Journal: Research

Article Title: Neutrophil Extracellular Traps-Mediated Intraplaque Angiogenesis and Microvascular Permeability Promote Rapid Plaque Progression following Myocardial Infarction

doi: 10.34133/research.1451

Figure Lengend Snippet: Pharmacological inhibition of ETS proto-oncogene 1 (ETS1) attenuates rapid plaque progression in nonculprit lesions following myocardial infarction (MI). (A) Schematic of the animal experimental modeling process. (B) Representative immunofluorescence staining images of CD31, ACKR1, fluorescein isothiocyanate (FITC)-dextran and vascular endothelial (VE)-cadherin across the indicated groups (scale bars = 100 μm for regular panels and 50 μm for zoom panels). (C to F) Quantification of intraplaque CD31 + area, CD31 + ACKR1 + area, FITC-dextran + area, and CD31 + Ve-cadherin + area relative to plaque area across the indicated groups ( n = 5 per group). Statistical analyses were performed using 1-way analysis of variance (ANOVA) with Bonferroni posttest (C to F).

Article Snippet: To inhibit ETS1, mice were treated with the small-molecule inhibitor TK216 (MCE, HY-122903) via oral gavage (100 mg/kg, twice daily) during the final 4 weeks of the protocol [ ].

Techniques: Inhibition, Immunofluorescence, Staining, Analysis

Journal: Research

Article Title: Neutrophil Extracellular Traps-Mediated Intraplaque Angiogenesis and Microvascular Permeability Promote Rapid Plaque Progression following Myocardial Infarction

doi: 10.34133/research.1451

Figure Lengend Snippet: Mechanism diagram. Myocardial infarction (MI) promotes nonculprit plaque rapid progression, a process that facilitates recurrent ischemic events. Mechanistically, we identify the transcription factor ETS proto-oncogene 1 (ETS1) as a key regulator that activates the vascular endothelial growth factor A (VEGFA)/vascular endothelial growth factor receptor 2 (VEGFR2) signaling pathway in ECs in response to elevated neutrophil extracellular traps (NETs) formation post-MI. This ETS1-mediated signaling promotes the formation of immature, hyperpermeable neovessels, culminating in intraplaque hemorrhage and subsequent rapid plaque progression in nonculprit plaques.

Article Snippet: To inhibit ETS1, mice were treated with the small-molecule inhibitor TK216 (MCE, HY-122903) via oral gavage (100 mg/kg, twice daily) during the final 4 weeks of the protocol [ ].

Techniques:

Journal: Advanced Science

Article Title: Chemotherapy‐Activated GSK3β‐DNMT1 Signaling Upregulates CD47 to Evade Macrophage Phagocytosis and Drive Temozolomide Resistance in Glioblastoma

doi: 10.1002/advs.77471

Figure Lengend Snippet: WIN 51708 disrupts the p‐GSK3β‐Y216‐DNMT1‐S977 interface to restore DNMT1 stability and overcome TMZ resistance in GBM. (A) Schematic of virtual screening steps for small molecule compounds. This panel was generated with BioRender.com. (B) The rank list of Top3 target compounds for disrupts the P‐GSK3β‐Y216 and DNMT1 S977 interaction. (C) Molecular docking model (left) and chemical structure (right) of WIN 51708 showing predicted binding at the p‐GSK3β‐Y216‐DNMT1‐S977 interface. (D) Dose‐response curves and IC 50 determination for WIN 51708 in U87‐R and GL261‐R cells by CCK‐8 assay. (E) CCK‐8 assay measuring TMZ‐induced cytotoxicity in U87‐R (left) and GL261‐R (right) cells co‐treated with DMSO or WIN 51708 at sub‐IC 50 concentrations. ( n = 6, * p < 0.05, ** p < 0.01, unpaired t‐ test). (F) Western blot analysis of DNMT1 phosphorylation and ubiquitination in U87‐S cells treated with TMZ, WIN 51708 or Substance P (SP). (G) Western blot analysis of DNMT1 phosphorylation and ubiquitination in U87‐R cells treated with WIN 51708 or SP. (H) Representative image (left) and phagocytosis (right) of patient‐derived GBM organoids (PDOs) growth after combined treatment of WIN 51708 and TMZ. (Scale bars, 20 µm). (I) Growth curve of PDOs after combined treatment of WIN 51708 and TMZ. ( n = 6, ** p < 0.01, unpaired t‐ test). (J) Schematic of combined treatment of WIN 51708 (5 mg kg − 1 , intraperitoneal) and TMZ (20 mg kg − 1 , oral gavage) in GL261‐R mouse model. (K) In vivo bioluminescent imaging (left) and quantification (right) of tumor bearing mice after combined treatment of WIN 51708 and TMZ in mTMZ‐R models. ( n = 6, * p < 0.05, ** p < 0.01, one‐way ANOVA). (L) Flow cytometry‐based in vivo phagocytosis (left) and quantification (right) in panel K. ( n = 3, * p < 0.05, ** p < 0.01, ns = not significant, one‐way ANOVA).

Article Snippet: To identify small‐molecule inhibitors that potentially disrupt the interaction between p‐GSK3β‐Y216 and the S977 region of DNMT1, virtual screening was performed using a bioactive compound library from the TargetMol database ( https://www.targetmol.cn ), comprising 17,760 known bioactive compounds.

Techniques: Generated, Binding Assay, CCK-8 Assay, Western Blot, Phospho-proteomics, Ubiquitin Proteomics, Derivative Assay, In Vivo, Imaging, Flow Cytometry

Journal: Nature Communications

Article Title: Molecular basis of diverse ligand recognition and species-specific pharmacology at the complement anaphylatoxin receptor C3aR

doi: 10.1038/s41467-026-76518-z

Figure Lengend Snippet: A Chemical structures of small molecule ligands of C3aR, SB290157 and JR14a, drawn using ChemDraw software. B SB290157/JR14a-induced G-protein-coupling measured using NanoBiT-based G-protein dissociation and GloSensor-based cAMP assays upon stimulation of HEK-293 cells expressing the indicated receptors. Data was normalized with respect to the response at the lowest ligand concentration treated as 100% (mean ± SEM; n = 3 independent experiments). C SB290157/JR14a-induced βarr1/2 recruitment measured using a NanoBiT-based assay upon stimulation of HEK-293 cells expressing the indicated receptors. Data was normalized to the response at the lowest ligand concentration, which was set to 1 (mean ± SEM; n = 3 independent experiments). Comparison of Emax and EC 50 values of the corresponding data are presented in Supplementary Table . Source data are provided as a file.

Article Snippet: Small-molecule compounds SB290157 and JR14a were obtained from MedChem Express (Cat. No: HY-101502A for SB290157; Cat. No: HY-138161 for JR14a).

Techniques: Software, Expressing, Concentration Assay, Comparison

Journal: Nature Communications

Article Title: Molecular basis of diverse ligand recognition and species-specific pharmacology at the complement anaphylatoxin receptor C3aR

doi: 10.1038/s41467-026-76518-z

Figure Lengend Snippet: A–K Structural comparison of the indicated structures, highlighting the key differences in the overall positioning of various ligands in the orthosteric pocket of the human and mouse C3aR. PDB: 8I9L for hC3a-hC3aR, 9KZK for mC3a-mC3aR, 9KV8 for hTLQP-21-mC3aR, 9KV6 for mTLQP-21-mC3aR, 8I95 for EP54-hC3aR, 9UMJ for EP54-mC3aR, 9KUT for JR14a-hC3aR, 9L0H for JR14a-mC3aR and 9KVP for SB290157-hC3aR complex.

Article Snippet: Small-molecule compounds SB290157 and JR14a were obtained from MedChem Express (Cat. No: HY-101502A for SB290157; Cat. No: HY-138161 for JR14a).

Techniques: Comparison

Journal: Nature Communications

Article Title: Molecular basis of diverse ligand recognition and species-specific pharmacology at the complement anaphylatoxin receptor C3aR

doi: 10.1038/s41467-026-76518-z

Figure Lengend Snippet: Selected interactions of the indicated ligands in the orthosteric pocket of the human and mouse C3aR, highlighting the conserved interactions with those of C3a. PDB: 8I9L for hC3a-hC3aR, 9KZK for mC3a-mC3aR, 9KV8 for hTLQP-21-mC3aR, 9KV6 for mTLQP-21-mC3aR, 8I95 for EP54-hC3aR, 9UMJ for EP54-mC3aR, 9KUT for JR14a-hC3aR, 9L0H for JR14a-mC3aR and 9KVP for SB290157-hC3aR complex.

Article Snippet: Small-molecule compounds SB290157 and JR14a were obtained from MedChem Express (Cat. No: HY-101502A for SB290157; Cat. No: HY-138161 for JR14a).

Techniques:

Journal: Nature Communications

Article Title: Molecular basis of diverse ligand recognition and species-specific pharmacology at the complement anaphylatoxin receptor C3aR

doi: 10.1038/s41467-026-76518-z

Figure Lengend Snippet: A Structural comparison of SB290157 and JR14a binding pose to human and mouse C3aR. B Structural comparison of SB290157- and JR14a-bound C3aR structure with the inactive C5aR1 reveals activation-dependent structural changes, including the outwards movement of TM6, TM7 and Helix8. C , D SB290157/JR14a-induced cAMP response and βarr1 recruitment measured using the GloSensor assay and NanoBiT-based assay, respectively, upon stimulation of HEK-293 cells expressing the indicated receptor mutants. Data were normalized with the response for the wild-type treated as 100% (mean; n = 3 independent experiments). Comparison of ligand pharmacology of the above data are presented in Supplementary Tables . Source data are provided as a file.

Article Snippet: Small-molecule compounds SB290157 and JR14a were obtained from MedChem Express (Cat. No: HY-101502A for SB290157; Cat. No: HY-138161 for JR14a).

Techniques: Comparison, Binding Assay, Activation Assay, Expressing