MiRNA-203a-5p alleviates the malignant progression of Wilms' tumor via targeting JAG1.

OBJECTIVE: To uncover the potential influence of microRNA-203a-5p (miRNA-203a-5p) on the malignant progression of Wilms' tumor (WT). PATIENTS AND METHODS: MiRNA-203a-5p levels in 49 paired WT and paracancerous tissues were determined by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). Prognostic value of miRNA-203a-5p in WT was assessed by the Kaplan-Meier method. Correlation between miRNA-203a-5p level and clinical data of WT patients was analyzed. In G401 and SK-NEP-1 cells, in vitro functions of miRNA-203a-5p in regulating metastatic abilities were explored. The interaction between miRNA-203a-5p and JAG1, and their regulatory role in the malignant progression of WT were evaluated by Dual-Luciferase reporter gene assay and rescue experiments. RESULTS: MiRNA-203a-5p was downregulated in WT tissues than that of paracancerous ones. WT patients expressing low level of miRNA-203a-5p had higher risk of lymphatic metastasis and worse prognosis. Overexpression of miRNA-203a-5p attenuated migratory and invasive abilities in G401 cells. On the contrary, knockdown of miRNA-203a-5p yielded the opposite trends in SK-NEP-1 cells. JAG1 was verified to be the direct gene binding miRNA-203a-5p, which was negatively regulated by miRNA-203a-5p in WT cells. Rescue experiments finally uncovered that miRNA-203a-5p alleviated the malignant progression of WT via negatively regulating JAG1. CONCLUSIONS: MiRNA-203a-5p is downregulated in WT and closely linked to lymphatic metastasis of WT patients. By negatively regulating JAG1, miRNA-203a-5p alleviates the malignant progression of WT.

Rosuvastatin inhibits inflammatory response and resists fibrosis after myocardial infarction.

OBJECTIVE: To study the effect of rosuvastatin on myocardial infarction in rats and its mechanism of action. MATERIALS AND METHODS: 24 Sprague-Dawley (SD) rats were randomly divided into 3 groups: intensive statin group (n=8), myocardial infarction control group (n=8) and sham-operation group (n=8). The left anterior descending coronary artery was ligated to establish myocardial infarction models. Rats in intensive statin group were treated with gavage via rosuvastatin (1 mg × kg) and 1.5 mL distilled water suspension at 3 d before operation, while rats in the other two groups received gavage via the same amount of distilled water till 4 weeks after operation. Venous blood was collected using capillary glass tubes at 3 d before operation (before medication) and the last day in the 4th week after operation. Interleukin-6 (IL-6) was detected via chemiluminescence assay, and tumor necrosis factor-α (TNF-α) was detected via immunofluorescence assay. Hematoxylin and eosin (HE) staining and Masson staining were performed for myocardium to detect the inflammation and fibrosis. Finally, the expressions of inflammatory protein p65, peroxisome proliferator-activated receptor (PPAR) and fibrin were detected via Western blotting, and the Snail expression was detected by immunohistochemical assay. RESULTS: The survival rate and cardiac function of rats in intensive statin group were superior to those in control group. HE staining and detection of blood IL-6 and TNF-α, and p65 and PPAR protein expressions revealed that the inflammatory levels in the body and myocardium of rats in intensive statin group were decreased compared with those in control group. Masson staining and detection of fibrin level showed that the myocardial fibrosis level of rats in intensive statin group was reduced compared with that in control group. CONCLUSIONS: Rosuvastatin can reduce the level of myocardial fibrosis through alleviating the inflammatory response in rats with myocardial infarction.

Operational definitions improve reliability of the age-related white matter changes scale.

BACKGROUND AND PURPOSE: Although the age-related white matter changes (ARWMC) scale has been advocated to be applicable to both MRI and CT for assessing the severity of WMC, its inter-rater reliability on CT is only fair. We aimed to operationalize the ARWMC scale and investigate the effect of this operationalization on the reliability and validity on MRI and CT. METHODS: Operational definitions of the ARWMC scale were derived from Erkinjuntti research criteria for subcortical vascular dementia and Scheltens scale. Using original and operationalized ARWMC scale, eight observers recorded the time for rating per MRI and per CT. We investigated the inter-rater and intrarater reliability as well as validity against volume using data from 97 stroke patients. RESULTS: Inter-rater reliability of the operationalized scale on CT (0.874, 95% confidence interval [0.780-0.934]) was better than the original scale (0.569, 95% confidence interval [0.247-0.775]). Its intrarater reliability on CT (0.869) and reliability on MRI (inter-rater: 0.860; intrarater: 0.838) was comparable with the original scale (CT intrarater: 0.750 and on MRI inter-rater: 0.845; intrarater: 0.853). The time required to administer the operationalized scale (4'2″ for MRI and 1'18″ for CT) was similar to that of the original scale (3'56″ for MRI and 1'16″ for CT). The original scale and operationalized scale also significantly correlated with WMC volume (operationalized scale ρ = 0.613, P < 0.001, original scale ρ = 0.638, P < 0.001). CONCLUSION: Operational definitions improve the inter-rater reliability of ARWMC scale on CT, and it correlates with volumetric measurement.