Effect of down—regulation of voltage—gated sodium channel Nav1.7 on activation of astrocytes and microglia in DRG in rats with cancer pain

AbstractObjectiveTo evaluate the effect of down-regulation of Nav1.7 on the activation of astrocytes and microglia in DRG of rats with cancer pain, and explore the transmission of the nociceptive information.MethodsLentiviral vector harboring RNAi sequence targeting the Nav1.7 gene was constructed, and Walker 256 breast cancer cell and morphine was injected to build the bone cancer pain model and morphine tolerance model in rats. Lentiviral vector was injected. Rats in each model were divided into 4 groups: model group, PBS group, vehicle group and LV-Nav1.7 group. The expression levels of GFAP and OX42 in dorsal root ganglia (DRG) were measured.ResultsAfter the animal model was built, the level of Nav1.7, GFAP and OX42 was improved obviously with the time prolonged, which was statistically significant (P<0.05). The expression level of GFAP and OX42 in the DRG in the LV-Nav1.7 group declined obviously compared to the model group, PBS group and vehicle group (P<0.05).ConclusionsIntrathecal injection of Navl.7 shRNA lentiviral vector can reduce the expression of Nav1.7 and inhibit the activation of astrocytes and microglia in DRG. The effort is also effective in morphine tolerance bone cancer pain model rats

2,4-Dibromo-6-tert-butyl­benzene-1,3-diol

In the title compound, C10H12Br2O2, a multiply substituted bromo­arene, the C—C—C angles within the aromatic ring are in the range 115.7 (7)-122.4 (7)°. In the crystal, mol­ecules are linked by O—H⋯O hydrogen bonds, but no π–π stacking is observed

Bis{2-eth­oxy-6-[2-(methyl­ammonio)ethyl­imino­meth­yl]phenolato}thio­cyanato­zinc(II) nitrate

In the title compound, [Zn(NCS)(C12H18N2O2)2]NO3, the ZnII ion is chelated by the phenolate O and imine N atoms from two zwitterionic Schiff base ligands and is also coordinated by the N atom of a thio­cyanate ligand, giving a distorted trigonal-bipyramidal geometry. Intra­molecular N—H⋯O hydrogen bonds are observed in the complex cation. The nitrate anions are linked to the complex cations through N—H⋯O hydrogen bonds

(Z)-1,3,4a-Trimethyl-5,5-diphenyl-6-oxa-1,3-diaza­bicyclo­[4.2.0]octane-2,4-dione

The title compound, C20H20N2O3, is a head-to-tail oxetane, one of the regioisomers obtained by the the Paternó–Büchi reaction of 1,3-dimethyl­thymine with benzophenone. The oxetane ring is folded, the dihedral angle between the C—O—C and C—C—C planes being 14.4 (2)°. The dihedral angle between the two phenyl rings is 64.3 (2)°. The pyrimidine ring adopts a boat conformation. The crystal structure involves weak C—H⋯O hydrogen bonds

Untargeted metabolomics of saliva in caries-active and caries-free children in the mixed dentition

ObjectiveTo compare the differences in salivary metabolites between caries-active and caries-free children in the mixed dentition, and explore their correlation with caries status.MethodsThe study involved 20 children (aged 8–9 years) in the mixed dentition, including 10 caries-active (aged 8.6 ± 0.49years) and 10 caries-free children(aged 8.5 ± 0.5years), with a male/female ratio of 1:1. The saliva samples were collected from all children. Metabolite extraction, LC-MS/MS-based untargeted metabolomics, qualitative and semi-quantitative analysis and bioinformatics analysis were performed to identify differential metabolites between the two sample groups. The differential metabolites identified were further analyzed in an attempt to find their correlations with caries status.ResultsIn the positive ion mode, a total of 1606 molecular features were detected in the samples of the two groups, 189 of which were differential metabolites when comparing the caries-active group with the caries-free group, including 104 up-regulated and 85 down-regulated metabolites. In the negative ion mode, a total of 532 molecular features were detected in the samples of two groups, 70 of which were differential metabolites when comparing the caries-active group with the caries-free group, including 37 up-regulated and 33 down-regulated metabolites. In the positive ion mode, two of the top 5 up-regulated differential metabolites were found in and annotated to specific metabolic pathways, whereas in the negative ion mode, only one of the top 5 up-regulated differential metabolites was found in and annotated to specific metabolic pathways. In both the positive and negative ion modes, the top 5 down-regulated differential metabolites were both annotated to the metabolic pathways. KEGG pathway enrichment analysis of differential metabolites showed that histamine and arachidonic acid identified in the positive ion mode, as well as succinate and L-histidine identified in the negative ion mode were enriched in the top 3 significantly altered pathways.ConclusionThe enriched differential metabolites including histamine, L-histidine and succinate were correlated with the presence of dental caries, but their role in the caries process needs to be further investigated