Nitrogen-containing organic compounds (NOCs) are key characteristic components in particulate matter (PM) from household solid fuel combustion, yet their personal exposure and class-dependent toxicity remain poorly characterized. We compared size-resolved personal exposure to particulate nitrated phenols (NPs) and nitro-PAHs (n-PAHs) among rural users of clean coal (CC), raw coal chunk (RCC), and biomass (BB), and evaluated representative compounds in A549 cells. Biomass users had the highest PM2.5-bound n-PAH exposure (up to 11.5-fold above clean coal), while NPs varied little across fuel groups (≤1.3-fold); CC and RCC users showed comparable PM2.5-bound NPs concentrations (64.0 ± 12.1 vs 57.4 ± 25.8 ng m–3, P = 0.545). n-PAHs exhibited greater cytotoxicity with lower IC50 values, whereas NPs produced stronger NF-κB activation by larger increases in p-IκB-α and COX-2 expression. Physicochemical descriptor analysis and molecular docking suggested that divergent biological responses may be partly attributable to differing hydrophobicity and protein interaction modes: hydrophobic contacts for n-PAHs, polar and hydrogen-bonding interactions for NPs. These results demonstrate clean heating transitions better mitigate n-PAH than NP exposure. NPs and n-PAHs differ substantially in cytotoxicity and NF-κB-mediated inflammation, providing a case study linking real-world personal exposure monitoring to molecular toxicology for health-risk-based prioritization of combustion-derived PM constituents.
Rong Feng, Hong-Mei Xu, Zhen-Xing Shen et al.· Environmental Science &...· 0 citations
Microplastics (MPs) pollution represents a pressing global environmental challenge, with studies increasingly highlighting their associated health risks. Although MPs have been detected in human lung tissues, the majority of existing research has concentrated on their physicochemical characteristics, environmental distribution and pulmonary health risks. Consequently, our understanding of the specific biological targets and effective intervention strategies against these risks remains limited. To identify therapeutic targets, we screened for pulmonary differential metabolites between normal mice and mice exposed to airborne MPs, derived from dust fall of 10 cities in China. Proteomics results showed adenosine 5'-monophosphate-activated protein kinase (AMPK) signalling pathway was one of critical targets. Through molecular docking and molecular dynamics stimulation, honokiol (HNK) was selected as therapeutic drug to regulate AMPK. In vitro results demonstrated that HNK significantly ameliorated autophagy inhibition in RAW264.7 cell, and alleviated mitochondrial dysfunction in BEAS-2B cell. Drug mechanism research revealed that HNK activated autophagy via the AMPK/mammalian target of rapamycin (AMPK/mTOR) pathway, and promoted mitophagy through the AMPK/E3 ubiquitin protein ligase parkin (AMPK/Parkin) pathway, thereby restoring mitochondrial function. Further targeted energy metabolomics analysis illustrated that HNK regulated the guanosine triphosphate to guanosine diphosphate (GTP/GDP) ratio, adenosine triphosphate (ATP) production, and nucleotide metabolism. These functions accelerated the restoration of autophagic flux, mitophagy reactivation and DNA repair. In conclusion, HNK effectively alleviates airborne MPs-induced autophagy inhibition, mitochondrial dysfunction and energy metabolism disorder via AMPK signalling, providing a promising intervention strategy for pulmonary injury caused by airborne MPs.
