Novel oral edaravone attenuates diastolic dysfunction of diabetic cardiomyopathy by activating the Nrf2 signaling pathway.

Oxidative stress plays a crucial role in the pathophysiology of diastolic dysfunction associated with diabetic cardiomyopathy. Novel oral edaravone (OED) alleviates oxidative stress by scavenging free radicals and may be suitable for the treatment of chronic diseases such as diabetic cardiomyopathy. Oral administration of OED to type 2 diabetic rats (induced by high-sugar/high-fat diet and intraperitoneal injection of streptozotocin) for 4 w decreased malondialdehyde and increased superoxide dismutase. Moreover, it significantly improved ratios of early to late diastolic peak velocity, myocardium hypertrophy accompanied by decreased cross-sectional areas of cardiomyocytes, the proportion of apoptotic cells, collagen volume fractions, and deposition of collagen I/III. In H9c2 cells, OED reduced reactive oxygen species, cell surface area, and numbers of terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling-positive cells induced by glucolipotoxicity. OED remarkably upregulated expression of the nuclear factor E2-related factor (Nrf2) signaling pathway both in vivo and in vitro. In addition, OED promoted Nrf2 nuclear translocation and upregulated nicotinamide adenine dinucleotide phosphate quinone oxidoreductase and heme oxygenase. Silencing of Nrf2 abolished the protective effect of OED in H9c2 cells. Our findings demonstrate that OED has the therapeutic potential to ameliorate diastolic dysfunction associated with diabetic cardiomyopathy. Its effect was mainly achieved by attenuating hyperglycemia and hyperlipidemia-induced cardiomyocyte hypertrophy, apoptosis, and fibrosis by activating the Nrf2 signaling pathway.

RPL34-AS1 functions as tumor suppressive lncRNA in esophageal cancer.

Ribosomal protein L34 antisense RNA 1 (RPL34-AS1) is novel long non-coding RNA, and was found to be down-regulated in colorectal cancer and gastric cancer. The role of RPL34-AS1 was still unknown in esophageal cancer. In our study, we found RPL34-AS1 expression levels in esophageal cancer tissue and specimens and cell lines were lower than in adjacent normal tissue specimens and normal esophageal cell line, respectively. In addition, esophageal cancer patients with Ⅲ-Ⅳ, T3-T4 or positive lymph node metastasis had lower RPL34-AS1expression levels than esophageal cancer patients with Ⅰ-Ⅱ, T1-T2 or negative lymph node metastasis, respectively. In survival analysis suggested esophageal cancer patients with low RPL34-AS1 expression had short overall survival than those with high RPL34-AS1 expression. Our in vitro experiments suggested RPL34-AS1 inhibits esophageal cancer cell proliferation, migration and invasion through down-regulating RPL34 expression. In conclusion, RPL34-AS1 functions as tumor suppressor in esophageal cancer.

[Correlation between age and average apparent diffusion coefficient in normal-appearing cerebral white matter].

OBJECTIVE: To quantitatively study the effect of ages on the average apparent diffusion coefficient (ADCav) of normal-appearing white matter. METHODS: Fifty patients with normal-appearing white matter were divided into four age groups, namely 16-30 years, (n=13), 31-45 years (n=12), 46-60 years (n=14) and >60 years (n=11). All the subjects were examined with conventional and trace-weighted diffusion imaging in three orthogonal directions. The ADCav of the white matter was measured and compared between various age groups. RESULTS: In the white matter, the ADCav of all the patients was (0.71+/-0.08) x 10(-3) mm2/s; the ADCav of the white matter in the first to fourth age groups were (0.69+/-0.06) x 10(-3) mm2/s, (0.71+/-0.07) x 10(-3) mm2/s, (0.71+/-0.09) x 10(-3) mm2/s, and (0.73+/-0.10) x 10(-3) mm2/s respectively. ADCav of patients between 16-30 years was significantly different from that of patients over 60 years of age (P=0.014). Patients older than 60 years had an ADCav of the white matter significantly higher than the value of (0.70+/-0.07) x 10(-3) mm2)/s in the total patients younger than 60 years (P=0.026). CONCLUSION: Water diffusibility shows a slight increase in human white matter with aging, possibly due to mild ultrastructural changes associated with aging.

Perfusion homogeneity of hepatic parenchyma in magnetic resonance imaging during splenoportography.

OBJECTIVE: To evaluate the homogeneity of hepatic parenchyma enhancement in magnetic resonance imaging during splenoportography (MRSP) in the portal phase. METHODS: MRSP was performed in 16 patients suspected of space-occupying lesions in the livers. The signal intensity of non-lesion abnormal perfusion areas and that of peripheral parenchyma were measured in all the scanning phases including unenhanced phase, portographic phase, equilibrium phase, and delayed phase. RESULTS: Perfusion abnormalities were observed in 8 non-lesion foci in the portal phase in 4 cases of hepatic cirrhosis, most frequently appearing in triangle or fan-like shapes (7/8) with unpredictable locations. Hepatic cirrhosis patients had more non-lesion perfusion abnormalities than non-cirrhosis patients. CONCLUSIONS: The presence of non-lesion perfusion abnormalities in MRSP does not affect the diagnosis of the disease, and more homogeneous enhancement of the hepatic parenchyma in the portal phase can be achieved in MRSP than in CT during arterial portography and magnetic resonance imaging during arterial portography.

Superparamagnetic iron oxide (Feridex)-enhanced MRI in diagnosis of focal hepatic lesions.

OBJECTIVE: To evaluate the diagnostic value of superparamagnetic iron oxide (SPIO)-enhanced magnetic resonance imaging (MRI) for hepatic focal solid lesions. METHODS: SPIO (Feridex)-enhanced MRI examination was performed in 28 cases of hepatic space-occupying lesions defined by CT or MRI or other methods. In post-contrast enhanced examination, the signal intensity and contrast-to-noise ratio (CNR) were measured in lesions and normal hepatic parenchyma in T2-weighted images (T2WI) and were compared with those in pre-contrast enhanced MRI. The number and morphology of the lesions were visualized for qualitative diagnostic analysis. RESULTS: In Feridex-enhanced MRI, the signal intensity of normal hepatic parenchyma was decreased while the CNR between lesions and normal liver tissues significantly improved in comparison with that in pre-contrast enhanced examination. CONCLUSION: Feridex-enhanced T2WI examination significantly improves detection of hepatic lesions and is valuable in diagnosing hepatic focal solid lesions.