2,5,7-Tris-tert-butyl-L-tryptophan

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.

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.

Ambient and indoor air pollution contributes annually to approximately seven million premature deaths. Air pollution is a complex mixture of gaseous and particulate materials. In particular, fine particulate matter (PM2.5) plays a major mortality risk factor particularly on cardiovascular diseases through mechanisms of atherosclerosis, thrombosis and inflammation. A review on the PM2.5-induced atherosclerosis is needed to better understand the involved mechanisms. In this review, we summarized epidemiology and animal studies of PM2.5-induced atherosclerosis. Vascular endothelial injury is a critical early predictor of atherosclerosis. The evidence of mechanisms of PM2.5-induced atherosclerosis supports effects on vascular function. Thus, we summarized the main mechanisms of PM2.5-triggered vascular endothelial injury, which mainly involved three aspects, including vascular endothelial permeability, vasomotor function and vascular reparative capacity. Then we reviewed the relationship between PM2.5-induced endothelial injury and atherosclerosis. PM2.5-induced endothelial injury associated with inflammation, pro-coagulation and lipid deposition. Although the evidence of PM2.5-induced atherosclerosis is undergoing continual refinement, the mechanisms of PM2.5-triggered atherosclerosis are still limited, especially indoor PM2.5. Subsequent efforts of researchers are needed to improve the understanding of PM2.5 and atherosclerosis. Preventing or avoiding PM2.5-induced endothelial damage may greatly reduce the occurrence and development of atherosclerosis.