Endothelial dysfunction is a primary pathophysiological change in sepsis. Macrophages are known to interact with vascular endothelial cells during the development of sepsis. Recently, drug delivery based on engineered macrophages was reported as an alternative approach for the management of diseases. Interleukin‐10 (IL10) is a well‐known anti‐inflammatory cytokine, which reduces inflammation and inhibits dysfunction of endothelial cells caused by sepsis. It is currently poorly understood whether genetically modified macrophages with overexpression of IL10 are able to restore endothelial integrity and function at the cellular level. In this study, we used lentiviral vectors to construct RAW264.7 macrophages engineered to overexpress IL10 (IL10‐eM) and investigated the effects of the IL10‐eM supernatant on LPS‐induced endothelial dysfunction using a noncontact coculture system. We found that cotreatment with IL10‐eM supernatant significantly attenuates the effects of LPS‐induced dysfunction of endothelial cells, including endothelial inflammatory response, endothelial permeability, and apoptosis. In addition, we discovered that LPS‐induced downregulation of VE‐cadherin and high production of reactive oxygen species were significantly attenuated upon IL10‐eM exposure. Furthermore, upregulation of IL6, TNFα, and Bax was decreased after treatment of cells with IL10‐eM supernatant. These results demonstrated that supernatant from engineered macrophages genetically modified with IL10 can effectively protect endothelial cells against LPS‐induced dysfunction in vitro, suggesting that exosomes from such engineered macrophages may have therapeutic effects against sepsis.

Background: Somatic copy number alteration (SCNA) usually accompanies the appearance of tumours; one common example is the 19q13.2 region amplification (AMP). Studies have shown that the 19q13.2 AMP might worsen the prognosis of patients with pancreatic cancer, and mediator complex subunit 29 (MED29) might be an amplified effector gene within this region. In this study, the role and molecular mechanism of MED29 in ovarian cancer (OvCa), one of the three major tumours in gynaecology, were discussed.Results: According to the transcriptome and survival data from the TCGA database, 19q13.2 AMP corresponded with a worse prognosis of OvCa patients (P = 0.0253), and individuals with 19q13.2 AMP showed increased levels of MED29 mRNA. From the GSE29450 dataset, we found that the gene expression of MED29 was significantly upregulated in OvCa and overexpression of MED29 in OvCa was related to shorter survival. Additionally, pathway analysis based on RNA-seq data indicated that MED29 could activate the expression of genes involved in cell proliferation. Moreover, knockdown of MED29 obvious inhibited the proliferation, invasion and migration of OVCAR3 and A2780 cells and arrested the cell cycle at the G2/M transition in vitro.Conclusion: MED29 could be used as a potential therapeutic target for OvCa treatment.