ABSTRACT
Aberrant modulation of mitochondrial dynamic network, which shifts the balance of fusion and fission towards fission, is involved in brain damage of various neurodegenerative diseases including Parkinson's disease, Huntington's disease and Alzheimer's disease. A recent research has shown that the inhibition of mitochondrial fission alleviates early brain injury after experimental subarachnoid hemorrhage, however, the underlying molecular mechanisms have remained to be elucidated. This study was undertaken to characterize the effects of the inhibition of dynamin-related protein-1 (Drp1, a dominator of mitochondrial fission) on blood-brain barrier (BBB) disruption and neuronal apoptosis following SAH and the potential mechanisms. The endovascular perforation model of SAH was performed in adult male Sprague Dawley rats. The results indicated Mdivi-1(a selective Drp1 inhibitor) reversed the morphologic changes of mitochondria and Drp1 translocation, reduced ROS levels, ameliorated the BBB disruption and brain edema remarkably, decreased the expression of MMP-9 and prevented degradation of tight junction proteins-occludin, claudin-5 and ZO-1. Mdivi-1 administration also inhibited the nuclear translocation of nuclear factor-kappa B (NF-κB), leading to decreased expressions of TNF-É, IL-6 and IL-1ß. Moreover, Mdivi-1 treatment attenuated neuronal cell death and improved neurological outcome. To investigate the underlying mechanisms further, we determined that Mdivi-1 reduced p-PERK, p-eIF2α, CHOP, cleaved caspase-3 and Bax expression as well as increased Bcl-2 expression. Rotenone (a selective inhibitor of mitochondrial complexes I) abolished both the anti-BBB disruption and anti-apoptosis effects of Mdivi-1. In conclusion, these data implied that excessive mitochondrial fission might inhibit mitochondrial complex I to become a cause of oxidative stress in SAH, and the inhibition of Drp1 by Mdivi-1 attenuated early brain injury after SAH probably via the suppression of inflammation-related blood-brain barrier disruption and endoplasmic reticulum stress-based apoptosis.
Subject(s)
Blood-Brain Barrier/drug effects , Dynamins/genetics , Mitochondria/drug effects , Mitochondrial Dynamics/drug effects , Quinazolinones/pharmacology , Subarachnoid Hemorrhage/drug therapy , Animals , Apoptosis/drug effects , Blood-Brain Barrier/metabolism , Claudin-5/genetics , Claudin-5/metabolism , Dynamins/antagonists & inhibitors , Dynamins/metabolism , Endoplasmic Reticulum Stress/drug effects , Interleukin-1beta/antagonists & inhibitors , Interleukin-1beta/genetics , Interleukin-1beta/metabolism , Interleukin-6/antagonists & inhibitors , Interleukin-6/genetics , Interleukin-6/metabolism , Male , Matrix Metalloproteinase 9/genetics , Matrix Metalloproteinase 9/metabolism , Mitochondria/genetics , Mitochondria/metabolism , Mitochondrial Dynamics/genetics , NF-kappa B/antagonists & inhibitors , NF-kappa B/genetics , NF-kappa B/metabolism , Occludin/genetics , Occludin/metabolism , Proto-Oncogene Proteins c-bcl-2/agonists , Proto-Oncogene Proteins c-bcl-2/genetics , Proto-Oncogene Proteins c-bcl-2/metabolism , Rats , Rats, Sprague-Dawley , Reactive Oxygen Species/antagonists & inhibitors , Reactive Oxygen Species/metabolism , Subarachnoid Hemorrhage/genetics , Subarachnoid Hemorrhage/mortality , Subarachnoid Hemorrhage/pathology , Subarachnoid Space/drug effects , Subarachnoid Space/metabolism , Subarachnoid Space/pathology , Survival Analysis , Tumor Necrosis Factor-alpha/antagonists & inhibitors , Tumor Necrosis Factor-alpha/genetics , Tumor Necrosis Factor-alpha/metabolism , Zonula Occludens-1 Protein/genetics , Zonula Occludens-1 Protein/metabolism , bcl-2-Associated X Protein/antagonists & inhibitors , bcl-2-Associated X Protein/genetics , bcl-2-Associated X Protein/metabolismABSTRACT
Removal of gaseous chlorobenzene (CB) by a biotrickling filter (BTF) filled with modified ceramics and multi-surface hollow balls during gas-liquid mass transfer at the steady state was by microbial degradation rather than dissolution in the spray liquid or emission into the atmosphere. The BTF was flexible and resistant to the acid environment of the spray liquid, with the caveat that the spray liquid should be replaced once every 6-7 days. The BTF, loaded with Lysinibacillus fusiformis, performed well for purification of high-loading CB gas. The maximum CB gas inlet loading rate, 103 g m(-3) h(-1), CB elimination capacity, 97 g m(-3) h(-1), and CB removal efficiency, 97.7 %, were reached at a spray liquid flow rate of 27.6 ml min(-1), an initial CB concentration of up to 1,300 mg m(-3), and an empty bed retention time of more than 45 s.
Subject(s)
Bacillaceae/metabolism , Chlorobenzenes/isolation & purification , Filtration/instrumentation , Air Pollutants/isolation & purification , Biodegradation, Environmental , Bioreactors/microbiology , Filtration/methodsABSTRACT
<p><b>OBJECTIVE</b>To investigate the plasma Big endothelin-1 levels in patients with gastric carcinoma before and after radical gastrectomy, and explore its clinical significance.</p><p><b>METHODS</b>One hundred and six patients with gastric carcinoma and 20 controls were enrolled. The Big ET-1 plasma levels were examined by enzyme-linked immuno absorbent assay before and on the 1st, 3rd, and 10th day after curative surgery, and then were tested every 3 months in the patients with advanced gastric cancer.</p><p><b>RESULTS</b>All patients, except those with stage I gastric cancer, had significantly higher mean plasma Big ET-1 levels compared with normal controls (P=0.000). Higher plasma Big ET-1 levels were associated with lymph node metastasis (P=0.020) and serosal infiltration (P=0.035). The plasma Big Endothelin-1 levels were markedly increased on the first post-operative day (1st POD) in all patients,but decreased on the 3rd POD with no significant difference compared to the preoperative levels. On the 10th POD, the patients with stage I and II gastric cancer showed marked reduction in plasma Big ET-1 levels (P=0.010 and P=0.000, respectively), whereas no significant difference was observed in stage III and IV patients. During the follow-up, the plasma Big ET-1 levels just before recurrence in stage II patients were significantly higher compared with the levels on the 10th POD (P=0.011).</p><p><b>CONCLUSIONS</b>Plasma Big ET-1 might be a reliable marker to determine the severity of gastric carcinoma. Monitoring plasma Big ET-1 levels after curative resection in stage II gastric cancer patients is valuable to predict recurrence.</p>
