Exposure Model Research Articles

Assessing lifetime occupational chrysotile inhalation exposure, respiratory symptoms, and lung cancer risk among brake maintenance workers in Malaysia.

This study aimed to estimate workers' occupational lifetime exposure to chrysotile and examine the respiratory symptoms and lung cancer risk. A total of 112 workers were interviewed about their occupational histories. Exposure modeling using information on the determinants of exposure was used to estimate chrysotile emissions. The cumulative lifetime exposure was then assessed for each worker. Respiratory symptoms were obtained using a validated questionnaire. Lung cancer mortality rate was also predicted using a model. Almost all the workers were male and young (mean age = 30 years, SD = 7). The estimated lifetime occupational chrysotile inhalation exposure ranged from 0.0001 to 0.0486 f/mL.years (median = 0.0018 f/mL.years, IQR = 0.486). A high prevalence of cough symptom (11.7%), and low estimated cancer risk (<1%) were reported. In conclusion, the lung cancer risk among our cohort of workers was at a low level because of lower cumulative lifetime occupational chrysotile exposure.

Green Tea Polyphenol Nanoparticles Reduce Anxiety Caused by Tobacco Smoking Withdrawal in Rats by Suppressing Neuroinflammation.

Repeated exposure to tobacco smoke causes neuroinflammation and neuroplasticity, which correlates with smoking withdrawal-induced anxiety. The purpose of this study was to investigate the anticipated involvement of antioxidant-rich nanoparticles (NPs) prepared by oxidation-triggered polymerization of green tea catechins in impacting these effects in a rat model of tobacco smoke exposure. Exposure to tobacco smoke was carried out for 2 h a day, 5 days a week, for a total of 36 days. Weekly behavioral tests were conducted prior to recommencing the exposure. Following a 20-day exposure period, rats were administered either distilled water or green tea (GT) NPs (20 mg/kg, orally) for an additional 16 days. Our findings revealed that tobacco smoke exposure induced anxiety-like behavior indicative of withdrawal, and this effect was alleviated by GT NPs. Tobacco smoke exposure caused a marked increase in the relative mRNA and protein expression of nuclear factor-kappa B (NF-κB) and reduced the relative mRNA and protein expression of brain-derived neurotrophic factor (BDNF) in the hippocampus (HIP) and hypothalamus (HYP) brain subregions. The intervention of GT NPs effectively inhibited these effects. Our findings demonstrate the potent protective role of GT NPs in reducing withdrawal-induced anxiety-like behavior, neuroinflammation, and neuroplasticity triggered by tobacco smoke exposure.

Cardiopulmonary effects of short-term ambient PM2.5 exposure: central air quality monitor data versus personal exposure models

Cardiopulmonary effects of short-term ambient PM2.5 exposure: central air quality monitor data versus personal exposure models

Assessing atmospheric pollution concentrations in Mexico for chronic exposure models: a remote sensing approach

Assessing atmospheric pollution concentrations in Mexico for chronic exposure models: a remote sensing approach

The effect of endocrine-disrupting chemicals in follicular fluid: The insights from oocyte to fertilization

Endocrine-disrupting chemicals (EDCs) exhibited the detriment in female reproductive health. Our objective was to investigate the individual and mixture effects of EDCs present in follicular fluid, the environment in which oocytes grow and develop, on early reproductive outcomes. We recruited 188 women seeking reproduction examination from the Study of Exposure and Reproductive Health (SEARCH) cohort between December 2020 and November 2021. We assessed the concentrations of 7 categories of 64 EDCs in follicular fluid, and measured early reproductive outcomes, including retrieved oocytes, mature oocytes, normal fertilized oocytes, and high-quality embryos. In this study Monomethyl phthalate (MMP) (2.17 ng/ml) were the compounds found in the highest median concentrations in follicular fluid. After adjusting for multiple testing, multivariate regression showed that multiple EDCs were significantly negatively associated with early assisted reproduction outcomes. For example, MMP showed a significant negative correlation with the number of high quality embryos (β: −0.1, 95 % CI: −0.15, −0.04). Specifically, eight types of EDCs were significantly negatively associated with four early assisted reproductive outcomes (β range: −0.2 ∼ -0.03). In the mixed exposure model, we found that mixtures of EDC were significantly negatively correlated with all four outcomes. In the quantile g-computation (QGCOMP) model, for each interquartile range increase in the concentration of EDC mixtures, the number of oocytes retrieved, mature oocytes, normally fertilized oocytes, and high-quality embryos decreased by 0.46, 0.52, 0.77, and 1.2, respectively. Moreover, we identified that phthalates (PAEs) predominantly contributed to the negative effects. Future research should validate our findings.

Effects of Several Tea-like Plants on Liver Injury Induced by Alcohol via Their Antioxidation, Anti-Inflammation, and Regulation of Gut Microbiota.

Liver injury induced by alcohol is a serious global health problem. Several tea-like plants are widely used as beverages, which are drunk like tea. In this study, the hepatoprotective effects of eight tea-like plant extracts with the intake of 200 mg/kg.bw/day were investigated and compared using a C57BL/6J mouse model of acute alcohol exposure, including sweet tea, vine tea, Rabdosia serra kudo, broadleaf holly leaf, mulberry leaf, bamboo leaf, Camellia nitidissima, and Akebia trifoliata peels. The results showed that the eight tea-like plants had hepatoprotective effects to different degrees against acute alcohol exposure via enhancing the activities of alcoholic metabolism enzymes, ameliorating oxidative stress and inflammation in the liver, as well as regulating gut microbiota. In particular, sweet tea, bamboo leaf, mulberry leaf, and Camellia nitidissima increased the activities of alcohol dehydrogenase or aldehyde dehydrogenase. Among these tea-like plants, sweet tea and Camellia nitidissima had the greatest hepatoprotective effects, and their bioactive compounds were determined by high-performance liquid chromatography. Chlorogenic acid, rutin, and ellagic acid were identified in sweet tea, and epicatechin, rutin, and ellagic acid were identified in Camellia nitidissima, which could contribute to their hepatoprotective action. These tea-like plants could be drunk or developed into functional food against alcoholic liver injury, especially sweet tea and Camellia nitidissima. In the future, the effects of sweet tea and Camellia nitidissima on chronic alcoholic liver diseases should be further investigated.

Personal inhalable paper dust exposure and potential determinants among paper industry workers in Ethiopia.

Excessive paper dust during paper production may harm the workers' respiratory health. We wanted to assess the inhalable paper dust levels and its determinants among paper industry workers. A study was conducted in Ethiopia to assess the level of personal inhalable paper dust exposure among four paper mills. A total of 150 samples were collected using the IOM sampler attached to Side Kick Casella pumps at a flow rate of 2L/min. The samples were analyzed in Nemko Norlab, Norway. Linear mixed-effect models were applied to identify determinants of inhalable paper dust. The geometric mean of personal inhalable paper dust was 3.3mg/m3 with 80% of the measurements exceeding the Swedish occupational exposure limit (OEL) of 2 mg/m3. The linear mixed-effects model showed that the level of dust was 28% higher when using high-speed than when using low-speed rewinding machines, while paper mills with an average of more than four machines per job group had 22% higher exposure than paper mills with a lower number of machines. Furthermore, working in packing and preparation was associated with higher dust exposure than in other areas. The dust exposure levels were above the Swedish OEL for 80% of the samples. This indicates that preventive measures should be established in the industry. The exposure model identified high-speed rewinding machines, a high number of machines, and work in preparation and packing as associated with high levels of paper dust exposure.

Associations of personal PM2.5-bound heavy metals and heavy metal mixture with lung function: Results from a panel study in Chinese urban residents

BackgroundThere are a few reports on the associations between fine particulate matter (PM2.5)-bound heavy metals and lung function. ObjectivesTo evaluate the associations of single and mixed PM2.5-bound heavy metals with lung function. MethodsThis study included 316 observations of 224 Chinese adults from the Wuhan-Zhuhai cohort over two study periods, and measured participants' personal PM2.5-bound heavy metals and lung function. Three linear mixed models, including the single constituent model, the PM2.5-adjusted constituent model, and the constituent residual model were used to evaluate the association between single metal and lung function. Mixed exposure models including Bayesian kernel machine regression (BKMR) model, weighted quantile sum (WQS) model, and Explainable Machine Learning model were used to assess the relationship between PM2.5-bound heavy metal mixtures and lung function. ResultsIn the single exposure analyses, significant negative associations of PM2.5-bound lead, antimony, and cadmium with peak expiratory flow (PEF) were observed. In the mixed exposure analyses, significant decreases in forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC), maximal mid-expiratory flow (MMF), and forced expiratory flow at 75% of the pulmonary volume (FEF75) were associated with the increased PM2.5-bound heavy metal mixture. The BKMR models suggested negative associations of PM2.5-bound lead and antimony with lung function. In addition, PM2.5-bound copper was positively associated with FEV1/FVC, MMF, and FEF75. The Explainable Machine Learning models suggested that FEV1/FVC, MMF, and FEF75 decreased with the elevated PM2.5-bound lead, manganese, and vanadium, and increased with the elevated PM2.5-bound copper. ConclusionsThe negative relationships were detected between PM2.5-bound heavy metal mixture and FEV1/FVC, MMF, as well as FEF75. Among the PM2.5-bound heavy metal mixture, PM2.5-bound lead, antimony, manganese, and vanadium were negatively associated with FEV1/FVC, MMF, and FEF75, while PM2.5-bound copper was positively associated with FEV1/FVC, MMF, and FEF75.

Tobacco cigarette smoking induces cerebrovascular dysfunction followed by oxidative neuronal injury with the onset of cognitive impairment.

While chronic smoking triggers cardiovascular disease, controversy remains regarding its effects on the brain and cognition. We investigated the effects of long-term cigarette smoke (CS) exposure (CSE) on cerebrovascular function, neuronal injury, and cognition in a novel mouse exposure model. Longitudinal studies were performed in CS or air-exposed mice, 2 hours/day, for up to 60 weeks. Hypertension and carotid vascular endothelial dysfunction (VED) occurred by 16 weeks of CSE, followed by reduced carotid artery blood flow, with oxidative stress detected in the carotid artery, and subsequently in the brain of CS-exposed mice with generation of reactive oxygen species (ROS) and secondary protein and DNA oxidation, microglial activation and astrocytosis. Brain small vessels exhibited decreased levels of endothelial NO synthase (eNOS), enlarged perivascular spaces with blood brain barrier (BBB) leak and decreased levels of tight-junction proteins. In the brain, amyloid-β deposition and phosphorylated-tau were detected with increases out to 60 weeks, at which time mice exhibited impaired spatial learning and memory. Thus, long-term CSE initiates a cascade of ROS generation and oxidative damage, eNOS dysfunction with cerebral hypoperfusion, as well as cerebrovascular and BBB damage with intracerebral inflammation, and neuronal degeneration, followed by the onset of impaired cognition and memory.

Integrated transcriptomic and proteomic analyses reveal the effects of chronic benzene exposure on the central nervous system in mice

Benzene exposure is known to cause serious damage to the human hematopoietic system. However, recent studies have found that chronic benzene exposure may also cause neurological damage, but there were few studies in this issue. The aim of this study was to investigate the mechanism of damage to the central nervous system (CNS) by chronic benzene exposure with a multi-omics analysis. We established a chronic benzene exposure model in C57BL/6J mice by gavage of benzene-corn oil suspension, identified the differentially expressed proteins (DEPs) and differentially expressed genes (DEGs) in mice brain using 4D Label-free proteomic and RNA-seq transcriptomic. We observed that the benzene exposure mice had a significant loss of body weight, reduction in complete blood counts, abnormally high MRI signals in brain white matter, as well as extensive brain edema and neural demyelination. 162 DEPs were identified by the proteome, including 98 up-regulated and 64 down-regulated proteins. KEGG pathway analysis of DEPs showed that they were mainly involved in the neuro-related signaling pathways such as metabolic pathways, pathways of neurodegeneration, chemical carcinogenesis, Alzheimer disease, and autophagy. EPHX1, GSTM1, and LIMK1 were identified as important candidate DEGs/DEPs by integrated proteomic and transcriptomic analyses. We further performed multiple validation of the above DEGs/DEPs using fluorescence quantitative PCR (qPCR), parallel reaction monitoring (PRM), immunohistochemistry, and immunoblotting to confirm the reliability of the multi-omics study. The functions of these DEGs/DEPs were further explored and analyzed, providing a theoretical basis for the mechanism of nerve damage caused by benzene exposure.

2243 Modification effect of disability profiles on the association of blood pressure and mortality among older long-term care people

Abstract Introduction Evidence of the optimal blood pressure target for older people with disability in long-term care is limited. We aim to estimate the associations of blood pressure with all-cause and cause-specific mortality in older people with different profiles of disability. Methods This prospective cohort study was based on the government-led long-term care program in Chengdu, China, including 41,004 consecutive disabled adults aged ≥60 years. The association between blood pressure and mortality was analysed with doubly robust estimation, which combined exposure model by inverse probability weighting and outcome model fitted with Cox regression. The non-linearity was examined by restricted cubic spline. The primary endpoint was all-cause mortality, and the secondary endpoints were cardiovascular and non-cardiovascular mortality. Results The associations between systolic blood pressure (SBP) and all-cause mortality were close to a U-shaped curve in mild–moderate disability group (Barthel index ≥40), and a reversed J-shaped in severe disability group (Barthel index &amp;lt;40). In mild–moderate disability group, SBP &amp;lt; 135 mmHg was associated with elevated all-cause mortality risks (HR 1.21, 95% CI, 1.10–1.33), compared to SBP between 135–150 mmHg. In severe disability group, SBP &amp;lt;150 mmHg increased all-cause mortality risks (HR 1.21, 95% CI, 1.16–1.27), compared to SBP between 150–170 mmHg. The associations were robust in subgroup analyses in terms of age, cardiovascular comorbidity and antihypertensive treatment. Diastolic blood pressure (DBP) &amp;lt; 67 mmHg (HR 1.29, 95% CI, 1.18–1.42) in mild–moderate disability group and &amp;lt; 79 mmHg (HR 1.15, 95% CI, 1.11–1.20) in severe disability group both demonstrated an increased all-cause mortality risk. Conclusion The optimal blood pressure range was higher in older long-term care people with severe disability than those with mild–moderate disability. This study provides new evidence for optimal individualised management of blood pressure in disabled older people in long-term care settings.

Low doses of acetyl trihexyl citrate plasticizer promote adipogenesis in hepatocytes and mice.

Accumulating epidemiological evidence underscores the association between pervasive environmental factors and an increased risk of metabolic diseases. Environmental chemicals, recognized disruptors of endocrine and metabolic processes, may contribute to the global prevalence of metabolic disorders, including obesity. Acetyl tributyl citrate (ATHC), categorized as a citric acid ester plasticizer, serves as a substitute for di-(2-ethylhexyl) phthalate (DEHP) in various everyday products. Despite its widespread use and the increasing risk of exposure in humans and animals due to its high leakage rates, information regarding the safety of exposure to environmentally relevant doses of ATHC remains limited. This study aimed to investigate the potential impact of ATHC exposure on metabolic homeostasis. Both in vivo and in vitro exposure models were used to characterize the effects induced by ATHC exposure. C57BL/6J male mice were subjected to a diet containing ATHC for 12weeks, and metabolism-related parameters were monitored and analyzed throughout and after the exposure period. Results indicated that sub-chronic dietary exposure to ATHC induced an increase in body fat percentage, elevated serum lipid levels, and increased lipid content in the liver tissue of mice. Furthermore, the effect of ATHC exposure on murine hepatocytes were examined and results indicated that ATHC significantly augmented lipid levels in AML12 hepatocytes, disrupting energy homeostasis and altering the expression of genes associated with fatty acid synthesis, uptake, oxidation, and secretion pathways. Conclusively, both in vivo and in vitro results suggest that exposure to low levels of ATHC may be linked to an elevated risk of obesity and fatty liver in mice. The potential implications of ATHC on human health warrant comprehensive evaluation in future studies.

DMD digital lithography optimization based on a hybrid genetic algorithm and improved exposure model

An efficient method to optimize digital micromirror device (DMD) lithography was proposed using a hybrid genetic algorithm integrated with an improved exposure model. The improved exposure model significantly refines traditional approaches by incorporating advanced parameters not previously considered, including the cross-transfer coefficient, detailed light source functions, and impulse response functions. These enhancements provide a comprehensive assessment of the entire optical imaging system’s impact on lithography quality and more accurately simulate the interactions of light with the photoresist. The hybrid method combines the robust optimization capabilities of genetic algorithms (GA) with this sophisticated exposure model, facilitating precise micromirror configurations and optimizing light distribution for specific lithographic patterns. This integration results in substantial improvements in lithographic precision, with improvements of up to 84% for hexagonal star patterns, 83% for arrow patterns, and 85% for embedded figure patterns. These advancements enhance imaging quality, reduce optical proximity distortions, and improve overall lithography performance, offering crucial insights into the precision and efficiency improvement of microelectronics fabrication processes.

Developmental exposure to nonylphenol leads to depletion of the neural precursor cell pool in the hippocampal dentate gyrus

Developmental exposure to nonylphenol (NP) results in irreversible impairments of the central nervous system (CNS). The neural precursor cell (NPC) pool located in the subgranular zone (SGZ), a substructure of the hippocampal dentate gyrus, is critical for the development of hippocampal circuits and some hippocampal functions such as learning and memory. However, the effects of developmental exposure to NP on this pool remain unclear. Thus, our aim was to clarify the impacts of developmental exposure to NP on this pool and to explore the potential mechanisms. Animal models of developmental exposure to NP were created by treating Wistar rats with NP during pregnancy and lactation. Our data showed that developmental exposure to NP decreased Sox2-and Ki67-positive cells in the SGZ of offspring. Inhibited activation of Shh signaling and decreased levels of its downstream mediators, E2F1 and cyclins, were also observed in pups developmentally exposed to NP. Moreover, we established the in vitro model in the NE-4C cells, a neural precursor cell line, to further investigate the effect of NP exposure on NPCs and the underlying mechanisms. Purmorphamine, a small purine-derived hedgehog agonist, was used to specifically modulate the Shh signaling. Consistent with the in vivo results, exposure to NP reduced cell proliferation by inhibiting the Shh signaling in NE-4C cells, and purmorphamine alleviated this reduction in cell proliferation by restoring this signaling. Altogether, our findings support the idea that developmental exposure to NP leads to inhibition of the NPC proliferation and the NPC pool depletion in the SGZ located in the dentate gyrus. Furthermore, we also provided the evidence that suppressed activation of Shh signaling may contribute to the effects of developmental exposure to NP on the NPC pool.

Lambda-cyhalothrin induces heart injury in chickens by regulating cytochrome P450 enzyme system and inhibiting Nrf2/HO-1 pathway

Lambda-cyhalothrin (LCT) is a common pyrethroid insecticide widely used for ectoparasite control and hygiene pest prevention in poultry and this study aimed to investigate the mechanisms of LCT-induced cardiac injury in chickens. Low, medium, and high-dose LCT exposure models in chickens were established and hematoxylin and eosin (H&E) staining, dihydroethidium (DHE) staining, TUNEL staining, immunofluorescence, biochemical analysis, and gene expression analysis were used to study the effects of LCT exposure on the chicken heart. The results showed that LCT exposure increased the serum levels of creatine kinase (CK) and lactate dehydrogenase (LDH), led to muscle fiber breakage and inflammatory cell infiltration and caused cardiac tissue damage. The DHE staining and biochemical analysis revealed that LCT exposure resulted in the excessive accumulation of ROS, decreased activities/levels of catalase (CAT), total superoxide dismutase (T-SOD), and glutathione (GSH), and increased levels of the oxidative damage marker malondialdehyde (MDA). The TUNEL staining indicated that LCT exposure increased apoptosis possibly through the elevated expression of pro-apoptotic genes in the mitochondrial pathway, the reduced expression of anti-apoptotic genes, the upregulation of pro-inflammatory factors and the downregulation of anti-inflammatory factors. Here, LCT exposure significantly inhibited the expression of genes in the Nrf2/HO-1 pathway and activated the expression of genes in the CYP450 enzyme system. Compared to the low-dose group, the high-dose LCT exposure group showed lower levels of apoptosis and inflammation, possibly related to the low oxidative stress levels mediated by the decreased expression of the CYP450 enzyme system. In conclusion, LCT exposure induces oxidative stress, apoptosis, and inflammation in chicken hearts, which may be associated with the inhibition of the Nrf2/HO-1 pathway and activation of the CYP450 enzyme system. This study provides a theoretical basis for the safer use of insecticides in poultry production.

Advancing the understanding of earthquake risk in Portugal

The assessment of earthquake risk at the national scale is crucial for the design and implementation of risk reduction measures. Due to its location in the southwest of the Eurasian plate, Portugal is exposed to moderate to strong seismic events, such as the well-known 1755 Lisbon earthquake. We reviewed existing studies covering exposure, seismic hazard, vulnerability, and risk assessment for Portugal, and performed probabilistic seismic hazard and risk analyses for the country using new model components. These include a new exposure model developed for the residential building stock using the 2021 national Building Census Survey, a recent exposure model for commercial and industrial buildings, updated vulnerability functions for 116 building classes, and the recently released European Probabilistic Seismic Hazard model. The seismic risk results include average annual economic losses, fatalities, buildings with complete damage, and population left homeless. These results allowed the identification of the regions in Portugal with the highest earthquake risk, as well as which building classes contribute the most to the overall impact.

A study on the mediating role of serum hormones in the effects of heavy metals on preeclampsia

Exposure to environmental heavy metals may pose a risk factor for developing preeclampsia (PE) modified through intervention. This case-control study aimed to investigate the association between serum heavy metal concentrations and PE in pregnant women and whether hormones served as mediating factors in the impact of heavy metals on PE. From October 2020 to 2022, 160 patients with PE and 160 pregnant women with normal deliveries were recruited at Dongguan Songshan Lake Central Hospital. Serum concentrations of manganese (Mn), nickel (Ni), copper (Cu), zinc (Zn), arsenic (As), cadmium (Cd), lead (Pb), β-human chorionic gonadotropin (β-hCG), progesterone (P), estradiol (E2), testosterone (T), cortisol (Cort), and cortisone (Cor) were measured. Logistic, restricted cubic splines, weighted quantile sum and multivariate linear regression models were employed to account for different aspects and explore the relationships among heavy metals, hormones, and PE. Mediation model analysis was performed to assess the role of hormones in mediation. The median concentrations of Mn, E2, and Cort were lower in the PE group than in the control group. The median concentrations of Cu, Zn, β-hCG, and T were higher in the PE than in the control. Mn, E2, and Cort showed negative associations with PE, while Cu, Zn, β-hCG, and T demonstrated positive associations, as determined through logistic regression. Mn, Cu, and Zn displayed linear dose-response relationships with PE. Zn and Cu had high weights in the positive association model of mixed heavy metal exposure with PE. The mediation analysis revealed that serum E2, P, T, Cort, and Cort/Cor might be potential mediators of the association between heavy metals (Mn, Cu, and Zn) and PE.

National, satellite-based land-use regression models for estimating long-term annual NO2 exposure across India

In India, scarcity of ground-based measurements of nitrogen dioxide (NO2) is a major challenge for estimating long-term exposure and associated health impacts. This study aimed to develop and validate a national-scale annual NO2 exposure model for India for 2019 and determine if model cross-validation predictive ability was improved by including non-continuous (manual) measurements along with reference-grade, continuous measurements.We used a supervised forward-addition linear regression method to fit land use regression (LUR) models developed with up to 804 Central Pollution Control Board ground monitoring stations (n = 157 continuous, n = 647 manual) and 209 spatial predictor variables, including satellite-based tropospheric NO2 columns. Two models were developed: one using continuous sites only and one using continuous and manual sites, with standard diagnostics and cross-validation (CV) methods. We also assessed if the kriging of final model residuals reduced spatial autocorrelation and improved model CV results. LUR coefficients for the best-performing model were applied to predictors for 2015–2021 and gridded at 100 m to estimate population-weighted exposure.The continuous sites-only model and combined continuous and manual sites models had CV-R2 values of 0.59 (root-mean-square error [RMSE]: 9.4 μg/m3) and 0.54 (RMSE: 8.3 μg/m3), respectively, and both included the satellite NO2 predictor. Kriging residuals increased the CV-R2 of the combined model to 0.70 (RMSE: 7.2 μg/m3) but offered no improvement for the continuous site model. National population-weighted average NO2 was 22.1 μg/m3 in 2019. We estimated over 92% of the Indian population was exposed to annual NO2 exceeding the WHO air quality guideline (10 μg/m3). In Delhi, Mumbai, and Kolkata, an estimated 45%, 100%, and 100% of the population, respectively, experienced annual NO2 levels that surpassed Indian standards (40 μg/m3). To our knowledge, this is the first such long-term NO2 LUR model specific to India, and predictions are available to interested researchers.

Promoting Glutathione Synthesis: A Possibility for Treating Cardiomyopathy Induced by a Maternal Western Diet.

The adverse effects of a Western diet on obesity and diabetes among reproductive-aged women pose a significant threat to the cardiovascular health of their offspring. Given the crucial role of glutathione metabolism and glutathione-related antioxidant defense systems in cardiovascular diseases through scavenging ROS and maintaining redox homeostasis, further exploration of their specific influence is imperative to develop therapeutic strategies for cardiomyopathy induced by a maternal Western diet. We developed a prenatal maternal Western diet exposure model in C57/B6 mice to investigate cardiac morphology and function through histological analysis and echocardiography. RNA sequencing and analysis were utilized to elucidate the mechanisms underlying the impact of a maternal Western diet and N-acetylcysteine treatment on cardiomyopathy. Additionally, ELISAs, transmission electron microscopy, and flow cytometry were employed to assess the antioxidant defense system and mitochondrial ROS levels in progenitor cardiomyocytes. N-acetylcysteine significantly mitigated cardiomyocyte hypertrophy, myocardial interstitial fibrosis, collagen type I accumulation, and left ventricular remodeling induced by a maternal Western diet, particularly in male offspring. Furthermore, N-acetylcysteine reversed the increase in apoptosis and the increase in the β/α-MyHC ratio in the myocardium of offspring that results from a maternal Western diet. RNA sequencing and GSEA revealed that the beneficial effects of N-acetylcysteine were linked to its ability to modulate oxidative phosphorylation pathways. Additionally, N-acetylcysteine treatment during pregnancy can markedly elevate glutathione levels, augment glutathione peroxidase (GPx) activity, and mitigate the accumulation of mitochondrial ROS caused by a maternal Western diet. N-acetylcysteine mitigated cardiomyopathy induced by a maternal Western diet by bolstering glutathione synthesis and enhancing GPx activity, thereby scavenging mitochondrial ROS and modulating oxidative phosphorylation pathways.

Understanding the Impacts of Presystemic Metabolism on the Human Oral Bioavailability of Chemicals.

Animal-free new approach methods promote chemical assessments based on the comparison between in vitro bioactivity and human internal concentrations, which necessitates a dependable knowledge of human oral bioavailability, i.e., the fraction of an orally ingested chemical that escapes from presystemic ("first-pass") metabolic processes and eventually enters systemic circulation. Using a physiologically based toxicokinetic model, we show how human oral bioavailability is impacted by presystemic metabolism within the gut lumen, gut wall, and liver and how this impact differs among chemicals with various permeability and stability properties. Our results highlight the gut lumen as a primary site of presystemic metabolism of certain chemicals, such as di-2-ethylhexyl phthalate (DEHP), for which the gut lumen may even exceed the liver in importance of presystemic metabolism due to these metabolic processes occurring in sequence. For chemicals with low transmembrane permeability and low stability, metabolism within the gut lumen is the most remarkable of the three presystemic metabolic processes. Notably, for chemicals that undergo substantial metabolism within the gut lumen, where the metabolites have high permeability, there is a notable discrepancy between the "theoretical bioavailability" (bioavailability of the unchanged parent compound) and the "apparent bioavailability" in measurement practices (bioavailability inferred from measured metabolites). Our work highlights the importance of considering presystemic metabolism, notably within the gut lumen, in human exposure and toxicokinetic modeling.