Transcriptomics analysis and benchmark concentration estimating-based in vitro test with IOSE80 cells to unveil the mode of action for female reproductive toxicity of bisphenol A at human-relevant levels.

Bisphenol A (BPA) is of great concern in public health, of which female reproductive toxicity is one major adverse health effect with the unclear mode of action (MOA) yet. Based on the principle of Toxicity Testing in the 21st Century, the purpose of this study is to explore the MOA for female reproductive toxicity using human normal ovarian epithelial cells IOSE80 at 28-day human-relevant-level exposure. A physiological based pharmacokinetic model was used to select the administration concentrations according to the BPA levels in female gonads at human actual exposure scenario. Enrichment KEGG pathways interrupted by BPA consisted of RNA transport, ribosome biogenesis in eukaryotes, cell cycle, cellular senescence, progesterone-mediated oocyte maturation, and oocyte meiosis. Increased relative mRNA and protein expressions of ERK and CDKN3, and proportion of S phase, as well as decreased proportion of G0/G1 phase were observed with increasing BPA concentrations, which could be partially inhibited by ERK inhibitor U0126. Among all the benchmark concentration lower confidence limits, mRNA expression of MAPK3 served as the lowest. In conclusion, the MOA of BPA induced female reproductive toxicity at human-relevant levels may include: key event (KE)1-ERK activation, KE2-increased expression of CDKN3, and KE3-cell cycle arrest. However, more in vivo studies may be needed to complete the MOA.

Total and Sn-2 Fatty Acid Profile in Human Colostrum and Mature Breast Milk of Women Living in Inland and Coastal Areas of China.

INTRODUCTION: Although lipid is the major energy source and exerts beneficial effects on infant growth, research on the composition of fatty acid (FA) at the sn-2 position of human milk (HM) in China and abroad is limited. OBJECTIVES: This study aimed to investigate the FA positional distribution in colostrum and mature HM of women living in the inland and coastal areas of China and explore the potential influences of geographical region and lactation stage on the FA profile of Chinese women. METHODS: Colostrum milk (n = 61) and mature milk (n = 56) samples were obtained longitudinally from healthy lactating women in Guangzhou and Chengdu, China. Gas chromatography was used to determine the total and sn-2 FA composition. RESULTS: Significant differences were observed in the FA profile of HM between different regions and lactation stages, with differences in polyunsaturated FA levels being the most pronounced. Nearly 70% of sn-2 FAs were saturated FAs, of which C16:0 accounted for approximately 75%. C8:0, C10:0, C18:0, C20:0, C22:0, and all of the unsaturated FAs were mainly located at the sn-1 and sn-3 positions, while C14:0, C15:0, and C16:0 were mainly at the sn-2 position. The proportion of C12:0 and C17:0 at sn-2 was approximately equivalent to that at the sn-1, 3 positions. CONCLUSIONS: The results indicate the variability in the FA profile of HM between regions and lactation stages. The contents of polyunsaturated FAs and sn-2 FAs, especially palmitic acid, should be paid more attention when optimizing infant formula.

Bibliometric Analysis of the Toxicity of Bisphenol A.

Bisphenol A (BPA) is used worldwide and research on the toxicity of BPA has advanced rapidly in the last few decades. This study aimed to evaluate the global scientific output of toxicity of BPA and explore the hot spots and research trends. All available articles related to the toxicity of BPA until 2022 were retrieved from the Web of Science Core Collection database. The VOSviewer, a bibliometric analysis software, was used to analyze the information of included articles, including countries/institutions, international cooperation, journals, citations, and keywords. Among 1644 retrieved articles, 1611 eligible studies were identified for analysis, and the annual publications increased with time in the past three decades. China and the United States were the most active contributors in this field. Chinese Academy of Sciences and the Dow chemical company conducted relatively more research than others about BPA toxicity. The journal "Chemosphere" published the most studies on "BPA toxicity". Before 2015, most research focused on estrogenic activity and the test system mainly utilized animal experiments. However, in recent years, research related to toxic mechanisms of BPA at the cellular level and the toxicity of its analogs have received widespread attention. Considering some critical research gaps, future research on BPA toxicology should probably focus on the molecular biology of toxic mechanism, mixture toxicity, and co-exposure of BPA substitutes. This study will help researchers understand past and current research trends, hot spots, and trends of toxicity studies of BPA and, thus, contribute to further research and risk management of BPA.

The level and efficacy of lutein in patients with age-related macular degeneration: a comprehensive systematic review and meta-analysis.

Background: Lutein has been linked with various visual performance disorders, including age-related macular degeneration (AMD). However, previous studies evaluating the association between serum lutein and the risk of AMD showed results, and the efficacy of lutein intake in AMD patients remains unclear. Methods: To comprehensively estimate the relationship between lutein and AMD, a systematic review and meta-analysis was conducted by searching eligible randomized clinical trials (RCT) and case-control studies to study the association between lutein and AMD on the Cochrane Library, MEDLINE, Elsevier, PubMed, Web of Knowledge, Chinese National Knowledge Infrastructure (CNKI), and Chinese Biomedical Database (CBM) databases until April 2020. The weighted mean difference (WMD) with 95% confidence interval (95% CI) was adopted as the primary effect estimate. Meta-analysis was conducted using STATA 12.0. Results: Nine studies with 855 participants were included in this meta-analysis. The NOS scoring of five case-control studies ranged 5-9. For RCTs, two studies were rated with a low risk of bias, one study with a moderate risk of bias and one with a high risk of bias. The results increased significantly in macular pigment optical density (MPOD) (WMD =0.069; 95% CI: 0.040-0.098, P=0.000) among AMD patients taking lutein supplementation, while there was no difference in circulating lutein levels between AMD patients and controls (WMD =0.00; 95% CI: -0.01 to 0.00, P=0.310). Subgroup analysis suggested that the dose and duration of supplementation could significantly influence the MPOD level in AMD patients. In particular, we observed a larger increase in MPOD of AMD patients using a higher dose (20 mg/d) and longer treatment (>6 months). Conclusions: Although current evidence does not support circulating lutein as a biomarker for early screening of the high-risk AMD population, this study is the first meta-analysis to explore the relationship between lutein in blood and AMD patients. Given that lutein has a high safety profile as indicated by many studies, it is reasonable to give the current analysis result that high dose (20 mg/d) and long duration (>6 months) of lutein intake could be beneficial to AMD patients.

Profiles of total and sn-2 fatty acid of human mature milk and their correlated factors: A cross-sectional study in China.

Fatty acid (FA) in breast milk is beneficial to the growth and neurodevelopment of infants. However, the structure profiles of breast milk FAs and the influencing factors which are crucial for normal function have not been fully elucidated. This study aimed to characterize the profiles of total and sn-2 FAs in human mature milk based on two representative urban areas in China and explore potential sociodemographic determinants. Mothers (n = 70) at 40-100 d postpartum from Beijing and Danyang were recruited according to unified inclusion and exclusion criteria. Total and sn-2 FA compositions were examined by gas chromatography and quantified. Using the Spearman correlation and multiple regression model, we found that the location and maternal education level were the most conspicuous correlated factor. The milk of mothers from Beijing had higher levels of the n-6 series of long-chain polyunsaturated fatty acids (LCPUFA) (C20:2, C20:3n-6, C20:4n-6, n-6PUFA/n-3PUFA, LA/ALA, and ARA/DHA) than that of Danyang, while the opposite was observed in the n-3 series of LCPUFA (C18:3n-3 and Total n-3PUFA). Compared to the milk of mothers with a high school degree or below, those with a bachelor's degree or above had lower SFAs (C10:0, C12:0, C14:0, and Total SFA), n-3 series of LCPUFA (C18:3n-3 and Total n-3PUFA), C18:1n-9t, and higher n-6 series of LCPUFA (C18:2n-6c, C20:2, C20:4n-6, Total n-6PUFA, and n-6PUFA/n-3PUFA). Maternal age, infant gender, pre-conception body mass index (BMI), parity, delivery mode, and gestational weight gain were also associated with total FAs. However, fewer associations were found between the above factors and sn-2 FAs. This study will promote an understanding of human breast milk's lipid profile and help develop a formula more suitable for infants.

Bioinformatics analysis and quantitative weight of evidence assessment to map the potential mode of actions of bisphenol A.

Bisphenol A (BPA) is a classical chemical contaminant in food, and the mode of action (MOA) of BPA remains unclear, constraining the progress of risk assessment. This study aims to assess the potential MOAs of BPA regarding reproductive/developmental toxicity, neurological toxicity, and proliferative effects on the mammary gland and the prostate potentially related to carcinogenesis by using the Comparative Toxicogenomics Database (CTD)-based bioinformatics analysis and the quantitative weight of evidence (QWOE) approach on the basis of the principles of Toxicity Testing in the 21st Century. The CTD-based bioinformatics analysis results showed that estrogen receptor 1, estrogen receptor 2, mitogen-activated protein kinase (MAPK) 1, MAPK3, BCL2 apoptosis regulator, caspase 3, BAX, androgen receptor, and AKT serine/threonine kinase 1 could be the common target genes, and the apoptotic process, cell proliferation, testosterone biosynthetic process, and estrogen biosynthetic process might be the shared phenotypes for different target organs. In addition, the KEGG pathways of the BPA-induced action might involve the estrogen signaling pathway and pathways in cancer. After the QWOE evaluation, two potential estrogen receptor-related MOAs of BPA-induced testis dysfunction and learning-memory deficit were proposed. However, the confidence and the human relevance of the two MOAs were moderate, prompting studies to improve the MOA-based risk assessment of BPA.

Effects of Malania oleifera Chun Oil on the Improvement of Learning and Memory Function in Mice.

BACKGROUND: The fruits of Malania oleifera Chun & S. K. Lee have been highly sought after medically because its seeds have high oil content (>60%), especially the highest known proportion of nervonic acid (>55%). Objective of the Study. The objective was to explore the effects of different doses of Malania oleifera Chun oil (MOC oil) on the learning and memory of mice and to evaluate whether additional DHA algae oil and vitamin E could help MOC oil improve learning and memory and its possible mechanisms. METHODS: After 30 days of oral administration of the relevant agents to mice, behavioral tests were conducted as well as detection of oxidative stress parameters (superoxide dismutase, malondialdehyde, and glutathione peroxidase) and biochemical indicators (acetylcholine, acetyl cholinesterase, and choline acetyltransferase) in the hippocampus. RESULTS: Experimental results demonstrated that MOC oil treatment could markedly improve learning and memory of mouse models in behavioral experiments and increase the activity of GSH-PX in hippocampus and reduce the content of MDA, especially the dose of 46.27 mg/kg. The addition of DHA and VE could better assist MOC oil to improve the learning and memory, and its mechanism may be related to the inhibition of oxidative stress and restrain the activity of AChE and also increase the content of ACh. CONCLUSION: Our results demonstrated that MOC oil treatment could improve learning and memory impairments. Therefore, we suggest that MOC oil is a potentially important resource for the development of nervonic acid products.

Copper in depressive disorder: A systematic review and meta-analysis of observational studies.

Copper (Cu) has been associated with mental disorders such as autism and epilepsy. So far, publications evaluating copper levels in patients with depressive disorder showed conflicted results. To derive a comprehensive estimation of the relationship between body burden of copper and depressive disorder and explore the possible role of copper in mental health, we performed a systematic review and meta-analysis. Relevant published data were obtained by searching PubMed, Web of Science, Chinese National Knowledge Infrastructure (CNKI) and Chinese Biomedical Database (CBM) before October 10, 2017. Weighted mean difference (WMD) with a 95% confidence interval (95%CI) was calculated using STATA 12.0. A total of 21 studies with 1487 patients and 943 controls were collected in this meta-analysis. Pooled analysis found that patients with depression had higher blood levels of copper than the controls without depression, while there was no difference of copper content in hair between the two groups. Subgroup analysis suggested that age had influence on the relationship between copper and depression. No evidence of publication bias was observed. This meta-analysis suggests that increased levels of blood copper might be associated with depressive disorder and therefore the possible role of copper as a biomarker of depression.