Environmental phenol exposures in 6- to 12-week-old infants: The Infant Feeding and Early Development (IFED) study.

BACKGROUND: Exposure to phenols, endocrine-disrupting chemicals used in personal care and consumer products, is widespread. Data on infant exposures are limited despite heightened sensitivity to endocrine disruption during this developmental period. We aimed to describe distributions and predictors of urinary phenol concentrations among U.S. infants ages 6-12 weeks. METHODS: The Infant Feeding and Early Development (IFED) study is a prospective cohort study of healthy term infants enrolled during 2010-2013 in the Philadelphia region. We measured concentrations of seven phenols in 352 urine samples collected during the 6- or 8- and/or 12-week study visits from 199 infants. We used linear mixed models to estimate associations of maternal, sociodemographic, infant, and sample characteristics with natural-log transformed, creatinine-standardized phenol concentrations and present results as mean percent change from the reference level. RESULTS: Median concentrations (µg/L) were 311 for methylparaben, 10.3 for propylparaben, 3.6 for benzophenone-3, 2.1 for triclosan, 1.0 for 2,5-dichlorophenol, 0.7 for BPA, and 0.3 for 2,4-dichlorophenol. Geometric mean methylparaben concentrations were approximately 10 times higher than published estimates for U.S. children ages 3-5 and 6-11 years, while propylparaben concentrations were 3-4 times higher. Infants of Black mothers had higher concentrations of BPA (83%), methylparaben (121%), propylparaben (218%), and 2,5-dichorophenol (287%) and lower concentrations of benzophenone-3 (-77%) and triclosan (-53%) than infants of White mothers. Triclosan concentrations were higher in breastfed infants (176%) and lower in infants whose mothers had a high school education or less (-62%). Phenol concentrations were generally higher in summer samples. CONCLUSIONS: Widespread exposure to select environmental phenols among this cohort of healthy U.S. infants, including much higher paraben concentrations compared to those reported for U.S. children, supports the importance of expanding population-based biomonitoring programs to infants and toddlers. Future investigation of exposure sources is warranted to identify opportunities to minimize exposures during these sensitive periods of development.

Environmental chemical-wide associations with immune biomarkers in US adults: A cross-sectional analysis.

Environmental chemical exposures influence immune system functions, and humans are exposed to a wide range of chemicals, termed the chemical "exposome". A comprehensive, discovery analysis of the associations of multiple chemical families with immune biomarkers is needed. In this study, we tested the associations between environmental chemical concentrations and immune biomarkers. We analyzed the United States cross-sectional National Health and Nutrition Examination Survey (NHANES, 1999-2018). Chemical biomarker concentrations were measured in blood or urine (196 chemicals, 17 chemical families). Immune biomarkers included counts of lymphocytes, neutrophils, monocytes, basophils, eosinophils, red blood cells, white blood cells, and mean corpuscular volume. We conducted separate survey-weighted, multivariable linear regressions of each log2-transformed chemical and immune measure, adjusted for relevant covariates. We accounted for multiple comparisons using a false discovery rate (FDR). Among 45,528 adult participants, the mean age was 45.7 years, 51.4% were female, and 69.3% were Non-Hispanic White. 71 (36.2%) chemicals were associated with at least one of the eight immune biomarkers. The most chemical associations (FDR<0.05) were observed with mean corpuscular volume (36 chemicals) and red blood cell counts (35 chemicals). For example, a doubling in the concentration of cotinine was associated with 0.16 fL (95% CI: 0.15, 0.17; FDR<0.001) increased mean corpuscular volume, and a doubling in the concentration of blood lead was associated with 61,736 increased red blood cells per µL (95% CI: 54,335, 69,138; FDR<0.001). A wide variety of chemicals, such as metals and smoking-related compounds, were highly associated with immune system biomarkers. This environmental chemical-wide association study identified chemicals from multiple families for further toxicological, immunologic, and epidemiological investigation.

Serum concentrations of legacy, alternative, and precursor per- and polyfluoroalkyl substances: a descriptive analysis of adult female participants in the MIREC-ENDO study.

BACKGROUND: Several legacy and emerging per- and polyfluoroalkyl substances (PFAS) have been regulated around the world. There is growing concern over the proliferation of alternative PFAS, as well as PFAS precursors. Biomonitoring data for PFAS are critical for assessing exposure and human health risk. METHODS: We collected serum samples from 289 adult female participants in a 2018-2021 follow-up study of the Maternal-Infant Research on Environmental Chemicals (MIREC) Canadian pregnancy cohort. Samples were analyzed for 40 PFAS using ultra-performance liquid chromatography-tandem mass spectrometry. For those compounds with > 50% detection, as well as the sum of these compounds, we describe serum concentrations and patterns of exposure according to sociodemographic and obstetrical history characteristics. RESULTS: 17 out of 40 PFAS were detected in > 50% of samples with 7 of these detected in > 97% of samples. Median [95th percentile] concentrations (µg/L) were highest for PFOS (1.62 [4.56]), PFOA (0.69 [1.52]), PFNA (0.38 [0.81]), and PFHxS (0.33 [0.92]). Geometric mean concentrations of PFOA and PFHxS were approximately 2-fold lower among those with more children (≥ 3 vs. 1), greater number of children breastfed (≥ 3 vs. ≤ 1), longer lifetime duration of breastfeeding (> 4 years vs. ≤ 9 months), and shorter time since last pregnancy (≤ 4 years vs. > 8 years). We observed similar patterns for PFOS, PFHpS, and the sum of 17 PFAS, though the differences between groups were smaller. Concentrations of PFOA were higher among "White" participants, while concentrations of N-MeFOSE, N-EtFOSE, 7:3 FTCA, and 4:2 FTS were slightly higher among participants reporting a race or ethnicity other than "White". Concentrations of legacy, alternative, and precursor PFAS were generally similar across levels of age, education, household income, body mass index, and menopausal status. CONCLUSIONS: We report the first Canadian biomonitoring data for several alternative and precursor PFAS. Our findings suggest that exposure to PFAS, including several emerging alternatives, may be widespread. Our results are consistent with previous studies showing that pregnancy and breastfeeding are excretion pathways for PFAS.

Development of interpretable machine learning models associated with environmental chemicals to predict all-cause and specific-cause mortality：A longitudinal study based on NHANES.

Limited information is available on potential predictive value of environmental chemicals for mortality. Our study aimed to investigate the associations between 43 of 8 classes representative environmental chemicals in serum/urine and mortality, and further develop the interpretable machine learning models associated with environmental chemicals to predict mortality. A total of 1602 participants were included from the National Health and Nutrition Examination Survey (NHANES). During 154,646 person-months of follow-up, 127 deaths occurred. We found that machine learning showed promise in predicting mortality. CoxPH was selected as the optimal model for predicting all-cause mortality with time-dependent AUROC of 0.953 (95%CI: 0.951-0.955). Coxnet was the best model for predicting cardiovascular disease (CVD) and cancer mortality with time-dependent AUROCs of 0.935 (95%CI: 0.933-0.936) and 0.850 (95%CI: 0.844-0.857). Based on clinical variables, adding environmental chemicals could enhance the predictive ability of cancer mortality (P < 0.05). Some environmental chemicals contributed more to the models than traditional clinical variables. Combined the results of association and prediction models by interpretable machine learning analyses, we found urinary methyl paraben (MP) and urinary 2-napthol (2-NAP) were negatively associated with all-cause mortality, while serum cadmium (Cd) was positively associated with all-cause mortality. Urinary bisphenol A (BPA) was positively associated with CVD mortality.

Enhanced electrophysiological activity and neurotoxicity screening of environmental chemicals using 3D neurons from human neural precursor cells purified with PSA-NCAM.

The assessment of neurotoxicity for environmental chemicals is of utmost importance in ensuring public health and environmental safety. Multielectrode array (MEA) technology has emerged as a powerful tool for assessing disturbances in the electrophysiological activity. Although human embryonic stem cell (hESC)-derived neurons have been used in MEA for neurotoxicity screening, obtaining a substantial and sufficiently active population of neurons from hESCs remains challenging. In this study, we successfully differentiated neurons from a large population of human neuronal precursor cells (hNPC) purified using a polysialylated neural cell adhesion molecule (PSA-NCAM), referred to as hNPCPSA-NCAM+. The functional characterization demonstrated that hNPCPSA-NCAM+-derived neurons improve functionality by enhancing electrophysiological activity compared to total hNPC-derived neurons. Furthermore, three-dimensional (3D) neurons derived from hNPCPSA-NCAM+ exhibited reduced maturation time and enhanced electrophysiological activity on MEA. We employed subdivided population analysis of active mean firing rate (MFR) based on electrophysiological intensity to characterize the electrophysiological properties of hNPCPSA-NCAM+-3D neurons. Based on electrophysiological activity including MFR and burst parameters, we evaluated the sensitivity of hNPCPSA-NCAM+-3D neurons on MEA to screen both inhibitory and excitatory neuroactive environmental chemicals. Intriguingly, electrophysiologically active hNPCPSA-NCAM+-3D neurons demonstrated good sensitivity to evaluate neuroactive chemicals, particularly in discriminating excitatory chemicals. Our findings highlight the effectiveness of MEA approaches using hNPCPSA-NCAM+-3D neurons in the assessment of neurotoxicity associated with environmental chemicals. Furthermore, we emphasize the importance of selecting appropriate signal intensity thresholds to enhance neurotoxicity prediction and screening of environmental chemicals.

Cohort profile update: The Canadian Maternal-Infant Research on Environmental Chemicals Child Development study (MIREC-CD PLUS).

BACKGROUND: The pan-Canadian Maternal-Infant Research on Environmental Chemicals (MIREC) study was established to determine whether maternal environmental chemical exposures were associated with adverse pregnancy outcomes in 2001 pregnant women. OBJECTIVES: The MIREC-Child Development (CD PLUS) study followed this cohort with the goal of assessing the potential effects of prenatal exposures on anthropometry and neurodevelopment in early childhood. POPULATION: MIREC families with children between the ages of 15 months and 5 years who had agreed to be contacted for future research (n = 1459) were invited to participate in MIREC-CD PLUS which combines data collected from an online Maternal Self-Administered Questionnaire with biomonitoring and neurodevelopment data collected from two in-person visits. PRELIMINARY RESULTS: Between April 2013 and March 2015, 803 children participated in the Biomonitoring visit where we collected anthropometric measures, blood, and urine from the children. The Behavioural Assessment System for Children-2, Behaviour Rating Inventory of Executive Function, MacArthur-Bates Communicative Development Inventories and the Communication subscale of the Adaptive Behaviour Scale from the Bayley Scales of Infant and Toddler Development-III are available on close to 900 children. There were 610 singleton children who completed in-person visits for neurodevelopment assessments including the Social Responsiveness Scale, Wechsler Preschool Primary Scale of Intelligence-III and NEuroPSYchological assessments (NEPSY). Currently, we are following the cohort into early adolescence to measure the impact of early life exposures on endocrine and metabolic function (MIREC-ENDO). CONCLUSIONS: Data collection for the MIREC-CD PLUS study is complete and analysis of the data continues. We are now extending the follow-up of the cohort into adolescence to measure the impact of early life exposures on endocrine and metabolic function (MIREC-ENDO). MIREC-CD PLUS is limited by loss to follow-up and the fact that mothers are predominately of higher socioeconomic status and 'White' ethnicity, which limits our generalizability. However, the depth of biomonitoring and clinical measures in MIREC provides a platform to examine associations of prenatal, infancy and childhood exposures with child growth and development.

Relationships of Liver X Receptor Antagonists and Atherosclerosis in Drinking Water from Six Chinese Major Cities.

While environmental factors have been considered contributors to atherosclerosis, it remains unclear whether drinking water promotes foam cell formation, the initial event of atherosclerosis. This study revealed that drinking water from six major cities in China, namely, Harbin, Jinan, Shanghai, Wuhan, Chongqing, and Zhuhai, significantly promoted foam cell formation in an in vitro macrophage model at a minimum concentration fold of 2. Moreover, cholesterol efflux was significantly impeded by all samples at 2-16-fold, while cholesterol influx was induced only by samples from Jinan and Chongqing at 16-fold, suggesting the dominant role of efflux in foam cell formation. Interestingly, except for the sample from Jinan, the samples exhibited complete inhibition of liver X receptor α (LXRα) activities at 160-fold, indicating the potential role of chemicals in drinking water in promoting foam cell formation by antagonizing LXRα. Through LXRα protein affinity selection-mass spectrometry, we identified ten LXRα-binding compounds, with efavirenz being revealed for the first time as a significant inducer of foam cell formation through LXRα antagonism. Overall, this study clarifies the atherosclerotic risks posed by drinking water and demonstrates the efavirenz-related atherosclerotic effects.

Correlates of plasma concentrations of per- and poly-fluoroalkyl substances among reproductive-aged Black women.

BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) are synthetic chemicals used in commercial and consumer goods. Black women are underrepresented in studies of PFAS exposure. METHODS: We performed a cross-sectional analysis of correlates of plasma PFAS concentrations among 1499 Black women aged 23-35 participating in the Study of Environment, Lifestyle, and Fibroids (SELF), a Detroit-based cohort study. At baseline (2010-2012), participants provided questionnaire data on socio-demographics; behaviors; diet; and menstrual, contraceptive, and reproductive histories. Using mass spectrometry in non-fasting plasma samples collected at enrollment, we quantified several PFAS, including perfluorohexane sulfonate (PFHxS), perfluorooctane sulfonate (PFOS), perfluorooctanoate (PFOA), perfluorononanoate (PFNA), perfluorodecanoate (PFDA), perfluoroundecanoate (PFUnDA), and 2-N-methyl-perfluorooctane sulfonamido acetate (MeFOSAA). We used linear regression to calculate percentage differences (%D) and 95 % confidence intervals (CIs) for associations between selected correlates and PFAS concentrations, adjusting for all other correlates. RESULTS: PFHxS, PFOS, PFOA, and PFNA were detected in ≥97 % of women; PFDA in 86 %; MeFOSAA in 70 %; and PFUnDA in 52 %. Age, income, education, and intakes of water, alcohol, and seafood were positively associated with several PFAS. Current smoking was positively associated with MeFOSAA. Body mass index was inversely associated with most PFAS, except PFHxS. Strong inverse associations (%D; 95 % CI) were observed between parity (≥3 vs. 0 births) and PFHxS (-34.7; -43.0, -25.1) and PFOA (-33.1; -39.2, -26.3); breastfeeding duration (≥6 months vs. nulliparous) and PFOA (-31.1; -37.8, -23.7), PFHxS (-24.2; -34.5, -12.3), and PFOS (-18.4; -28.3, -7.1); recent birth (<2 years ago vs. nulliparous) and PFOA (-33.1; -39.6, -25.8), PFHxS (-29.3; -39.0, -18.1), PFNA (-25.2; -32.7, -16.8), and PFOS (-18.3; -28.3, -6.9); and intensity of menstrual bleed (heavy vs. light) and PFHxS (-18.8; -28.3, -8.2), PFOS (-16.4; -24.9, -7.1), PFNA (-10.5; -17.8, -2.6), and PFOA (-10.0; -17.2, -2.1). Current use of depot medroxyprogesterone acetate (DMPA) was positively associated with PFOS (20.2; 1.4, 42.5), PFOA (16.2; 1.5, 33.0), and PFNA (15.3; 0.4, 32.4). CONCLUSIONS: Reproductive factors that influence PFAS elimination showed strong associations with several PFAS (reduced concentrations with parity, recent birth, lactation, heavy menstrual bleeding; increased concentrations with DMPA use).

Environmental pollutant exposure associated with altered early-life gut microbiome: Results from a birth cohort study.

Emerging evidence shows that the gut microbiota interacts with environmental pollutants, but the effect of early exposure on the neonatal microbiome remains unknown. We investigated the association between maternal exposure to environmental pollutants and changes in early-life gut microbiome development. We surveyed 16S rRNA gene on meconium and fecal samples (at 1, 3, and 6 months) from the Brazilian birth cohort, and associated with levels of metals, perfluoroalkyl chemicals (PFAS), and pesticides in maternal and umbilical cord blood. The results indicate that the magnitude of the microbiome changes associated with increasing pollutant exposure was bigger in cesarean-section (CS) born and CS-born-preterm babies, in relation to vaginally (VG) delivered infants. Breastfeeding was associated with a stronger pollutant-associated effect on the infant feces, suggesting that the exposure source could be maternal milk. Differences in microbiome effects associated with maternal or cord blood pollutant concentrations suggest that fetal exposure time - intrauterine or perinatal - may matter. Finally, despite the high developmental microbiota variability, specific microbionts were consistently affected across all pollutants, with taxa clusters found in samples from infants exposed to the highest toxicant exposure. The results evidence that perinatal exposure to environmental pollutants is associated with alterations in gut microbiome development which may have health significance.

Perspectives of peripartum people on opportunities for personal and collective action to reduce exposure to everyday chemicals: Focus groups to inform exposure report-back.

Participants in biomonitoring studies who receive personal exposure reports seek information to reduce exposures. Many chemical exposures are driven by systems-level policies rather than individual actions; therefore, change requires engagement in collective action. Participants' perceptions of collective action and use of report-back to support engagement remain unclear. We conducted virtual focus groups during summer 2020 in a diverse group of peripartum people from cohorts in the Environmental influences on Child Health Outcomes (ECHO) Program (N = 18). We assessed baseline exposure and collective action experience, and report-back preferences. Participants were motivated to protect the health of their families and communities despite significant time and cognitive burdens. They requested time-conscious tactics and accessible information to enable action to reduce individual and collective exposures. Participant input informed the design of digital report-back in the cohorts. This study highlights opportunities to shift responsibility from individuals to policymakers to reduce chemical exposures at the systems level.

Individual and mixture associations of perfluoroalkyl substances on liver function biomarkers in the Canadian Health Measures Survey.

BACKGROUND: Perfluoroalkyl substances can disrupt hepatic metabolism and may be associated with liver function biomarkers. We examined individual and mixture associations of PFAS on liver function biomarkers in a representative sample of Canadian adults. We explored the potential for effect modification by sex and body mass index, as well as by physical activity level which may attenuate the deleterious effect of PFAS on metabolic disorders. METHODS: We analyzed data from participants aged 20-74 from the Canadian Health Measures Survey. We used linear regression to examine associations between plasma concentrations of PFOA, PFOS, PFHxS, PFNA, PFDA, and PFUDA on serum concentrations of aspartate aminotransferase (AST), gamma-glutamyltransferase (GGT), alkaline phosphatase (ALP), alanine aminotransferase (ALT) and total bilirubin. We used quantile g-computation to estimate associations with a PFAS mixture for each simultaneous, one-quartile change in PFAS concentrations. RESULTS: Each doubling of PFOA, PFOS, PFHxS, or PFNA concentrations was associated with higher AST, GGT, and ALP concentrations. Each doubling of PFOA concentrations was associated with 16.5% (95%CI: 10.4, 23.0) higher GGT concentrations among adults not meeting Canada's physical activity guidelines vs. 6.6% (95%CI: -1.6, 15.5) among those meeting these guidelines. Sex and BMI also modified some associations, though to a lesser extent. We did not observe associations between ALT and PFOA (1.2% change; 95%CI: -2.5, 4.9), PFOS (2.2% change; 95%CI: -0.8, 5.3), or PFHxS (1.5% change; 95%CI: -0.4, 3.4). We also did not observe consistent associations for PFDA and PFUDA or with total bilirubin. In quantile g-computation models, each simultaneous one-quartile increase in the PFAS mixture was positively associated with AST (7.5% higher; 95%CI: 4.0, 10.4), GGT (9.7% higher; 95%CI: 1.7, 17.0), and ALP (2.8% higher; 95%CI: 0.5, 5.4). CONCLUSION: Higher plasma concentrations of PFOA, PFOS, PFHxS, and PFNA - both individually and as a mixture - were associated with higher serum concentrations of liver function biomarkers. These results contribute to emerging evidence suggesting that higher levels of physical activity appear to be protective against the hepatotoxic effects of PFOA. This work contributes to a growing body of evidence supporting the hepatotoxic effects of PFAS.

A novel chemo-phenotypic method identifies mixtures of salpn, vitamin D3, and pesticides involved in the development of colorectal and pancreatic cancer.

Environmental chemical (EC) exposures and our interactions with them has significantly increased in the recent decades. Toxicity associated biological characterization of these chemicals is challenging and inefficient, even with available high-throughput technologies. In this report, we describe a novel computational method for characterizing toxicity, associated biological perturbations and disease outcome, called the Chemo-Phenotypic Based Toxicity Measurement (CPTM). CPTM is used to quantify the EC "toxicity score" (Zts), which serves as a holistic metric of potential toxicity and disease outcome. CPTM quantitative toxicity is the measure of chemical features, biological phenotypic effects, and toxicokinetic properties of the ECs. For proof-of-concept, we subject ECs obtained from the Environmental Protection Agency's (EPA) database to the CPTM. We validated the CPTM toxicity predictions by correlating 'Zts' scores with known toxicity effects. We also confirmed the CPTM predictions with in-vitro, and in-vivo experiments. In in-vitro and zebrafish models, we showed that, mixtures of the motor oil and food additive 'Salpn' with endogenous nuclear receptor ligands such as Vitamin D3, dysregulated the nuclear receptors and key transcription pathways involved in Colorectal Cancer. Further, in a human patient derived cell organoid model, we found that a mixture of the widely used pesticides 'Tetramethrin' and 'Fenpropathrin' significantly impacts the population of patient derived pancreatic cancer cells and 3D organoid models to support rapid PDAC disease progression. The CPTM method is, to our knowledge, the first comprehensive toxico-physicochemical, and phenotypic bionetwork-based platform for efficient high-throughput screening of environmental chemical toxicity, mechanisms of action, and connection to disease outcomes.

Expression of antimicrobial peptides associated with different susceptibilities to environmental chemicals in Drosophila suzukii and Drosophila melanogaster.

Drosophila suzukii is a serious agricultural pest. The evolved morphology of the female D. suzukii assists in penetrating the surface of fresh fruit and spawns eggs with its unique ovipositor. Conversely, Drosophila melanogaster, a taxonomically close species with D. suzukii, largely inhabits decaying and fermenting fruits and is consistently exposed to extensive environmental chemicals, such as 2-phenylethanol, ethanol, and acetic acid, produced by microorganisms. Considering the distinct habitats of the two flies, D. suzukii is thought to be more susceptible to environmental chemicals than D. melanogaster. We investigated the significantly higher survival rate of D. melanogaster following exposure to 2-phenylethanol, ethanol, and acetic acid. A comparison of the expression of antimicrobial peptides (AMPs) between the two flies treated with chemicals established that AMPs were generally more abundantly induced in D. melanogaster than in D. suzukii, particularly in the gut and fat body. Among the AMPs, the induction of genes (Diptericin A, Diptericin B, and Metchnikowin), which are regulated by the immune deficiency (IMD) pathway, was significantly higher than that of Drosomycin, which belongs to the Toll pathway in chemical-treated D. melanogaster. A transgenic RNAi fly (D. melanogaster) with silenced expression of AMPs and Relish, a transcription factor of the IMD pathway, exhibited significantly reduced survival rates than the control fly. Our results suggest that AMPs regulated by the IMD pathway play an important role in the chemical tolerance of D. melanogaster, and these flies are adapted to their habitats by physiological response.

Assessment of fibrotic pathways induced by environmental chemicals using 3D-human liver microtissue model.

Exposure to environmental chemicals, particularly those with persistent and bioaccumulative properties have been linked to liver diseases. Induction of fibrotic pathways is considered as a pre-requirement of chemical induced liver fibrosis. Here, we applied 3D in vitro human liver microtissues (MTs) composed of HepaRG, THP-1 and hTERT-HSC that express relevant hepatic pathways (bile acid, sterol, and xenobiotic metabolism) and can recapitulate key events of liver fibrosis (e.g. extracellular matrix-deposition). The liver MTs were exposed to a known profibrotic chemical, thioacetamide (TAA) and three representative environmental chemicals (TCDD, benzo [a] pyrene (BaP) and PCB126). Both TAA and BaP triggered fibrotic pathway related events such as hepatocellular damage (cytotoxicity and decreased albumin release), hepatic stellate cell activation (transcriptional upregulation of α-SMA and Col1α1) and extracellular matrix remodelling. TCDD or PCB126 at measured concentrations did not elicit these responses in the 3D liver MTs system, though they caused cytotoxicity in HepaRG monoculture at high concentrations. Reduced human transcriptome (RHT) analysis captured molecular responses involved in liver fibrosis when MTs were treated with TAA and BaP. The results suggest that 3D, multicellular, human liver microtissues represent an alternative, human-relevant, in vitro liver model for assessing fibrotic pathways induced by environmental chemicals.

The role of macrophage polarization and function in environmental toxicant-induced cancers.

Macrophages are a critical member of the innate immune system and can intensify tumor invasiveness and assist the growth of neoplastic cells. Moreover, they have the capability to reinforce immunosuppression and angiogenesis. Various investigations suggest that health-related issues, including inflammatory disorders and neoplastic diseases may be caused by environmental toxicant exposure. However, it is still unclear what role these environmental toxicants play in causing carcinogenesis by disturbing the mechanisms of migration, polarization, differentiation, and immune-stimulatory functions of macrophages. Accordingly, in this article, we will explore the interaction between environmental chemicals and inflammatory macrophage processes at the molecular level and their association with tumor progression and carcinogenesis.

Analytical challenges in human exposome analysis with focus on environmental analysis combined with metabolomics.

Environmental factors, such as chemical exposures, are likely to play a crucial role in the development of several human chronic diseases. However, how the specific exposures contribute to the onset and progress of various diseases is still poorly understood. In part, this is because comprehensive characterization of the chemical exposome is a highly challenging task, both due to its complex dynamic nature as well as due to the analytical challenges. Herein, the analytical challenges in the field of exposome research are reviewed, with specific emphasis on the sampling, sample preparation, and analysis, as well as challenges in the compound identification. The primary focus is on the human chemical exposome, that is, exposures to mixtures of environmental chemicals and its impact on human metabolome. In order to highlight the recent progress in the exposome research in relation to human health and disease, selected examples of human exposome studies are presented.

Solid-phase microextraction for the human biomonitoring of environmental chemicals: Current applications and future perspectives.

Sample preparation is one of the crucial steps in the analytical chemistry including human biomonitoring studies. Although there are several traditional approaches available, solid-phase microextraction is emerged as one of the pioneering techniques due to its simplicity, rapidness, wide applicability, and miniaturization of traditional sample preparation (e.g., use of less or no organic solvents). There are few earlier review articles available on the advancements in solid-phase microextraction and its use for the measurement of environmental chemicals in various types of environmental samples. However, a collective information on applicability and current usage of solid-phase microextraction for the human biomonitoring of environmental chemicals are scarce, nonetheless, rising demands on innovative analytical approaches for human biomonitoring studies. Hence, in this review article, we covered the application of solid-phase microextraction as extraction/purification methods for more than 15 classes of environmental chemicals to assess their respective exposure levels and associated health outcomes in various human population reported across the globe. Further, a detailed discussion on various types of matrix used, nature of coupled analytical instrumentations, and limitations and future perspectives of solid-phase microextraction for human biomonitoring studies is presented in this review.

Acute Ethanol Exposure during Synaptogenesis Rapidly Alters Medium Spiny Neuron Morphology and Synaptic Protein Expression in the Dorsal Striatum.

Fetal alcohol spectrum disorders are caused by the disruption of normal brain development in utero. The severity and range of symptoms is dictated by both the dosage and timing of ethanol administration, and the resulting developmental processes that are impacted. In order to investigate the effects of an acute, high-dose intoxication event on the development of medium spiny neurons (MSNs) in the striatum, mice were injected with ethanol on P6, and neuronal morphology was assessed after 24 h, or at 1 month or 5 months of age. Data indicate an immediate increase in MSN dendritic length and branching, a rapid decrease in spine number, and increased levels of the synaptic protein PSD-95 as a consequence of this neonatal exposure to ethanol, but these differences do not persist into adulthood. These results demonstrate a rapid neuronal response to ethanol exposure and characterize the dynamic nature of neuronal architecture in the MSNs. Although differences in neuronal branching and spine density induced by ethanol resolve with time, early changes in the caudate/putamen region have a potential impact on the execution of complex motor skills, as well as aspects of long-term learning and addictive behavior.

Hokkaido birth cohort study on environment and children's health: cohort profile 2021.

BACKGROUND: The Hokkaido Study on Environment and Children's Health is an ongoing study consisting of two birth cohorts of different population sizes: the Sapporo cohort and the Hokkaido cohort. Our primary objectives are to (1) examine the effects that low-level environmental chemical exposures have on birth outcomes, including birth defects and growth retardation; (2) follow the development of allergies, infectious diseases, and neurobehavioral developmental disorders, as well as perform a longitudinal observation of child development; (3) identify high-risk groups based on genetic susceptibility to environmental chemicals; and (4) identify the additive effects of various chemicals, including tobacco. METHODS: The purpose of this report is to provide an update on the progress of the Hokkaido Study, summarize recent results, and suggest future directions. In particular, this report provides the latest details from questionnaire surveys, face-to-face examinations, and a collection of biological specimens from children and measurements of their chemical exposures. RESULTS: The latest findings indicate different risk factors of parental characteristics on birth outcomes and the mediating effect between socioeconomic status and children that are small for the gestational age. Maternal serum folate was not associated with birth defects. Prenatal chemical exposure and smoking were associated with birth size and growth, as well as cord blood biomarkers, such as adiponectin, leptin, thyroid, and reproductive hormones. We also found significant associations between the chemical levels and neuro development, asthma, and allergies. CONCLUSIONS: Chemical exposure to children can occur both before and after birth. Longer follow-up for children is crucial in birth cohort studies to reinforce the Developmental Origins of Health and Disease hypothesis. In contrast, considering shifts in the exposure levels due to regulation is also essential, which may also change the association to health outcomes. This study found that individual susceptibility to adverse health effects depends on the genotype. Epigenome modification of DNA methylation was also discovered, indicating the necessity of examining molecular biology perspectives. International collaborations can add a new dimension to the current knowledge and provide novel discoveries in the future.

Change of gene expression profiles in human cardiomyocytes and macrophages infected with SARS-CoV-2 and its significance. / 人心肌细胞和巨噬细胞感染SARS-CoV-2åŽåŸºå› è¡¨è¾¾è°±çš„å˜åŒ–åŠå ¶æ„ä¹‰.

OBJECTIVES: Coronavirus disease 2019 (COVID-19) is an acute respiratory infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). SARS-CoV-2 can damage the myocardium directly, or activate the immune system, trigger a cytokine storm, and cause inflammatory cells to infiltrate the myocardial tissue and damage the myocardium. This study is based on the sequencing data to analyze the changes in gene expression of cardiomyocytes and macrophages after SARS-CoV-2 infection, and explore the potential effects of SARS-CoV-2 on the heart and immune system. METHODS: The public data set GSE151879 was retrieved. The online software Network Analyst was used to preprocess the data, and the differentially expressed genes (DEGs) [log2(fold change)>2, adjusted P-value<0.05] screening between the infection group and the control group in cardiomyocytes, human embryonic stem cell-derived cardiomyocytes, and macrophages were screened. Consistent common differentially expressed genes (CCDEGs) with the same expression pattern in cardiomyocytes and macrophages were obtained, and the online analysis software String was used to conduct enrichment analysis of their biological functions and signal pathways. Protein-protein interaction network, transcription factor-gene interaction network, miRNA-gene interaction network and environmental chemical-gene interaction network were established, and Cytoscape 3.72 was used to perform visualization. RESULTS: After data standardization, the data quality was excellent and it can ensure reliable results. Myocardial cell infection with SARS-CoV-2 and gene expression spectrum were changed significantly, including a total of 484 DEGs in adult cardiomyoblasts, a total of 667 DEGs in macrophages, and a total of 1 483 DEGs in human embryo source of cardiomyopathy. The Stum, mechanosensory transduction mediator homolog (STUM), dehydrogenase/reductase 9 (DHRS9), calcium/calmodulin dependent protein kinase II beta (CAMK2B), claudin 1(CLDN1), C-C motif chemokine ligand 2 (CCL2), TNFAIP3 interacting protein 3 (TNIP3), G protein-coupled receptor 84 (GPR84), and C-X-C motif chemokine ligand 1 (CXCL1) were identical in expression patterns in 3 types of cells. The protein-protein interaction suggested that CAMK2B proteins may play a key role in the antiviral process in 3 types of cells; and silicon dioxide (SiO2), benzodiazepine (BaP), nickel (Ni), and estradiol (E2) affect anti-SARS-CoV-2 processes of the 3 types of cells. CONCLUSIONS: CAMK2B, CLDN1, CCL2, and DHRS9 genes play important roles in the immune response of cardiomyocytes against SARS-CoV-2. SiO2, BaP, Ni, E2 may affect the cell's antiviral process by increasing the toxicity of cardiomyocytes, thereby aggravating SARS-CoV-2 harm to the heart.