Up-regulation of FOS-like antigen 1 contributes to neuronal apoptosis in the cortex of rat following traumatic brain injury.

Neuronal apoptosis is an important process of secondary brain injury which is induced by neurochemical signaling cascades after traumatic brain injury (TBI). Present study was designed to investigate whether FOS-like antigen 1 (Fra-1) is involved in the neuronal apoptosis. Western blot analysis and immunohistochemistry in a rat TBI model revealed a significant increase in the expression of Fra-1 in the ipsilateral brain cortex, which was in parallel with increase in the expression of active caspase-3. With immunofluorescence double-labeling, Fra-1 was colocalized with active caspase-3 and with NeuN, a neuronal marker. In an in vitro cell injury model, H2O2 exposure induced cell apoptosis and reduced cell viability and at the same time, a similar increased expression of active caspase-3, p53 and Fra-1 was found in PC12 cells. Down-regulation of Fra-1 through transfection with Fra-1 siRNA remarkably elevated cell viability, reduced the expression of active caspase-3 and p53, and decreased apoptosis of PC12 cells after H2O2 exposure. Taken together, present findings suggest that Fra-1 may be involved in the induction of neuronal apoptosis through up-regulating p53 signaling pathway and that this action may contribute to the secondary neuropathological process after TBI.

Spatial and temporal variation of soil organic carbon in the North China Plain.

The organic carbon, permeability test, grain size, chemical composition, and mineral composition were analyzed for 147 samples collected from the Luan River catchment, Hebei province, China, to quantitatively characterize the effects of land use, climate change, sedimentary environment, mineral composition, and chemical composition on the spatial and temporal variation of soil organic carbon (SOC). The results indicate that there was higher SOC content and stronger variation in the south plain than in the northern low mountain. The effects of land use, climate change, and sedimentary environment on SOC distribution were greater than the effects of mineral composition and chemical composition. The cropping systems in the Luan River catchment resulted in significant difference in SOC concentration between the south plain and north mountain. The precipitation mainly transmitted its effects through the sedimentary environment to SOC, which caused the stronger temporal variation in SOC from June to October in the south plain. The north mountain did not have significant temporal variation because of the lower hydraulic conductivity of the sedimentary sequence. The spatial variation of SOC was correlated with land use, and their temporal variation was attributed to climate change and sedimentary environment. Apart from land use, the decision maker can also affect the organic carbon mineral and sequence through the sedimentary environment.

Hck Promotes Neuronal Apoptosis Following Intracerebral Hemorrhage.

The hematopoietic cell kinase (Hck) is a member of the Src family protein kinases which regulates many signal transduction pathways including cell growth, proliferation, differentiation, migration, and apoptosis. However, the expression and function of Hck after intracerebral hemorrhage (ICH) are unknown. Western blot, immunohistochemistry, and immunofluorescence showed that Hck was obviously up-regulation in neurons adjacent to the hematoma after ICH. In addition, the temporary raise of Hck expression was paralleled with the expression of p53, Bax, and active caspase-3, suggesting that Hck was involved in neuronal apoptosis. Hck siRNA dramatically decrease hemin-induced expression of p53, Bax, and active caspase-3 as well as the amount of apoptotic SH-SY5Y cells in vitro. Furthermore, Hck interacted with p53. Hence, Hck might promote neuronal apoptosis via p53 signaling pathway after ICH.

Upregulated Expression of Karyopherin α2 is Involved in Neuronal Apoptosis Following Intracerebral Hemorrhage in Adult Rats.

Karyopherin α2 (KPNA2) plays a central role in nucleocytoplasmic transport. It is involved in controlling the flow of genetic information and the modulation of diverse cellular activities. Here we explored the KPNA2's roles during the pathophysiological processes of intracerebral hemorrhage (ICH). An ICH rat model was built and evaluated according to behavioral testing. Using Western blot, immunohistochemistry, and immunofluorescence, significant upregulation of KPNA2 was found in neurons in brain areas surrounding the hematoma following ICH. Increasing KPNA2 level was found to be accompanied by the upregulation of active caspase-3, Bax, and decreased expression of Bcl-2. Besides, KPNA2 co-localized well with active caspase-3 in neurons, indicating its potential role in neuronal apoptosis. What's more, knocking down KPNA2 by RNA-interference in PC12 cells reduced active caspase-3 expression. Thus, KPNA2 may play a role in promoting the brain secondary damage following ICH.

Complex of Lauric Acid Monoglyceride and Cinnamaldehyde Ameliorated Subclinical Necrotic Enteritis in Yellow-Feathered Broilers by Regulating Gut Morphology, Barrier, Inflammation and Serum Biochemistry.

This experiment investigated the benefits of plant essential oil (EO) composed with lauric acid monoglyceride and cinnamaldehyde on necrotic enteritis-challenged broilers. A total of 180 1-day-old healthy yellow-feathered broilers were randomly divided into 4 groups with 3 replicates of 15 chicks each. The experimental groups were as follows: the control group (CON) was fed with the basal diet and was not challenged by Eimeria acervulina (EA) and Clostridium perfringens (CP); CPEA group was also fed with a basal diet, but infected with CP and EA; CPEA_EO350 group and CPEA_EO500 group were fed with a basal diet supplemented with 350 and 500 mg/kg EO, respectively, and all infected with CP and EA. On the 7th day, each bird in the CPEA group, CPEA_EO350 group and CPEA_EO500 group was orally administrated with 1 mL Eimeria acervulina containing 5000 oocytes/mL, and the birds of the CON group were orally administrated with 1 mL normal saline. From the 15th day, 1 mL of CP type A CVCC-2030 strain (about 5 × 108 cfu/mL) was orally inoculated into each bird of the CPEA, CPEA_EO350 and CPEA_EO500 groups for three consecutive days. Similarly, the CON group was orally given 1 mL of normal saline. The CPEA stimulation reduced the average daily gain (ADG) of broilers, increased the feed-to-gain ratio (F:G), and increased the intestinal lesions of the broilers (p < 0.01), indicating that CPEA stimulation was clinically successful. Compared with the CPEA group, the ADG of CPEA_EO350 and CPEA_EO500 increased, the F:G decreased (p < 0.01), and the intestinal score of CPEA_EO500 decreased (p < 0.01). The expression of the tight junction protein of the jejunum and ileum on 21d was upregulated (p < 0.01), and the expression of jejunum inflammation factors TNF-α on 21d and jejunum and ileum inflammatory factor IL-6 on 28d were also downregulated. The CPEA_EO350 and CPEA_EO500 increased antioxidant capacity. To sum up, 350 and 500 mg/kg of lauric acid monoglyceride and cinnamaldehyde complex plant essential oils can improve ADG and F:G, improve intestinal morphology and the body's antioxidant capacity, and downregulate the expression of inflammatory factors. The concentration of 500 mg/kg performed even better.

Insights into Biodegradation Related Metabolism in an Abnormally Low Dissolved Inorganic Carbon (DIC) Petroleum-Contaminated Aquifer by Metagenomics Analysis.

In petroleum-contaminated aquifers, biodegradation is always associated with various types of microbial metabolism. It can be classified as autotrophic (such as methanogenic and other carbon fixation) and heterotrophic (such as nitrate/sulfate reduction and hydrocarbon consumption) metabolism. For each metabolic type, there are several key genes encoding the reaction enzymes, which can be identified by metagenomics analysis. Based on this principle, in an abnormally low dissolved inorganic carbon (DIC) petroleum-contaminated aquifer in North China, nine groundwater samples were collected along the groundwater flow, and metagenomics analysis was used to discover biodegradation related metabolism by key genes. The major new finding is that autotrophic metabolism was revealed, and, more usefully, we attempt to explain the reasons for abnormally low DIC. The results show that the methanogenesis gene, Mcr, was undetected but more carbon fixation genes than nitrate reduction and sulfate genes were found. This suggests that there may be a considerable number of autotrophic microorganisms that cause the phenomenon of low concentration of dissolved inorganic carbon in contaminated areas. The metagenomics data also revealed that most heterotrophic, sulfate, and nitrate reduction genes in the aquifer were assimilatory sulfate and dissimilatory nitrate reduction genes. Although there was limited dissolved oxygen, aerobic degrading genes AlkB and Cdo were more abundant than anaerobic degrading genes AssA and BssA. The metagenomics information can enrich our microorganic knowledge about petroleum-contaminated aquifers and provide basic data for further bioremediation.

[Microbial Community Distributions in Soils of an Oil Exploitation Site].

To design a reasonable and effective remediation scheme for soil in contaminated sites, it is necessary to understand the microbial communities in the soil. Samples were collected at different depths (0 cm to 400 cm) in four locations: one that was persistently contaminated and near an oil well, one that was historically contaminated in the middle of the site, one in a mud pit, and one in farmland. High-throughput sequencing of the V4 region of 16S rRNA in these samples was performed. In addition to physico-chemical properties of the soil, the α-diversity, species composition, and differences in species between groups of microorganisms were analyzed, and a principal coordinate analysis and canonical correlation analysis were conducted. Results showed that oil and salt contents in soils were the dominant factors affecting microbial community structure. Hydrocarbon-degrading microorganisms were abundant in oil-contaminated soils, whereas halophilic hydrocarbon-degrading microorganisms were present in soils with high salt contents. Therefore, hydrocarbon-degrading microorganisms might be useful in remediation of oil-contaminated sites.

USP11, Deubiquitinating Enzyme, Associated with Neuronal Apoptosis Following Intracerebral Hemorrhage.

Protein ubiquitination is a dynamic two-way process that can be reversed or regulated by deubiquitinating enzymes (DUB). USP11, located on the X chromosome, 6 is a member of USP subclass of the DUB family. Here, we demonstrate that USP11 may be involved in neuronal apoptosis in the processes of intracerebral hemorrhage (ICH). From the results of Western blot, immunohistochemistry, and immunofluorescence, we obtained a significant up-regulation of USP11 in neurons adjacent to the hematoma following ICH. Increasing USP11 level was found to be accompanied by the up-regulation of active caspase-3, Fas receptor (Fas), Fas ligand (FasL), and active caspase-8. Besides, USP11 co-localized well with active caspase-3 in neurons, indicating its potential role in neuronal apoptosis. What is more, knocking down USP11 by RNA-interference in PC12 cells reduced active caspase-3 expression. Thus, USP11 may play a role in promoting the brain secondary damage following ICH.

Inhibitory influence of ginsenoside Rb(3) on activation of strychnine-sensitive glycine receptors in hippocampal neurons of rat.

Whole-cell patch-clamp technique was used to investigate the effect of ginsenoside Rb(3) (Rb(3)), an active constituent of Panax ginseng, on glycine receptor activity in immature hippocampal neurons, which were dissociated acutely from hippocampal CA(1) area in Sprague-Dawley rats aging 10-14 days using the method of enzyme digestion with mechanical dissociation. As a result, glycine elicited an inward current (I(gly)) in a concentration-dependent manner in approximately 86% of those isolated neurons tested. This current was strychnine-sensitive. Rb(3) itself did not elicit any membrane currents. However, coapplication of Rb(3) inhibited peak current of I(gly). This depressant effect of Rb(3) varied with its concentrations. At a concentration of 0.1 micromol/L, ginsenoside Rb(3) had the most significant inhibition, with a net reduction of 31% in average. Moreover, the inhibition of I(gly) by Rb(3) did not depend on the membrane potential. Rb(3) (0.1 micromol/L) presented inhibitory effect on I(gly) mainly at higher glycine concentrations (>100 micromol/L), and decreased maximal glycine efficacy. This effect was the same as that of a non-competitive antagonist of glycine receptors. Finally, we found that Rb(3) prolonged the time constant of activation of I(gly). It is therefore suggested that ginsenoside Rb(3), possibly as a non-competitive antagonist, could inhibit strychnine-sensitive glycine current at a dose-dependent manner in acutely dissociated hippocampal CA(1) neurons of young rats, and decrease of affinity of glycine to receptors and delay of receptor activation may be involved in this inhibition. Inhibitory effect of ginsenoside Rb(3) on I(gly) is possibly one of the bases of many pharmacological actions of Panax ginseng.

Up-regulation of PSMB4 is associated with neuronal apoptosis after neuroinflammation induced by lipopolysaccharide.

Proteasomes are major intracellular extralysosomal organelle for protein degradation and a central source of antigenic peptides in the endogenous pathway. Proteasome beta-4 subunit (PSMB4) was recently identified as potential cancer driver genes in several tumors. However, information regarding its regulation and possible function in the central nervous system is still limited. The present study was designed to elucidate dynamic changes in PSMB4 expression and distribution in the cerebral cortex in a lipopolysaccharide (LPS)-induced neuroinflammation rat model. It was found that PSMB4 expression was increased significantly in apoptotic neurons in the brain cortex after LPS injection. Moreover, there was a concomitant up-regulation of active caspase-3, cyclin D1, and CDK4 in vivo and vitro studies. In addition, these three proteins in cortical primary neurons were decreased after knocking down PSMB4 by siRNA. Collectively, these results suggested that PSMB4 may be involved in neuronal apoptosis in neuroinflammation after LPS injection.

Antidepressant-like effects of auraptenol in mice.

Depression is a major psychiatric disorder affecting nearly 21% of the world population and imposes a substantial health burden on society. Current available antidepressants are not adequate to meet the clinical needs. Here we report that auraptenol, an active component of the traditional Chinese medicine, angelicae dahuricae radix, had antidepressant-like effects in mice models of depression. In mouse forced swimming test and tail suspension test, two validated models of depression, auraptenol dose-dependently decreased the immobility duration within the dose range of 0.05-0.4 mg/kg. In addition, the antidepressant-like effects of auraptenol was significantly averted by a selective serotonin 5-HT1A receptor antagonist WAY100635 (1 mg/kg). These doses that affected the immobile response did not affect locomotor activity. In summary, this study for the first time identified an active component from the herbal medicine angelicae dahuricae radix that possesses robust antidepressant-like efficacy in mice. These data support further exploration for the possibility of developing auraptenol as a novel antidepressant agent in the treatment of major depression disorders.