Acute lung injury (ALI) is accompanied by overactivation of multiple pro‐inflammatory factors. Cytochrome P450 1A1 (CYP1A1) has been shown to aggravate lung injury in response to hyperoxia. However, the relationship between CYP1A1 and lipopolysaccharide (LPS)‐induced ALI is unknown. In this study, CYP1A1 was shown to be upregulated in mouse lung in response to LPS. Using CYP1A1‐deficient (CYP1A1−/−) mice, we found that CYP1A1 knockout enhanced LPS‐induced ALI, as evidenced by increased TNF‐α, IL‐1β, IL‐6, and nitric oxide in lung; these effects were mediated by overactivation of NF‐κB and iNOS. Furthermore, we found that aspartate aminotransferase, lactate dehydrogenase, creatine kinase, and creatinine levels were elevated in serum of LPS‐induced CYP1A1−/− mice. Altogether, these data provide novel insights into the involvement of CYP1A1 in LPS‐induced lung injury.

Aryl hydrocarbon receptor (AhR) plays an important role in inflammation and immunity as a new therapeutic target for infectious disease and sepsis. Punicalagin (PUN) is a Chinese herbal monomer extract of pomegranate peel that has beneficial anti-inflammatory, antioxidant and anti-infective effects. However, whether PUN is a ligand of AhR, its effect on AhR expression, and its signaling pathway remain poorly understood. In this study, we found that PUN was a unique polyphenolic compound that upregulated AhR expression at the transcriptional level, and regulated the AhR nongenomic pathway. AhR expression in lipopolysaccharide-induced macrophages was upregulated by PUN in vitro and in vivo in a time- and dose-dependent manner. Using specific inhibitors and siRNA, induction of AhR by PUN depended on sequential phosphorylation of 90-kDa ribosomal S6 kinase (p90RSK), which was activated by the mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) and phosphoinositide-dependent protein kinase (PDK)1 pathways. PUN promoted p90RSK-mediated activator protein-1 (AP-1) activation. AhR knockout or inhibitors reversed suppression of interleukin (IL)-6 and IL-1β expression by PUN. PUN decreased Listeria load and increased macrophage survival via AhR upregulation. In conclusion, we identified PUN as a novel selective AhR modulator involved in AhR expression via the MEK/ERK and PDK1 pathways targeting p90RSK/AP-1 in inflammatory macrophages, which inhibited macrophage inflammation and promoted bactericidal activity.

Objective. To explore the value of the injury severity score (ISS) and the new injury severity score (NISS) for evaluating injuries and predicting complications (pneumonia and respiratory failure) and poor prognoses (in‐hospital tracheal intubation, extended length of hospital stay, ICU admission, prolonged ICU stay, and death) in patients with thoracic trauma. Methods. The data of consecutive patients with thoracic trauma who were admitted to the department of cardiothoracic surgery of a tertiary hospital between January 2018 and December 2021 were retrospectively collected. ISS and NISS were calculated for each patient. The study outcomes were complications and poor prognoses. The differences in ISS and NISS between patients with complications and poor prognoses and patients without the abovementioned conditions were compared using the Mann‒Whitney U test. Discrimination and calibration of ISS and NISS in predicting outcomes were compared using the area under the receiver operating characteristic (ROC) curve (AUC) and Hosmer‒Lemeshow (H‐L) statistic. Results. A total of 310 patients were included. ISS and NISS of patients with complications and poor prognoses were greater than those of patients without complications and poor prognoses, respectively. The discrimination of ISS in predicting pneumonia, respiratory failure, in‐hospital tracheal intubation, extended length of hospital stay, ICU admission, prolonged ICU stay, and death (AUCs: 0.609, 0.721, 0.848, 0.784, 0.763, 0.716, and 0.804, respectively) was not statistically significantly different from that of NISS in predicting the corresponding outcomes (AUCs: 0.628, 0.712, 0.795, 0.767, 0.750, 0.750, and 0.818, respectively). ISS showed better calibration than NISS for predicting pneumonia, respiratory failure, in‐hospital tracheal intubation, extended length of hospital stay, and ICU admission but worse calibration for predicting prolonged ICU stay and death. Conclusion. ISS and NISS are both suitable for injury evaluation. There was no statistically significant difference in discrimination between ISS and NISS, but they had different calibrations when predicting different outcomes.

Neutrophilic granule protein (NGP) was identified as a granular protein in neutrophils, but its function in macrophages has not been fully understood. In our prior investigation, NGP was observed to be significantly upregulated in macrophages following stimulation with lipopolysaccharide (LPS) or Escherichia coli (E.coli). Furthermore, NGP demonstrated an anti-inflammatory effect by inhibiting the NF-κB signaling pathway through its extracellular distribution. Nitric oxide (NO), as a crucial factor in the immune regulation of macrophages mainly controlled by inducible nitric oxide synthase (iNOS), plays an indispensable role in the eradication of bacteria. However, the regulatory effects of NGP on NO remains unknown. In this study, we observed an upregulation and central role of Nos2, the gene encoding iNOS, in macrophages with high NGP expression induced by LPS. Overexpression of NGP significantly enhanced NO production in LPS-induced macrophages, while NGP knockout attenuated NO production. Furthermore, exogenous complementation experiments confirmed that NGP primarily exerted its up-regulatory effect on iNOS/NO through intracellular distribution. Additionally, RNA sequencing (RNA-seq) and immunoprecipitation-mass spectrometry (IP-MS) analyses revealed that NGP predominantly regulated NO levels via the JAK2/STAT1 pathway. Finally, our in vitro and in vivo experiments provided evidence supporting the involvement of NGP in bacterial clearance through modulation of NO. The evidence suggests that NGP plays a crucial role in regulating NO production and promoting bacterial clearance in macrophages, making it a promising target for the prevention and treatment of infectious diseases.