Background: Exosomes have been recognized as being more effective than direct stem cell differentiation into functional target cells for protecting against tissue injury and promoting tissue repair. Our previous study demonstrated the protective effect of adipose-derived stem cells (ADSCs) on lipopolysaccharide (LPS)-induced acute lung injury and the effect of autophagy on ADSC functions, but the role of ADSC-derived exosomes (ADSC-Exos) and autophagy-mediated regulation of ADSC-Exos in LPS-induced pulmonary microvascular barrier damage remain unclear. Methods: LPS-induced pulmonary microvascular barrier injury was detected after ADSC-Exos pretreatment. Effects of autophagy on the function and bioactive miRNAs components of ADSC-Exos were assessed after inhibiting the cells autophagy in advance. Results: ADSC-Exo culture resulted in significant alleviation of LPS-induced microvascular barrier injury. The inhibition of autophagy markedly weakened the therapeutic effect of ADSC-Exos. In addition, autophagy inhibition changed the expression levels of the five specific miRNAs in exosomes; interleukin-1β（IL-1β）preconditioning promoted the expression of miR(miRNA)-21a but lowered the expressions of let-7-a-1, miR-143 and miR-145a, and did not affect the expression of miR-451a. Autophagy inhibition, however, has prohibited the expressions of all these miRNAs under IL-1β preconditioning. Conclusion: Our results indicate that ADSC-Exos protect against LPS-induced pulmonary microvascular barrier damage. Autophagy is a positive mediator of exosome function at least partly through controlling the expression of bioactive miRNAs in exosomes.

Small extracellular vesicles (sEVs) have been recognized to be more effective than direct stem cell differentiation into functional target cells in preventing tissue injury and promoting tissue repair. Our previous study demonstrated the protective effect of adipose-derived stem cells (ADSCs) on lipopolysaccharide (LPS)-induced acute lung injury and the effect of autophagy on ADSC functions, but the role of ADSC-derived sEVs (ADSC-sEVs) and autophagy-mediated regulation of ADSC-sEVs in LPS-induced pulmonary microvascular barrier damage remains unclear. After treatment with sEVs from ADSCs with or without autophagy inhibition, LPS-induced human pulmonary microvascular endothelial cell (HPMVECs) barrier damage was detected. LPS-induced acute lung injury in mice was assessed in vivo after intravenous administration of sEVs from ADSCs with or without autophagy inhibition. The effects of autophagy on the bioactive miRNA components of ADSC-sEVs were assessed after prior inhibition of cell autophagy. We found that ADSC-sEV effectively alleviated LPS-induced apoptosis, tight junction damage and high permeability of PMVECs. Moreover, in vivo administration of ADSC-sEV markedly inhibited LPS-triggered lung injury. However, autophagy inhibition, markedly weakened the therapeutic effect of ADSC-sEVs on LPS-induced PMVECs barrier damage and acute lung injury. In addition, autophagy inhibition, prohibited the expression of five specific miRNAs in ADSC-sEVs -under LPS-induced inflammatory conditions. Our results indicate that ADSC-sEVs protect against LPS-induced pulmonary microvascular barrier damage and acute lung injury. Autophagy is a positive mediator of sEVs function, at least in part through controlling the expression of bioactive miRNAs in sEVs.

Background: Small extracellular vesicles (sEVs) have been recognized to be more effective than direct stem cell differentiation into functional target cells in preventing tissue injury and promoting tissue repair. Our previous study demonstrated the protective effect of adipose-derived stem cells (ADSCs) on lipopolysaccharide (LPS)-induced acute lung injury and the effect of autophagy on ADSC functions, but the role of ADSC-derived sEVs (ADSC-sEVs) and autophagy-mediated regulation of ADSC-sEVs in LPS-induced pulmonary microvascular barrier damage remains unclear. Methods: After treatment with sEVs from ADSCs with or without autophagy inhibition, LPS-induced human pulmonary microvascular endothelial cell (HPMVECs) barrier damage was detected. LPS-induced acute lung injury in mice was assessed in vivo after intravenous administration of sEVs from ADSCs with or without autophagy inhibition. The effects of autophagy on the bioactive miRNA components of ADSC-sEVs were assessed after prior inhibition of cell autophagy. Results: We found that ADSC-sEV effectively alleviated LPS-induced apoptosis, tight junction damage and high permeability of PMVECs. Moreover, in vivo administration of ADSC-sEV markedly inhibited LPS-triggered lung injury. However, autophagy inhibition, markedly weakened the therapeutic effect of ADSC-sEVs on LPS-induced PMVECs barrier damage and acute lung injury. In addition, autophagy inhibition, prohibited the expression of five specific miRNAs in ADSC-sEVs -under LPS-induced inflammatory conditions. Conclusions: Our results indicate that ADSC-sEVs protect against LPS-induced pulmonary microvascular barrier damage and acute lung injury. Autophagy is a positive mediator of sEVs function, at least in part through controlling the expression of bioactive miRNAs in sEVs.

Purpose This study aimed to identify risk factors for pulmonary hemorrhage (PH) and higher-grade PH that complicate computed tomography (CT)-guided percutaneous lung biopsy (CT-PNLB) and establish predictive models to quantify the risk. Methods A total of 2653 cases of CT-PNLB were enrolled. Multivariate logistic regression was used to identify independent risk factors to develop a nomogram prediction model. The model was assessed using the area under the curve (AUC) of the receiver operator characteristic (ROC) and calibration curves and validated in the validation group. Results PH occurred in 23.52% (624/2653) of cases, and higher-grade PH occurred in 7.09% (188/2653) of cases. The parameters of lesion size, puncture depth, and contact to pleura were identified as risk factors of PH and higher-grade PH in the logistic regression model, besides the position as a risk factor for PH. The AUC of the PH prediction model was 0.776 [95% confidence interval (CI): 0.752–0.800], whereas that of the validation group was 0.743 (95% CI: 0.706–0.780). The AUC of the higher-grade PH prediction model was 0.782 (95% CI: 0.742–0.832), whereas that of the validation group was 0.769 (95% CI: 0.716–0.822). The calibration curves of the model showed good agreement between the predicted and actual probability in the development and validation groups. Conclusion We identified risk factors associated with PH and higher-grade PH after PNLBs. Furthermore, we developed and validated two risk prediction models for PNLB-related PH and higher-grade PH risk prediction and clinical decision support. Key messages What is already known on this topic Pulmonary hemorrhage (PH) and other hemorrhagic complications are the most common complication in CT-guided percutaneous lung biopsy (CT-PNLB), except pneumothorax. However, the risk factors associated with PH remain controversial, and research on models of PH and higher-grade PH is also limited. What this study adds The parameters of lesion size, puncture depth, and contact to pleura were identified as risk factors of PH and higher-grade PH in the logistic regression model, besides the position as a risk factor for PH. In addition, we developed and validated two risk prediction models for PNLB-related PH and higher-grade PH risk prediction and clinical decision support. How this study might affect research, practice, or policy Of all the predictors, the position is the key factor to be considered by the operator. Moreover, two risk prediction models show good discrimination and calibration characteristics to identify patients at high risk of hemorrhage and higher-grade PH after PNLB, so these could assist clinicians in avoiding risk factors in advance.

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