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db1976  (MedChemExpress)


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    MedChemExpress db1976
    Characterization and Targeting Ability of D-NVs and D-FNVs. ( A ) Representative immunofluorescence images showing FOLR2 and CD68 expression in the aortic root sections from mice fed with a chow diet or a high-fat diet. ( B ) TEM image of D-FNVs, confirming their spherical morphology. Scale bar: 100 nm. ( C ) Western blot analysis of scavenger receptor A (SR-A) and Toll-like receptor 4 (TLR4) expression in macrophage-derived nanovesicles (D-NVs and D-FNVs). ( D - E ) Particle size and zeta potential of D-NVs and D-FNVs. ( F ) Encapsulation efficiency of D-NVs and D-FNVs. ( G ) Loading efficiency of D-NVs and D-FNVs. ( H ) Stability of D-NVs and D-FNVs evaluated by monitoring particle size and zeta potential over 10 days. ( I ) Release profile of <t>DB1976</t> from D-FNVs under different pH conditions (pH 7.4 and pH 6.5) at 37 °C. ( J ) Representative confocal fluorescence images of macrophages incubated with DiI-labeled D-NVs or D-FNVs (red) and stained with DiO (green). Scale bar: 50 μm. ( K ) Confocal images of macrophages treated with ox-LDL and subsequently incubated with DiI-labeled D-NVs or D-FNVs. Scale bar: 50 μm. ( L ) Confocal images of ox-LDL–treated macrophages incubated with DiI-labeled D-FNVs in the presence or absence of free folate. Scale bar: 50 μm. ( M – O ) Quantification of relative fluorescence intensity (RFI) per cell showing uptake of D-NVs and D-FNVs ( M ), uptake of D-NVs and D-FNVs in ox-LDL–treated macrophages ( N ), and competition assay with free folate ( O ). One-way ANOVA with Tukey’s multiple comparison post hoc test was used for statistical analysis. Data are presented as the mean ± standard deviation (SD). * p < 0.05, ** p < 0.01, *** p < 0.001, and **** p < 0.0001
    Db1976, supplied by MedChemExpress, used in various techniques. Bioz Stars score: 95/100, based on 29 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
    https://www.bioz.com/result/db1976/product/MedChemExpress
    Average 95 stars, based on 29 article reviews
    db1976 - by Bioz Stars, 2026-02
    95/100 stars

    Images

    1) Product Images from "Folate-modified biomimetic nanovesicles loaded with a PU.1 inhibitor alleviate atherosclerosis by suppressing inflammation"

    Article Title: Folate-modified biomimetic nanovesicles loaded with a PU.1 inhibitor alleviate atherosclerosis by suppressing inflammation

    Journal: Journal of Nanobiotechnology

    doi: 10.1186/s12951-025-03825-w

    Characterization and Targeting Ability of D-NVs and D-FNVs. ( A ) Representative immunofluorescence images showing FOLR2 and CD68 expression in the aortic root sections from mice fed with a chow diet or a high-fat diet. ( B ) TEM image of D-FNVs, confirming their spherical morphology. Scale bar: 100 nm. ( C ) Western blot analysis of scavenger receptor A (SR-A) and Toll-like receptor 4 (TLR4) expression in macrophage-derived nanovesicles (D-NVs and D-FNVs). ( D - E ) Particle size and zeta potential of D-NVs and D-FNVs. ( F ) Encapsulation efficiency of D-NVs and D-FNVs. ( G ) Loading efficiency of D-NVs and D-FNVs. ( H ) Stability of D-NVs and D-FNVs evaluated by monitoring particle size and zeta potential over 10 days. ( I ) Release profile of DB1976 from D-FNVs under different pH conditions (pH 7.4 and pH 6.5) at 37 °C. ( J ) Representative confocal fluorescence images of macrophages incubated with DiI-labeled D-NVs or D-FNVs (red) and stained with DiO (green). Scale bar: 50 μm. ( K ) Confocal images of macrophages treated with ox-LDL and subsequently incubated with DiI-labeled D-NVs or D-FNVs. Scale bar: 50 μm. ( L ) Confocal images of ox-LDL–treated macrophages incubated with DiI-labeled D-FNVs in the presence or absence of free folate. Scale bar: 50 μm. ( M – O ) Quantification of relative fluorescence intensity (RFI) per cell showing uptake of D-NVs and D-FNVs ( M ), uptake of D-NVs and D-FNVs in ox-LDL–treated macrophages ( N ), and competition assay with free folate ( O ). One-way ANOVA with Tukey’s multiple comparison post hoc test was used for statistical analysis. Data are presented as the mean ± standard deviation (SD). * p < 0.05, ** p < 0.01, *** p < 0.001, and **** p < 0.0001
    Figure Legend Snippet: Characterization and Targeting Ability of D-NVs and D-FNVs. ( A ) Representative immunofluorescence images showing FOLR2 and CD68 expression in the aortic root sections from mice fed with a chow diet or a high-fat diet. ( B ) TEM image of D-FNVs, confirming their spherical morphology. Scale bar: 100 nm. ( C ) Western blot analysis of scavenger receptor A (SR-A) and Toll-like receptor 4 (TLR4) expression in macrophage-derived nanovesicles (D-NVs and D-FNVs). ( D - E ) Particle size and zeta potential of D-NVs and D-FNVs. ( F ) Encapsulation efficiency of D-NVs and D-FNVs. ( G ) Loading efficiency of D-NVs and D-FNVs. ( H ) Stability of D-NVs and D-FNVs evaluated by monitoring particle size and zeta potential over 10 days. ( I ) Release profile of DB1976 from D-FNVs under different pH conditions (pH 7.4 and pH 6.5) at 37 °C. ( J ) Representative confocal fluorescence images of macrophages incubated with DiI-labeled D-NVs or D-FNVs (red) and stained with DiO (green). Scale bar: 50 μm. ( K ) Confocal images of macrophages treated with ox-LDL and subsequently incubated with DiI-labeled D-NVs or D-FNVs. Scale bar: 50 μm. ( L ) Confocal images of ox-LDL–treated macrophages incubated with DiI-labeled D-FNVs in the presence or absence of free folate. Scale bar: 50 μm. ( M – O ) Quantification of relative fluorescence intensity (RFI) per cell showing uptake of D-NVs and D-FNVs ( M ), uptake of D-NVs and D-FNVs in ox-LDL–treated macrophages ( N ), and competition assay with free folate ( O ). One-way ANOVA with Tukey’s multiple comparison post hoc test was used for statistical analysis. Data are presented as the mean ± standard deviation (SD). * p < 0.05, ** p < 0.01, *** p < 0.001, and **** p < 0.0001

    Techniques Used: Immunofluorescence, Expressing, Western Blot, Derivative Assay, Zeta Potential Analyzer, Encapsulation, Fluorescence, Incubation, Labeling, Staining, Competitive Binding Assay, Comparison, Standard Deviation

    PU.1 is upregulated in macrophages of advanced atherosclerotic lesions and promotes inflammation through IL-1β/NF-κB signaling. ( A ) Boxplot showing expression levels of PU.1 in early versus advanced atherosclerotic plaques based on the GSE43292 dataset. ( B ) UMAP plot of single-cell RNA sequencing data depicting major immune and stromal cell populations in atherosclerotic lesions. ( C ) UMAP feature plot showing SPI1 (encoding PU.1) expression predominantly enriched in macrophages. ( D ) Representative immunofluorescence staining of PU.1 (green) and CD68 (red) in aortic root sections from chow diet– and high fat diet–fed mice. Nuclei were counterstained with DAPI (blue). Scale bar: 200 μm. ( E ) CUT&Tag analysis showing genome-wide binding of PU.1 in macrophages. Heatmap indicates PU.1 enrichment near transcription start sites (TSS). ( F ) Genomic distribution of PU.1 binding peaks identified by CUT&Tag. ( G – H ) Representative CUT&Tag tracks showing PU.1 binding at the promoters of pro-inflammatory cytokines. ( I ) Dual-luciferase reporter assay confirming the transcriptional activation of the IL-1β promoter by PU.1 overexpression (OE). ( J ) Western blot showing that PU.1 knockdown suppressed ox-LDL–induced IL-1β expression and NF-κB pathway activation (p-IκB and p-p65). ( K ) Western blot demonstrating that IL-1β knockdown reversed PU.1-induced NF-κB activation. ( L ) Western blot analysis showing that the PU.1 inhibitor DB1976 attenuated ox-LDL–induced IL-1β expression and NF-κB activation. ( M ) qRT-PCR analysis of pro-inflammatory cytokines (IL-1β, IL-6, TNF-α, MCP-1) in macrophages treated with ox-LDL with or without DB1976. One-way ANOVA with Tukey’s multiple comparison post hoc test was used for statistical analysis. Data are presented as the mean ± standard deviation (SD). * p < 0.05, ** p < 0.01, *** p < 0.001, and **** p < 0.0001
    Figure Legend Snippet: PU.1 is upregulated in macrophages of advanced atherosclerotic lesions and promotes inflammation through IL-1β/NF-κB signaling. ( A ) Boxplot showing expression levels of PU.1 in early versus advanced atherosclerotic plaques based on the GSE43292 dataset. ( B ) UMAP plot of single-cell RNA sequencing data depicting major immune and stromal cell populations in atherosclerotic lesions. ( C ) UMAP feature plot showing SPI1 (encoding PU.1) expression predominantly enriched in macrophages. ( D ) Representative immunofluorescence staining of PU.1 (green) and CD68 (red) in aortic root sections from chow diet– and high fat diet–fed mice. Nuclei were counterstained with DAPI (blue). Scale bar: 200 μm. ( E ) CUT&Tag analysis showing genome-wide binding of PU.1 in macrophages. Heatmap indicates PU.1 enrichment near transcription start sites (TSS). ( F ) Genomic distribution of PU.1 binding peaks identified by CUT&Tag. ( G – H ) Representative CUT&Tag tracks showing PU.1 binding at the promoters of pro-inflammatory cytokines. ( I ) Dual-luciferase reporter assay confirming the transcriptional activation of the IL-1β promoter by PU.1 overexpression (OE). ( J ) Western blot showing that PU.1 knockdown suppressed ox-LDL–induced IL-1β expression and NF-κB pathway activation (p-IκB and p-p65). ( K ) Western blot demonstrating that IL-1β knockdown reversed PU.1-induced NF-κB activation. ( L ) Western blot analysis showing that the PU.1 inhibitor DB1976 attenuated ox-LDL–induced IL-1β expression and NF-κB activation. ( M ) qRT-PCR analysis of pro-inflammatory cytokines (IL-1β, IL-6, TNF-α, MCP-1) in macrophages treated with ox-LDL with or without DB1976. One-way ANOVA with Tukey’s multiple comparison post hoc test was used for statistical analysis. Data are presented as the mean ± standard deviation (SD). * p < 0.05, ** p < 0.01, *** p < 0.001, and **** p < 0.0001

    Techniques Used: Expressing, RNA Sequencing, Immunofluorescence, Staining, Genome Wide, Binding Assay, Luciferase, Reporter Assay, Activation Assay, Over Expression, Western Blot, Knockdown, Quantitative RT-PCR, Comparison, Standard Deviation

    The anti-atherosclerotic effects of the D-FNVs. ( A - D ) BMDMs were co-treated with ox-LDL (100 µg/mL) and various formulations (free DB1976, D-NVs, D-FNVs). The levels of IL-1β, IL-6, TNF-α, and MCP-1 in the supernatant were measured by ELISA. ( E , F ) Flow cytometry analysis and quantification of intracellular ROS levels in BMDM cells treated with ox-LDL (100 µg/mL) and various formulations (free DB1976, D-NVs, D-FNVs), respectively, at 2 mM DB1976 for 24 h. ( G , H ) Flow cytometry analysis and quantification of apoptosis rates in BMDMs treated with ox-LDL (100 µg/mL) and various formulations (free DB1976, D-NVs, D-FNVs) at 2 mM DB1976 for 24 h. One-way ANOVA with Tukey’s multiple comparison post hoc test was used for statistical analysis. Data are presented as the mean ± standard deviation (SD). * p < 0.05, ** p < 0.01, *** p < 0.001, and **** p < 0.0001
    Figure Legend Snippet: The anti-atherosclerotic effects of the D-FNVs. ( A - D ) BMDMs were co-treated with ox-LDL (100 µg/mL) and various formulations (free DB1976, D-NVs, D-FNVs). The levels of IL-1β, IL-6, TNF-α, and MCP-1 in the supernatant were measured by ELISA. ( E , F ) Flow cytometry analysis and quantification of intracellular ROS levels in BMDM cells treated with ox-LDL (100 µg/mL) and various formulations (free DB1976, D-NVs, D-FNVs), respectively, at 2 mM DB1976 for 24 h. ( G , H ) Flow cytometry analysis and quantification of apoptosis rates in BMDMs treated with ox-LDL (100 µg/mL) and various formulations (free DB1976, D-NVs, D-FNVs) at 2 mM DB1976 for 24 h. One-way ANOVA with Tukey’s multiple comparison post hoc test was used for statistical analysis. Data are presented as the mean ± standard deviation (SD). * p < 0.05, ** p < 0.01, *** p < 0.001, and **** p < 0.0001

    Techniques Used: Enzyme-linked Immunosorbent Assay, Flow Cytometry, Comparison, Standard Deviation

    Biodistribution and pharmacokinetics of D-NVs and D-FNVs in vivo. ( A ) Fluorescence imaging of DiD fluorescent signals in aortic tissues. ApoE −/− mice fed a high-fat diet for 3 months were intravenously administered DiD-labeled D-NVs or D-FNVs. Ex vivo fluorescence imaging of aortic tissues was performed using IVIS. ( B ) Quantitative analysis of DiD fluorescent signals in aortic tissues. ( C ) Confocal laser scanning microscopy (CLSM) images of DiD-labeled D-NVs and D-FNVs accumulated in atherosclerotic plaques of aortic root sections. Plaques are outlined by white dashed lines. Scale bar: 200 μm. ( D ) Biodistribution of D-NVs and D-FNVs in major organs (heart, liver, spleen, lung, and kidney) evaluated at 24 and 48 h after intravenous administration of DiD-labeled nanovesicles.( E ) DB1976 concentration in aortic tissues after administration of free DB1976, D-NVs, or D-FNVs. ( F ) Plasma pharmacokinetics of DB1976 following intravenous administration of free DB1976, D-NVs, or D-FNVs. ( G ) DB1976 distribution in major organs at 24 h after injection. One-way ANOVA with Tukey’s multiple comparison post hoc test was used for statistical analysis. Data are presented as the mean ± standard deviation (SD). * p < 0.05, ** p < 0.01, *** p < 0.001, and **** p < 0.0001
    Figure Legend Snippet: Biodistribution and pharmacokinetics of D-NVs and D-FNVs in vivo. ( A ) Fluorescence imaging of DiD fluorescent signals in aortic tissues. ApoE −/− mice fed a high-fat diet for 3 months were intravenously administered DiD-labeled D-NVs or D-FNVs. Ex vivo fluorescence imaging of aortic tissues was performed using IVIS. ( B ) Quantitative analysis of DiD fluorescent signals in aortic tissues. ( C ) Confocal laser scanning microscopy (CLSM) images of DiD-labeled D-NVs and D-FNVs accumulated in atherosclerotic plaques of aortic root sections. Plaques are outlined by white dashed lines. Scale bar: 200 μm. ( D ) Biodistribution of D-NVs and D-FNVs in major organs (heart, liver, spleen, lung, and kidney) evaluated at 24 and 48 h after intravenous administration of DiD-labeled nanovesicles.( E ) DB1976 concentration in aortic tissues after administration of free DB1976, D-NVs, or D-FNVs. ( F ) Plasma pharmacokinetics of DB1976 following intravenous administration of free DB1976, D-NVs, or D-FNVs. ( G ) DB1976 distribution in major organs at 24 h after injection. One-way ANOVA with Tukey’s multiple comparison post hoc test was used for statistical analysis. Data are presented as the mean ± standard deviation (SD). * p < 0.05, ** p < 0.01, *** p < 0.001, and **** p < 0.0001

    Techniques Used: Drug discovery, In Vivo, Fluorescence, Imaging, Labeling, Ex Vivo, Confocal Laser Scanning Microscopy, Concentration Assay, Clinical Proteomics, Injection, Comparison, Standard Deviation

    Therapeutic efficacy of free DB976, D-NVs, D-FNVs on atherosclerosis ( A ) Schematic illustration of the development of an atherosclerotic mouse model and the treatment protocol with various formulations (Saline, free DB1976, D-NVs, and D-FNVs) at a dose of 2 mg/kg DB1976 per injection. ( B ) Representative photographs of En face Oil Red O (ORO)-stained aortas collected from atherosclerotic mice after treatment with the indicated formulations. ( C ) Quantitative analysis of the aortic lesion area, expressed as the mean ± SD. ( D - E ) Representative microphotographs and quantitative analysis of Oil Red O-stained aortic root sections from mice treated with different formulations. Scale bar: 500 μm. ( F ) Representative hematoxylin and eosin (H&E)-stained aortic root sections from the different treatment groups. Scale bar: 500 μm. ( G ) Quantification of the percentage of necrotic core area in aortic root plaques (mean ± SD). One-way ANOVA with Tukey’s multiple comparison post hoc test was used for statistical analysis. Data are presented as the mean ± standard deviation (SD). * p < 0.05, ** p < 0.01, *** p < 0.001, and **** p < 0.0001
    Figure Legend Snippet: Therapeutic efficacy of free DB976, D-NVs, D-FNVs on atherosclerosis ( A ) Schematic illustration of the development of an atherosclerotic mouse model and the treatment protocol with various formulations (Saline, free DB1976, D-NVs, and D-FNVs) at a dose of 2 mg/kg DB1976 per injection. ( B ) Representative photographs of En face Oil Red O (ORO)-stained aortas collected from atherosclerotic mice after treatment with the indicated formulations. ( C ) Quantitative analysis of the aortic lesion area, expressed as the mean ± SD. ( D - E ) Representative microphotographs and quantitative analysis of Oil Red O-stained aortic root sections from mice treated with different formulations. Scale bar: 500 μm. ( F ) Representative hematoxylin and eosin (H&E)-stained aortic root sections from the different treatment groups. Scale bar: 500 μm. ( G ) Quantification of the percentage of necrotic core area in aortic root plaques (mean ± SD). One-way ANOVA with Tukey’s multiple comparison post hoc test was used for statistical analysis. Data are presented as the mean ± standard deviation (SD). * p < 0.05, ** p < 0.01, *** p < 0.001, and **** p < 0.0001

    Techniques Used: Drug discovery, Saline, Injection, Staining, Comparison, Standard Deviation

    D-FNVs ameliorated inflammation in an atherosclerotic mouse model. ( A , B ) Representative images of plaques within the aortic root subjected to immunofluorescent staining for the macrophage marker CD68. Scale bar: 100 μm. ( C – F ) Levels of IL-1β, IL-6, TNF-α, and MCP-1 in aortic tissues collected from atherosclerotic mice treated with various formulations (saline, DB1976, D-NVs, D-FNVs). ( G – J ) Levels of IL-1β, IL-6, TNF-α, and MCP-1 in blood serum collected from the same groups of atherosclerotic mice. The n values are all biological replicates. One-way ANOVA with Tukey’s multiple comparison post hoc test was used for statistical analysis. Data are presented as the mean ± standard deviation (SD). * p < 0.05, ** p < 0.01, and *** p < 0.001. **** p < 0.0001
    Figure Legend Snippet: D-FNVs ameliorated inflammation in an atherosclerotic mouse model. ( A , B ) Representative images of plaques within the aortic root subjected to immunofluorescent staining for the macrophage marker CD68. Scale bar: 100 μm. ( C – F ) Levels of IL-1β, IL-6, TNF-α, and MCP-1 in aortic tissues collected from atherosclerotic mice treated with various formulations (saline, DB1976, D-NVs, D-FNVs). ( G – J ) Levels of IL-1β, IL-6, TNF-α, and MCP-1 in blood serum collected from the same groups of atherosclerotic mice. The n values are all biological replicates. One-way ANOVA with Tukey’s multiple comparison post hoc test was used for statistical analysis. Data are presented as the mean ± standard deviation (SD). * p < 0.05, ** p < 0.01, and *** p < 0.001. **** p < 0.0001

    Techniques Used: Staining, Marker, Saline, Comparison, Standard Deviation



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