Comprehensive Analysis of Ferroptosis- and Immune-Related Signatures to Improve the Prognosis and Diagnosis of Kidney Renal Clear Cell Carcinoma.

Background: Almost 40% of patients with kidney renal clear cell carcinoma (KIRC) with advanced cancers eventually develop to metastases, and their 5-year survival rates are approximately 10%. Aberrant DNA methylations are significantly associated with the development of KIRC. The aim of our present study was to identify suitable ferroptosis- and immune-related (FI) biomarkers correlated with aberrant methylations to improve the prognosis and diagnosis of KIRC. Methods: ChAMP and DESeq2 in R (3.6.2) were used to screen the differentially expressed methylation probes and differentially expressed genes, respectively. Univariate and multivariate Cox regression were used to identify the overall survival (OS)-related biomarkers. Results: We finally identified five FI biomarkers (CCR4, CMTM3, IFITM1, MX2, and NR3C2) that were independently correlated with the OS of KIRC. The area under the curve value of the receiver operating characteristic value of prognosis model was 0.74, 0.68, and 0.72 in the training, validation, and entire cohorts, respectively. The sensitivity and specificity of the diagnosis model were 0.8698 and 0.9722, respectively. In addition, the prognosis model was also significantly correlated with several immune cells and factors. Conclusion: Our present study suggested that these five FI-DEGs (CCR4, CMTM3, IFITM1, MX2, and NR3C2) could be used as prognosis and diagnosis biomarkers for patients with KIRC, but further cross-validation clinical studies are still needed to confirm them.

[Effects of polychlorinated biphenyl on the expression of c-fos and c-jun in mesenchymal cells of rats].

OBJECTIVE: To study the effects of polychlorinated biphenyl (PCB126) on the expression of c-fos and c-jun in mesenchymal cells (MSCs) of rats. METHODS: MSCs were separated by percoll cell separating medium (density 1.073 g/cm3). After being cultured and transferred, the cells were divided into a control group, a low-dose group (10(-7) mol/L PCB126) and a high-dose group (10(-6) mol/L PCB126). The cellular growth rate and the expression of c-fos and c-jun protein were analyzed by MTT, immunofluorescence chemical assay, RT-PCR and Western blot. RESULTS: The cellular growth rate in the low-and high-dose group were 13.8% and 19.1% at 12 h, 31.5% and 36.1% at 24 h, 42.5% and 43.6% at 48 h, respectively (P < 0.01). The positive rates of c-fos expression in the low-and high-dose groups were 54.6% and 51.3% at 12 h, and 83.2% and 73.0% at 24 h. The expression of c-fos mRNA detected by RT-PCR was upregulated at 30 min and 1h in PCB126 groups. The expression of c-jun mRNA were much higher in PCB126 groups than that in the control group. The expression of c-fos and c-jun protein was upregulated in the low-and high-dose groups at 12 h and 24 h. CONCLUSION: PCB126 could promote the proliferation of MSCs and upregulate the expression of cancer associated gene c-fos and c-jun. The effect of PCB126 on the function of MSCs might be associated with the abnormal expression of c-fos and c-jun gene.

[Effect of mechanical strain on differentiation of mesenchymal stem cells into osteoblasts].

This study sought to elucidate the effect of mechanical strain on the differentiation of mesenchymal stem cells into osteoblasts. Under the conditons of inducing osteoblasts, Immunohistochemical methods and RT-PCR technology were applied in osteogenic supplements medium to detect: (1) the expression of Alkaline phosphatase (ALP), Type I collagen (COL I ), Osterx (Osx) and Osteocalcin (OCN) mRNA, with cyclic strain (3%, 0.5 Hz) applied for 15 min, 30 min, 1 h, 2 h, 4 h, 3 d, 7 d, 14 d; (2) the expression of Osx mRNA and OCN mRNA with 3% strain for 1 h. The results showed: (1) ALP mRNA expression was higher at 7 days; COL I mRNA expression was greater obviously at 7 days and 14 days than that at 3 days and that of the unstrained cells; (2) the expression of Osx mRNA was up-regulated after 15min by strain stimulation,which was significantly increased at 30 min and 1 h in the unstrained cells. The expression of OCN mRNA was not affected in the unstrained cells at 15 min, whereas strain could promote the expression of OCN mRNA at this period. The expression of OCN mRNA was more obviously upregulated in the strained cells at 30 min and 1 h when compared with that in the unstrained cells; (3) the strain (1% and 3%) significantly promoted the expression of Osx mRNA; 10% strain had a little effect on Osx mRNA expression. The expression of OCN mRNA was up-regulated by 3% strain, whereas it had little effect at 1% and 10% strain. In summary, mechanical strain can promote the differentiation of mesenchymal stem cells into osteoblasts.