2,5,7-Trichlorolichexanthone

Under the background of global industrialization, PM2.5 has become the fourth-leading risk factor for ischemic stroke worldwide, according to the 2019 GBD estimates. This highlights the hazards of PM2.5 for ischemic stroke, but unfortunately, PM2.5 has not received the attention that matches its harmfulness. This article is the first to systematically describe the molecular biological mechanism of PM2.5-induced ischemic stroke, and also propose potential therapeutic and intervention strategies. We highlight the effect of PM2.5 on traditional cerebrovascular risk factors (hypertension, hyperglycemia, dyslipidemia, atrial fibrillation), which were easily overlooked in previous studies. Additionally, the effects of PM2.5 on platelet parameters, megakaryocytes activation, platelet methylation, and PM2.5-induced oxidative stress, local RAS activation, and miRNA alterations in endothelial cells have also been described. Finally, PM2.5-induced ischemic brain pathological injury and microglia-dominated neuroinflammation are discussed. Our ultimate goal is to raise the public awareness of the harm of PM2.5 to ischemic stroke, and to provide a certain level of health guidance for stroke-susceptible populations, as well as point out some interesting ideas and directions for future clinical and basic research.

Rationale & objective: Increasing evidence has linked ambient fine particulate matter (ie, particulate matter no larger than 2.5 μm [PM2.5]) to chronic kidney disease (CKD), but their association has not been fully elucidated, especially in regions with high levels of PM2.5 pollution. This study aimed to investigate the long-term association of high PM2.5 exposure with incident CKD in mainland China. Study design: Prospective cohort study. Setting & participants: 72,425 participants (age ≥18 years) without CKD were recruited from 121 counties in Hunan Province, China. Exposure: Annual mean PM2.5 concentration at the residence of each participant derived from a long-term, full-coverage, high-resolution (1 × 1 km2), high-quality dataset of ground-level air pollutants in China. Outcomes: Incident CKD during the interval between the baseline examination of each participant (2005-2017) and the end of follow-up through 2018. Analytical approach: Cox proportional hazards models were used to estimate the independent association of PM2.5 with incident CKD and the joint association of PM2.5 with temperature or humidity on the development of PM2.5-related CKD. Restricted cubic splines were used to model exposure-response relationships. Results: Over a median follow-up of 3.79 (IQR, 2.03-5.48) years, a total of 2,188 participants with incident CKD were identified. PM2.5 exposure was associated with incident CKD with an adjusted hazard ratio of 1.71 (95% CI, 1.58-1.85) per 10-μg/m3 greater long-term exposure. Multiplicative interactions between PM2.5 and humidity or temperature on incident CKD were detected (all P < 0.001 for interaction), whereas an additive interaction was detected only for humidity (relative risk due to interaction, 3.59 [95% CI, 0.97-6.21]). Limitations: Lack of information on participants' activity patterns such as time spent outdoors. Conclusions: Greater long-term ambient PM2.5 pollution is associated with incident CKD in environments with high PM2.5 exposure. Ambient humidity has a potentially synergetic effect on the association of PM2.5 with the development of CKD. Plain-language summary: Exposure to a form of air pollution known as fine particulate matter (ie, particulate matter ≤2.5 μm [PM2.5]) has been linked to an increased risk of chronic kidney disease (CKD), but little is known about how PM2.5 affects CKD in regions with extremely high levels of PM2.5 pollution. This longitudinal cohort study in China investigates the effect of PM2.5 on the incidence of CKD and whether temperature or humidity interact with PM2.5. Our findings suggest that long-term exposure to high levels of ambient PM2.5 significantly increased the risk of CKD in mainland China, especially in terms of cumulative average PM2.5. The associations of PM2.5 and incident CKD were greater in high-humidity environments. These findings support the recommendation that reducing PM2.5 pollution should be a priority to decrease the burden of associated health risks, including CKD.

PM2.5 exposure has been demonstrated to correlate with neurological disorders recently. Ferroptosis is recognized as a newly found programmed form of cell death associated with neurodegenerative diseases, while glutathione peroxidase 4 (GPX4) is a key regulator of ferroptosis. However, the relationship between PM2.5 -induced neurotoxicity and ferroptosis is still unclear. The current study aims to investigate if ferroptosis is involved in neurotoxicity post PM2.5 exposure and its underlying mechanism. The PM2.5 -treated neuronal Neuro-2a (N2A) and SH-SY5Y cells were applied to the current study. The results showed that PM2.5 significantly increased the neuronal cell death, yet the ferroptosis antagonist Ferrostain-1 (Fer-1) markedly decreased the cell death induced by PM2.5 . Western blot further confirmed that ferroptosis was triggered post PM2.5 treatment in N2A cells by decreasing expressions of GPX4 and ferritin heavy chain (FTH), as well as enhancing expressions of ferritin light chain (FTL) and transferrin receptor protein (TFRC). Meanwhile, PM2.5 treatment augmented neuronal oxidative damage and mitochondrial dysfunction. The bioinformatic analysis indicated that CREB could be the regulator of GPX4, and our results showed that ERK/CREB pathway was down-regulated in N2A cells post PM2.5 treatment. The addition of ERK1/2 agonist post PM2.5 treatment significantly inhibit ferroptosis via increasing the expression of GPX4. Taken together, the present study demonstrated that PM2.5 -induced ferroptosis via inhibiting ERK/CREB pathway, and these findings will advance our knowledge of PM2.5 -induced cytotoxicity in the nervous system.