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Effects of rexinoid treatment on macrophage gene and protein expression in the desiccation stress dry eye model and potential macrophage-derived <t>IGF-1/IGF-1R</t> signaling axis. ( A ) Heatmaps showing z -score–scaled expression of selected latent-time–associated genes in four treatment groups (NS, None [untreated], Veh, and NEt-3IB) in conjunctival monocyte/macrophage lineage cells sorted from CD45⁺ cells after 5 days of desiccating stress (DS5) ( P adj < 0.001). Genes are organized into five functional categories. The color scale represents z -scores of normalized expression ( blue , low; red , high). These data show desiccating stress–associated shifts in macrophage gene programs and their modulation by NEt-3IB, including enrichment of reparative and growth factor–related genes such as Igf1 . Full gene names for the abbreviations are provided in . ( B ) Representative flow cytometry histograms and quantification validating selected macrophage-associated markers in conjunctival immune cells. ( Left ) Representative histograms of CX3CR1 staining with fluorescence-minus-one (FMO) control, with corresponding quantification of the percentage of CD45⁺CD11b⁺CX3CR1⁺ cells. ( Right ) Representative histograms of IGF-1 staining with FMO control, with corresponding quantification of the percentage of CD45⁺CD11b⁺Mrc1⁺IGF-1⁺ cells. Compared with DS5 no treatment and DS5+vehicle controls, DS5+NEt-3IB increased the proportion ofx CX3CR1⁺ and Mrc1⁺IGF-1⁺ myeloid cells. Each dot represents one biological replicate; bars show mean ± SEM. Statistical significance is indicated as shown: ** P < 0.01; **** P < 0.001; **** P < 0.0001; ns, not significant. ( C ) Representative immunofluorescence images showing IGF-1R/WGA/DAPI staining of wholemount conjunctiva showing surface view ( top ) and βIII-tubulin/IGF-1R/DAPI staining in the cornea ( bottom ). IGF-1R localization is shown because IGF-1 is produced by ocular surface resident macrophages, suggesting a potential macrophage-derived IGF-1/IGF-1R signaling axis acting on ocular surface epithelial and neural compartments during DS. Scale bar : 100 µm.
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(A) Differentially expressed genes and overall expression trends of cortical neurons from seven different groups. “D vs A”: log₂FC of KCls vs Control, “G vs D”: log₂FC of MDZs vs KCls. (B) Gene expression profiles of commonly secreted neuronal factors under KCl, and MDZ conditions. IGF1 is highlighted by a red dashed line. (C) Validation of IGF1and BDNF expression by RT-qPCR. n.s. P >0.05, * P < 0.05, ** P < 0.01, **** P < 0.0001. n=3. (D-E) Representative images and quantification of EdU assay after IGFBP3 experiment in GL261 cells. Scale bar = 100 μm. (F-G) Representative images and quantification of EdU assay after <t>Linsitinib</t> <t>(OSI-906)</t> treated experiments in GL261 cells. Scale bar = 200 μm. (H-I) Activation of the IGF1 downstream PI3K/AKT signaling pathway in glioma cells and its quantitative analysis. (J-K) PI3K/AKT signaling pathway change after IGFBP3 incubation in glioma cells. n.s. P >0.05, * P< 0.05, ** P< 0.01, *** P< 0.001, **** P< 0.0001. n=3.
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(A) Differentially expressed genes and overall expression trends of cortical neurons from seven different groups. “D vs A”: log₂FC of KCls vs Control, “G vs D”: log₂FC of MDZs vs KCls. (B) Gene expression profiles of commonly secreted neuronal factors under KCl, and MDZ conditions. IGF1 is highlighted by a red dashed line. (C) Validation of IGF1and BDNF expression by RT-qPCR. n.s. P >0.05, * P < 0.05, ** P < 0.01, **** P < 0.0001. n=3. (D-E) Representative images and quantification of EdU assay after IGFBP3 experiment in GL261 cells. Scale bar = 100 μm. (F-G) Representative images and quantification of EdU assay after <t>Linsitinib</t> <t>(OSI-906)</t> treated experiments in GL261 cells. Scale bar = 200 μm. (H-I) Activation of the IGF1 downstream PI3K/AKT signaling pathway in glioma cells and its quantitative analysis. (J-K) PI3K/AKT signaling pathway change after IGFBP3 incubation in glioma cells. n.s. P >0.05, * P< 0.05, ** P< 0.01, *** P< 0.001, **** P< 0.0001. n=3.
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Representative images of IHC staining. IHC staining of TNBC specimens was performed as described in the Methods section with antibodies to IR, <t>IGF-1R,</t> pErk1/2, and FOXO3a. The images are shown in 40× magnification. Abbreviations: IGF-1R, IGR-1 receptor; IHC, immunohistochemistry; IR, insulin receptor; pErk1/2, phosphorylated Erk1/2; TNBC, triple negative breast cancer.
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Representative images of IHC staining. IHC staining of TNBC specimens was performed as described in the Methods section with antibodies to IR, <t>IGF-1R,</t> pErk1/2, and FOXO3a. The images are shown in 40× magnification. Abbreviations: IGF-1R, IGR-1 receptor; IHC, immunohistochemistry; IR, insulin receptor; pErk1/2, phosphorylated Erk1/2; TNBC, triple negative breast cancer.
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Representative images of IHC staining. IHC staining of TNBC specimens was performed as described in the Methods section with antibodies to IR, <t>IGF-1R,</t> pErk1/2, and FOXO3a. The images are shown in 40× magnification. Abbreviations: IGF-1R, IGR-1 receptor; IHC, immunohistochemistry; IR, insulin receptor; pErk1/2, phosphorylated Erk1/2; TNBC, triple negative breast cancer.
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Representative images of IHC staining. IHC staining of TNBC specimens was performed as described in the Methods section with antibodies to IR, <t>IGF-1R,</t> pErk1/2, and FOXO3a. The images are shown in 40× magnification. Abbreviations: IGF-1R, IGR-1 receptor; IHC, immunohistochemistry; IR, insulin receptor; pErk1/2, phosphorylated Erk1/2; TNBC, triple negative breast cancer.
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Representative images of IHC staining. IHC staining of TNBC specimens was performed as described in the Methods section with antibodies to IR, <t>IGF-1R,</t> pErk1/2, and FOXO3a. The images are shown in 40× magnification. Abbreviations: IGF-1R, IGR-1 receptor; IHC, immunohistochemistry; IR, insulin receptor; pErk1/2, phosphorylated Erk1/2; TNBC, triple negative breast cancer.
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Image Search Results


Effects of rexinoid treatment on macrophage gene and protein expression in the desiccation stress dry eye model and potential macrophage-derived IGF-1/IGF-1R signaling axis. ( A ) Heatmaps showing z -score–scaled expression of selected latent-time–associated genes in four treatment groups (NS, None [untreated], Veh, and NEt-3IB) in conjunctival monocyte/macrophage lineage cells sorted from CD45⁺ cells after 5 days of desiccating stress (DS5) ( P adj < 0.001). Genes are organized into five functional categories. The color scale represents z -scores of normalized expression ( blue , low; red , high). These data show desiccating stress–associated shifts in macrophage gene programs and their modulation by NEt-3IB, including enrichment of reparative and growth factor–related genes such as Igf1 . Full gene names for the abbreviations are provided in . ( B ) Representative flow cytometry histograms and quantification validating selected macrophage-associated markers in conjunctival immune cells. ( Left ) Representative histograms of CX3CR1 staining with fluorescence-minus-one (FMO) control, with corresponding quantification of the percentage of CD45⁺CD11b⁺CX3CR1⁺ cells. ( Right ) Representative histograms of IGF-1 staining with FMO control, with corresponding quantification of the percentage of CD45⁺CD11b⁺Mrc1⁺IGF-1⁺ cells. Compared with DS5 no treatment and DS5+vehicle controls, DS5+NEt-3IB increased the proportion ofx CX3CR1⁺ and Mrc1⁺IGF-1⁺ myeloid cells. Each dot represents one biological replicate; bars show mean ± SEM. Statistical significance is indicated as shown: ** P < 0.01; **** P < 0.001; **** P < 0.0001; ns, not significant. ( C ) Representative immunofluorescence images showing IGF-1R/WGA/DAPI staining of wholemount conjunctiva showing surface view ( top ) and βIII-tubulin/IGF-1R/DAPI staining in the cornea ( bottom ). IGF-1R localization is shown because IGF-1 is produced by ocular surface resident macrophages, suggesting a potential macrophage-derived IGF-1/IGF-1R signaling axis acting on ocular surface epithelial and neural compartments during DS. Scale bar : 100 µm.

Journal: Investigative Ophthalmology & Visual Science

Article Title: Rexinoid NEt-3IB Promotes Resident Macrophage Gene Expression and Mitigates Desiccation-Induced Ocular Surface Disease

doi: 10.1167/iovs.67.4.31

Figure Lengend Snippet: Effects of rexinoid treatment on macrophage gene and protein expression in the desiccation stress dry eye model and potential macrophage-derived IGF-1/IGF-1R signaling axis. ( A ) Heatmaps showing z -score–scaled expression of selected latent-time–associated genes in four treatment groups (NS, None [untreated], Veh, and NEt-3IB) in conjunctival monocyte/macrophage lineage cells sorted from CD45⁺ cells after 5 days of desiccating stress (DS5) ( P adj < 0.001). Genes are organized into five functional categories. The color scale represents z -scores of normalized expression ( blue , low; red , high). These data show desiccating stress–associated shifts in macrophage gene programs and their modulation by NEt-3IB, including enrichment of reparative and growth factor–related genes such as Igf1 . Full gene names for the abbreviations are provided in . ( B ) Representative flow cytometry histograms and quantification validating selected macrophage-associated markers in conjunctival immune cells. ( Left ) Representative histograms of CX3CR1 staining with fluorescence-minus-one (FMO) control, with corresponding quantification of the percentage of CD45⁺CD11b⁺CX3CR1⁺ cells. ( Right ) Representative histograms of IGF-1 staining with FMO control, with corresponding quantification of the percentage of CD45⁺CD11b⁺Mrc1⁺IGF-1⁺ cells. Compared with DS5 no treatment and DS5+vehicle controls, DS5+NEt-3IB increased the proportion ofx CX3CR1⁺ and Mrc1⁺IGF-1⁺ myeloid cells. Each dot represents one biological replicate; bars show mean ± SEM. Statistical significance is indicated as shown: ** P < 0.01; **** P < 0.001; **** P < 0.0001; ns, not significant. ( C ) Representative immunofluorescence images showing IGF-1R/WGA/DAPI staining of wholemount conjunctiva showing surface view ( top ) and βIII-tubulin/IGF-1R/DAPI staining in the cornea ( bottom ). IGF-1R localization is shown because IGF-1 is produced by ocular surface resident macrophages, suggesting a potential macrophage-derived IGF-1/IGF-1R signaling axis acting on ocular surface epithelial and neural compartments during DS. Scale bar : 100 µm.

Article Snippet: The following primary antibodies were used: βIII-tubulin (ab215037; Abcam, Cambridge, UK) and human/mouse IGF-1R (AF-305-NA; R&D Systems, Minneapolis, MN, USA).

Techniques: Expressing, Derivative Assay, Functional Assay, Flow Cytometry, Staining, Fluorescence, Control, Immunofluorescence, Produced

(A) Differentially expressed genes and overall expression trends of cortical neurons from seven different groups. “D vs A”: log₂FC of KCls vs Control, “G vs D”: log₂FC of MDZs vs KCls. (B) Gene expression profiles of commonly secreted neuronal factors under KCl, and MDZ conditions. IGF1 is highlighted by a red dashed line. (C) Validation of IGF1and BDNF expression by RT-qPCR. n.s. P >0.05, * P < 0.05, ** P < 0.01, **** P < 0.0001. n=3. (D-E) Representative images and quantification of EdU assay after IGFBP3 experiment in GL261 cells. Scale bar = 100 μm. (F-G) Representative images and quantification of EdU assay after Linsitinib (OSI-906) treated experiments in GL261 cells. Scale bar = 200 μm. (H-I) Activation of the IGF1 downstream PI3K/AKT signaling pathway in glioma cells and its quantitative analysis. (J-K) PI3K/AKT signaling pathway change after IGFBP3 incubation in glioma cells. n.s. P >0.05, * P< 0.05, ** P< 0.01, *** P< 0.001, **** P< 0.0001. n=3.

Journal: bioRxiv

Article Title: Midazolam suppresses glioma progression by attenuating neuronal activity and downregulating IGF1 signaling

doi: 10.64898/2026.03.31.715727

Figure Lengend Snippet: (A) Differentially expressed genes and overall expression trends of cortical neurons from seven different groups. “D vs A”: log₂FC of KCls vs Control, “G vs D”: log₂FC of MDZs vs KCls. (B) Gene expression profiles of commonly secreted neuronal factors under KCl, and MDZ conditions. IGF1 is highlighted by a red dashed line. (C) Validation of IGF1and BDNF expression by RT-qPCR. n.s. P >0.05, * P < 0.05, ** P < 0.01, **** P < 0.0001. n=3. (D-E) Representative images and quantification of EdU assay after IGFBP3 experiment in GL261 cells. Scale bar = 100 μm. (F-G) Representative images and quantification of EdU assay after Linsitinib (OSI-906) treated experiments in GL261 cells. Scale bar = 200 μm. (H-I) Activation of the IGF1 downstream PI3K/AKT signaling pathway in glioma cells and its quantitative analysis. (J-K) PI3K/AKT signaling pathway change after IGFBP3 incubation in glioma cells. n.s. P >0.05, * P< 0.05, ** P< 0.01, *** P< 0.001, **** P< 0.0001. n=3.

Article Snippet: After 24 h incubation in Neu-CMs with or without 1ug/ml IGF1 binding protein-3 (Sigma, USA) [ ] , 100 μM IGF 1R inhibitor Linsitinib (OSI-906) (Sellect, USA) [ , ] or exogenous IGF1 factor (MCE, USA), the proliferation of glioma cells was detected by EdU assay.

Techniques: Expressing, Control, Gene Expression, Biomarker Discovery, Quantitative RT-PCR, EdU Assay, Activation Assay, Incubation

Representative images of IHC staining. IHC staining of TNBC specimens was performed as described in the Methods section with antibodies to IR, IGF-1R, pErk1/2, and FOXO3a. The images are shown in 40× magnification. Abbreviations: IGF-1R, IGR-1 receptor; IHC, immunohistochemistry; IR, insulin receptor; pErk1/2, phosphorylated Erk1/2; TNBC, triple negative breast cancer.

Journal: Journal of the Endocrine Society

Article Title: Insulin receptor expression and its association with hyperinsulinemia in triple negative breast cancer

doi: 10.1210/jendso/bvag041

Figure Lengend Snippet: Representative images of IHC staining. IHC staining of TNBC specimens was performed as described in the Methods section with antibodies to IR, IGF-1R, pErk1/2, and FOXO3a. The images are shown in 40× magnification. Abbreviations: IGF-1R, IGR-1 receptor; IHC, immunohistochemistry; IR, insulin receptor; pErk1/2, phosphorylated Erk1/2; TNBC, triple negative breast cancer.

Article Snippet: Primary antibodies were anti-IR Ab (ab137747, Abcam, Cambridge, MA, RRID:AB_3717506) 1:300 dilution, anti-IGF-1R Ab (#3027, Cell Signaling, Danvers, CA, RRID:AB_2122378) 1:200 dilution, anti-FOXO3a Ab (#12829, Cell Signaling, RRID:AB_2636990) 1:3200 dilution, and anti-pErk1/2 (Thr202/Tyr204) Ab (#4370, Cell Signaling, RRID:AB_2315112) 1:400 dilution.

Techniques: Immunohistochemistry

Representative images of protein localization for IR, IGF1R, FOXO3a, and pErk1/2. IHC staining of TNBC specimens was performed and evaluated for localization of proteins. The images are shown in 40× magnification. Abbreviations: IGF-1R, IGR-1 receptor; IHC, immunohistochemistry; IR, insulin receptor; pErk1/2, phosphorylated Erk1/2; TNBC, triple negative breast cancer.

Journal: Journal of the Endocrine Society

Article Title: Insulin receptor expression and its association with hyperinsulinemia in triple negative breast cancer

doi: 10.1210/jendso/bvag041

Figure Lengend Snippet: Representative images of protein localization for IR, IGF1R, FOXO3a, and pErk1/2. IHC staining of TNBC specimens was performed and evaluated for localization of proteins. The images are shown in 40× magnification. Abbreviations: IGF-1R, IGR-1 receptor; IHC, immunohistochemistry; IR, insulin receptor; pErk1/2, phosphorylated Erk1/2; TNBC, triple negative breast cancer.

Article Snippet: Primary antibodies were anti-IR Ab (ab137747, Abcam, Cambridge, MA, RRID:AB_3717506) 1:300 dilution, anti-IGF-1R Ab (#3027, Cell Signaling, Danvers, CA, RRID:AB_2122378) 1:200 dilution, anti-FOXO3a Ab (#12829, Cell Signaling, RRID:AB_2636990) 1:3200 dilution, and anti-pErk1/2 (Thr202/Tyr204) Ab (#4370, Cell Signaling, RRID:AB_2315112) 1:400 dilution.

Techniques: Immunohistochemistry

Overall survival for women with breast cancer based on IR and IGF-1R protein expression in KMPlot.com . KMPlot.com was used to generate overall survival Kaplan-Meier plots. The dataset used was not from our cohort but from Tang and colleagues ; n = 65 patients had IR (A) and IGF1R (B) protein expression available. The patients were split using the “auto select best cutoff” percentile option in KMPlot. No other restrictions were added to the analysis. The plots show hazard ratios with 95% confidence intervals in parentheses . Abbreviations: IGF-1R, IGR-1 receptor; IR, insulin receptor.

Journal: Journal of the Endocrine Society

Article Title: Insulin receptor expression and its association with hyperinsulinemia in triple negative breast cancer

doi: 10.1210/jendso/bvag041

Figure Lengend Snippet: Overall survival for women with breast cancer based on IR and IGF-1R protein expression in KMPlot.com . KMPlot.com was used to generate overall survival Kaplan-Meier plots. The dataset used was not from our cohort but from Tang and colleagues ; n = 65 patients had IR (A) and IGF1R (B) protein expression available. The patients were split using the “auto select best cutoff” percentile option in KMPlot. No other restrictions were added to the analysis. The plots show hazard ratios with 95% confidence intervals in parentheses . Abbreviations: IGF-1R, IGR-1 receptor; IR, insulin receptor.

Article Snippet: Primary antibodies were anti-IR Ab (ab137747, Abcam, Cambridge, MA, RRID:AB_3717506) 1:300 dilution, anti-IGF-1R Ab (#3027, Cell Signaling, Danvers, CA, RRID:AB_2122378) 1:200 dilution, anti-FOXO3a Ab (#12829, Cell Signaling, RRID:AB_2636990) 1:3200 dilution, and anti-pErk1/2 (Thr202/Tyr204) Ab (#4370, Cell Signaling, RRID:AB_2315112) 1:400 dilution.

Techniques: Expressing