Y-FAs. cytochrome P450 (CYP)-soluble epoxide hydrolase U test. N.S., non-significant. dihydroxy-FAs. P values have been determined by t-test or Mann hitney U test. N.S., non-significant.In EAE SCs, AA metabolites via the COX-1/2 pathway have been abundant ( 500 pmol/g). In EAE SCs, AA metabolites by means of the COX-1/2 pathway were abundant ( 500 pmol/g). TPPU treatment didn’t influence fluxes inside the COX and 5-LO pathways but showed a equivalent TPPU treatment did not have an effect on fluxes in the COX and 5-LO pathways but showed a equivalent trend in the 12/15-LO pathway with that of plasma (Figure 4A). CB1 Activator Gene ID Levels of EpETrE andInt. J. Mol. Sci. 2021, 22, 4650 Int. J. Mol. Sci. 2021, 22, x FOR PEER REVIEWof six of 612trend inside the 12/15-LO pathway with that of plasma (Figure 4A). Levels of EpETrE and EpDPE (10000 pmol/g) in SCs were equivalent to these in plasma (10000 nmol/L), EpDPE (10000 metabolites (EpOME and EpODE) have been 50-fold decrease than those while C18-PUFA pmol/g) in SCs had been equivalent to those in plasma (10000 nmol/L), in although C18-PUFA metabolites (EpOME and EpODE) had been 50-fold reduce have been observed plasma (Figure 4B). Similar trends of EpFA and dihydroxy-FA profiles than those in plasma (Figure 4B). Comparable trends in the inhibition of DiHETrE and DiHODE, as wellbe- an amongst SCs and plasma, including EpFA and dihydroxy-FA profiles have been observed as tween SCs and plasma, such as the inhibition TPPU penetrating effectively into the SCs improve of EpOME (Figure 4B) possibly CaMK II Activator drug resulting from of DiHETrE and DiHODE, at the same time as a rise of Good correlations within because of TPPU penetrating efficiently discovered, SCs (Figure 1B). EpOME (Figure 4B) possibly C20 or C22-PUFA metabolites have been into thesuch as (Figure vs. EpDPE and DiHDPE inside C20 or(Figure 4C). metabolites have been identified, such EpETrE 1B). Positive correlations vs. DiHETE C22-PUFA as EpETrE vs. EpDPE and DiHDPE vs. DiHETE (Figure 4C).Figure four. PUFA fluxes in EAE SCs. PUFA fluxes in EAE SCs. (A) Levels of AA and EPA metabolites in each pathway. (B) Figure 4. PUFA fluxes in EAE SCs. PUFA fluxes in EAE SCs. (A) Levels of AA and EPA metabolites in each pathway. Levels of LA, AA, ALA, and EPA metabolites in the CYP-sEH pathway. (C) Correlation matrix of EpFAs and dihydroxy(B) Levels of LA, AA,determinedEPA metabolites within the CYP-sEH pathway. (C) Correlation matrix of EpFAs and dihydroxyALA, and by t-test or Mann hitney U test. N.S., non-significant. FAs. P values were FAs. P values have been determined by t-test or Mann hitney U test. N.S., non-significant.2.3. TPPU Reduced Dihydroxy-FA Production with an Accompanying Boost of EpFAs in EAE Mice 2.3. TPPU Decreased Dihydroxy-FA Production with an Accompanying Enhance of EpFAs in Differential lipid levels were computed for TPPU vs. control groups that were repreEAE Mice sented as a scatter plotlevels wereThis plot clearlyTPPU vs. handle groups thatalmostrepreDifferential lipid (Figure 5). computed for displayed the aggregation of have been each of the dihydroxy-FAs (like five). This plot clearly displayed the aggregation of nearly sented as a scatter plot (Figure12,13-DiHOME and 15,16-DiHODE) and trihydroxy-FAs all (which include 9,10,13-TriHOME and 9,12,13-TriHOME) into quadrant III (log10(TPPU/vehicle) the dihydroxy-FAs (for example 12,13-DiHOME and 15,16-DiHODE) and trihydroxy-FAs (such 9,10,13-TriHOME and 9,12,13-TriHOME) into quadrant III (log (Figure 5). This 0 as 0 in both plasma and SC) having a couple of exceptions which include 4,5-DiHDPE(TPPU/vehicle)was in ten accompaniedand an up-regulation of som.
