lncRNA­miRNA­mRNA network in female offspring born from obese dams.

Maternal obesity is associated with disturbance of lipid metabolism and obesity in offspring; however, the pathogenesis is still unclear. The present study elucidated the role of potential lipid metabolism-associated long non-coding RNA (lncRNA) and identified the pathways involved in mice born to obese dams. In the present study, maternal obesity was induced by feeding a high-fat diet for 10 weeks in female C57/BL6 mice, whereas control mice were fed a standard diet. All female mice mated with healthy male mice and were allowed to deliver spontaneously. The results demonstrated that female offspring from obese dams presented a tendency to become overweight in the first 8 weeks after birth; however, maternal obesity did not significantly alter the body weight of male offspring. RNA-sequencing analysis was performed on female offspring liver at 3 weeks old. Significantly dysregulated lncRNAs and downstream targets in female offspring liver were identified using bioinformatics analysis. lncRNA, microRNA (miRNA or miR) and mRNA expression levels in liver and AML12 cells were assessed using reverse transcription-quantitative PCR. A total of 8 upregulated and 17 downregulated lncRNAs were demonstrated in offspring from obese dams and lncRNA Lockd was indicated to be a key dysregulated lncRNA. Competing endogenous RNA (ceRNA) models suggested that the lncRNA Lockd/miR-582-5p/Elovl5 pathway was key for lipid metabolism in the liver of offspring from obese dams. Finally, small interfering RNA and miRNA inhibitor transfection was used to evaluate the ceRNA models in AML12 cells. Taken together, the results of the present study indicated that lncRNA Lockd-miR-582-5p-Elovl5 network may be disrupted in lipid metabolism and lead to obesity in the offspring of obese dams. This research will provide new insights into the molecular mechanism of obesity and lipid metabolism disorder.

Comprehensive bioinformatics analysis of the E2F family in human clear cell renal cell carcinoma.

Clear cell renal cell carcinoma (ccRCC) originates from renal tubular epithelial cells and is the most common pathological renal cell carcinoma type with the worst prognosis. The relationship between the expression, prognosis and mechanism of ccRCC and the E2F family remains challenging. In the present study, RNA sequencing and clinical data of ccRCC from The Cancer Genome Atlas and two datasets, GSE36895 and GSE53757, from the Gene Expression Omnibus were used to identify the role of the E2F family in ccRCC. A total of 10 groups of tumor tissues and paired-normal tissues from patients with ccRCC were verified by reverse transcription-quantitative PCR. the expression, tumor grade and stage, prognosis and regulatory mechanism of the E2F family in ccRCC were analyzed. It was found that the expression levels of E2F1 to 4 and 6 to 8 were higher in ccRCC tissues than in normal tissues, whereas the expression level of E2F5 was lower in the former than in the latter. The expression levels of E2F1 to 8 were correlated with tumor stage and grade. Low expression of E2F1 to 5 and 7 to 8 was significantly associated with longer overall survival, disease-specific survival and progression-free survival times. The data revealed that the E2F family rarely has genetic mutations. The expression of E2F1, E2F2, E2F5, E2F7 and E2F8 was significantly correlated with DNA methylation, and E2F1 to E2F7 were significantly correlated with copy number and the data showed that the expression of E2Fs was significantly correlated with the cell cycle. The results of the present study suggested that E2F family genes may be potential targets for ccRCC molecular diagnosis and targeted therapy.

Age-dependent down-regulation of DNA polymerase δ1 in human lymphocytes.

Aging progress and degeneracy of functional activity are mainly attributed to the decreased DNA repair potential. DNA polymerase (pol) δ activity plays an essential role in genome stability by virtue of its crucial DNA replication and repair capacity. To order to clarify the role of DNA pol δ in aging progression, we firstly examined the expressions of its catalytic subunit named DNA pol δ1 in human lymphocytes at different age stages, respectively, and then observed the effect of diseases on DNA pol δ1 in vivo and of nutriture on its expressions in 2BS cells in vitro. Blood samples from the healthy subjects and patients with diabetes mellitus and coronary heart disease were collected, respectively, for analysis of transcription and protein expressions of DNA pol δ1 by RT-PCR and western blot. 2BS cells of PD30 and PD47 were incubated in both normal medium and other mediums of different nutritures for verifying the differential expressions of DNA pol δ1. Results showed that the mRNA expression of DNA pol δ1 decreased substantially with age and the protein levels were well consistent with gene levels. Furthermore, there were no significant differences in DNA pol δ1 expressions between the groups of healthy individuals and the age matched patients. In addition, DNA pol δ1 gene expression levels were not affected by nutritional status in vitro. Our findings collectively confirmed that the down-regulations of DNA pol δ1 are age-related and have little bearing on diseases and nutritures. DNA pol δ1 has great potential for a new biomarker of aging.

[Value of the electrocardiographic Cornell criteria for detecting left ventricular hypertrophy in elderly men].

OBJECTIVE: To explore the value of electrocardiographic (ECG) Cornell criteria for detecting left ventricular hypertrophy (LVH) in elderly Chinese men. METHODS: Since 1990, 244 autopsies were performed in our hospital in elderly men, LVH was determined in these autopsy hearts and correlated to ECG LVH signs recorded within 3 months before death according to Cornell (SV3+RaVL) and Sokolow-Lyon criteria (SV1+RV5 or RV6). The reference value of Cornell criteria was obtained based on values from autopsied healthy hearts, the sensitivity and specificity of Cornell and Sokolow-Lyon criteria for detecting left ventricular hypertrophy in these elderly men were calculated. RESULTS: There were significantly correlations between QRS amplitudes of Cornell and Sokolow-Lyon criteria and autopsy left ventricular wall thickness in these hearts. The reference value of Cornell criteria (SV3+RaVL) was 2.9 mV. The sensitivity of Sokolow-Lyon and Cornell criteria for detecting LVH was 25.4% and 34.3% (P<0.05 vs Sokolow-Lyon criteria), respectively. CONCLUSION: Voltage (SV3+RaVL)>or=2.9 mV might be a suitable diagnostic value for detecting left ventricular hypertrophy in Chinese elderly men.