Exogenous Chemicals Research Articles

Advances in the metabolism and phytoremediation of pesticides in horticultural plants.

Advances in the metabolism and phytoremediation of pesticides in horticultural plants.

Exposure assessment of 113 exogenous chemicals simultaneously in serum samples from children in north Shandong, China, and their association with sex, age, and body mass index

Exposure assessment of 113 exogenous chemicals simultaneously in serum samples from children in north Shandong, China, and their association with sex, age, and body mass index

Recent Advances in Structure, Biofunction, Detection, and Disease Therapeutic Targeting of Cytochrome P450.

The heme monooxygenase cytochrome P450 (CYPs), which play a major role in human drug metabolism, is predominantly found in the liver and intestines. CYPs are essential for the metabolism of therapeutic drugs and the treatment of diseases. It catalyzes the oxidative metabolism of several endogenous and exogenous chemicals. The expression and biological functions of CYP are affected by environmental factors, genetic variations, and physiological conditions, which can lead to adverse effects and reduce the therapeutic efficacy of drugs in humans. Therefore, there has been considerable interest in the development of probes that can detect the activity of CYPs in complex living systems. This review explores the recent advancements in our understanding of the structure and function of CYPs. It highlights the need to develop specific probes for various CYP subtypes using nonoptical, fluorescent, and bioluminescent substrates. Furthermore, it summarizes the potential of certain CYP subtypes as therapeutic targets for various diseases. Finally, the challenges and prospects of probes for monitoring CYP activity are explored.

Endocrine chemical disraptors and female reproductive health. Literature review

The review presents data from systematic reviews and metaanalyses addressing the issue of the eff ts of endocrine chemical disraptors (ECDs) on women’s reproductive health. ECDs are defi as exogenous chemicals or combinations of chemicals that aff t any aspect of hormone action and cause adverse health eff ts to the intact organism and/or its off as a result of changes in endocrine function. Currently, the mechanisms of adverse eff ts of many ECDs have been disclosed. It is suggested that ECDs can act as steroid agonists or antagonists by binding to sex steroid receptors. ECDs may also act through non-genomic mechanisms by blocking G protein-coupled receptors. Finally, interference with the action of steroids can contribute to infl through various mechanisms, including the inability to limit the production of reactive oxygen species. This systematic review was contains the most relevant data over the past 5 years on the adverse eff ts of ECD on the health of a woman and her child. Cochrane, MEDLINE, PubMed information bases were evaluated.

Engineered orthogonal and obligate bacterial commensalism mediated by a non-standard amino acid.

Microorganisms can be genetically engineered for intrinsic biological containment based on synthetic chemical provision. However, reliance on an exogenous chemical limits the contexts where a contained microorganism could survive. Here we design an orthogonal obligate commensalism in Escherichia coli that autonomously creates environments permissive for survival of a partner microbe. We engineer one E. coli strain (the producer) to biosynthesize a non-standard amino acid (nsAA) from simple carbon sources through heterologous expression. We engineer a second E. coli strain (the utilizer) to rely on the same nsAA for growth as a synthetic auxotroph, with a 14-day escape rate of 2.8 × 10-9 escapees per colony-forming unit. Co-culture experiments show utilizer dependence on the producer, with no escape detected during co-inoculation of ~107 colony-forming units of utilizer and a non-producer E. coli strain. Dependence is maintained within a simplified synthetic maize root-associated community. This work provides ecological insights and presents a potential biocontainment strategy independent of an exogenous chemical.

Advances in the Localization and Regulation of P-glycoprotein in Different Tissues and Organs.

P-glycoprotein(P-gp)is an ATP-dependent efflux transporter that is distributed in many tissues and organs.P-gp can selectively pump endogenous substrates and exogenous chemicals from the cell to the outside of the cell to maintain a stable endo-environment.However,it meanwhile restricts the entry of therapeutic drug into tissues and organs,and in particular,mediates the multidrug resistance of tumor cells to chemotherapeutic drugs.Therefore,understanding the localization of P-gp in different tissues and organs may be an important breakthrough point for disease treatment.In this paper,we mainly review the molecular structure,transport mechanism,localization,and regulation of P-gp in different tissues and organs,providing reference for the subsequent treatment of diseases.

Maternal benzo[a]pyrene exposure during critical gestational periods impairs offspring neurological development in rats: a mechanistic study of the Wnt/β-catenin signaling pathway.

Mid-gestation is a critical period for the development of the nervous system. Exposure to exogenous harmful chemicals during this period may lead to longterm neurological developmental abnormalities in offspring. Benzo[a]pyrene (B[a]P) is a commonly occurring neurotoxic environmental pollutant that can pass through the placental barrier and blood-brain barrier (BBB), thereby affecting placental nerve development. To investigate the neurotoxic mechanism of B[a]P on offspring exposed in mid-gestation, pregnant rats were exposed to B[a]P (25 mg/kg) from gestation days 8 to 14. Meanwhile, as an agonist of Wnt/β-catenin signaling pathway, lithium chloride (LiCl) was administered to observe the intervention effects. The results showed that in rats exposed to B[a]P in mid-gestation, the developmental nodes of the offspring were delayed, and the neurosensory sensitivity of the offspring was reduced. These offspring also had cognitive impairments in adulthood. Subsequent morphological and protein experiments showed that the exposed offspring had reduced neuronal complexity in the CA1 region of the hippocampus, decreased β-catenin expression, and increased GSK-3β expression in the hippocampal tissue. However, all these indexes can be reversed by LiCl. These results suggest that B[a]P exposed in mid-gestation pregnancy may lead to neurological damage in the offspring by downregulating the Wnt/β-catenin signaling pathway.

Abstract 7448: Developing virtual staining algorithm of colon cancer organoids using holotomography and deep learning

Abstract Colon cancer organoids hold great potential for studying the development of colon cancer. To assess their physiological and developmental status, both morphological parameters (e.g., cell shape and volume) and functional parameters (e.g., presence of proliferating cells or pluripotent stem cells) are crucial. However, current fluorescence labeling methods are invasive, potentially damaging or altering the organoids, making them disposable. To overcome this limitation, it is essential to develop a non-invasive method for monitoring organoids for long-term. We propose a solution that integrates holotomography and deep learning. Holotomography is a label-free imaging technique that measures the 3D refractive index distribution of samples without requiring any exogenous labeling. While this technique operates within a label-free framework, the resulting images provide only structural information and lack functional information. This limitation makes it challenging for researchers to distinguish cellular and subcellular structures with specific function. We address this challenge by leveraging deep learning to provide both structural and functional information through virtual staining of label-free images. Specifically, we construct a paired dataset using correlative holotomography, which captures both label-free images and their corresponding fluorescence images. Using supervised learning, we train a neural network to map label-free images to their corresponding fluorescence counterparts. Once trained, the neural network can automatically predict virtual fluorescence images from label-free inputs without exposing the organoids to any exogenous chemicals. To validate the accuracy of the trained neural network, we first acquire label-free images of the organoids and input them into the network. After obtaining the network-generated virtual fluorescence images, we chemically stain the same organoids. Finally, we compare the chemically stained images with the virtual images produced by the neural network to evaluate its performance. By combining the safety of label-free imaging with the precision of artificial intelligence, our technology eliminates critical barriers to organoid research and translation. This breakthrough accelerates the development of scalable and safe organoid therapies, bringing us closer to a future where lab-grown organoids revolutionize regenerative medicine and save lives. Citation Format: Juyeon Park, Geon Kim, YongKeun Park. Developing virtual staining algorithm of colon cancer organoids using holotomography and deep learning [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 7448.

Advances in the study of death receptor 5.

DR5, a receptor with the highest affinity for TRAIL under physiological conditions, selectively induces apoptosis in specific target cells such as tumor and aberrant immune cells, while minimally affecting normal cells. The TRAIL-DR5 signaling pathway is a crucial regulatory mechanism when the body responds to various exogenous interference factors, including viruses, chemicals, and radiation. This pathway plays a vital role in maintaining physiological homeostasis and in the pathological development of various diseases. Different modulations of DR5, such as upregulation, activation, and antagonism, hold significant potential for therapeutic applications in tumors, cardiovascular diseases, autoimmune diseases, viral infections, and radiation injuries. This article provides an overview of the current research progress on DR5, including the status and prospects of its clinical applications.

The potent human CAR activator CITCO is a non-genotoxic hepatic tumour-promoting agent in humanised constitutive androstane receptor mice but not in wild-type animals

A large number of drugs and compounds produced by the chemical and agrochemical industry, often referred to as ‘non-genotoxic carcinogens’ (NGC), score as tumour promotors in rodent models. It is unclear whether these compounds act similarly in humans. The most extensively investigated compounds have been the anti-convulsive drugs, phenobarbital (PB), and phenytoin. Liver tumours induced by PB are dependent upon the activation of the constitutive androstane receptor (CAR). However, marked species differences in CAR activation by exogenous chemicals exist with some being much more potent activators of human CAR, e.g., 6-(4-chlorophenyl)imidazo[2,1-β][1,3]thiazole-5-carbaldehyde-O-(3,4-dichlorobenzyl)oxime (CITCO). We have compared CITCO-induced tumour formation in the livers of mice in which murine CAR has been replaced with its human counterpart. Our findings reveal that CITCO-dependent liver tumours are only formed in mice-expressing human CAR and not in wild-type animals. In addition, contrary to one of the proposed mechanisms of NGC carcinogenicity, we show that CITCO did not induce a hyperplastic response in the liver of the humanised mice. These data raise some key questions about the mechanism of action of NGCs and identify the limitations of current rodent carcinogenicity test systems in relation to risk assessment.

Application of small interfering RNA technology in cytochrome P450 gene modulation.

Application of small interfering RNA technology in cytochrome P450 gene modulation.

Chemical exposure in females of childbearing age associated with sex hormones: Evidence from an untargeted exposomic approach.

Chemical exposure in females of childbearing age associated with sex hormones: Evidence from an untargeted exposomic approach.

Electrode- and Label-Free Assessment of Electrophysiological Firing Rates through Cytochrome C Monitoring via Raman Spectroscopy.

In vitro neurotoxicology aims to assess and predict the side effects of exogenous chemicals toward the human brain. Among the exploited approaches, electrophysiological techniques stand out for the high spatiotemporal resolution and sensitivity, with the patch clamp considered the gold standard technique for such purposes. However, structural toxicity and metabolic effects may elude detection when only the electrical activity is measured, highlighting the need for integrating electrophysiological recordings with complementary approaches such as optical methods. In this study, we describe an integrated platform for recording neuronal electrical activity and performing chemical analysis with a noninvasive label-free optical imaging, Raman spectroscopy. Specifically, we developed a protocol that maximizes the signal-to-noise ratio while avoiding the crosstalk of the electrical and spectroscopical readouts and any phototoxicity associated with the laser exposure. Synchronous and sequential electrical-optical measurements were carried out and compared, with the sequential approach being more suitable for the longitudinal investigation and correlation of the neuronal electrical activity to the intracellular content of reduced cytochrome C, lipids, proteins, and nucleic acids. Data analysis shows a strong correlation between the metabolic status of the single cells and the overall neuronal firing rate, suggesting the electrode- and label-free assessment of the neuronal firing rates through the monitoring of cytochrome C via Raman spectroscopy when multielectrode array devices with high electrical noise and impedance are used. Conversely, the neuronal firing rate and the reduced cytochrome C content were not correlated to lipids, proteins, and nucleic acids. Thus, this study demonstrates the crosstalk of the neuronal firing rate and reduced cytochrome C as downstream and upstream features of the neuronal metabolic activity and that through the monitoring of the de novo synthesis of lipids, proteins, and nucleic acids, Raman spectroscopy provides additional information for a more accurate assessment of the acute and chronic neurotoxicity.

Connotation of Plant Growth Regulators on Seed Germination

Seed germination is a complex physiological process influenced by various internal and external factors. The initial requirements for seed germination include suitable temperature (depending on the seed type), moisture, and oxygen. The endosperm serves as a reservoir of food and contains hormones that initiate seed germination. Both endogenous (produced within the seed) and exogenous (externally applied) hormones play a crucial role in germination and the early growth of seedlings. Plant growth activators enhance seed germination and promote growth, while retardants inhibit both germination and growth processes and may induce dormancy. Growth inhibitors, therefore, can be strategically applied to prolong seed viability during storage. Furthermore, various exogenous chemicals are employed to regulate seed and plant growth processes. These hormones and chemicals not only influence germination but also help to determine the seed's chemistry, providing insights into its physiology and predicting its behavior under different conditions.

Distribution of Environmental Phenols into Follicular Fluid and Urine of Women Attending Infertility Clinic.

Infertility and environmental pollution are two globally prevalent and related issues. To explore women's reproductive health, the composition of follicular fluid (FF) has been studied and it was found that changes to its composition, including the presence of exogenous chemicals, can adversely affect the fertilization process. Two groups of women (idiopathic infertility and controls) who were patients at a fertility clinic were recruited for this study. Samples of urine and FF were gathered from each participant to determine the concentration of 14 common phenols (four parabens, six bisphenols, two benzophenones, and two naphthols). Associations between phenol concentrations (free and total) in both matrices were described using Spearman's correlation coefficient and were compared between two groups by the Mann-Whitney U test. Eight phenols were quantified in more than 50% of the urine samples, while only three parabens were quantified in hydrolyzed FF samples, and only methylparaben was quantified in non-hydrolyzed FF samples. Conjugates were the predominant form in FF samples. However, a significant correlation of 0.533 (p < 0.0001) was observed between free and total methylparaben concentrations in FF. Differences in concentrations between cases and controls in both matrices were not statistically significant, except for benzophenone-3 in urine, with a higher median observed in the control group (p = 0.04). The total paraben concentrations in urine and FF samples were rather weakly correlated (r = 0.232-0.473), implying that urine concentrations may not be appropriate for predicting their concentration in FF.

The Role of Environmental Endocrine Disruptors on Leydig Cell Death and Senescen.

Environmental endocrine disruptors, as exogenous chemicals that interfere with hormonal behavior, are known to cause testicular Leydig cell death and senescence. The incidence of diseases of the male reproductive system has been increasing over the past half-century. Genetic defects alone cannot explain the rapid increase in incidence, and there is growing evidence that environmental factors or lifestyle changes are responsible for the high incidence in recent years. Testicular Leydig cells occupy an important role in the male reproductive system. In this study, we review the mechanisms by which environmental endocrine disruptors promote both death and senescence of testicular Leydig cells, refine the former into two programmed death modes, apoptosis, and autophagy, and further explore the interactions among them, thus summarizing the advances of the toxic effects of environmental endocrine disruptors on testicular Leydig cells, and expecting to provide a new therapeutic idea.

Application of nano-TiO 2 @adsorbent composites in the treatment of dye wastewater: A review

A large amount of wastewater with a high dye content is discharged from the textile printing and dyeing industry. Synthetic dyes, which are essentially exogenous chemicals, predominantly exhibit the property of poor biodegradability. Consequently, they are capable of persisting stably within the environment over protracted time spans. The high-chroma dye wastewater not only results in severe water pollution but also breaks ecological balance, thereby rendering it a pivotal and formidable facet in the realm of industrial wastewater treatment. Consequently, the treatment of printing and dyeing wastewater prior to its discharge is of utmost necessity. This article offers a relatively comprehensive exposition of the treatment methods for dye wastewater, with a specific focus on the adsorption method, the photocatalysis method, and their respective characteristics. Nano-TiO 2 @adsorbent composites, which integrate the advantages of adsorption and photocatalysis, have been widely studied for the treatment of dye wastewater. This paper provides a broad overview of the classifications, the adsorption-photocatalytic mechanism, and influencing factors of nano-TiO 2 @adsorbent composites. Nano-TiO 2 @adsorbent composites integrate the processes of adsorption, catalysis, and degradation, thereby significantly improving the efficiency of photocatalytic degradation for organic pollutants by titanium dioxide catalysts. Furthermore, the suggestion for the research and development of photocatalyst @textile composite materials for dye wastewater treatment is put forward in this article.

Alkaloids are associated with increased microbial diversity and metabolic function in poison frogs.

Alkaloids are associated with increased microbial diversity and metabolic function in poison frogs.

Association of ADH1B and ALDH2 genotypes with the risk of lung adenocarcinoma.

The incidence of lung adenocarcinoma (LAD) is increasing worldwide. Single-nucleotide polymorphisms in aldehyde dehydrogenase 2 family member gene ( ALDH2 ) rs671 and alcohol dehydrogenase 1B ( ADH1B ) rs1229984 are common and functionally important genetic variants to metabolize endogenous and exogenous aldehyde chemicals, related to cancer. This is a case-control study. A total of 150 newly diagnosed LAD patients were from Kaohsiung Medical University Hospital, Taiwan, between 2019 and 2022. Two control groups, TWB-1 ( n = 600) and TWB-2 ( n = 29 683), were selected from Taiwan Biobank (TWB), and the case patients were frequency-matched with TWB-1 based on age category (30-60 or >60 years old), sex, and education levels. Logistic regression models were employed to analyze the association between two genetic variants and LAD risk. A significant association was noted between ALDH2 and LAD risk. Those with ALDH2 rs671 *2/*2 in TWB-1 and TWB-2 controls had a 2.68-fold (95% CI = 1.43-4.99) and a 1.83-fold (95% CI = 1.07-3.11) increased risk of LAD, respectively, compared with those with ALDH2 rs671 *1/*1 or *1/*2 , after adjusting for covariates. This association was particularly pronounced in females. No overall significant association between ADH1B rs1229984 and LAD risk was observed. The findings indicate a strong and robust risk association between ALDH2 rs671*2/*2 and LAD in the Taiwan population, particularly in Taiwanese female adults.

Biotransformation of Tetrabromobisphenol A and Its Analogs by Selected Gut Bacteria Strains: Implications for Human Health.

Knowledge of the biotransformation of tetrabromobisphenol A (TBBPA) and its related contaminants by human gut microbiota (GM) remains unexplored. Here, TBBPA and its four analogs were incubated with mixed GM strains, and nine rhamnosylated or debrominated transformation products (TPs) were discovered. Remarkably, rhamnosylation was identified as a common and unique microbial transformation pathway for these contaminants, and six of the seven rhamnosylated TPs were reported for the first time. Additionally, a kinetic transformation study also showed a rapid and strong bioaccumulation of TBBPA and TPs by Clostridium manihotivorum. Genomic analysis and phylogenetic studies identified C1.1_02053 as the gene encoding the C. manihotivorum working rhamnosyltransferase (CmRT), showing elevated gene expression with higher TBBPA exposure. Molecular docking identified five critical amino acid residues in CmRT that catalyze TBBPA rhamnosylation, and molecular dynamics simulations further confirmed the stability of the CmRT-TBBPA complex. Dynamic metabolomics analysis showed microbial growth-dependent disturbing effects in C. manihotivorum upon TBBPA exposure, and key metabolic pathways related to rhamnosyltransferase showed changes closely related to the transformation process. These findings provide insights into the unique transformation of environmental contaminants by the GM and highlight the disturbing effects of exogenous chemicals on the GM, as well as the potential impacts on overall human health.