Background: Necroptosis is a novel programmed cell death pathway proposed in 2005, which is mainly activated by the tumor necrosis factor (TNF) family and mediates cellular disassembly via receptor interacting serine/threonine kinase 1 (RIPK1), receptor interacting serine/threonine kinase 3 (RIPK3) and mixed lineage kinase domain like pseudokinase (MLKL). We tried to analyze the relationship of necroptosis-related genes (NRGs) expression with colon adenocarcinoma (COAD) and propose potential therapeutic targets through immunological analysis. Methods: First, we evaluated the expression of NRGs in COAD patients and constructed a prognostic signature. The prognostic signature was validated using The Cancer Genome Atlas (TCGA)-COAD and GSE39582 datasets, respectively. And the Kaplan-Meier analysis, receiver operating characteristic (ROC) curves, and principal component analysis were used to evaluate the signature. Then we analyzed the enrichment of NRGs in the signature using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. Finally, we analyzed the immunological characteristics of the COAD patients by single sample gene set enrichment analysis (ssGSEA) and predicted the possible immune checkpoints. Results: We constructed a prognostic signature with 8 NRGs (RIPK3, MLKL, TRAF2, CXCL1, RBCK1, CDKN2A, JMJD7-PLA2G4B and CAMK2B). The Kaplan-Meier analysis, ROC curves, and principal component analysis demonstrated good predictivity of the signature. In addition, we constructed a nomogram with good individualized predictive ability (C-index =0.772). The immunological analysis revealed that the prognosis of COAD was associated with autoimmune function, and we proposed 10 potential therapeutic targets. Conclusions: Overall, we constructed an NRGs prognostic signature and suggested potential therapeutic targets for the COAD treatment.

Our previous study has confirmed that astrocytes overexpressing neurogenic differentiation factor 1 (NEUROD1) in the spinal cord can be reprogrammed into neurons under in vivo conditions. However, whether they can also be reprogrammed into neurons under in vitro conditions remains unclear, and the mechanisms of programmed conversion from astrocytes to neurons have not yet been clarified. In the present study, we prepared reactive astrocytes from newborn rat spinal cord astrocytes using the scratch method and infected them with lentivirus carrying NEUROD1. The results showed that NEUROD1 overexpression reprogrammed the cultured reactive astrocytes into neurons in vitro with an efficiency of 13.4%. Using proteomic and bioinformatic analyses, 1952 proteins were identified, of which 92 were differentially expressed. Among these proteins, 11 were identified as candidate proteins in the process of reprogramming based on their biological functions and fold-changes in the bioinformatic analysis. Furthermore, western blot assay revealed that casein kinase II subunit alpha (CSNK2A2) and pinin (PNN) expression in NEUROD1-overexpressing reactive astrocytes was significantly increased, suggesting that NEUROD1 can directly reprogram spinal cord-derived reactive astrocytes into neurons in vitro, and that the NEUROD1-CSNK2A2-PNN pathway is involved in this process. This study was approved by the Animal Ethics Committee of Fujian Medical University, China (approval No. 2016-05) on April 18, 2016.

The aim of this study was to develop nomograms to predict long-term overall survival and cancer-specific survival of patients with osteosarcoma. We carried out univariate and multivariate analyses and set up nomograms predicting survival outcome using osteosarcoma patient data collected from the Surveillance, Epidemiology and End Results (SEER) program of the National Cancer Institute (2004–2011, n = 1426). The patients were divided into a training cohort (2004–2008, n = 863) and a validation cohort (2009–2011, n = 563), and the mean follow-up was 55 months. In the training cohort, 304 patients (35.2%) died from osteosarcoma and 91 (10.5%) died from other causes. In the validation cohort, 155 patients (27.5%) died from osteosarcoma and (12.3%) died from other causes. Nomograms predicting overall survival (OS) and cancer-specific survival (CSS) were developed according to 6 clinicopathologic factors (age, tumor site, historic grade, surgery, AJCC T/N, and M), with concordance indexes (C-index) of 0.725 (OS) and 0.718 (CSS), respectively. The validation C-indexes were 0.775 and 0.742 for OS and CSS, respectively. Our results suggest that we have successfully developed highly accurate nomograms for predicting 5-year OS and CSS for osteosarcoma patients. These nomograms will help surgeons customize treatment and monitoring strategies for osteosarcoma patients.