Comprehensive Analysis of lncRNA-mRNA Expression Profiles in Depression-like Responses of Mice Related to Polystyrene Nanoparticle Exposure.

Plastics in the environment can break down into nanoplastics (NPs), which pose a potential threat to public health. Studies have shown that the nervous system constitutes a significant target for nanoplastics. However, the potential mechanism behind nanoplastics' neurotoxicity remains unknown. This study aimed to investigate the role of lncRNA in the depressive-like responses induced by exposure to 25 nm polystyrene nanoplastics (PS NPs). Forty mice were divided into four groups administered doses of 0, 10, 25, and 50 mg/kg via gavage for 6 months. After conducting behavioral tests, RNA sequencing was used to detect changes in mRNAs, miRNAs, and lncRNAs in the prefrontal cortex of the mice in the 0 and 50 mg/kg PS NPs groups. The results revealed that mice exposed to chronic PS NPs developed depressive-like responses in a dose-dependent manner. It was demonstrated that 987 mRNAs, 29 miRNAs, and 116 lncRNAs were significantly different between the two groups. Then, a competing endogenous RNA (ceRNA) network containing 6 lncRNAs, 18 miRNAs, and 750 mRNAs was constructed. Enrichment results suggested that PS NPs may contribute to the onset of depression-like responses through the activation of axon guidance, neurotrophin-signaling pathways, and dopaminergic synapses. This study provided evidence of the molecular relationship between PS NPs and depression-like responses.

FDX1 regulates leydig cell ferroptosis mediates PM2.5-induced testicular dysfunction of mice.

Epidemiological studies have established an association between chronic exposure to PM2.5 and male infertility. However, the underlying mechanisms were not fully revealed. In this study, we established mice models exposed to PM2.5 for 16 weeks, and a significant decrease in sperm quality accompanied by an increase in testosterone levels were observed after PM2.5 exposure. Moreover, treatment with ferrostatin-1 (Fer-1), a specific ferroptosis inhibitor, effectively mitigated PM2.5-induced testicular dysfunction in mice. And lipid peroxidation and ferritin accumulation were found to be significantly increased in Leydig cells of testes with a PM2.5-dose dependent manner. Further investigations revealed that TM-3 cells, a mouse Leydig cell line, were prone to ferroptosis after PM2.5 exposure, and the cell viability was partly rescued after the intervention of Fer-1. Furthermore, our results supported that the ferroptosis of TM-3 cells was attributed to the upregulation of ferredoxin 1 (FDX1), which was the protein transferring electrons to cytochrome P450 family 11 subfamily A member 1 to aid lysing cholesterol to pregnenolone at initial of steroidogenesis. Mechanically, PM2.5-induced FDX1 upregulation resulted in cellular ROS elevation and ferrous iron overload, which together initiated an autoxidation process of polyunsaturated fatty acids in the cell membrane of Leydig cells until the accumulated lipid peroxides triggered ferroptotic cell death. Simultaneously, upregulation of FDX1 promoted steroidogenesis and let to an increased level of testosterone. In summary, our work suggested that FDX1, a mediator involving steroidogenesis, was a key regulator in PM2.5-induced Leydig cells ferroptosis.

Site-specific Atg13 methylation-mediated autophagy regulates epithelial inflammation in PM2.5-induced pulmonary fibrosis.

Fine particulate matters (PM2.5) increased the risk of pulmonary fibrosis. However, the regulatory mechanisms of lung epithelium in pulmonary fibrosis remained elusive. Here we developed PM2.5-exposure lung epithelial cells and mice models to investigate the role of autophagy in lung epithelia mediating inflammation and pulmonary fibrosis. PM2.5 exposure induced autophagy in lung epithelial cells and then drove pulmonary fibrosis by activation of NF-κB/NLRP3 signaling pathway. PM2.5-downregulated ALKBH5 protein expression promotes m6A modification of Atg13 mRNA at site 767 in lung epithelial cells. Atg13-mediated ULK complex positively regulated autophagy and inflammation in epithelial cells with PM2.5 treatment. Knockout of ALKBH5 in mice further accelerated ULK complex-regulated autophagy, inflammation and pulmonary fibrosis. Thus, our results highlighted that site-specific m6A methylation on Atg13 mRNA regulated epithelial inflammation-driven pulmonary fibrosis in an autophagy-dependent manner upon PM2.5 exposure, and it provided target intervention strategies towards PM2.5-induced pulmonary fibrosis.

Mechanism of YY1 mediating autophagy dependent ferroptosis in PM2.5 induced cardiac fibrosis.

Epidemiological studies have demonstrated strong associations between exposure to ambient fine particulate matter (PM2.5) and cardiac disease. To investigate the potential mechanism of cardiac fibrosis induced by PM2.5, we established PM2.5 exposure models in vivo and in vitro, and then cardiac fibrosis was evaluated. The ferroptosis and ferritinophagy was detected to characterize the effects of PM2.5 exposure. The results indicated that PM2.5 exposure could induce cardiac fibrosis in mice. YY1 was induced by PM2.5 exposure and then increased NCOA4, a cargo receptor for ferritinophagy, which interacted with FHC and promoted the transport of ferritin to the autophagosome for degradation. The release of large amounts of free iron from ferritinophagy led to lipid peroxidation directly via the Fenton reaction, thereby triggering ferroptosis. Moreover, siNCOA4 could partly restore the FHC protein level in HL-1 cells and inhibit the occurrence of downstream ferroptosis. Functionally, NCOA4 knockdown inhibited ferroptosis and alleviated HL-1 cell death induced by PM2.5. Ferroptosis inhibitor (Ferrostatin-1) could reverse the promoting effect of ferritinophagy mediated ferroptosis on cardiac fibrosis induced by PM2.5 exposure in mice. Our study indicated that PM2.5 induced cardiac fibrosis through YY1 regulating ferritinophagy-dependent ferroptosis.

Moderate physical activity against effects of short-term PM2.5 exposure on BP via myokines-induced inflammation.

Exposure to PM2.5 increases blood pressure (BP) and cardiovascular morbidity and mortality. We conducted a randomized controlled panel study in Shijiazhuang, China among 55 healthy college students randomly assigned to either the control (CON) or SPORTS group with intervention of 2000 m jogging in 20 min for 3 times in 4 days, and 3-round health examinations from November 15, 2020 to December 6, 2020. We aimed to evaluate whether moderate physical activity (PA) protected BP health against PM2.5 exposure and explore potential mechanisms through myokines and inflammation. Individual PM2.5 exposure was calculated based on outdoor and indoor PM2.5 concentration monitoring data as well as time-activity diary of each subject. In the CON group, the exposure-response curve for SBP was linear with a threshold concentration of approximately 31 µg/m3, while an increment of SBP level was 4.38 mm Hg (95%CI: 0.17 mm Hg, 8.59 mm Hg) at lag03 for each 10-µg/m3 increase in PM2.5, using linear mixed-effect models. For inflammatory indicators, PM2.5 exposure was associated with significant increases in eosinophil counts and proportion in CON group, but decreases in MCP-1 and TNF-α in SPORTS group. Meanwhile, higher myokines including CLU and IL-6 were observed in SPORTS group compared to the CON group. Further mediation analyses revealed that eosinophil counts mediated the elevated BP in CON group, whereas MCP-1 and TNF-α were also crucial mediating cytokines for the SPORTS group, as well as CLU and IL-6 acted as mediators on BP and inflammation indicators in SPORTS group. This study suggests that moderate PA could counteract the elevated BP induced by PM2.5 exposure via myokines-suppressed inflammation pathways.

Association between ambient particulate matter exposure and metabolic syndrome risk: A systematic review and meta-analysis.

Although the association between ambient particulate matter and metabolic syndrome (MetS) has been investigated, the effect of particulate matter (PM) on MetS is inconclusive. We conducted a systematic review and meta-analysis to study the association between long-term ambient PM exposure and MetS risk. The data from five databases were extracted to analyze the association between ambient PM exposure and MetS risk. A random-effects model was performed to estimate the overall risk effect. The present systematic review and meta-analysis illustrated that an increase of 5 µg/m3 in annual PM2.5 or PM10 concentration was associated with 14% or 9% increases of MetS risk, respectively (PM2.5, RR = 1.14, 95%CI [1.03, 1.25]; PM10, RR = 1.09, 95%CI [1.00, 1.19]). The population-attributable risk (PAR) was 12.28% for PM2.5 exposure or 8.26% for PM10 exposure, respectively. There was statistical association between PM2.5 exposure and risk of MetS in male proportion ≥50%, Asia, related disease or medication non-adjustment subgroup as well as cohort study subgroups, respectively. The significant association between PM10 exposure and risk of MetS was observed in male proportion ≥50% and calories intake adjustment subgroups, respectively. Sensitivity analyses showed the robustness of our results. No publication bias was detected. In conclusion, there was positive association between long-term PM exposure and MetS risk. 12.28% of MetS risk could be attributable to PM2.5 exposure.