Background Human urine-derived stem cells (USCs)-derived exosomes (USC-Exo) could improve kidney ischemia/reperfusion injury (IRI), while the underlying mechanisms of this protective effect remain unclear. Methods Human USCs and USC-Exo were isolated and verified by morphology and specific biomarkers. The effects of USC-Exo on ferroptosis and kidney injury were detected in the IRI-induced acute kidney injury (AKI) model in C57BL/6 mice. The effects of USC-Exo on ferroptosis and lncRNA taurine-upregulated gene 1 (TUG1) were detected in hypoxia/reoxygenation (H/R)-treated human proximal tubular epithelial cells (HK-2). The interaction of SRSF1 and TUG1, ACSL4 was checked via RNA pull-down/RIP and RNA stability assays. The effects of LncRNA TUG1 on SRSF1/ACSL4-mediated ferroptosis were verified in H/R-treated HK-2 cells and the IRI-induced AKI mouse models. Results USC-Exo treatment improved kidney injury and ameliorated ferroptosis in IRI-induced AKI mouse models. USC-Exo were rich in lncRNA TUG1, which suppressed ferroptosis in HK-2 cells exposed to H/R. Mechanistically, lncRNA TUG1 regulates the stability of ACSL4 mRNA by interacting with RNA-binding protein SRSF1. In addition, SRSF1 upregulation or ACSL4 downregulation partially reversed the protective effect of lncRNA TUG1 on ferroptosis in H/R-treated HK-2 cells. Further, ACSL4 upregulation partially reversed TUG1’s repression on kidney injury and ferroptosis in IRI-induced AKI mice. Conclusion Collectively, lncRNA TUG1 carried by USC-Exo regulated ASCL4-mediated ferroptosis by interacting with SRSF1 and then protected IRI-induced AKI. Potentially, USC-Exo rich in lncRNA TUG1 can serve as a promising therapeutic method for IRI-AKI.

Abstract. Livin is a novel member of the inhibitor of apoptosis protein family that has been reported to be overexpressed in various types of human malignancy. Although several studies have demonstrated that livin may be used as an effective target for tumor therapy, few studies have investigated its role in human lung adenocarcinoma. In the present study, two different methods were used in order to investigate the tumor-suppressing effect of livin in human lung adenocarcinoma cells. Firstly, small interfering (si)RNA technology was used to down regulate livin expression; siRNA-mediated knockdown of livin was confirmed using reverse transcription quantitative polymerase chain reaction and western blot analysis, and cell proliferations was assessed using an MTT assay in vitro. Secondly, inhibition of livin expression was induced through the synergistic inhibitory effect between flavopiridol and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). Experimental results revealed that, following transfection of the livin gene-silencing vector, the gene expression of livin was markedly decreased, SPC-A1 cell proliferation was significantly reduced and the therapeutic effect of the chemotherapy drug cisplatin was markedly improved. This growth inhibitory effect was also observed in the flavopiridol and TRAIL combination treatment group. In the flavopiridol and TRAIL combination treatment group, the protein expression of livin was significantly reduced and the survival rate of SPC-A1 cells was significantly lower than the flavopiridol and TRAIL single operation group. In conclusion, the RNA silencing and the synergistic inhibitory effect between flavopiridol with TRAIL was able to effectively inhibit the expression of livin, significantly decrease SPC-A1 tumor cell proliferation and significantly enhance sensitivity to the chemotherapy drug cisplatin. These findings suggest that livin may be used as a novel target for tumor gene therapy.

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Objective The role of tumor-infiltrating lymphocytes (TILs) has not yet been characterized in sarcomas. The aim of this bioinformatics study was to explore the effect of TILs on sarcoma survival and genome alterations. Methods Whole-exome sequencing, transcriptome sequencing, and survival data of sarcoma were obtained from The Cancer Genome Atlas. Immune infiltration scores were calculated using the Tumor Immune Estimation Resource. Potential associations between abundance of infiltrating TILs and survival or genome alterations were examined. Results Levels of CD4+ T cell infiltration were associated with overall survival of patients with pan-sarcomas, and higher CD4+ T cell infiltration levels were associated with better survival. Somatic copy number alterations, rather than mutations, were found to correlate with CD4+ T cell infiltration levels. Conclusions This data mining study indicated that CD4+ T cell infiltration levels predicted from RNA sequencing could predict sarcoma prognosis, and higher levels of CD4+ T cells infiltration indicated a better chance of survival.