Iron and ferritin effects on intensive care unit mortality: A meta-analysis.

BACKGROUND: The effect of serum iron or ferritin parameters on mortality among critically ill patients is not well characterized. AIM: To determine the association between serum iron or ferritin parameters and mortality among critically ill patients. METHODS: Web of Science, Embase, PubMed, and Cochrane Library databases were searched for studies on serum iron or ferritin parameters and mortality among critically ill patients. Two reviewers independently assessed, selected, and abstracted data from studies reporting on serum iron or ferritin parameters and mortality among critically ill patients. Data on serum iron or ferritin levels, mortality, and demographics were extracted. RESULTS: Nineteen studies comprising 125490 patients were eligible for inclusion. We observed a slight negative effect of serum ferritin on mortality in the United States population [relative risk (RR) 1.002; 95%CI: 1.002-1.004). In patients with sepsis, serum iron had a significant negative effect on mortality (RR = 1.567; 95%CI: 1.208-1.925). CONCLUSION: This systematic review presents evidence of a negative correlation between serum iron levels and mortality among patients with sepsis. Furthermore, it reveals a minor yet adverse impact of serum ferritin on mortality among the United States population.

Macrophage exosomes transfer angiotensin II type 1 receptor to lung fibroblasts mediating bleomycin-induced pulmonary fibrosis.

BACKGROUND: Macrophages are involved in the pathogenesis of idiopathic pulmonary fibrosis, partially by activating lung fibroblasts. However, how macrophages communicate with lung fibroblasts is largely unexplored. Exosomes can mediate intercellular communication, whereas its role in lung fibrogenesis is unclear. Here we aim to investigate whether exosomes can mediate the crosstalk between macrophages and lung fibroblasts and subsequently induce fibrosis. METHODS: In vivo, bleomycin (BLM)-induced lung fibrosis model was established and macrophages infiltration was examined. The effects of GW4869, an exosomes inhibitor, on lung fibrosis were assessed. Moreover, macrophage exosomes were injected into mice to observe its pro-fibrotic effects. In vitro, exosomes derived from angiotensin II (Ang II)-stimulated macrophages were collected. Then, lung fibroblasts were treated with the exosomes. Twenty-four hours later, protein levels of α-collagen I, angiotensin II type 1 receptor (AT1R), transforming growth factor-ß (TGF-ß), and phospho-Smad2/3 (p-Smad2/3) in lung fibroblasts were examined. The Student's t test or analysis of variance were used for statistical analysis. RESULTS: In vivo, BLM-treated mice showed enhanced infiltration of macrophages, increased fibrotic alterations, and higher levels of Ang II and AT1R. GW4869 attenuated BLM-induced pulmonary fibrosis. Mice with exosomes injection showed fibrotic features with higher levels of Ang II and AT1R, which was reversed by irbesartan. In vitro, we found that macrophages secreted a great number of exosomes. The exosomes were taken by fibroblasts and resulted in higher levels of AT1R (0.22 ±â€Š0.02 vs. 0.07 ±â€Š0.02, t = 8.66, P = 0.001), TGF-ß (0.54 ±â€Š0.05 vs. 0.09 ±â€Š0.06, t = 10.00, P < 0.001), p-Smad2/3 (0.58 ±â€Š0.06 vs. 0.07 ±â€Š0.03, t = 12.86, P < 0.001) and α-collagen I (0.27 ±â€Š0.02 vs. 0.16 ±â€Š0.01, t = 7.01, P = 0.002), and increased Ang II secretion (62.27 ±â€Š7.32 vs. 9.56 ±â€Š1.68, t = 12.16, P < 0.001). Interestingly, Ang II increased the number of macrophage exosomes, and the protein levels of Alix (1.45 ±â€Š0.15 vs. 1.00 ±â€Š0.10, t = 4.32, P = 0.012), AT1R (4.05 ±â€Š0.64 vs. 1.00 ±â€Š0.09, t = 8.17, P = 0.001), and glyceraldehyde-3-phosphate dehydrogenase (2.13 ±â€Š0.36 vs. 1.00 ±â€Š0.10, t = 5.28, P = 0.006) were increased in exosomes secreted by the same number of macrophages, indicating a positive loop between Ang II and exosomes production. CONCLUSIONS: Exosomes mediate intercellular communication between macrophages and fibroblasts plays an important role in BLM-induced pulmonary fibrosis.

Author Correction: Mir-21 Mediates the Inhibitory Effect of Ang (1-7) on AngII-induced NLRP3 Inflammasome Activation by Targeting Spry1 in lung fibroblasts.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Mir-21 Mediates the Inhibitory Effect of Ang (1-7) on AngII-induced NLRP3 Inflammasome Activation by Targeting Spry1 in lung fibroblasts.

MicroRNA-21 (mir-21) induced by angiotensin II (AngII) plays a vital role in the development of pulmonary fibrosis, and the NLRP3 inflammasome is known to be involved in fibrogenesis. However, whether there is a link between mir-21 and the NLRP3 inflammasome in pulmonary fibrosis is unknown. Angiotensin-converting enzyme 2/angiotensin(1-7) [ACE2/Ang(1-7)] has been shown to attenuate AngII-induced pulmonary fibrosis, but it is not clear whether ACE2/Ang(1-7) protects against pulmonary fibrosis by inhibiting AngII-induced mir-21 expression. This study's aim was to investigate whether mir-21 activates the NLRP3 inflammasome and mediates the different effects of AngII and ACE2/Ang(1-7) on lung fibroblast apoptosis and collagen synthesis. In vivo, AngII exacerbated bleomycin (BLM)-induced lung fibrosis in rats, and elevated mir-21 and the NLRP3 inflammasome. In contrast, ACE2/Ang(1-7) attenuated BLM-induced lung fibrosis, and decreased mir-21 and the NLRP3 inflammasome. In vitro, AngII activated the NLRP3 inflammasome by up-regulating mir-21, and ACE2/Ang(1-7) inhibited NLRP3 inflammasome activation by down-regulating AngII-induced mir-21. Over-expression of mir-21 activated the NLRP3 inflammasome via the ERK/NF-κB pathway by targeting Spry1, resulting in apoptosis resistance and collagen synthesis in lung fibroblasts. These results indicate that mir-21 mediates the inhibitory effect of ACE2/Ang(1-7) on AngII-induced activation of the NLRP3 inflammasome by targeting Spry1 in lung fibroblasts.