Isolation and characterization of a bio-agent antagonistic to diatom, <i>Stephanodiscus hantzschii</i>

Kang, Y.-H.,Kim, J.-D.,Kim, B.-H.,Kong, D.-S.,Han, M.-S. Blackwell Science Ltd 2005 Journal of applied microbiology Vol.98 No.5

<P>Abstract</P><P>Aims: </P><P>Identification of bacterium HYK0203-SK02 and its lysis of <I>Stephanodiscus hantzschii</I>.</P><P>Methods and Results: </P><P>In an effort to identify a bio-agent capable of controlling <I>S. hantzschii</I> blooms, we used the algal lawn method to identify 76 bacteria in relevant water samples. Of these, the seven isolate showed algicidal activity against <I>S. hantzschii</I>; isolate HYK0203-SK02 exhibited the strongest algicidal activity, and was used for further analysis. 16S rDNA sequencing of this isolate allowed us to identify HYK0203-SK02 as a strain of <I>Pseudomonas putida</I> (99·2%). Growth of <I>S. hantzschii</I> was strongly suppressed by bacteria in all growth phases, with the strongest algicidal activity noted against diatoms in the exponential stage (5–18 days). Host range assays revealed that isolate HYK0203-SK02 also strongly inhibited the growth of <I>Microcystis aeruginosa</I>, but stimulated growth of the diatom <I>Cyclotella</I> sp., which has a similar structure to that of <I>S. hantzschii</I>. Biochemical assays revealed that the algicidal substance seemed to be localized in the cytoplasmic membrane of this newly identified algicidal bacterium.</P><P>Conclusion: </P><P>The algicidal bacteria <I>P. putida</I> HYK0203-SK02 caused cell lysis and death of not only diatom <I>S. hantzschii</I> but also cyanobacteria <I>M. aeruginosa</I>, dramatically. Algicidal substance might be located at the compartment of cytoplasmic membrane.</P><P>Significance and Impact of the Study: </P><P>Taken together, our results indicate that <I>P. putida</I> HYK0203-SK02 may be a potential bio-agent for future use in controlling freshwater diatomic blooms.</P>

Glycyrrhizic acid affords robust neuroprotection in the postischemic brain via anti-inflammatory effect by inhibiting HMGB1 phosphorylation and secretion

Kim, S.W.,Jin, Y.,Shin, J.H.,Kim, I.D.,Lee, H.K.,Park, S.,Han, P.L.,Lee, J.K. Blackwell Science ; Academic Press 2012 Neurobiology of disease Vol.46 No.1

High mobility group box 1 (HMGB1) is an endogenous danger signal molecule. In a previous report, we showed that HMGB1 is massively released during NMDA-induced acute damaging process in the postischemic brain and triggers inflammatory processes, like microglial activation. siRNA-mediated HMGB1 knockdown markedly reduced infarct volumes, confirming the crucial role played by HMGB1 in the postischemic brain. In the present study, we showed neuroprotective effects of glycyrrhizin (GL) in the postischemic rat brain after middle cerebral artery occlusion (MCAO). GL, a triterpene present in the roots and rhizomes of licorice, Glycyrrhiza glabra, has been shown to have anti-inflammatory and anti-viral effects. It has been reported that GL binds directly to HMGB1, and inhibits its chemoattractant and mitogenic activities. The administration of GL (10mg/kg) intravenously at 3 or 6h after MCAO reduced infarct volumes to 12.9+/-4.2% and 46.2+/-9.9%, respectively, of untreated control. This neuroprotective effect was accompanied by improvements in motor impairment and neurological deficits and suppressions of microglia activation and proinflammatory cytokine induction. Interestingly, GL almost completely blocked HMGB1 secretion in the postischemic brain and in lipopolysaccharide (LPS)-treated microglia cells. Furthermore, HMGB1 phosphorylation, which is the initial step for HMGB1 secretion, and the interaction between HMGB1 and protein kinase C (PKC) or calcium/calmodulin-dependent protein kinase IV (CaMKIV) were suppressed dose-dependently by GL. Here, we hypothesized that the blockage for the putative phosphorylation sites in HMGB1 by GL might be attributed to this suppression. In addition to the anti-inflammatory effects, we found that GL has anti-excitotoxic and anti-oxidative effects in neurons. Together these results indicate that GL has neuroprotective efficacy in the postischemic brain via its anti-inflammatory, anti-excitotoxic, and anti-oxidative effects and in particular, it exerts anti-inflammatory effect, at least in part, by inhibiting HMGB1 secretion.

Neuroprotection by urokinase plasminogen activator in the hippocampus

Cho, E.,Lee, K.J.,Seo, J.W.,Byun, C.J.,Chung, S.J.,Suh, D.C.,Carmeliet, P.,Koh, J.Y.,Kim, J.S.,Lee, J.Y. Blackwell Science ; Academic Press 2012 Neurobiology of disease Vol.46 No.1

Tissue plasminogen activator (tPA) and urokinase plasminogen activator (uPA), which are both used for thrombolytic treatment of acute ischemic stroke, are serine proteases that convert plasminogen to active plasmin. Although recent experimental evidences have raised controversy about the neurotoxic versus neuroprotective roles of tPA in acute brain injury, uPA remains unexplored in this context. In this study, we evaluated the effect of uPA on neuronal death in the hippocampus of mice after kainate-induced seizures. In the normal brain, uPA was localized to both nuclei and cytosol of neurons. Following severe kainate-induced seizures, uPA completely disappeared in degenerating neurons, whereas uPA-expressing astrocytes substantially increased, suggesting reactive astrogliosis. uPA-knockout mice were more vulnerable to kainate-induced neuronal death than wild-type mice. Consistent with this, inhibition of uPA by intracerebral injection of the uPA inhibitor UK122 increased the level of neuronal death. In contrast, prior administration of recombinant uPA significantly attenuated neuronal death. Collectively, these results indicate that uPA renders neurons resistant to kainate-induced excitotoxicity. Moreover, recombinant uPA suppressed cell death in primary cultures of hippocampal neurons exposed to H<SUB>2</SUB>O<SUB>2</SUB>, zinc, or various excitotoxins, suggesting that uPA protects against neuronal injuries mediated by the glutamate receptor, or by oxidation- or zinc-induced death signaling pathways. Considering that tPA may facilitate neurodegeneration in acute brain injury, we suggest that uPA, as a neuroprotectant, might be beneficial for the treatment of acute brain injuries such as ischemic stroke.

Neuroprotective effect of a cell-free extract derived from human adipose stem cells in experimental stroke models

Jeon, D.,Chu, K.,Lee, S.T.,Jung, K.H.,Ban, J.J.,Park, D.K.,Yoon, H.J.,Jung, S.,Yang, H.,Kim, B.S.,Choi, J.Y.,Kim, S.H.,Kim, J.M.,Won, C.H.,Kim, M.,Lee, S.K.,Roh, J.K. Blackwell Science ; Academic Press 2013 Neurobiology of disease Vol.54 No.-

A recent study suggested that a cell-free extract of human adipose stem cells (hASCs-E) has beneficial effects on neurological diseases by modulating the host environment. Here, we investigated the effects of hASCs-E in several experimental models of stroke in vitro (oxygen and glucose deprivation, OGD) and in vivo (transient or permanent focal cerebral ischemia and intracerebral hemorrhage, ICH). Ischemia was induced in vitro in Neuro2A cells, and the hASCs-E was applied 24h before the OGD or concurrently. Focal cerebral ischemia was induced by unilateral intraluminal thread occlusion of the middle cerebral artery (MCA) in rats for 90min or permanently, or by unilateral MCA microsurgical direct electrocoagulation in mice. The ICH model was induced with an intracerebral injection of collagenase in rats. The hASCs-E was intraperitoneally administered 1h after the stroke insults. Treatment of the hASCs-E led to a substantially high viability in the lactate dehydrogenase and WST-1 assays in the in vitro ischemic model. The cerebral ischemic and ICH model treated with hASCs-E showed decreased ischemic volume and reduced brain water content and hemorrhage volume. The ICH model treated with hASCs-E exhibited better performance on the modified limb placing test. The expression of many genes related to inflammation, immune response, and cell-death was changed substantially in the ischemic rats or neuronal cells treated with the hASCs-E. These results reveal a neuroprotective role of hASCs-E in animal models of stroke, and suggest the feasible application of stem cell-based, noninvasive therapy for treating stroke.

Autophagy activation and neuroprotection by progesterone in the G93A-SOD1 transgenic mouse model of amyotrophic lateral sclerosis

Kim, J.,Kim, T.Y.,Cho, K.S.,Kim, H.N.,Koh, J.Y. Blackwell Science ; Academic Press 2013 Neurobiology of disease Vol.59 No.-

Progesterone (PG) exerts neuroprotective effects under conditions such as brain ischemia, traumatic brain injury, and spinal cord injury. Previously, we reported that PG activates autophagy, a potential neuroprotective mechanism, in cortical astrocytes. In the present study, we explored the possibility that PG, by activating autophagy in spinal cord cells, protects against motoneuron degeneration in transgenic (Tg) mice expressing the human G93A-SOD1 (superoxide dismutase 1) mutant, a model of amyotrophic lateral sclerosis. PG treatment increased autophagic flux in G93A-SOD1 Tg spinal cord astrocyte cultures and mice. In addition, PG treatment reduced mutant SOD1 protein levels and motoneuronal death. Inhibition of autophagy with 3-methyladenine (3MA) reversed these PG effects, indicating that activation of autophagy contributed to the PG neuroprotection. PG effects in vivo were tested by intraperitoneally injecting male G93A-SOD1 Tg mice with different doses of PG (2, 4, or 8mg/kg) or vehicle from 70days of age until death. Measurements of motor functions using rota-rod tests showed that the onset of symptoms was not different among groups, but the progression of motor dysfunction was significantly delayed in the PG-treated group compared with the vehicle control group. The average lifespan was also prolonged in the PG-injected group. Histological examinations revealed that PG treatment substantially reduced the death of spinal motoneurons at 14weeks of age with a concomitant decrease in mutant SOD1 levels. Our results demonstrated that PG delays neurodegenerative progress in G93A-SOD1 transgenic mice, possibly through activation of autophagy in the spinal cord.

Copper/zinc chelation by clioquinol reduces spinal cord white matter damage and behavioral deficits in a murine MOG-induced multiple sclerosis model

Choi, B.Y.,Jang, B.G.,Kim, J.H.,Seo, J.N.,Wu, G.,Sohn, M.,Chung, T.N.,Suh, S.W. Blackwell Science ; Academic Press 2013 Neurobiology of disease Vol.54 No.-

The present study aimed to evaluate the therapeutic potential of clioquinol (CQ), a metal chelator, on multiple sclerosis pathogenesis. Experimental autoimmune encephalomyelitis was induced by immunization with myelin oligodendrocyte glycoprotein (MOG(35-55)) in female mice. Three weeks after the initial immunization, demyelination and immune cell infiltration in the spinal cord were analyzed. CQ (30mg/kg) was given by gavage once per day for the entire experimental course. CQ profoundly reduced the daily clinical score and incidence rate of EAE mice. The CQ-mediated inhibition of the clinical course of EAE was accompanied by suppression of demyelination and reduced infiltration by encephalitogenic immune cells including CD4, CD8, CD20 and F4/80 positive cells. CQ also remarkably inhibited EAE-associated BBB disruption and MMP-9 activation. Autophagy contributes to clearance of aggregated proteins in astrocytes and neurons. The present study found that EAE increased the induction of autophagy and CQ further increased this expression. Furthermore, the present study found that post-treatment with CQ also reduced the clinical score of EAE and spinal cord demyelination. These results demonstrate that CQ inhibits the clinical features and neuropathological changes associated with EAE. The present study suggests that transition metals may be involved in several steps of multiple sclerosis pathogenesis.

Multilocus sequence typing for the analysis of clonality among Candida albicans strains from a neonatal intensive care unit.

Song, Eun Song,Shin, Jong Hee,Jang, Hee-Chang,Choi, Min Ji,Kim, Soo Hyun,Bougnoux, Marie-Elisabeth,d'Enfert, Christophe,Choi, Young Youn Blackwell Science ; BIOS scientific publishers Ltd 2014 Medical mycology Vol.52 No.6

<P>Nosocomial Candida albicans infections are a significant problem in neonatal intensive care units (NICUs). We investigated the clonality of C. albicans isolates recovered over an 8-year period from neonates at a NICU. We also validated multilocus sequence typing (MLST) compared with pulsed-field gel electrophoresis (PFGE) for the genotyping of C. albicans strains from the same NICU. A total of 43 clinical isolates (10 blood, 19 urine, and 14 other) were obtained from 43 neonates between 2005 and 2012. Clonal strains were defined as the isolation of two or more strains with identical or similar genotypes as determined with both MLST and PFGE. Using MLST, the 43 isolates yielded 25 diploid sequence types (DSTs) and 10 DSTs were shared by 28 isolates (65.1%). Among the 28 isolates sharing 10 DSTs, isolates from each of seven DSTs had the same or similar PFGE pattern. In addition, two sets of isolates that differed by MLST at only one locus had the same or similar PFGE pattern. Overall, when the MLST and PFGE results were combined, 22 isolates (51.2%) shared eight genotypes, suggesting clonal strains. Strains from each of seven genotypes (total, 19 isolates) were isolated among the 22 clonal strains within a 6-month period, whereas three strains of one genotype were obtained over a 3-year interval. Our findings suggest that horizontal transmission of C. albicans may occur more frequently than vertical transmission among NICU patients and that MLST appears to be a useful method for genotyping C. albicans strains isolated from NICU patients.</P>

Fmr1 deletion enhances and ultimately desensitizes CB₁ signaling in autaptic hippocampal neurons

Straiker, A.,Min, K.T.,Mackie, K. Blackwell Science ; Academic Press 2013 Neurobiology of disease Vol.56 No.-

Fragile X Syndrome (FXS) is a heritable form of mental retardation caused by a non-coding trinucleotide expansion of the FMR1 gene leading to loss of expression of this RNA binding protein. Mutations in this gene are strongly linked to enhanced Group I metabotropic glutamate receptor (mGluR) signaling. A recent report found that mGluR5-dependent endogenous cannabinoid signaling is enhanced in hippocampal slices from fmr1 knockout mice, suggesting a link between FXS and cannabinoid signaling. Alterations in cannabinoid signaling have an impact on learning and memory and may therefore be linked to some aspects of the FXS phenotype. We have used autaptic hippocampal neurons cultured from fmr1 knockout mice to further explore the interaction between endocannabinoid signaling and FMRP. These neurons express several robust forms of retrograde endocannabinoid signaling including depolarization induced suppression of excitation (DSE) and a metabotropic form (MSE) that results from Group I mGluR activation. We now report that young fmr1 neurons exhibit considerably enhanced DSE, likely via increased production of 2-AG, rather than enhanced mGluR-MSE. We find that depolarizations as brief as 50ms, which do not ordinarily produce DSE, routinely inhibited glutamate release. Furthermore, as neuronal cultures mature, CB<SUB>1</SUB>-receptor signaling strongly desensitizes. Our results suggest that loss of FMRP broadly affects the endocannabinoid signaling system, possibly through local 2-AG over production. Furthermore, the net effect of the loss of FMRP may actually be diminished cannabinoid signaling due to receptor desensitization as an adaptation to 2-AG overproduction.

Sitagliptin increases tau phosphorylation in the hippocampus of rats with type 2 diabetes and in primary neuron cultures

Kim, D.H.,Huh, J.W.,Jang, M.,Suh, J.H.,Kim, T.W.,Park, J.S.,Yoon, S.Y. Blackwell Science ; Academic Press 2012 Neurobiology of disease Vol.46 No.1

Increasing evidence supports an association between Alzheimer's disease (AD) and diabetes. In this context, anti-diabetic agents such as rosiglitazone and glucagon-like peptide (GLP)-1 have been reported to reduce pathologies associated with AD, including tau hyperphosphorylation, suggesting that such agents might be used to treat AD. One such anti-diabetic agent is sitagliptin, which acts through inhibition of dipeptidyl peptidase (DPP)-IV to increase GLP-1 levels. Given this action, sitagliptin would be predicted to reduce AD pathology. Accordingly, we investigated whether sitagliptin is effective in attenuating AD pathologies, focusing on tau phosphorylation in the OLETF type 2 diabetic rat model. Unexpectedly, we found that sitagliptin was not effective against pathological tau phosphorylation in the hippocampus of OLETF type 2 diabetes rats, and instead aggravated it. This paradoxically increased tau phosphorylation was attributed to activation of the tau kinase, GSK3β (glycogen synthase kinase 3β). Sitagliptin also increased ser-616 phosphorylation of the insulin receptor substrate (IRS)-1, suggesting increased insulin resistance in the brain. These phenomena were recapitulated in primary rat cortical neurons treated with sitagliptin, further confirming sitagliptin's effects on AD-related pathologies in neurons. These results highlight the need for caution in considering the use of sitagliptin in AD therapy.

PCV12 THE ECONOMIC BURDEN OF ATRIAL FIBRILLATION AND FLUTTER IN KOREA

Jo, M.,Kim, E.,Kim, H.,Yun, S. Blackwell Science 2010 Value in health Vol.13 No.7