Network-Based Identification of Key Toxic Compounds in Airborne Chemical Exposome

Environmental Science & Technology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 14, 2025

Air pollution is a leading contributor to the global disease burden. However, complex nature of chemicals which humans are exposed through inhalation has obscured identification key compounds responsible for diseases. Here, we develop network topology-based framework identify toxic in airborne chemical exposome. Using cardiovascular diseases (CVDs) as model disease, found that modules various closely linked CVDs. The proximity compound target can indicate extent toxicity induced by compounds. By integrating mass spectrometry-based external exposure concentrations and machine learning-predicted internal concentrations, established comprehensive linkage connecting disease-related risk These findings were subsequently validated using data on regional scale. This work provides an effective strategy identifying within environmental exposomes establishes new paradigm understanding pathogenicity air pollution.

Language: Английский

---

New insights into the mechanism of triphenyl phosphate and its metabolite diphenyl phosphate in diabetic kidney disease

Ecotoxicology and Environmental Safety, Journal Year: 2025, Volume and Issue: 291, P. 117877 - 117877

Published: Feb. 1, 2025

Diabetic kidney disease is a significant complication of diabetes mellitus, and exposure to certain chemicals may play role in its development. Triphenyl phosphate (TPHP) commonly used plastics flame retardants. This study aims investigate the potential impact TPHP metabolite diphenyl (DPHP) on diabetic using various methods, including network toxicology, molecular docking, cell experiments like CCK8 assay real-time-PCR. The research examined relationship between urinary DPHP levels function American adults data from National Health Nutrition Examination Survey (NHANES) 2017 March 2020. Additionally, explored targets action for toxicity analysis, conducted protein interaction functional aspects through Gene Ontology Kyoto Encyclopedia Genes Genomes enrichment analysis. Furthermore, identified key proteins involved experimental verification by treating cells with DPHP. Toxicity analysis showed that could cause dose-dependent mouse podocyte clone 5 (MPC5) mesangial (MES13). also detected mRNA expression core molecularly docked results indicated statistically regulation most MPC5, MES13, human kidney-2 cells.

Language: Английский

---

Triphenyl phosphate induces lipid metabolism disorder and promotes obesity through PI3K/AKT signaling pathway

Environment International, Journal Year: 2025, Volume and Issue: 198, P. 109428 - 109428

Published: April 1, 2025

Triphenyl phosphate (TPHP) is a widely used organic flame retardant that has been reported as potential environmental obesogen. However, the impact and mechanism of action TPHP on adipose tissue are still unclear. This study investigates lipid metabolism disorders through in vivo vitro experiments. Male female BALB/c mice were exposed to (0, 1, 10, 150 mg/kg/day) for 60 days, 3T3-L1 preadipocytes treated with concentrations 0.1, 10 μM) during differentiation. The results showed exposure could cause gender specific dyslipidemia, male exhibiting dose-dependent increases inguinal coefficient, adipocyte hypertrophy, upregulation differentiation adipogenesis-related genes. In contrast, did not show significant changes morphology. suggested might promote occurrence adiposity by disrupting homeostasis tissue. During maturation process preadipocytes, led increased accumulation disrupted simultaneous activation adipogenesis lipolysis. Multiple omics data peroxisome proliferator-activated receptor γ (PPARγ) signaling pathway fatty acid was core induced metabolic dysfunction. Further research activated PI3K/AKT pathway, PI3K inhibitor (LY294002) rescue droplet formation normalize expression adipogenic markers. These findings confirm obesogen can disrupt white PPARγ pathways, higher susceptibility males. provides compelling evidence obesogenic effects information risk assessment organophosphorus retardants.

Language: Английский

---

Mechanisms underlying targeted mitochondrial therapy for programmed cardiac cell death

Frontiers in Physiology, Journal Year: 2025, Volume and Issue: 16

Published: April 11, 2025

Heart diseases are common clinical diseases, such as cardiac fibrosis, heart failure, hypertension and arrhythmia. Globally, the incidence rate mortality of increasing by years. The main mechanism disease is related to cellular state. Mitochondrion organ energy supply, participating in various signal transduction pathways playing a vital role occurrence development disease. This review summarizes cell death patterns molecular mechanisms associated with mitochondrial dysfunction.

Language: Английский

---

Mechanism of Nano‐Microplastics Exposure‐Induced Myocardial Fibrosis: DKK3‐Mediated Mitophagy Dysfunction and Pyroptosis

Journal of Biochemical and Molecular Toxicology, Journal Year: 2025, Volume and Issue: 39(5)

Published: April 22, 2025

ABSTRACT Nano‐microplastics (NMPs), as environmental pollutants, are widely present in nature and pose potential threats to biological health. This study aims investigate the mechanisms by which NMPs inhibit mitophagy through suppression of dickkopf‐related protein 3 (DKK3) expression, leading NOD‐like receptor family, pyrin domain containing (NLRP3) inflammasome‐mediated cardiomyocyte pyroptosis promoting myocardial fibrosis. Healthy adult male C57BL/6 mice were administered NMP solution via gavage, their cardiac function was monitored. The results showed that exposure significantly reduced left ventricular ejection fraction (LVEF) fractional shortening (LVFS) increased extent Transcriptome sequencing identified 14 differentially expressed genes (DEGs), including MYL7. Using random forest algorithm functional enrichment analysis, DKK3 a key gene. In Vitro experiments further confirmed downregulate thereby inhibiting pyroptosis. elucidates molecular induce fibrosis provides new theoretical bases targets for diagnosis treatment heart diseases.

Language: Английский

---

Adipogenic Effects of Cresyl Diphenyl Phosphate (Triphenyl Phosphate Alternative) through Peroxisome Proliferator-Activated Receptor Gamma Pathway: A Comprehensive Study Integrating In Vitro, In Vivo, and In Silico from Molecule to Health Risk

Environmental Science & Technology, Journal Year: 2024, Volume and Issue: 58(42), P. 18631 - 18641

Published: Oct. 9, 2024

Cresyl diphenyl phosphate (CDP), a novel organophosphate ester (OPE), has been detected in various environmental and human samples. However, there is very limited knowledge regarding its toxicity, mechanisms of action, potential health risks. Using new alternative methods (NAMs), across the molecular interactions, signaling pathways, cell functions, animal effects, population risks, we investigated adipogenic effects associated risks CDP legacy OPE triphenyl (TPHP) by acting on peroxisome proliferator-activated receptor gamma (PPARγ). Among 19 screened OPEs, bound to PPARγ with highest binding potency, followed TPHP. activated through fitting into pocket strong hydrophobicity hydrogen bond interactions; exhibited higher potency compared In 3T3-L1 cells, enhanced PPARγ-mediated adipogenesis activity, exhibiting greater than The intracellular concentration receptor-bound concentrations (RBC) were also those TPHP both HEK293 cells cells. mice, exposure pathway, leading an increased white adipose tissue weight gain. Overall, could bind activate PPARγ, thereby promoting preadipocyte differentiation development tissue. Its obesogenic should be high concern.

Language: Английский

---

Cresyl diphenyl phosphate (a novel organophosphate ester) induces hepatic steatosis by directly binding to liver X receptor α: From molecule action to risk assessment

Environment International, Journal Year: 2024, Volume and Issue: 194, P. 109168 - 109168

Published: Nov. 26, 2024

Language: Английский

---