The association between plasma IgG N-glycosylation and neonatal hypoxic-ischemic encephalopathy: a case-control study.

Introduction: Hypoxic-ischemic encephalopathy (HIE) is one of severe neonatal brain injuries, resulting from inflammation and the immune response after perinatal hypoxia and ischemia. IgG N-glycosylation plays a crucial role in various inflammatory diseases through mediating the balance between anti-inflammatory and pro-inflammatory responses. This study aimed to explore the effect of IgG N-glycosylation on the development of HIE. Methods: This case-control study included 53 HIE patients and 57 control neonates. An ultrahigh-performance liquid chromatography (UPLC) method was used to determine the features of the plasma IgG N-glycans, by which 24 initial glycan peaks (GPs) were quantified. Multivariate logistic regression was used to examine the association between initial glycans and HIE, by which the significant parameters were used to develop a diagnostic model. Though receiver operating characteristic (ROC) curves, area under the curve (AUC) and 95% confidence interval (CI) were calculated to assess the performance of the diagnostic model. Results: There were significant differences in 11 initial glycans between the patient and control groups. The levels of fucosylated and galactosylated glycans were significantly lower in HIE patients than in control individuals, while sialylated glycans were higher in HIE patients (p < 0.05). A prediction model was developed using three initial IgG N-glycans and fetal distress, low birth weight, and globulin. The ROC analysis showed that this model was able to discriminate between HIE patients and healthy individuals [AUC = 0.798, 95% CI: (0.716-0.880)]. Discussion: IgG N-glycosylation may play a role in the pathogenesis of HIE. Plasma IgG N-glycans are potential noninvasive biomarkers for screening individuals at high risk of HIE.

Legacy and novel brominated flame retardants in animal-derived foods from China Total Diet Study (CTDS): Temporal trends, evidence of substitution, and dietary exposure assessment.

Based on the 6th China Total Diet Study (CTDS) conducted in 2016-2019, the occurrence of both legacy and novel brominated flame retardants (BFRs) was measured in animal-derived foods collected across China. Most BFRs could be frequently detected in food samples, indicating their ubiquity in the environment. Decabromodiphenyl ethane (DBDPE), a typical novel BFR, presented the highest contamination level, whereas legacy BFRs, including decabrominated diphenyl ether (BDE-209), tetrabromobisphenol A (TBBPA), and hexabromocyclododecane (HBCDD), still presented high detection frequencies and relatively abundant proportions in total BFRs. Compared with previous CTDSs conducted from 2007 to 2011, the levels and estimated dietary intakes (EDIs) of most BFRs showed a significant downtrend, which suggested that flame retardant consumption in China has transferred from legacy BFRs to novel BFRs (mainly DBDPE) and from BFRs to other kinds of flame retardants. Based on probabilistic estimation, the median EDIs of mainly used BFRs for the Chinese population ranged from 41.0 to 1.67 × 103 pg/kg bw/day, and meat consumption was the primary source in dietary BFR intake. By conducting the margin of exposure (MOE) approach or comparing with the reference dose (RfD), it can be concluded that daily dietary intakes of BFRs were still unable to cause significant health risks to the general population in China.

Legacy brominated flame retardants in human milk from the general population in Beijing, China: Biomonitoring, temporal trends from 2011 to 2018, and nursing infant's exposure assessment.

Three kinds of legacy brominated flame retardants (BFRs), including eight polybrominated diphenyl ether (PBDE) congeners, tetrabromobisphenol A (TBBPA), and three hexabromocyclododecane (HBCDD) isomers, were analyzed in 105 human milk samples collected in 2018 from Beijing, China. The tested BFRs all showed high detection frequencies, and HBCDD was the most abundant BFR, with a median level of 7.64 × 103 pg/g lipid, followed by BDE-153 (389 pg/g lipid), BDE-209 (283 pg/g lipid), and TBBPA (271 pg/g lipid). By comparing the results of the present study with those of our previous Beijing human milk surveys conducted in 2014 and 2011, the contamination of TBBPA and HBCDD increased steadily from 2011 to 2018, whereas that of PBDEs decreased sharply during this period. Our results suggested that the production and consumption of BFRs in China have shifted from PBDEs to other FRs. Education level and the consumption of animal-derived foods such as eggs and meat were identified as major influencing factors for some BFRs. For nursing infants, the median levels of lower bound BFR daily intake via human milk ingestion ranged from 4.62 × 10-2 ng/kg bw/day for BDE-154 to 30.6 ng/kg bw/day for HBCDD. The daily intake of most BFRs by breastfeeding is unlikely to pose significant health risks for Beijing nursing infants. However, the minimum margin of exposure (MOE) of HBCDD was below its threshold value, which indicated that its daily intake might raise health concerns for some breastfed infants.

Organophosphorus flame retardants in breast milk from Beijing, China: Occurrence, nursing infant's exposure and risk assessment.

Organophosphorus flame retardants (OPFRs) are widely used chemicals, whereas data on OPFRs in human being is limited. In this study, thirteen OPFRs were measured in 105 breast milk samples collected from Beijing mothers in 2018. The ∑13OPFRs ranged from

Serum levels of novel brominated flame retardants (NBFRs) in residents of a major BFR-producing region: Occurrence, impact factors and the relationship to thyroid and liver function.

Five currently used novel brominated flame retardants (NBFRs) were determined in 172 serum samples collected from nonoccupational residents of a major BFR-producing region. All the 5 NBFRs presented high detection frequencies (DFs, >90%), and decabromodiphenyl ethane (DBDPE), a substitute of decabrominated diphenyl ethers (deca-BDE), was the most abundant NBFR. The levels of DBDPE were from

Polybrominated diphenyl ethers in serum from residents living in a brominated flame retardant production area: Occurrence, influencing factors, and relationships with thyroid and liver function.

Polybrominated diphenyl ethers (PBDEs) have been used as flame retardants (FRs) in China for decades, even after they were identified as persistent organic pollutants. In this study, serum samples were collected from 172 adults without occupational exposure who were residents of a well-known FR production region (Laizhou Bay, north China), and PBDE congeners were measured to assess their occurrence, congener profile and influencing factors in serum. Moreover, the relationships between serum concentrations of PBDEs and thyroid/liver function indicators were analyzed to evaluate whether human exposure to PBDEs would lead to thyroid/liver injury. All 8 PBDE congeners were detected at higher frequencies and serum concentrations than those found in general populations. The median levels of ∑PBDEs, BDE-209 and ∑3-7PBDEs (sum of tri-to hepta-BDEs) were 64.5, 56.9 and 7.2 ng/g lw (lipid weight), respectively, which indicated that deca-BDE was the primarily produced PBDE in Laizhou Bay and that the lower brominated BDEs were still ubiquitous in the environment. Gender was a primary influencing factor for some BDE congeners in serum; their levels in female serum samples were significantly lower than those in male serum samples. Serum PBDE levels showed a downward trend with increased body mass index (BMI), which might reflect the increasing serum lipid contents. Serum levels of some BDE congeners were significantly positively correlated with certain thyroid hormones and antibodies, including free triiodothyronine (fT3), total triiodothyronine (tT3), total thyroxine (tT4) and thyroid peroxidase antibody (TPO-Ab). Levels of some congeners were significantly negatively correlated with some types of serum lipid, including cholesterol (CHOL), low density lipoprotein (LDL) and total triglyceride (TG). Other than serum lipids, only two liver function indicators, total protein (TP) and direct bilirubin (DBIL), were significantly correlated with certain BDE congeners (BDE-100 and BDE-154). Our results provide new evidence on the thyroid-disrupting and hepatotoxic effects of PBDEs.

Polybrominated diphenyl ethers and decabromodiphenyl ethane in paired hair/serum and nail/serum from corresponding chemical manufacturing workers and their correlations to thyroid hormones, liver and kidney injury markers.

We detected the polybrominated diphenyl ethers (PBDEs) or decabromodiphenyl ethane (DBDPE) in paired hair-serum and nail-serum samples collected from the corresponding chemical manufacturing workers. The levels of decabrominated diphenyl ether (BDE-209) or DBDPE in the serum, hair and nail samples were all significantly higher than those reported in other studies, and the "work place" (pretreatment or posttreatment workshop) was the primary influencing factor that affected the levels of specific BFRs in vivo. For BDE-209 workers, the BDE-209 in both the hair and nail samples were significantly and positively related to the BDE-209 in the serum, indicating that both hair and nails can be used as noninvasive biomatrices to reflect internal exposure to BDE-209. In DBDPE workers, hair rather than nails was more suitable for use as a noninvasive biomatrix to infer the DBDPE exposure level. A series of serum biomarkers reflecting thyroid hormones and liver and kidney injuries were tested to calculate the correlations between hair or nail BFR levels and the levels of the biomatrices. The BDE-209 in the hair samples was significantly and positively correlated with the total protein (TP), and the nail BDE-209 level was significantly and positively related to the total bilirubin (TBIL), indirect bilirubin (IDBIL) and uric acid (UA). The DBDPE in hair was significantly and positively correlated with the thyroid hormones free triiodothyronine (fT3) and total triiodothyronine (tT3) and kidney injury markers, including blood urea nitrogen (BUN), creatinine (CRE) and cystatin C (Cys-C). In addition, the nail DBDPE levels were significantly and positively correlated with the albumin/globulin (A/G), BUN, CRE and Cys-C but negatively correlated with the TP and globulin (GLO). Our findings provide preliminary evidence that hair and nails can be used as noninvasive biomatrices for assessing internal BFR exposure and health damage in occupational workers.

Hepatotoxicity of decabromodiphenyl ethane (DBDPE) and decabromodiphenyl ether (BDE-209) in 28-day exposed Sprague-Dawley rats.

Decabromodiphenyl ether (BDE-209) and its substitute decabromodiphenyl ethane (DBDPE) are heavily used in various industrial products as flame retardant. They have been found to be persistent in the environment and have adverse health effects in humans. Although some former studies have reported toxic effects of BDE-209, the study of DBDPE's toxic effects is still in its infancy, and the effects of DBDPE on hepatotoxicity are also unclear. This study aimed to evaluate and compare the hepatotoxicity induced by BDE-209 and DBDPE using a rat model. Sprague-Dawley rats were administered DBDPE or BDE-209 (5, 50, 500 mg/kg bodyweight) intragastrically once a day for 28 days. Twenty-four hours after the end of treatment, the rats were sacrificed, and body liver weight, blood biochemical parameters, liver pathology, oxidative stress, inflammation, pregnane X receptor (PXR), constitutive androstane receptor (CAR), and changes in cytochrome P450 (CYP3A) enzymes were measured. Our results showed that both BDE-209 and DBDPE could cause liver morphological changes, induce oxidative stress, increase γ-glutamyl transferase and glucose levels in serum, and down-regulate PXR, CAR, and CYP3A expression. In addition, BDE-209 was found to increase liver weight and the ratio of liver/body weight, lead to elevated total bilirubin and indirect bilirubin levels in serum, and induce inflammation. The present study indicated that BDE-209 and DBDPE may interfere with normal metabolism in rats through oxidative stress and inflammation, which inhibit PXR and CAR to induce the expression of CYP3A enzymes, and finally produce hepatotoxic effects and cause liver damage in rats. Comparatively, our results show that the damage caused by BDE-209 was more serious than that caused by DBDPE.

A comparison of the thyroid disruption induced by decabrominated diphenyl ethers (BDE-209) and decabromodiphenyl ethane (DBDPE) in rats.

In recent years, decabromodiphenyl ethane (DBDPE), a new alternative flame retardant to the decabrominated diphenyl ethers (BDE-209), is widely used in a variety of products. Previous studies have indicated that DBDPE, like BDE-209, could disrupt thyroid function. However, compared with BDE-209, the degrees of thyrotoxicosis induced by DBDPE were not clear. In addition, the mechanism of thyrotoxicosis induced by DBDPE or BDE-209 was still under further investigation. In this study, male rats as a model were orally exposed to DBDPE or BDE-209 by 5, 50, 500 mg/kg bw/day for 28 days. Then, we assessed the thyrotoxicosis of DBDPE versus BDE-209 and explored the mechanisms of DBDPE and BDE-209-induced thyrotoxicosis. Results showed that decreased free triiodothyronine (FT3) and increased thyroid-stimulating hormone (TSH) and thyrotropin-releasing hormone (TRH) in serum were observed in both 500 mg/kg bw/day BDE-209 and DBDPE group. Decreased total thyroxine (TT4), total T3 (TT3), and free T4 (FT4) were only observed in BDE-209 group but not in DBDPE group. Histological examination and transmission electron microscope examination showed that high level exposure to BDE-209 and DBDPE both caused significant changes in histological structure and ultrastructure of the thyroid gland. Additionally, oxidative damages of thyroid gland (decreased SOD and GSH activities, and increased MDA content) were also observed in both BDE-209 and DBDPE groups. TG contents in the thyroid gland was reduced in BDE-209 group but not in DBDPE group. Both BDE-209 and DBDPE affected the expression of hypothalamic-pituitary-thyroid (HPT) axis related genes. These findings suggested that both BDE-209 and DBDPE exposure could disrupt thyroid function in the direction of hypothyroidism and the underlying mechanism was likely to be oxidative stress and perturbations of HPT axis. However, DBDPE was found to be less toxic than BDE-209.

Tetrabromobisphenol A, hexabromocyclododecane isomers and polybrominated diphenyl ethers in foodstuffs from Beijing, China: Contamination levels, dietary exposure and risk assessment.

Hexabromocyclododecane (HBCD), tetrabromobisphenol A (TBBPA) and polybrominated diphenyl ether (PBDEs) are three legacy brominated flame retardants (BFRs); however, they are still produced and used in China. In this study, these three BFRs were measured in commonly consumed animal-based and plant-based foodstuffs from Beijing, China, and the dietary intakes of these BFRs by adults in Beijing were estimated to assess the related health concerns. The median levels of TBBPA in animal-based foodstuffs ranged from

Cardiovascular toxicity of decabrominated diphenyl ethers (BDE-209) and decabromodiphenyl ethane (DBDPE) in rats.

Recent reports indicated that decabrominated diphenyl ether (BDE-209) and decabromodiphenyl ethane (DBDPE) exist extensively in the environment. The toxicity of BDE-209 has been reported in quite a few studies, whereas the data of DBDPE are relatively rare. However, databases regarding cardiovascular toxicities of both BDE-209 and DBDPE are lacking. In this study, we investigated the vascular/cardiac trauma induced by DBDPE after oral exposure and compared the results with those of BDE-209 using rat model. Male rats were orally administered with corn oil containing DBDPE or BDE-209 (5, 50, 500 mg/kg/day) for 28 days, then oxidative stress, morphological and ultrastructural changes of the heart and abdominal aorta, levels of creatine kinase (CK) and lactate dehydrogenase (LDH), inflammatory cytokines, endothelin-1 (ET-1), and intercellular adhesion molecule-1 (ICAM-1) in the serum were monitored. Results showed that BDE-209 and DBDPE caused heart and abdominal aorta morphological and ultrastructural damage, serum CK and LDH elevation, and antioxidant enzyme activity changes. BDE-209 and DBDPE-induced inflammation was characterized by the upregulation of key inflammatory mediators, including interleukin-1beta (IL-1ß), IL-6, IL-10, and tumor necrosis factor alpha (TNFα). Additionally, BDE-209 and DBDPE led to endothelial dysfunction, as evidenced by the ET-1 and ICAM-1 elevation. Our findings demonstrated that BDE-209 and DBDPE could induce oxidative stress, inflammation, and eventually lead to endothelial dysfunction and cardiovascular injury. Compared to DBDPE, these toxic responses were stronger in the hearts and abdominal aorta of Sprague-Dawley rats exposed to BDE-209. Our findings indicated a potential deleterious effect of BDE-209 and DBDPE on the cardiovascular system.

An Updated Systematic Review and Meta-analysis of Association Between Adiponectin Gene Polymorphisms and Coronary Artery Disease.

Coronary artery disease (CAD) is a significant contributor to global health burden. Adiponectin gene single nucleotide polymorphisms (SNPs) have been associated with CAD susceptibility, but with inconsistent results across the studies. We present, in this study, an updated meta-analysis to discern the genetic susceptibility of adiponectin SNPs in relation to CAD. PubMed and EMBASE databases were used to identify the relevant published articles using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Pooled odds ratios and 95% confidence intervals were generated to assess the strength of the associations. Thirty-five articles with a total of 28,947 participants (mean age 55.3 years, 11,632 cases/17,315 controls, 19,443 males/8353 females, and 1151 persons with unspecified gender data) were included. The dominant, recessive, and additive models were applied. We found that the SNPs +45T>G (rs2241766), -4034A>C (rs822395), and -11391G>A (rs17300539) were linked to CAD development. In addition, +276G>T (rs1501299) SNP was associated with a decreased susceptibility to CAD among Caucasians. We did not find an association between the CAD susceptibility and the -11377C>G (rs266729) SNP. These observations offer new potential genetic biomarker candidates in relation to CAD, and warrant further research in independent world populations.