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Enamine Ltd
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Santa Cruz Biotechnology
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Bazedoxifene (acetate)-D (TSE-424 (acetate)-D) is the D-crystal form compound of Bazedoxifene acetate (HY-A0036). Bazedoxifene acetate is an orally active, nonsteroidal selective estrogen receptor modulator (SERM), with IC50s of 23 nM and 99 nM for ERα
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Image Search Results
Journal: International Journal of Biological Sciences
Article Title: Bazedoxifene Targets gp130 Signaling to Suppress Fibroblast Activation in Pathological Cutaneous Fibrosis: Insights from Spatial Transcriptomics and scRNA-seq Data
doi: 10.7150/ijbs.137778
Figure Lengend Snippet: Bazedoxifene inhibits fibroblast migration, myofibroblast differentiation, and ECM production in keloid-derived fibroblasts. (A) Schematic illustration of the experimental design. Primary fibroblasts were isolated from keloid tissues and normal skin tissues obtained from patients and treated with Bazedoxifene for functional assays. (B) A CCK-8 assay was used to evaluate cell viability of NDFs and KDFs treated with increasing concentrations of Bazedoxifene for 48 h. The shaded area indicates concentrations at which cell viability remained above 90%. (C) Representative images of scratch wound healing assays showing KDF migration at 0 h, 24 h, and 48 h following treatment with Bazedoxifene (0, 2.5, and 5 μM). White lines indicate the wound boundaries. (D) Quantification of wound closure area in scratch assays. (E) Representative images of Transwell migration assays of fibroblasts treated with Bazedoxifene (0, 2.5, and 5 μM) for 24 h and 48 h. Scale bar: 500 μm. (F) Quantification of migrated cells per field in Transwell migration assays. (G) Relative mRNA expression levels of ACTA2 , COL1A1 , COL3A1 , and FN1 following Bazedoxifene treatment, determined by qRT-PCR. (H) Western blot analysis of FN1, COL3A1, COL1A1, and α-SMA protein expression relative to GAPDH in KDFs treated with Bazedoxifene. (I) Densitometric quantification of relative protein levels normalized to GAPDH. (J) Representative immunofluorescence staining of α-SMA, COL1A1, COL3A1, and FN1 (green) in KDFs treated with Bazedoxifene. (K) Quantification of relative fluorescence intensity of α-SMA, COL1A1, COL3A1, and FN1. Data are presented as mean ± SD (n = 3). Statistical significance was determined using one-way ANOVA followed by multiple comparisons test. *P < 0.05 , **P < 0.01 , ***P < 0.001. NDF, normal dermal fibroblast; KDF, keloid-derived fibroblast.
Article Snippet:
Techniques: Migration, Derivative Assay, Isolation, Functional Assay, CCK-8 Assay, Expressing, Quantitative RT-PCR, Western Blot, Analysis, Immunofluorescence, Staining, Fluorescence, Cell Viability Assay, Wound Healing Assay, Transwell Assay, Real-time Polymerase Chain Reaction
Journal: International Journal of Biological Sciences
Article Title: Bazedoxifene Targets gp130 Signaling to Suppress Fibroblast Activation in Pathological Cutaneous Fibrosis: Insights from Spatial Transcriptomics and scRNA-seq Data
doi: 10.7150/ijbs.137778
Figure Lengend Snippet: Bazedoxifene attenuates IL-11/IL-6-induced fibroblast migration, myofibroblast differentiation, and ECM production. (A-D) Relative mRNA expression levels of fibrotic genes ACTA2 (A), COL1A1 (B), COL3A1 (C), and FN1 (D) in NDFs under IL-11 or IL-6 stimulation with Bazedoxifene (0, 2.5, and 5 μM), as determined by qRT-PCR. (E) Western blot analysis of FN1, COL3A1, COL1A1, and α-SMA protein expression relative to GAPDH in NDFs under IL-11 or IL-6 stimulation with Bazedoxifene (Low, 2.5 μM; High, 5 μM). (F, G) Densitometric quantification of relative protein levels normalized to GAPDH under IL-11 stimulation (F) or IL-6 stimulation (G). (H) Representative images of scratch wound healing assays showing NDF migration at 0 h, 12 h, and 24 h under IL-11 or IL-6 stimulation with or without Bazedoxifene (5 μM). White lines indicate the wound boundaries. (I) Quantification of migration area in scratch wound healing assays. (J) Representative images of Transwell migration assays showing NDF migration at 48 h under IL-11 or IL-6 stimulation with or without Bazedoxifene (5 μM). (K) Quantification of migrated cells in Transwell migration assays. Data are presented as mean ± SD (n = 3). Statistical significance was determined using one-way ANOVA followed by multiple comparisons test. * P < 0.05 , ** P < 0.01 , *** P < 0.001 . NDF, normal dermal fibroblast; Baz, Bazedoxifene.
Article Snippet:
Techniques: Migration, Expressing, Quantitative RT-PCR, Western Blot, Analysis, Real-time Polymerase Chain Reaction
Journal: International Journal of Biological Sciences
Article Title: Bazedoxifene Targets gp130 Signaling to Suppress Fibroblast Activation in Pathological Cutaneous Fibrosis: Insights from Spatial Transcriptomics and scRNA-seq Data
doi: 10.7150/ijbs.137778
Figure Lengend Snippet: Genetic silencing of IL6ST supports gp130 as the principal mediator of the antifibrotic effects of Bazedoxifene. (A) Relative IL6ST mRNA expression in KDFs following transfection with two independent IL6ST siRNAs, as determined by qRT-PCR. (B) Western blot analysis of gp130 expression after IL6ST knockdown in KDFs. (C) Densitometric quantification of gp130 protein levels normalized to GAPDH. siIL6ST-1 was selected for subsequent experiments. (D) Relative mRNA expression of ACTA2 , COL1A1 , COL3A1 , and FN1 in KDFs following IL6ST knockdown with or without Bazedoxifene treatment, as determined by qRT-PCR. (E) Western blot analysis of FN1, COL3A1, COL1A1, and α-SMA protein expression following IL6ST knockdown with or without Bazedoxifene treatment in KDFs. (F) Densitometric quantification of relative protein levels normalized to GAPDH. (G-J) Relative mRNA expression levels of ACTA2 , COL1A1 , COL3A1 , and FN1 in IL-11-stimulated NDFs following IL6ST knockdown with or without Bazedoxifene treatment, as determined by qRT-PCR. (K) Western blot analysis of FN1, COL3A1, COL1A1, and α-SMA protein expression in IL-11-stimulated NDFs following IL6ST knockdown with or without Bazedoxifene treatment. (L-O) Densitometric quantification of relative protein levels normalized to GAPDH. Data are presented as mean ± SD (n = 3). Statistical significance was determined using one-way ANOVA followed by multiple comparisons test. *P < 0.05, **P < 0.01, ***P < 0.001; ns, not significant .
Article Snippet:
Techniques: Expressing, Transfection, Quantitative RT-PCR, Western Blot, Analysis, Knockdown, Real-time Polymerase Chain Reaction
Journal: International Journal of Biological Sciences
Article Title: Bazedoxifene Targets gp130 Signaling to Suppress Fibroblast Activation in Pathological Cutaneous Fibrosis: Insights from Spatial Transcriptomics and scRNA-seq Data
doi: 10.7150/ijbs.137778
Figure Lengend Snippet: Bazedoxifene attenuates dermal fibrosis in vivo . (A) Study design of the bleomycin-induced skin fibrosis model and Bazedoxifene treatment regimen (n = 6 biologically independent mice per group). (B) Representative images of HE and Masson trichrome staining of skin tissues from Sham, Bleo+DMSO, and Bleo+Baz groups at post-injection day 60 (PID60). Scale bar: 100 μm. Quantification of dermal thickness and relative collagen content is shown on the right. Samples were collected from six mice per group, and data are presented as mean ± SD. Statistical significance was determined using one-way ANOVA followed by multiple comparisons test. * P < 0.05 , ** P < 0.01 , *** P < 0.001. (C) Representative images of picrosirius red staining under polarized light (top), collagen orientation analysis (middle), and FN1 immunofluorescence staining (bottom) in skin tissues from the indicated groups. Collagen orientation analysis was conducted on picrosirius red-stained images using OrientationJ software. Scale bar: 100 μm. (D) Quantification of relative COL1/COL3 ratio (left) and relative FN1 density (right). Samples were collected from six mice per group, and data are presented as mean ± SD. Statistical significance was determined using one-way ANOVA followed by multiple comparisons test. * P < 0.05 , ** P < 0.01 , *** P < 0.001 . (E) Quantitative analysis of collagen fiber orientation distribution by OrientationJ software. Representative orientation distribution curves from two independent fields are shown. The Bleo+DMSO group exhibited a pronounced peak in orientation distribution, indicating increased collagen alignment along a dominant direction. Additional representative fields are presented in A. (F) Study design of the patient-derived keloid xenograft model and Bazedoxifene treatment regimen (n = 8 biologically independent mice per group). (G) Gross view of excised keloid xenografts at postoperative day 33 (POD33) following treatment with DMSO or Bazedoxifene. Quantification of keloid reduction ratio is shown on the right. Data are presented as mean ± SD (n = 8 pairs of xenografts). Statistical significance was determined using paired two-tailed Student's t-test. * P < 0.05 , ** P < 0.01 , *** P < 0.001. (H) Representative images of Masson trichrome staining (left), picrosirius red staining under polarized light (upper-middle), and collagen orientation analysis (lower middle) in xenograft tissues. Quantification of relative collagen content and relative COL1/COL3 ratio is shown on the right. Data are presented as mean ± SD (n = 8 pairs of xenografts). Statistical significance was determined using paired two-tailed Student's t-test. * P < 0.05 , ** P < 0.01 , *** P < 0.001. (I) Quantitative analysis of collagen fiber orientation distribution in xenograft tissues using OrientationJ software. Representative orientation distribution curves from two independent fields are shown. The DMSO group exhibited a pronounced peak in orientation distribution, indicating increased collagen alignment, which was attenuated by Bazedoxifene treatment. Additional representative fields are shown in B. (J) Representative FN1 immunofluorescence staining in xenograft tissues and quantification of relative FN1 density. Data are presented as mean ± SD (n = 8 pairs of xenografts). Statistical significance was determined using paired two-tailed Student's t-test. * P < 0.05 , ** P < 0.01 , *** P < 0.001 . Bleo, bleomycin; Baz, Bazedoxifene.
Article Snippet:
Techniques: In Vivo, Staining, Injection, Analysis, Immunofluorescence, Software, Derivative Assay, Xenograft Assay, Two Tailed Test
Journal: International Journal of Biological Sciences
Article Title: Bazedoxifene Targets gp130 Signaling to Suppress Fibroblast Activation in Pathological Cutaneous Fibrosis: Insights from Spatial Transcriptomics and scRNA-seq Data
doi: 10.7150/ijbs.137778
Figure Lengend Snippet: Bazedoxifene suppresses myofibroblast differentiation in vivo . (A) Scheme of the spatial transcriptomic analysis workflow. Skin tissues were collected from the bleomycin-induced fibrosis model. (B) Unsupervised clustering showing 6 cell types within the tissue. (C) Dot plot of representative marker gene expression for cell-type annotation of spatial clusters. (D) Cell-type annotation of spatial clusters, identifying fibroblasts, keratinocytes, hair follicle cells, skeletal muscle cells, Schwann cells, nerve bundles, and other cell types. (E) Spatial distribution of myofibroblast differentiation scores across tissue sections. (F) Quantitative comparison of myofibroblast differentiation scores between DMSO and Baz groups. Data are presented as mean ± SD. Statistical significance was determined using a two-tailed Student's t-test. (G) Representative immunofluorescence staining of α-SMA (red) and DAPI (blue) in dermal regions of skin tissues from the bleomycin-induced fibrosis model (upper) and patient-derived keloid xenograft model (lower left). Scale bars: 100 μm. Quantification of relative α-SMA-positive signal is shown on the lower right. Violin plots (left) represent the bleomycin-induced fibrosis model, and paired comparisons (right) represent the keloid xenograft model. Data are presented as mean ± SD. Statistical significance was determined using a two-tailed Student's t-test for the bleomycin-induced fibrosis model and a paired Student's t-test for the keloid xenograft model. * P < 0.05 , ** P < 0.01 , *** P < 0.001; ns, not significant. Baz, Bazedoxifene; Bleo, bleomycin.
Article Snippet:
Techniques: In Vivo, Analysis, Tissue, Marker, Gene Expression, Comparison, Two Tailed Test, Immunofluorescence, Staining, Derivative Assay, Xenograft Assay, T-Test, Spatial Transcriptomics
Journal: International Journal of Biological Sciences
Article Title: Bazedoxifene Targets gp130 Signaling to Suppress Fibroblast Activation in Pathological Cutaneous Fibrosis: Insights from Spatial Transcriptomics and scRNA-seq Data
doi: 10.7150/ijbs.137778
Figure Lengend Snippet: Transcriptomic analysis reveals suppression of fibroblast activation-related signaling by Bazedoxifene. (A) Schematic illustration of the RNA sequencing workflow. Keloid-derived fibroblasts were treated with Bazedoxifene (5 μM) or vehicle control followed by total RNA extraction and bulk RNA sequencing to investigate transcriptional changes. Transcriptomic analyses identified changes in pathways associated with ECM production, myofibroblast differentiation, and cell migration. (B) Volcano plot showing DEGs in Bazedoxifene-treated keloid fibroblasts compared with vehicle controls. Representative genes associated with fibrotic remodeling are marked. DEGs were identified according to the predefined cutoff criteria (|log2FC| ≥ 1, p < 0.05). (C) Ingenuity Pathway Analysis (IPA) of canonical signaling pathways enriched among DEGs following Bazedoxifene treatment. (D) Gene Ontology (GO) enrichment analysis of downregulated biological processes following Bazedoxifene treatment. (E, G, I) Gene set enrichment analysis (GSEA) demonstrating suppression of gene sets associated with ECM production (E), myofibroblast differentiation (G), and cell migration (I) in Bazedoxifene-treated fibroblasts compared with controls. Heatmaps show the expression patterns of representative genes within each gene set. (F, H, J) RNA-seq coverage tracks visualized using the Integrative Genomics Viewer (IGV) showing reduced transcriptional signals of representative genes involved in ECM production ( COL1A1 ), myofibroblast differentiation ( ACTA2 ), and cell migration ( NEDD9 ). Data were generated from three biologically independent samples per group. DEG, differentially expressed gene.
Article Snippet:
Techniques: Analysis, Activation Assay, RNA Sequencing, Derivative Assay, Control, RNA Extraction, Bulk RNA Sequencing, Migration, Protein-Protein interactions, Expressing, Generated
Journal: International Journal of Biological Sciences
Article Title: Bazedoxifene Targets gp130 Signaling to Suppress Fibroblast Activation in Pathological Cutaneous Fibrosis: Insights from Spatial Transcriptomics and scRNA-seq Data
doi: 10.7150/ijbs.137778
Figure Lengend Snippet: Bazedoxifene Suppresses the PI3K-AKT-mTOR Pathway Downstream of the gp130 Axis. (A) KEGG pathway enrichment analysis of DEGs in Bazedoxifene-treated keloid fibroblasts compared with vehicle controls. The PI3K/AKT signaling pathway was among the top significantly enriched pathways. (B) Gene set enrichment analysis (GSEA) demonstrating suppression of the PI3K/AKT signaling pathway following Bazedoxifene treatment. (C) Western blot analysis of p-mTOR, mTOR, p-PIK3CA, PIK3CA, p-AKT, and AKT protein expression relative to GAPDH in fibroblasts treated with Bazedoxifene (0, 2.5, and 5 μM). (D) Densitometric quantification of relative phosphorylation levels of mTOR, PIK3CA, and AKT normalized to their corresponding total proteins (n = 3). (E) Representative immunofluorescence staining of p-mTOR (green), α-SMA (red), and DAPI (blue) in skin tissues from the bleomycin-induced skin fibrosis model. Dashed boxes indicate the regions shown at higher magnification on the right. Scale bar: 100 μm. (F) Quantification of relative p-mTOR fluorescence intensity (n = 6, left) and line-scan fluorescence intensity profile (right) showing the spatial distribution of p-mTOR (green) relative to α-SMA (red). (G) Schematic Diagram illustrating that Bazedoxifene inhibits gp130-mediated signaling to fibroblast activation in cutaneous fibrosis, as validated by in vitro and in vivo models. Data are presented as mean ± SD. Statistical significance was determined using one-way ANOVA followed by multiple comparisons test. * P < 0.05 , ** P < 0.01 , *** P < 0.001 . DEG, differentially expressed gene. Bleo, bleomycin; Baz, Bazedoxifene.
Article Snippet:
Techniques: Analysis, Western Blot, Expressing, Phospho-proteomics, Immunofluorescence, Staining, Fluorescence, Activation Assay, In Vitro, In Vivo
Journal: Nature Communications
Article Title: Mitochondrial vulnerability underlies myocarditis from COVID-19 mRNA vaccine
doi: 10.1038/s41467-026-71295-1
Figure Lengend Snippet: a – c LVEF was measured at 0 and 5 days post-administration of mRNA-1273 in Polg +/D257A mice treated with vehicle ( a ; n = 6), testosterone enanthate (TTE) ( b ; n = 5), or bazedoxifene acetate (BZA) ( c ; n = 6). n represents biologically independent mice. All experiments were performed using male mice aged 8–10 weeks. The centre line indicates the median, the box limits indicate IQR (25th-75th percentiles), and the whiskers extend to 1.5 x IQR ( a – c ). Two-tailed, paired Student’s t -test ( a – c ). Source data are provided as a Source Data file.
Article Snippet: Mice were also intraperitoneally treated with 3 mg/kg
Techniques: Two Tailed Test
Journal: Oncology Letters
Article Title: Synergistic effect of bazedoxifene and abemaciclib co‑treatment in triple‑negative breast cancer cells in vitro
doi: 10.3892/ol.2024.14688
Figure Lengend Snippet: Effects of bazedoxifene, abemaciclib and their combination on cell viability. Co-treatment with bazeboxifene and abemaciclib in (A) SUM159, (B) MDA-MB-231 and (C) 4T1 cells exhibited a synergistic effect, and inhibited cell viability more significantly than either drug monotherapy or DMSO. Data are presented as the mean ± standard deviation. **P<0.01, ***P<0.001, ****P<0.0001. CI<1 indicates a synergistic effect, CI>1 indicates an antagonistic effect and CI=1 indicates an additive effect. Ac, abemaciclib; Ac0.25, 0.25 µM Ac; Ac0.5, 0.5 µM Ac; Bz, bazedoxifene; Bz0.5, 0.5 µM Bz; Bz5, 5 µM Bz; CI, combination index; ns, not significant.
Article Snippet:
Techniques: Standard Deviation
Journal: Oncology Letters
Article Title: Synergistic effect of bazedoxifene and abemaciclib co‑treatment in triple‑negative breast cancer cells in vitro
doi: 10.3892/ol.2024.14688
Figure Lengend Snippet: Effects of bazedoxifene, abemaciclib and their combination on IL-6/STAT3 signaling and downstream targets. Western blot analysis of pSTAT3, STAT3, cyclin D1 and GAPDH after treatment with DMSO, bazedoxifene, abemaciclib or bazedoxifene plus abemaciclib in (A) SUM159 and (B) MDA-MB-231 cells. Abemaciclib monotherapy induced pSTAT3 and cyclin D1, while the bazedoxifene plus abemaciclib combination combated this induction. Ac, abemaciclib; Ac1, 1 µM Ac; Bz, bazedoxifene; Bz5, 5 µM Bz; Bz10, 10 µM Bz; p, phosphorylated.
Article Snippet:
Techniques: Western Blot
Journal: Oncology Letters
Article Title: Synergistic effect of bazedoxifene and abemaciclib co‑treatment in triple‑negative breast cancer cells in vitro
doi: 10.3892/ol.2024.14688
Figure Lengend Snippet: Effects of bazedoxifene, abemaciclib and their combination on cell cycle progression. Cell cycle analysis of (A) SUM159 cells, including (B) quantification, and (C) MDA-MB-231 cells, including (D) quantification, after treatment with DMSO, bazedoxifene, abemaciclib or the bazedoxifene plus abemaciclib combination. The strongest G 0 /G 1 blockage was induced by the bazedoxifene plus abemaciclib combination. Ac, abemaciclib; Ac1, 1 µM Ac; Bz, bazedoxifene; Bz5, 5 µM Bz; Bz10, 10 µM Bz.
Article Snippet:
Techniques: Cell Cycle Assay
Journal: Oncology Letters
Article Title: Synergistic effect of bazedoxifene and abemaciclib co‑treatment in triple‑negative breast cancer cells in vitro
doi: 10.3892/ol.2024.14688
Figure Lengend Snippet: Effects of bazedoxifene, abemaciclib and their combination on cell migration. The migration of (A) SUM159, (B) MDA-MB-231 and (C) 4T1 cells was inhibited to a greater extent when cells were treated with bazedoxifene plus abemaciclib compared with either monotherapy or DMSO. Images were captured at a magnification of ×10. Data are presented as the mean ± standard deviation. *P<0.05, **P<0.01, ***P<0.001, ****P<0.0001. Ac, abemaciclib; Ac1, 1 µM Ac; Ac2, 2 µM Ac; Bz, bazedoxifene; Bz5, 5 µM Bz; Bz10, 10 µM Bz.
Article Snippet:
Techniques: Migration, Standard Deviation
Journal: Oncology Letters
Article Title: Synergistic effect of bazedoxifene and abemaciclib co‑treatment in triple‑negative breast cancer cells in vitro
doi: 10.3892/ol.2024.14688
Figure Lengend Snippet: Effects of bazedoxifene, abemaciclib and their combination on cell invasion. The invasion of (A) SUM159, (B) MDA-MB-231 and (C) 4T1 cells was inhibited to a greater extent when cells were treated with bazedoxifene plus abemaciclib, compared with either monotherapy or DMSO. Images were captured at a magnification of ×10. Data are presented as the mean ± standard deviation. *P<0.05, **P<0.01, ***P<0.001, ****P<0.0001. Ac, abemaciclib; Ac0.25, 0.25 µM Ac; Ac1, 1 µM Ac; Bz, bazedoxifene; Bz5, 5 µM Bz.
Article Snippet:
Techniques: Standard Deviation
Journal: Oncology Letters
Article Title: Synergistic effect of bazedoxifene and abemaciclib co‑treatment in triple‑negative breast cancer cells in vitro
doi: 10.3892/ol.2024.14688
Figure Lengend Snippet: Effects of bazedoxifene, abemaciclib and their combination on apoptosis. Apoptosis analysis of (A) MDA-MB-231 cells after treatment with DMSO, bazedoxifene, abemaciclib, or the bazedoxifene plus abemaciclib combination, and (B) its quantification. The greatest induction of apoptosis was achieved by the bazedoxifene plus abemaciclib combination compared with either monotherapy or DMSO treatment. Ac, abemaciclib; Ac1, 1 µM Ac; Bz, bazedoxifene; Bz10, 10 µM Bz; DN, double negative (negative for FITC and PI, indicative of live cells); FITC_positive, only positive for FITC (indicative of cells in early apoptosis); DP, double positive (positive for FITC and PI, indicative of cells in late apoptosis); PI_positive, only positive for PI (indicative of dead cells).
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Techniques: