RNA sequencing reveals dynamic expression of lncRNAs and mRNAs in caprine endometrial epithelial cells induced by Neospora caninum infection.

BACKGROUND: The effective transmission mode of Neospora caninum, with infection leading to reproductive failure in ruminants, is vertical transmission. The uterus is an important reproductive organ that forms the maternal-fetal interface. Neospora caninum can successfully invade and proliferate in the uterus, but the molecular mechanisms underlying epithelial-pathogen interactions remain unclear. Accumulating evidence suggests that host long noncoding RNAs (lncRNAs) play important roles in cellular molecular regulatory networks, with reports that these RNA molecules are closely related to the pathogenesis of apicomplexan parasites. However, the expression profiles of host lncRNAs during N. caninum infection has not been reported. METHODS: RNA sequencing (RNA-seq) analysis was used to investigate the expression profiles of messenger RNAs (mRNAs) and lncRNAs in caprine endometrial epithelial cells (EECs) infected with N. caninum for 24 h (TZ_24h) and 48 h (TZ_48 h), and the potential functions of differentially expressed (DE) lncRNAs were predicted by using Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis of their mRNA targets. RESULTS: RNA-seq analysis identified 1280.15 M clean reads in 12 RNA samples, including six samples infected with N. caninum for 24 h (TZ1_24h-TZ3_24h) and 48 h (TZ1_48h-TZ3_48h), and six corresponding control samples (C1_24h-C3_24h and C1_48h-C3_48h). Within the categories TZ_24h-vs-C_24h, TZ_48h-vs-C_48h and TZ_48h-vs-TZ_24h, there were 934 (665 upregulated and 269 downregulated), 1238 (785 upregulated and 453 downregulated) and 489 (252 upregulated and 237 downregulated) DEmRNAs, respectively. GO enrichment and KEGG analysis revealed that these DEmRNAs were mainly involved in the regulation of host immune response (e.g. TNF signaling pathway, MAPK signaling pathway, transforming growth factor beta signaling pathway, AMPK signaling pathway, Toll-like receptor signaling pathway, NOD-like receptor signaling pathway), signaling molecules and interaction (e.g. cytokine-cytokine receptor interaction, cell adhesion molecules and ECM-receptor interaction). A total of 88 (59 upregulated and 29 downregulated), 129 (80 upregulated and 49 downregulated) and 32 (20 upregulated and 12 downregulated) DElncRNAs were found within the categories TZ_24h-vs-C_24h, TZ_48h-vs-C_48h and TZ_48h-vs-TZ_24h, respectively. Functional prediction indicated that these DElncRNAs would be involved in signal transduction (e.g. MAPK signaling pathway, PPAR signaling pathway, ErbB signaling pathway, calcium signaling pathway), neural transmission (e.g. GABAergic synapse, serotonergic synapse, cholinergic synapse), metabolism processes (e.g. glycosphingolipid biosynthesis-lacto and neolacto series, glycosaminoglycan biosynthesis-heparan sulfate/heparin) and signaling molecules and interaction (e.g. cytokine-cytokine receptor interaction, cell adhesion molecules and ECM-receptor interaction). CONCLUSIONS: This is the first investigation of global gene expression profiles of lncRNAs during N. caninum infection. The results provide valuable information for further studies of the roles of lncRNAs during N. caninum infection.

1H-NMR-guided isolation of enantiomeric coumarin-monoterpenes with anti-inflammatory activity from Gerbera piloselloides.

1H-NMR guided fractionation led to the isolation of twenty-two coumarin monoterpenes from the whole plant of Gerbera piloselloides, among which fourteen were undescribed. All coumarin monoterpenes were initially found to be racemates without optical activity. Subsequently, eleven pairs of optically pure enantiomers were successfully separated by chiral phase HPLC. Their structures and absolute configurations were unambiguously determined based on their spectroscopic data, calculated/experimental electronic circular dichroism (ECD) data, and X-ray diffraction analysis. Bioassays in LPS-treated RAW 264.7 cells revealed that the four compounds possessed moderate anti-inflammatory activity. In addition, the correlations between the cotton effect (CE) from δ-lactone at approximately 210-220 nm in CD spectra and γ-C or the ring fused at γ-C of the skeleton were reported for the first time.

The outcome of surgical and non-surgical treatments for traumatic optic neuropathy: a comparative study of 685 cases.

Background: The choice and efficacy of surgical or/and surgical treatments for traumatic optic neuropathy (TON) remained controversial by now. This study aims to present the outcomes of surgical and nonsurgical treatments for TON in our center. Methods: A total of 685 consecutive patients were retrospectively included in the study. And divided into surgical and non-surgical groups. All cases were treated with corticosteroids for 3 days after admission. Endoscopic optic decompression was applied to 479 patients of surgical group; The other 206 patients of nonsurgical were administered with corticosteroids alone. The visual outcomes before and after treatment were compared with Wilcoxon rank and tests. The improvement rate between two groups were compared with chi-square test. Results: The visual acuity (VA) after treatment was significantly better than that before treatment (P=0.000). Overall VA improvement rate in the surgical group was better than that in non-surgical group (42.8% vs. 35.4%) with no significant difference (P=0.072). The VA improvement rate was significant greater in the surgical group than that in the non-surgical group in the patients with NLP before treatment (P=0.028). The VA improvement rate was better in the surgical group than that in the non-surgical group (71.9% vs. 57.8%) but with no significant difference. The final overall VA was 0.1 or better in 43 cases; 104 cases were able to count fingers; hand motion (HM) became perceivable in 132 cases; light perception (LP) was achieved in 53 cases; and no light perception (NLP) remained in 353 cases. Conclusions: Endoscopic optic nerve decompression (EOND) combined with corticosteroids or corticosteroids alone could reach the improvement for patients with TON. The EOND combined with corticosteroids could achieve better VA improvement in patients with NLP.

Silencing Tautomerization to Isolate Unstable Physalins from Physalis minima.

The inherent structural instability of some physalins has hampered the isolation and identification of these compounds for approximately 50 years, and an effective method to overcome these challenges remains unavailable. In the present study, the unprecedented tautomerization mechanism of unstable physalins was elucidated by performing isotopic labeling experiments and DFT calculations, which led to the successful separation of tautomers and isolation of highly pure products for the first time. As a result, 15 new physalins, physaminins A-O (1-15), as well as 17 known analogues (16-32), were isolated from the whole plants of Physalis minima L. The chemical structures of the new compounds were established by performing a comprehensive analysis of spectroscopic data, and their absolute configurations were confirmed by using computational ECD calculations and/or single-crystal X-ray diffraction analyses. All obtained isolates were evaluated for their antiproliferative effects against four human cancer cell lines (A549, HepG2, MCF-7, and SCG-7901) and two noncancerous cell lines (RAW 264.7 and human normal hepatocytes L02), as well as their anti-inflammatory activities by measuring their abilities to inhibit NO production in LPS-stimulated murine RAW 264.7 cells in vitro. Compounds 1-5, 13, 16, 18, 19, 23, and 30 exerted significant antiproliferative effects on the four human cancer lines, with IC50 values ranging from 0.2(0) to 24.7(2) µM, and these compounds were not toxic to the two noncancerous cell lines at a concentration of 10 µM. Moreover, compounds 7, 10, 11, 12, 14, 17, 22, and 27 significantly inhibited NO production, with IC50 values ranging from 2.9(1) to 9.5(2) µM.

Sex- and size-dependent accumulation of Dechlorane Plus flame retardant in a wild frog-eating snake Amphiesma stolata.

Despite several studies having addressed the bioaccumulation of Dechlorane Plus (DP) flame retardant in wildlife, there is still a dearth of information for reptiles in general and for snakes in particular. Here, we report the residue levels and trophic transfer of syn-, anti-, and anti-Cl11-DP in a frog-eating snake-namely, the striped keelback snake Amphiesma stolata-from a DP hotspot in South China. The concentrations of syn-, anti-, and anti-Cl11-DP in A. stolata ranged from 1.06-21.2, 2.13-21.5, and 0.16-10.6 ng/g lipid weight, respectively, with significantly higher levels in males compared with females. Statistical analysis showed that the concentrations of these chemicals were negatively correlated with body sizes (length and mass) of the snake. The fractional abundance of anti-DP (fanti) did not significantly differ either between the sexes or between A. stolata and its diet (i.e., frogs). However, fanti showed positive correlations with the snake's body size and negative correlations with ∑DP concentrations (summed concentrations of syn- and anti-DP), indicating that body size and DP residue levels are important factors influencing DP isomeric profiles in these snakes. Biomagnification factors estimated based on the relationship between A. stolata and frogs were 0.49 ± 0.01 (mean ± SE), 0.44 ± 0.09, and 1.79 ± 0.54 for syn-, anti-, and anti-Cl11-DP, respectively, suggesting trophic dilution of syn- and anti-DP and a mild biomagnification of anti-Cl11-DP from frogs to snakes.

Bioaccumulation and maternal transfer of two understudied DDT metabolites in wild fish species.

While the secondary metabolites of DDT such as 2,2-bis(chlorophenyl)-1-chloroethylene (DDMU) and 2,2-bis(chlorophenyl)methane (DDM) have been detected in the environment for several decades, knowledge is extremely limited on their bioaccumulation characteristics. Here, we reported the bioaccumulation and maternal transfer of p,p'-DDMU and p,p'-DDM in two wild fishes, i.e., the northern snakehead (Channa argus) and crucian carp (Carassius auratus), from a DDT contaminated site in South China. The hepatic concentrations of p,p'-DDMU and p,p'-DDM in the fish were up to 549 and 893 ng/g lipid weight, contributing 5.3% and 3.2% in average to ΣDDXs (the sum concentrations of DDT and its 6 metabolites), respectively. The residues of p,p'-DDMU and p,p'-DDM in the fish exhibited interspecific and intraspecific variations, resulting from the differences in lipid content, sex, and body sizes (length and mass) between or within species. Both p,p'-DDMU and p,p'-DDM were consistently detected in the fish eggs, demonstrating their maternal transfer in female fish. The mean eggs to liver lipid-normalized concentration (E/L) ratios of p,p'-DDMU and p,p'-DDM were 0.98 and 1.77 in the northern snakehead, 0.35 and 0.01 in crucian carp, respectively; which were comparable to or even exceeded those of DDT and its major metabolites calculated in the same individual. Statistical analyses of the data showed that the E/L ratios were positively correlated with body sizes of the fish, but negatively correlated with the hepatic concentrations of p,p'-DDMU and p,p'-DDM in females; suggesting the influences of fish sizes and the mother body residues on their maternal transfer efficiencies.

Halogenated flame retardants in wild, prey-sized mud carp from an e-waste recycling site in South China, 2006-2016: Residue dynamics and ecological risk assessment.

The crude e-waste recycling has been regulated in China since the late 2000s; however, information on the recent levels and the ecological risks of e-waste derived contaminants such as halogenated flame retardants (HFRs) in the e-waste sites are limited. We therefore examined the concentrations of several HFRs in wild, prey-sized mud carps collected from a typical e-waste site in 2006, 2011 and 2016, to understand the exposure dynamics and ecological risk of these chemicals. Several ecological and biological parameters including δ15N, δ13C, body size and lipid content of the fish were also examined, to ensure an overall uniformity of the sample set among the sampling years. Among the HFRs measured, polybrominated diphenyl ethers (PBDEs) were detected at the highest concentrations (contributing >90% to ∑HFRs), followed by Dechlorane Plus (DPs), polybrominated biphenyls (PBBs), and alternative brominated flame retardants (ABFRs). The fish concentrations of ∑PBDEs, ∑PBBs and ∑DPs significantly dropped by 65%, 57% and 53% from 2006 to 2011, and 12%, 74% and 51% from 2011 to 2016, respectively; likely reflecting the positive impact of the environmental regulations on crude e-waste recycling. The ∑ABFRs concentrations were also decreased by 80% from 2006 to 2011, but increased by 127% from 2011 to 2016; suggesting possible fresh input of these novel HFRs in recent years. In addition to the changes in the HFR concentrations, contaminant profiles in the fish were also changed, possibly due to environmental degradation of the HFRs. Despite our conservative method of risk assessment, we found that PBDEs posed an important risk both for the mud carp and for piscivorous wildlife that inhabit the e-waste site.

Role of delayed wider endoscopic optic decompression for traumatic optic neuropathy: a single-center surgical experience.

BACKGROUND: The aim of the present study was to discuss the efficacy of delayed wider endoscopic optic decompression in traumatic optic neuropathy (TON). METHODS: A total of 479 patients were treated with corticosteroids and delayed wider endoscopic optic decompression, including the injury-to-surgery interval, within 2 weeks in patients with no light perception (NLP), and within 1 month in patients with residual eyesight. Based on the traditional decompression range, the superior wall of the optic canal was further decompressed. The preoperative and postoperative visual acuities (VAs) were reviewed, and the therapeutic efficacy was analyzed. RESULTS: The final VA was 0.1 or better in 29 cases, finger count in 79 cases, hand motion in 99 cases, light perception (LP) in 25 cases, and NLP in 247 cases. A total of 136 patients (136/383, 35.5%) recovered after NLP treatment, and 78 patients (69/96, 71.9%) had improved residual eyesight. The improvement rate in patients with residual eyesight was significantly higher than that of patients with NLP (P<0.01). Moreover, the total VA after treatment was better than that before surgery (P<0.01). CONCLUSIONS: Delayed wider optic nerve decompression plus corticosteroids remains an effective and safe therapeutic strategy for patients with delayed treatment intervals of more than 1 week, especially for those with residual eyesight within 1 month.

Overexpression of CD155 is associated with PD-1 and PD-L1 expression on immune cells, rather than tumor cells in the breast cancer microenvironment.

BACKGROUND: CD155 is an immune checkpoint protein in cancers and interacts with ligands to regulate the immune microenvironment. The expression of CD155 is correlated with the prognosis and pathological features of breast cancer. AIM: To investigate the expression status of CD155 and the association with exhausted CD4+ helper and CD8+ cytotoxic tumor infiltrating lymphocytes (TILs) and PD-L1 in the breast cancer microenvironment. METHODS: One hundred and twenty-six breast cancer patients with invasive ductal breast cancer were consecutively recruited into this study. Immunohistochemistry was used to detect the expression CD155, PD-L1 and PD-1 on tumor-infiltrating immune cells and tumor cells in the microenvironment. RESULTS: The proportion of patients with CD155 expression was higher in triple negative breast cancer (72.7%) than in Luminal A patients (22.2%, P < 0.05). Patients with positive CD155 expression had a higher percentage of CD4+/PD-1+ helper TILs (30%) than patients with negative CD155 expression (21%, P < 0.05). Patients with positive CD155 expression also had higher cell counts of exhausted CD4+ TILs [47 vs 20/high-power fields (HPF)] and unexhausted CD8+ TILs (30 vs 17/HPF) than patients with negative expression (P < 0.05). CD155 expression was correlated with increased PD-L1 expression in immune cells, 0.8% and 0.02% immune cells expressed PD-L1 in patients with positive and negative CD155 expression, respectively (P < 0.05). CONCLUSION: CD155 was related to an inhibitory immune breast cancer microenvironment. CD155 was associated with a high proportion of exhausted CD4+ and unexhausted CD8+ TILs and high PD-L1 expression in immune cells.

Overexpression of an Immune Checkpoint (CD155) in Breast Cancer Associated with Prognostic Significance and Exhausted Tumor-Infiltrating Lymphocytes: A Cohort Study.

PURPOSE: The immune checkpoint inhibitor is approved for breast cancer treatment, but the low expression of PD-L1 limits the immunotherapy. CD155 is another immune checkpoint protein in cancers and interacts with ligands to regulate immune microenvironment. This study is aimed at investigating the expression of CD155 and the association with prognosis and pathological features of breast cancer. METHODS: 126 patients were recruited this cohort study consecutively, and CD155 expression on tumor cells was detected by immunohistochemistry. The Kaplan-Meier survival curve and Cox hazard regression model were used to estimate the association. RESULTS: 38.1% patients had an overexpression of CD155, and the proportion of tumor cells with CD155 overexpression was 17%, 39%, 37%, and 62% among Luminal A, Luminal B, HER2-positive, and triple negative breast cancer cases, respectively (p < 0.05). Patients with CD155 overexpression had the Ki-67 index significantly higher than that of patients with low expression (42% vs. 26%). Though the number of tumor-infiltrating lymphocytes was higher among patients with CD155 overexpression (144/HPF vs. 95/HPF), the number of PD-1+ lymphocytes was significantly higher (52/HPF vs. 25/HPF, p < 0.05). Patients of CD155 overexpression had the disease-free and overall survival decreased by 13 months and 9 months, respectively (p < 0.05). CD155 overexpression was associated with an increased relapse (HR = 13.93, 95% CI 2.82, 68.91) and death risk for breast cancer patients (HR = 5.47, 1.42, 20.99). CONCLUSIONS: Overexpression of CD155 was correlated with more proliferative cancer cells and a dysfunctional immune microenvironment. CD155 overexpression introduced a worse relapse-free and overall survival and might be a potential immunotherapy target for breast cancer.

Contaminant-related oxidative distress in common kingfisher (Alcedo atthis) breeding at an e-waste site in South China.

The crude electronic waste (e-waste) recycling has caused severe contamination of polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs) in the local environment, begging the question of whether wildlife like birds living at e-waste sites are suffering from adverse effects. We examined several oxidative status markers and their relationships with hepatic concentrations of PCBs and PBDEs in common kingfisher (Alcedo atthis) that inhabit an e-waste site in South China. The results showed that the mean concentrations of ∑PCBs (19100 ng/g) and ∑PBDEs (507 ng/g) in kingfishers from e-waste site were several orders of magnitude higher than those in the species from a reference site. Correspondingly, hepatic concentrations of malondialdehyde (MDA) and reactive oxygen species (ROS) in kingfishers from the e-waste site were significantly higher than those detected in the reference population, suggesting oxidative distress in the birds breeding at the e-waste site. The activities of superoxide dismutase (SOD) and catalase (CAT) in the liver from the exposed group were significantly lower compared with the reference group, while the opposite trend was observed for glutathione peroxidase (GPx). Significantly positive correlations were observed between PCB or PBDE concentrations and the levels of MDA and ROS; while negative correlations were found for enzymatic activities of SOD and CAT. Overall, our results may suggest a potential linkage between exposure to e-waste-derived pollutants and elevated oxidative stress, thereby indicating a potential oxidative stress-related health effects in common kingfisher breeding at the e-waste site.

Bioaccumulation characteristics of PBDEs and alternative brominated flame retardants in a wild frog-eating snake.

While a large body of studies have examined polybrominated diphenyl ethers (PBDEs) and alternative brominated flame retardants (ABFRs) in wildlife, information on the bioaccumulation of these contaminants in reptiles in general, and snakes in particular, are scarce. We investigated the bioaccumulation characteristics of PBDEs and several ABFRs including decabromodiphenyl ethane (DBDPE), 1,2-bis(2,4,6-tribromophenoxy) ethane (BTBPE), hexabromobenzene (HBB) and pentabromotoluene (PBT) in a frog-eating snake, the striped keelback snake (Amphiesma stolata), from an e-waste recycling site in South China. The concentrations of ∑PBDEs and ∑ABFRs in the snakes ranged 53-5200 and 3.1-87 ng/g lipid weight, respectively; with higher levels in males than females. Additionally, the concentrations of BDE-28, -47, and -66 were positively correlated with snake size (snout-vent length and body mass), while negative correlations were found for most of the higher brominated PBDE congeners and HBB, PBT and BTBPE. The biomagnification factors (BMFs) estimated in the snake/frog relationship indicated a mild to moderate biomagnification of BDE-28, -47, -66, -100, -153 and -154 (with mean BMFs of 1.1-5.3), while a lack of magnification for the other PBDE congeners and all the ABFRs. This is the first report on the sex- and size-related accumulation and biomagnification potentials of PBDEs and ABFRs in snakes.

Contamination of organohalogen chemicals and hepatic steatosis in common kingfisher (Alcedo atthis) breeding at a nature reserve near e-waste recycling sites in South China.

Severe pollution of organohalogen compounds (OHCs) including PBDEs, PCBs and DDTs is demonstrated in e-waste recycling sites and metropolis in South China, but relatively little is known of their impacts on wildlife that inhabits nature reserves in this region, especially those located at the neighborhood areas of e-waste recycling sites. In the present study, PBDEs, PCBs and DDTs as well as liver histological changes were examined in common kingfisher breeding at a nature reserve (Shimentai National Nature Reserve, SNNR) near a notorious e-waste recycling site in South China. Mean ∑PBDEs (84.9 ng/g lipid weight), ∑PCBs (397 ng/g) and ∑TEQs (total toxic equivalent of coplanar PCBs, 2.68 ng/g) concentrations in kingfishers from SNNR were approximately 2-, 5-, and 4-fold higher than those detected in a reference population, respectively; suggesting contamination of the e-waste-derived OHCs in SNNR. Mean ∑DDTs concentration (2150 ng/g) in kingfishers from SNNR was also higher (~2-fold) than that from the reference samples. While ∑DDTs dominated the composition of the OHCs at both sampling sites, ∑PCBs was also important in kingfishers from SNNR, averaging 15% of ∑OHCs. Histological examination of the liver showed steatosis occurred in 60% of the kingfishers from SNNR. Birds with hepatic steatosis had significantly (p = 0.03) higher ∑TEQs than those without steatosis. Similar trends were also found for ∑PCBs and ∑DDTs, although it is not statistically significant. It therefore seems likely that the hepatic steatosis were associated with the relatively high body-burden of OHCs, although the possibility of other factors resulting in hepatic steatosis cannot be ruled out.

Biomagnification of PBDEs and alternative brominated flame retardants in a predatory fish: Using fatty acid signature as a primer.

Information on biomagnification of alternative brominated flame retardants (ABFRs) is limited and results are inconclusive, due in part to uncertainty in the understanding of predator/prey relationships. In the present study, a predatory fish, Channa argus, and several forage fish species were obtained from an ABFR contaminated site. The predator/prey relationships were identified based on fatty acid (FA) signatures in the predator and prey. Biomagnification factors (BMFs) for several ABFRs including decabromodiphenyl ethane (DBDPE), 1,2­bis(2,4,6­tribromophenoxy) ethane (BTBPE), hexabromobenzene (HBB), pentabromotoluene (PBT), and pentabromoethylbenzene (PBEB) were estimated based on the identified predator/prey relationships. The results showed that crucian carp was the main prey of C. argus, contributing to 71%-100% to its total diet. The mean BMFs for DBDPE, BTBPE, and HBB were 0.06, 0.40, and 0.91, respectively, indicating trophic dilution of these ABFRs. However, biomagnification of PBT and PBEB, with BMFs of 2.09 and 2.13, respectively, was observed. The BMFs for PBT, PBEB and HBB were comparable to or even higher than those for some polybrominated diphenyl ether (PBDE) congeners estimated in the same individual predator, indicating that these emerging pollutants may pose significant environmental risks. The BMFs for ABFRs and PBDEs were significantly and negatively correlated to the log KOWs of these chemicals, suggesting that the biomagnification of these chemicals was depressed due to their superhydrophobic nature.

Alstonlarsines A-D, Four Rearranged Indole Alkaloids from Alstonia scholaris.

Four indole alkaloids, alstonlarsines A-D (1-4), were isolated from Alstonia scholaris and structurally characterized. Compound 1 possesses a new carbon skeleton with a cage-shaped 9-azatricyclo[4.3.1.03,8]decane motif, and compounds 2-4 feature a rare carbon skeleton that was found in nature for the first time. Plausible biosynthetic routes for 1-4 are proposed. Compound 1 showed DRAK2 inhibitory activity with an IC50 value of 11.65 ± 0.63 µΜ.

MicroRNA-21 attenuates BDE-209-induced lipid accumulation in THP-1 macrophages by downregulating Toll-like receptor 4 expression.

Growing evidence demonstrates a possible response of specific microRNA (miRNA) to environmental pollutant stimuli in multiple biological processes. We previously reported that a persistent organic pollutant, decabromodiphenyl ether (BDE-209), can enhance Toll-like receptor 4 (TLR4)-dependent lipid uptake in THP-1 macrophages; whether miRNAs are involved in this process remains unclear. In the present study, we investigated the levels of several miRNAs related to TLR4 signaling, including miRs-9, -21, -27b, -125b, -132, -146a, -147, -155, and -let-7e, in THP-1 macrophages after stimulation by BDE-209 and oxidized low-density lipoprotein. The results showed that the levels of miR-21 were significantly suppressed by BDE-209 at concentrations of 6.25, 12.5 and 25 µM, in a dose-dependent manner; whereas there was no significant changes for the other miRNAs investigated. Moreover, the suppression of miR-21 was accompanied by an upregulated TLR4 expression, at both mRNA and protein levels. Further analysis showed that the up-regulated TLR4 induced by BDE-209 was inhibited in macrophages transfected with miR-21 mimic; meanwhile opposite results were exhibited when an anti-miR-21 inhibitor was transfected to the macrophages. Additionally, transfection with miR-21 mimic effectively attenuated BDE-209-induced lipid accumulation in macrophages. Together, these data illustrate that miR-21 inhibits BDE-209-triggered lipid accumulation in macrophages through down-regulating TLR4 expression.

Polychlorinated biphenyls in apple snails from an abandoned e-waste recycling site, 2010-2016: A temporal snapshot after the regulatory efforts and the bioaccumulation characteristics.

The rudimentary recycling of electronic waste (e-waste) has been banned in China since the late 2000s, leaving many abandoned e-waste sites. However, knowledge is limited on the concentrations and fates of the e-waste derived contaminants such as polychlorinated biphenyls (PCBs) in these abandoned sites. In this work, we assessed the temporal trend of PCB concentrations in the year 2010, 2012, and 2016 at an abandoned e-waste site in South China, using apple snail as a bioindicator. The mean ∑PCBs concentrations in apple snails sampled in 2016 (53.2 ng/g dry weight) was approximately 11-fold higher than that (4.68 ng/g dry weight) in apple snails from a reference site. The result suggested that the abandoned e-waste recycling site was still heavily polluted by PCBs, despite of the fact that crude e-waste recycling processes have been prohibited for nearly 10 years. The concentrations of ∑PCBs were significantly decreased in 2016 compared to those in 2010 (mean: 115 ng/g dry weight) and 2012 (mean: 92.3 ng/g dry weight), but there were no significant differences in the concentrations between 2010 and 2012. Regarding the congener profiles, the contributions of lower chlorinated congeners (tri- and tetra-PCBs) in the snails tended to be higher over the years. The ∑PCBs in snails were significantly correlated with those in soils. Additionally, PCB profiles in snails resembled those in soils. These results suggested that apple snails can be used as an ideal bioindicator for PCBs in the paddy soils. Field determined biota-soil accumulation factors (BSAFs) for PCBs ranged from 0.31 to 1.9, with most of the values being 1-2; indicating that theoretical BSAFs can be used to predict the bioaccumulation of PCBs in the snails with a reasonable degree of certainty.

Decarbromodiphenyl ether (BDE-209) promotes monocyte-endothelial adhesion in cultured human aortic endothelial cells through upregulating intercellular adhesion molecule-1.

There is growing evidence that exposure to persistent organic pollutants (POPs) is statistically associated with incidence of cardiovascular disease (CVD) or its risk factors. Decarbromodiphenyl ether (BDE-209) is a new POP which exists extensively in human tissues, but its potential effects on CVD have so far received less focus. The adhesion of circulating monocytes to endothelial cells is one of the critical underlying steps in the initiation and development of CVD. In the present study, we investigated the effect of BDE-209 on the adhesion of THP-1 monocytes to human aortic endothelial cells (HAECs) and identified the molecular mechanisms involved. Our results showed that 6.25, 12.5 and 25 µM of BDE-209 exposures caused significant increases in monocyte-endothelial cell adhesion, in a dose-dependent manner. Mechanistically, BDE-209 exposure increased the expression of intercellular adhesion molecule-1 (ICAM-1). Moreover, the up-regulation of ICAM-1 was accompanied by a decrease in the expression of microRNA-141 (miR-141). Furthermore, the up-regulation of ICAM-1 and the increased adhesion induced by BDE-209 could be reversed by miR-141 supplement. Taken together, our results show that BDE-209 potentiates monocyte-endothelial cell interaction via miR-141/ICAM-1 pathway in HAECs.

Decabromodiphenyl ether (BDE-209) enhances foam cell formation in human macrophages via augmenting Toll-like receptor 4-dependent lipid uptake.

Growing epidemiological evidence is substantiating an association between exposure to persistent organic pollutants (POPs) and incidence of atherosclerosis. Decabromodiphenyl ether (BDE-209) is a new POP which presents extensively in human populations; whether this contaminant is potentially arteriosclerotic remains unclear. In this study, we investigated the effects of BDE-209 on macrophage-derived foam cell formation, a hallmark of early atherosclerosis, using THP-1-derived macrophages incubated with oxidized low-density lipoprotein (oxLDL) as a foam cell model. The results showed that 6.25, 12.5 and 25.0 µM of BDE-209 significantly enhanced lipid accumulation inside the foam cells, in a dose-dependent manner. Further mechanism assays suggested that BDE-209 significantly increased the expression of Toll-like receptor 4 (TLR4), a signal transducing integral membrane protein mediating lipid uptake in macrophages, at both the mRNA and protein levels. In contrast, there was no significant changes for several key regulators involving in lipid efflux, lipogenesis, and lipid oxidation in macrophages. Furthermore, the augmented lipid accumulation was almost completely abrogated by treatment with an anti-TLR4 antibody. Together, these data illustrate that BDE-209 enhances oxLDL-induced macrophage foam cell formation via augmenting TLR4-dependent lipid uptake in the cells.