Brain‐derived neurotrophic factor precursor (proBDNF) has been reported to strengthen the dysfunction of monocytes/macrophages in animal studies. However, it is still unknown the roles of proBDNF in the dysfunction of monocytes in the inflammatory diseases in humans. In the present study, we showed that proBDNF and pan neurotrophic receptor p75 were significantly upregulated in monocytes from healthy donors (HD) after lipopolysaccharide treatment. Exogenous proBDNF treatment upregulated CD40 and proinflammatory cytokines expression in monocytes including interleukin (IL)‐1β, IL‐6, and tumor necrosis factor (TNF)‐α. In Stanford type‐A acute aortic dissection (AAD) patients, proBDNF was upregulated in CD14 ⁺ CD163 ⁺ CX3CR1 ⁺ M2‐ but not CD14 ⁺ CD68 ⁺ CCR2 ⁺ M1‐like monocytes. In addition, sera from AAD patients activated gene expression of proinflammatory cytokines in cultured PBMCs from HD, which was attenuated by proBDNF monoclonal antibody (Ab‐proB) treatment. These findings suggested that upregulation of proBDNF in M2‐like monocytes may contribute to the proinflammatory response in the AAD.

The aim of this study was to identify the role of the precursor of the brain‐derived neurotrophic factor (pro‐BDNF) in myocardial hypoxia/reoxygenation injury (H/R) and to address the underlying mechanisms. For this purpose, myocardial microvascular endothelial cells (MMECs) exposed to a high concentration of glucose (30 mM) for 48 h were subjected to 4 h of hypoxia followed by 2 h of reoxygenation. Terminal deoxynucleotidyl transferase (TdT) dUTP nick‐end labeling (TUNEL) staining and flow‐cytometric analysis were performed to detect apoptosis. Cell scratch and capillary‐like‐structure formation assays were employed to evaluate cell function. The levels of apoptosis‐related proteins were evaluated by Western blotting and immunofluorescence assays. Our results showed that H/R resulted in MMEC injury, as indicated by significant increases in TUNEL‐positive cell numbers and a reduction in MMEC migration and in capillary‐like‐structure formation coupled with increased pro‐BDNF protein expression. In addition, overexpression of pro‐BDNF in MMECs via a viral vector led to increased pro‐BDNF expression, and this upregulation induced apoptosis. Mechanistic experiments revealed that H/R did not influence BDNF, JNK, and caspase 3 expression, but upregulated pro‐BDNF, p75^NTR, sortilin, phospho‐JNK, and cleaved caspase 3 protein levels. In contrast, neutralization of endogenous pro‐BDNF with an antibody significantly attenuated H/R‐induced upregulation of pro‐BDNF, p75^NTR, sortilin, p‐JNK, and cleaved caspase 3 protein levels, indicating that p75^NTR‐sortilin signaling and activation of JNK and caspase 3 may be involved in these effects. In conclusion, H/R‐induced injury may be mediated by pro‐BDNF, at least in part through the regulation of p75^NTR‐sortilin signaling and activation of JNK and caspase 3.

Objective: The aim of this study is to compare the effect of bronchial blockers (BB) and double-lumen tubes (DLT) on patients' postoperative recovery after lung resection.

The underlying mechanism of endothelial dysfunction during the aortic dissection (AD) remains unclear. The present study is aimed to uncover the intrinsic mechanism regulating the endocytosis of circulating exosomes by endothelial cells after AD takes place. Circulating exosomes extracted from both AD-patients and healthy donors (HD) were characterized and applied to human umbilical vein endothelial cells (HUVECs) in vitro with or without the co-exposure of lipopolysaccharide (LPS). The endocytosis of exosomes and inflammatory severity were evaluated. Besides, the JMJD6 expression pattern was explored, and si-RNA to knock down the JMJD6 expression was performed to test its role in exosome endocytosis. Here, it was firstly shown that circulating exosomes of the AD patients were statistically higher than the HD. In vitro, the endocytosis of both AD- and HD-exosomes was both enhanced under the co-existence of the LPS, and the uptake of AD-exosomes instead of the control exosomes further worsened the LPS-induced cell injury and gene transcriptions of serial pro-inflammatory cytokines through the p65 signaling. Notably, LPS challenged ECs exhibited increased JMJD6 expression, and silencing JMJD6 effectively decreased the LPS enhanced exosome endocytosis, and attenuated the LPS + AD-exosomes induced cell pro-inflammatory injury. The findings above indicate that LPS co-exposure enhances the AD-exosomes endocytosis by the ECs and further aggravates the inflammatory injury; Targeting on the cellular JMJD6 shall mitigate AD-exosomes endocytosis, which might serve as a potential therapeutic approach for the endothelial dysfunction.