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The identification of novel age‐related biomarkers represents an area of intense research interest. Despite multiple studies associating DNA damage with aging, there is a glaring paucity of DNA damage‐based biomarkers of age, mainly due to the lack of precise methods for genome‐wide surveys of different types of DNA damage. Recently, we developed two techniques for genome‐wide mapping of the most prevalent types of DNA damage, single‐strand breaks and abasic sites, with nucleotide‐level resolution. Herein, we explored the potential of genomic patterns of DNA damage identified by these methods as a source of novel age‐related biomarkers using mice as a model system. Strikingly, we found that models based on genomic patterns of either DNA lesion could accurately predict age with higher precision than the commonly used transcriptome analysis. Interestingly, the informative patterns were limited to relatively few genes and the DNA damage levels were positively or negatively correlated with age. These findings show that previously unexplored high‐resolution genomic patterns of DNA damage contain useful information that can contribute significantly to both practical applications and basic science. [ABSTRACT FROM AUTHOR]

We aimed to investigate the potential predictive efficacy of triglyceride–glucose (T/Gly) index for gestational diabetes mellitus (GDM) in a systematic review and meta-analysis. Cohort studies demonstrating the association between T/Gly index measured at the first trimester or before pregnancy and the subsequent incidence of GDM were identified by search of PubMed, Embase, China National Knowledge Infrastructure, and WanFang databases. A random-effect model incorporating the heterogeneity was applied to pool the results. Five cohort studies including 382,213 women were included in this meta-analysis. Compared to those with the lowest category of T/Gly index, women with the highest category of T/Gly index were independently associated with higher risk of subsequent GDM (odds ratio [OR]: 2.52, 95% confidence interval [CI]: 1.33 ∼ 4.67, I2=65%, p=.004) after adjustment of potential confounding factors including age, body mass index, and family history of diabetes. The association was stronger in prospective cohort studies than retrospective cohort studies (p for subgroup difference=.007), and a significant association was detected in Asian women (OR: 3.30, 95% CI: 1.50–7.28, p =.003), but not in non-Asian women (OR: 0.96, 95% CI: 0.35–2.63, p=.94). Higher T/Gly index may independently predict the risk of GDM in Asian women. [ABSTRACT FROM AUTHOR]

microRNAs (miRNAs) are non-coding RNA transcripts thought to be instrumental in controlling eukaryotic cell function. This study aimed to identify miRNAs associated with the differential expression of estrogen receptor α (ERα) and progesterone receptor (PR) in uterine endometrial cancer. First, the pathology of Ishikawa and KLE cell lines was identified by transplant and biopsy. Expression levels of ERα and PR and their response to estrogen and progesterone were examined, and total RNA was isolated to identify differentially expressed miRNAs by microarray analysis. miRNAs targeting ESR1 and PGR were predicted by miRANDA and TargetScan software, and their expression levels in cell lines and in patient samples were validated by real-time RT-PCR. Ishikawa and KLE represent estrogen-dependent and estrogen-independent endometrial cancers, respectively. As identified by miRNA microarray, 126 miRNAs were differentially expressed between the two cell lines; hsa-miR-100 and hsa-miR-99a were predicted to target ESR1, and hsa-miR-378 and hsa-miR-768-3p to target PGR. The differential expression of these miRNAs between Ishikawa and KLE was consistent in vivo and in vitro. Hsa-miR-100 was significantly down-regulated in the estrogen-dependent endometrial cancer samples as compared to the estrogen-independent samples and thus has the potential to target ESR1.

Transcatheter arterial chemotherapy (TAC) and transarterial chemoembolization (TACE) have greatly benefited patients suffering from gynecologic malignancies. In cervical cancer treatment, TACE appears to be more effective than TAC. We compared the pharmacokinetics of TACE with those of TAC in an animal study. Twelve female dogs were randomly divided into 2 groups (n=6), and carboplatin was applied at a concentration of 1.2 mg/kg. Carboplatin and lipiodol-carboplatin were administered by perfusion into the bilateral internal iliac arteries of the animals in the two groups, respectively. Plasma and tissues from the ovaries and uterus were collected for analysis at various time points after TAC or TACE. Pharmacokinetic analysis indicated that the uterine tissue area under the concentration (AUC) of carboplatin was approximately 2 times higher in the TACE group than in the TAC group (P<0.01). By contrast, the ovarian tissue AUC of carboplatin was much lower in the TACE group than in the TAC group (P<0.01), and was much lower than the uterine tissue AUC (P<0.01) in both groups. The plasma AUC of carboplatin was more than 2 times higher in the TACE group than in the TAC group (P<0.01). In conclusion, a pharmacological advantage of TACE treatment with lipiodol-carboplatin for gynecologic malignancies was observed.