A novel pyroptosis-related gene signature exhibits distinct immune cells infiltration landscape in Wilms' tumor.

BACKGROUND: Wilms' tumor (WT) is the most common renal tumor in childhood. Pyroptosis, a type of inflammation-characterized and immune-related programmed cell death, has been extensively studied in multiple tumors. In the current study, we aim to construct a pyroptosis-related gene signature for predicting the prognosis of Wilms' tumor. METHODS: We acquired RNA-seq data from TARGET kidney tumor projects for constructing a gene signature, and snRNA-seq data from GEO database for validating signature-constructing genes. Pyroptosis-related genes (PRGs) were collected from three online databases. We constructed the gene signature by Lasso Cox regression and then established a nomogram. Underlying mechanisms by which gene signature is related to overall survival states of patients were explored by immune cell infiltration analysis, differential expression analysis, and functional enrichment analysis. RESULTS: A pyroptosis-related gene signature was constructed with 14 PRGs, which has a moderate to high predicting capacity with 1-, 3-, and 5-year area under the curve (AUC) values of 0.78, 0.80, and 0.83, respectively. A prognosis-predicting nomogram was established by gender, stage, and risk score. Tumor-infiltrating immune cells were quantified by seven algorithms, and the expression of CD8( +) T cells, B cells, Th2 cells, dendritic cells, and type 2 macrophages are positively or negatively correlated with risk score. Two single nuclear RNA-seq samples of different histology were harnessed for validation. The distribution of signature genes was identified in various cell types. CONCLUSIONS: We have established a pyroptosis-related 14-gene signature in WT. Moreover, the inherent roles of immune cells (CD8( +) T cells, B cells, Th2 cells, dendritic cells, and type 2 macrophages), functions of differentially expressed genes (tissue/organ development and intercellular communication), and status of signaling pathways (proteoglycans in cancer, signaling pathways regulating pluripotent of stem cells, and Wnt signaling pathway) have been elucidated, which might be employed as therapeutic targets in the future.

Magnet-targeted delivery of bone marrow-derived mesenchymal stem cells improves therapeutic efficacy following hypoxic-ischemic brain injury.

Stem cell transplantation may represent a feasible therapeutic option for the recovery of neurological function in children with hypoxic-ischemic brain injury; however, the therapeutic efficacy of bone marrow-derived mesenchymal stem cells largely depends on the number of cells that are successfully transferred to the target. Magnet-targeted drug delivery systems can use a specific magnetic field to attract the drug to the target site, increasing the drug concentration. In this study, we found that the double-labeling using superparamagnetic iron oxide nanoparticle and poly-L-lysine (SPIO-PLL) of bone marrow-derived mesenchymal stem cells had no effect on cell survival but decreased cell proliferation 48 hours after labeling. Rat models of hypoxic-ischemic brain injury were established by ligating the left common carotid artery. One day after modeling, intraventricular and caudal vein injections of 1 × 105 SPIO-PLL-labeled bone marrow-derived mesenchymal stem cells were performed. Twenty-four hours after the intraventricular injection, magnets were fixed to the left side of the rats' heads for 2 hours. Intravoxel incoherent motion magnetic resonance imaging revealed that the perfusion fraction and the diffusion coefficient of rat brain tissue were significantly increased in rats treated with SPIO-PLL-labeled cells through intraventricular injection combined with magnetic guidance, compared with those treated with SPIO-PLL-labeled cells through intraventricular or tail vein injections without magnetic guidance. Hematoxylin-eosin and terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) staining revealed that in rats treated with SPIO-PLL-labeled cells through intraventricular injection under magnetic guidance, cerebral edema was alleviated, and apoptosis was decreased. These findings suggest that targeted magnetic guidance can be used to improve the therapeutic efficacy of bone marrow-derived mesenchymal stem cell transplantation for hypoxic-ischemic brain injury. This study was approved by the Animal Care and Use Committee of The Second Hospital of Dalian Medical University, China (approval No. 2016-060) on March 2, 2016.

The effect of magnetic guiding BMSCs on hypoxic-ischemic brain damage via magnetic resonance imaging evaluation.

Hypoxic-ischemic brain damage (HIBD) is a critical disease in pediatric neurosurgery with high mortality rate and frequently leads to neurological sequelae. The role of bone marrow mesenchymal stem cells (BMSCs) in neuroprotection has been recognized. However, using the imaging methods to dynamically assess the neuroprotective effects of BMSCs is rarely reported. In this study, BMSCs were isolated, cultured and identified. Flow cytometry assay had shown the specific surface molecular markers of BMSCs, which indicated that the cultivated cells were purified BMSCs. The results demonstrated that CD29 and CD90 were highly expressed, whilst CD45 and CD11b were negatively expressed. Further, BMSCs were transplanted into Sprague Dawley (SD) rats established HIBD via three ways, including lateral ventricle (LV) injection, tail vein (TV) injection, and LV injection with magnetic guiding. Magnetic resonance imaging (MRI) was used to monitor and assess the treatment effect of super paramagnetic iron oxide (SPIO)-labeled BMSCs. The mean kurtosis (MK) values from diffusion kurtosis imaging (DKI) exhibited the significant differences. It was found that the MK value of HIBD group increased compared with that in Sham. At the meantime, the MK values of LV + HIBD, TV + HIBD and Magnetic+LV + HIBD groups decreased compared with that in HIBD group. Among these, the MK value reduced most significantly in Magnetic+LV + HIBD group. MRI illustrated that the treatment effect of Magnetic+LV + HIBD group was best. In addition, HE staining and TUNEL assay measured the pathological changes and apoptosis of brain tissues, which further verified the MRI results. All data suggest that magnetic guiding BMSCs, a targeted delivery way, is a new strategic theory for HIBD treatment. The DKI technology of MRI can dynamically evaluate the neuroprotective effects of transplanted BMSCs in HIBD.