Interferon regulatory factor 1-Rab27a regulated extracellular vesicles promote liver ischemia/reperfusion injury.

The role and regulators of extracellular vesicle (EV) secretion in hepatic ischemia/reperfusion (IR) injury have not been defined. Rab27a is a guanosine triphosphatase known to control EV release. Interferon regulatory factor 1 (IRF-1) is a transcription factor that plays an important role in liver IR and regulates certain guanosine triphosphatases. However, the relationships among IRF-1, Rab27a, and EV secretion are largely unknown. Here, we show induction of IRF-1 and Rab27a both in vitro in hypoxic hepatocytes and in vivo in warm IR and orthotopic liver transplantation livers. Interferon γ stimulation, IRF-1 transduction, or IR promoted Rab27a expression and EV secretion. Meanwhile, silencing of IRF-1 decreased Rab27a expression and EV secretion. Rab27a silencing decreased EV secretion and liver IR injury. Ten putative IRF-1 binding motifs in the 1,692-bp Rab27a promoter region were identified. Chromatin immunoprecipitation and electrophoretic mobility shift assay verified five functional IRF-1 binding motifs, which were confirmed by a Rab27a promoter luciferase assay. IR-induced EVs contained higher oxidized phospholipids (OxPL). OxPLs on the EV surface activated neutrophils through the toll-like receptor 4 pathway. OxPL-neutralizing E06 antibody blocked the effect of EVs and decreased liver IR injury. CONCLUSION: These findings provide a novel mechanism by which IRF-1 regulates Rab27a transcription and EV secretion, leading to OxPL activation of neutrophils and subsequent hepatic IR injury. (Hepatology 2018;67:1056-1070).

Metrical analysis of disc-condyle relation with different splint treatment positions in patients with TMJ disc displacement.

OBJECTIVE: To evaluate the effect of bite positions characterizing different splint treatments (anterior repositioning and stabilization splints) on the disc-condyle relation in patients with TMJ disc displacement with reduction (DDwR), using magnetic resonance imaging (MRI). MATERIAL AND METHODS: 37 patients, with a mean age of 18.8±4.3 years (7 male and 30 females) and diagnosed with DDwR based on the RDC/TMD, were recruited. MRI metrical analysis of the spatial changes of the disc/condyle, as well as their relationships, was done in three positions: maximum intercuspation (Position 1), anterior repositioning splint position (Position 2), and stabilization splint position (Position 3). Disc/condyle coordinate measurements and disc condyle angles were determined and compared. RESULTS: In Position 1, the average disc-condyle angle was 53.4° in the 60 joints with DDwR, while it was -13.3° with Position 2 and 30.1° with Position 3. The frequency of successful "disc recapture" with Position 2 was significantly higher (58/60, 96.7%) than Position 3 (20/60, 33.3%). In Positions 2 and 3, the condyle moved forward and downward while the disc moved backward. The movements were, however, more remarkable with Position 2. CONCLUSIONS: Anterior repositioning of the mandible improves the spatial relationship between the disc and condyle in patients with DDwR. In addition to anterior and inferior movement of the condyle, transitory posterior movement of the disc also occurred.

Metrical analysis of disc-condyle relation with different splint treatment positions in patients with TMJ disc displacement

Abstract Objective: To evaluate the effect of bite positions characterizing different splint treatments (anterior repositioning and stabilization splints) on the disc-condyle relation in patients with TMJ disc displacement with reduction (DDwR), using magnetic resonance imaging (MRI). Material and Methods: 37 patients, with a mean age of 18.8±4.3 years (7 male and 30 females) and diagnosed with DDwR based on the RDC/TMD, were recruited. MRI metrical analysis of the spatial changes of the disc/condyle, as well as their relationships, was done in three positions: maximum intercuspation (Position 1), anterior repositioning splint position (Position 2), and stabilization splint position (Position 3). Disc/condyle coordinate measurements and disc condyle angles were determined and compared. Results: In Position 1, the average disc-condyle angle was 53.4° in the 60 joints with DDwR, while it was −13.3° with Position 2 and 30.1° with Position 3. The frequency of successful "disc recapture" with Position 2 was significantly higher (58/60, 96.7%) than Position 3 (20/60, 33.3%). In Positions 2 and 3, the condyle moved forward and downward while the disc moved backward. The movements were, however, more remarkable with Position 2. Conclusions: Anterior repositioning of the mandible improves the spatial relationship between the disc and condyle in patients with DDwR. In addition to anterior and inferior movement of the condyle, transitory posterior movement of the disc also occurred.