Oleuropein ameliorated lung ischemia-reperfusion injury by inhibiting TLR4 signaling cascade in alveolar macrophages

Lung ischemia–reperfusion (I/R) injury is a common postoperative complication in patients with lung transplantation, pulmonary embolism, and cardiopulmonary bypass. Lung I/R injury is a sterile inflammatory process that leads to lung dysfunction, and is an important cause of patient death. Effectively alleviating lung I/R injury can thus improve the prognosis of patients. In this study, we created a mouse model of lung I/R injury by transient unilateral left pulmonary artery occlusion. 6–8 weeks male C57BL/6 mice were randomly assigned to four groups: Sham, I/R, I/R + oleuropein (OLE) and OLE. OLE (50 mg/kg) was orally 24 h and 30 min before anesthesia. Measurement of lung pathohistological, isolated alveolar macrophages (AMs), inflammatory mediators, TLR4 and its downstream factors (MyD88, NF-κB) were performed. We then evaluated the ability of oleuropein (OLE) to ameliorate I/R-induced lung injury and explored the possible molecular mechanisms. OLE ameliorated I/R-induced lung injury and edema and decreased inflammatory factors in lung tissue and bronchoalveolar lavage fluid. This protection required toll-like receptor 4 (TLR4). OLE significantly inhibited I/R-induced expression of TLR4 and its downstream factors in lung tissue and alveolar macrophages. In addition, hypoxia-inducible factor 1α protein accumulated in TLR4-mediated lung I/R injury, and further induced the production of inflammatory factors. Collectively, these data suggest that OLE ameliorates I/R-induced lung injury. The mechanism responsible for its protective effect may involve inhibition of the I/R-induced inflammatory response by downregulating the TLR4 signaling cascade in AMs.     

Suppression of macrophage-mediated xenogeneic rejection by the ectopic expression of human CD177

Cellular xenogeneic rejection by the innate immune system is a major immunological obstruction that needs to be overcome for the successful clinical use of xenografts. Our focus has been on macrophage-mediated xenogeneic rejection, since suppressing macrophage function has considerable potential for practical applications in the area of xenotransplantation. We report herein on an investigation of the suppressive effect of human CD177 (hCD177) against macrophage-mediated xenogeneic rejection. Wild type swine aortic endothelial cell (SEC) and an SEC transfectant with hCD177 (SEC/hCD177) were co-cultured with macrophages, and the degree of cytotoxicity was evaluated by WST-8 assays, and phagocytosis was examined using Calcein-AM labeling methods. The expression of anti/pro-inflammatory cytokines was evaluated by RT-qPCR and the phosphorylation of SHP-1 on macrophages in co-culture was evaluated by Western blotting. The result of cytotoxicity assays indicated that hCD177 suppressed M1 macrophage-mediated xenogeneic rejection (vs. SEC, p < 0.0001). Similarly, the result of phagocytosis assays indicated that hCD177 suppressed it (vs. SEC, p < 0.05). In addition, hCD177 significantly suppressed the expression of IL-1β, a pro-inflammatory cytokine, in M1 macrophages (vs. SEC, p < 0.01). Luciferase assays using THP1-Lucia NF-kB also showed a significant difference in NF-kB activation (vs. SEC, p < 0.001). In addition, hCD177 was found to induce the phosphorylation of SHP-1 in M1 macrophages (vs. SEC, p < 0.05). These findings indicate that hCD177 suppresses M1 macrophage-mediated xenogeneic rejection, at least in part via in the phosphorylation of SHP-1.     

The Chinese version of the Addiction Severity Index (ASI-C): Reliability,validity, and responsiveness in Chinese patients with alcohol dependence

We evaluated the reliability, validity, and responsiveness of the Chinese version of the 5th edition Addiction Severity Index (ASI-C-5) in Chinese male alcohol-dependent inpatients. Three hundred and fifty-four inpatients with alcohol dependence from five regions of China were interviewed in person by five trained interviewers using the ASI-C-5. Responses were then analyzed for internal consistency reliability, discriminant validity, criterion validity, and responsiveness. Forty subjects were re-interviewed 7 days later to assess test–retest reliability. The ASI-C-5 had good internal consistency, with an overall standardized Cronbach's alpha of 0.79. The Cronbach's alpha values for internal consistency of domain CSs ranged from 0.48 to 0.95, and were above 0.60 for six domains. The 7 day test–retest reliability was acceptable as evidenced by high Pearson correlation coefficients (0.75–0.92, p < 0.01) for 6 of 7 domain CSs. Correlation coefficients between the seven domain CSs ranged from 0.007 to 0.390 (p < 0.05 or 0.01 two-sided), indicating strong discriminant validity. The correlation coefficient between the alcohol dependence composite score of ASI-C-5 and the Alcohol Use Disorders Identification Test (AUDIT) was 0.69 (p < 0.01), indicating good criterion validity. The frequency of extreme scores was low, except for significant floor effects in the “Drugs” and “Legal Status” domains. Collectively, these findings suggest that the ASI-C-5 exhibited strong reliability, validity, and responsiveness in Chinese male alcohol-dependent inpatients.     

工读男生与普通男生攻击性行为的对照研究

目的了解工读男生和普通男生的攻击性行为现状,探究工读男生的攻击性特点。方法以班级为单位整群随机选取河南省郑州市工读学校、洛阳市工读学校学生90名为实验组,选取新乡市第一中学初中学生90名为对照组,均施以基本情况调查表及攻击性问卷调查。结果年龄与言语攻击因子、愤怒因子、敌意因子呈负相关(P<0.05);工读男生较普通男生在攻击性和躯体攻击差异有统计学意义(P<0.05);高攻击水平分组中,工读男生较普通中学男生表现出更高的言语攻击;低攻击水平分组中,工读男生与普通中学男生在躯体攻击上差异有统计学意义(P<0.05)。结论工读男生有更高的攻击性,躯体攻击较为突出。高攻击性的工读男生更多使用言语攻击,低攻击性的工读男生有更多的躯体攻击倾向。     

Decreased microRNA miR-181c expression in peripheral blood mononuclear cells correlates with elevated serum levels of IL-7 and IL-17 in patients with myasthenia gravis

miR-181c is a newly identified negative regulator of immune cell activation. In this study, we aimed to investigate the expression and functional role of miR-181c in myasthenia gravis (MG). miR-181c showed significant downregulation in peripheral blood mononuclear cells (PBMCs) from MG patients compared with healthy controls, with lower expression in generalized patients than in ocular ones. MG patients also had increased serum IL-7 and IL-17 levels. Additionally, serum IL-7 level presents a positive correlation with the serum IL-17 level. miR-181c levels were negatively correlated with serum levels of IL-7 and IL-17 in either generalized patients or ocular patients. A luciferase reporter assay revealed that miR-181c could directly bind to the 3′-UTR of interleukin-7. Forced expression of miR-181c led to decreased IL-7 and IL-17 release in cultured PBMCs, while depletion of miR-181c increased the secretion of these two proinflammatory cytokines. The results from our study suggested for the first time that miR-181c was able to negatively regulate the production of proinflammatory cytokines IL-7 and IL-17 in MG patients, and it is a novel potential therapeutic target for MG.