Staged Construction of Pluripotent Stem Cell Lung Models for Assessing Respiratory Toxicity of Environmental Pollutants.

Due to factors such as smoking, air pollution, and an aging population, the prevention and control of chronic respiratory diseases in China are becoming more severe. Combining current epidemiological investigations, exposure to environmental pollutants such as atmospheric pollutants, persistent organic pollutants, and heavy metals may have adverse effects on lung development. Lung differentiation models are crucial tools for elucidating the process of lung development.

Visualization of FDA Adverse Drug Reaction Reports: Development and Usability Study of the VisDrugs Web Server.

Background: Adverse drug reactions (ADRs) are a major concern in drug safety, and the FDA Adverse Event Reporting System (FAERS) provides valuable ADR data. However, analyzing FAERS data is complex and requires bioinformatics expertise. Despite the vast amount of ADR data available, there is a lack of user-friendly tools that enable efficient visualization and comparison of ADRs for researchers and health care professionals.

Development and application of meta-analysis in environmental health research.

The Adverse Outcome Pathway (AOP) framework is a foundational approach in environmental pollutant research, encompassing the detrimental effects of pollutants across biological levels from molecules to populations. Toxicogenomics (TGx), which integrates omics technologies with toxicology, plays a crucial role in AOPs by elucidating the relationships between chemical exposure, molecular initiating events (MIEs), and key events (KEs) across various biological levels using animal and cell model-based data. However, since some MIEs (e.

Developmental toxicity and skin sensitization potential of synthetic phenolic antioxidants and butylated hydroxytoluene transformation products: Insights from human embryonic stem cell models.

Synthetic phenolic antioxidants (SPAs) are commonly used in food, cosmetics, and other products for their antioxidant properties and stability. However, increasing evidence links excessive SPA use to adverse effects, including developmental issues in animals. Given the widespread use of SPAs in cosmetics, there is a growing need to assess their potential health risks, particularly whether safe to be used during pregnancy.

Integrative transcriptomics analysis reveals convergent toxicological effects of perfluorooctanoic acid and perfluorooctane sulfonate on human liver: Evidence from multiple models.

Perfluorooctanoic acid and perfluorooctane sulfonate are well-known eight-carbon per- and polyfluoroalkyl substances (8C-PFAS) potentially toxic for the human liver. However, direct experimental evidence demonstrating their toxicity on the human liver remains limited. Consequently, this study aimed to extrapolate the 8C-PFAS liver toxicity mechanisms by leveraging omics data to integrate mouse and human findings.

Revealing the neurodevelopmental toxicity of face mask-derived microplastics to humans based on neural organoids.

The massive use of face masks during and after the COVID-19 pandemic has raised global concerns about environmental issues. Microplastics released from face masks pose great threats to ecosystems and human health. However, the potentially hazardous effects of face mask-derived microplastics (FMMs) on humans remain poorly understood.

DDX18 coordinates nucleolus phase separation and nuclear organization to control the pluripotency of human embryonic stem cells.

Pluripotent stem cells possess a unique nuclear architecture characterized by a larger nucleus and more open chromatin, which underpins their ability to self-renew and differentiate. Here, we show that the nucleolus-specific RNA helicase DDX18 is essential for maintaining the pluripotency of human embryonic stem cells. Using techniques such as Hi-C, DNA/RNA-FISH, and biomolecular condensate analysis, we demonstrate that DDX18 regulates nucleolus phase separation and nuclear organization by interacting with NPM1 in the granular nucleolar component, driven by specific nucleolar RNAs.

Advancing Environmental Toxicology : From Immortalized Cancer Cell Lines to 3D Models Derived from Stem Cells.

In recent years, rapid industrial development has resulted in the production and exposure of a substantial number of compounds to the human body. This has created an urgent need in environmental toxicology for models that are efficient, accurate, and cost-effective in evaluating the health impacts of these compounds on humans. Over the past seven decades, various cancer cell lines and immortalized cell lines have made significant contributions to the advancement of research on organ toxicity.

Recent advances in environmental toxicology: Exploring gene editing, organ-on-a-chip, chimeric animals, and in silico models.

In our daily life, we are exposed to various environmental pollutants in multiple ways. At present, we mainly rely on animal models and two-dimensional cell culture models to evaluate the toxicity of environmental pollutants. Nevertheless, results in animal models do not always apply to humans because of differences between species, while two-dimensional cell culture models cannot replicate the in vivo microenvironments, making it difficult to predict the true toxic response of environmental pollutants in humans.

Formation of persistent free radicals from epigallocatechin Gallate in tea processing and their implications on DNA damage and cell cytotoxicity.

Tea is widely consumed in both beverages and food. Epigallocatechin gallate (EGCG) is the most crucial active ingredient in tea. Currently, knowledges on transformation processes of EGCG during tea processing are lacking.

Assessment and Comparison of Early Developmental Toxicity of Six Per- and Polyfluoroalkyl Substances with Human Embryonic Stem Cell Models.

Per- and polyfluoroalkyl substances (PFAS) are extensively utilized in varieties of products and tend to accumulate in the human body including umbilical cord blood and embryos/fetuses. In this study, we conducted an assessment and comparison of the potential early developmental toxicity of perfluorooctanoic acid (PFOA), undecafluorohexanoic acid (PFHxA), heptafluorobutyric acid, perfluorooctanesulfonate (PFOS), perfluorohexanesulfonate, and perfluorobutyric acid at noncytotoxic concentrations relevant to human exposure using models based on human embryonic stem cells in both three-dimensional embryoid body (EB) and monolayer differentiation configurations. All six compounds influenced the determination of cell fate by disrupting the expression of associated markers in both models and, in some instances, even led to alterations in the formation of cystic EBs.

Assessing developmental neurotoxicity of emerging environmental chemicals using multiple in vitro models: A comparative analysis.

Newly synthesized chemicals are being introduced into the environment without undergoing proper toxicological evaluation, particularly in terms of their effects on the vulnerable neurodevelopment. Thus, it is important to carefully assess the developmental neurotoxicity of these novel environmental contaminants using methods that are closely relevant to human physiology. This study comparatively evaluated the potential developmental neurotoxicity of 19 prevalent environmental chemicals including neonicotinoids (NEOs), organophosphate esters (OPEs), and synthetic phenolic antioxidants (SPAs) at environment-relevant doses (100 nM and 1 μM), using three commonly employed in vitro neurotoxicity models: human neural stem cells (NSCs), as well as the SK-N-SH and PC12 cell lines.

Unexpected hydroxyl radical production in brewed tea under sunlight.

Tea is one of the world's most popular and widely consumed beverages. It is a common pastime to enjoy a cup of tea in the sunshine. However, little attention has been given to understanding the possible photochemical reactions occurring beneath the calm surface of brewed tea.

Understanding the effects of per- and polyfluoroalkyl substances on early skin development: Role of ciliogenesis inhibition and altered microtubule dynamics.

Per- and polyfluoroalkyl substances (PFAS) are a class of highly stable chemicals, widely used in everyday products, and widespread in the environment, even in pregnant women. While epidemiological studies have linked prenatal exposure to PFAS with atopic dermatitis in children, little is known about their toxic effects on skin development, especially during the embryonic stage. In this study, we utilized human embryonic stem cells to generate non-neural ectoderm (NNE) cells and exposed them to six PFAS (perfluorooctanoic acid (PFOA), undecafluorohexanoic acid (PFHxA), heptafluorobutyric acid (PFBA), perfluorooctane sulfonate (PFOS), perfluorohexane sulfonate (PFHxS) and perfluorobutyric acid (PFBS)) during the differentiation process to assess their toxicity to early skin development.

Typical neonicotinoids and organophosphate esters, but not their metabolites, adversely impact early human development by activating BMP4 signaling.

Recent studies have highlighted the presence of potentially harmful chemicals, such as neonicotinoids (NEOs) and organophosphate esters (OPEs), in everyday items. Despite their potential threats to human health, these dangers are often overlooked. In a previous study, we discovered that NEOs and OPEs can negatively impact development, but liver metabolism can help mitigate their harmful effects.

Developmental toxicity assessment of neonicotinoids and organophosphate esters with a human embryonic stem cell- and metabolism-based fast-screening model.

In recent years, neonicotinoids (NEOs) and organophosphate esters (OPEs) have been widely used as substitutes for traditional pesticides and brominated flame-retardants, respectively. Previous studies have shown that those compounds can be frequently detected in environmental and human samples, are able to penetrate the placental barrier, and are toxic to animals. Thus, it is reasonable to speculate that NEOs and OPEs may have potential adverse effects in humans, especially during development.

Transcriptomic Integration Analyses Uncover Common Bisphenol A Effects Across Species and Tissues Primarily Mediated by Disruption of JUN/FOS, EGFR, ER, PPARG, and P53 Pathways.

Bisphenol A (BPA) is a common endocrine disruptor widely used in the production of electronic, sports, and medical equipment, as well as consumer products like milk bottles, dental sealants, and thermal paper. Despite its widespread use, current assessments of BPA exposure risks remain limited due to the lack of comprehensive cross-species comparative analyses. To address this gap, we conducted a study aimed at identifying genes and fundamental molecular processes consistently affected by BPA in various species and tissues, employing an effective data integration method and bioinformatic analyses.

MYC acetylated lysine residues drive oncogenic cell transformation and regulate select genetic programs for cell adhesion-independent growth and survival.

The MYC oncogenic transcription factor is acetylated by the p300 and GCN5 histone acetyltransferases. The significance of MYC acetylation and the functions of specific acetylated lysine (AcK) residues have remained unclear. Here, we show that the major p300-acetylated K148(149) and K157(158) sites in human (or mouse) MYC and the main GCN5-acetylated K323 residue are reversibly acetylated in various malignant and nonmalignant cells.

Development of a simplified human embryonic stem cell-based retinal pre-organoid model for toxicity evaluations of common pollutants.

Objective: To explore the retinal toxicity of pharmaceuticals and personal care products (PPCPs), flame retardants, bisphenols, phthalates, and polycyclic aromatic hydrocarbons (PAHs) on human retinal progenitor cells (RPCs) and retinal pigment epithelial (RPE) cells, which are the primary cell types at the early stages of retinal development, vital for subsequent functional cell type differentiation, and closely related to retinal diseases.

Materials And Methods: After 23 days of differentiation, human embryonic stem cell (hESC)-based retinal pre-organoids, containing RPCs and RPE cells, were exposed to 10, 100, and 1000 nM pesticides (butachlor, terbutryn, imidacloprid, deltamethrin, pendimethalin, and carbaryl), flame retardants (PFOS, TBBPA, DBDPE, and TDCIPP), PPCPs (climbazole and BHT), and other typical pollutants (phenanthrene, DCHP, and BPA) for seven days. Then, mRNA expression changes were monitored and compared.

Pollution effects on retinal health: A review on current methodologies and findings.

In our daily life, we are exposed to numerous industrial chemicals that may be harmful to the retina, which is a delicate and sensitive part of our eyes. This could lead to irreversible changes and cause retinal diseases or blindness. Current retinal environmental health studies primarily utilize animal models, isolated mammalian retinas, animal- or human-derived retinal cells, and retinal organoids, to address both pre- and postnatal exposure.

Developmental toxicity assessments for TBBPA and its commonly used analogs with a human embryonic stem cell liver differentiation model.

Tetrabromobisphenol A (TBBPA) is widely used in industrial production as a halogenated flame retardant (HFR). Its substitutes and derivatives are also commonly employed as HFRs. Consequently, they can be frequently detected in environmental and human samples.

Abnormal neural differentiation in response to graphene quantum dots through histone modification interference.

Graphene quantum dots (GQDs) have been broadly applied in biomedicine in recent years, and their environmental exposure and toxicological impacts have raised increasing concerns. The nanosafety assessment on the nervous system is one of the most important aspects, and potential effects of GQDs on neurodevelopment and the underlying mechanism are still elusive. In this study, the neural developmental toxicities of OH-GQDs and NH-GQDs were investigated using the mouse embryonic stem cells (mESCs).