Extracellular vesicles-transmitted long non-coding RNA MTUS2-5 promotes proliferation and vascularization of human vascular endothelial cells in patients with Budd-Chiari syndrome.

The high rates of misdiagnosis and untreated mortality with regard to Budd-Chiari syndrome (BCS) indicated the need to screen effective biomarkers. The aim of this study was to explore the function of extracellular vesicles (EVs) in patients with BCS as well as associated mechanisms. First, differentially expressed long non-coding RNAs (lncRNAs) from EVs separated from serum between BCS and healthy controls were screened using microarray analysis. Second, the proliferation, migration and tube formation of human vascular endothelial cells (HUVECs) were detected after EVs treatment, along with vascular endothelial growth factor (VEGF) levels and inflammatory factors from the cell supernatant. Last, the overexpressed lncRNA was transfected into the cells to further explore the mechanisms involved. Extracellular vesicles of BCS patients have significantly higher levels of lncRNA MTUS2-5 than healthy controls. Apparently, treatment with EVs from BCS or the ones transfected with plasmids that overexpress lncRNA MTUS2-5 enhances proliferation, migration and angiogenesis capacity. The results were considerably better than those obtained from treatment with EVs from healthy controls or transfection with the normal control plasmid, which also elevated the level of VEGF and inflammatory factors. Furthermore, FOS and PTGS2 were potentially regulated by the lncRNA MTUS2-5 transmitted by EVs. The lncRNA MTUS2-5 in EVs plays an important role in angiogenesis in the Budd-Chiari syndrome.

The effectiveness of Q6 and PIPER 6-year-old models on quantification of the change of child sitting posture with AEB and its impact on child's injures in frontal crash.

OBJECTIVE: Automatic Emergency Braking (AEB) has a direct impact on the effectiveness of the restraint systems in providing protection toward child occupants. The objective is to evaluate the effectiveness of Q6 and PIPER 6-year-old models in predicting the kinematic responses of child models, and further to quantify and analyze the child injuries during a frontal crash with and without AEB. METHODS: The finite element model of a booster seat has been validated through a full vehicle test. Based on the validated finite element model, two sled test finite element models for the rear seat booster seat with Q6 and PIPER 6-year-old models were constructed. AEB condition was imposed on above the two models and the kinematic responses of sitting posture including head, neck and chest have been compared in detail. The peak head displacement and neck curvature of Q6 dummy and PIPER 6-year-old models have been compared with the test data from child volunteers. Based on the child model with better predictive capability for kinematic response under AEB, child injuries were evaluated and analyzed for the 50 km/h frontal crash test with and without AEB. Last, this study discussed the effects of internal neck and chest structure difference between Q6 and PIPER 6-year-old models on child kinematic response and the injury risks. RESULTS: Under AEB condition, PIPER 6-year-old model has higher head displacement and lower trunk displacement than Q6 dummy model, and the peak head displacement and neck curvature of PIPER 6-year-old model are similar to the test data of child volunteers. During the 50 km/h frontal crash simulation with pre-crash AEB, the HIC15, Head acceleration 3 ms, Nij decrease 43.7%, 19.6% and 28.8%, respectively and the chest deflection increases 15.5% compared to the simulation without AEB. CONCLUSIONS: This study shows that PIPER 6-year-old model is more suitable for the quantification of sitting posture change under AEB due to its higher biofidelity. The pre-crash AEB can substantially reduce the head, neck injuries. But it also increases the chest injury due to the chest pre-compression. Future efforts are recommended to lower the child chest injury by integrating AEB with active pre-tensioning seatbelts.

MiR-550a-3p restores damaged vascular smooth muscle cells by inhibiting thrombomodulin in an in vitro atherosclerosis model.

Thrombomodulin (TM) is involved in the pathological process of atherosclerosis; however, the underlying mechanism remains unclear. Oxidised low-density lipoprotein (Ox-LDL; 100 µg/mL) was used to induce human vascular smooth muscle cells (HVSMCs) into a stable atherosclerotic cell model. The expression levels of miR-550a-3p and TM were detected by real-time reverse transcription-polymerase chain reaction. Cell proliferation was estimated using CCK8 and EDU assays. Wound scratch and transwell assays were used to measure the ability of cells to invade and migrate. Propidium iodide fluorescence-activated cell sorting was used to detect apoptosis and cell cycle changes. A dual-luciferase reporter assay was performed to determine the binding of miR-550a-3p to TM. Our results suggested the successful development of a cellular atherosclerosis model. Our data revealed that TM overexpression significantly promoted the proliferation, invasion, migration, and apoptosis of HVSMCs as well as cell cycle changes. Upregulation of miR-550a-3p inhibited the growth and metastasis of HVSMCs. Furthermore, miR-550a-3p was confirmed to be a direct target of TM. Restoration of miR-550a-3p expression rescued the effects of TM overexpression. Thus, miR-550a-3p might play a role in atherosclerosis and, for the first time, normalised the function of injured vascular endothelial cells by simultaneous transfection of TM and miR-550a-3p. These results suggest that the miR-550a-3p/TM axis is a potential therapeutic target for atherosclerosis.