Association between perfluoroalkyl and polyfluoroalkyl substances exposure and fetal overgrowth: A prospective birth cohort study conducted in China.

BACKGROUND: Prenatal exposure to perfluoroalkyl and polyfluoroalkyl substances (PFASs) has been associated with gestational diabetes mellitus, obesity or overweight in childhood, but data on fetal overgrowth outcomes including macrosomia and large for gestational age (LGA) and among gestational age diverse infants remain scarce. OBJECTIVE: To evaluate the association between maternal PFASs exposure and macrosomia and LGA, with exploration of the interaction between PFASs exposure and gestational age on fetal overgrowth. METHODS: A total of 1441 mother-infants pairs from Guangxi Zhuang Birth Cohort of China were analyzed. Nine PFASs were measured in maternal serum using ultra-high liquid performance chromatographytandem mass spectrometry. Multivaraible logistical regression and generalized additive models were performed for individual PFAS exposures, piecewise regression analysis was used to estimate the breakpoint values for the non-linear dose-response relationships. Bayesian Kernel Machine Regression was performed for PFASs mixture. RESULTS: In single pollutant models, maternal PFDA and PFOA exposure showed U-shaped relationship with macrosomia and LGA. When PFDA concentration exceeded 0.32 ng/mL was significantly positively associated with risks of LGA and macrosomia (OR=4.66, 95%CI: 1.26, 17.17; OR=14.43, 95%CI: 2.64, 79.02; respectively), while a negatively association was observed when level below 0.32 ng/mL. When PFOA concentration exceeded 1.20 ng/mL was significantly associated with increased risk of macrosomia (OR=7.75, 95%CI: 1.36, 44.06). In mixed exposure models, mixture of PFASs was positively associated with macrosomia, as well as associated with LGA when all the PFASs were at their 30th percentile or below. The maximum risk of LGA was reached when concentrations of PFUnA, PFDA, or PFBS were at the highest concentrations and the gestational age at the minimum of this study. CONCLUSIONS: Maternal exposure to PFDA, PFOA and PFASs mixture were non-monotonically associated with macrosomia and LGA, the direction of the associations depends on the level of exposure.

Effects of household environmental exposure and ventilation in association with adverse birth outcomes: A prospective cohort study in rural China.

Prenatal exposure to outdoor air pollution have been associated with birth outcomes. However, there is limited evidence on the adverse effects of household indoor air pollution worldwide, much less in rural areas of China. This study aimed to explore the associations of household environmental factors (primary cooking fuel, housing renovation, and home ventilation) with four adverse birth outcomes (preterm birth (PTB), small for gestational age (SGA), low birth weight (LBW), and term low birth weight (T-LBW)). We conducted a cohort study involving 10,324 pregnancies in women who delivered a live-born infant from 2015 to 2018 in Guangxi, China. Risk ratios and 95% confidence intervals (CI) were estimated with control for reproductive history, lifestyle, home environmental confounders, and other potential confounders. A total of 5.4% of the infants were PTB, 10.7% were SGA, 5.5% had LBW, and 3.0% had T-LBW. Household-use induction cookers as the primary cooking fuel during pregnancy was associated with SGA (RR = 1.31, 95% CI: 1.07-1.60), LBW (1.41, 1.09-1.82), and T-LBW(1.62, 1.16-2.26), as compared with household-use gas as the primary cooking fuel. Housing renovation within one year before pregnancy was associated with PTB (1.45, 1.06-1.98) and LBW (1.56, 1.17-2.09), while housing renovation during pregnancy was associated with a higher risk of SGA only in moderate home ventilation conditions (3.74, 1.69-8.28). Our findings suggested that household-use induction cookers as the primary cooking fuel increased the risks of SGA, LBW, and T-LBW. In addition, housing renovation within one year before pregnancy increased the risks of PTB and LBW. Proper home ventilation may reduce the effect on the association between housing renovation during pregnancy and SGA.

Prenatal exposure to bisphenols and risk of preterm birth: Findings from Guangxi Zhuang birth cohort in China.

Preterm birth (PTB), a serious adverse birth outcome, is the leading cause of perinatal mortality and morbidity. Bisphenols induce endocrine disruption that spreads across the placenta, which may affect fetal growth and development. However, the effects of bisphenols on PTB, particularly their combined effects, remain unknown. This study investigated the association between prenatal bisphenol exposure and PTB. Study participants were 2023 mother-infant pairs that were selected from the Guangxi Zhuang Birth Cohort. Maternal serum bisphenol levels were measured using ultrahigh performance liquid chromatography-tandem mass spectrometry, and pregnancy outcomes were obtained from medical records. Multivariate logistic regression, restricted cubic spline, principal component analysis (PCA), quantile g-computation (Qgcomp), and Bayesian kernel machine regression (BKMR) were used to examine the association between serum bisphenol levels and PTB. Ln-transformed BPA concentrations were associated with an increased risk of PTB only in female infants (OR = 1.30, 95% CI: 1.02, 1.64). Ln-transformed bisphenol F (BPF) concentrations were positively associated with the risk of PTB (OR = 1.73, 95% CI: 1.18, 2.55). Inverse U-shaped relationships were observed between bisphenol B (BPB), bisphenol S (BPS), and tetrabromobisphenol A (TBBPA) levels and the risk of PTB (P-overall < 0.05, P-non-linear < 0.05). After sex stratification, the association between BPA analogs and PTB was only observed in males. In Qgcomp analysis, bisphenol mixtures were related to an increased risk of PTB (OR = 1.52, 95% CI: 1.04, 2.21), with BPF (43.7%), BPS (29.6%) and BPA (26.8%) having the greatest positive contribution. Results indicate that prenatal exposure to bisphenol mixtures might increase the risk of PTB, which might be primarily driven by BPA, BPF and BPS. There may also be sex-specific and nonmonotonic dose-dependent effects.

Integrated profiling identifies ITGB3BP as prognostic biomarker for hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a highly malignant tumor. In this study, we sought to identify a novel biomarker for HCC by analyzing transcriptome and clinical data. The R software was used to analyze the differentially expressed genes (DEGs) in the datasets GSE74656 and GSE84598 downloaded from the Gene Expression Omnibus database, followed by a functional annotation. A total of 138 shared DEGs were screened from two datasets. They were mainly enriched in the "Metabolic pathways" pathway (Padj = 8.21E-08) and involved in the carboxylic acid metabolic process (Padj = 0.0004). The top 10 hub genes were found by protein-protein interaction analysis and were upregulated in HCC tissues compared to normal tissues in The Cancer Genome Atlas database. Survival analysis distinguished 8 hub genes CENPE, SPDL1, Hyaluronan-mediated motility receptor, Rac GTPase activating protein 1, Thyroid hormone receptor interactor 13, cytoskeleton-associated protein (CKAP) 2, CKAP5, and Integrin subunit beta 3 binding protein (ITGB3BP) were considered as prognostic hub genes. Multivariate cox regression analysis indicated that all the prognostic hub genes were independent prognostic factors for HCC. Furthermore, the receiver operating characteristic curve revealed that the 8-hub genes model had better prediction performance for overall survival compared to the T stage (p = 0.008) and significantly improved the prediction value of the T stage (p = 0.002). The Human Protein Atlas showed that the protein expression of ITGB3BP was upregulated in HCC, so the expression of ITGB3BP was further verified in our cohort. The results showed that ITGB3BP was upregulated in HCC tissues and was significantly associated with lymph node metastasis.

Maternal overweight but not paternal overweight before pregnancy is associated with shorter newborn telomere length: evidence from Guangxi Zhuang birth cohort in China.

BACKGROUND: Telomere length (TL) is variable at birth and is inversely associated with body mass index (BMI) in adulthood. A growing number of evidences suggested that a higher maternal pre-pregnancy BMI results in adverse offspring health outcomes, especially shorter newborn TL. However, a newborn's genetic endowment is equally derived from both parents, the association between parental pre-pregnancy BMI and newborn TL has been rarely discussed. We aimed to determine the association between parental pre-pregnancy BMI and newborn TL. METHODS: A total of 1082 parent-newborn pairs were recruited from the Guangxi Zhuang Birth Cohort (GZBC). TL in cord blood was measured using quantitative real-time polymerase chain reaction (qPCR) and expressed as the ratio of telomere copy number to single-copy gene number (T/S). A series of linear regressions were performed to assess the associations between parental pre-pregnancy BMI and newborn TL. RESULTS: Mothers who were overweight before pregnancy had significantly shorter cord blood telomere length in their newborns than those who were normal weight before pregnancy [percentage change: - 7.96% (95% CI: - 14.49 to - 0.69%; P = 0.032)]. Further analysis of the combined effects of parental weight status on newborn TL showed that TL was significantly shortened among newborns whose mothers were overweight and fathers were of healthy weight when compared with those whose mothers and fathers were both of normal weight [percentage change: - 8.38% (95% CI: - 15.47 to - 0.92%; P = 0.028)]. Subgroup analysis indicated these effects were more pronounced among male newborns and those whose paternal age < 31 years or maternal age ≥ 28 years at delivery. CONCLUSIONS: Maternal pre-pregnancy overweight, but not paternal pre-pregnancy overweight is associated with shorter newborn TL. Weight control in reproductive women and effective healthy weight management before pregnancy may be of particular benefit for improving longevity and life quality of offspring.

LINC02499, a novel liver-specific long non-coding RNA with potential diagnostic and prognostic value, inhibits hepatocellular carcinoma cell proliferation, migration, and invasion.

AIM: Liver-specific non-coding RNAs have been reported to play crucial roles in hepatocellular carcinoma (HCC). We investigated the possible biological performance of a novel liver-specific long non-coding RNA, LINC02499, in HCC. METHODS: The association between LINC02499 expression and HCC was evaluated based on The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases, and then confirmed in a HCC cohort by quantitative real-time polymerase chain reaction. The effects of LINC02499 on HCC cells were verified by gain- and loss-of-function assays. Pathway enrichment analyses were used to explore the potential mechanism of LINC02499 in HCC. RESULTS: LINC02499 expression was remarkably decreased in HCC tissues compared to adjacent non-tumor tissues based on TCGA (P < 0.001) and GEO databases (P < 0.001) and our HCC cohort (P < 0.001). Decreased LINC02499 was also significantly associated with poorer overall survival in both the TCGA database (P = 0.009) and our HCC cohort (P = 0.002). Furthermore, the receiver operating characteristic analysis indicated that LINC02499 showed a good performance in HCC diagnosis (area under the curve = 0.879, P < 0.001), and both sensitivity and specificity were 83.8%. In addition, up- and downregulated LINC02499 significantly impacted proliferation, migration, and invasion abilities of HCC cells in vitro. Pathway enrichment analyses revealed that the potential target genes of LINC02499 were involved in "Complement and coagulation cascades" and "Butanoate metabolism" pathways. CONCLUSION: LINC02499 could be a potential novel diagnostic and prognostic biomarker for HCC patients, and it could exert a tumor suppressor role in the progression of HCC.