Acute lung injury (ALI) is the leading cause of morbidity and mortality in critically ill patients. Neutrophil extracellular traps (NETs) have been well documented in the ALI model of bacterial infection. In the present study, we demonstrated that poly I:C could induce pulmonary NETs. Upon poly I:C intratracheal inoculation, neutrophil infiltration in the bronchoalveolar lavage fluid (BALF) was significantly increased. Furthermore, the inflammatory cytokines IL-1β, IL-6, and TNF-α in the lung were also significantly elevated. Neutrophil depletion abolished NETs and decreased both neutrophil infiltration and IL-1β in the lung. As expected, DNase I, an inhibitor of MPO and NADPH, decreased pulmonary inflammation and NETs. Blocking of the poly I:C receptor TLR3 reduced lung inflammation and NETs. The MAPK kinase inhibitor p38 diminished the formation of NETs and restored the expression of the tight junction protein claudin-5 in the mouse lung when challenged with poly I:C. In summary, poly I:C induced the formation of pulmonary NETs and ALI, which may be associated with the activation of p38 MAPK and the decreased expression of claudin-5.
Zhongyong thinking (Doctrine of the Mean) is a traditional Confucius interpersonal style with emphasis on interpersonal harmony and connection. In contemporary society, is Zhongyong thinking beneficial to, or has Zhongyong thinking become an old-fashioned idea with trivial or even detrimental influence on mental health? The current study explored the relationship of Zhongyong thinking and mental health measures in two studies. Study 1 was a cross-sectional survey involving a large representative sample of 8,178 Chinese undergraduate students. We found that Zhongyong thinking was negatively associated with anxiety ( r = −.23, p < .01) and depressive symptoms ( r = −.32, p < .01), but positively associated with self-esteem ( r = .28, p < .01). Compared with low-Zhongyong group, those who scored high on the Zhongyong Thinking Scale had substantially lower scores on anxiety and depressive symptoms, and had higher scores on self-esteem and life satisfaction. In Study 2, we experimentally intervened in Zhongyong thinking in 30 mildly depressed students, comparing mental health outcomes with a randomized control group ( n = 30) who received regular supportive group intervention. We found that training in Zhongyong thinking was more effective in alleviating depressive symptoms compared with the control group. The two studies prove from different aspects that Zhongyong thinking still plays an important role in regulating mental distress and maintaining subjective well-being among contemporary Chinese young adults. Why Zhongyong thinking is beneficial, and how to transmit this traditional cultural heritage to promote emotion regulation strategies are discussed.
Background Thrombotic events cannot be completely prevented by antithrombotics, implicating a therapeutic gap due to inflammation, a not yet sufficiently addressed mechanism. Neutrophil extracellular traps (NETs) are an essential interface between inflammation and thrombosis, but exactly how the NETotic process is initiated and maintained during arterial thrombosis remains incompletely understood. Methods and results We found that the plasma concentrations of C5a were higher in patients with ST-elevation myocardial infarction (STEMI) than in patients with angina and higher in mice with left common carotid artery (LCCA) thrombosis induced by FeCl3 than in control mice. We observed that the thrombus area and weight were decreased and that NET formation in the thrombi was reduced in the group treated with the selective C5aR1 receptor inhibitor PMX53 compared with the NaCl group. In vitro, NETosis was observed when C5a was added to neutrophil cultures, and this effect was reversed by PMX53. In addition, our data showed that C5a increased the production of mitochondrial reactive oxygen species (ROS) and that the promotion of NET formation by C5a was mitochondrial ROS (Mito-ROS) dependent. Furthermore, we found that C5a induced the production of Mito-ROS by inhibiting mitochondrial STAT3 activity. Conclusions By inhibiting mitochondrial STAT3 to elicit Mito-ROS generation, C5a triggers the generation of NETs to promote the development of arterial thrombosis. Hence, our study identifies complement C5a as a potential new target for the treatment and prevention of thrombosis.
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