Protective activity of a novel resveratrol analogue,HS-1793, against DNA damage in 137Cs-irradiated CHO-K1 cells

Resveratrol has received considerable attention as a polyphenol with anti-oxidant, anti-carcinogenic, and anti-inflammatory effects. Radiation is an important component of therapy for a wide range of malignant conditions. However, it causes damage to normal cells and, hence, can result in adverse side effects. This study was conducted to examine whether HS-1793, a novel resveratrol analogue free from the restriction of metabolic instability and the high dose requirement of resveratrol, induces a protective effect against radiation-induced DNA damage. HS-1793 effectively scavenged free radicals and inhibited radiation-induced plasmid DNA strand breaks in an in vitro assay. HS-1793 significantly decreased reactive oxygen species and cellular DNA damage in 2 Gy-irradiated Chinese hamster ovary (CHO)-K1 cells. In addition, HS-1793 dose-dependently reduced the levels of phosphorylated H2AX in irradiated CHO-K1 cells. These results indicate that HS-1793 has chemical radioprotective activity. Glutathione levels and superoxide dismutase activity in irradiated CHO-K1 cells increased significantly following HS-1793 treatment. The enhanced biological anti-oxidant activity and chemical radioprotective activity of HS-1793 maintained survival of irradiated CHO-K1 cells in a clonogenic assay. Therefore, HS-1793 may be of value as a radioprotector to protect healthy tissue surrounding tumor cells during radiotherapy to obtain better tumor control with a higher dose.     

The Relationship Between Cardiac Resynchronization Therapy and Diastolic Function

Cardiac resynchronization therapy (CRT) improves measures of systolic function and clinical status. However, its effect on diastolic function is not well established. Commonly used parameters of diastolic function are measured from echocardiography, using pulse wave and tissue Doppler technologies, as well as timing and deformation data. Review of the existing studies that address the relationship between diastolic function and CRT shows conflicting data, but general trends can be deduced. Baseline elevated filling pressure appears to identify patients most likely to derive improvement in that particular parameter. Intrinsic relaxation does not appear to be significantly impacted by CRT. Generally, changes in diastolic properties after CRT appear to be linked to changes in systolic function. Specific therapy aimed at diastolic asynchrony is lacking, partly due to an unclear relationship between diastolic asynchrony and diastolic dysfunction, and the inability to specifically impact diastolic timing with a systolic intervention such as CRT.     

Disparate genomic characteristics of concurrent endometrial adenocarcinoma and ovarian granulosa cell tumor,revealed by targeted next-generation sequencing

Concurrence of both endometrial adenocarcinoma and ovarian adult granulosa cell tumor (aGCT) is believed to be related to high estrogen milieu, but genomic alterations of the concurrent endometrial adenocarcinoma and aGCT are not known. For this, we analyzed an uterine endometrial adenocarcinoma and an ovarian aGCT in a same patient by a targeted next generation sequencing (NGS). We found a germline mutation in STK11 (p.L113fs). The endometrial adenocarcinoma harbored FGFR2 and TP53 mutations and the aGCT harbored a FOXL2 (p.C134?W) mutation. These germline and somatic mutations have been reported in non-concurrent tumors. These two tumors harbored 20 CNAs but only one CNA was exactly overlapped in the tumors. Our findings indicate that the concurrent endometrial adenocarcinoma and aGCT in this patient might not be genetically related to each other at germline or somatic level and suggest that such concurrence might be originated from non-genetic backgrounds including stimulated estrogen milieu.     

Application of diffusional kurtosis imaging to detect occult brain damage in multiple sclerosis and neuromyelitis optica

Multiple sclerosis (MS) and neuromyelitis optica (NMO) are two common types of inflammatory demyelinating disease of the central nervous system. Early distinction of NMO from MS is crucial but quite challenging. In this study, 13 NMO spectrum disorder patients (Expanded Disability Status Scale (EDSS) of 3.0 ± 1.7, ranging from 2 to 6.5; disease duration of 5.3 ± 4.7 years), 17 relapsing–remitting MS patients (EDSS of 2.6 ± 1.4, ranging from 1 to 5.5; disease duration of 7.9 ± 7.8 years) and 18 healthy volunteers were recruited. Diffusional kurtosis imaging was employed to discriminate NMO and MS patients at the early or stable stage from each other, and from healthy volunteers. The presence of alterations in diffusion and diffusional kurtosis metrics in normal‐appearing white matter (NAWM) and diffusely increased mean diffusivity (MD) in the cortical normal‐appearing gray matter (NAGM) favors the diagnosis of MS rather than NMO. Meanwhile, normal diffusivities and kurtosis metrics in all NAWM as well as increases in MD in the frontal and temporal NAGM suggest NMO. Our results suggest that diffusion and diffusional kurtosis metrics may well aid in discriminating the two diseases.