Health risk assessment of heavy metal(loid)s in road dust via dermal exposure pathway from a low latitude plateau provincial capital city: The importance of toxicological verification.

The human health risk assessment through the dermal exposure of metal (loid)s in dust from low latitude and high geological background plateau cities was largely unknown. In this study, the road dust samples were harvested from a typical low-latitude plateau provincial capital city Kunming, Southwest China. The total concentration and dermal bioaccessibility of heavy metal (loid)s in road dust were determined, and their health risks as well as cytotoxicity on human skin keratinocytes were also assessed. The average concentrations of As (28.5 mg/kg), Cd (2.65 mg/kg), Mn (671 mg/kg), and Zn (511 mg/kg) exceeded the soil background values. Arsenic had the highest bioaccessibility after 2 h (3.79%), 8 h (4.24%), and 24 h (16.6%) extraction. The dermal pathway when bioaccessibility is considered has a higher hazard quotient than the conventional method using total metal(loid)s in the dust. In addition, toxicological verification suggested that the dust extracts suppressed the cell viability, increased the reactive oxygen species (ROS) level and DNA damage, and eventually activated the mitochondria-mediated apoptosis pathway, evidenced by the upregulation of Caspase-3/9, Bax, and Bak-1. Cadmium was positively correlated with the mRNA expression of Bax. Taken together, our data indicated that both dermal bioaccessibility and cytotoxicity should be considered for accurate human skin health risk assessment of heavy metal(loid)s in road dust, which may provide new insight for accurate human health risk assessment and environmental management.

A novel approach to assess the health risk of aryl hydrocarbon receptor-bound contaminants via inhalation exposure using CYP1A1 expression as a biomarker.

Polycyclic aromatic hydrocarbons (PAHs) and dioxins are potential causes of multiple diseases by activating the aryl hydrocarbon receptor (AhR) pathway. Health risk assessment of chemicals primarily relies on the relative potency factor (RPF), although its accuracy may be limited when solely using EC50 values. The induction of cytochrome P4501A1 (CYP1A1) serves as a biomarker for AhR activation and is an integrator of dioxin-like toxicity. Here, we present a method for evaluating the risks associated with AhR activation using mathematical models of dose-CYP1A1 induction. The dose-effect curves for certain PAHs and dioxins, including Ant, BghiP, 1,2,3,4,7,8-HxCDD, and others, exhibited a non-classical S-shaped form. The toxic equivalent factor (TEF) profiles revealed a broad range of toxic equivalent factor values. The TEFs for PAHs ranged from approximately 0.01 to 6, with higher values being observed when the concentration was less than 10-10 M, with the exceptions of Ace, Phe, and BghiP. Most congeners of dioxins got the lowest TEF value at around 10-10 M, ranging from 0.04 to 1.00. The binding affinity of AhR to ligands did not display a strong correlation with the EC50 of CYP1A1 expression, suggesting that the AhR-mediated effects of PAHs and dioxins are not fixed but instead fluctuate with the dose. Air samples acquired from a parking area were used to compare the proficiency of RPF and our current approach. In the current method, naphthalene and chrysene were the primary contributors of PAHs to AhR-mediated risks in parking lots air samples, respectively. However, the contributions of naphthalene and chrysene could be disregarded in the RPF approach.

TBK1-medicated DRP1 phosphorylation orchestrates mitochondrial dynamics and autophagy activation in osteoarthritis.

Mitochondrial dynamics, including mitochondrial fission and fusion, are critical for maintaining mitochondrial functions. Evidence shows that TANK-binding kinase 1 (TBK1) regulates mitochondrial fusion and fission and then mitophagy. Since a previous study demonstrates a strong correlation between mitophagy and osteoarthritis (OA), we herein investigated the potential role of TBK1 in OA process and mitochondrial functions. We demonstrated a strong correlation between TBK1 and OA, evidenced by significantly downregulated expression of TBK1 in cartilage tissue samples of OA patients and in the chondrocytes of aged mice, as well as TNF-α-stimulated phosphorylation of TBK1 in primary mouse chondrocytes. TBK1 overexpression significantly attenuated TNF-α-induced apoptosis and abnormal mitochondrial function in primary mouse chondrocytes. Furthermore, TBK1 overexpression induced remodeling of mitochondrial morphology by directly phosphorylating dynamin-related protein 1 (DRP1) at Ser637, abolishing the fission of DRP1 and preventing its fragmentation function. Moreover, TBK1 recruitment and DRP1 phosphorylation at Ser637 was necessary for engulfing damaged mitochondria by autophagosomal membranes during mitophagy. Moreover, we demonstrated that APMK/ULK1 signaling contributed to TBK1 activation. In OA mouse models established by surgical destabilization of the medial meniscus, intraarticular injection of lentivirus-TBK1 significantly ameliorated cartilage degradation via regulation of autophagy and alleviation of cell apoptosis. In conclusion, our results suggest that the TBK1/DRP1 pathway is involved in OA and pharmacological targeting of the TBK1-DRP1 cascade provides prospective therapeutic benefits for the treatment of OA.

Associations between urinary monohydroxylated polycyclic aromatic hydrocarbons and unexplained recurrent spontaneous abortion and health risk assessment in a large case-control study in China.

Polycyclic aromatic hydrocarbons (PAHs) are a group of environmental endocrine disruptors with known carcinogenic, reproductive, and developmental toxicity. Important knowledge gaps remain regarding the relationship between PAH exposure and unexplained recurrent spontaneous abortion (URSA). In the present study, twelve monohydroxylated polycyclic aromatic hydrocarbons (OH-PAHs) were measured in the urine of 413 URSA cases and 434 controls. The main OH-PAHs measured in this study were monohydroxy metabolites of naphthalene, followed by fluorene and phenanthrene. After the creatinine correction, the median concentration of urinary OH-PAHs in the control group (17.4 µg/g Creatinine) was higher than that in the case group (14.2 µg/g Creatinine). There was no positive relationship between PAH exposure and URSA using binary logistic regression analysis. Among 847 Chinese women of childbearing age, residential environment, type of drinking water, and education level were the influencing factors of PAH exposure. The health risk assessment showed that over 98% of women had a carcinogenic risk with carcinogenic risk values above the acceptable level (10-6). Although this large-scale case-control study did not observe an association between PAH exposure and URSA, more attention should be paid to the high carcinogenic risk due to PAH exposure in women of reproductive age.

Co-exposure health risk of benzo[a]pyrene with aromatic VOCs: Monoaromatic hydrocarbons inhibit the glucuronidation of benzo[a]pyrene.

Occupational workers and residents near petrochemical industry facilities are exposed to multiple contaminants on a daily basis. However, little is known about the co-exposure effects of different pollutants based on biotransformation. The study examined benzo[a]pyrene (BaP), a representative polycyclic aromatic hydrocarbon related to the petrochemical industry, to investigate changes in toxicity and co-exposure mechanism associated with different monoaromatic hydrocarbons (MAHs). A central composite design method was used to simulate site co-exposure scenarios to reveal biotransformation of BaP when co-exposed with benzene, toluene, chlorobenzene, or nitrobenzene in microsome systems. BaP metabolism depended on MAH concentration, and association of MAH with microsome concentration/incubation time. Particularly, MAH co-exposure negatively affected BaP glucuronidation, an important phase Ⅱ detoxification process. BaP metabolite intensities decreased to 43%-80% for OH-BaP-G, and 32%-71% for diOH-BaP-G in co-exposure system with MAHs, compared with control group. Furthermore, glucuronidation was affected by competitive and time-dependent inhibition. Co-exposure significantly decreased gene expression of UGT 1A10 and BCRP/ABCG2 in HepG2 cells, which are involved in BaP detoxification through metabolism and transmembrane transportation. Therefore, human co-exposure to multiple contaminants may deteriorate toxic effects of these chemicals by disturbing metabolic pathways. This study provides a reference for assessing toxic effects and co-exposure risks of pollutants.

Construction of Benzimidazolone Derivatives via Aryl Iodide Catalyzed Intramolecular Oxidative C-H Amination.

The first aryl iodide catalyzed intramolecular C-H amination of phenylurea has been disclosed for high-efficiency synthesis of benzimidazolone derivatives in excellent yields (up to 97%) by an operationally simple one-step organocatalytic oxidative process. Fluorinated protic alcohols can efficiently accelerate the conversion of this transformation. The straightforward method has good functional group tolerance and can be performed with an inexpensive and readily accessible catalyst with high proficiency.

Levels and health risks of urinary phthalate metabolites and the association between phthalate exposure and unexplained recurrent spontaneous abortion: a large case-control study from China.

Phthalate acid esters (PAEs) are environmental endocrine disruptors that can interfere with endocrine processes and cause adverse reproductive outcomes. The link between PAE exposure and unexplained recurrent spontaneous abortion (URSA) remains unknown. In this study, nine urinary metabolites of PAEs (mPAEs) were measured in 594 URSA cases and 569 healthy controls. The measured mPAEs were ubiquitously detected and present at higher levels (median: 203 ng/mL) in the URSA cases than in the controls (median: 161 ng/mL). Multiple logistic regression analysis showed that URSA was associated with higher concentrations of mono (2-ethyl-5-hydroxyhexyl) phthalate (mEHHP), mono (2-ethylhexyl) phthalate (mEHP), and mono-ethyl phthalate (mEP) and lower concentrations of mono-isobutyl phthalate (miBP). Moreover, a quantile-based g-computation (QGC) model revealed a positive association between mPAEs mixture and URSA. The URSA cases showed significantly higher concentrations of di-(2-ethylhexyl) phthalate (DEHP) than the controls. This was consistent with the health risk assessment, which suggested that DEHP is the main contributors to potential non-carcinogenic risk. DEHP accounted for over 80% of total risk. The large case-control study results suggest that PAE exposure may increase the risk of URSA, and that policy-makers and public health experts should pay more attention to DEHP exposure.

Non-IgE mediated mast cell activation.

Mast cells (MCs) are innate immune cells that are scattered in tissues throughout the organism being particularly abundant at sites exposed to the environment such as the skin and mucosal surfaces. Generally known for their role in IgE-mediated allergies, they have also important functions in the maintenance of tissue integrity by constantly sensing their microenvironment for signals by inflammatory triggers that can comprise infectious agents, toxins, hormones, alarmins, metabolic states, etc. When triggered their main function is to release a whole set of inflammatory mediators, cytokines, chemokines, and lipid products. This allows them to organize the ensuing innate immune and inflammatory response in tight coordination with resident tissue cells, other rapidly recruited immune effector cells as well as the endocrine and exocrine systems of the body. To complete these tasks, MCs are endowed with a large repertoire of receptors allowing them to respond to multiple stimuli or directly interact with other cells. Here we review some of the receptors expressed on MCs (ie, receptors for Immunoglobulins, pattern recognition receptors, nuclear receptors, receptors for alarmins, and a variety of other receptors) and discuss their functional implication in the immune and inflammatory response focusing on non-IgE-mediated activation mechanisms.

Identifying Dermal Uptake as a Significant Pathway for Human Exposure to Typical Semivolatile Organic Compounds in an E-Waste Dismantling Site: The Relationship of Contaminant Levels in Handwipes and Urine Metabolites.

Dermal exposure to semivolatile organic compounds (SVOCs) has recently attracted widespread attention; understanding these exposures is particularly important for people whose skin is frequently exposed to different pollution surfaces. In this study, handwipes were collected from exposed occupational workers and local residents near a typical electronic waste (e-waste) dismantling area; urine samples were also sampled. The wipes were analyzed for three typical SVOCs: polybrominated diphenyl ethers (PBDEs), polycyclic aromatic hydrocarbons (PAHs), and organophosphate flame retardants (OPFRs). The median levels of PAHs, OPFRs, and PBDEs in handwipes from e-waste dismantlers were 96.0, 183, and 238 ng, respectively. The analytes were higher in the handwipes collected from workers than those from residents, indicating that they were subjected to greater dermal exposure during primitive e-waste dismantling activities. Among the three SVOCs, the strongest correlation was found between triphenyl phosphate (TPhP) in handwipes and diphenyl phosphate (DPhP) in paired urine; the next strongest correlations were between PAHs and PBDEs and their corresponding urinary metabolites. The results showed that TPhP contributed the highest exposure to e-waste dismantlers via dermal exposure. Our research highlights the importance of dermal exposure to TPhP, which should be considered in future exposure risk assessments.

Influence of nutrients on the bioaccessibility and transepithelial transport of polybrominated diphenyl ethers measured using an in vitro method and Caco-2 cell monolayers.

Previous research has shown the absorption of polybrominated diphenyl ethers (PBDEs) in the human gastrointestinal tract, but limited attention has been given to the influence of nutrients on PBDE absorption from food matrices. We investigated the effects of nutrients (oil, starch, protein, and dietary fiber) on the absorption and transport of PBDEs in a Caco-2 cell model and bioaccessibility of PBDEs by an in vitro gastrointestinal digestion method. The results showed that the accumulation ratios of PBDE congeners in Caco-2 cells were higher in the nutrient addition groups (oil: 26.7-50.6%, starch: 27.0-58.7%, protein: 12.1-44.1%, and dietary fiber: 28.2-55.1%) than the control group (7.17-36.1%), whereas the transport ratios were lower (oil: 2.30-7.20%, starch: 1.55-9.15%, protein: 1.04-8.78%, and dietary fiber: 0.85-7.04%) than control group (3.78-11.1%). Additionally, the PBDE bioaccessibility could be increased by adding the nutrients, particularly oil and starch. This study clarified the differences in PBDE absorption in the presence of nutrients using the in vitro digestion and Caco-2 cell model. The findings showed that nutrients were an important factor that promoted PBDE absorption in the gastrointestinal tract. Therefore, it is important to focus on a novel dietary strategy of food consumption with contaminant compounds to protect human health.

Organophosphate flame retardants, tetrabromobisphenol A, and their transformation products in sediment of e-waste dismantling areas and the flame-retardant production base.

Due to the prohibition of polybrominated diphenyl ethers, organophosphate flame retardants (OPFRs) and tetrabromobisphenol A (TBBPA) have become emerging flame retardants. However, knowledge about their occurrence, especially their transformation products, is still limited. This study collected sediment samples from two rivers, i.e., Lianjiang River (located at an e-waste dismantling area) and Xiaoqing River (situated at a flame retardant production base), to investigate the occurrence, composition, and spatiality distribution of OPFRs, TBBPA, and their transformation products. Both targets were detected in the Lianjiang River in the range of 220-1.4 × 104 and 108-3.1 × 103 ng/g dw (dry weight) for OPFRs and TBBPA, and 0.11-2.35 and 4.8-414 ng/g dw for their respective transformation products, respectively. The concentrations of OPFRs and TBBPA in the Xiaoqing River ranged from 4.15 to 31.5 and 0.76-2.51 ng/g dw, respectively, and no transformation products were detected. Different compositional characteristics of OPFRs and distinct spatial distribution from mainstream and tributary observed between the two rivers are attributed to the difference in the local industries. Spatial distribution and principal component analysis indicated that e-waste dismantling activities could be a vital source of local pollution. Besides, the confluence of tributaries seemed to determine the contaminant levels in the Xiaoqing River. Also, concentration ratios and Spearman's correlation between metabolites and parent chemicals were analyzed. Low concentration ratios (3.6 ×10-4 to 0.16) indicated a low transformation degree, and Spearman's correlation analysis suggested transformation products were partly stemming from commercial products. Considering the limited study of these transformation products, more studies on their sources, transform mechanism, and toxicity are required.

Exploring Neurofeedback Training for BMI Power Augmentation of Upper Limbs: A Pilot Study.

Electroencephalography neurofeedback (EEG-NFB) training can induce changes in the power of targeted EEG bands. The objective of this study is to enhance and evaluate the specific changes of EEG power spectral density that the brain-machine interface (BMI) users can reliably generate for power augmentation through EEG-NFB training. First, we constructed an EEG-NFB training system for power augmentation. Then, three subjects were assigned to three NFB training stages, based on a 6-day consecutive training session as one stage. The subjects received real-time feedback from their EEG signals by a robotic arm while conducting flexion and extension movement with their elbow and shoulder joints, respectively. EEG signals were compared with each NFB training stage. The training results showed that EEG beta (12-40 Hz) power increased after the NFB training for both the elbow and the shoulder joints' movements. EEG beta power showed sustained improvements during the 3-stage training, which revealed that even the short-term training could improve EEG signals significantly. Moreover, the training effect of the shoulder joints was more obvious than that of the elbow joints. These results suggest that NFB training can improve EEG signals and clarify the specific EEG changes during the movement. Our results may even provide insights into how the neural effects of NFB can be better applied to the BMI power augmentation system and improve the performance of healthy individuals.

New Mixed Bromine/Chlorine Transformation Products of Tetrabromobisphenol A: Synthesis and Identification in Dust Samples from an E-Waste Dismantling Site.

The large-scale production and usage of tetrabromobisphenol A (TBBPA) and its analogues have caused widespread contamination, raising concern about their potential endocrine disruption effects on both humans and ecosystems. In the present study, debromination and unknown mixed bromine/chlorine transformation products of TBBPA (X-BBPA) were screened in dust samples from an e-waste dismantling site. Five monochloro products (2-chloro-2',6,6'-TriBBPA, 2-chloro-2',6-DiBBPA, 2-chloro-2',6'-DiBBPA, 2-chloro-2'-MoBBPA, and 2-chloro-6-MoBBPA) and two dichloro products (2,2'-dichloro-6,6'-DiBBPA and 2,2'-dichloro-6-MoBBPA) were successfully synthesized and structurally identified. TBBPA and its transformation products were detected by comparison of their mass spectra and retention times with those of synthetic standards. The mean concentration of X-BBPA was 1.63 × 104 ng/g in e-waste dismantling workshop dust samples based on dry weight, which was at a similar level to TBBPA. However, it was 1 order of magnitude lower than the concentrations of the debromination congeners. Thus, both debromination and chlorine-bromine exchange may be important reactions during the thermal processing of e-waste. The results on mixed chlorinated/brominated TBBPA transformation products provided new insights into TBBPA transformation. The elevated levels of the transformation products of TBBPA suggested that these products should be targeted to avoid underestimation of possible health risks.

Derivatization gas chromatography negative chemical ionization mass spectrometry for the analysis of trace organic pollutants and their metabolites in human biological samples.

Gas chromatography negative chemical ionization mass spectrometry (GC-NCI-MS) is a preferred instrumental approach for the trace and ultra-trace analysis of various toxic organics and their metabolites in human biological fluids. Specifically, the method has played an important role in the highly sensitive and specific quantitative detection of persistent highly halogenated compounds in environmental matrices and biota during the past few decades. However, for the analysis of toxic metabolites with active hydrogen atoms, such as acids, alcohols, and phenolic compounds, from biological matrixes or organics without electronegative atoms or groups, a derivatization step is often needed prior to GC analysis. Such derivatization aims to change the properties of targets to improve their separation, increase their volatility, and enhance the sensitivity of instrumental detection. This review summarizes three derivatization strategies commonly used for GC methods, i.e., alkylation, silylation, and acylation, together with their application combined with GC-NCI-MS for the high sensitivity analysis of toxic organic metabolites in the human body. The advantages and disadvantages of each derivatization method and potential directions for future applications are discussed. Given the broad variety of applications as well as the compound-specific sensitivity for the ultra-trace analysis of target xenobiotics in human biological fluids, subsequent studies are required to develop convenient, faster derivatization procedures and reagents better suited for routine analysis. Graphical abstract.

The exposure risk of typical VOCs to the human beings via inhalation based on the respiratory deposition rates by proton transfer reaction-time of flight-mass spectrometer.

The respiratory deposition rates are the important analytical parameters for human health risk assessment related to the environmental volatile organic compounds (VOCs). In present study, the deposition rates from the linear regressions of CH2O, CH5N, C2H6O, C2H4O2, C3H8O, C6H6, C7H8, C8H8, and C8H10 of 120 healthy volunteers were obtained with significantly different from the respective calculated deposition rates. The CH2O (formaldehyde) has the highest deposition rate, indicating the highest associated exposure risk of CH2O if the persons are exposed to the same concentrations of these VOCs through inhalation. In order to explore the effects of the breathing models and sampling time on the deposition rates of VOCs, volunteers were first asked to breathe successively with nasal-in-nasal-out, oral-in-nasal-out, and oral-in-oral-out breathing models before and after three meals for three days. Sampling time variation has no effect on the deposition rates of selected VOCs, while the deposition rates of C2H4O2, C3H8O, C6H6, C7H8 and C8H10 by nasal-in-nasal-out were significantly different from oral-in-oral-out and nasal-in-oral-out models. Among all the breathing models, nasal-in-oral-out comprises the entire respiratory system. In order to further validate the results, the deposition rates of the selected VOCs were calculated in 120 healthy volunteers using nasal-in-oral-out breathing model for unlimited time after the conventional lung function examination. Difference in gender and body mass index had no effect on the deposition rates of VOCs, while the age affects the deposition rates of CH2O, CH5N and C2H4O2. Positive correlation analysis between lung function factors and deposition rates revealed that the individuals with larger lung function factors are more susceptible to deposit the VOCs. Overall, the main conclusion can be drawn that the respiratory deposition rates were influenced by the physiological factors. Therefore, the major objective for future research is to accurately calculate the deposition rates of environmental VOCs for health-risk assessment.

Simultaneous determination of polybrominated diphenyl ethers, polycyclic aromatic hydrocarbons and their hydroxylated metabolites in human hair: a potential methodology to distinguish external from internal exposure.

A new method for the simultaneous detection of 20 polybrominated diphenyl ethers (PBDEs), 16 polycyclic aromatic hydrocarbons (PAHs), 4 hydroxyl PBDEs (OH-PBDEs) and 10 hydroxyl PAHs (OH-PAHs) in human hair has been developed for the first time. External target analytes from hair (hair-Ex) were ultrasonically extracted with acetone, while the internal target analytes (hair-In) were obtained with further digestion and liquid-liquid extraction of washed hair. Alkaline digestion with liquid-liquid extraction under alkaline and re-acidification combination conditions was the key procedure to successfully extract both parent and metabolic compounds from hair. Both external and internal extracts were purified with gel permeation chromatography, and the parent compounds were subsequently separated from their hydroxylated metabolites with a silica solid phase extraction column prior to instrumental analysis. GC-MS-MS, GC-MS and HPLC-MS-MS were used to analyze PAHs, PBDEs and their hydroxylated metabolites, respectively. The method showed satisfactory accuracy as well as precision, and the recoveries of PBDEs, PAHs, OH-PBDEs and OH-PAHs ranged from 62%-145%, 48%-135%, 60%-146% and 60%-88%, respectively. The developed method was validated in a pilot biomonitoring campaign. All parent analytes were approximately 100% detected in both hair-In and hair-Ex, while no OH-PBDEs were detected in hair-In and hair-Ex. All OH-PAHs were approximately 100% detected in hair-In with a mean Σ10OH-PAHs concentration of 174.7 ng per g dry weight (dw), and the concentration in hair-Ex was 18 times lower than that in hair-In with a relatively lower detection frequency. Both partial least squares discriminant analysis (PLS-DA) and Spearman correlation analysis with the concentration of analytes confirmed that the developed method performed well to distinguish the internal from external exposure to target analytes in hair.

Persistent DNA methylation changes in zebrafish following graphene quantum dots exposure in surface chemistry-dependent manner.

Modified nano-graphene quantum dots (M-GQDs) are widely used in bioimaging, drug delivery, and chemical engineering. Because M-GQDs could induce reactive oxygen species and DNA damage, we hypothesized that M-GQDs modulate DNA methylation. To test this hypothesis, zebrafish were exposed to reduced, hydroxylated, or aminated GQDs (graphene quantum dots) at different concentrations for 7 days; global DNA methylation in liver, gill, and intestine was then studied. M-GQDs induced global DNA hypermethylation in various tissues in a dose-dependent manner. The global DNA methylation of reduced and aminated GQDs exposure showed a significant increase in intestines even at low concentrations (2 mg/L), suggesting that intestines are the main target for these two M-GQDs. The effects of global DNA methylation were evaluated 14 days after exposure had ceased. DNA methylation in the livers of exposure groups was significantly higher than in control zebrafish. Global DNA methylation increased in livers of zebrafish even after exposure to aminated GQDs (2 mg/L) had ceased, indicating a more complex mechanism of DNA methylation deregulation. The present results showed that chemical groups in the surface of GQDs are a critical factor for modulating DNA methylation.

Urinary parabens in adults from South China: Implications for human exposure and health risks.

Parabens are a kind of preservatives widely used in cosmetic and personal care products and ubiquitously detected in the environment. However, little is known on human exposure to these chemicals. Our study mainly investigated the urinary parabens in adults from South China to evaluate the cumulative risk of paraben exposure. A total of 562 urine samples were collected from adult workers for the determination of methyl paraben (MeP), ethyl paraben (EtP), propyl paraben (PrP), butyl paraben, and benzyl parabens. High detection frequencies (≥98%) were observed for MeP, EtP, and PrP with median concentrations of 8.88, 5.11, and 1.44 µg/L, respectively. Urinary parabens was 4.5-46.2 fold higher in urine of females than those in males. Urinary MeP was associated with alcohol drinking and a history of tumor, while urinary PrP was negatively associated with education levels of the subjects. There were not significant associations between urinary concentrations of parabens and body mass index, which indicated that obesity was not associated with paraben exposure. Also, parabens did not correlate with human dietary habits. Although the total estimated daily intake (TEDI) of the major compound MeP and EtP in adult workers was lower than the acceptable daily intake (ADI), the TEDI of PrP exceed the ADI for a very few subjects, especially for females and low-educated ones, suggesting potential health risks.

A Transcriptomic Insight into the Impact of Colon Cancer Cells on Mast Cells.

Mast cells (MCs) are one of the first immune cells recruited to a tumor. It is well recognized that MCs accumulate in colon cancer lesion and their density is associated with the clinical outcomes. However, the molecular mechanism of how colon cancer cells may modify MC function is still unclear. In this study, primary human MCs were generated from CD34⁺ progenitor cells and a 3D coculture model was developed to study the interplay between colon cancer cells and MCs. By comparing the transcriptomic profile of colon cancer-cocultured MCs versus control MCs, we identified a number of deregulated genes, such as MMP-2, VEGF-A, PDGF-A, COX2, NOTCH1 and ISG15, which contribute to the enrichment of cancer-related pathways. Intriguingly, pre-stimulation with a TLR2 agonist prior to colon cancer coculture induced upregulation of multiple interferon-inducible genes as well as MHC molecules in MCs. Our study provides an alternative approach to study the influence of colon cancer on MCs. The transcriptome signature of colon cancer-cocultured MCs may potentially reflect the mechanism of how colon cancer cells educate MCs to become pro-tumorigenic in the initial phase and how a subsequent inflammatory signal-e.g., TLR2 ligands-may modify their responses in the cancer milieu.

Low-concentration BPF induced cell biological responses by the ERα and GPER1-mediated signaling pathways in MCF-7 breast cancer cells.

Bisphenol F (BPF), one of the alternatives to bisphenol A (BPA), can induce proliferation through the nuclear estrogen receptor ERα (estrogen receptor alpha) pathway in human breast cancer MCF-7 cells. However, the roles of membrane estrogen receptor GPER1 (G-protein-coupled receptor 1)-mediated signaling pathways in MCF-7 cell proliferation caused by BPF are unclear. The influence of BPF on MCF-7 cells was evaluated in terms of cell proliferation, intracellular calcium (Ca2+) fluctuations, and reactive oxygen species (ROS) generation. The molecular mechanisms of the cellular responses to low doses of BPF were studied through detecting the activations of ERα and GPER1-regulated PI3K/PKB or AKT (phosphatidylinotidol 3-kinase/protein kinase B) and ERK1/2 (extracellular-signa1-regulated kinase 1/2) signals. At 0.01-1 µM, BPF significantly promoted cell proliferation and elevated the levels of intracellular ROS and Ca2+. At these concentrations, BPF also significantly upregulated protein expressions of ERα, GPER1, c-myc, and cyclin D and phosphorylations of PKB and ERK1/2. Specific signal inhibitors decreased PKB and ERK1/2 phosphorylations and attenuated the effects of BPF. Silencing of GPER1 also significantly decreased BPF-induced cell proliferation. These results indicate that activating the GPER1-PI3K/PKB and ERK1/2 signals by low doses of BPF can regulate the response of MCF-7 cells and that ERα also influences the effects of exposure to BPF on the cells. The present study suggests a new mechanism by which BPF exerts relevant estrogenic action in cancer cells and also highlights the potential risks in using BPF as an alternative to BPA.