The STING-IRF3 pathway contributes to paraquat-induced acute lung injury.

Immune and inflammatory responses play significant roles in paraquat (PQ)-induced acute lung injury (ALI), but the specific mechanisms remain unclear. Our study aimed to investigate the action of STING-IRF3 signaling on PQ-induced ALI in mice. Following PQ administration, samples were collected at 2, 12, 24, and 48 h for in vivo studies, and 24 h for in vitro studies. Following PQ administration (30 mg/kg, i.p.), injury to mouse lungs was evaluated by H&E staining and wet/dry ratios, and lung oxidative damage was evaluated by MDA and SOD assays. The mRNA levels of Sting, Irf3, and Ifnß were detected by RT-PCR, the expression of STING and IRF3 were assessed by western blotting and IHC/IF, and the secretion of IFNß was detected by ELISA. In vivo, PQ administration induced pathological changes and increased wet/dry ratios in lungs after 48 h. Sting, Irf3, and Ifnß mRNA levels in lung tissues, STING and pIRF3 protein levels in lung tissues, and IFNß secretion in serum, were upregulated by PQ in a time-dependent manner. PQ administration promoted IRF3 nuclear translocation in lung tissues after 48 h. The above changes were all attenuated by dexamethasone treatment (5 mg/kg, i.p., qd). In vitro, PQ induced STING and IRF3 translocation. Irf3 or Sting silencing decreased the mRNA levels and supernatant secretion of IFNß in PQ-treated RAW264.7 mouse macrophages. Sting silencing also inhibited the protein and mRNA levels of IRF3 in vitro. Our study suggests that STING-IRF3 signaling contributes to PQ-induced ALI, providing new information for future treatment strategies.

Mesenchymal Stem Cells Alleviate Acute Lung Injury and Inflammatory Responses Induced by Paraquat Poisoning.

BACKGROUND Mesenchymal stem cells (MSCs) show anti-oxidative and anti-inflammatory effects that have prompted further research into their potential applications in treating paraquat (PQ) poisoning cases in emergency rooms. We assessed the protective effects, underlying mechanisms, and secondary inflammatory responses of MSCs on PQ-induced acute lung injury. MATERIAL AND METHODS Sprague-Dawley rats were injected intraperitoneally with PQ (20 µg per gram of body weight). MSCs were injected through the caudal vein 1 h after PQ treatment. The severity of lung injury and oxidative stress and levels of inflammatory mediators were examined with and without MSC grafting. Expression levels of TLR4, NF-kappaB, p65, Nrf2, HO-1, and activated caspase-3 protein were determined by Western blotting. RESULTS Administration of MSCs significantly decreased the levels of TNF-alpha, IL-1ß, and IL-6 and polymorphonuclear neutrophil (PMN) count in the bronchoalveolar lavage fluid (BALF) of rats with PQ-induced ALI. In addition, MSC also effectively reduced the wet-to-dry lung weight ratio, lung injury score, and the levels of MDA and 8-OHdG. Conversely, MSC increased SOD and GSH-PX activity in the lung tissue. Moreover, MSC significantly upregulated HO-1, Nrf-2 protein expression in the lung tissue. In contrast, the levels of TLR4, NF-kappaB p65 and activated caspase-3 protein were decreased in MSC-treated rats (P<0.05). CONCLUSIONS Treatment with MSCs overexpressed Nrf2 gene and activated downstream antioxidant HO-1, leading to inhibit oxidative stress, cell apoptosis and inflammatory response in lung tissue, thereby significantly improving PQ-induced acute lung injury in rats.

Large-scale sensitivity adjustment for Gd-HMME room temperature phosphorescence oxygen sensing.

The oxygen sensing enhancement based on room temperature phosphorescence (RTP) of Gd-HMME adjusted by imidazole was studied. The phosphorescence intensity IP0 and the Stern-Volmer equations under different imidazole concentration were obtained, and the physical mechanism of imidazole regulating the oxygen quenching constant KSV was analyzed. It was found that the KSV value increased by ∼46 folds in the range of 12.4(1)-576.1(5) kPa-1, and the large-scale variation of KSV is conducive to the realization of high precision oxygen concentration measurement in a wide range. In addition, the standard deviation σ of continuous measurement results was given, and the limit of detection (LOD) was determined to be 6.6 ppm.

The protective effects of bone mesenchymal stem cells on paraquat-induced acute lung injury via the muc5b and ERK/MAPK signaling pathways.

OBJECTIVE: To evaluate the protective effect of bone mesenchymal stem cells (BMSCs) on paraquat (PQ)-induced acute lung injury (ALI) and investigate the possible underlying mechanisms. METHODS: Male Sprague Dawley rats were treated with BMSCs (3 × 106) 1 h after intraperitoneal injection of PQ. The cell apoptosis rate and mitochondrial membrane potential in rat pulmonary alveolar type II epithelial (ATII) cells were quantitated by flow cytometry. IL-17, IL-6, and MUC5B levels in bronchoalveolar lavage fluid (BALF) and ATII culture medium were measured. Lung tissues were collected to determine the wet-to-dry (W/D) ratios and lung injury scores, in addition to the protein and mRNA expression levels of ERK1/2, Bcl-2, Bax, and muc5b. RESULTS: BMSCs had decreased mRNA expression of Muc5b in lung tissue of rats with PQ-induced ALI as shown by RNA-seq. Treatment with BMSCs also alleviated the PQ-induced increases in protein expression in the BALF and reduced the concentration of IL-17, IL-6, and Muc5b in both the BALF and ATII culture medium. In addition, the ATII cell apoptosis rate and mitochondrial membrane potential, as well as the W/D ratios, were decreased by BMSC treatment. Moreover, BMSCs ameliorated the expression levels of Bax mRNA and active caspase-3 proteins and increased Bcl-2 mRNA expression. Furthermore, BMSCs attenuated ERK1/2 activation upon PQ-induced ALI in lung tissue. CONCLUSION: BMSC therapy can protect against PQ-induced ALI in rats. A possible mechanism is the suppression of the muc5b and ERK/MAPK signaling pathways, resulting in an improvement in the endothelial permeability and a decrease in inflammation and cell apoptosis.

Protective Effects of a Rho Kinase Inhibitor on Paraquat-Induced Acute Lung Injuries in Rats.

Fasudil, a rock kinase inhibitor, can inhibit systemic inflammation and prevent paraquat (PQ)-induced acute lung injuries in rats; however, the mechanisms for these protective effects remain elusive. This study investigated how the Rho/ROCK signaling pathway enables fasudil to protect against acute lung injuries in PQ-treated rats. Wistar rats (n = 240) were pretreated with fasudil (10 and 30 mg/kg, i.p.) 1 h prior to PQ administration. When compared to rats with PQ-induced lung injuries, rats pretreated with fasudil had significantly fewer polymorphonuclear neutrophils and lower concentrations of protein, TNF-α, IL-1ß, and IL-6 in their bronchoalveolar lavage fluid. Moreover, fasudil also reduced the Evans Blue content, wet-to-dry weight ratio, lung injury scores, and levels malondialdehyde and 8-hydroxy-2 deoxyguanosine, but increased superoxide dismutase activity in lung tissue. Furthermore, Rho, ROCK1 expression and the levels of phosphorylated MYPT-1 in lung tissues were drastically decreased in fasudil-treated rats, whereas ZO-1 protein expression was significantly increased (p < 0.05). We found that fasudil downregulated bax and activated caspase-3 mRNA expression but upregulated Bcl-2 mRNA expression. In vitro experiments showed that the levels of TNF-α, IL-1ß, and IL-6 secreted by human pulmonary microvascular endothelial cells treated with PQ were attenuated by fasudil. Fasudil inhibited the upregulation Rho and ROCK protein expression and downregulation of ZO-1 protein expression in HPMVECs induced with PQ. Higher concentrations of fasudil produced greater affects than lower concentrations. Fasudil improved endothelial permeability and inhibited inflammation, oxidative stress, and cell apoptosis to alleviate acute lung injuries in PQ-treated rats. Fasudil exerted these therapeutic effects by inhibiting the Rho/ROCK signaling pathway.

Combined experimental and theoretical investigation of the gas bubble motion in an acoustic field.

The objective of this paper is to apply the combined experimental and theoretical method to investigate the various behaviors of gas bubbles in an acoustic field. In the experiments, high-speed video and ultrasonic processor are used to capture the transient evolution of gas bubble patterns, as well as velocity profiles. In the theoretical analysis, the theories of primary and secondary Bjerknes forces and buoyancy force are introduced to accurately demonstrate the variations of bubble volume and motion. Results are presented for gas bubbles with the radius of 1.4mm under an acoustic field with a frequency of 18kHz, for three cases, namely single bubble rising in a quiescent liquid, acoustic single bubble oscillation and two bubbles coalescence conditions. The results show that the fragments around the single gas bubble presents the periodical behaviors, namely, splitting, attraction, and secondary splitting motion. The centroid of the single gas bubble almost oscillates without motion upwards or downwards, because of the equilibrium of the primary Bjerknes force caused by acoustic waves and the effect of the buoyancy force. For the two coalescing bubbles, the resultant of buoyancy, primary and secondary Bjerknes forces acting on two bubbles are same in magnitude, but in opposite direction, which indicates that two gas bubbles attract each other and and coalesce into one.