The dyes 3,3'-diethyloxadicarbocyanine iodide (DODI) and 3,3'-diethylthiadicarbocyanine iodide (DTDI) were investigated using laser and conventional flash photolysis techniques. In both cases direct excitation results in the formation of a photo-isomer having an absorption similar to and slightly to the red of the normal ground state absorption. The quantum efficiency for photo-isomer formation in both cases is less than 0.1. The quantum efficiency for intersystem crossing to the triplet state was observed to be < 0.01 in both cases and the triplet state extinction coefficients and spectra were therefore obtained by energy transfer techniques. The quantum efficiencies for fluorescence and radiative lifetimes obtained indicated that the fluorescence lifetimes were 1.24 and 1.20 ns for DODI and DTDI respectively.
Aim
To create an irreversible pulpitis gene signature from microarray data of healthy and inflamed dental pulps, followed by a bioinformatics approach using connectivity mapping to identify therapeutic compounds that could potentially treat pulpitis.
Methodology
The Gene Expression Omnibus (GEO) database, an international public repository of genomics data sets, was searched for human microarray datasets assessing pulpitis. An irreversible pulpitis gene expression signature was generated by differential expression analysis. The statistically significant connectivity map (ssCMap) method was used to identify compounds with a highly correlating gene expression pattern. qPCR was used to validate novel pulpitis genes. An ex vivo pulpitis model was used to test the effects of the compounds identified, and the level of inflammatory cytokines was measured with qPCR, ELISA and multiplex array. Means were compared using the t‐test or ANOVA with the level of significance set at p ≤ .05.
Results
Pulpitis gene signatures were created using differential gene expression analysis at cutoff points p = .0001 and .000018. Top upregulated genes were selected as potential pulpitis biomarkers. Among these, IL8, IL6 and MMP9 were previously identified as pulpitis biomarkers. Novel upregulated genes, chemokine (C‐C motif) ligand 21 (CCL21), metallothionein 1H (MT1H) and aquaporin 9 (AQP9) were validated in the pulp tissue of teeth clinically diagnosed with irreversible pulpitis using qPCR. ssCMap analysis identified fluvastatin (Statin) and dequalinium chloride (Quaternary ammonium) as compounds with the strongest correlation to the gene signatures (p = .0001). Fluvastatin reduced IL8, IL6, CCL21, AQP9 (p < .001) and MMP9 (p < .05) in the ex vivo pulpitis model, while dequalinium chloride reduced AQP9 (p < .001) but had no significant effect on the other biomarkers.
Conclusions
AQP9, MT1H and CCL21 were identified and validated as novel biomarkers for pulpitis. Fluvastatin and dequalinium chloride identified by the ssCMap as potential therapeutics for pulpitis reduced selected pulpitis biomarkers in an ex vivo pulpitis model. In vivo testing of these licenced drugs is warranted.
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