Fig 2: Treatment with IL-6 counteracts the ISLR knockdown-induced facilitating effects on the tumour progression and glycolysis of NSCLC cells. After pre-treatment with IL-6 (100 ng/ml) for 48 h, (A) proliferation, (B) invasion, (C) apoptosis and (D) glycolysis were determined colony formation, Transwell, flow cytometry and western blotting assays. (E) A summary figure for this study: ISLR promotes tumour progression and glycolysis of NSCLC cells by inactivating the IL-6/JAK/STAT3 pathway. *P<0.05 vs. si-NC + IL-6 group; #P<0.05 vs. control group. ISLR, immunoglobulin superfamily containing leucine-rich repeat; NC, negative control; si, small interfering RNA; NSCLC, non-small cell lung cancer; HK-2, hexokinase 2; Glut-1, glucose transporter 1; LDHA, lactate dehydrogenase A; JAK, Janus kinase.

Fig 3: Sal B restrains metabolic reprogramming-relevant genes LDHA and GLUT1 in NSCLC cells. (a–f) Western blots for measuring LDHA and GLUT1 expressions in 200 μM Sal B-treated NCI-H2030 as well as NCI-H2030 cells. (g, h) Immunofluorescence for investigating the expression of LDHA and GLUT1 in 200 μM Sal B-exposed NCI-H2030 and NCI-H1650 cells. Bar = 10 μM. ∗∗P < 0.01; ∗∗∗P < 0.001.

Fig 4: Knockout of TLR4 in CRC reprograms cancer metabolism in vivo.A Protein expression of SREBP-1c, ACC, FASN, CPT-1, MCAD, GLUT-1, and β-catenin in the tumor tissues of mouse models inoculated with wild-type HCT116 cells or HCT116TLR4-KO cells under different dietary interventions. B–D In iTRAQ proteomics study, the gene ontology (GO) pathway enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of the biological functions of the differentially expressed proteins in the wild-type HCT116 or HCT116TLR4-KO tumor tissues dissected from HFD mice. E STRING analysis of the highlighted metabolic enzymes that show significant differences between the wild-type HCT116 or HCT116TLR4-KO tumor tissues. F ATP levels of the tumor tissues of the mouse models inoculated with wild-type HCT116 cells or HCT116TLR4-KO cells under the dietary intervention. G Quantification of the β-catenin expressions in the tumor tissues of mouse models inoculated with wild-type HCT116 cells or HCT116TLR4-KO cells under different dietary interventions. Data are shown as means ± SEM. n = 4 and 5 mice in each group. *p < 0.05, **p < 0.01 compared with CD-HCT116, a < 0.05 compared with CD-HCT116TLR4-KO, b < 0.05, bb<0.01 compared with HFD-HCT116TLR4-KO. CD-HCT116TLR4-KO mice inoculated with TLR4-KO HCT116 cells had CD diet, HFD-HCT116TLR4-KO mice inoculated with TLR4-KO HCT116 cells had HFD diet, CD-HCT116 mice inoculated with HCT116 cells had CD diet, HFD-HCT116 mice inoculated with HCT116 cells had HFD diet. ACC acetyl-CoA carboxylase, FASN fatty acid synthase, CPT1 carnitine palmitoyltransferase-1, MCAD medium-chain acyl-CoA dehydrogenase, GLUT1 glucose transporter, SREBP-1c sterol regulatory element-binding transcription factor-1.

Fig 5: IL-17B/IL-17Rb/CXCL5 signaling is a vessel-to-OPC signal in white matter vasculatureHuman brain microvascular endothelial cells were stimulated with IL-17 ligands A–E (250 ng/mL) and CXCL5 levels measured in conditioned media 48 h after stimulation (*p = 0.0372 by Kruskal-Wallis H test; **post-hoc comparison for IL-17B versus no ligand, adjusted p = 0.0178) (A). Phalloidin+ cellular area in O4+ OPCs grown in vitro exposed to vehicle (top panel) or recombinant CXCL5 (bottom panel) for 48 h (p < 0.0001, F = 9.82 by one-way ANOVA) (B). Approach for CXCL5 transgenic-viral gain of function in subcortical white matter of Tie2-Cre;tdTomato mice (top panel) (C). PDGFRα+ OPC (green) labeling in GFP-transduced Tie2-Cre;tdTomato mice (red, left panel) and CXCL5-GFP-transduced Tie2-Cre;tdTomato mice (right panel). Representative masked cellular profiles of PDGFRα+ cell area (bottom panels). Schematic of anti-IL-17B antibody treatment (top panel) (D). PDGFRα+ OPC (green) labeling in control IgG-treated Tie2-Cre:tdT mice (left panel) and anti-IL-17B IgG-treated Tie2-Cre:tdT mice (right panel). Representative masked cellular profiles of PDGFRα+ cell area (bottom panels). Proportion of OPCs per unit distance from vessel (0–35 μm) in each condition (total measured cell number per condition in parentheses) (E). Average distance of OPCs to vessel (***p = 0.0005, F = 6.06 by one-way ANOVA; **adjusted p = 0.0039; *adjusted p = 0.0168) (F). Average in vivo PDGFRα+ OPC cell area (**p = 0.0068, F = 7.38 by one-way ANOVA; **adjusted p = 0.002) (G). Graph of co-localized CXCL5+/GLUT-1+ voxels in anti-IL-17B IgG-treated animals (n = 4/grp; *p = 0.018) (H). Error bars represent S.E.M.Scale bars: 10 μm