FBW7 protects against spinal cord injury by mitigating inflammation-associated neuronal apoptosis in mice.

Spinal cord injury (SCI) leads to severe and long-lasting neurological disability. Presently, the lack of effective therapies for SCI is largely attributable to an incomplete understanding of its pathogenesis. F-box and WD repeat domain-containing protein 7 (FBW7, also known as FBXW7) is a type of E3 ubiquitin ligase complex, and plays essential roles in regulating different pathological and physiological processes. In this study, we attempted to explore the effects of FBW7 on SCI progression by the in vivo and in vitro experiments. SCI mice showed significantly reduced expression of FBW7 in spinal cord tissues. Promoting FBW7 expression via intrathecal injection of AAV9/FBW7 effectively improved locomotor function in SCI mice. Neuronal death in spinal cords of SCI mice was obviously ameliorated by FBW7 over-expression, along with greatly decreased expression of cleaved Caspase-3. In addition, microglial activation in spinal cord specimens was detected in SCI mice through increasing Iba-1 expression levels, which was, however, attenuated in SCI mice injected with AAV9/FBW7. Additionally, FBW7 over-expression dramatically restrained inflammatory response in spinal cord tissues of SCI mice, as evidenced by the down-regulated expression of tumor necrosis factor-α (TNF-α) and interleukin 1ß (IL-1ß) through blocking the activation of nuclear factor-κB (NF-κB) signaling. These anti-inflammatory effects of FBW7 were confirmed in LPS-stimulated mouse microglial BV2 cells. Finally, our in vitro studies showed that conditional medium (CM) collected from LPS-incubated BV2 cells markedly induced apoptosis in the isolated primary spinal neurons; However, this effect was overtly ameliorated by CM from LPS-exposed BV2 cells over-expressing FBW7. Thus, FBW7-regulated inflammation in microglial cells was involved in the amelioration of neuronal apoptosis during SCI development. Collectively, these findings illustrated that FBW7 expression was down-regulated in spinal cords of SCI mice, and promoting its expression could effectively mitigate SCI progression by repressing microglial inflammation and neuronal death.

[Control Measure Effects on the Effluent Quality from Extensive Green Roofs Based on Stabilized Sludge Recycling].

Substrate type is an important factor affecting the quality of water deriving from rainfall onto extensively green roofed areas. Here, stabilized sludge was used as the main nutrient component of the substrate combined with biochar and a dual-substrate structure. Five green roof pilot facilities were constructed, and the effect of control measures on effluent quality was analyzed. The results showed that the stabilized sludge dosage was 3%, and the annual average mass concentrations of total nitrogen (TN) and nitrate nitrogen (NO3--N) were 3.27 mg·L-1 and 1.61 mg·L-1. The use of stabilized sludge as a nutrient component under real rainfall and temperature conditions in Shanghai did not cause significant leaching of TN and NO3--N. In order to further improve the quality of the effluent, biochar was used as an amendment measure. As a result, the concentrations of TN and NO3--N in the effluent were decreased to 2.16 mg·L-1 and 1.38 mg·L-1, respectively. Using an adsorption layer of pumice can alleviate the leaching of total phosphorus (TP) and chemical oxygen demand (COD). For the total nitrogen budget of each pilot facility, the retained TN was about 55% of the original TN after one year of operation. Thus, stabilized sludge could be used as a nutrient substrate to meet the long-term requirements of plants. In the substrate with biochar, the retained TN in the substrate and the NO3--N concentration in the effluent was decreased, which was related to the mineralization of organics during dry periods and the enhancement of denitrification during rainfall periods. Stabilized sludge was not a polluting source of N but was a source of P. Using biochar and a dual-substrate structure can effectively reduce the TN and COD load of the tested green roof facilities.

[The relationship of peroxisome proliferator activated receptor γ ligands activity in nucleated cell and interleukin-6 level in septic rats].

OBJECTIVE: To observe the relationship between activity of peroxisome proliferator activated receptor γ (PPARγ) in nucleated cell and level of pro-inflammatory mediator interleukin-6 (IL-6) in plasma of rats with sepsis. METHODS: According to the random number table, 90 male Sprague-Dawley (SD) rats were randomly divided into three groups, namely control group, sham operation group and sepsis group. Each group was further divided into three subgroups according to postoperative time points, i.e. 12, 24 and 48-hour subgroups. Each subgroup consisted of 10 rats. Sepsis was reproduced by cecal ligation and puncture (CLP). The PPARγ activity in nucleated cells and IL-6 level in plasma were detected by enzyme-linked immunosorbent assay (ELISA). RESULTS: The PPARγ activity in nucleated cells was significantly decreased at 12, 24 and 48 hours in sepsis group (A value: 0.279±0.004, 0.264±0.009, 0.245±0.012) compared with control group (0.292±0.007, 0.293±0.004, 0.293±0.005) and sham operation group (0.295±0.008, 0.295±0.006, 0.294±0.007), while the IL-6 level was significantly increased in sepsis group (ng/L: 365.25±15.53, 507.16±20.86, 437.89±25.09) compared with control group (43.54±11.10, 48.82±10.62, 42.96±9.52) and sham operation group (42.43±6.77, 40.32±6.48, 44.10±9.36, all P<0.05). When septic condition became worse, the PPARγ activity in nucleated cells of sepsis group lowered, and IL-6 level was gradually elevated after operation, reaching the peak at 24 hours, and then gradually lowered, and the difference of the value between any two time points was all statistically significant (all P<0.05). There was a negative correlation between the PPARγ activity in nucleated cells and IL-6 level in 12-hour subgroup of sepsis group (r=-0.703, P=0.023). CONCLUSION: In septic rats, the PPARγ activity in nucleated cells was lowered while the pro-inflammatory mediator IL-6 level in plasma elevated, and there was a negative correlation between PPARγ activity and IL-6 level.

[Oxidative stress status in patients with chronic obstructive pulmonary disease and its relation to glucocorticoid receptor levels].

OBJECTIVE: To study changes in the levels of systematic and airway local oxidative stress in patients in different stages of chronic obstructive pulmonary diseases (COPD), and explore the association between oxidative stress and glucocorticoid receptor (GR) level in the peripheral blood leukocytes. METHODS: The levels of malonaldehyde (MDA), glutathione (GSH), superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX) in induced sputum and plasma, as well as GR levels in peripheral blood leukocytes and plasma levels of cortisol and adrenocorticotrophic hormone (ACTH), were examined in 33 patients with acute exacerbations of COPD (AECOPD, group A), 27 with stable COPD (group B), and 28 healthy volunteers (including 15 smokers as group C, and 15 nonsmokers as group D). RESULTS: MDA level in induced sputum and plasma decreased, whereas the levels of GSH, SOD and GSH-PX increased significantly in the order of groups A, B, C, and D (P<0.05). The activity of SOD in induced sputum and plasma were significantly lower in group C than in group D. No significant difference was noted in the other oxidative stress indices between groups C and D (P>0.05). The plasma levels of cortisol and ACTH showed no significant difference between the 4 groups, while the GR level in peripheral blood leukocytes increased significantly in the order of groups A, B, C and D (1565-/+719, 2069-/+488, 2739-/+926, and 4793 -/+1415 U, respectively, P<0.05). After controlling for the factor of smoking status, the plasma and sputum SOD activity were both positively correlated to GR, with the partial correlation coefficient of 0.512 and 0.564, respectively (P<0.001). CONCLUSION: Patients in different stages of COPD, especially those with AECOPD, may sustain systematic and local oxidation and anti-oxidation imbalance. Decreased SOD activity may contribute to GR level decrement in peripheral blood leukocytes in these patients.