Journal: Frontiers in Cell and Developmental Biology

Article Title: Multimodal profiling uncovers an aging-associated ETS1-MYO1B vascular niche responsive to ipragliflozin

doi: 10.3389/fcell.2026.1968248

Figure Lengend Snippet: Inflammatory stimulation induces a MYO1B-positive endothelial-to-pericyte-like transition (A) Joint UMAP of VE3 and Pericyte_2-related cells in the merged dataset. (B) Distribution of diffusion pseudotime (DPT) in UMAP space. (C) Distribution of clusters reclustered according to DPT results. (D) Pseudotime violin plots for pseudotime-associated clusters. (E) Expression distributions of PDGFRB, CDH5, CDKN1A, ETS1, MYO1B, ICAM1, TGFBR2 and ZEB2 in the joint UMAP. (F) Relative mRNA expression of PDGFRB and MYO1B in HMEC-1 cells under control, TGF-β1 and TGF-β1+IL-1β. (G) Flow-cytometry distributions of PDGFRB and MYO1B in HMEC-1 cells comparing control and TGF-β1+IL-1β. (H) SA-β-gal staining and PDGFRB/DAPI, MYO1B/DAPI and CD31/DAPI immunofluorescence images under control, TGF-β1 and TGF-β1+IL-1β.

Article Snippet: To establish an inflammatory/TGF-β stimulation model, HMEC-1 cells were treated with recombinant human TGF-β1 (Abclonal, RP01458) and recombinant human IL-1β (Abclonal, RP00002) at 10 ng/mL each for 7 days.

Techniques: Diffusion-based Assay, Expressing, Control, Flow Cytometry, Staining, Immunofluorescence

Journal: Frontiers in Cell and Developmental Biology

Article Title: Multimodal profiling uncovers an aging-associated ETS1-MYO1B vascular niche responsive to ipragliflozin

doi: 10.3389/fcell.2026.1968248

Figure Lengend Snippet: ETS1 regulates MYO1B expression and induces cellular senescence (A) TF regulon-MYO1B correlation volcano plot showing the correlation between transcription-factor activity and MYO1B expression. (B) Diagram of the scTenifoldKnk virtual-knockdown and predicted-age-change module. (C) Differential-regulation scatter plot after virtual ETS1 knockout. (D) Forest plot of age-associated odds ratios for ETS1, ELF1 and ERG in the age-clock model. (E) Bar plot ranking ETS1 and inferred downstream genes by predicted age change after virtual knockdown. (F) Effect of siETS1 on MYO1B mRNA under TGF-β1/IL-1β. (G) ChIP-qPCR showing ETS1 enrichment at the MYO1B promoter; histone H3 and IgG were used as controls. (H) Representative SA-β-gal images of NC and siETS1 groups under TGF-β1/IL-1β.

Article Snippet: To establish an inflammatory/TGF-β stimulation model, HMEC-1 cells were treated with recombinant human TGF-β1 (Abclonal, RP01458) and recombinant human IL-1β (Abclonal, RP00002) at 10 ng/mL each for 7 days.

Techniques: Expressing, Activity Assay, Knockdown, Knock-Out, ChIP-qPCR

Journal: Frontiers in Cell and Developmental Biology

Article Title: Multimodal profiling uncovers an aging-associated ETS1-MYO1B vascular niche responsive to ipragliflozin

doi: 10.3389/fcell.2026.1968248

Figure Lengend Snippet: Identification of Ipragliflozin as a potential modulator of ETS1-MYO1B axis (A) ETS1 virtual-screening workflow. (B) Candidate ranking by primary docking affinity and redocking best affinity, with the top candidates labeled. (C) PLIP interaction profile, stacked bars show hydrophobic, hydrogen-bond, pi-stacking, pi-cation, salt-bridge and halogen interactions for candidate molecules. (D) Flexible segments, pocket-domain segments, DNA-binding domain and other residues in the AlphaFold-predicted ETS1 structure. (E) RMSD of the whole protein and pocket domain during MD. The pocket domain was defined as residues 83-93, 325-341 and 393-403. (F) Integrated residue C-alpha RMSF and pLDDT plot for simultaneous assessment of residue flexibility and structure-prediction confidence. (G) Integrated plot of hydrogen-bond occupancy and MM/GBSA residue contribution for the shared key residues SER332, LEU90, ASN86, THR330, GLN339, GLY328, PRO334 and GLN336. (H) Minimum heavy-atom distance fluctuations from the shared key residues to the ligand over time. (I) OCTET detection of binding responses between ipragliflozin and ETS1 at different concentrations. (J) Effect of ipragliflozin on MYO1B mRNA under TGF-β1/IL-1β. (K) Effect of ipragliflozin on MYO1B promoter ChIP-qPCR. (L) Effect of ipragliflozin on MYO1B flow-cytometry signal.

Article Snippet: To establish an inflammatory/TGF-β stimulation model, HMEC-1 cells were treated with recombinant human TGF-β1 (Abclonal, RP01458) and recombinant human IL-1β (Abclonal, RP00002) at 10 ng/mL each for 7 days.

Techniques: Screening, Docking Assay, Labeling, Binding Assay, Residue, ChIP-qPCR, Flow Cytometry

Journal: Pharmaceuticals

Article Title: CB2 Receptor Activation Attenuates IL-1β-Induced Inflammatory Transcriptomic Networks in Human Gingival Fibroblasts

doi: 10.3390/ph19091406

Figure Lengend Snippet: HU-308 attenuates IL-1β-induced interleukin expression in human gingival fibroblasts. Human gingival fibroblasts (HGFs) were divided into three experimental groups: untreated Control (black bars), IL-1β (10 ng/mL)-stimulated cells (red bars), and cells treated with IL-1β followed by the selective CB2 receptor agonist HU-308 (10 μM; blue bars). Twenty-four hours after IL-1β stimulation, transcript levels of proinflammatory and anti-inflammatory interleukins were quantified. IL-1β stimulation significantly increased the expression of the pro-inflammatory cytokines IL1B, IL6, IL23A, IL33, IL11, IL1α, and IL24, and treatment with HU-308 attenuated the IL-1β-induced expression of these cytokines, indicating suppression of the inflammatory response ( A – F ). In contrast, IL10 exhibited reduced expression following IL-1β stimulation, and HU-308 treatment partially restored its expression, supporting a shift toward a less inflammatory phenotype following CB2 receptor activation ( G ). Data are presented as mean ± SEM from three independent biological replicates ( n = 3 per group). Statistical significance was determined by one-way ANOVA followed by Tukey’s multiple-comparison test. * p < 0.05, ** p < 0.01, *** p < 0.001, and **** p < 0.0001 was considered statistically significant.

Article Snippet: Recombinant human IL-1β was obtained from (InvivoGen, San Diego, CA, USA), reconstituted in water according to the manufacturer’s instructions, and used at a final concentration of 10 ng/mL.

Techniques: Expressing, Control, Activation Assay, Comparison

Journal: Pharmaceuticals

Article Title: CB2 Receptor Activation Attenuates IL-1β-Induced Inflammatory Transcriptomic Networks in Human Gingival Fibroblasts

doi: 10.3390/ph19091406

Figure Lengend Snippet: HU-308 modulates IL-1β-induced chemokine expression in human gingival fibroblasts. Human gingival fibroblasts (HGFs) were divided into three experimental groups: untreated Control (black bars), IL-1β (10 ng/mL)-stimulated cells (red bars), and cells treated with IL-1β followed by the selective CB2 receptor agonist HU-308 (10 μM; blue bars). Twenty-four hours after IL-1β stimulation, transcript levels of inflammatory chemokines were quantified. IL-1β stimulation significantly increased the expression of CXCL5, CXCL8, CXCL16, CCL20, and CCL28, consistent with activation of chemokine-mediated inflammatory signaling ( A – E ). Treatment with HU-308 attenuated the IL-1β-induced expression of these chemokines, indicating suppression of inflammatory chemokine responses and reduced potential for immune-cell recruitment ( A – E ). Data are presented as mean ± SEM from three independent biological replicates ( n = 3 per group). Statistical significance was determined by one-way ANOVA followed by Tukey’s multiple-comparison test. * p < 0.05, *** p < 0.001, and **** p < 0.0001 was considered statistically significant.

Article Snippet: Recombinant human IL-1β was obtained from (InvivoGen, San Diego, CA, USA), reconstituted in water according to the manufacturer’s instructions, and used at a final concentration of 10 ng/mL.

Techniques: Expressing, Control, Activation Assay, Immune Cell, Comparison

Journal: Pharmaceuticals

Article Title: CB2 Receptor Activation Attenuates IL-1β-Induced Inflammatory Transcriptomic Networks in Human Gingival Fibroblasts

doi: 10.3390/ph19091406

Figure Lengend Snippet: HU-308 attenuates IL-1β-induced matrix metalloproteinase expression in human gingival fibroblasts. Human gingival fibroblasts (HGFs) were divided into three experimental groups: untreated Control (black bars), IL-1β (10 ng/mL)-stimulated cells (red bars), and cells treated with IL-1β followed by the selective CB2 receptor agonist HU-308 (10 μM; blue bars). Twenty-four hours after IL-1β stimulation, transcript levels of MMP1, MMP3, and MMP10 were quantified. IL-1β stimulation significantly increased the expression of all three matrix metalloproteinases, consistent with enhanced extracellular matrix degradation and tissue remodeling associated with periodontal inflammation ( A – C ). Treatment with HU-308 significantly attenuated the IL-1β-induced expression of MMP1, MMP3, and MMP10, suggesting that CB2 receptor modulation suppresses matrix-degrading pathways and may contribute to the preservation of periodontal tissue integrity ( A – C ). Data are presented as mean ± SEM from three independent biological replicates ( n = 3 per group). Statistical significance was determined by one-way ANOVA followed by Tukey’s multiple-comparison test. * p < 0.05, ** p < 0.01, *** p < 0.001, and **** p < 0.0001 was considered statistically significant.

Article Snippet: Recombinant human IL-1β was obtained from (InvivoGen, San Diego, CA, USA), reconstituted in water according to the manufacturer’s instructions, and used at a final concentration of 10 ng/mL.

Techniques: Expressing, Control, Tissue, Preserving, Comparison

Journal: Pharmaceuticals

Article Title: CB2 Receptor Activation Attenuates IL-1β-Induced Inflammatory Transcriptomic Networks in Human Gingival Fibroblasts

doi: 10.3390/ph19091406

Figure Lengend Snippet: HU-308 partially restores IL-1β-induced alterations in collagen gene expression in human gingival fibroblasts. Human gingival fibroblasts (HGFs) were divided into three experimental groups: untreated Control (black bars), IL-1β (10 ng/mL)-stimulated cells (red bars), and cells treated with IL-1β followed by the selective CB2 receptor agonist HU-308 (10 μM; blue bars). Twenty-four hours after IL-1β stimulation, transcript levels of COL1A1, COL3A1, COL11A1, and COL12A1 were quantified. IL-1β stimulation significantly reduced the expression of collagen-associated genes, consistent with impaired extracellular matrix synthesis and tissue remodeling during periodontal inflammation ( A – D ). Treatment with HU-308 partially restored the expression of these collagen transcripts toward control levels, suggesting that CB2 receptor activation may preserve extracellular matrix homeostasis and limit IL-1β-induced connective tissue damage ( A – D ). Data are presented as mean ± SEM from three independent biological replicates ( n = 3 per group). Statistical significance was determined by one-way ANOVA followed by Tukey’s multiple-comparison test. * p < 0.05, ** p < 0.01 and *** p < 0.001 was considered statistically significant.

Article Snippet: Recombinant human IL-1β was obtained from (InvivoGen, San Diego, CA, USA), reconstituted in water according to the manufacturer’s instructions, and used at a final concentration of 10 ng/mL.

Techniques: Gene Expression, Control, Expressing, Tissue, Activation Assay, Comparison

Journal: Pharmaceuticals

Article Title: CB2 Receptor Activation Attenuates IL-1β-Induced Inflammatory Transcriptomic Networks in Human Gingival Fibroblasts

doi: 10.3390/ph19091406

Figure Lengend Snippet: HU-308 modulates IL-1β-induced nitric oxide and oxidative stress-related gene expression in human gingival fibroblasts. Human gingival fibroblasts (HGFs) were divided into three experimental groups: untreated Control (black bars), IL-1β (10 ng/mL)-stimulated cells (red bars), and cells treated with IL-1β followed by the selective CB2 receptor agonist HU-308 (10 μM; blue bars). Twenty-four hours after IL-1β stimulation, transcript levels of NOS3, PRKG1 and PDE5A were quantified. IL-1β stimulation significantly altered the expression of genes involved in nitric oxide signaling, reflecting activation of redox-associated inflammatory pathways ( A – C ). Treatment with HU-308 modulated the IL-1β-induced expression of these genes, partially restoring their expression toward control levels and suggesting that CB2 receptor activation attenuates redox imbalance and nitric oxide signaling dysregulation associated with inflammatory activation ( A – C ). Data are presented as mean ± SEM from three independent biological replicates ( n = 3 per group). Statistical significance was determined by one-way ANOVA followed by Tukey’s multiple-comparison test. * p < 0.05, ** p < 0.01, *** p < 0.001, and **** p < 0.0001 was considered statistically significant.

Article Snippet: Recombinant human IL-1β was obtained from (InvivoGen, San Diego, CA, USA), reconstituted in water according to the manufacturer’s instructions, and used at a final concentration of 10 ng/mL.

Techniques: Gene Expression, Control, Expressing, Activation Assay, Comparison

Journal: Pharmaceuticals

Article Title: CB2 Receptor Activation Attenuates IL-1β-Induced Inflammatory Transcriptomic Networks in Human Gingival Fibroblasts

doi: 10.3390/ph19091406

Figure Lengend Snippet: HU-308 modulates IL-1β-associated changes in solute carrier transporter transcript expression in human gingival fibroblasts. Human gingival fibroblasts (HGFs) were divided into three experimental groups: untreated Control (black bars), IL-1β (10 ng/mL)-stimulated cells (red bars), and cells treated with IL-1β followed by the selective CB2 receptor agonist HU-308 (10 μM; blue bars). Twenty-four hours after IL-1β stimulation, transcript levels of SLC2A1, SLC2A3, SLC2A5, SLC5A13, and SLC2A14 were quantified. IL-1β stimulation significantly altered the expression of SLC2A1, SLC2A3, SLC2A5, SLC2A13, and SLC2A14, and HU-308 treatment significantly modified several of these IL-1β-associated transcriptional responses ( A – E ). These findings demonstrate changes in transporter-associated transcript abundance but do not establish corresponding alterations in substrate uptake, glucose utilization, glycolytic activity, or cellular metabolic flux. Data are presented as mean ± SEM from three independent biological replicates ( n = 3 per group). Statistical significance was determined by one-way ANOVA followed by Tukey’s multiple-comparison test. * p < 0.05, ** p < 0.01, *** p < 0.001, and **** p < 0.0001 was considered statistically significant.

Article Snippet: Recombinant human IL-1β was obtained from (InvivoGen, San Diego, CA, USA), reconstituted in water according to the manufacturer’s instructions, and used at a final concentration of 10 ng/mL.

Techniques: Expressing, Control, Modification, Activity Assay, Comparison

Journal: Pharmaceuticals

Article Title: CB2 Receptor Activation Attenuates IL-1β-Induced Inflammatory Transcriptomic Networks in Human Gingival Fibroblasts

doi: 10.3390/ph19091406

Figure Lengend Snippet: GPCR-related transcript modulation by IL-1β and HU-308 treatment in human gingival fibroblasts. Human gingival fibroblasts (HGFs) were divided into three experimental groups: untreated Control (black bars), IL-1β (10 ng/mL)-stimulated cells (red bars), and cells treated with IL-1β followed by the selective CB2 receptor agonist HU-308 (10 μM; blue bars). Twenty-four hours after IL-1β stimulation, transcript levels of GPR160, GPR180, GPR157, GPR61, GPR173, GPR155, GPR107, GPR75, GPR78, and GPR4 were quantified. IL-1β stimulation significantly altered the expression of multiple GPCR-related genes, including increased expression of GPR160, GPR180, GPR157, GPR61, GPR173, GPR155, GPR107, and GPR75, while reducing the expression of GPR78 and GPR4, indicating inflammatory remodeling of GPCR-associated signaling pathways in human gingival fibroblasts ( A – J ). Treatment with HU-308 modified several IL-1β-associated changes in GPCR-related transcript expression ( A – J ). These changes represent transcriptional associations and should not be interpreted as evidence of altered receptor activity or direct functional cross-talk with CB2. Data are presented as mean ± SEM from three independent biological replicates ( n = 3 per group). Statistical significance was determined by one-way ANOVA followed by Tukey’s multiple-comparison test. * p < 0.05, ** p < 0.01, *** p < 0.001, and **** p < 0.0001 was considered statistically significant.

Article Snippet: Recombinant human IL-1β was obtained from (InvivoGen, San Diego, CA, USA), reconstituted in water according to the manufacturer’s instructions, and used at a final concentration of 10 ng/mL.

Techniques: Control, Expressing, Protein-Protein interactions, Modification, Activity Assay, Functional Assay, Comparison

Journal: Pharmaceuticals

Article Title: CB2 Receptor Activation Attenuates IL-1β-Induced Inflammatory Transcriptomic Networks in Human Gingival Fibroblasts

doi: 10.3390/ph19091406

Figure Lengend Snippet: Schematic summary of the coordinated anti-inflammatory effects of CB2 receptor activation in IL-1β-stimulated human gingival fibroblasts. IL-1β stimulation establishes a pro-inflammatory transcriptional landscape characterized by coordinated upregulation of inflammatory cytokines, chemokines, matrix metalloproteinases (MMPs), glucose transporter (SLC2/GLUT) genes, and multiple G protein-coupled receptor (GPCR)-related transcripts, together with suppression of collagen-associated genes and nitric oxide (NO)/cGMP signaling components. Collectively, these changes promote inflammatory amplification, extracellular matrix degradation, metabolic reprogramming, impaired tissue repair, and disruption of periodontal homeostasis ( left panel ). Pharmacological modulation of the cannabinoid receptor type 2 (CB2) with the selective agonist HU-308 shifts this inflammatory landscape toward a more homeostatic phenotype (center panel). HU-308 broadly attenuates IL-1β-induced inflammatory responses by reducing the expression of pro-inflammatory cytokines, chemokines, MMPs, glucose transporter-related genes, and several GPR-associated transcripts, while restoring collagen gene expression, NO/cGMP signaling, and selected receptor-associated pathways ( right panel ). Upward and downward arrows beneath each biological domain summarize the direction of transcript changes for individual genes following IL-1β stimulation (red arrows) and subsequent HU-308 treatment (blue arrows). Overall, the integrated pathway analysis demonstrates that CB2 modulation functions as an upstream regulator of multiple interconnected biological networks, including inflammatory signaling, extracellular matrix remodeling, redox homeostasis, metabolic adaptation, and GPR-associated signaling, rather than acting on a single molecular pathway, thereby supporting a systems-level mechanism through which CB2 modulation may preserve periodontal tissue homeostasis during inflammation. This figure represents a conceptual summary of selected transcriptional patterns and does not constitute a statistically derived gene-network, pathway-enrichment, or genome-wide differential-expression analysis.

Article Snippet: Recombinant human IL-1β was obtained from (InvivoGen, San Diego, CA, USA), reconstituted in water according to the manufacturer’s instructions, and used at a final concentration of 10 ng/mL.

Techniques: Activation Assay, Amplification, Tissue, Disruption, Expressing, Gene Expression, Analysis, Derivative Assay, Genome Wide, Quantitative Proteomics

Journal: Cell Reports Medicine

Article Title: A biomimetic hybrid membrane vesicle nanoplatform attenuates tendinopathy through neuroinflammation modulation and tendon regeneration

doi: 10.1016/j.xcrm.2026.102937

Figure Lengend Snippet: MSM-DTM adsorbs inflammatory cytokines, suppresses TSPCs inflammation and senescence, and promotes tenogenic differentiation and migration (A) The remaining concentrations of TNF-α, IL-1β, IL-6, IFN-γ, LPS, and NGF were detected by ELISA after co-culture with different concentrations of MSM. (B and C) RT-qPCR of IL-6 and CCL-2 in TSPCs under different treatments. (D) Western blot of COL1A2, MMP3, and TNMD. (E) ELISA of TNF-α, IL-6, and IFN-γ in supernatants. (F)Western blot of p16 and p21 after 7 days of treatment. (G) β-Galactosidase staining analysis after 7 days of treatment. Scale bars, 100 μm. (H and I) Immunofluorescence and quantification of TNMD and TNC after 14-day treatment. Scale bars, 50 μm. (J) Relative mRNA expression of tenogenic differentiation markers SCX and TNC. (K and L) Representative images and quantification of Transwell assay. Scale bars, 100 μm. (M and N) Representative images and quantification of wound healing assay. Scale bars, 100 μm. Statistical comparisons were performed with one-way ANOVA with Tukey’s multiple comparisons test. Data are presented as the mean ± SD, n = 3. Ns, no significance, ∗ p < 0.05, ∗∗ p < 0.01, ∗∗∗ p < 0.001 between groups.

Article Snippet: IL-1β ELISA kit , ABclonal , RK00001.

Techniques: Migration, Enzyme-linked Immunosorbent Assay, Co-Culture Assay, Quantitative RT-PCR, Western Blot, Staining, Immunofluorescence, Expressing, Transwell Assay, Wound Healing Assay

Journal: Cell Reports Medicine

Article Title: A biomimetic hybrid membrane vesicle nanoplatform attenuates tendinopathy through neuroinflammation modulation and tendon regeneration

doi: 10.1016/j.xcrm.2026.102937

Figure Lengend Snippet: MSM-DTM alleviates TSPCs senescence via JAK-STAT pathway suppression (A) Volcano plot of differentially expressed genes between control and IL-1β groups. (B) Heatmap of gene expression in control, IL-1β, and MSM-DTM groups. (C) KEGG pathway analysis. (D) Excessive activation of the JAK-STAT pathway induces senescence of TSPCs. (E) Western blot of p-JAK2, JAK2, p-STAT3, and STAT3 in TSPCs. (F) Western blot of p16 and p21 in TSPCs. (G) β-Galactosidase staining analysis after 7 days of treatment. Scale bars, 100 μm. (H) The ratio of phosphorylated STAT3 expression to total STAT3 expression. (I and J) Relative expression levels of p16 and p21 proteins. Statistical comparisons were performed with one-way ANOVA with Tukey’s multiple comparisons test. Data are presented as the mean ± SD, n = 3. Ns, no significance, ∗ p < 0.05, ∗∗ p < 0.01, ∗∗∗ p < 0.001 between groups. BP, biological process; CC, cellular component; MF, molecular function.

Article Snippet: IL-1β ELISA kit , ABclonal , RK00001.

Techniques: Control, Gene Expression, Activation Assay, Western Blot, Staining, Expressing

Journal: Cell Reports Medicine

Article Title: A biomimetic hybrid membrane vesicle nanoplatform attenuates tendinopathy through neuroinflammation modulation and tendon regeneration

doi: 10.1016/j.xcrm.2026.102937

Figure Lengend Snippet:

Article Snippet: IL-1β ELISA kit , ABclonal , RK00001.

Techniques: Recombinant, Lysis, Hydroxyproline Assay, Enzyme-linked Immunosorbent Assay, Isolation, SYBR Green Assay, Bicinchoninic Acid Protein Assay, Staining, Software