PDIA3-regulted inflammation and oxidative stress contribute to the traumatic brain injury (TBI) in mice.

Traumatic brain injury (TBI) is a leading cause of death and disability throughout the world. However, the molecular mechanism contributing to TBI still remains unclear. Protein disulfide isomerases (PDI) are a family of redox chaperones, which catalyze formation or isomerization of disulfide bonds in proteins. PDIA3, a critical member of PDI family, is a multi-functional protein, playing critical roles in modulating inflammation, apoptosis and oxidative stress under various kinds of disease conditions. Nevertheless, its regulatory effects on TBI have far from to be known. In the present study, we attempted to explore the modulation of neuroinflammatory responses by PDIA3 and its contribution to oxidative stress and cell death after TBI in the wild type (PDIA+/+) and PDIA3 knockout (PDIA3+/+) C57BL/6 mice. Results here suggested that PDIA3 expression was markedly up-regulated in the late trauma human brain tissues, which was verified in the PDIA3+/+ mice at 24 h after TBI. PDIA-/- provided significant improvements in cognitive impairments and contusion volume induced by TBI. Apoptosis in brain samples was also alleviated in TBI mice with PDIA3 deficiency. Significantly, PDIA3-/- mitigated neuroinflammation after TBI in mice, as evidenced by the reduced expression of pro-inflammatory factors interleukin (IL)-6, tumor necrosis factor-α (TNF-α) and IL-1ß, while the enhanced anti-inflammatory regulator IL-10. These anti-inflammatory activities by PDIA3-/- were associated with the decrease in phosphorylated nuclear factor kappa B (NF-κB)/p65. PDIA3-/- mice following TBI showed attenuated oxidative stress, as proved by the restored superoxide dismutase (SOD) and glutathione (GSH) activities, and the down-regulated malondialdehyde (MDA) levels in brain samples. These effects regulated by PDIA3 were confirmed in OGDR-treated astrocytes. Collectively, these data demonstrated a detrimental role of PDIA3 in regulating TBI, providing an effective therapeutic target for TBI treatment in future.

Cdc42 Promotes Schwann Cell Proliferation and Migration Through Wnt/ß-Catenin and p38 MAPK Signaling Pathway After Sciatic Nerve Injury.

Schwann cells (SCs) are unique glial cells in the peripheral nerve and may secrete multiple neurotrophic factors, adhesion molecules, extracellular matrix molecules to form the microenvironment of peripheral nerve regeneration, guiding and supporting nerve proliferation and migration. Cdc42 plays an important regulatory role in dynamic changes of the cytoskeleton. However, there is a little study referred to regulation and mechanism of Cdc42 on glial cells after peripheral nerve injury. The present study investigated the role of Cdc42 in the proliferation and migration of SCs after sciatic nerve injury. Cdc42 expression was tested, showing that the mRNA and protein expression levels of Cdc42 were significantly up-regulated after sciatic nerve injury. Then, we isolated and purified SCs from injuried sciatic nerve at day 7. The purified SCs were transfected with Cdc42 siRNA and pcDNA3.1-Cdc42, and the cell proliferation, cell cycle and migration were assessed. The results implied that Cdc42 siRNA remarkably inhibited Schwann cell proliferation and migration, and resulted in S phase arrest. While pcDNA3.1-Cdc42 showed a contrary effect. Besides, we also observed that Cdc42 siRNA down-regulated the protein expression of ß-catenin, Cyclin D1, c-myc and p-p38, which were up-regulated by pcDNA3.1-Cdc42. Meanwhile, the inhibitor of Wnt/ß-catenin and p38 MAPK signaling pathway IWP-2 and SB203580 significantly inhibited the effect of pcDNA3.1-Cdc42 on cell proliferation and migration. Overall, our data indicate that Cdc42 regulates Schwann cell proliferation and migration through Wnt/ß-catenin and p38 MAPK signaling pathway after sciatic nerve injury, which provides further insights into the therapy of the sciatic nerve injury.

Predictors for Massive Blood Loss During Posterior Correction of Congenital Scoliosis in Pre-school Children:A Retrospective Observation.

Objective To investigate the predictors for massive blood loss during posterior correction of congenital scoliosis in pre-school children. Methods Totally 124 children under six years of age,who received posterior correction of congenital scoliosis,were divided into two groups according to the ratio of intraoperative blood loss (BL) and estimated blood volume (EBV). Massive blood loss was defined as BL/EBV>0.15,and minor or moderate blood loss as BL/EBV≤0.15. All the records,including demographics,intraoperative fluids,pre- or postoperative laboratory parameters,and the length of hospital stay,were compared between these two groups. Results There were 57 children in the moderate or minor blood loss group and 67 children in the massive blood loss group. When compared with moderate or minor blood loss group,children in massive blood loss group had significantly lower body weight,shorter body height,longer anesthesia period,and more autologous or allogeneic transfusion (P<0.05). Binary Logistic regression analysis showed that body weight lower than 15 kg was the independent predictor for massive blood loss (OR=0.435,95% CI=0.197-0.962). Conclusions The incidence of massive blood loss is about 54% in children under six years of age who have received posterior correction of congenital scoliosis. The body weight of lower than 15 kg is an independent predictor for massive blood loss during the surgery.

Evaluation of risk factors for arytenoid dislocation after endotracheal intubation: a retrospective case-control study.

OBJECTIVE: To investigate the risk factors for postoperative arytenoid dislocation. METHODS: From September 2003 to August 2013, the records of 16 patients with a history of postoperative arytenoid dislocation were reviewed. Patients matched in terms of date and type of procedures were chosen as the controls (n=16). Recorded data for all patients were demographics, smoking status, alcoholic status, preoperative physical status, airway evaluation, intubation procedures, preoperative laboratory test results, anesthetic consumption and intensive care unit stay. For arytenoid dislocation cases, we further analyzed the incidences of the left and right arytenoid dislocation, and the outcomes of surgical repair and conservative treatment. Categorical variables were presented as frequencies and percentages, and were compared using the chi-squared test. Continuous variables were expressed as means±SD and compared using the Student's unpaired t-test. To determine the predictors of arytenoid dislocation, a logistic regression model was used for multivariate analysis. RESULTS: Sixteen patients with postoperative arytenoid dislocation were enrolled, with a median age of 52 years. Most postoperative arytenoid dislocation patients (15/16, 93.75%) received surgical repair, except one patient who recovered after conservative treatment. None of the postoperative arytenoid dislocation patients were smokers. Red blood cell (P=0.044) and hemoglobin (P=0.031) levels were significantly lower among arytenoid dislocation cases compared with the controls. CONCLUSIONS: Non-smoking and anemic patients may be susceptible to postoperative arytenoid dislocation. However, neither of them was independent risk factor for postoperative arytenoid dislocation.

SNX9 Inhibits Cell Proliferation and Cyst Development in Autosomal Dominant Polycystic Kidney Disease via Activation of the Hippo-YAP Signaling Pathway.

Autosomal dominant polycystic kidney disease (ADPKD) is a complex process, involving the alteration of multiple genes and signaling pathways, and the pathogenesis of ADPKD remains largely unknown. Here, we demonstrated the suppressive role of sorting nexin 9 (SNX9) during ADPKD development. Sorting nexin 9 expression was detected in the kidney tissues of ADPKD patients, for the first time, and SNX9 expression was also detected in Pkd1 knockout (Pkd1 -/-) and control mice. Subsequently, a series of gain- and loss-of-function studies were performed, to explore the biological roles and underlying molecular mechanisms of SNX9 in ADPKD progression. The expression of SNX9 was significantly downregulated in ADPKD patients and Pkd1 -/- mice compared with control individuals and wild-type mice (Pkd1+/+), respectively. The ectopic expression of SNX9 significantly inhibited ADPKD cell proliferation, renal cyst formation and enlargement, whereas these effects were promoted by SNX9 silencing. Mechanistically, we found that SNX9 interacted directly with yes-associated protein (YAP) and increased the large tumor suppressor kinase 1-mediated phosphorylation of YAP, resulting in the cytoplasmic retention of YAP, the decreased transcriptional activity of the YAP/TEA domain transcription factor 4 complex, and, consequently, the inhibition of Hippo target gene expression and ADPKD development. Taken together, our findings provided novel insights into the role played by SNX9 during ADPKD pathogenesis and may reveal novel therapeutic approaches for ADPKD and related kidney diseases.