Fig 2: Docosahexaenoic acid (DHA) metabolites biosynthesis. (A) Schematic illustration of the D-series of resolvins (RvD), protectins (PD) and maresins (MaR) biosynthesis’ pathway showing the enzymes involved, 5-LO, 15-LO and 12-LO as well as their intermediates substrates 17-HDOHEand 14-HDOHE. (B) Comparison of the mean levels of each DHA metabolite (RvD2, rvD3, RvD4, RvD5, PD1 and 17-HDOHE) between samples derived from non-CF and CF subjects (top) and from male and female CF patients (bottom). (Mann-Whitney test. *p<0.05), **p<0.01).

Fig 3: 5-LO localization in hNEC. Typical 5-LO (green) immuno-fluorescence confocal images of airway (nasal: hNEC and bronchial: hBE) epithelial cells primary cultures derived from 9 different subjects with different CFTR mutations. The non-CF (WT, left) and CF (right) female (F) and male (M) airway primary cultures were (A) grown at ALI on permeable filters, embedded in paraffin and sliced or (B) grown on glass coverslips. Nucleus were stained in DAPI (blue). Bar=10µm.

Fig 4: Age-linked reductions in LXA4 result in cognitive impairment.a, b Levels of lipoxin A4 (LXA4) in plasma (a) and brain (b) of young (3 month old) or aged (12 month old) Swiss mice. (Plasma: N = 12 for 3 mo, N = 15 for 12 mo; Brain: N = 7 for 3 mo, N = 15 for 12 mo mice). c Step-down latency of young or aged mice in the inhibitory avoidance task to assess short-term memory (STM: 1 h after training; N = 20 for 3 mo; N = 15 for 12 mo mice). d Number of trials required for each mouse to reach the criteria during the training session in the inhibitory avoidance fear task (N = 23 for WT; N = 13 for 5-LOX−/−). e, f Step-down latency of 5-LOX−/− or WT mice (3 month old) in the inhibitory avoidance task to assess short-term (e; STM: 1 h after training; N = 7 WT and N = 15 5-LOX−/− mice) or long-term memory (f; LTM: 24 h after training; N = 23 for WT; N = 13 for 5-LOX−/−). For a, b, and d, two-tailed unpaired Student’s t-test. For c, e, and f, two-tailed unpaired Mann–Whitney (*p < 0.05; ****p < 0.0001). Graphs show means ± standard error of the mean (SEM). Each dot represents an individual. g Fear memory extinction assessed by step-down latency of 5-LOX−/− or WT after repeated test sessions 12–15 days after original conditioning session (N = 10 WT and N = 10 5-LOX−/− mice). Repeated measures one-way ANOVA with Šidák post hoc test (*p < 0.05). Graphs show means ± SEM.

Fig 5: Cells with overexpression of 5-LOX (marked with red chromogene) in early intramucosal adenocarcinomas inside the polyp—positive epithelium