Dynamic expression of H19 and MALAT1 and their correlation with tumor progression biomarkers in a multistage hepatocarcinogenesis model.

Hepatocellular carcinoma (HCC) progresses sequentially in a stepwise pattern. Long noncoding RNA (lncRNA) can regulate the complex cascade of hepatocarcinogenesis. Our study aimed to elucidate the expression profile of H19 and MALAT1 during the different stages of hepatocarcinogenesis and the correlation between H19 and MALAT1 with the genes implicated in the carcinogenesis cascade. We employed a chemically induced hepatocarcinogenesis murine model to mimic the successive stages of human HCC development. Using real-time PCR, we analyzed the expression patterns of H19 and MALAT1, as well as the expression of biomarkers implicated in the Epithelial-Mesenchymal transition (EMT). The protein expression of the mesenchymal marker vimentin was also evaluated using immunohistochemistry in the stepwise induced stages. The histopathological evaluation of the liver tissue sections revealed significant changes during the experiment, with HCC developing at the final stage. Throughout the stages, there was a dynamic significant increase in the expression of H19 and MALAT1 compared to the normal control. Nevertheless, there was no significant difference between each stage and the preceding one. The tumor progression biomarkers (Matrix Metalloproteinases, vimentin, and ß-catenin) exhibited the same trend of steadily increasing levels. However, in the case of Zinc finger E-box-binding homeobox 1 and 2 (ZEB1 and ZEB2), the significant elevation was only detected at the last stage of induction. The correlation between lncRNAs and the tumor progression biomarkers revealed a strong positive correlation between the expression pattern of H19 and MALAT1 with Matrix Metalloproteinases 2 and 9 and vimentin. Our findings imply that genetic and epigenetic alterations influence HCC development in a stepwise progressive pattern.

The diagnostic efficacy of circulating miRNAs in monitoring the early development of colitis-induced colorectal cancer.

Early detection of colorectal cancer and monitoring the progress in colon carcinogenesis stages is essential to reduce mortality. Therefore, there is continuous search for noninvasive biomarkers with high stability and good sensitivity and specificity. miRNAs have attracted attention as promising biomarkers as they are stably expressed in circulation. The aim of our study is to evaluate the aberrant expression of circulating miRNAs during the stepwise progress of colitis-associated colon cancer. This was accomplished through assessing the expression levels of five miRNAs (miR-141, miR-15b, miR-17-3p, miR-21, and miR-29a) in serum and their corresponding tissue samples through the different cycles of colorectal carcinogenesis cascade using the azoxymethane/dextran sulfate sodium murine model. We also compared the diagnostic performance of these selected miRNAs with the conventional tumor biomarkers CEA and CA 19-9. The results of our study revealed that the expression levels of those miRNAs were dynamically changing in accordance with the tumor development state. Moreover, their aberrant expression in serum was statistically correlated with that in tissue. Our data also revealed that serum miR-15b, miR-21, and miR-29a showed the best performance in terms of diagnostic power. Our findings highlight the efficiency of these circulating miRNAs not only for early diagnostics purposes, but also for monitoring progress in the colorectal carcinogenesis process, and therefore encouraging integrating these noninvasive biomarkers into the clinical diagnostic settings beside the traditional diagnostic markers for accurate screening of the early progress of colon carcinogenesis.

Does Season of Reported Dietary Intake Influence Diet Quality? Analysis From the Women's Health Initiative.

We evaluated the role of seasonality in self-reported diet quality among postmenopausal women participating in the Women's Health Initiative (WHI). A total of 156,911 women completed a food frequency questionnaire (FFQ) at enrollment (1993-1998). FFQ responses reflected intake over the prior 3-month period, and seasons were defined as spring (March-May), summer (June-August), fall (September-November), and winter (December-February). FFQ data were used to calculate the Alternate Healthy Eating Index (AHEI), a measure of diet quality that has a score range of 2.5-87.5, with higher scores representing better diet quality. In multivariable linear regression models using winter as the reference season, AHEI scores were higher in spring, summer, and fall (all P values < 0.05); although significant, the variance was minimal (mean AHEI score: winter, 41.7 (standard deviation, 11.3); summer, 42.2 (standard deviation, 11.3)). Applying these findings to hypothesis-driven association analysis of diet quality and its relationship with chronic disease risk (cardiovascular disease) showed that controlling for season had no effect on the estimated hazard ratios. Although significant differences in diet quality across seasons can be detected in this population of US postmenopausal women, these differences are not substantial enough to warrant consideration in association studies of diet quality.

Solvent-free and one-pot synthesis of silver and zinc oxide nanoparticles: Activity toward cell membrane component and insulin signaling pathway in experimental diabetes.

OBJECTIVE: To investigate and compare between the effect of both silver nanoparticles (AgNPs) and zinc oxide nanoparticles (ZnONPs) on insulin signaling pathway and insulin sensitivity in experimental diabetes. Preparation of AgNPs and ZnONPs in their solid state were carried out using pullulan (Natural polymer) as both reducing and stabilizing agent. The synthesis of these nanoparticles in a large scale were carried out without using any solvents. The experimental male albino rats received diluted solutions of AgNPs and ZNONPs. After the experimental period, blood was withdrawn; erythrocyte membrane lipids were extracted and fatty acids were determined by HPLC. Oxidant, antioxidant profile and phosphatidylinositol 3-kinase (PI3K) were estimated. RESULTS: It was observed that the as synthesized AgNPs and ZnONPs have nearly spherical shape with small size due to the stabilization effect of pullulan as proved by UV-vis spectroscopy (UV-vis), Transmission electron microscy (TEM) and Field emission scanning electron microscopy (FESEM), Zeta potential, Dynamic light scattering (DLS) and X-ray diffraction (XRD) techniques. The average hydrodynamic size of the formed AgNPs was 15 nm which is considered as very small size when compared with that of ZnONPs (above 50 nm). Fasting blood sugar was significantly increased in diabetic group along with elevation of MDA and DNA damage indicating the oxidative properties of streptozotocin. Whereas, the treatment with nanoparticles significantly attenuated these elevations. CONCLUSION: AgNPs and ZnONPs represent promising materials in attenuating diabetic complications and insulin resistance in experimental diabetes; no Impressive differences were observed between the effect of ZnONPs and AgNPs in this current research.