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Antonia Janssen Sebastian Fiebiger Helena Bros Laura Hertwig Silvina Romero-Suarez Isabell Hamann Coralie Chanvillard Judith Bellmann-Strobl Friedemann Paul Jason M. Millward Carmen Infante-Duarte 《PloS one》2015,10(6)
We previously demonstrated that epigallocatechin-3-gallate (EGCG) synergizes with the immunomodulatory agent glatiramer acetate (GA) in eliciting anti-inflammatory and neuroprotective effects in the relapsing-remitting EAE model. Thus, we hypothesized that mice with chronic EAE may also benefit from this combination therapy. We first assessed how a treatment with a single dose of GA together with daily application of EGCG may modulate EAE. Although single therapies with a suboptimal dose of GA or EGCG led to disease amelioration and reduced CNS inflammation, the combination therapy had no effects. While EGCG appeared to preserve axons and myelin, the single GA dose did not improve axonal damage or demyelination. Interestingly, the neuroprotective effect of EGCG was abolished when GA was applied in combination. To elucidate how a single dose of GA may interfere with EGCG, we focused on the anti-inflammatory, iron chelating and anti-oxidant properties of EGCG. Surprisingly, we observed that while EGCG induced a downregulation of the gene expression of heme oxygenase-1 (HO-1) in affected CNS areas, the combined therapy of GA+EGCG seems to promote an increased HO-1 expression. These data suggest that upregulation of HO-1 may contribute to diminish the neuroprotective benefits of EGCG alone in this EAE model. Altogether, our data indicate that neuroprotection by EGCG in chronic EAE may involve regulation of oxidative processes, including downmodulation of HO-1. Further investigation of the re-dox balance in chronic neuroinflammation and in particular functional studies on HO-1 are warranted to understand its role in disease progression. 相似文献
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D Roode R Liebschutz S Maulik T Friedemann D Benton D Kristofferson 《Nucleic acids research》1988,16(5):1857-1859
BIONET has made considerable progress in developing communication links among molecular biologists and biochemists worldwide. We describe these efforts and also note the many new enhancements to the BIONET system itself. 相似文献
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A ground section was prepared from a lower right M3 attributed to Gigantopithecus blacki as close as possible to axial plane of the mesial cusps. Daily cross striations were imaged, measured and counted in each cusp using polarised light microscopy. Long-period striae of Retzius were counted in the lateral enamel and their periodicity determined from counts and measurements of daily cross striations between adjacent striae. Cross striation spacings in the cusps were between 3.8 microm at the enamel dentine junction and 6 microm close to the enamel surface. Cuspal enamel formation times were long (800 days in the protoconid and 620 days in the metaconid). Linear enamel thickness was as much as 3.75 mm in the protoconid. There were 63 and 61 long-period striae of Retzius in the mesial aspects of the lateral enamel and the periodicity was 11 days. Lateral enamel formation took 1493 and 1291 days and when summed with cuspal enamel formation times totalled 4 years in the protoconid and 3.5 in the metaconid. Relative enamel thickness was 23, calculated through the mesial cusps. This falls short of that in the so-called 'thick hyper-thick' enamel described in 'robust' australopithecines to which Gigantopithecus blacki has previously been compared in both its dental and mandibular morphology. With respect to enamel thickness, therefore, Gigantopithecus blacki falls squarely among an increasingly large number of Miocene hominoids that can all be described as having 'thick enamel'. 相似文献