Rac1 relieves neuronal injury induced by oxygenglucose deprivation and re-oxygenation via regulation of mitochondrial biogenesis and function.

Certain microRNAs (miRNAs) can function as neuroprotective factors after reperfusion/ischemia brain injury. miRNA-142-3p can participate in the occurrence and development of tumors and myocardial ischemic injury by negatively regulating the activity of Rac1, but it remains unclear whether miRNA-142-3p also participates in cerebral ischemia/reperfusion injury. In this study, a model of oxygen-glucose deprivation/re-oxygenation in primary cortical neurons was established and the neurons were transfected with miR-142-3p agomirs or miR-142-3p antagomirs. miR-142-3p expression was down-regulated in neurons when exposed to oxygen-glucose deprivation/re-oxygenation. Over-expression of miR-142-3p using its agomir remarkably promoted cell death and apoptosis induced by oxygen-glucose deprivation/re-oxygenation and improved mitochondrial biogenesis and function, including the expression of peroxisome proliferator-activated receptor-γ coactivator-1α, mitochondrial transcription factor A, and nuclear respiratory factor 1. However, the opposite effects were produced if miR-142-3p was inhibited. Luciferase reporter assays verified that Rac Family Small GTPase 1 (Rac1) was a target gene of miR-142-3p. Over-expressed miR-142-3p inhibited NOX2 activity and expression of Rac1 and Rac1-GTPase (its activated form). miR-142-3p antagomirs had opposite effects after oxygen-glucose deprivation/re-oxygenation. Our results indicate that miR-142-3p down-regulates the expression and activation of Rac1, regulates mitochondrial biogenesis and function, and inhibits oxygen-glucose deprivation damage, thus exerting a neuroprotective effect. The experiments were approved by the Committee of Experimental Animal Use and Care of Central South University, China (approval No. 201703346) on March 7, 2017.

[Response of black soil organic carbon, nitrogen and its availability to longterm fertilization].

Based on the long-term fertilization experiments, effects of various fertilization practices on the soil organic carbon (SOC) and total nitrogen (TN) in the surface (0-20 cm) and subsurface (20-40 cm) black soil in northeast China were studied. Results showed that, compared with the CK, long-term application of organic manure, especially the combination of mineral fertilizers and organic manure significantly increased the organic SOC and TN in the surface soil. Application of mineral fertilizers plus organic manure with conventional (NPM) and high application (N2P2M2) rate increased SOC significantly by 24. 6% and 25.1% , and TN by 29.5% and 32.8%, respectively. However, there was no significant difference among the treatments for SOC and TN at the subsurface. Compared with the CK (CKh), mineral fertilizer plus organic manure (NPM and N2P2M2) did not only increase the soil microbial biomass carbon (SMBC) and nitrogen (SMBN) , dissolved organic carbon (DOC) and nitrogen (DN), but also significantly increased the ratio of SMBC and DOC to SOC, SMBN and TN to TN. Application of the NPM and N2P2M2 increased the value of SMBC/SOC by 0.36 to 0.59 and SMBN/TN by 1.21 to 1.95 percentage points, respectively. The value of DOC/SOC and DN/TN ranged from 0.53% to 0.72% and 1.41% to 1.78%, respectively. This result indicated that SMBC, SMBN, DOC, DN and SMBC/ SOC, SMBN/TN, DOC/SOC, DN/TN were more sensitive than SOC and TN to long-term fertilization in the soil profile, and were better indicators for the impact of long-term fertilization soil fertility. The concluded that the application of manure especially manure plus mineral fertilizers can increase soil nutrients activity in the surface and subsurface black soil, acting as a helpful practice to improve soil fertility and the ability of nutrient supply, while it may cause potential environment pollution on carbon and nitrogen loss in the agroecosystem.

Preconditioning of intravenous parecoxib attenuates focal cerebral ischemia/reperfusion injury in rats.

BACKGROUND: Several studies suggest that cyclooxygenase-2 (COX-2) contributes to the delayed progression of ischemic brain damage. This study was designed to investigate whether COX-2 inhibition with parecoxib reduces focal cerebral ischemia/reperfusion injury in rats. METHODS: Ninety male Sprague-Dawley rats were randomly assigned to three groups: the sham group, ischemia/reperfusion (I/R) group and parecoxib group. The parecoxib group received 4 mg/kg of parecoxib intravenously via the vena dorsalis penis 15 minutes before ischemia and again at 12 hours after ischemia. The neurological deficit scores (NDSs) were evaluated at 24 and 72 hours after reperfusion. The rats then were euthanized. Brains were removed and processed for hematoxylin and eosin staining, Nissl staining, and measurements of high mobility group Box 1 protein (HMGB1) and tumor necrosis factor-α (TNF-α) levels. Infarct volume was assessed with 2,3,5-triphenyltetrazolium chloride (TTC) staining. RESULTS: The rats in the I/R group had lower NDSs (P < 0.05), larger infarct volume (P < 0.05), lower HMGB1 levels (P < 0.05), and higher TNF-α levels (P < 0.05) compared with those in the sham group. Parecoxib administration significantly improved NDSs, reduced infarct volume, and decreased HMGB1 and TNF-α levels (P < 0.05). CONCLUSIONS: Pretreatment with intravenous parecoxib was neuroprotective. Its effects may be associated with the attenuation of inflammatory reaction and the inhibition of inflammatory mediators.