathological studies of COVID-19 and SARS, a sharp decrease in T lymphocytes leads to the breakdown of the immune system. The cellular immune system of children differs from that of adults may be the keystone of atypical clinical manifestations or even covert infection. The frequent childhood vaccinations and repeated pathogens infections might be resulting in trained immunity of innate immune cells, immune fitness of adaptive immune cells or cross-protection of antibodies in the children. Therefore, due to lack of specific vaccine, some vaccines for tuberculosis, influenza and pneumonia may have certain application potential for the front-line health workers in the prevention and control of COVID-19. However, for high-risk susceptible populations, such as the elderly with basic diseases such as hypertension and diabetes, it is necessary to explore the acclimatization effect of the planned immune process on their immunity to achieve the trained immunity or immune fitness, so as to improve their own antiviral ability.

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.

Context: Sepsis is now the leading cause of death in the noncardiovascular intensive care unit (ICU).Objective: To investigate whether polymorphisms in IL21 gene contribute to sepsis susceptibility.Materials and methods: Three single-nucleotide polymorphisms of IL21 (rs907715, rs2055979, rs12508721) were genotyped by TaqMan assay in patients with sepsis and control subjects.Results: Polymorphisms rs2055979 and rs12508721 in IL21 were more frequent in sepsis patients compared to general population. But allele frequency of rs907715 was not significantly different between sepsis patients and control subjects.Conclusion: Polymorphisms in IL21 may be associated with sepsis risk.