Journal: Stem Cell Research & Therapy

Article Title: IL-1β modulates inflammatory response of human bone marrow-derived MSCs and neutrophil recruitment in vitro via NF-kB-associated signaling

doi: 10.1186/s13287-026-05029-x

Figure Lengend Snippet: IL-1β stimulation increases expression of neutrophil recruitment and NF-kB signaling genes by BM-hMSCs. Heatmap clustering of the Z-score of the top 20 differentially expressed genes between unstimulated control BM-hMSCs (3 replicates, 1 donor, green) and IL-1 β stimulated BM-hMSCs (3 replicates, 1 donor, purple). Red color indicates higher expression of the genes and blue color indicates decreased expression A . Protein expression of CXCL1 (10 replicates, 4 donors), CCL2 (4 replicates, 2 donors), CXCL5 (4 replicates, 2 donors), and CXCL8/IL-8 (7 replicates, 3 donors) in BM-hMSCs secretome measured by ELLA or ELISA. Data are presented as median, and statistical analysis was performed using unpaired t-test with Welch’s correction B . Bar plot of the top 20 significant Gene Ontology (GO) biological processes representing IL- 1β induced upregulated differentially expressed genes C IL-1 β, Interleukin-1β; BM-hMSCs, Bone marrow derived human mesenchymal cells; CCL2, chemokine (C–C motif) ligand 2; CXCL1, chemokine (C-X-C motif) ligand 1; CXCL2, chemokine (C-X-C motif) ligand 1; CXCL8, chemokine (C-X-C motif) ligand 8; ****, p < 0,0001

Article Snippet: CXCL1 was measured in diluted 1:1 or undiluted CM samples using Quantikine ELISA (cat# DGR00B, R&D Systems).

Techniques: Expressing, Control, Enzyme-linked Immunosorbent Assay, Derivative Assay

Journal: Cell metabolism

Article Title: Metabolic stress sensing by epithelial RXRα links westernization of diet with Crohn’s disease

doi: 10.1016/j.cmet.2025.11.008

Figure Lengend Snippet: (A) Representative transmission electron microscopy (TEM) images of Paneth cells (marked by dotted line) from Gpx4 +/− IEC and WT mice after 3-month exposure to a PUFA-enriched Western diet. Note that endoplasmic reticulum (ER) (black arrows) appears dilated in Paneth cells of Gpx4 +/− IEC mice. Scale bars, 2 μm; BM indicates the basement membrane ( n = 3 mice per genotype). (B) Quantification of Paneth cells showing narrow ER cisternae or moderately or strongly enlarged ER cisternae in TEM images of indicated genotypes after exposure to a PUFA-enriched Western diet ( n = 3 mice per genotype). (C–E) Enteritis histology score (C) and representative H&E images (D and E) of WT and Gpx4 ΔPC mice exposed to a PUFA-enriched Western diet for 1 month (WT, n = 10; Gpx4 ΔPC , n = 19), and each dot represents an experimental animal. Note the infiltration of immune cells into the bowel wall (D) and a granuloma-like lesion (E) in Gpx4 ΔPC mice. Scale bars, 100 μm. (F–I) Representative images of immunolabeled CD4 + T cells (F), CD20 + B cells (G), MPO + neutrophils (H), and F4/80 + macrophages (I) in WT and Gpx4 ΔPC mice exposed to a PUFA-enriched Western diet for 1 month. Scale bars, 100 μm. (J) Quantification of CXCL1 in supernatant of small intestinal tissue explants by ELISA after 24 h of indicated genotypes exposed to a PUFA-enriched Western diet for 1 month (WT, n = 26; Gpx4 ΔPC , n = 27). (K) Shannon and Simpson diversity indices of small intestinal stool samples of WT and Gpx4 ΔPC mice exposed to a PUFA-enriched Western diet for 1 month, as assessed by shotgun metagenomics sequencing (WT, n = 14; Gpx4 ΔPC , n = 6). Data represented as mean ± SEM (unpaired Student’s t test) (B, J, and K) and median (Mann-Whitney U test) (C). ns, not significant; ** p < 0.01, *** p < 0.001.

Article Snippet: HX531 (Tocris, Cat. No. 3912) at a dose of 50 mg/kg bodyweight or vehicle was administered via oral gavage twice daily and 9-cis-retinoic acid (Sigma Aldrich, R4643) at a dose of 50 mg/kg bodyweight or vehicle or 13-cis-retinoic acid (Sigma Aldrich, R3255) at a dose of 30 mg/kg bodyweight or vehicle was administered via oral gavage daily and anti-CXCL1 antibody (R&D Systems, MAB4531) at a dose of 100μg/100μl/mouse/day or IgG (R&D Systems, AB-105-C) was administered once daily via intraperitoneal injection to WT and Gpx4 ΔPC mice.

Techniques: Transmission Assay, Electron Microscopy, Western Blot, Membrane, Immunolabeling, Enzyme-linked Immunosorbent Assay, Metagenomics, Sequencing, MANN-WHITNEY

Journal: Cell metabolism

Article Title: Metabolic stress sensing by epithelial RXRα links westernization of diet with Crohn’s disease

doi: 10.1016/j.cmet.2025.11.008

Figure Lengend Snippet: (A and B) Enteritis histology score (A) and representative H&E images (B) of indicated genotypes exposed to a PUFA-enriched Western diet for 1 month (WT, n = 17; Rxrα ΔPC , n = 8; Gpx4 ΔPC , n = 13; Gpx4/Rxrα ΔPC , n = 16), and each dot represents an experimental animal. Scale bars, 100 μm. (C–F) Representative images of immunolabeled MPO + neutrophils (C), F4/80 + macrophages (D), CD4 + T cells (E), and CD20 + B cells (F) in Gpx4 ΔPC and Gpx4/Rxrα ΔPC mice exposed to a PUFA-enriched Western diet for 1 month. Scale bars, 100 μm. (G and H) CXCL1 quantification of indicated MODE-K IECs stimulated with vehicle, AA, or SDA for 24 h, as determined in the supernatant by ELISA (G) ( n ≥ 11) and determined by qPCR after 8 h of stimulation (H) ( n = 3). (I and J) Chromatin immunoprecipitation indicating a binding of RXRα to the promoter region of CXCL1 in si Gpx4 IECs stimulated with AA (I) and SDA for 4 h (J) ( n = 4 for si Gpx4 AA immunoglobulin G [IgG] and RXRα, n = 3 for si Gpx4 SDA IgG and RXRα). (K and L) Enteritis histology score (K) and representative H&E images (L) of Gpx4 ΔPC mice exposed to a PUFA-enriched Western diet for 1 month and treated with a monoclonal antibody against CXCL1 or IgG control for the last 3 days of the experiment ( n = 10 each group), and each dot represents an experimental animal. Scale bars, 100 μm. Data represented as median (Kruskal-Wallis test with Dunn’s correction) (A), mean ± SEM (one-way ANOVA with post hoc Bonferroni) (G and H), mean ± SEM (unpaired Student’s t test) (I and J), and median (Mann-Whitney U test) (K). * p < 0.05, ** p < 0.01, *** p < 0.001, **** p < 0.0001.

Article Snippet: HX531 (Tocris, Cat. No. 3912) at a dose of 50 mg/kg bodyweight or vehicle was administered via oral gavage twice daily and 9-cis-retinoic acid (Sigma Aldrich, R4643) at a dose of 50 mg/kg bodyweight or vehicle or 13-cis-retinoic acid (Sigma Aldrich, R3255) at a dose of 30 mg/kg bodyweight or vehicle was administered via oral gavage daily and anti-CXCL1 antibody (R&D Systems, MAB4531) at a dose of 100μg/100μl/mouse/day or IgG (R&D Systems, AB-105-C) was administered once daily via intraperitoneal injection to WT and Gpx4 ΔPC mice.

Techniques: Western Blot, Immunolabeling, Enzyme-linked Immunosorbent Assay, Chromatin Immunoprecipitation, Binding Assay, Control, MANN-WHITNEY

Journal: Cell metabolism

Article Title: Metabolic stress sensing by epithelial RXRα links westernization of diet with Crohn’s disease

doi: 10.1016/j.cmet.2025.11.008

Figure Lengend Snippet: (A) CXCL1 quantification of indicated MODE-K IECs stimulated with vehicle, AA, and SDA for 24 h and co-treated with the RXRα antagonist HX531 or vehicle, determined in the supernatant by ELISA ( n = 3). (B–D) CXCL1 quantification of indicated MODE-K IECs stimulated with vehicle, AA, and SDA for 24 h and co-treated with the RXRα agonists bexarotene (B), 9- cis retinoic acid (C), or 13- cis retinoic acid (D) compared with vehicle as determined in the supernatant by ELISA (B and D, n = 4; C, n ≥ 6). (E–I) Enteritis histology score (E) and representative H&E images (F–I) of Gpx4 ΔPC mice exposed to a PUFA-enriched Western diet for 1 month and treated with vehicle ( n = 23), the RXRα antagonist HX531 ( n = 8), the RXRα agonist 9- cis retinoic acid ( n = 11), or the RXRα agonist 13- cis retinoic acid ( n = 7) for the last 3 days of the experiment, and each dot represents an experimental animal. Scale bars, 100 μm. (J and K) Enteritis histology score (J) and representative H&E images (K) of Xpb1 ΔIEC mice exposed to a PUFA-enriched Western diet for 1 month and treated with vehicle ( n = 6) or the RXRα agonist 13- cis retinoic acid ( n = 6) for the last 3 days of the experiment, and each dot represents an experimental animal. Scale bars, 100 μm. (L) Schematic representation of experimental design in TriNetX. 85,338 patients with acne that received oral isotretinoin treatment were compared with 85,259 age- and sex-matched patients with acne that never received isotretinoin treatment. Incidence of CD or UC development was assessed after 1 year in both groups. (M) Forest plot indicating the OR of developing UC and CD in isotretinoin (13- cis retinoic acid)-treated and untreated patients with acne after 1 year, as retrospectively assessed by analysis from medical records in TriNetX. Data represented as mean ± SEM (one-way ANOVA with post hoc Bonferroni) (A–E) and median (Mann-Whitney U test) (J). * p < 0.05, ** p < 0.01, *** p < 0.001, **** p < 0.0001.

Article Snippet: HX531 (Tocris, Cat. No. 3912) at a dose of 50 mg/kg bodyweight or vehicle was administered via oral gavage twice daily and 9-cis-retinoic acid (Sigma Aldrich, R4643) at a dose of 50 mg/kg bodyweight or vehicle or 13-cis-retinoic acid (Sigma Aldrich, R3255) at a dose of 30 mg/kg bodyweight or vehicle was administered via oral gavage daily and anti-CXCL1 antibody (R&D Systems, MAB4531) at a dose of 100μg/100μl/mouse/day or IgG (R&D Systems, AB-105-C) was administered once daily via intraperitoneal injection to WT and Gpx4 ΔPC mice.

Techniques: Enzyme-linked Immunosorbent Assay, Western Blot, MANN-WHITNEY