Environment & Health最新文献

Aging is a significant global health challenge, with neurodegenerative diseases severely affecting the quality of life in the elderly. Di-(2-ethylhexyl) phthalate (DEHP), a commonly used plasticizer in food packaging, has been identified as an environmental contaminant with thyroid hormone (TH) disruption and neurotoxic effects. Myelination in the central nervous system is crucial for neurological function, and oligodendrocytes play a central role in this process by forming myelin around axons. THs regulate oligodendrocyte differentiation and the expression of myelin-related genes. This study investigates whether environmental exposure to DEHP in aging mice disrupts thyroid hormone signaling and contributes to myelin damage. 22-month-old male C57BL/6J mice were orally administered DEHP at doses of 0, 0.2, 20, and 200 mg/kg·bw/day (mg/kg·bw/d) for 30 days (d). Nissl staining revealed significant neuronal loss in the cerebellum at higher DEHP doses. Luxol Fast Blue staining showed notable hypomyelination in DEHP-treated mice. Immunofluorescence results demonstrated an increase in oligodendrocyte progenitor cells (NG2⁺), while mature (CC1⁺) and myelinating oligodendrocytes (MBP⁺) were significantly reduced, indicating impaired oligodendrocyte differentiation and myelination. Furthermore, KLF9, a transcriptional regulator critical for oligodendrocyte differentiation, was downregulated. TH levels (T3, T4), transporters (MCT8, OATP1C1), and receptors (TRα, TRβ) were decreased locally, while deiodinases (DIO2, DIO3) were upregulated, reflecting disruption in thyroid signaling. Environmental exposure to DEHP disrupts thyroid hormone signaling in aged mice, impairing oligodendrocyte differentiation and myelin formation. This process is accompanied by microglial activation and neuroinflammation, which may serve as a pathological basis for neuronal loss and further neurodegeneration. Daily oral intake of plasticizer DEHP may induce cerebellar demyelination, contributing to neurodegeneration in the elderly. These results highlight that inappropriate exposure to environmental pollutants, such as DEHP, could increase the risk of cerebellar dysfunction and neurodegeneration in elderly individuals.

Major depressive disorder (MDD) has been recently linked to air pollution exposure; nevertheless, the biological mechanisms underlying this association remain underinvestigated. Air pollution might modulate the microRNA (miRNA) content of neuron-derived extracellular vesicles (NdEVs), potentially mirroring brain epigenetic alterations. In the present study, we investigated the relationship between air pollution, NdEV miRNAs, and MDD severity in a population of 200 patients with depression. After signing informed consent, participants compiled questionnaires about demographics, lifestyle and clinical history, and donated a blood sample. MDD severity was assessed by five scales. Particulate matter ≤2.5 μm (PM_2.5) and nitrogen dioxide (NO₂) exposure was assigned based on participants' residential address. Plasma NdEVs were obtained by L1CAM immunocapture. NdEV miRNAs were queried by RT-qPCR (microarray) following a two-stage approach. Associations between air pollutants, NdEV miRNAs, and MDD severity were assessed by multivariable regression models. The regulatory function of NdEV miRNAs was investigated by gene target and pathway analysis. As a result, exposure to NO₂ was associated with decreased levels of miR-191 and miR-24, while PM_2.5 was negatively associated with miR-191, miR-223, miR-24, miR-320, miR-451, miR-572, and miR-638. Decreased miR-126, miR-19b, miR-320, miR-451, miR-572, and miR-638 were associated with higher MDD severity scores. Target genes at the interface between air pollution exposure and MDD severity were mainly involved in inflammation and cell cycle regulation. These findings suggest that air pollutants might modulate MDD severity by triggering NdEV miRNA alterations. Longitudinal studies are needed to evaluate whether NdEV miRNAs might serve as novel biomarkers for MDD prognosis.

The current nationwide wet bulb globe temperature (WBGT) threshold (33 °C) of Japan's heat warning system (HWS) does not adequately account for regional variations in heat sensitivity and heatstroke mortality. In this study, we aimed to determine the critical WBGT threshold for effectively mitigating preventable heatstroke mortality across Japan. To this end, daily heatstroke mortality data (ICD-10: X30; 2010-2019) for all 47 prefectures of Japan were analyzed using a time-stratified case-crossover design based on a conditional quasi-Poisson regression combined with a distributed lag nonlinear model. Assuming that heatstroke mortality is preventable via interventions when prompted by Japan's HWS, the WBGT threshold required to reduce 50% of preventable heatstroke mortalities ("target50") was estimated; subgroup analyses by age, sex, and summer phase were also conducted. According to the results, 9702 heatstroke mortalities were recorded during the study period, with more cases observed in late summer and among older individuals. Further, the current HWS threshold (WBGT_max 33 °C) only accounted for 2%-3% of preventable heat-related deaths during summer months. However, a new critical threshold (WBGT_max approximately 31 °C), enabling the realization of target50 in most prefectures, was identified. Notably, northern regions required lower thresholds. Significant differences between summer phases (lower thresholds for early summer than those for late summer), as well as regional and demographic variations in heat sensitivity, were also observed. The application of the identified critical threshold, WBGT_max approximately 31 °C, aligned with the national target of reducing preventable heatstroke mortalities by half. Therefore, the findings of this study provide a scientific basis for revisiting Japan's HWS and improving mitigation measures.

Non-antibiotic drugs (NADs) used in human therapy may induce antibiotic resistance selection and dissemination in vitro. However, the potential risks of antibiotic resistance emergence associated with environmental NAD pollution have not been addressed. Here, we conducted a multidisciplinary study on river water microcosms using growth kinetics, qPCR, metagenomics, 16S rRNA sequencing, and liquid chromatography-tandem mass spectrometry (LC-MS/MS) to determine whether NADs alter river bacterial ecology and select for antibiotic resistance genes (ARGs). Four NADs with different mechanisms of action were included at a high (mg/L) and low (μg/L) dose to establish dose-response relationships: chlorpromazine (antipsychotic), diclofenac (anti-inflammatory), diphenhydramine (antihistamine), and fluoxetine (antidepressant). Although the community response to NAD pollution was compound-specific and dose-dependent, all NADs and doses were stable in the environment, altered the composition and activity of bacterial communities, and selected for several ARGs, mostly β-lactamases and aminoglycoside resistance genes, some of which were associated with horizontal gene transfer genes. Pseudomonas (including some ARG-harboring subpopulations) was identified as a key player in the response to NAD pollution. Here, we demonstrate NAD-driven antibiotic resistance selection in complex aquatic communities, raising concerns about the collateral effects on human and environmental health due to the extensive anthropocentric use of NADs.