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Objective To explore the regulative effect and mechanism of cytochrome P450 1A1 (CYP1A1) on regulating lipopolysaccharide (LPS)-induced arginase-1 (Arg-1) expression in macrophages. Methods After mouse macrophage-like cell line RAW264.7 (RAW) was treated with 10 mg/L LPS for 0, 12 and 24 h, respectively (n=3 for each time point), the expression of CYP1A1 and Arg-1 at mRNA and protein levels were measured by RT-PCR and Western blotting. Negative control RAW(NC/RAW) cells, CYP1A1-overexpression RAW (CYP1A1/RAW) cells, CYP1A1-knockout RAW (CYP1A1 KO/RAW) cells and CYP1A1 hydroxylase-activity mutant RAW (CYP1A1m/RAW) cells were constructed, respectively, and then the cells were treated with LPS and further detected with RT-PCR and Western blotting for the expression and activation levels of Arg-1 and signal transducer and activators of transcription-6 (STAT6). Then STAT 6 inhibitor AS1517499 was added to treat the CYP1A1 KO/RAW cells and NC/RAW cells, and the mRNA and protein expression of Arg-1 was measured again after LPS or PBS treatment. CYP1A1 epoxidase inhibitor, nordihydroguaiaretic acid (NDGA) and 12 (S)-HETE were introduced to treat normal RAW cells, the mRNA and protein levels of Arg-1 and activity of STAT6 were detected after LPS or PBS treatment. Results LPS-induced CYP1A1 and Arg-1 were highly expressed in staggering peaks in RAW cells (P < 0.05). Overexpression of CYP1A1 inhibited LPS-induced Arg-1 expression and STAT6 activation in RAW cells, while CYP1A1 knockout enhanced above effects (P < 0.05). STAT6 inhibitor AS1517499 abolished the enhancement of CYP1A1 knockout (P < 0.05). CYP1A1 hydroxylase-activity mutation or 12(S)-HETE simulation had no effect on the expression of Arg-1 (P>0.05), while CYP1A1 epoxidase-activity inhibitor NDGA enhanced Arg-1 expression and STAT6 activation (P < 0.05). Conclusion CYP1A1 can inhibit Arg-1 expression by reducing STAT6 activation in LPS-induced macrophages, and CYP1A1 hydroxylase-activity or its proinflammatory metabolism 12(S)-HETE has no effect on this regulation, while CYP1A1 epoxidase-activity may be involved in this effect.

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objective To investigate the role of trichostatin A (TSA) and its mechanism on secretory function of peripheral lymph node cells in mice. Methods The adult male C57BL/6 mice were sacrificed and their peripheral lymph nodes (LN), mesenteric lymph nodes (MLN), Peyer's patches (PP), spleen (SP), bone marrow (BM) and thymus (Thy) were collected. The mRNA levels of musculin (MSC), interleukin-17 A (IL-17A) and interleukin-22 (IL-22) in above immune organs were detected by real-time quantity polymerase chain reaction (qPCR). Then the cell suspensions with high mRNA levels of MSC, IL-17A and IL-22, were prepared and randomly divided into 6 groups, including control group, 1 μg/mL lipopolysaccharide (LPS) group, 1 μg/mL LPS+10 ng/mL TSA group, 1 μg/mL LPS +30 ng/mL TSA group and 1 μg/mL LPS + 50 ng/mL TSA group. After the above cells were cultured under 37 ℃ and 5% CO2 for 6, 12 or 24 h, the supernatant and cells were collected. The secretion levels of tumor necrosis factor-α (TNF-α) and interleukin-10 (IL-10) from the supernatant were measured by enzyme linked immunosorbent assay (ELISA), while the optimal time point of TSA treatment was determined. And then, the mRNA levels of MSC, IL-17A and IL-22 were detected by qPCR at this time point. Results Our results suggested that the mouse LN had highly expressed MSC, IL-17A, and IL-22 when compared with BM (P < 0.01, P < 0.05), and similar results were seen when compared with Thy (P < 0.05). Compared with the LPS group, different concentrations of TSA decreased the secretion levels of TNF-α and IL-10 (P < 0.01, P < 0.05), and at the same time, the treatment down-regulated the expression levels of IL-17A and IL-22 (P < 0.01), while up-regulated that of MSC (P < 0.01, P < 0.05). The best time point was identified as 12 h. Conclusion TSA inhibits the secretory function of LN cells stimulated by LPS, which might be related with the changes of MSC, IL-17A and IL-22 expression

Biomechanics, which provides a good insight into the mechanical properties of various parts and tissues of living organisms, is an important part of medical science and provides the fundamental theoretical knowledge of mechanics for medical science. Biomechanics helps to provide a precise model of complex tissues, improves the quantitative measurement of mechanical properties, offers some assistance to engineering applications, and aids in the clinical management of the patient. Meanwhile, advanced experimental and computational biomechanics has become an important component for understanding the physiological and pathological conditions of human biological tissues. Analysis of the role of collagen in airway mechanics quantifies macro- and micro-scale approaches to airway mechanics and pathological changes associated with collagen deposition in airway disease in the quest to treat airway pathology and address airway defects [[9]]. [Extracted from the article]