Hexavalent chromium [Cr(IV)], a well-known industrial waste product and an environmental pollutant, is recognized as a human carcinogen. But its mechanisms of carcinogenicity remain unclear, and recent studies suggest that DNA methylation may play an important role in the carcinogenesis of Cr(IV). The aim of our study was to investigate the effects of Cr(IV) on cell cycle progress, global DNA methylation, and DNA methylation of p16 gene. A human B lymphoblastoid cell line and a human lung cell line A549 were exposed to 5–15 µM potassium dichromate or 1.25–5 µg/cm² lead chromate for 2–24 hours. Cell cycle was arrested at G₁ phase by both compounds in 24 hours exposure group, but global hypomethylation occurred earlier than cell cycle arrest, and the hypomethylation status maintained for more than 20 hours. The mRNA expression of p16 was significantly up-regulated by Cr(IV), especially by potassium dichromate, and the mRNA expression of cyclin-dependent kinases (CDK4 and CDK6) was significantly down-regulated. But protein expression analysis showed very little change of p16 gene. Both qualitative and quantitative results showed that DNA methylation status of p16 remained unchanged. Collectively, our data suggested that global hypomethylation was possibly responsible for Cr(IV) - induced G₁ phase arrest,but DNA methylation might not be related to up-regulation of p16 gene by Cr(IV).

The diagnostic value of the concentration of circulating cell-free DNA (cfDNA) for breast cancer has generated inconsistent results. The aim of this study was to evaluate the first diagnostic value of the concentration of cfDNA for breast cancer by meta-analysis. Studies were retrieved by searching PubMed, Cochrane Library, and Web of Science before June 2018. Sensitivity, specificity, diagnostic odds ratio (DOR), the summary receiver operating characteristic (SROC) curve, and the area under curve (AUC) were used to summarize overall diagnostic performance. The random-effects model was used to calculate the pooled statistics. Subgroup analysis and meta-regression analysis were carried out to detect the source of heterogeneity. A total of 13 studies were identified with 1,087 breast cancer patients and 720 healthy controls. Overall, the pooled sensitivity and specificity of concentration of cfDNA for breast cancer were 87% (95% CI, 73–94%) and 87% (95% CI, 79–93%), respectively. The pooled DOR was 32.93 (95% CI, 13.52–80.19) and the SROC curve revealed an AUC of 0.93 (95% CI, 0.91–0.95). Meta-regression analysis showed that no covariate had a significant correlation with relative DOR (RDOR). Publication bias was not detected in this meta-analysis. This meta-analysis indicates that the concentration of cfDNA has potential first diagnostic value for breast cancer and plasma may be a better source of cfDNA for detection of breast cancer.

High-mobility group box 1 (HMGB1) functions as a proinflammatory cytokine and is one of the most intriguing molecules in inflammatory disorders and cancers. Notably, HMGB1 is a potential therapeutic target and novel biomarker in related diseases. However, the diagnostic value of HMGB1 for benign and malignant asbestos-related diseases (ARDs) remains unclear. In this work, we detected preoperative serum HMGB1 levels in Chinese asbestos-exposed (AE) and ARDs populations and further evaluated the diagnostic value of HMGB1 in patients with certain types of ARDs, including those with pleural plaques, asbestosis, or malignant mesothelioma (MM). The experimental data presented that the serum level of HMGB1 was significantly elevated in AE and ARDs subjects. Our findings indicated that serum HMGB1 is a sensitive and specific biomarker for discriminating asbestosis- and MM-affected individuals from healthy or AE individuals. In addition, serum matrix metalloproteinases 2 and 9 are not correlated with HMGB1 in ARDs. Thus, our study provides supporting evidence for HMGB1 as a potential biomarker either for the clinical diagnosis of high-risk AE cohorts or for evaluating ARDs.

The presence of perfluoroalkyl acids (PFAAs) and chlorinated polyfluoroalkyl ether sulfonates (Cl-PFAESs) in humans has attracted great attention in recent decades. However, information on their exposure sources and the influence of age and gender on Cl-PFAES concentrations in human serum is still limited. In this study, eighty-five serum samples were collected from the general population in Anji, China, and analyzed for perfluoroalkyl carboxylates (PFCAs), perfluoroalkyl sulfonates (PFSAs), and Cl-PFAESs. Perfluorooctane sulfonate (PFOS; mean, 5.9 ng/mL) and perfluorooctanoate (PFOA; 3.3 ng/mL) were the predominant PFAAs in human serum. The serum concentrations of C8-C12 PFCAs, perfluorohexane sulfonate, and PFOS were significantly (rs = 0.40-0.98, p < 0.01) correlated with one another. In human serum, the mean percentages of branched isomers for PFOA, perfluorohexane sulfonate, and PFOS were 97.3%, 92.6%, and 66%, respectively. These results suggest that the major source of PFCAs and PFSAs in human serum was direct exposure. The mean 6:2Cl-PFAES (6.0 ng/mL) serum concentration was higher than PFOA (p < 0.01). The mean 6:2Cl-PFAES concentrations in male and female serum were 6.5 ng/mL and 5.6 ng/mL, respectively. A significant increase in 6:2Cl-PFAES concentrations with age was found in males (rs = 0.50, p = 0.001). The 6:2Cl-PFAES concentration was positively correlated with C8-C12 PFCAs and PFOS in human serum (rs = 0.44-0.91, p < 0.01), indicating that they may have common exposure sources. Overall, this study first investigated the roles of age and gender on human serum concentrations of Cl-PFAESs and provided baseline information on the occurrence of Cl-PFAESs in the general Chinese population.