SUMO1-modified DNA methyltransferase 1 induces DNA hypermethylation of VWC2 in the development of colorectal cancer.

Aberrant DNA methylation of genes is closely linked to many aspects of tumor development. This study focuses on the effect of DNA hypermethylation of von Willebrand factor C domain containing 2 (VWC2) on colorectal cancer (CRC) progression and the underpinning mechanism. According to data in the bioinformatic systems, VWC2 had the highest degree of DNA methylation in colonic adenocarcinoma, and it showed DNA hypermethylation in rectal adenocarcinoma as well. CRC and the para-tumorous tissues were collected from 86 patients. VWC2 was expressed at low levels in CRC samples and inversely correlated with tumor stage and tumor biomarker expression. DNA hypermethylation and reduced expression of VWC2 were also detected in CRC cell lines HCT-116 and HT29. VWC2 overexpression suppressed the malignant growth of cells in vitro and in vivo. Co-immunoprecipitation and western blot assays showed that small ubiquitin-like modifier 1 (SUMO1) mediated SUMOylation of DNA methyltransferase 1 (DNMT1) and strengthened its protein stability, which promoted DNA methylation and suppression of the VWC2 gene. In summary, this study demonstrates that SUMO1-mediated activation of DNMT1 induces DNA methylation and downregulation of VWC2 in CRC to augment cancer development.

Association Between Exposure to Per- and Polyfluoroalkyl Substances and Birth Outcomes: A Systematic Review and Meta-Analysis.

Background: A large body of emerging evidence suggests that per- and polyfluoroalkyl substances (PFAS) affect birth outcomes in various pathways, but the evidence is inconsistent. Therefore, this study aimed to systematically review the epidemiological evidence on PFAS exposure and birth outcomes. Methods: Three electronic databases were searched for epidemiological studies through February 13, 2021. We used random-effects meta-analysis for eight birth outcome indicators to calculate summary effect estimates for various exposure types. The risk of bias and the overall quality and level of evidence for each exposure-outcome pair were assessed. Results: The initial search identified 58 potentially eligible studies, of which 46 were ultimately included. Many PFAS were found to have previously unrecognized statistically significant associations with birth outcomes. Specifically, birth weight (BW) was associated with PFAS, with effect sizes ranging from -181.209 g (95% confidence interval (CI) = -360.620 to -1.798) per 1 ng/ml increase in perfluoroheptanesulfonate (PFHpS) to -24.252 g (95% CI = -38.574 to -9.930) per 1 ln (ng/ml) increase in perfluorodecaoic acid (PFDA). Similar patterns were observed between other PFAS and birth outcomes: perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) with birth length (BL) and ponderal index (PI), PFOS and perfluorododecanoic acid (PFDoDA) with head circumference (HC), PFHpS with gestational age (GA), and perfluorononanoic acid (PFNA) and PFHpS with preterm birth (PTB). Additionally, PFDA showed a statistically significant association with small for gestational age (SGA). The level of the combined evidence for each exposure-outcome pair was considered to be "moderate". Conclusion: This study showed that PFAS exposure was significantly associated with increased risks of various adverse birth outcomes and that different birth outcome indicators had different degrees of sensitivity to PFAS. Further studies are needed to confirm our results by expanding the sample size, clarifying the effects of different types or doses of PFAS and the time of blood collection on birth outcomes, and fully considering the possible confounders.

Traffic noise and adiposity: a systematic review and meta-analysis of epidemiological studies.

Traffic noise has attracted much attention as a significant and intractable public health threat. This study was designed as a systematical review to explore the association of traffic noise with different indicators of obesity, thus providing updated quantitative estimates for the pooled effect estimates of the existing literature. We conducted an extensive search for epidemiological studies that investigated the association of traffic noise with obesity in three electronic databases till February 23, 2021. We used random-effects meta-analysis to calculate the summary effect estimates for each 10-dB(A) increase in noise and compared the highest with the lowest category of noise in relation to seven obesity indicators. Meanwhile, we assessed the risk of bias and the overall quality of the evidence of each study as well as the level of evidence for each exposure-outcome pair. The initial search identified 30 studies, 13 of which were ultimately included. The meta-analysis for the highest versus the lowest category of noise exposure was generally associated with higher waist circumfluence (WC) ranging from 0.326 cm (95% confidence interval (CI) = 0.078, 0.574) to 0.705 cm (95% CI = 0.071, 1.340) and higher odds of central obesity ranging from 1.055 (95% CI = 1.000, 1.109) to 1.167 (95% CI = 1.037, 1.298). When the continuous exposure (each 10 dB(A) increase in noise) was introduced, similar results were found. This study indicated positive associations of traffic noise with WC and central obesity. However, in consideration of some limitations, there is an urgent need for future studies to increase the sample size, discriminate the etiological differences in different noise and obesity indicators, and thoroughly consider socioeconomic status.