Fig 2: Effects of HMGB1 on hyperplastic mucosa surrounding CRC. Investigation of the role of HMGB1 in mucosal immunity and epithelial differentiation using biopsy specimens from 10 cases of CRC with hyperplastic mucosa surrounding the cancer lesions. (A) Histological appearance of the mucosa distant from CRC focus (C) and the hyperplastic mucosa surrounding CRC focus (H). Scale bar = 100 μm. (B–E) Protein levels of HMGB1 (B), Ki67 (proliferation) (C), ALP and MUC2 levels (epithelial differentiation) (D), and DEF and BA (intestinal flora maintenance) (E). (F–H) Flow cytometry for activated CD8 (CD8+IFNγ+) (F), exhausted CD8 (CD8+PDL1+) (G) and naïve CD8 (CD8+CD62L+) (H). (I–K) Relationships between HMGB1 and activated CD8 cells (CD8+IFNγ+) (I), or exhausted CD8 (CD8+PDL1+) (J), or naïve CD8 (CD8+CD62L+) (K). (I–K) Dots represent each case of cancer (C) and hyperplastic mucosa (H). Error bars: standard deviation of 10 cases and three independent trials. Statistical differences were calculated using analysis of variance with Bonferroni correction. Regression analysis was performed using Spearman’s correlation test. HMGB1, high-mobility group box-1; C, control non-hyperplastic mucosa distant from cancer lesion (more than 5 cm); H, hyperplastic mucosa surrounding cancer lesion (within 1 cm); MUC2, mucin 2; ALP, alkaline phosphatase; αDEF, α-defensin; BA, butyric acid; IFNγ, interferon γ; PDL1, programmed cell death ligand-1.

Fig 3: Regulation of Staphylococcus_xylosus and Staphylococcus_lentus on the process of liver fibrosis in mice. The pure cultures (109 CFU) of the three kinds of gut microbiota (Staphylococcus_lentus, Aerococcus_viridans and Staphylococcus_xylosus) were given to mice by gavage to make them become the dominant microflora in the intestine, and then the liver fibrosis model of mice was induced by the intraperitoneal injection of CCl4 (0.5 µL/g). A, B Sirius red staining and immunohistochemical assays were conducted to assess the degree of liver fibrosis in mice (N = 10, scale bar = 50 µm), Brown-Forsythe and Welch ANOVA with Games-Howell’s post-hoc. C Different detection kits were applied to measure the concentrations of ALT, AST and ALP in mouse blood samples, Brown-Forsythe and Welch ANOVA with Games-Howell’s post-hoc. N = 10. D The concentrations of IBiL, TBiL and DBiL in mouse blood samples were assessed, one-way ANOVA with Tukey’s post-hoc for IBil, Brown-Forsythe and Welch ANOVA with Games-Howell’s post-hoc for TBil and DBil. N = 10. E Comparison of the hydroxyproline (Hyp) level using a commercial kit. N = 10. **P < 0.01, ****P < 0.0001 vs. Control. #P < 0.05, ##P < 0.01, ###P < 0.001, ####P < 0.0001 vs. CCl4. S_xylosus: Staphylococcus_xylosus, S_lentus: Staphylococcus_lentus, A_viridans: Aerococcus_viridans. Data are presented of three independent assays

Fig 4: Effect of LMWCP on the serum levels of bone turnover markers.The ALP activities (A), BAP levels (B), OCN levels (C), P1NP levels (D), CTX levels (E), and TRAP levels (F) of sham, OVX, and OVX + LMWCP (at different LMWCP concentrations) rats were determined. Data represent the mean values of three independent experiments; #, p < 0.05; ##, p < 0.01; ###, p < 0.001 (when compared with the sham group); *, p < 0.05; **, p < 0.01 (when compared with the OVX group).

Fig 5: Isomangiferin contributes to the osteogenic differentiation of H2O2-stimulated BMSCs. (a) Molecular formula of isomangiferin. (b) CCK-8 assays showed the effects of isomangiferin (2.5, 5, 10 μM) on H2O2-stimulated BMSCs for 24 h. The OD450 value was measured. (c) ALP activity detection showed the ALP activity in BMSCs upon the treatment of isomangiferin (2.5, 5, 10 μM) and 100 μM H2O2 for 24 h. (d) Alizarin Red staining showed the osteogenic differentiation degree of BMSCs upon the treatment of isomangiferin (2.5, 5, 10 μM) and 100 μM H2O2 for 24 h. (e) Immunoblot showed the expression of Runx2 and BMP2 in BMSCs upon the treatment of isomangiferin (2.5, 5, 10 μM) and 100 μM H2O2 for 24 h. **p < 0.01, H2O2 vs control, ## p < 0.01, H2O2+\documentclass[10pt]{article}\usepackage{wasysym}\usepackage[substack]{amsmath}\usepackage{amsfonts}\usepackage{amssymb}\usepackage{amsbsy}\usepackage[mathscr]{eucal}\usepackage{mathrsfs}\usepackage{pmc}\usepackage[Euler]{upgreek}\pagestyle{empty}\oddsidemargin -1.0in\begin{document}\[{\text{H}}_{\text{2}}{\text{O}}_{2}^{+}]\]\end{document} isomangiferin, vs H2O2. IS, isomangiferin.