CVB3 is a single positive-strand enterovirus, and a common pathogen in myocarditis etiology. Although a number of antiviral candidates are under development, specific targeted therapy is not available for CVB3. Ferroptosis is a new type of regulatory cell death discovered in recent years. In this study, our team provided the first evidence that ferroptosis existed in CVB3 infection in vivo and in vitro by iron overload, and massive accumulation of lipid peroxides. Mechanistically, we construct a classical model of HeLa cells following a time-course infection (6, 12, 24, 36, 48 h) with CVB3 (MOI = 10). We demonstrated that the TFRC gene plays an important role in promoting ferroptosis in CVB3 infection and downregulation of TFRC attenuated the ferroptosis. Interestingly, we observed that TFRC was nuclear translocation induced by the CVB3, which was predominantly localized in the cell membrane, but redistributed to the nucleus during CVB3 infection. Moreover, we found that the transcription factor Sp1 was an essential factor that could bind to the TFRC promoter and upregulate the TFRC transcription. Collectively, these results suggest that the Sp1/TFRC/Fe axis may provide a new target for the development of therapies against CVB3 infection.

No abstract

Background Serum creatinine (SCr) is unreliable in detecting acute changes in kidney function. Early recognition of contrast-induced acute kidney injury (CI-AKI) can provide better opportunities for preventive interventions. Therefore, the purpose of this study is to examine the value of the combined detection of urinary neutrophil gelatinase-associated lipocalin (NGAL), insulin-like growth factor binding protein-7 (IGFBP-7), and tissue inhibitor of metalloproteinase-2 (TIMP-2) in the early diagnosis of children with CI-AKI. Methods A prospective, single-center clinical trial was performed and included 172 children aged 0–18 years. The dynamic changes of urinary NGAL, IGFBP-7, and TIMP-2 levels in children with intravascular injection of contrast medium were investigated to determine whether they can diagnose CI-AKI early. Results CI-AKI occurred in 20 of 137 enrolled patients, and the incidence was 14.59%. In the CI-AKI group, urinary levels of NGAL, IGFBP-7, TIMP-2, and [IGFBP-7]*[TIMP-2] were significantly increased 2 h after angiography and remained at high levels at 6 h. Using a cutoff value of 36.274 ng/mL, the specificity was 70.0%, and the sensitivity was 68.4% for the prediction of CI-AKI, which was excellent for urinary NGAL. When both urinary IGFBP-7 and TIMP-2 were used together, urinary [IGFBP-7]*[TIMP-2] at 0.417(ng/mL) 2 /1000 was regarded as the cutoff value. The specificity was 80.0%, and the sensitivity was 81.2%. Conclusions NGAL, IGFBP-7, and TIMP-2 concentrations in the urine of children after receiving injections of contrast medium increased faster than SCr and had good clinical value for the early diagnosis of CI-AKI in children. The combination of IGFBP-7 and TIMP-2 was better than either analyte alone.