CeO2 nanoparticles protect against the progression of cardiac dysfunction and remodeling by attenuation of myocardial oxidative stress, ER stress, and inflammatory processes probably through their autoregenerative antioxidant properties.

Purpose. The aim of this study is to develop and compare performance of radiomics signatures using texture features extracted from noncontrast enhanced CT (NECT) and contrast enhanced CT (CECT) images for preoperative predicting risk categorization and clinical stage of thymomas. Materials and Methods. Between January 2010 and October 2018, 199 patients with surgical resection and histopathologically confirmed thymoma were enrolled in this retrospective study. We extracted 841 radiomics features separately from volume of interest (VOI) in NECT and CECT images. The features with poor reproducibility and highly redundancy were removed. Then a least absolute shrinkage and selection operator method (LASSO) logistic regression model with 10-fold cross validation was used for further feature selection and radiomics signatures build. The predictive performances of radiomics signatures were assessed by receiver operating characteristic (ROC) analysis. The areas under the receiver operating characteristic curve (AUC) between radiomics signatures were compared by using Delong test. Result. In differentiating high risk thymomas from low risk thymomas, the AUC, sensitivity, and specificity were 0.801(95% CI 0.740–0.863), 0.752 and 0.767 for radiomics signature based on NECT images, and 0.827 (95% CI 0.771 -0.884), 0.798, and 0.722 for radiomics signature based on CECT images. But there was no significant difference (p=0.365) between them. In differentiating advanced stage thymomas from early stage thymomas, the AUC, sensitivity, and specificity were 0.829 (95%CI 0.757-0.900), 0.712, and 0.806 for radiomics signature based on NECT images and 0.860 (95%CI 0.803-0.917), 0.699, and 0.889 for radiomics signature based on CECT images. There was no significant difference (p=0.069) between them. The accuracy was 0.819 for radiomics signature based on NECT images, 0.869 for radiomics signature based on CECT images, and 0.779 for radiologists. Both radiomics signatures had a better performance than radiologists. But there was significant difference (p = 0.025) only between CECT radiomics signature and radiologists. Conclusion. Radiomics signatures based on texture analysis from NECT and CECT images could be utilized as noninvasive biomarkers for differentiating high risk thymomas from low risk thymomas and advanced stage thymomas from early stage thymoma. As a quantitative method, radiomics signature can provide complementary diagnostic information and help to plan personalized treatment for patients with thymomas.

The objective of this study was to determine if macrophage migration inhibitory factor (MIF) is upregulated in the bladder during persistent cystitis. MIF is a pro-inflammatory cytokine found pre-formed in the urothelium. Previous findings showed that acute bladder inflammation increased MIF release into the bladder lumen while upregulating MIF and CD74 (MIF receptor) in the bladder. Because the effects of persistent cystitis on MIF and CD74 are not known, MIF and CD74 changes in the bladder were examined after short-term (1-day) or persistent (8-day) cyclophosphamide (CYP)-induced bladder inflammation. Anesthetized male Sprague-Dawley rats received either a single CYP treatment (150 mg/kg, ip; saline, control) and examined 1 day after treatment (short-term), or repeated CYP doses (20-75 mg/ kg, ip; saline, control; every third day for 8 days) and examined after 8 days of treatment (persistent). MIF protein levels in urine and bladder were determined. In addition, Mif, CD74, and cox-2 expression in the bladder was determined. Histology verified cystitis and MIF and CD74 immunoreactivity in the bladder. Repeated CYP doses were decreased to avoid toxicity. Short-term or repeated low CYP doses (40 mg/kg; 8 days) increased urinary MIF and decreased bladder MIF amounts while upregulating bladder Mif and CD74 mRNA expression. Persistent CYP-induced bladder inflammation (even at 40 mg/kg; 8-day treatment) also upregulated other inflammatory cytokines (CCL5, IL-11, iNOS) in the bladder. Short-term and persistent (low dose) CYP cystitis are associated with markedly increased MIF release into the urine and upregulation of Mif and CD74 in bladder. This supports the hypothesis that MIF and CD74 play a significant role in both acute and persistent stages of bladder inflammation.

BackgroundMacrophage migration inhibitory factor (MIF) is a pro-inflammatory cytokine involved in cystitis and a non-cognate ligand of the chemokine receptor CXCR4 in vitro. We studied whether CXCR4-MIF associations occur in rat bladder and the effect of experimental cystitis.Methods and FindingsTwenty male rats received saline or cyclophosphamide (40 mg/kg; i.p.; every 3rd day) to induce persistent cystitis. After eight days, urine was collected and bladders excised under anesthesia. Bladder CXCR4 and CXCR4-MIF co-localization were examined with immunhistochemistry. ELISA determined MIF and stromal derived factor-1 (SDF-1; cognate ligand for CXCR4) levels. Bladder CXCR4 expression (real-time RTC-PCR) and protein levels (Western blotting) were examined. Co-immunoprecipitations studied MIF-CXCR4 associations.Urothelial basal and intermediate (but not superficial) cells in saline-treated rats contained CXCR4, co-localized with MIF. Cyclophosphamide treatment caused: 1) significant redistribution of CXCR4 immunostaining to all urothelial layers (especially apical surface of superficial cells) and increased bladder CXCR4 expression; 2) increased urine MIF with decreased bladder MIF; 3) increased bladder SDF-1; 4) increased CXCR4-MIF associations.ConclusionsThese data demonstrate CXCR4-MIF associations occur in vivo in rat bladder and increase in experimental cystitis. Thus, CXCR4 represents an alternative pathway for MIF-mediated signal transduction during bladder inflammation. In the bladder, MIF may compete with SDF-1 (cognate ligand) to activate signal transduction mediated by CXCR4.