Short- and long-term exposure to particulate matter (PM) 2.5 instigates adverse health effect upon the cardiovascular (CV) system. Disclosing the molecular events by which PM2.5 evokes CV injuries is essential in developing effective risk-reduction strategy. Here we found that rats after intratracheally instillation with PM2.5 displayed increased circulating level of ANGII, the major bioactive peptide in renin-angiotensin-system (RAS), which resulted from the elevation of ANGII production in the vascular endothelium. Further investigations demonstrated that activation of IRE1α/XBP1s branch of unfolded protein response (UPR) was essential for augmented vascular ANGII signaling in response to PM2.5 exposure, whose effects strictly depends on the assembly of XBP1s/HIF1α transcriptional complex. Moreover, ablation of IRE1/XBP1/HIFα-dependent ACE/ANGII/AT1R axis activation inhibited oxidative stress and proinflammatory response in the vascular endothelial cells induced by PM2.5. Therefore, we conclude that PM2.5 exposure instigates endoplasmic reticulum instability, leading to the induction of IRE1α/XBP1s branch of UPR and links HIF1α transactivation to mediate ANGII-dependent endothelial dysfunction. Identifying novel therapeutic targets to alleviate ER stress and restore local RAS homeostasis in the endothelium may be helpful for the management of PM2.5-induced CV burden.

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One of the health hazards of PM2.5 exposure is to induce pulmonary inflammatory responses. In our previous study, we demonstrated that exposing both the immortalized and primary human bronchial epithelial cells to PM2.5 results in a significant upregulation of VEGF production, a typical signaling event to trigger chronic airway inflammation. Further investigations showed that PM2.5 exposure strongly induces ATR/CHK1/p53 cascade activation, leading to the induction of DRAM1-dependent autophagy to mediate VEGF expression by activating Src/STAT3 pathway. In the current study, we further revealed that TIGAR was another transcriptional target of p53 to trigger autophagy and VEGF upregulation in Beas-2B cells after PM2.5 exposure. Furthermore, LKB1, but not ATR and CHK1, played a critical role in mediating p53/TIGAR/autophagy/VEGF pathway activation also by linking to Src/STAT3 signaling cascade. Therefore, on combination of the previous report, we have identified both ATR/CHK1/p53/DRAM1- and LKB1/p53/TIGAR- dependent autophagy in mediating VEGF production in the bronchial epithelial cells under PM2.5 exposure. Moreover, the in vivo study further confirmed VEGF induction in the airway potentially contributed to the inflammatory responses in the pulmonary vascular endothelium of PM2.5-treated rats. Therefore, blocking VEGF expression or autophagy induction might be the valuable strategies to alleviating PM2.5-induced respiratory injuries.

Objective: To explore the main active components of Hohgardi-9 and its mechanism treating in ALI. Methods: Through searching the TCMSP database, we obtained the main components and action targets of Hohgardi-9, and the targets related to ALI were analyzed as the possible targets of Hohgardi-9. Then, the compound target network was constructed using Cytoscape software and obtained the key compounds of Hohgardi-9 acting on ALI. The blood entering components of Hohgardi-9 were analyzed by metabonomics. Using a string database to investigate the interaction between proteins of possible targets of Hohgardi-9, Gene Ontology (GO) function annotation and Tokyo Encyclopedia of the genome (KEGG) pathway enrichment analysis were carried out at the same time to predict its mechanism. Finally, the ALI rat model verified the pharmacodynamic effects and key targets of Huhgridi-9. Results: The network pharmacology and blood component analysis results showed that 27 potentially active components such as quercetin, herbacetin, izoteolin, and columbinetin acetate were the major functional components in Hohgardi-9. Those might act on NF kappa B signalling pathway, toll-like receptor signalling pathway, and TNF signalling pathway through key targets such as RELA (p65), TLR4, etc. In vivo experiments showed that Hohgardi-9 significantly improved lung tissue injury and pulmonary edema in ALI rats. At the same time, the Hohgardi-9 intervention could significantly reduce the mRNA expression levels of TRL4, TNFa, IL-1 β, and ICAM1 in ALI rats. Conclusion: Hohgardi-9 revealed ALI through the inhibiting inflammatory factor apoptosis-related gene expression.

Har Gabur is the carbide obtained from pig manure by burning. The fluorescent carbon dots (CDs) of Har Gabur were successfully synthesized through simulating the digestion process of human gastrointestinal tract. Transmission Electron Microscope (TEM) analysis showed that the average size of the prepared Har Gabur CDs was 4 nm, with good solubility in water and strong fluorescence under UV irradiation. The X-ray and Raman results showed that the Har Gabur CDs were mainly composed of oxygen "O" and carbon "C" elements, in the forms of "C=O" and "C-O." The bond energy results showed that the nitrogen "N" atom presented as "C-N" form, which indicated that Har Gabur CDs also contain "N." In photobleaching assay, Har Gabur CDs showed excellent light stability compared with ordinary organic dye, fluorescein, and Rhodamine B. The fluorescence intensity of Har Gabur CDs was fairly stable within a wide pH range of 3-10. When L-lysine and L-cysteine were applied for the passivation stage, the relative quantum yields were improved by 1.53 and 3.68 times, respectively. Finally, the fluorescence properties of Har Gabur CDs were tested in cells and zebrafish, illustrating that Har Gabur CD has potential in the application of biological labeling and imaging.