HO-1 mediates the anti-inflammatory actions of Sulforaphane in monocytes stimulated with a mycoplasmal lipopeptide.

Exposure to Mycoplasma pneumoniae leads to lung inflammation through a host defense pathway. Increasing evidence has indicated that the mycoplasma-derived membrane lipoprotein, or its analogue macrophage-activating lipopeptide-2 (MALP-2), excretes LPS as an immune system-stimulating substance and plays a crucial role in pathological injury during M. pneumoniae infection. It has been established that Sulforaphane confers anti-inflammatory properties. However, the underlying mechanism responsible for the inhibitory actions of Sulforaphane in the context of mycoplasmal pneumoniae are poorly understood. Here, we report that Sulforaphane is an inducer of heme oxygenase (HO)-1, a cytoprotective enzyme that catalyzes the degradation of heme through signaling pathways in human monocytes. Sulforaphane stimulated NF-E2-related factor 2 (Nrf2) translocation from the cytosol to the nucleus, and small interfering RNA-mediated knock-down of Nrf2 significantly inhibited Sulforaphane-induced HO-1 expression. Additionally, PI3K/Akt and ROS were also involved in Sulforaphane-induced Nrf2 activation and HO-1 expression, as revealed by the pharmacological inhibitors LY294002 and NAC. Moreover, Sulforaphane treatment inhibited MALP-2-induced pro-inflammatory cytokine secretion and pulmonary inflammation in mice, as well as MALP-2-triggered NF-κB activation. Furthermore, SnPP, a selective inhibitor of HO-1, reversed the inhibitory actions of Sulforaphane, while a carbon monoxide-releasing molecule, CORM-2, caused a significant decrease in MALP-2-induced cytokine secretion. Collectively, these results suggest that Sulforaphane functions as a suppressor of the MALP-2-induced inflammatory response, not only by inhibiting the expression of cytokines and the induction of HO-1 but also by diminishing NF-κB activation in cultured monocytes and the lungs of mice.

Risk factors analysis of sudden death in patients suspected with pulmonary thromboembolism in emergency room / 中华危重病急救医学

Objective To explore the correlative factors of sudden death in patients suspected with pulmonary thromboembolism (PTE) in emergency room (ER).Methods A retrospective analysis was conducted.The clinical data of 12 patients with sudden death suspected with PTE (sudden death group) in ER of the Air Force General Hospital from January 2011 to June 2014 were analyzed.The non-sudden death group included 35 patients during the same time period who were diagnosed with PTE based on findings of CT pulmonary arteriography (CTPA) and showed no sudden death in ER.Factors,including sex,age,previous operation,tumor,syncope,dyspnea,bilateral or unilateral edema of lower extremity,heart rate (HR),white blood cell count (WBC),D-dimer,arterial partial pressure of oxygen (PaO2),arterial partial pressure of carbon dioxide (PaCO2) and typical clinical manifestation of electrocardiogram (SⅠTⅢQⅢ),were compared between the two groups.The potential predictors of sudden death of PTE were analyzed by logistic regression analysis.Results Young age (years old:51.3±15.5 vs.62.3±14.4),lower PaO2 [mmHg (1 mmHg =0.133 kPa):49.9± 12.3 vs.62.7± 10.2],higher HR (bpm:122.0± 19.5 vs.89.1 ± 18.5) and higher WBC (× 109/L:13.8 ± 6.9 vs.7.2 ± 2.5) were found in sudden death group as compared with those in non-sudden death group (P ＜ 0.05 or P ＜ 0.01).There was no significant differences in D-dimer level and PaCO2 between sudden death group and non-sudden death group [D-dimer (pg/L):986 (891,3 230) vs.2089 (598,3 397),PaCO2 (mmHg):33.0 (28.6,43.4)vs.36.5 (32.9,41.0),both P ＞ 0.05].The syncope,antineoplaston treatment or tumor metastasis within 6 months,operation in previous 4 months,bilateral asymmetrical edema in sudden death group were more than those of the non-sudden death group,and chest pain was less (P ＜ 0.05 or P ＜ 0.01).Difference in gender,dyspnea and typical SⅠTⅢQⅢ in electrocardiogram were not significant between the two groups (all P ＞ 0.05).It was shown by multiple logistic regression analysis that higher HR [odds ratio (OR) =1.124,95％ confidence interval (95％CI) =1.024-1.235,P =0.014] and higher WBC (OR =1.347,95％CI =1.043-1.738,P =0.022) were identified as independent risk factors of sudden death for PTE.Conclusions Gender,dyspnea,typical S Ⅰ TⅢQⅢ in electrocardiogram,PaCO2 and D-dimer seem unrelated to sudden death of patients with PTE.Young age,chest pain,syncope,bilateral asymmetrical edema,antineoplaston treatment or tumor metastasis within 6 months,operation in previous 4 months and low PaO2 were potential predictors of sudden death according to the univariate analysis.Higher WBC and higher HR are independent risk factors of sudden death for PTE patients.