Journal: Cellular and Molecular Gastroenterology and Hepatology

Article Title: Fibroblast Growth Factor 20 Attenuates Colitis by Restoring Impaired Intestinal Epithelial Barrier Integrity and Modulating Macrophage Polarization via S100A9 in an NF-κB-Dependent Manner

doi: 10.1016/j.jcmgh.2025.101486

Figure Lengend Snippet: The loss of FGF20 increases colonic S100A9 expression in DSS-induced mice. ( A ) Heat maps of differentially expressed proteins in the colonic tissue of FGF20 KO and WT mice with or without colitis. ( B ) Volcano diagram of proteomic analysis in FGF20 KO and WT mice with colitis. ( C ) Relative expression data of S100A9 in FGF20 KO and WT mice with or without colitis (n = 4). ( D, E ) The expression of S100A9 in the colonic tissue of each group of mice was tested by Western blot (n = 3) and immunohistochemistry (n = 4). Data are represented as mean ± SEM. Scale bar, 50 μm. ∗ P < .05, ∗∗ P < .01, ∗∗∗ P < .001.

Article Snippet: For the S100A9 inhibitor experiment, paquinimod (HY-100442, ABR 25757, MCE) was intraperitoneal injected to model group mice every day at a dose of 10 mg/kg, when they began to drink 2% DSS.

Techniques: Expressing, Western Blot, Immunohistochemistry

Journal: Cellular and Molecular Gastroenterology and Hepatology

Article Title: Fibroblast Growth Factor 20 Attenuates Colitis by Restoring Impaired Intestinal Epithelial Barrier Integrity and Modulating Macrophage Polarization via S100A9 in an NF-κB-Dependent Manner

doi: 10.1016/j.jcmgh.2025.101486

Figure Lengend Snippet: Inhibition of S100A9 protects against colitis in FGF20 KO mice. Eight-week-old male FGF20 KO mice and WT littermates were given 2% DSS in drinking water for 5 days, followed by normal drinking water for an additional 5 days. In the meanwhile, paquinimod (10 mg/kg) was injected via the intraperitoneal route for 10 days. ( A, B ) Body weight and colon length of FGF20 KO mice and WT mice with colitis, treated with paquinimod or vehicle. ( C ) Histologic morphology of FGF20 KO mice and WT mice with colitis, treated with paquinimod or vehicle. Top , H&E staining; bottom , PAS staining. Scale bar, 100 μm and 50 μm. ( D ) Immunoblot analysis of colonic IL6 and iNOS in FGF20 KO mice and WT mice with colitis, treated with paquinimod or vehicle (n = 6). Data are represented as mean ± SEM; ∗ P < .05, ∗∗∗ P < .001.

Article Snippet: For the S100A9 inhibitor experiment, paquinimod (HY-100442, ABR 25757, MCE) was intraperitoneal injected to model group mice every day at a dose of 10 mg/kg, when they began to drink 2% DSS.

Techniques: Inhibition, Injection, Staining, Western Blot

Journal: Cellular and Molecular Gastroenterology and Hepatology

Article Title: Fibroblast Growth Factor 20 Attenuates Colitis by Restoring Impaired Intestinal Epithelial Barrier Integrity and Modulating Macrophage Polarization via S100A9 in an NF-κB-Dependent Manner

doi: 10.1016/j.jcmgh.2025.101486

Figure Lengend Snippet: AAV-S100A9 attenuates the protective effects of FGF20-overexpression against DSS-induced colitis. Six-week-old male WT mice were treated with AAV-FGF20, AAV-S100A9, or AAV-GFP by tail vein injection. After 4 weeks of AAV injection, all mice were given 2% DSS in drinking water for 5 days, followed by normal drinking water for an additional 5 days. ( A ) The expression of S100A9 after AAV-S100A9 treatment was determined by Western blot (n = 6). ( B, C ) Body weights and colon length of AAV-FGF20-treated mice and AAV-GFP-treated mice with colitis, treated with AAV-S100A9 or not were measured. ( D ) Histologic morphology of AAV-FGF20-treated mice and AAV-GFP-treated mice with colitis, treated with AAV-S100A9 or not. Top , H&E staining; bottom , PAS staining. Scale bar, 100 μm and 50 μm. ( E ) Immunoblot analysis of colonic IL6 and iNOS in AAV-FGF20-treated mice and AAV-GFP-treated mice with colitis, treated with AAV-S100A9 or not (n = 6). Data are represented as mean ± SEM; ∗ P < .05, ∗∗ P < .01, ∗∗∗ P < .001.

Article Snippet: For the S100A9 inhibitor experiment, paquinimod (HY-100442, ABR 25757, MCE) was intraperitoneal injected to model group mice every day at a dose of 10 mg/kg, when they began to drink 2% DSS.

Techniques: Over Expression, Injection, Expressing, Western Blot, Staining

Journal: Cellular and Molecular Gastroenterology and Hepatology

Article Title: Fibroblast Growth Factor 20 Attenuates Colitis by Restoring Impaired Intestinal Epithelial Barrier Integrity and Modulating Macrophage Polarization via S100A9 in an NF-κB-Dependent Manner

doi: 10.1016/j.jcmgh.2025.101486

Figure Lengend Snippet: Inhibition of S100A9 mitigated the deterioration of FGF20 KO on intestinal barrier function in DSS-induced colitis. Eight-week-old male FGF20 KO mice and WT littermates were given 2% DSS in drinking water for 5 days, followed by normal drinking water for an additional 5 days. In the meanwhile, paquinimod (10 mg/kg) was injected via the intraperitoneal route for 10 days. ( A ) Western blot and quantitation of colonic ZO-2, occludin, and claudin 1 expression in FGF20 KO mice and WT mice with colitis, treated with paquinimod or vehicle (n = 6). ( B ) Representative fluorescence images of Ki67, and the percentage of Ki67-positive cells in FGF20 KO mice and WT mice with colitis, treated with paquinimod or vehicle. Scale bar, 50 μm (n ≥ 5). ( C ) Immunoblot analysis of colonic Bax and Bcl-2 expression in FGF20 KO mice and WT mice with colitis, treated with paquinimod or vehicle (n = 6). Data are represented as mean ± SEM; ∗ P < .05, ∗∗∗ P < .001.

Article Snippet: For the S100A9 inhibitor experiment, paquinimod (HY-100442, ABR 25757, MCE) was intraperitoneal injected to model group mice every day at a dose of 10 mg/kg, when they began to drink 2% DSS.

Techniques: Inhibition, Injection, Western Blot, Quantitation Assay, Expressing, Fluorescence

Journal: Cellular and Molecular Gastroenterology and Hepatology

Article Title: Fibroblast Growth Factor 20 Attenuates Colitis by Restoring Impaired Intestinal Epithelial Barrier Integrity and Modulating Macrophage Polarization via S100A9 in an NF-κB-Dependent Manner

doi: 10.1016/j.jcmgh.2025.101486

Figure Lengend Snippet: FGF20 regulates claudin-1 through S100A9 in DSS-induced colitis mice. ( A ) Representative fluorescence images of colonic claudin-1 from FGF20 KO mice and WT mice with colitis, treated with paquinimod or vehicle. ( B ) Representative fluorescence images of colonic claudin-1 from AAV-FGF20-treated mice and AAV-GFP-treated mice with colitis, treated with AAV-S100A9 or not. Scale bar, 50 μm.

Article Snippet: For the S100A9 inhibitor experiment, paquinimod (HY-100442, ABR 25757, MCE) was intraperitoneal injected to model group mice every day at a dose of 10 mg/kg, when they began to drink 2% DSS.

Techniques: Fluorescence

Journal: Cellular and Molecular Gastroenterology and Hepatology

Article Title: Fibroblast Growth Factor 20 Attenuates Colitis by Restoring Impaired Intestinal Epithelial Barrier Integrity and Modulating Macrophage Polarization via S100A9 in an NF-κB-Dependent Manner

doi: 10.1016/j.jcmgh.2025.101486

Figure Lengend Snippet: AAV-S100A9 abolished the protect effects of FGF20 overexpression on intestinal barrier function in DSS-induced colitis. Six-week-old male WT mice were treated with AAV-FGF20, AAV-S100A9, or AAV-GFP by tail vein injection. After 4 weeks of AAV injection, all mice were given 2% DSS in drinking water for 5 days, followed by normal drinking water for an additional 5 days. ( A ) Western blot and quantitation of colonic ZO-2, occludin, and claudin-1 expression in AAV-FGF20-treated mice and AAV-GFP-treated mice with colitis, treated with AAV-S100A9 or not (n = 6). ( B ) Representative fluorescence images of Ki67, and the percentage of Ki67-positive cells in AAV-FGF20-treated mice and AAV-GFP-treated mice with colitis, treated with AAV-S100A9 or not (n ≥ 5), Scale bar, 50 μm. ( C ) The expression of level of Bax and Bcl-2 in AAV-FGF20-treated mice and AAV-GFP-treated mice with colitis, treated with AAV-S100A9 or not, were detected by Western blot (n = 6). Data are represented as mean ± SEM; ∗ P < .05, ∗∗ P < .01, ∗∗∗ P < .001. n.s., no significance.

Article Snippet: For the S100A9 inhibitor experiment, paquinimod (HY-100442, ABR 25757, MCE) was intraperitoneal injected to model group mice every day at a dose of 10 mg/kg, when they began to drink 2% DSS.

Techniques: Over Expression, Injection, Western Blot, Quantitation Assay, Expressing, Fluorescence

Journal: Cellular and Molecular Gastroenterology and Hepatology

Article Title: Fibroblast Growth Factor 20 Attenuates Colitis by Restoring Impaired Intestinal Epithelial Barrier Integrity and Modulating Macrophage Polarization via S100A9 in an NF-κB-Dependent Manner

doi: 10.1016/j.jcmgh.2025.101486

Figure Lengend Snippet: The inhibition of FGF20 on M1-like macrophage polarization in DSS-induced colitis was S100A9-dependent. ( A, B ) mRNA expression levels of macrophage M1 ( IL-6 , TNF-α , IL-1β , and MCP-1 ) and M2 ( IL-10 , Arg-1, Fizz1 , and Ym1 ) polarization-related gene in FGF20 KO mice and WT mice with colitis, treated with paquinimod or vehicle, were quantitatively determined by quantitative PCR (n ≥ 4). ( C, D ) mRNA expression levels of macrophage M1 ( IL-6 , TNF-α , IL-1β , and MCP-1 ) and M2 ( IL-10 , Arg-1, Fizz1 , and Ym1 ) polarization-related gene in AAV-FGF20-treated mice and AAV-GFP-treated mice with colitis, treated with AAV-S100A9 or not, were quantitatively determined by quantitative PCR (n ≥ 4). ( E ) Representative images of immunofluorescence staining of colon sections from FGF20 KO mice and WT mice with colitis, treated with paquinimod or vehicle. Scale bar, 50 μm. ( F ) Representative images of immunofluorescence staining of colon sections from AAV-FGF20-treated mice and AAV-GFP-treated mice with colitis, treated with AAV-S100A9 or not. Scale bar, 50 μm. Data are represented as mean ± SEM; ∗ P < .05, ∗∗ P < .01, ∗∗∗ P < .001. n.s., no significance.

Article Snippet: For the S100A9 inhibitor experiment, paquinimod (HY-100442, ABR 25757, MCE) was intraperitoneal injected to model group mice every day at a dose of 10 mg/kg, when they began to drink 2% DSS.

Techniques: Inhibition, Expressing, Real-time Polymerase Chain Reaction, Immunofluorescence, Staining

Journal: Cellular and Molecular Gastroenterology and Hepatology

Article Title: Fibroblast Growth Factor 20 Attenuates Colitis by Restoring Impaired Intestinal Epithelial Barrier Integrity and Modulating Macrophage Polarization via S100A9 in an NF-κB-Dependent Manner

doi: 10.1016/j.jcmgh.2025.101486

Figure Lengend Snippet: FGF20 inhibits NF-κB pathway through S100A9 in DDS-induced mice. ( A ) KEGG Enrichment Analysis of proteomics data from the colonic tissue of FGF20 KO and WT mice with or without colitis. ( B ) Immunoblot analysis of colonic p-P65, P65, p-IκBα, and IκBα from FGF20 KO and WT mice with or without colitis (n = 6). ( C ) Immunoblot analysis of colonic p-P65, P65, p-IκBα, and IκBα contents in AAV-FGF20- or AAV-GFP-treated mice with or without colitis. ( D ) Immunoblot analysis of colonic p-P65, P65, p-IκBα, and IκBα contents in FGF20 KO mice and WT mice with colitis, treated with paquinimod or vehicle (n = 6). ( E ) Immunoblot analysis of colonic p-P65, P65, p-IκBα, and IκBα contents in AAV-FGF20-treated mice and AAV-GFP-treated mice with colitis, treated with AAV-S100A9 or not (n = 6). Data are represented as mean ± SEM; ∗ P < .05, ∗∗ P < .01, ∗∗∗ P < .001.

Article Snippet: For the S100A9 inhibitor experiment, paquinimod (HY-100442, ABR 25757, MCE) was intraperitoneal injected to model group mice every day at a dose of 10 mg/kg, when they began to drink 2% DSS.

Techniques: Western Blot

Journal: Cellular and Molecular Gastroenterology and Hepatology

Article Title: Fibroblast Growth Factor 20 Attenuates Colitis by Restoring Impaired Intestinal Epithelial Barrier Integrity and Modulating Macrophage Polarization via S100A9 in an NF-κB-Dependent Manner

doi: 10.1016/j.jcmgh.2025.101486

Figure Lengend Snippet: FGF20 inhibits M1-like macrophage polarization in NF-κB-dependent manner in vitro. Primary peritoneal macrophages were isolated from WT mice and FGF20 KO mice and used for subsequent in vitro experiments. ( A ) Immunoblot analysis of expression of iNOS, TNF-α, IL6, S100A9, p-P65, P65, p-IκBα, and IκBα in LPS-stimulated primary peritoneal macrophages, treated with or without BAY11-7082 (n = 3). ( B ) Representative immunofluorescence images and its fluorescence densities of LPS-stimulated primary peritoneal macrophages, treated with or without BAY11-7082 (n = 6). Data are represented as mean ± SEM; ∗∗ P < .01, ∗∗∗ P < .001.

Article Snippet: For the S100A9 inhibitor experiment, paquinimod (HY-100442, ABR 25757, MCE) was intraperitoneal injected to model group mice every day at a dose of 10 mg/kg, when they began to drink 2% DSS.

Techniques: In Vitro, Isolation, Western Blot, Expressing, Immunofluorescence, Fluorescence

Journal: Radiology

Article Title: Single-Dose Neoadjuvant AKT Pathway Inhibitor Reduces Growth of Hepatocellular Carcinoma after Laser Thermal Ablation in Small-Animal Model

doi: 10.1148/radiol.2019190115

Figure Lengend Snippet: Single-dose neoadjuvant phosphoinositide 3-kinase (PI3K)/mammalian target of rapamycin (mTOR) inhibition prior to thermal ablation reduces hepatocellular carcinoma (HCC) tumor growth after laser thermal ablation in vivo. (a) Representative photographs of N1S1 HCC tumor–bearing mice in the vehicle + sham ablation, vehicle + laser ablation, BEZ235 + sham ablation, and BEZ235 + laser ablation groups. (b) Graph shows tumor volumes up to 7 days after ablation. Data are mean ± standard error of the mean (nine or more mice per group). Data were analyzed by using two-way analysis of variance followed by post-hoc pairwise comparison with the Tukey test. P < .001 for the interaction of drug or ablation treatment and postablation time conditions. * = P < .001 and .001 (vehicle + sham vs vehicle + laser and BEZ235 + sham); ** = P < .001 (vehicle + sham vs BEZ235 + laser); *** = P = .04 (vehicle + laser vs BEZ235 + laser) and P = .005 (BEZ235 + sham vs BEZ235 + laser); and **** = P = .94 (vehicle + laser vs BEZ235 + sham).

Article Snippet: For in vivo experiments, dual PI3K/mTOR inhibitor BEZ235 (Selleck Chemicals, Houston, Tex) was dissolved in N -Methyl-2-pyrrolidone (NMP) and polyethylene glycol (PEG-300; Sigma-Aldrich, St Louis, Mo) (NMP/PEG, 10/90, vol/vol) at a concentration of 5 mg/mL per manufacturer instructions.

Techniques: Inhibition, In Vivo

Journal: Radiology

Article Title: Single-Dose Neoadjuvant AKT Pathway Inhibitor Reduces Growth of Hepatocellular Carcinoma after Laser Thermal Ablation in Small-Animal Model

doi: 10.1148/radiol.2019190115

Figure Lengend Snippet: Fold-change in Isoform-specific Serine or Threonine Phosphorylation of AKT in Hepatocellular Carcinoma Cells Following Moderate Heat Stress without or with PI3K/mTOR Inhibition

Article Snippet: For in vivo experiments, dual PI3K/mTOR inhibitor BEZ235 (Selleck Chemicals, Houston, Tex) was dissolved in N -Methyl-2-pyrrolidone (NMP) and polyethylene glycol (PEG-300; Sigma-Aldrich, St Louis, Mo) (NMP/PEG, 10/90, vol/vol) at a concentration of 5 mg/mL per manufacturer instructions.

Techniques: Inhibition

Journal: Radiology

Article Title: Single-Dose Neoadjuvant AKT Pathway Inhibitor Reduces Growth of Hepatocellular Carcinoma after Laser Thermal Ablation in Small-Animal Model

doi: 10.1148/radiol.2019190115

Figure Lengend Snippet: Cellular Function Activation State of HCC Cells Following Moderate Heat Stress without or with PI3K/mTOR Inhibition

Article Snippet: For in vivo experiments, dual PI3K/mTOR inhibitor BEZ235 (Selleck Chemicals, Houston, Tex) was dissolved in N -Methyl-2-pyrrolidone (NMP) and polyethylene glycol (PEG-300; Sigma-Aldrich, St Louis, Mo) (NMP/PEG, 10/90, vol/vol) at a concentration of 5 mg/mL per manufacturer instructions.

Techniques: Cell Function Assay, Activation Assay, Inhibition

Journal: Radiology

Article Title: Single-Dose Neoadjuvant AKT Pathway Inhibitor Reduces Growth of Hepatocellular Carcinoma after Laser Thermal Ablation in Small-Animal Model

doi: 10.1148/radiol.2019190115

Figure Lengend Snippet: Proposed mechanism of increased hepatocellular carcinoma (HCC) cell killing and reduced postablation tumor growth with neoadjuvant phoshoinositide 3-kinase (PI3K)/mammalian target of rapamycin (mTOR)/protein kinase B (AKT) pathway inhibition in combination with moderate heat stress and thermal ablation. Top: Incomplete thermal ablation of HCC cells induces activation of PI3K/mTORC2-dependent activating phosphorylation of AKT at serine (Ser) 473 and threonine (Thr) 308, which promotes cell survival, growth, and proliferation mechanisms while inhibiting cell death mechanisms, thereby resulting in local tumor recurrence and progression. Bottom: Neoadjuvant dual PI3K/mTOR inhibitor BEZ235 prior to thermal ablation prevents thermal ablation–induced activation of AKT signaling, which promotes cell death mechanisms while preventing cell survival, growth, and proliferation mechanisms, thereby resulting in a reduction in local tumor recurrence and progression.

Article Snippet: For in vivo experiments, dual PI3K/mTOR inhibitor BEZ235 (Selleck Chemicals, Houston, Tex) was dissolved in N -Methyl-2-pyrrolidone (NMP) and polyethylene glycol (PEG-300; Sigma-Aldrich, St Louis, Mo) (NMP/PEG, 10/90, vol/vol) at a concentration of 5 mg/mL per manufacturer instructions.

Techniques: Inhibition, Activation Assay