Neuroprotection of quercetin on central neurons against chronic high glucose through enhancement of Nrf2/Glo-1 mediated by phosphorylation regulation

OBJECTIVE To investigate the neuroprotective effects of quercetin on central neurons against chronic high glucose in central neurons,in relation to Nrf2/ARE/Glo-1 activation.METHODS SH-SY5Y cells were cultured with high glucose(HG,70 mmol·L^(-1)),4-fold of the normal glucose(17.5 mmol·L^(-1)).Quercetin was set three concentrations(5,10,20μmol·L^(-1)),with Nrf2 activator sulforaphane(SFN)as a positive group(2.5μmol·L^(-1)).After 72 h,cells were collected for glyoxalase 1(Glo-1)activity and GSH level were by spectrophotometry;advanced glycation end-products(AGEs)as well as nuclear Nrf2 and p-Nrf2 levels by immunofluorescence;Glo-1,γ-glutamycysteine synthase(γ-GCS),Nrf2 and p-Nrf2 protein levels by Western blotting,and Glo-1 andγ-GCS m RNA levels by real-time qP CR.RESULTS Quercetin increased the cell viability of SH-SY5Y cells,and upregulated the levels of Glo-1 activity,protein,and m RNA in SH-SY5Y cells cultured with HG,accompanied by the elevated levels of glutathione,a cofactor of Glo-1 activity,and the reduced levels of AGEs.Meanwhile,quercetin could increase p-Nrf2 and Nrf2 levels in nucleus as well as p-Nrf2 levels in cytosol of SH-SY5Y cells exposed to chronic HG,accompanied by the elevated protein expression and m RNA levels ofγ-GCS,a known target gene of Nrf2/ARE signaling.Moreover,a PKC activator or a p38MAPK inhibitor pretreatment could significantly increase the protein expression ofγ-GCS in HG condition,but an alkylating agent for sulfydryl of cysteine in Keap 1,a negative regulator of Nrf2,pretreatment only showed an increased tendency ofγ-GCS protein,compared with without pretreatment;however,after pretreatment with those tool drugs,co-treatment with quercetin and HG had similar results to those of single tool drug pretreatment followed by HG exposure.CONCLUSION Firstly,quercetin can enhance Glo-1 function in central neurons,which is mediated by activation of Nrf2/ARE pathway,then exerts the neuroprotection against HG induced damage;moreover,PKC and p38 MAPK pathways may be involved in Nrf2 inactivation in chronic HG condition.

High-continuity genome assembly of the jellyfish Chrysaora quinquecirrha

DEAR EDITOR,The Atlantic sea nettle(Chrysaora quinquecirrha)has an important evolutionary position due to its high ecological value.However,due to limited sequencing technologies and complex jellyfish genomic sequences,the current C.quinquecirrha genome assembly is highly fragmented.Here,we used the most advanced high-throughput chromosome conformation capture(Hi-C)technology to obtain high-coverage sequencing data of the C.quinquecirrha genome.We then anchored these data to the previously published contig-level assembly to improve the genome.Finally,a high-continuity genome sequence of C.quinquecirrha was successfully assembled,which contained 1882 scaffolds with a N50 length of 3.83 Mb.The N50 length of the genome assembly was 5.23 times longer than the previously released one,and additional analysis revealed that it had a high degree of genomic continuity and accuracy.Acquisition of the high-continuity genome sequence of C.quinquecirrha not only provides a basis for the study of jellyfish evolution through comparative genomics but also provides an important resource for studies on jellyfish growth and development.

Sleep-associated movement disorders and the risk of cardiovascular disease: A systematic review and metaanalysis

AIM:To investigate whether an association exists between sleep-associated movement disorders and cardiovascular disease(CVD).METHODS:Several studies have observed the relationship of sleep-associated movement disorders such as restless legs syndrome(RLS)and periodic limb movements during sleep with CVD,but the results were still contradictory.We performed an extensive literature search on Pub Med,Medline and Web of Science published from inception to December 2014.Additional studies were manually searched from bibliographies of retrieved studies.Meta-analyses were conducted with Stata version 12.0(Stata Corp,College Station,Texas).Pooled odds ratios(ORs)and 95%CIs were calculated to assess the strength of association using the random effects model.Sensitivity and subgroup analyses were performed to explore the underlying sources of heterogeneity.The publication bias was detected using Egger’s test and Begg’s test.RESULTS:A total of 781 unique citations were indentified from electronic databases and 13 articles in English were finally selected.Among these studies,nine are cohort studies;two are case-control studies;and two are cross-sectional studies.The results showed that the summary OR of CVD associated with sleepassociated movement was 1.51(95%CI:1.29-1.77)in a random-effects model.There was significant heterogeneity between individual studies(P for heterogeneity=0.005,I2=57.6%).Further analysis revealed that a large-scale cohort study may account for this heterogeneity.A significant association was also found between RLS and CVD(OR=1.54,95%CI:1.24-1.92).In a fixed-effects model,we determined a significant relationship between sleep-associatedmovement disorders and coronary artery disease(CAD)(OR=1.34,95%CI:1.16-1.54;P for heterogeneity=0.210;I2=30.0%).Our meta-analysis suggests that sleep-associated movement disorders are associated with prevalence of CVD and CAD.CONCLUSION:This finding indicates that sleep-associated movement disorders may prove to be predictive of underlying CVD.