ABSTRACT
BACKGROUND: Emerging evidence has revealed that circular RNAs (circRNAs) have roles in regulating the complex pathologies of sepsis-induced acute lung injury (sepsis-ALI). Herein, this work aimed to investigate the potential role and mechanism of circPalm2 in the process of sepsis-ALI. METHODS: Primary mice pulmonary microvascular endothelial cells (MPVECs) in functional group were exposed to lipopolysaccharide (LPS). Levels of genes and proteins were measured by qRT-PCR and western blotting. Functional experiments were conducted using In vitro functional experiments were conducted using cell counting kit-8 assay, 5-ethynyl-2'-deoxyuridine (EdU) assay, flow cytometry and ELISA analysis. The binding between miR-450b-5p and circPalm2 or ROCK1 (Rho Associated Coiled-Coil Containing Protein Kinase 1) was validated using dual-luciferase reporter, RNA immunoprecipitation and pull-down assays. RESULTS: LPS treatment caused the increase of circPalm2 and ROCK1, as well as the decrease of miR-450b-5p in MPVECs. Knockdown of circPalm2 attenuated LPS-induced proliferation arrest, apoptosis, and production of proinflammatory cytokine IL-6, IL-ß and TNF-α in MPVECs. Mechanistically, circPalm2 sequestered miR-450b-5p to up-regulate ROCK1 expression, revealing the circPalm2/miR-450b-5p/ROCK1 feedback loop. Moreover, the protective functions mediated by circPalm2 silencing on MPVECs under LPS exposure were abolished by miR-129-5p inhibition or ROCK1 overexpression. CONCLUSION: CircPalm2 knockdown can alleviate LPS-evoked MPVEC apoptosis and inflammation via miR-450b-5p/ROCK1 axis, suggesting the potential involvement of this ceRNA network in sepsis-ALI and a broader approach for the therapy of sepsis-ALI.
Subject(s)
Acute Lung Injury , MicroRNAs , RNA, Circular , Sepsis , rho-Associated Kinases , Animals , Mice , Acute Lung Injury/chemically induced , Acute Lung Injury/genetics , Apoptosis , Endothelial Cells/metabolism , Inflammation/genetics , Inflammation/complications , Lipopolysaccharides , MicroRNAs/genetics , MicroRNAs/metabolism , Sepsis/complications , RNA, Circular/genetics , rho-Associated Kinases/genetics , rho-Associated Kinases/metabolismABSTRACT
BACKGROUND: Tibial tuberosity-trochlear groove distance(TT-TG) is a measurement to assist in the diagnosis and treatment of patellar instability, however it still has some limitations. Our study was to modify the accepted measurement method and seek a more reliable and standardized method. METHODS: The data of 65 healthy controls and 49 patients with bilateral patellar instability from 2010 to 2016 were collected and analyzed by CT. The TT-TG, tibial maximal mediolateral axis (MML), and their ratio [i.e., the modified-TT-TG (M-TT-TG)] were compared between the two groups. RESULTS: The MML (71.9±12.0 vs. 71.3±10.9) was not significantly different between the two groups (P>0.05). However, the TT-TG(18.1±6.0 vs. 13.1±2.9) and M-TT-TG (0.25±0.08 vs. 0.19±0.04) were significantly different between the two groups (P<0.05). A TT-TG of >15mm was found in 24.5% of healthy controls and 71.5% of patients. The healthy controls with a TT-TG of >15mm were compared with the patients; although no significant difference was found in the TT-TG (16.8±1.5 vs. 18.1±6.0), the healthy controls had a significantly larger MML (76.9±12.7 vs. 71.9±10.9) and significantly smaller M-TT-TG (0.22±0.04 vs. 0.25±0.08). A total of 53.1% of patients but only 6.9% of healthy controls had an M-TT-TG of >0.25. CONCLUSION: The M-TT-TG is a more reliable and standardized way to measure the effect of the TT-TG with the goal of reducing the false-positive rate associated with the standard measurement technique. The normal M-TT-TG ranges from 0.11 to 0.25, with an M-TT-TG of >0.25 being associated with patellofemoral malalignment. LEVEL OF EVIDENCE: III.
