Complement decay-accelerating factor inhibits inflammation-induced myopia development.

Myopia is regarded as a worldwide epidemic ocular disease, has been proved related to inflammation. CD55, also known as decay-accelerating factor (DAF) can modulate the activation of complement through inhibiting the formation of complement 3 convertase and its dysregulation is involved in various inflammatory diseases. To investigate the association between CD55 and myopia, and to test whether CD55 can inhibit myopia development by suppressing inflammation in the eye, we use three different animal models including monocular form-deprivation myopia, myopia induced by TNF-α administration and allergic conjunctivitis animal model to reveal the CD55 in myopia development. The tears of thirty-eight participants with different spherical equivalents were collected and CD55 in the tears were also analyzed. Complement 3 and complement 5 levels increased while CD55 levels decreased in allergic conjunctivitis and myopic eyes. After anti-inflammatory drugs administration, CD55 expression was increased in monocular form-deprivation myopia model. We also found inflammatory cytokines TGF-ß, IL-6, TNF-α, and IL-1ß may enhance complement 3 and complement 5 activation while CD55 level was suppressed contrary. Moreover, lower CD55 levels were found in the tears of patients with myopia with decreased diopter values. Finally, CD55-Fc administration on the eyelids can inhibit the elongation of axial length and change of refractive error. CD55-Fc application also suppress myopia development subsequent to complement 3 and complement 5 reduction and can lower myopia-specific (MMP-2 and TGF-ß) cytokine expression in TNF-α induced myopia animal model. This suggests that CD55 can inhibit myopia development by suppression of complement activation and eventual down-regulation of inflammation.

Development of a rapid aptamer-chemiluminescence sensor for detecting glyphosate pesticide residue in soybeans.

Glyphosate (GLY) is a widely used herbicide worldwide, particularly in cultivating genetically modified soybeans resistant to GLY. However, routine multi-residue analysis does not include GLY due to the complexity of soybean matrix components that can interfere with the analysis. This study presented the development of an aptamer-based chemiluminescence (Apt-CL) sensor for rapidly screening GLY pesticide residue in soybeans. The GLY-binding aptamer (GBA) was developed to bind to GLY specifically, and the remaining unbound aptamers were adsorbed onto gold nanoparticles (AuNPs). The signal was in the form of luminol-H2O2 emission, catalyzed by the aggregation of AuNPs in a chemiluminescent reaction arising from the GLY-GBA complex. The outcomes demonstrated a robust linear relationship between the CL intensity of GLY-GBA and the GLY concentration. In the specificity test of the GBA, only GLY and Profenofos were distinguished among the fifteen tested pesticides. Furthermore, the Apt-CL sensor was conducted to determine GLY residue in organic soybeans immersed in GLY as a real sample, and an optimal linear concentration range for detection after extraction was found to be between 0.001 and 10 mg/L. The Apt-CL sensor exploits the feasibility of real-time pesticide screening in food safety.

Lung metastasis-Harnessed in-Situ adherent porous organic nanosponge-mediated antigen capture for A self-cascaded detained dendritic cells and T cell infiltration.

The infiltration of cytotoxic T lymphocytes promises to suppress the most irresistible metastatic tumor for immunotherapy, yet immune privilege and low immunogenic responses in these aggressive clusters often restrict lymphocyte recruitment. Here, an in situ adherent porous organic nanosponge (APON) doubles as organ selection agent and antigen captor to overcome immune privilege is developed. With selective organ targeting, the geometric effect of APON composed of disc catechol-functionalized covalent organic framework (COF) boosts the drug delivery to lung metastases. Along with a self-cascaded immune therapy, the therapeutic agents promote tumor release of damage-associated molecular patterns (DAMPs), and then, in situ deposition of gels to capture these antigens. Furthermore, APON with catechol analogs functions as a reservoir of antigens and delivers autologous DAMPs to detain dendritic cells, resulting in a sustained enhancement of immunity. This disc sponges (APON) at lung metastasis as antigen reservoirs and immune modulators effectively suppress the tumor in 60 days and enhanced the survival rate.

Galectin-12 modulates Kupffer cell polarization to alter the progression of nonalcoholic fatty liver disease.

Nonalcoholic fatty liver disease is caused by an imbalance in lipid metabolism and immune response to pose a risk factor for liver fibrosis. Recent evidence indicates that M2 macrophages secrete transforming growth factor-ß1, which contributes to liver fibrosis. Galectin-12 has been demonstrated to regulate lipid metabolism and macrophage polarization. The purpose of this study is to investigate the role of galectin-12 in the development of nonalcoholic fatty liver disease and fibrosis. Liver tissue from wild-type C57BL/6 mice fed with a high-fat diet containing cholesterol and cholic acid for 4-12 weeks was used to examine galectin-12 expression and its correlation with nonalcoholic fatty liver disease. Furthermore, the effects of galectin-12 on M2 macrophages during the progression of nonalcoholic fatty liver disease were investigated by studying Kupffer cells from galectin-12 knockout mice and doxycycline-inducible Gal12-/-THP-1 cells. Ablation of galectin-12 promoted M2 polarization of Kupffer cells, as indicated by higher levels of M2 markers, such as arginase I and chitinase 3-like protein 3. Furthermore, the activation of signal transducer and activator of transcription 6 was significantly higher in Gal12-/- macrophages activated by interleukin-4, which was correlated with higher levels of transforming growth factor-ß1. Moreover, Gal12-/- macrophage-conditioned medium promoted hepatic stellate cells myofibroblast differentiation, which was indicated by higher α-smooth muscle actin expression levels compared with those treated with LacZ control medium. Finally, we demonstrated that galectin-12 knockdown negatively regulated the suppressor of cytokine signaling 3 levels. These findings suggested that galectin-12 balances M1/M2 polarization of Kupffer cells to prevent nonalcoholic fatty liver disease progression.

Bisphenol A Coupled with a High-Fat Diet Promotes Hepatosteatosis through Reactive-Oxygen-Species-Induced CD36 Overexpression.

Bisphenol A (BPA) is an endocrine-disrupting chemical that affects lipid metabolism and contributes to non-alcoholic fatty liver disease (NAFLD). The mechanism of BPA exposure in hepatic lipid accumulation and its potential effect on NAFLD remain unclear. This study investigated the effect of BPA-exposure-induced hepatic lipid deposition on the pathology of NAFLD and its underlying mechanism in vitro and in vivo. BPA increased intracellular reactive oxygen species (ROS) levels, and promoted fatty acid uptake through upregulation of a free fatty acid uptake transporter, cluster of differentiation 36 (CD36), in HUH-7 cells. Additionally, C57BL/6 mice administered a high-fat/high-cholesterol/high-cholic acid diet (HFCCD) and BPA (50 mg/kg body weight) for 8 weeks developed a steatohepatitis-like phenotype, characterized by alpha-smooth muscle actin (α-SMA, an indicator of hepatic fibrosis) and cleaved caspase 3 (an indicator of apoptosis) in hepatic tissue; moreover, they had a higher oxidative stress index of 8-hydroxydeoxyguanosine (8-OHdG) in liver tissue compared to the control group. Treatment with ROS scavenger n-acetylcysteine (NAC) ameliorated BPA-mediated HFCCD-induced lipid accumulation and steatohepatitis in the livers of treated mice. Our study indicates that BPA acts synergistically to increase hepatic lipid uptake and promote NAFLD development by stimulating ROS-induced CD36 overexpression.

Visualization and (Semi-)quantification of submicrometer plastics through scanning electron microscopy and time-of-flight secondary ion mass spectrometry.

Increasing numbers of studies have demonstrated the existence of nanoplastics (1-999 nm) in the environment and commercial products, but the current technologies for detecting and quantifying nanoplastics are still developing. Herein, we present a combination of two techniques, e.g., scanning electron microscopy (SEM) and time-of-flight secondary ion mass spectrometry (ToF-SIMS), to analyze submicron-sized plastics. A drop-casting of a 20-nL particle suspension on a Piranha solution-cleaned silicon wafer with dry ice incubation and subsequent freeze-drying was used to suppress the coffee-ring effect. SEM images were used to quantify particles, and this technique is applicable for 0.195-1.04-µm polystyrene (PS), 0.311-µm polyethylene terephthalate (PET), and 0.344-µm polyethylene (PE) at a minimum concentration of 2.49 × 109 particles/mL. ToF-SIMS could not quantify the particle number, while it could semi-quantitatively estimate number ratios of submicron PE, PET, polyvinyl chloride (PVC), and PS particles in the mixture. Analysis of submicron plastics released from three hot water-steeped teabags (respectively made of PET/PE, polylactic acid (PLA), and PET) was revisited. The SEM-derived sizes and particle numbers were comparable to those measured by a nanoparticle tracking analysis (NTA) regardless of whether or not the hydro-soluble oligomers were removed. ToF-SIMS further confirmed the number ratios of different particles from a PET/PE composite teabag leachate. This method shows potential for application in analyzing more-complex plastic particles released from food contact materials.

Bisphenol A-induced DNA damages promote to lymphoma progression in human lymphoblastoid cells through aberrant CTNNB1 signaling pathway.

Lymphoma is a group of blood cancers that develop from the immune system, and one of the main risk factors is associated with exposure to environmental chemicals. Bisphenol A (BPA) is a common chemical used in the manufacture of materials in polycarbonate and epoxy plastic products and can interfere with the immune system. BPA is considered to possibly induce lymphoma development by affecting the immune system, but its potential mechanisms have not been well established. This study performed a gene-network analysis of microarray data sets in human lymphoma tissues as well as in human cells with BPA exposure to explore module genes and construct the potential pathway for lymphomagenesis in response to BPA. This study provided evidence that BPA exposure resulted in disrupted cell cycle and DNA damage by activating CTNNB1, the initiator of the aberrant constructed CTNNB1-NFKB1-AR-IGF1-TWIST1 pathway, which may potentially lead to lymphomagenesis.

Optimization of alkali fusion process for determination of I-129 in solidified radwastes by neutron activation.

This study determines the optimum temperature for the alkali fusion process used to effectively separate iodine from solidified radwaste attaining low-level 129I by neutron activation. The alkali fusion temperature was adjusted to 120, 200, and 400 °C to approach the optimum conditions associated with a good statistical distribution of the measured 129I data and high chemical recovery yield. Statistical analysis revealed that the optimum temperature of the alkali fusion process was 200 °C, displaying good central tendency and low variance of the measured 129I data, and the respective chemical recovery yields were higher than other temperatures. The optimum fusion condition provides more reliable scaling factors (129I/137Cs) of radwaste.

Study on the correlation of bisphenol A exposure, pro-inflammatory gene expression, and C-reactive protein with potential cardiovascular disease symptoms in young adults.

Bisphenol A (BPA) is a plasticizer used in the manufacture of polycarbonate and epoxy resins. It was found that higher urinary BPA levels are more likely to be associated with coronary artery disease (CVD). In recent years, the increasing incidence of CVD among young people is observed, which may be related with inflammation rather than the traditional triple-H risk factors. BPA is an endocrine-disrupting chemical, and can induce oxidative stress and chronic inflammation since its estrogenic effect. Inflammatory responses could come from the stimulation of IκB kinases (IKKs) by estrogen receptors (ERs). Therefore, this study investigated the association of BPA exposure with the gene expression of pro-inflammatory response (ERs and IKKs), an inflammation biomarker of CVD (C-reactive protein, CRP), and physiologic index potency of CVD development symptoms in young adults. This study divided BPA exposure levels into high and low groups based on the median plasma BPA level (4.34 ng/mL), and found that the high BPA group obviously had higher BMI, blood pressure, plasma CRP levels, and gene expression of ERß and IKKß. BMI and gene expression of IKKß were also positively correlated with plasma CRP secretion. Furthermore, the study subjects with potential CVD development symptoms had the increased levels of BPA (OR 2.10, 95% CI 0.83-5.39), CRP (OR 2.61, 95% CI 1.03-10.6) and IKKß (OR 4.29, 95% CI 1.51-15.6). These results indicated that exposure to BPA is potentially associated with expression of pro-inflammatory genes related to CRP secretion, which may promote the risk of CVD development symptoms in young adults. This study highlighted the possible connection between BPA exposure and CVD development but the mechanism between them needs to be further explored.

Capturing Amyloid-ß Oligomers by Stirring with Microscaled Iron Oxide Stir Bars into Magnetic Plaques to Reduce Cytotoxicity toward Neuronal Cells.

Soluble amyloid-ß oligomers (oAß42)-induced neuronal death and inflammation response has been recognized as one of the major causes of Alzheimer's disease (AD). In this work, a novel strategy adopting silica-coated iron oxide stir bar (MSB)-based AD therapy system via magnetic stirring-induced capture of oAß42 into magnetic plaques (mpAß42) and activation of microglia on cellular plaque clearance was developed. With oAß42 being effectively converted into mpAß42, the neurotoxicity toward neuronal cells was thus greatly reduced. In addition to the good preservation of neurite outgrowth through the diminished uptake of oAß42, neurons treated with oAß42 under magnetic stirring also exhibited comparable neuron-specific protein expression to those in the absence of oAß42. The phagocytic uptake of mpAß42 by microglia was enhanced significantly as compared to the counterpart of oAß42, and the M1 polarization of microglia often occurring after the uptake of oAß42 restricted to an appreciable extent. As a result, the inflammation induced by pro-inflammatory cytokines was greatly alleviated.

A simple approach for the ultrasensitive detection of paraquat residue in adzuki beans by surface-enhanced Raman scattering.

Paraquat (PQ), a broad-spectrum contact herbicide, has been used in many countries for controlling weed growth in agriculture because of its quick-acting and nonselective contact with green plant tissue. PQ is also toxic to humans, and even contributes to the development of neurodegenerative diseases. However, PQ is generally excluded from pesticide residue monitoring programs due to the lack of suitable determination methods. Thus, this study developed a detection method combined with simple extraction and surface-enhanced Raman spectroscopy (SERS) to rapidly determine and quantify the PQ residue on legumes without destructive procedures and high-cost instruments. Following the extraction procedure of the QuPPe-method, however, we took whole adzuki beans (Vigna angularis) extracted via a mixture of methanol and 1% formic acid at room temperature and followed by a 1 min cleanup by SPE. The PQ values for adzuki beans determined by LC/MSMS showed that regardless of whether extraction was followed by the QuPPe-method or the method we proposed, a consistent and low relative standard deviation (RSD) below <22% was found. In this study, we proposed to extract PQ on the surface of the beans by shaking briefly with solvent, and then the PQ molecules were detected and quantified by depositing Ag nanoparticles (AgNPs) and performing SERS within 10 min. Using a coating of deposited Ag nanoparticles, SERS can achieve a limit of detection (LOD) for PQ on the order of 1 µg L-1 (∼4 × 10-9 M) and a method detection limit (MDL) for adzuki beans of 0.8 µg kg-1 (∼3.3 × 10-9 M). This sensitivity at the ppb level absolutely met the maximum residue limit (MRL) for PQ in dried beans as declared by most countries, including the US (0.3 mg kg-1), Australia (1.0 mg kg-1) and Taiwan (0.2 mg kg-1). Taiwan will ban the use of PQ as a defoliating agent for harvest in adzuki bean fields in 2019; therefore, developing a method for detecting PQ residues in the field or in import markets is necessary for consumer health and for authorities. This study provided an opportunity to utilize SERS in the field of on-site pesticide residue screening.

Unexpected dose response of HaCaT to UVB irradiation.

Application of high-dosage UVB irradiation in phototherapeutic dermatological treatments present health concerns attributed to UV-exposure. In assessing UV-induced photobiological damage, we investigated dose-dependent effects of UVB irradiation on human keratinocyte cells (HaCaT). Our study implemented survival and apoptosis assays and revealed an unexpected dose response wherein higher UVB-dosage induced higher viability. Established inhibitors, such as AKT- (LY294002), PKC- (Gö6976, and Rottlerin), ERK- (PD98059), P38 MAPK- (SB203580), and JNK- (SP600125), were assessed to investigate UV-induced apoptotic pathways. Despite unobvious contributions of known signaling pathways in dose-response mediation, microarray analysis identified transcriptional expression of UVB-response genes related to the respiratory-chain. Observed correlation of ROS-production with UVB irradiation potentiated ROS as the underlying mechanism for observed dose responses. Inability of established pathways to explain such responses suggests the complex nature underlying UVB-phototherapy response.

From the Cover: Comparative Proteomics Reveals Silver Nanoparticles Alter Fatty Acid Metabolism and Amyloid Beta Clearance for Neuronal Apoptosis in a Triple Cell Coculture Model of the Blood-Brain Barrier.

Silver nanoparticles (AgNPs) enter the central nervous system through the blood-brain barrier (BBB). AgNP exposure can increase amyloid beta (Aß) deposition in neuronal cells to potentially induce Alzheimer's disease (AD) progression. However, the mechanism through which AgNPs alter BBB permeability in endothelial cells and subsequently lead to AD progression remains unclear. This study investigated whether AgNPs disrupt the tight junction proteins of brain endothelial cells, and alter the proteomic metabolism of neuronal cells underlying AD progression in a triple cell coculture model constructed using mouse brain endothelial (bEnd.3) cells, mouse brain astrocytes (ALT), and mouse neuroblastoma neuro-2a (N2a) cells. The results showed that AgNPs accumulated in ALT and N2a cells because of the disruption of tight junction proteins, claudin-5 and ZO-1, in bEnd.3 cells. The proteomic profiling of N2a cells after AgNP exposure identified 298 differentially expressed proteins related to fatty acid metabolism. Particularly, AgNP-induced palmitic acid production was observed in N2a cells, which might promote Aß generation. Moreover, AgNP exposure increased the protein expression of amyloid precursor protein (APP) and Aß generation-related secretases, PSEN1, PSEN2, and ß-site APP cleaving enzyme for APP cleavage in ALT and N2a cells, stimulated Aß40 and Aß42 secretion in the culture medium, and attenuated the gene expression of Aß clearance-related receptors, P-gp and LRP-1, in bEnd.3 cells. Increased Aß might further aggregate on the neuronal cell surface to enhance the secretion of inflammatory cytokines, MCP-1 and IL-6, thus inducing apoptosis in N2a cells. This study suggested that AgNP exposure might cause Aß deposition and inflammation for subsequent neuronal cell apoptosis to potentially induce AD progression.

Ambient PM2.5 in the residential area near industrial complexes: Spatiotemporal variation, source apportionment, and health impact.

This study systemically investigated the ambient PM2.5 (n=108) with comprehensive analyses of the chemical composition, identification of the potential contributors, and estimation of the resultant respiratory physician visits in the residential regions near energy-consuming and high-polluting industries in central Taiwan. The positive matrix fraction (PMF) model with chemical profiles of trace metals, water-soluble ions, and organic/elemental carbons (OC/EC) was applied to quantify the potential sources of PM2.5. The influences of local sources were also explored using the conditional probability function (CPF). Associations between the daily PM2.5 concentration and the risk of respiratory physician visits for the elderly (≥65years of age) were estimated using time-series analysis. A seasonal variation, with higher concentrations of PM2.5, metals (As, Cd, Sb, and Pb), OC/EC and ions (i.e., NO3-, SO42- and NH4+) in the winter than in the spring and summer, was observed. Overall, an increase of 10µgm-3 in the same-day PM2.5 was associated with an ~2% (95% CI: 1.5%-2.5%) increase in respiratory physician visits. Considering the health benefits of an effective reduction, we suggest that the emission from coal combustion (23.5%), iron ore and steel industry (17.1%), and non-ferrous metallurgy (14.4%), accounting for ~70% of the primary PM2.5 in the winter are prioritized to control.

An integrative transcriptomic analysis reveals bisphenol A exposure-induced dysregulation of microRNA expression in human endometrial cells.

Bisphenol A (BPA) are commonly used in the manufacture of polycarbonate plastics. Higher BPA exposure levels have been found in patients with endometrial hyperplasia that is one of risk factors of endometrial cancer (EC). Aberrant microRNAs (miRNAs) regulation has been observed in the development of cancer. Thus, this study investigated whether BPA exposure can disrupt miRNA regulation and its gene expression regarding to EC carcinogenic progress. Microarray experiments of miRNA and mRNA were performed in human endometrial cancer RL95-2 cells with treatment of low-to-moderate (10, 103 and 105nM) BPA to explore the aberrant genes corresponding to human EC progression. According to the analysis of KEGG pathway and Cytoscape gene network, this study identified that BPA exposure reduced miR-149 expression to down-regulate DNA repair gene ARF6 (ADP-ribosylation factor 6) and tumor protein p53 (TP53), and up-regulate CCNE2 (cyclin E2) potentially to interrupt cell cycle. BPA also increased miR-107 to suppress hedgehog signaling factors, suppressor of fused homolog (SUFU) and GLI family zinc finger 3 (GLI3) to activate hedgehog signaling for cell proliferation underlying carcinogenesis. Furthermore, the BPA-induced cell proliferation was attenuated by transfection with miR-149 mimic and miR-107 inhibitor. These findings provided an insight into potential epigenetic mechanism of BPA exposure on the risk of endometrial carcinogenesis.

Effects of silver nanoparticles on the interactions of neuron- and glia-like cells: Toxicity, uptake mechanisms, and lysosomal tracking.

Silver nanoparticles (AgNPs) are commonly used nanomaterials in consumer products. Previous studies focused on its effects on neurons; however, little is known about their effects and uptake mechanisms on glial cells under normal or activated states. Here, ALT astrocyte-like, BV-2 microglia and differentiated N2a neuroblastoma cells were directly or indirectly exposed to 10 nm AgNPs using mono- and co-culture system. A lipopolysaccharide (LPS) was pretreated to activate glial cells before AgNP treatment for mimicking NP exposure under brain inflammation. From mono-culture, ALT took up the most AgNPs and had the lowest cell viability within three cells. Moreover, AgNPs induced H2 O2 and NO from ALT/activated ALT and BV-2, respectively. However, AgNPs did not induce cytokines release (IL-6, TNF-α, MCP-1). LPS-activated BV-2 took up more AgNPs than normal BV-2, while the induction of ROS and cytokines from activated cells were diminished. Ca2+ -regulated clathrin- and caveolae-independent endocytosis and phagocytosis were involved in the AgNP uptake in ALT, which caused more rapid NP translocation to lysosome than in macropinocytosis and clathrin-dependent endocytosis-involved BV-2. AgNPs directly caused apoptosis and necrosis in N2a cells, while by indirect NP exposure to bottom chamber ALT or BV-2 in Transwell, more apoptotic upper chamber N2a cells were observed. Cell viability of BV-2 also decreased in an ALT-BV-2 co-culturing study. The damaged cells correlated to NP-mediated H2 O2 release from ALT or NO from BV-2, which indicates that toxic response of AgNPs to neurons is not direct, but indirectly arises from AgNP-induced soluble factors from other glial cells.

HDAC2 and HDAC5 Up-Regulations Modulate Survivin and miR-125a-5p Expressions and Promote Hormone Therapy Resistance in Estrogen Receptor Positive Breast Cancer Cells.

Intrinsic or acquired resistance to hormone therapy is frequently reported in estrogen receptor positive (ER+) breast cancer patients. Even though dysregulations of histone deacetylases (HDACs) are known to promote cancer cells survival, the role of different HDACs in the induction of hormone therapy resistance in ER+ breast cancer remains unclear. Survivin is a well-known pro-tumor survival molecule and miR-125a-5p is a recently discovered tumor suppressor. In this study, we found that ER+, hormone-independent, tamoxifen-resistant MCF7-TamC3 cells exhibit increased expression of HDAC2, HDAC5, and survivin, but show decreased expression of miR-125a-5p, as compared to the parental tamoxifen-sensitive MCF7 breast cancer cells. Molecular down-regulations of HDAC2, HDAC5, and survivin, and ectopic over-expression of miR-125a-5p, increased the sensitivity of MCF7-TamC3 cells to estrogen deprivation and restored the sensitivity to tamoxifen. The same treatments also further increased the sensitivity to estrogen-deprivation in the ER+ hormone-dependent ZR-75-1 breast cancer cells in vitro. Kaplan-Meier analysis and receiver operating characteristic curve analysis of expression cohorts of breast tumor showed that high HDAC2 and survivin, and low miR-125a-5p, expression levels correlate with poor relapse-free survival in endocrine therapy and tamoxifen-treated ER+ breast cancer patients. Further molecular analysis revealed that HDAC2 and HDAC5 positively modulates the expression of survivin, and negatively regulates the expression miR-125a-5p, in ER+ MCF7, MCF7-TamC3, and ZR-75-1 breast cancer cells. These findings indicate that dysregulations of HDAC2 and HDAC5 promote the development of hormone independency and tamoxifen resistance in ERC breast cancer cells in part through expression regulation of survivin and miR-125a-5p.

Influence of silver and titanium dioxide nanoparticles on in vitro blood-brain barrier permeability.

An in vitro blood-brain barrier (BBB) model being composed of co-culture with endothelial (bEnd.3) and astrocyte-like (ALT) cells was established to evaluate the toxicity and permeability of Ag nanoparticles (AgNPs; 8nm) and TiO2 nanoparticles (TiO2NPs; 6nm and 35nm) in normal and inflammatory central nervous system. Lipopolysaccharide (LPS) was pre-treated to simulate the inflammatory responses. Both AgNPs and Ag ions can decrease transendothelial electrical resistance (TEER) value, and cause discontinuous tight junction proteins (claudin-5 and zonula occludens-1) of BBB. However, only the Ag ions induced inflammatory cytokines to release, and had less cell-to-cell permeability than AgNPs, which indicated that the toxicity of AgNPs was distinct from Ag ions. LPS itself disrupted BBB, while co-treatment with AgNPs and LPS dramatically enhanced the disruption and permeability coefficient. On the other hand, TiO2NPs exposure increased BBB penetration by size, and disrupted tight junction proteins without size dependence, and many of TiO2NPs accumulated in the endothelial cells were observed. This study provided the new insight of toxic potency of AgNPs and TiO2NPs in BBB.

Dust levels of polybrominated diphenyl ethers (PBDEs) and polybrominated dibenzo-p-dioxins/furans (PBDD/Fs) in the Taiwanese elementary school classrooms: Assessment of the risk to school-age children.

Elementary school classroom dust is an important source of exposure to polybrominated dibenzo-p-dioxins/furans and diphenyl ethers (PBDD/DF/DEs) for school-age children. Our goal is thus to investigate concentrations of PBDD/DF/DEs in elementary school classroom dust to further assess the impact on school-age children via ingestion. The dust from classrooms, including both normal (NR) and computer classrooms (CR), was collected from six urban and four rural schools. Fourteen PBDEs and twelve PBDD/Fs were measured using high-resolution gas-chromatography/high-resolution mass-spectrometry. The mean levels of Σ14PBDEs in NR and CR dust from the urban classrooms were 370 and 2510ng/g and those whose dust from the rural classrooms were 464 and 1780ng/g. The means of ΣPBDD/Fs were 0.0401ng-WHO2005-TEQ/g (concentration: 4.72ng/g) in urban NR dust, 0.0636ng-WHO2005-TEQ/g (7.51ng/g) in urban CR dust, 0.0281ng-WHO2005TEQ/g (3.60ng/g) in rural NR dust, and 0.0474ng-WHO2005TEQ/g (6.28ng/g) in rural CR dust. The PBDEs pattern in NR dust was quite different from that in CR dust, but the PBDD/Fs patterns in NR and CR dust were similar. A linearly significant correlation coefficient (n=20, r=0.862, p<0.001) was found between ΣPBDEs and ΣPBDD/Fs in NR and CR dust, indicating that the PBDEs and PBDD/Fs in the dust may be from the same sources in the elementary school classrooms. This study assessed the risks (daily intake and cancer and non-cancer risks) of PBDEs and PBDD/Fs for the children from the classroom dust, and the calculated risk values did not exceed the related thresholds. With regard to the exposure scenarios for school-age children in an indoor environment, the results suggest that they might ingest more dust PBDD/DF/DEs in their homes than in the schools. In conclusion, the exposure of Taiwanese elementary school children to PBDD/DF/DEs via indoor dust was with a safe range based on our findings.

An Integrative Transcriptomic Analysis for Identifying Novel Target Genes Corresponding to Severity Spectrum in Spinal Muscular Atrophy.

Spinal muscular atrophy (SMA) is an inherited neuromuscular disease resulting from a recessive mutation in the SMN1 gene. This disease affects multiple organ systems with varying degrees of severity. Exploration of the molecular pathological changes occurring in different cell types in SMA is crucial for developing new therapies. This study collected 39 human microarray datasets from ArrayExpress and GEO databases to build an integrative transcriptomic analysis for recognizing novel SMA targets. The transcriptomic analysis was conducted through combining weighted correlation network analysis (WGCNA) for gene module detection, gene set enrichment analysis (GSEA) for functional categorization and filtration, and Cytoscape (visual interaction gene network analysis) for target gene identification. Seven novel target genes (Bmp4, Serpine1, Gata6, Ptgs2, Bcl2, IL6 and Cntn1) of SMA were revealed, and are all known in the regulation of TNFα for controlling neural, cardiac and bone development. Sequentially, the differentially expressed patterns of these 7 target genes in mouse tissues (e.g., spinal cord, heart, muscles and bone) were validated in SMA mice of different severities (pre-symptomatic, mildly symptomatic, and severely symptomatic). In severely symptomatic SMA mice, TNFα was up-regulated with attenuation of Bmp4 and increase of Serpine1 and Gata6 (a pathway in neural and cardiac development), but not in pre-symptomatic and mildly symptomatic SMA mice. The severely symptomatic SMA mice also had the elevated levels of Ptgs2 and Bcl2 (a pathway in skeletal development) as well as IL6 and Cntn1 (a pathway in nervous system development). Thus, the 7 genes identified in this study might serve as potential target genes for future investigations of disease pathogenesis and SMA therapy.