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pcsk9  (Boster Bio)


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    Structured Review

    Boster Bio pcsk9
    Full fabrication and application schematic diagram of <t>GelMA-VEGF/ECM-PCSK9</t> composite hydrogel and the related signaling pathway of PCSK9 that promotes BMSC osteogenic differentiation.
    Pcsk9, supplied by Boster Bio, used in various techniques. Bioz Stars score: 94/100, based on 1 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
    https://www.bioz.com/result/pcsk9/product/Boster Bio
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    Images

    1) Product Images from "A composite hydrogel enables the spatiotemporal delivery of distinct cytokines to drive the native vascularized bone regeneration"

    Article Title: A composite hydrogel enables the spatiotemporal delivery of distinct cytokines to drive the native vascularized bone regeneration

    Journal: Bioactive Materials

    doi: 10.1016/j.bioactmat.2026.02.048

    Full fabrication and application schematic diagram of GelMA-VEGF/ECM-PCSK9 composite hydrogel and the related signaling pathway of PCSK9 that promotes BMSC osteogenic differentiation.
    Figure Legend Snippet: Full fabrication and application schematic diagram of GelMA-VEGF/ECM-PCSK9 composite hydrogel and the related signaling pathway of PCSK9 that promotes BMSC osteogenic differentiation.

    Techniques Used:

    Construction and characterization of GelMA-VEGF/ECM-PCSK9 composite hydrogel. A Schematic diagram showing the process of composite hydrogel construction; B) Photographs of GelMA-VEGF hydrogel and GelMA-VEGF/ECM-PCSK9 hydrogel formation after UV light respectively; C i) Electron microscopic image of pure GelMA hydrogel, with a scale of 100 μm; ii) Enlarged electron microscopic image of GelMA hydrogel, with a scale of 50 μm; D) i The electron microscope image of the combination of GelMA hydrogel and ECM, with a scale of 100 μm; ii Electron microscope magnified image of GelMA hydrogel combined with ECM, with a scale of 50 μm; E) The infrared spectrum (FITR) diagram of the acellular ECM, GelMA hydrogel and GelMA/ECM composite hydrogel contains common basic energy groups; F) Load rate of PCSK9 in ECM; G) Release rate of VEGF loaded with GelMA hydrogel and GelMA/ECM composite hydrogel respectively; H) Release rate of PCSK9 loaded with ECM and GelMA/ECM composite hydrogel respectively; I) Release rate of VEGF and PCSK9 loaded in GelMA and GelMA/ECM on different time points respectively; J) Release rate of VEGF and PCSK9 respectively when loaded in GelMA/ECM; K) The swelling rate of GelMA gel and GelMA/ECM composite gel dissolved in PBS (n = 6); L) Degradation rate of GelMA hydrogel and GelMA/ECM composite gel in vitro (n = 6).∗means that compared with the control group, p < 0.05; ∗means that compared with the control group, p < 0.01; ∗∗∗means that compared with the control group, p < 0.001.
    Figure Legend Snippet: Construction and characterization of GelMA-VEGF/ECM-PCSK9 composite hydrogel. A Schematic diagram showing the process of composite hydrogel construction; B) Photographs of GelMA-VEGF hydrogel and GelMA-VEGF/ECM-PCSK9 hydrogel formation after UV light respectively; C i) Electron microscopic image of pure GelMA hydrogel, with a scale of 100 μm; ii) Enlarged electron microscopic image of GelMA hydrogel, with a scale of 50 μm; D) i The electron microscope image of the combination of GelMA hydrogel and ECM, with a scale of 100 μm; ii Electron microscope magnified image of GelMA hydrogel combined with ECM, with a scale of 50 μm; E) The infrared spectrum (FITR) diagram of the acellular ECM, GelMA hydrogel and GelMA/ECM composite hydrogel contains common basic energy groups; F) Load rate of PCSK9 in ECM; G) Release rate of VEGF loaded with GelMA hydrogel and GelMA/ECM composite hydrogel respectively; H) Release rate of PCSK9 loaded with ECM and GelMA/ECM composite hydrogel respectively; I) Release rate of VEGF and PCSK9 loaded in GelMA and GelMA/ECM on different time points respectively; J) Release rate of VEGF and PCSK9 respectively when loaded in GelMA/ECM; K) The swelling rate of GelMA gel and GelMA/ECM composite gel dissolved in PBS (n = 6); L) Degradation rate of GelMA hydrogel and GelMA/ECM composite gel in vitro (n = 6).∗means that compared with the control group, p < 0.05; ∗means that compared with the control group, p < 0.01; ∗∗∗means that compared with the control group, p < 0.001.

    Techniques Used: Microscopy, In Vitro, Control

    Angiogenic capacity formulations of HUVECs in response to different composite biomaterial in vitro. A) Calcein/PI staining of HUVECs seeded on glass slides, showing the cell migration profiles of HUVECs treated with different material groups, scale bar = 200 μm; B) Quantitative analysis of the intercellular blank areas in each group, with the baseline group serving as the negative control; C) Angiogenic images of HUVECs co-cultured with different composite materials for 4 h and 8 h respectively, scale bar = 250 μm; D–G) Quantitative assessment of angiogenic capacity in each group via ImageJ software analysis of key angiogenic parameters. Abbreviations: NC = negative control group; V = exogenous VEGF protein-only group; GV=GelMA + exogenous VEGF protein group; GVE = GelMA + VEGF + ECM group; GVEP= GelMA/VEGF + ECM/PCSK9 group. Statistical notations: ∗∗means that compared with the control group, p < 0.01; ns = no significant difference between group.
    Figure Legend Snippet: Angiogenic capacity formulations of HUVECs in response to different composite biomaterial in vitro. A) Calcein/PI staining of HUVECs seeded on glass slides, showing the cell migration profiles of HUVECs treated with different material groups, scale bar = 200 μm; B) Quantitative analysis of the intercellular blank areas in each group, with the baseline group serving as the negative control; C) Angiogenic images of HUVECs co-cultured with different composite materials for 4 h and 8 h respectively, scale bar = 250 μm; D–G) Quantitative assessment of angiogenic capacity in each group via ImageJ software analysis of key angiogenic parameters. Abbreviations: NC = negative control group; V = exogenous VEGF protein-only group; GV=GelMA + exogenous VEGF protein group; GVE = GelMA + VEGF + ECM group; GVEP= GelMA/VEGF + ECM/PCSK9 group. Statistical notations: ∗∗means that compared with the control group, p < 0.01; ns = no significant difference between group.

    Techniques Used: In Vitro, Staining, Migration, Negative Control, Cell Culture, Software, Control

    The effect of different composite hydrogel on the osteogenic differentiation of BMMSC in vitro. Cultivate BMMSC for osteogenic differentiation in osteogenic medium with GelMA, GelMA-VEGF, GelMA-VEGF/ECM, ECM-PCSK9, and GelMA-VEGF/ECM-PCSK9 for 7 days respectively. A,B) The cell nucleus was stained with DAPI (blue), RUNX2 was stained with RUNX2 antibody (green), and COL1A1 was stained with COL1A1 antibody (red), with a scale bar of 200 μm. C,D) The quantitative analysis results of COL1A1 and RUNX2 immunofluorescence images; E,F) Quantitative analysis of ALP staining and ARS staining for BMMSC co-culture with different kinds of hydrogels; G) ALP staining result for BMMSC co-culture with different kinds of hydrogels for 7days, scale bar = 200 μm; F) ARS staining result for BMMSC co-culture with different kinds of hydrogels for 14days, scale bar = 200 μm; I, J) After 7 and 14 days of co-culture with different combinations of composite hydrogels and BMMSC for osteogenesis and differentiation, the PCR experiment results of osteogenesis related indicators suggest that compared with the control group. G = simple GelMA hydrogel group, GV=GelMA hydrogels + VEGF protein group, GV/E = GelMA + VEGF/ECM group, EP = ECM + PCSK9 protein group, GVEP=GelMA + VEGF/ECM + PCSK9 protein group, the significant differences between the groups are expressed as ∗ p < 0.05, ∗∗p < 0.01, ∗∗∗p < 0.001, and ns means there is no significant difference between the groups.
    Figure Legend Snippet: The effect of different composite hydrogel on the osteogenic differentiation of BMMSC in vitro. Cultivate BMMSC for osteogenic differentiation in osteogenic medium with GelMA, GelMA-VEGF, GelMA-VEGF/ECM, ECM-PCSK9, and GelMA-VEGF/ECM-PCSK9 for 7 days respectively. A,B) The cell nucleus was stained with DAPI (blue), RUNX2 was stained with RUNX2 antibody (green), and COL1A1 was stained with COL1A1 antibody (red), with a scale bar of 200 μm. C,D) The quantitative analysis results of COL1A1 and RUNX2 immunofluorescence images; E,F) Quantitative analysis of ALP staining and ARS staining for BMMSC co-culture with different kinds of hydrogels; G) ALP staining result for BMMSC co-culture with different kinds of hydrogels for 7days, scale bar = 200 μm; F) ARS staining result for BMMSC co-culture with different kinds of hydrogels for 14days, scale bar = 200 μm; I, J) After 7 and 14 days of co-culture with different combinations of composite hydrogels and BMMSC for osteogenesis and differentiation, the PCR experiment results of osteogenesis related indicators suggest that compared with the control group. G = simple GelMA hydrogel group, GV=GelMA hydrogels + VEGF protein group, GV/E = GelMA + VEGF/ECM group, EP = ECM + PCSK9 protein group, GVEP=GelMA + VEGF/ECM + PCSK9 protein group, the significant differences between the groups are expressed as ∗ p < 0.05, ∗∗p < 0.01, ∗∗∗p < 0.001, and ns means there is no significant difference between the groups.

    Techniques Used: In Vitro, Staining, Immunofluorescence, Co-Culture Assay, Control

    After adding different concentrations of PCSK9 to BMMSC for osteogenic induction, western blotting (WB) experiment was performed to evaluate the expression of phosphorylated proteins and total proteins among different osteogenic differentiation relevant signaling pathways. A) WB images of different signaling pathways that related to osteogenic differentiation after adding different concentrations of PCSK9; B-D) Quantitative analysis results of phosphorylated protein and total protein. Compared with the control group, ∗ means p < 0.05, ∗∗ means p < 0.01.
    Figure Legend Snippet: After adding different concentrations of PCSK9 to BMMSC for osteogenic induction, western blotting (WB) experiment was performed to evaluate the expression of phosphorylated proteins and total proteins among different osteogenic differentiation relevant signaling pathways. A) WB images of different signaling pathways that related to osteogenic differentiation after adding different concentrations of PCSK9; B-D) Quantitative analysis results of phosphorylated protein and total protein. Compared with the control group, ∗ means p < 0.05, ∗∗ means p < 0.01.

    Techniques Used: Western Blot, Expressing, Protein-Protein interactions, Control



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    H1N1 infection affects cell viability, inflammatory cytokine secretion and interactions between HBEpiCs and THP-1 cells. (A) CCK-8 assay revealed that HBEpiC viability decreased in a concentration-dependent manner following H1N1 infection. (B) ELISA revealed that the levels of IL-1β, IL-6, TNF-α, and IL-8 in HBEpiCs decreased with increasing H1N1 infection. (C) CCK-8 assay indicated that supernatants from H1N1-infected HBEpiC cultures reduced the viability of THP-1 cells in a dose-dependent manner. (D) ELISA results suggested that the levels of inflammatory cytokines (IL-1β, IL-6, TNF-α and IL-8) in THP-1 cells were decreased following exposure to supernatants from H1N1-infected HBEpiC cultures. (E) Cell adhesion assay revealed that the number of THP-1 cells adhering to HBEpiCs increased with increasing H1N1 concentration (scale bar, 10 μ m). Arrow indicates THP-1 cells that remain attached to the surface of HBEpiCs, highlighting the adhesion interaction between the two cell types. (F) Transwell assay suggested that H1N1 infection enhanced the migration capacity of THP-1 cells, with increased migration observed at higher virus concentrations (scale bar, 50 μ m). The data are presented as the mean ± standard deviation; ** P<0.01, *** P<0.001 vs. control. H1N1, influenza A; HBEpiCs, human bronchial epithelial cells; ELISA, enzyme-linked immunosorbent assay; IL, interleukin; TNF-α, tumor necrosis factor-α; Con, control; MOI, multiplicity of infection.

    Journal: International Journal of Molecular Medicine

    Article Title: Triptolide exerts antiviral effects and alleviates influenza A-induced pneumonia by inhibiting the overactivation of absent in melanoma 2 signaling in immune cells

    doi: 10.3892/ijmm.2026.5829

    Figure Lengend Snippet: H1N1 infection affects cell viability, inflammatory cytokine secretion and interactions between HBEpiCs and THP-1 cells. (A) CCK-8 assay revealed that HBEpiC viability decreased in a concentration-dependent manner following H1N1 infection. (B) ELISA revealed that the levels of IL-1β, IL-6, TNF-α, and IL-8 in HBEpiCs decreased with increasing H1N1 infection. (C) CCK-8 assay indicated that supernatants from H1N1-infected HBEpiC cultures reduced the viability of THP-1 cells in a dose-dependent manner. (D) ELISA results suggested that the levels of inflammatory cytokines (IL-1β, IL-6, TNF-α and IL-8) in THP-1 cells were decreased following exposure to supernatants from H1N1-infected HBEpiC cultures. (E) Cell adhesion assay revealed that the number of THP-1 cells adhering to HBEpiCs increased with increasing H1N1 concentration (scale bar, 10 μ m). Arrow indicates THP-1 cells that remain attached to the surface of HBEpiCs, highlighting the adhesion interaction between the two cell types. (F) Transwell assay suggested that H1N1 infection enhanced the migration capacity of THP-1 cells, with increased migration observed at higher virus concentrations (scale bar, 50 μ m). The data are presented as the mean ± standard deviation; ** P<0.01, *** P<0.001 vs. control. H1N1, influenza A; HBEpiCs, human bronchial epithelial cells; ELISA, enzyme-linked immunosorbent assay; IL, interleukin; TNF-α, tumor necrosis factor-α; Con, control; MOI, multiplicity of infection.

    Article Snippet: Cell supernatants were collected and analyzed using Human TNF-α High Sensitivity ELISA Kit [cat. no. EK182HS; Hangzhou Multi Sciences (Lianke) Biotech Co., Ltd.], Human IL-8 ELISA Kit [cat. no. EK108; Hangzhou Multi Sciences (Lianke) Biotech Co., Ltd.], a human IL-1β ELISA kit [EH0185; Hangzhou Multi Sciences (Lianke) Biotech Co., Ltd.] and IL-6 [cat. no. EK1217; Hangzhou Multi Sciences (Lianke) Biotech Co., Ltd.] according to the manufacturer's instructions.

    Techniques: Infection, CCK-8 Assay, Concentration Assay, Enzyme-linked Immunosorbent Assay, Cell Adhesion Assay, Transwell Assay, Migration, Virus, Standard Deviation, Control

    TP modulates the inflammatory response and immune cell activity in H1N1-infected HBEpiCs and THP-1 cells. (A) No significant changes were observed in HBEpiCs treated with various concentrations of TP (5, 10 and 20 nM) following H1N1 infection compared with the control. (B) After TP treatment, the levels of the inflammatory cytokines IL-1β, IL-6, TNF-α and IL-8 in HBEpiCs were markedly lower than those in the untreated group. (C) The viability of THP-1 cells pretreated with H1N1-infected HBEpiC culture supernatant decreased after TP treatment. (D) The levels of IL-1β, IL-6, TNF-α, and IL-8 in THP-1 cells were markedly lower after TP treatment. (E) The adhesion of THP-1 cells to HBEpiCs induced by H1N1 infection decreased in a dose-dependent manner with increasing TP concentration (scale bar, 10 μ m). Arrow indicates THP-1 cells that remain attached to the surface of HBEpiCs, highlighting the adhesion interaction between the two cell types. (F) The migration capacity of THP-1 cells was markedly reduced when the supernatant from H1N1-infected HBEpiC cultures was treated with TP (scale bar, 50 μ m). The data are presented as the mean ± standard deviation; * P<0.05, ** P<0.01, *** P<0.001 vs. control. TP, triptolide; H1N1, influenza A; HBEpiCs, human bronchial epithelial cells; IL, interleukin; TNF-α, tumor necrosis factor-α; Con, control.

    Journal: International Journal of Molecular Medicine

    Article Title: Triptolide exerts antiviral effects and alleviates influenza A-induced pneumonia by inhibiting the overactivation of absent in melanoma 2 signaling in immune cells

    doi: 10.3892/ijmm.2026.5829

    Figure Lengend Snippet: TP modulates the inflammatory response and immune cell activity in H1N1-infected HBEpiCs and THP-1 cells. (A) No significant changes were observed in HBEpiCs treated with various concentrations of TP (5, 10 and 20 nM) following H1N1 infection compared with the control. (B) After TP treatment, the levels of the inflammatory cytokines IL-1β, IL-6, TNF-α and IL-8 in HBEpiCs were markedly lower than those in the untreated group. (C) The viability of THP-1 cells pretreated with H1N1-infected HBEpiC culture supernatant decreased after TP treatment. (D) The levels of IL-1β, IL-6, TNF-α, and IL-8 in THP-1 cells were markedly lower after TP treatment. (E) The adhesion of THP-1 cells to HBEpiCs induced by H1N1 infection decreased in a dose-dependent manner with increasing TP concentration (scale bar, 10 μ m). Arrow indicates THP-1 cells that remain attached to the surface of HBEpiCs, highlighting the adhesion interaction between the two cell types. (F) The migration capacity of THP-1 cells was markedly reduced when the supernatant from H1N1-infected HBEpiC cultures was treated with TP (scale bar, 50 μ m). The data are presented as the mean ± standard deviation; * P<0.05, ** P<0.01, *** P<0.001 vs. control. TP, triptolide; H1N1, influenza A; HBEpiCs, human bronchial epithelial cells; IL, interleukin; TNF-α, tumor necrosis factor-α; Con, control.

    Article Snippet: Cell supernatants were collected and analyzed using Human TNF-α High Sensitivity ELISA Kit [cat. no. EK182HS; Hangzhou Multi Sciences (Lianke) Biotech Co., Ltd.], Human IL-8 ELISA Kit [cat. no. EK108; Hangzhou Multi Sciences (Lianke) Biotech Co., Ltd.], a human IL-1β ELISA kit [EH0185; Hangzhou Multi Sciences (Lianke) Biotech Co., Ltd.] and IL-6 [cat. no. EK1217; Hangzhou Multi Sciences (Lianke) Biotech Co., Ltd.] according to the manufacturer's instructions.

    Techniques: Activity Assay, Infection, Control, Concentration Assay, Migration, Standard Deviation

    Substrate characterisation in 2D and 3D cell culture—biological responses and physical properties with different compositions. (a) hPSC confluence in 2D growth factor-reduced Matrigel (Geltrex), laminin 521, fibrin-laminin hydrogel, and fibrin gel after 4 d; scale bar = 100 μ m. (b) hPSCs cultured in 3D hydrogels. Top panel: fibrin (5 mg ml −1 ) gel. Bottom panel: Alphagel containing structures resembling pluripotent spheroids; scale bar = 200 μ m. Scanning electron microscopy of (c) fibrin gel and (d) Alphagel; scale bar = 1 μ m, magnification 20 K X, iProbe = 13 pA, 2.00 kV, Working Distancee = 4.4 mm for both images. (e) Young’s moduli in hydrogels with varying fibrin and laminin concentrations. One-way ANOVA; ** = p < 0.01, *** = p < 0.001, and **** = p < 0.0001. (f) Cell viability of hPSCs cultured in Alphagel, fibrin-only hydrogels, and 2D standard substrates. Mean ± sandard error of the mean displayed. t -test; * = p < 0.05. (g) ELISA of laminin 521 in culture media used with acellular Alphagel and (h) the calculated amount of fibrin-bound laminin.

    Journal: Materials Futures

    Article Title: A clinically defined and xeno-free hydrogel system for regenerative medicine

    doi: 10.1088/2752-5724/ae4e4d

    Figure Lengend Snippet: Substrate characterisation in 2D and 3D cell culture—biological responses and physical properties with different compositions. (a) hPSC confluence in 2D growth factor-reduced Matrigel (Geltrex), laminin 521, fibrin-laminin hydrogel, and fibrin gel after 4 d; scale bar = 100 μ m. (b) hPSCs cultured in 3D hydrogels. Top panel: fibrin (5 mg ml −1 ) gel. Bottom panel: Alphagel containing structures resembling pluripotent spheroids; scale bar = 200 μ m. Scanning electron microscopy of (c) fibrin gel and (d) Alphagel; scale bar = 1 μ m, magnification 20 K X, iProbe = 13 pA, 2.00 kV, Working Distancee = 4.4 mm for both images. (e) Young’s moduli in hydrogels with varying fibrin and laminin concentrations. One-way ANOVA; ** = p < 0.01, *** = p < 0.001, and **** = p < 0.0001. (f) Cell viability of hPSCs cultured in Alphagel, fibrin-only hydrogels, and 2D standard substrates. Mean ± sandard error of the mean displayed. t -test; * = p < 0.05. (g) ELISA of laminin 521 in culture media used with acellular Alphagel and (h) the calculated amount of fibrin-bound laminin.

    Article Snippet: Apolipoprotein B (APOB) secretion in the supernatant was quantified using the human APOB ELISA quantification kit (Mabtech, no. 3715-1H-6) according to the product literature.

    Techniques: Cell Culture, Electron Microscopy, Enzyme-linked Immunosorbent Assay

    Characterisation of iHeps derived in Alphagel, fibrin-only hydrogels, and Matrigel. (a) Key hepatocyte markers in Alphagel-derived iHeps. ALB = albumin, HNF = hepatocyte nuclear factor, CYP2A6 = Cytochrome P450 2A6, CD147 = cluster of differentiation protein 147, and E-CAD = E-cadherin. Scale bar = 25 μ m. (b) Key hepatocyte markers by gene expression (qPCR): CCAAT/enhancer-binding protein alpha (CEBPA), T-box transcription factor 3= TBX3, alpha-fetoprotein = AFP. (c) Albumin secretion (ELISA) and (d) CYP3A4 activity (P450-Glo TM ) in PHHs versus iHeps cultured in various gels (day 22). HCM = Hepatocyte Culture Media (Lonza). (e) LDL uptake (red) in Alphagel-derived iHeps versus hPSCs. Scale bar = 100 μ m. (f) CDFDA secretion (green) in Alphagel-derived iHeps versus hPSCs. Top panel scale bar = 20 μ m; bottom panel scale bar = 50 μ m. One-way ANOVA was used; * = p < 0.05, ** = p < 0.01, *** = p < 0.001, and **** = p < 0.0001.

    Journal: Materials Futures

    Article Title: A clinically defined and xeno-free hydrogel system for regenerative medicine

    doi: 10.1088/2752-5724/ae4e4d

    Figure Lengend Snippet: Characterisation of iHeps derived in Alphagel, fibrin-only hydrogels, and Matrigel. (a) Key hepatocyte markers in Alphagel-derived iHeps. ALB = albumin, HNF = hepatocyte nuclear factor, CYP2A6 = Cytochrome P450 2A6, CD147 = cluster of differentiation protein 147, and E-CAD = E-cadherin. Scale bar = 25 μ m. (b) Key hepatocyte markers by gene expression (qPCR): CCAAT/enhancer-binding protein alpha (CEBPA), T-box transcription factor 3= TBX3, alpha-fetoprotein = AFP. (c) Albumin secretion (ELISA) and (d) CYP3A4 activity (P450-Glo TM ) in PHHs versus iHeps cultured in various gels (day 22). HCM = Hepatocyte Culture Media (Lonza). (e) LDL uptake (red) in Alphagel-derived iHeps versus hPSCs. Scale bar = 100 μ m. (f) CDFDA secretion (green) in Alphagel-derived iHeps versus hPSCs. Top panel scale bar = 20 μ m; bottom panel scale bar = 50 μ m. One-way ANOVA was used; * = p < 0.05, ** = p < 0.01, *** = p < 0.001, and **** = p < 0.0001.

    Article Snippet: Apolipoprotein B (APOB) secretion in the supernatant was quantified using the human APOB ELISA quantification kit (Mabtech, no. 3715-1H-6) according to the product literature.

    Techniques: Derivative Assay, Gene Expression, Binding Assay, Enzyme-linked Immunosorbent Assay, Activity Assay, Cell Culture

    Characterisation of iHeps cultured in Hepatogel and its effect on cell retention after intra-hepatic cell transplantation. (a) Differentially expressed genes in iHeps: Hepatologel, Alphagel, Matrigel, and adult PHHs. (b) A heat map summarising the differential gene expression of a hepatic 24-gene panel across replicates of Matrigel, Alphagel, and Hepatogel (normalised to hPSC). (c) Albumin ELISA of culture media and (d) luciferin-based measure of CYP3A4 activity: 2 d after completion of iHep differentiation and 2 d after plating PHHs. One-way ANOVA; * = p < 0.05, ** = p < 0.01, *** = p < 0.001, and **** = p < 0.0001. (e) Mouse livers 3 d after intra-hepatic injection with H-iHeps in Hepatogel and 0.9% saline. Red box = area magnified. * = site of injection, dotted white lines demarcate engrafted cell mass. Scale bar = 1 mm. (f) Human albumin (stained red) in engrafted iHeps 3 d after intra-hepatic injection. Scale bar = 100 μ m. (g) H-iHeps identified by albumin staining on liver histology 3 d after intra-hepatic injection. (h) ELISA of mouse serum for human albumin after injection with H-iHeps in Hepatogel and 0.9% saline over time. Day 0 = serum levels before injection. T -test; *** = p < 0.001 and **** = p < 0.0001.

    Journal: Materials Futures

    Article Title: A clinically defined and xeno-free hydrogel system for regenerative medicine

    doi: 10.1088/2752-5724/ae4e4d

    Figure Lengend Snippet: Characterisation of iHeps cultured in Hepatogel and its effect on cell retention after intra-hepatic cell transplantation. (a) Differentially expressed genes in iHeps: Hepatologel, Alphagel, Matrigel, and adult PHHs. (b) A heat map summarising the differential gene expression of a hepatic 24-gene panel across replicates of Matrigel, Alphagel, and Hepatogel (normalised to hPSC). (c) Albumin ELISA of culture media and (d) luciferin-based measure of CYP3A4 activity: 2 d after completion of iHep differentiation and 2 d after plating PHHs. One-way ANOVA; * = p < 0.05, ** = p < 0.01, *** = p < 0.001, and **** = p < 0.0001. (e) Mouse livers 3 d after intra-hepatic injection with H-iHeps in Hepatogel and 0.9% saline. Red box = area magnified. * = site of injection, dotted white lines demarcate engrafted cell mass. Scale bar = 1 mm. (f) Human albumin (stained red) in engrafted iHeps 3 d after intra-hepatic injection. Scale bar = 100 μ m. (g) H-iHeps identified by albumin staining on liver histology 3 d after intra-hepatic injection. (h) ELISA of mouse serum for human albumin after injection with H-iHeps in Hepatogel and 0.9% saline over time. Day 0 = serum levels before injection. T -test; *** = p < 0.001 and **** = p < 0.0001.

    Article Snippet: Apolipoprotein B (APOB) secretion in the supernatant was quantified using the human APOB ELISA quantification kit (Mabtech, no. 3715-1H-6) according to the product literature.

    Techniques: Cell Culture, Transplantation Assay, Gene Expression, Enzyme-linked Immunosorbent Assay, Activity Assay, Injection, Saline, Staining

    Full fabrication and application schematic diagram of GelMA-VEGF/ECM-PCSK9 composite hydrogel and the related signaling pathway of PCSK9 that promotes BMSC osteogenic differentiation.

    Journal: Bioactive Materials

    Article Title: A composite hydrogel enables the spatiotemporal delivery of distinct cytokines to drive the native vascularized bone regeneration

    doi: 10.1016/j.bioactmat.2026.02.048

    Figure Lengend Snippet: Full fabrication and application schematic diagram of GelMA-VEGF/ECM-PCSK9 composite hydrogel and the related signaling pathway of PCSK9 that promotes BMSC osteogenic differentiation.

    Article Snippet: VEGF, ELISA kit for VEGF and PCSK9 were purchased from Boster company (Wuhan, China).

    Techniques:

    Construction and characterization of GelMA-VEGF/ECM-PCSK9 composite hydrogel. A Schematic diagram showing the process of composite hydrogel construction; B) Photographs of GelMA-VEGF hydrogel and GelMA-VEGF/ECM-PCSK9 hydrogel formation after UV light respectively; C i) Electron microscopic image of pure GelMA hydrogel, with a scale of 100 μm; ii) Enlarged electron microscopic image of GelMA hydrogel, with a scale of 50 μm; D) i The electron microscope image of the combination of GelMA hydrogel and ECM, with a scale of 100 μm; ii Electron microscope magnified image of GelMA hydrogel combined with ECM, with a scale of 50 μm; E) The infrared spectrum (FITR) diagram of the acellular ECM, GelMA hydrogel and GelMA/ECM composite hydrogel contains common basic energy groups; F) Load rate of PCSK9 in ECM; G) Release rate of VEGF loaded with GelMA hydrogel and GelMA/ECM composite hydrogel respectively; H) Release rate of PCSK9 loaded with ECM and GelMA/ECM composite hydrogel respectively; I) Release rate of VEGF and PCSK9 loaded in GelMA and GelMA/ECM on different time points respectively; J) Release rate of VEGF and PCSK9 respectively when loaded in GelMA/ECM; K) The swelling rate of GelMA gel and GelMA/ECM composite gel dissolved in PBS (n = 6); L) Degradation rate of GelMA hydrogel and GelMA/ECM composite gel in vitro (n = 6).∗means that compared with the control group, p < 0.05; ∗means that compared with the control group, p < 0.01; ∗∗∗means that compared with the control group, p < 0.001.

    Journal: Bioactive Materials

    Article Title: A composite hydrogel enables the spatiotemporal delivery of distinct cytokines to drive the native vascularized bone regeneration

    doi: 10.1016/j.bioactmat.2026.02.048

    Figure Lengend Snippet: Construction and characterization of GelMA-VEGF/ECM-PCSK9 composite hydrogel. A Schematic diagram showing the process of composite hydrogel construction; B) Photographs of GelMA-VEGF hydrogel and GelMA-VEGF/ECM-PCSK9 hydrogel formation after UV light respectively; C i) Electron microscopic image of pure GelMA hydrogel, with a scale of 100 μm; ii) Enlarged electron microscopic image of GelMA hydrogel, with a scale of 50 μm; D) i The electron microscope image of the combination of GelMA hydrogel and ECM, with a scale of 100 μm; ii Electron microscope magnified image of GelMA hydrogel combined with ECM, with a scale of 50 μm; E) The infrared spectrum (FITR) diagram of the acellular ECM, GelMA hydrogel and GelMA/ECM composite hydrogel contains common basic energy groups; F) Load rate of PCSK9 in ECM; G) Release rate of VEGF loaded with GelMA hydrogel and GelMA/ECM composite hydrogel respectively; H) Release rate of PCSK9 loaded with ECM and GelMA/ECM composite hydrogel respectively; I) Release rate of VEGF and PCSK9 loaded in GelMA and GelMA/ECM on different time points respectively; J) Release rate of VEGF and PCSK9 respectively when loaded in GelMA/ECM; K) The swelling rate of GelMA gel and GelMA/ECM composite gel dissolved in PBS (n = 6); L) Degradation rate of GelMA hydrogel and GelMA/ECM composite gel in vitro (n = 6).∗means that compared with the control group, p < 0.05; ∗means that compared with the control group, p < 0.01; ∗∗∗means that compared with the control group, p < 0.001.

    Article Snippet: VEGF, ELISA kit for VEGF and PCSK9 were purchased from Boster company (Wuhan, China).

    Techniques: Microscopy, In Vitro, Control

    Angiogenic capacity formulations of HUVECs in response to different composite biomaterial in vitro. A) Calcein/PI staining of HUVECs seeded on glass slides, showing the cell migration profiles of HUVECs treated with different material groups, scale bar = 200 μm; B) Quantitative analysis of the intercellular blank areas in each group, with the baseline group serving as the negative control; C) Angiogenic images of HUVECs co-cultured with different composite materials for 4 h and 8 h respectively, scale bar = 250 μm; D–G) Quantitative assessment of angiogenic capacity in each group via ImageJ software analysis of key angiogenic parameters. Abbreviations: NC = negative control group; V = exogenous VEGF protein-only group; GV=GelMA + exogenous VEGF protein group; GVE = GelMA + VEGF + ECM group; GVEP= GelMA/VEGF + ECM/PCSK9 group. Statistical notations: ∗∗means that compared with the control group, p < 0.01; ns = no significant difference between group.

    Journal: Bioactive Materials

    Article Title: A composite hydrogel enables the spatiotemporal delivery of distinct cytokines to drive the native vascularized bone regeneration

    doi: 10.1016/j.bioactmat.2026.02.048

    Figure Lengend Snippet: Angiogenic capacity formulations of HUVECs in response to different composite biomaterial in vitro. A) Calcein/PI staining of HUVECs seeded on glass slides, showing the cell migration profiles of HUVECs treated with different material groups, scale bar = 200 μm; B) Quantitative analysis of the intercellular blank areas in each group, with the baseline group serving as the negative control; C) Angiogenic images of HUVECs co-cultured with different composite materials for 4 h and 8 h respectively, scale bar = 250 μm; D–G) Quantitative assessment of angiogenic capacity in each group via ImageJ software analysis of key angiogenic parameters. Abbreviations: NC = negative control group; V = exogenous VEGF protein-only group; GV=GelMA + exogenous VEGF protein group; GVE = GelMA + VEGF + ECM group; GVEP= GelMA/VEGF + ECM/PCSK9 group. Statistical notations: ∗∗means that compared with the control group, p < 0.01; ns = no significant difference between group.

    Article Snippet: VEGF, ELISA kit for VEGF and PCSK9 were purchased from Boster company (Wuhan, China).

    Techniques: In Vitro, Staining, Migration, Negative Control, Cell Culture, Software, Control

    The effect of different composite hydrogel on the osteogenic differentiation of BMMSC in vitro. Cultivate BMMSC for osteogenic differentiation in osteogenic medium with GelMA, GelMA-VEGF, GelMA-VEGF/ECM, ECM-PCSK9, and GelMA-VEGF/ECM-PCSK9 for 7 days respectively. A,B) The cell nucleus was stained with DAPI (blue), RUNX2 was stained with RUNX2 antibody (green), and COL1A1 was stained with COL1A1 antibody (red), with a scale bar of 200 μm. C,D) The quantitative analysis results of COL1A1 and RUNX2 immunofluorescence images; E,F) Quantitative analysis of ALP staining and ARS staining for BMMSC co-culture with different kinds of hydrogels; G) ALP staining result for BMMSC co-culture with different kinds of hydrogels for 7days, scale bar = 200 μm; F) ARS staining result for BMMSC co-culture with different kinds of hydrogels for 14days, scale bar = 200 μm; I, J) After 7 and 14 days of co-culture with different combinations of composite hydrogels and BMMSC for osteogenesis and differentiation, the PCR experiment results of osteogenesis related indicators suggest that compared with the control group. G = simple GelMA hydrogel group, GV=GelMA hydrogels + VEGF protein group, GV/E = GelMA + VEGF/ECM group, EP = ECM + PCSK9 protein group, GVEP=GelMA + VEGF/ECM + PCSK9 protein group, the significant differences between the groups are expressed as ∗ p < 0.05, ∗∗p < 0.01, ∗∗∗p < 0.001, and ns means there is no significant difference between the groups.

    Journal: Bioactive Materials

    Article Title: A composite hydrogel enables the spatiotemporal delivery of distinct cytokines to drive the native vascularized bone regeneration

    doi: 10.1016/j.bioactmat.2026.02.048

    Figure Lengend Snippet: The effect of different composite hydrogel on the osteogenic differentiation of BMMSC in vitro. Cultivate BMMSC for osteogenic differentiation in osteogenic medium with GelMA, GelMA-VEGF, GelMA-VEGF/ECM, ECM-PCSK9, and GelMA-VEGF/ECM-PCSK9 for 7 days respectively. A,B) The cell nucleus was stained with DAPI (blue), RUNX2 was stained with RUNX2 antibody (green), and COL1A1 was stained with COL1A1 antibody (red), with a scale bar of 200 μm. C,D) The quantitative analysis results of COL1A1 and RUNX2 immunofluorescence images; E,F) Quantitative analysis of ALP staining and ARS staining for BMMSC co-culture with different kinds of hydrogels; G) ALP staining result for BMMSC co-culture with different kinds of hydrogels for 7days, scale bar = 200 μm; F) ARS staining result for BMMSC co-culture with different kinds of hydrogels for 14days, scale bar = 200 μm; I, J) After 7 and 14 days of co-culture with different combinations of composite hydrogels and BMMSC for osteogenesis and differentiation, the PCR experiment results of osteogenesis related indicators suggest that compared with the control group. G = simple GelMA hydrogel group, GV=GelMA hydrogels + VEGF protein group, GV/E = GelMA + VEGF/ECM group, EP = ECM + PCSK9 protein group, GVEP=GelMA + VEGF/ECM + PCSK9 protein group, the significant differences between the groups are expressed as ∗ p < 0.05, ∗∗p < 0.01, ∗∗∗p < 0.001, and ns means there is no significant difference between the groups.

    Article Snippet: VEGF, ELISA kit for VEGF and PCSK9 were purchased from Boster company (Wuhan, China).

    Techniques: In Vitro, Staining, Immunofluorescence, Co-Culture Assay, Control

    After adding different concentrations of PCSK9 to BMMSC for osteogenic induction, western blotting (WB) experiment was performed to evaluate the expression of phosphorylated proteins and total proteins among different osteogenic differentiation relevant signaling pathways. A) WB images of different signaling pathways that related to osteogenic differentiation after adding different concentrations of PCSK9; B-D) Quantitative analysis results of phosphorylated protein and total protein. Compared with the control group, ∗ means p < 0.05, ∗∗ means p < 0.01.

    Journal: Bioactive Materials

    Article Title: A composite hydrogel enables the spatiotemporal delivery of distinct cytokines to drive the native vascularized bone regeneration

    doi: 10.1016/j.bioactmat.2026.02.048

    Figure Lengend Snippet: After adding different concentrations of PCSK9 to BMMSC for osteogenic induction, western blotting (WB) experiment was performed to evaluate the expression of phosphorylated proteins and total proteins among different osteogenic differentiation relevant signaling pathways. A) WB images of different signaling pathways that related to osteogenic differentiation after adding different concentrations of PCSK9; B-D) Quantitative analysis results of phosphorylated protein and total protein. Compared with the control group, ∗ means p < 0.05, ∗∗ means p < 0.01.

    Article Snippet: VEGF, ELISA kit for VEGF and PCSK9 were purchased from Boster company (Wuhan, China).

    Techniques: Western Blot, Expressing, Protein-Protein interactions, Control

    Vectorized IFNβ drives durable signaling and complete tumor regression in human glioblastoma models in vivo (A) Sustained hIFNβ secretion in human GBM6 cells treated with AAV9-hIFNβ (red, MOI = 4E5 vg/cell) or recombinant hIFNβ cytokine (r-hIFNβ, purple, 47 IU/mL, equivalent to 114 pg/mL), measured by ELISA at indicated time points. 50% media washouts every 5 h for the first 20 h in the r-hIFNβ condition mimic in vivo cytokine clearance (half-life = 4–5 h). Full media exchanges were performed at 24, 48, 72, and 96 h post-treatment. (B) Number of differentially expressed genes (DEGs, p -Adj<0.01) in GBM6 cells 24–96 h post-treatment with AAV9-hIFNβ or r-hIFNβ vs. media controls. (C) Enrichment scores for type I IFN and TNFα response pathways across treatments and time points. (D) Heatmap of the top 10 IFN and TNFα response genes (Log2FC vs. media controls) in GBM6 cells treated as in (A). (E) Schematic of orthotopic PDX (SF11411) and cell line-derived xenograft ([CDX], GBM6-FLuc) studies in athymic nu/nu mice treated intratumorally with saline, AAV9-GFP, or AAV9-hIFNβ via CED. (F) Kaplan-Meier survival curves for PDX mice treated as in (E). Saline = black, AAV9-GFP (2E11 vg/brain) = blue, AAV9-hIFNβ (2E11 vg/brain) = red. Vertical dashed line = day of treatment (day 9). p < 0.04 by log-rank (Mantel-Cox) test. n = 30 (10 per treatment arm). (G) Longitudinal BLI of GBM6-FLuc tumor growth in CDX mice treated as in (E). Saline = black, AAV9-GFP (2E11 vg/brain) = blue, AAV9-hIFNβ (2E11 vg/brain) = red. Thin lines = individual mice, thick lines = geometric mean. Vertical dashed line = day of treatment (day 9). ∗ p < 0.04 by Kruskal-Wallis test with Dunn’s multiple comparisons correction on day 22. n = 30 (10 per treatment arm). (G′) Representative BLI images from each treatment group 11 days post-treatment. (H) Kaplan-Meier survival curves for CDX mice. p < 0.001 by log-rank (Mantel-Cox) test. (I) Distribution of treatment responses in CDX by BLI flux (photons/second) at day 27. Tumor free = BLI flux <2.5 × 10 5 p/s, tumor reduction = ≥30% decrease from assignment on day 9, no change = between 30% decrease and 20% increase from assignment on day 9, tumor growth = ≥20% increase from assignment on day 9, death = mice that died before day 27. (J) Dose-response analysis of AAV9-hIFNβ efficacy in CDX mice. AAV9-GFP (2E11 vg/brain) = blue, AAV9-hIFNβ hi (2E11 vg/brain) = solid red, and AAV9-hIFNβ lo (1E11 vg/brain) = dashed red. Thin lines = individual mice, thick lines = geometric mean. Vertical dashed line = day of treatment (day 9). ∗∗ p < 0.02 by Kruskal-Wallis test with Dunn’s multiple comparisons correction on day 20. n = 45 (15 per treatment arm). For data interpretation, tumor burden threshold = 2.5 × 10 5 . (J′) Representative BLI images of tumors 11 days post-treatment. (K) Kaplan-Meier survival curves from (J). p < 0.002 (AAV9-hIFNβ hi), p < 0.005 (AAV9-hIFNβ lo) by log-rank (Mantel-Cox) test compared to AAV9-GFP. (I) Distribution of treatment responses in CDX mice at day 27 by BLI flux as in (I).

    Journal: Molecular Therapy Oncology

    Article Title: AAV immuno-gene therapy platform delivering vectorized cytokines defines a new modality for high-grade glioma treatment

    doi: 10.1016/j.omton.2026.201183

    Figure Lengend Snippet: Vectorized IFNβ drives durable signaling and complete tumor regression in human glioblastoma models in vivo (A) Sustained hIFNβ secretion in human GBM6 cells treated with AAV9-hIFNβ (red, MOI = 4E5 vg/cell) or recombinant hIFNβ cytokine (r-hIFNβ, purple, 47 IU/mL, equivalent to 114 pg/mL), measured by ELISA at indicated time points. 50% media washouts every 5 h for the first 20 h in the r-hIFNβ condition mimic in vivo cytokine clearance (half-life = 4–5 h). Full media exchanges were performed at 24, 48, 72, and 96 h post-treatment. (B) Number of differentially expressed genes (DEGs, p -Adj<0.01) in GBM6 cells 24–96 h post-treatment with AAV9-hIFNβ or r-hIFNβ vs. media controls. (C) Enrichment scores for type I IFN and TNFα response pathways across treatments and time points. (D) Heatmap of the top 10 IFN and TNFα response genes (Log2FC vs. media controls) in GBM6 cells treated as in (A). (E) Schematic of orthotopic PDX (SF11411) and cell line-derived xenograft ([CDX], GBM6-FLuc) studies in athymic nu/nu mice treated intratumorally with saline, AAV9-GFP, or AAV9-hIFNβ via CED. (F) Kaplan-Meier survival curves for PDX mice treated as in (E). Saline = black, AAV9-GFP (2E11 vg/brain) = blue, AAV9-hIFNβ (2E11 vg/brain) = red. Vertical dashed line = day of treatment (day 9). p < 0.04 by log-rank (Mantel-Cox) test. n = 30 (10 per treatment arm). (G) Longitudinal BLI of GBM6-FLuc tumor growth in CDX mice treated as in (E). Saline = black, AAV9-GFP (2E11 vg/brain) = blue, AAV9-hIFNβ (2E11 vg/brain) = red. Thin lines = individual mice, thick lines = geometric mean. Vertical dashed line = day of treatment (day 9). ∗ p < 0.04 by Kruskal-Wallis test with Dunn’s multiple comparisons correction on day 22. n = 30 (10 per treatment arm). (G′) Representative BLI images from each treatment group 11 days post-treatment. (H) Kaplan-Meier survival curves for CDX mice. p < 0.001 by log-rank (Mantel-Cox) test. (I) Distribution of treatment responses in CDX by BLI flux (photons/second) at day 27. Tumor free = BLI flux <2.5 × 10 5 p/s, tumor reduction = ≥30% decrease from assignment on day 9, no change = between 30% decrease and 20% increase from assignment on day 9, tumor growth = ≥20% increase from assignment on day 9, death = mice that died before day 27. (J) Dose-response analysis of AAV9-hIFNβ efficacy in CDX mice. AAV9-GFP (2E11 vg/brain) = blue, AAV9-hIFNβ hi (2E11 vg/brain) = solid red, and AAV9-hIFNβ lo (1E11 vg/brain) = dashed red. Thin lines = individual mice, thick lines = geometric mean. Vertical dashed line = day of treatment (day 9). ∗∗ p < 0.02 by Kruskal-Wallis test with Dunn’s multiple comparisons correction on day 20. n = 45 (15 per treatment arm). For data interpretation, tumor burden threshold = 2.5 × 10 5 . (J′) Representative BLI images of tumors 11 days post-treatment. (K) Kaplan-Meier survival curves from (J). p < 0.002 (AAV9-hIFNβ hi), p < 0.005 (AAV9-hIFNβ lo) by log-rank (Mantel-Cox) test compared to AAV9-GFP. (I) Distribution of treatment responses in CDX mice at day 27 by BLI flux as in (I).

    Article Snippet: 24, 48, 72, and 96 h after treatment, cell supernatants were collected and IFN variant levels were measured using IFN ELISA kits following the manufacturer’s instructions (human IFNα [PBL Cat# 41135-1], human IFNβ [PBL Cat#41410], and human IFNγ [R&D Systems Cat#: DIF50C]).

    Techniques: In Vivo, Recombinant, Enzyme-linked Immunosorbent Assay, Derivative Assay, Saline

    Spatial transcriptomics reveals rapid, localized transcriptional remodeling of the tumor microenvironment following vectorized hIFNβ treatment (A) Coronal brain sections from representative human GBM6-FLuc CDX mice collected pre-treatment (0 h, n = 1) or 48 h ( n = 1) after intratumoral AAV9-hIFNβ infusion (2E11 vg/brain), stained with H&E (left) and subjected to Visium Spatial Gene Expression profiling (right). Annotated clusters were assigned based on anatomical localization and marker gene expression. Dashed lines denote tumor borders. Scale bars, 1 mm. (B) Top 10 marker genes for each spatially resolved cluster identified across 0 h and 48 h datasets. Values are shown as log-normalized expression centered at 0 (Seurat “scale.data”). (C) Spatial expression of canonical human GBM tumor markers ( CD44 , VIM , TOP2A , and NOTCH1 ) delineating tumor and peri-tumor regions before (0 h) (top) and after (bottom) (48 h) AAV9-hIFNβ treatment. (D) Expression maps of the human IFNβ payload and hallmark IFN-response genes ( CXCL10 , IFIT1 , and IFIT2 ), demonstrating tumor-restricted transgene expression and induction of an IFN-specific transcriptional program within 48 h. (E) Spatial expression of host mouse immune-response genes ( Gfap , Ifitm3 , and Irf7 ) showing localized activation of astroglial and innate immune pathways proximal to the tumor. (F) Integrated datasets (0 and 48 h) visualized using canonical correlation analysis (CCA), showing distinct clustering of tumor and peri-tumor regions (left) and enrichment of IFN-response gene module expression (right). (G) Volcano plot depicting differential gene expression between 0- and 48-h tumor clusters. Red, IFN-response genes; gray, other significantly upregulated genes ( p -Adj <0.01); blue, non-significant. (H) Top enriched Gene Ontology (GO) terms among upregulated genes in 48-h tumor cells, highlighting interferon and inflammatory response pathways (∗∗ p -Adj <0.01; ∗ p -Adj <0.05).

    Journal: Molecular Therapy Oncology

    Article Title: AAV immuno-gene therapy platform delivering vectorized cytokines defines a new modality for high-grade glioma treatment

    doi: 10.1016/j.omton.2026.201183

    Figure Lengend Snippet: Spatial transcriptomics reveals rapid, localized transcriptional remodeling of the tumor microenvironment following vectorized hIFNβ treatment (A) Coronal brain sections from representative human GBM6-FLuc CDX mice collected pre-treatment (0 h, n = 1) or 48 h ( n = 1) after intratumoral AAV9-hIFNβ infusion (2E11 vg/brain), stained with H&E (left) and subjected to Visium Spatial Gene Expression profiling (right). Annotated clusters were assigned based on anatomical localization and marker gene expression. Dashed lines denote tumor borders. Scale bars, 1 mm. (B) Top 10 marker genes for each spatially resolved cluster identified across 0 h and 48 h datasets. Values are shown as log-normalized expression centered at 0 (Seurat “scale.data”). (C) Spatial expression of canonical human GBM tumor markers ( CD44 , VIM , TOP2A , and NOTCH1 ) delineating tumor and peri-tumor regions before (0 h) (top) and after (bottom) (48 h) AAV9-hIFNβ treatment. (D) Expression maps of the human IFNβ payload and hallmark IFN-response genes ( CXCL10 , IFIT1 , and IFIT2 ), demonstrating tumor-restricted transgene expression and induction of an IFN-specific transcriptional program within 48 h. (E) Spatial expression of host mouse immune-response genes ( Gfap , Ifitm3 , and Irf7 ) showing localized activation of astroglial and innate immune pathways proximal to the tumor. (F) Integrated datasets (0 and 48 h) visualized using canonical correlation analysis (CCA), showing distinct clustering of tumor and peri-tumor regions (left) and enrichment of IFN-response gene module expression (right). (G) Volcano plot depicting differential gene expression between 0- and 48-h tumor clusters. Red, IFN-response genes; gray, other significantly upregulated genes ( p -Adj <0.01); blue, non-significant. (H) Top enriched Gene Ontology (GO) terms among upregulated genes in 48-h tumor cells, highlighting interferon and inflammatory response pathways (∗∗ p -Adj <0.01; ∗ p -Adj <0.05).

    Article Snippet: 24, 48, 72, and 96 h after treatment, cell supernatants were collected and IFN variant levels were measured using IFN ELISA kits following the manufacturer’s instructions (human IFNα [PBL Cat# 41135-1], human IFNβ [PBL Cat#41410], and human IFNγ [R&D Systems Cat#: DIF50C]).

    Techniques: Spatial Transcriptomics, Staining, Gene Expression, Marker, Expressing, Activation Assay

    Scheme of the fabrication of the microcarriers and delivery of engineered nanovesicles for photoaging therapy. Abbreviations: HDF, human dermal fibroblast; Exos, exosomes; Emvs, engineered nanovesicles; HDF COL1A1 Emvs, Emvs derived from HDFs transfected with COL1A1 plasmid (COL1A1 mRNA–encapsulating nanovesicles); ROS, reactive oxygen species; COL1A1, collagen type I alpha 1 chain.

    Journal: Materials Today Bio

    Article Title: Microcarriers encapsulating COL1A1 mRNA-loaded nanovesicles for skin photoaging treatment

    doi: 10.1016/j.mtbio.2026.103126

    Figure Lengend Snippet: Scheme of the fabrication of the microcarriers and delivery of engineered nanovesicles for photoaging therapy. Abbreviations: HDF, human dermal fibroblast; Exos, exosomes; Emvs, engineered nanovesicles; HDF COL1A1 Emvs, Emvs derived from HDFs transfected with COL1A1 plasmid (COL1A1 mRNA–encapsulating nanovesicles); ROS, reactive oxygen species; COL1A1, collagen type I alpha 1 chain.

    Article Snippet: The concentration of human type I procollagen was measured using a human type I procollagen ELISA kit (Elabscience Biotechnology, China) according to the manufacturer's instructions.

    Techniques: Derivative Assay, Transfection, Plasmid Preparation

    In vivo biosafety evaluation. a) In vivo imaging of subcutaneous injection sites across different groups. b) Quantification of relative fluorescence intensity (n = 5). c) Histological analysis via H&E staining of the heart, liver, spleen, lung, and kidney tissues. d) ELISA quantification of IL-6 levels and TNF-α levels (n = 5). e) Quantification of ALT, AST, CREA, and UA levels (n = 3). The scale bar is 300 μm in c).

    Journal: Materials Today Bio

    Article Title: Microcarriers encapsulating COL1A1 mRNA-loaded nanovesicles for skin photoaging treatment

    doi: 10.1016/j.mtbio.2026.103126

    Figure Lengend Snippet: In vivo biosafety evaluation. a) In vivo imaging of subcutaneous injection sites across different groups. b) Quantification of relative fluorescence intensity (n = 5). c) Histological analysis via H&E staining of the heart, liver, spleen, lung, and kidney tissues. d) ELISA quantification of IL-6 levels and TNF-α levels (n = 5). e) Quantification of ALT, AST, CREA, and UA levels (n = 3). The scale bar is 300 μm in c).

    Article Snippet: The concentration of human type I procollagen was measured using a human type I procollagen ELISA kit (Elabscience Biotechnology, China) according to the manufacturer's instructions.

    Techniques: In Vivo, In Vivo Imaging, Injection, Fluorescence, Staining, Enzyme-linked Immunosorbent Assay

    IFN-γ suppresses tumor growth and invasion. (A) Cytokine profiling of co-culture supernatants via ELISAs: IFN-γ, IL-1β, IL-6, IL-10, TGF-β and TNF-α. (B-D) Spatial expression patterns of IFN-γ. (B) Immunofluorescence imaging of the invasive front in SSIT, showing DAPI (blue), IBA-1 + macrophages (red) and IFN-γ + signals (green), and grayscale intensity distribution. (C) Immunofluorescence imaging of TIM and NIM, showing DAPI (blue), IBA-1 + macrophages (red) and IFN-γ + signals (green). (D) Quantification of relative IFN-γ expression in TIM and NIM. (E) Representative Ki-67 immunohistochemistry images of SSIT cases stratified into IFN-γ-high and IFN-γ-low groups (n=5 each; median split). (F) Quantification of Ki-67 index comparing the two groups. (G) EdU staining demonstrating dose-dependent suppression of TtT/GF pituitary adenoma cell proliferation by IFN-γ (0–100 ng/ml; 48 h). (H) Representative flow cytometry histograms for cell cycle analysis of cells treated with IFN-γ (0–100 ng/ml) in the absence (0 µM) or presence (5 µM) of ruxolitinib. (I) Stacked bar plot showing the percentages of cells in the G 1 , S and G 2 /M phases under the same treatment conditions. (A) One-way ANOVA with Tukey's post hoc multiple comparisons test. (D and F) Unpaired two-tailed Student's t-test. *P<0.05, **P<0.01, ***P<0.001, ****P<0.0001. CTRL, control; DMC, digested mucosal culture; EdU, 5-ethynyl-2′-deoxyuridine; IBA-1, ionised calcium binding adaptor molecule 1; MTC, mucosal tissue culture; NIM, non-invaded mucosa; ns, not significant; PE-A, phycoerythrin-area; SSIT, sphenoid sinus-invasive tumor; TIM, tumor-invaded mucosa.

    Journal: Molecular Medicine Reports

    Article Title: Elevated IgG levels induce an M2-to-M1 phenotypic shift in mucosal macrophages and restrict the growth of invasive sphenoid sinus pituitary adenomas

    doi: 10.3892/mmr.2026.13878

    Figure Lengend Snippet: IFN-γ suppresses tumor growth and invasion. (A) Cytokine profiling of co-culture supernatants via ELISAs: IFN-γ, IL-1β, IL-6, IL-10, TGF-β and TNF-α. (B-D) Spatial expression patterns of IFN-γ. (B) Immunofluorescence imaging of the invasive front in SSIT, showing DAPI (blue), IBA-1 + macrophages (red) and IFN-γ + signals (green), and grayscale intensity distribution. (C) Immunofluorescence imaging of TIM and NIM, showing DAPI (blue), IBA-1 + macrophages (red) and IFN-γ + signals (green). (D) Quantification of relative IFN-γ expression in TIM and NIM. (E) Representative Ki-67 immunohistochemistry images of SSIT cases stratified into IFN-γ-high and IFN-γ-low groups (n=5 each; median split). (F) Quantification of Ki-67 index comparing the two groups. (G) EdU staining demonstrating dose-dependent suppression of TtT/GF pituitary adenoma cell proliferation by IFN-γ (0–100 ng/ml; 48 h). (H) Representative flow cytometry histograms for cell cycle analysis of cells treated with IFN-γ (0–100 ng/ml) in the absence (0 µM) or presence (5 µM) of ruxolitinib. (I) Stacked bar plot showing the percentages of cells in the G 1 , S and G 2 /M phases under the same treatment conditions. (A) One-way ANOVA with Tukey's post hoc multiple comparisons test. (D and F) Unpaired two-tailed Student's t-test. *P<0.05, **P<0.01, ***P<0.001, ****P<0.0001. CTRL, control; DMC, digested mucosal culture; EdU, 5-ethynyl-2′-deoxyuridine; IBA-1, ionised calcium binding adaptor molecule 1; MTC, mucosal tissue culture; NIM, non-invaded mucosa; ns, not significant; PE-A, phycoerythrin-area; SSIT, sphenoid sinus-invasive tumor; TIM, tumor-invaded mucosa.

    Article Snippet: Human IFN-γ, IL-1β, IL-6, IL-10, TGF-β and TNF-α levels were quantified using commercial ELISA kits (Human IFN-γ ELISA kit, cat. no. E-EL-H0108; Human IL-1β ELISA kit, cat. no. E-EL-H0149; Human IL-6 ELISA kit, cat. no. E-EL-H0102; Human IL-10 ELISA kit, cat. no. E-EL-H0103; Human TGF-β ELISA kit, cat. no. E-EL-H0110; Human TNF-α ELISA kit, cat. no. E-EL-H0109; Wuhan Elabscience Biotechnology Co., Ltd.).

    Techniques: Co-Culture Assay, Expressing, Immunofluorescence, Imaging, Immunohistochemistry, Staining, Flow Cytometry, Cell Cycle Assay, Two Tailed Test, Control, Binding Assay

    Elevated IgG levels drive macrophage M2-to-M1 reprogramming. (A) Sphenoid sinus-invasive tumor cases stratified into CD19-high (n=5) and CD19-low (n=5) groups based on the cohort median of CD19 + B cell density, with (B) quantitative analyses of macrophage polarization (M1-like versus M2-like). (C) Dural-invasive tumor and non-invasive tumor cases stratified into IgG-high (n=27) and IgG-low (n=26) groups based on the cohort median of relative IgG immunohistochemistry staining intensity, with (D) quantitative analyses of M1-like/M2-like macrophage proportions. (E and F) RAW264.7 macrophages were pre-polarized with IL-4 (20 ng/ml) or with lipopolysaccharide (100 ng/ml) plus IFN-γ (20 ng/ml) for 24 h, followed by IgG (10 µg/ml) exposure. Relative (E) IL-6 and (F) TNF-α mRNA expression in RAW264.7 macrophages pre-polarized to M0, M1 or M2 states. (G) Representative flow cytometric cell-cycle profiles of TtT/GF cells following the indicated treatments. (H) Stacked bar plot summarizing the percentages of cells from (G) in G 1 , S and G 2 /M phases. (I) Representative images from the scratch wound assay at 0, 24, 48 and 72 h under the indicated treatments. (J) Quantification of scratch wound closure. (K) Representative western blot images showing total STAT1, p-STAT1, total STAT3, p-STAT3 and β-actin levels in cells treated with IFN-γ (100 ng/ml), IL-6 (100 ng/ml), IFN-γ + IL-6 (50 ng/ml each), ruxolitinib (5 µM) or IFN-γ + IL-6 (50 ng/ml each) plus ruxolitinib (5 µM), as indicated. (L) Densitometric semi-quantification of p-STAT1/STAT1 (ratio). (B and D) Unpaired two-tailed Student's t-test. (E, F, J and L) One-way ANOVA with Tukey's post hoc multiple comparisons test. *P<0.05, ***P<0.001, ****P<0.0001. CTRL, control; IBA-1, ionised calcium binding adaptor molecule 1; ns, not significant; p-, phosphorylated; PE-A, phycoerythrin-area.

    Journal: Molecular Medicine Reports

    Article Title: Elevated IgG levels induce an M2-to-M1 phenotypic shift in mucosal macrophages and restrict the growth of invasive sphenoid sinus pituitary adenomas

    doi: 10.3892/mmr.2026.13878

    Figure Lengend Snippet: Elevated IgG levels drive macrophage M2-to-M1 reprogramming. (A) Sphenoid sinus-invasive tumor cases stratified into CD19-high (n=5) and CD19-low (n=5) groups based on the cohort median of CD19 + B cell density, with (B) quantitative analyses of macrophage polarization (M1-like versus M2-like). (C) Dural-invasive tumor and non-invasive tumor cases stratified into IgG-high (n=27) and IgG-low (n=26) groups based on the cohort median of relative IgG immunohistochemistry staining intensity, with (D) quantitative analyses of M1-like/M2-like macrophage proportions. (E and F) RAW264.7 macrophages were pre-polarized with IL-4 (20 ng/ml) or with lipopolysaccharide (100 ng/ml) plus IFN-γ (20 ng/ml) for 24 h, followed by IgG (10 µg/ml) exposure. Relative (E) IL-6 and (F) TNF-α mRNA expression in RAW264.7 macrophages pre-polarized to M0, M1 or M2 states. (G) Representative flow cytometric cell-cycle profiles of TtT/GF cells following the indicated treatments. (H) Stacked bar plot summarizing the percentages of cells from (G) in G 1 , S and G 2 /M phases. (I) Representative images from the scratch wound assay at 0, 24, 48 and 72 h under the indicated treatments. (J) Quantification of scratch wound closure. (K) Representative western blot images showing total STAT1, p-STAT1, total STAT3, p-STAT3 and β-actin levels in cells treated with IFN-γ (100 ng/ml), IL-6 (100 ng/ml), IFN-γ + IL-6 (50 ng/ml each), ruxolitinib (5 µM) or IFN-γ + IL-6 (50 ng/ml each) plus ruxolitinib (5 µM), as indicated. (L) Densitometric semi-quantification of p-STAT1/STAT1 (ratio). (B and D) Unpaired two-tailed Student's t-test. (E, F, J and L) One-way ANOVA with Tukey's post hoc multiple comparisons test. *P<0.05, ***P<0.001, ****P<0.0001. CTRL, control; IBA-1, ionised calcium binding adaptor molecule 1; ns, not significant; p-, phosphorylated; PE-A, phycoerythrin-area.

    Article Snippet: Human IFN-γ, IL-1β, IL-6, IL-10, TGF-β and TNF-α levels were quantified using commercial ELISA kits (Human IFN-γ ELISA kit, cat. no. E-EL-H0108; Human IL-1β ELISA kit, cat. no. E-EL-H0149; Human IL-6 ELISA kit, cat. no. E-EL-H0102; Human IL-10 ELISA kit, cat. no. E-EL-H0103; Human TGF-β ELISA kit, cat. no. E-EL-H0110; Human TNF-α ELISA kit, cat. no. E-EL-H0109; Wuhan Elabscience Biotechnology Co., Ltd.).

    Techniques: Immunohistochemistry, Staining, Expressing, Scratch Wound Assay Assay, Western Blot, Two Tailed Test, Control, Binding Assay

    Anti-CD47 mAb enhances ADCP to suppress tumor cell proliferation. (A) Immunofluorescence staining of CD47 (red) and DAPI (blue) in a representative subset of non-invasive tumor, dural-invasive tumor and sphenoid sinus-invasive tumor cases (n=10 per group). (B) Paired comparison of CD47 fluorescence intensity at the IF versus the TC. (C) RAW264.7 macrophages were pre-polarized with IL-4 (20 ng/ml) or with lipopolysaccharide (100 ng/ml) plus IFN-γ (20 ng/ml) for 24 h, followed by anti-CD47 mAb (10 µg/ml) treatment for 12 h. Quantitative PCR was used to analyze polarization/activation markers. (D) Schematic illustrating anti-CD47 mAb-mediated blockade of the CD47-SIRPα axis and enhancement of ADCP. (E) EdU assay of TtT/GF cell proliferation in a Transwell co-culture with anti-CD47 mAb-treated polarized macrophages. (F) Quantification of EdU-positive cells. (G) Representative microscopy images and flow cytometry plots showing macrophage phagocytosis of pHrodo™ Red-labeled GFP-TtT/GF cells. (H) Quantification of phagocytosis (%). (B) Paired two-tailed Student's t-test. (C, F and H) One-way ANOVA with Tukey's post hoc multiple comparisons test. **P<0.01, ***P<0.001, ****P<0.0001. ADCP, antibody-dependent cellular phagocytosis; Arg-1, arginase 1; EdU, 5-ethynyl-2′-deoxyuridine; FcγR, Fcγ receptor; GFP, green fluorescent protein; IF, invasive front; mAb, monoclonal antibody; NOS2, nitric oxide synthase 2; ns, not significant; PE, phycoerythrin; SIRPα, signal regulatory protein-α; SSCA, side scatter area; TC, tumor core.

    Journal: Molecular Medicine Reports

    Article Title: Elevated IgG levels induce an M2-to-M1 phenotypic shift in mucosal macrophages and restrict the growth of invasive sphenoid sinus pituitary adenomas

    doi: 10.3892/mmr.2026.13878

    Figure Lengend Snippet: Anti-CD47 mAb enhances ADCP to suppress tumor cell proliferation. (A) Immunofluorescence staining of CD47 (red) and DAPI (blue) in a representative subset of non-invasive tumor, dural-invasive tumor and sphenoid sinus-invasive tumor cases (n=10 per group). (B) Paired comparison of CD47 fluorescence intensity at the IF versus the TC. (C) RAW264.7 macrophages were pre-polarized with IL-4 (20 ng/ml) or with lipopolysaccharide (100 ng/ml) plus IFN-γ (20 ng/ml) for 24 h, followed by anti-CD47 mAb (10 µg/ml) treatment for 12 h. Quantitative PCR was used to analyze polarization/activation markers. (D) Schematic illustrating anti-CD47 mAb-mediated blockade of the CD47-SIRPα axis and enhancement of ADCP. (E) EdU assay of TtT/GF cell proliferation in a Transwell co-culture with anti-CD47 mAb-treated polarized macrophages. (F) Quantification of EdU-positive cells. (G) Representative microscopy images and flow cytometry plots showing macrophage phagocytosis of pHrodo™ Red-labeled GFP-TtT/GF cells. (H) Quantification of phagocytosis (%). (B) Paired two-tailed Student's t-test. (C, F and H) One-way ANOVA with Tukey's post hoc multiple comparisons test. **P<0.01, ***P<0.001, ****P<0.0001. ADCP, antibody-dependent cellular phagocytosis; Arg-1, arginase 1; EdU, 5-ethynyl-2′-deoxyuridine; FcγR, Fcγ receptor; GFP, green fluorescent protein; IF, invasive front; mAb, monoclonal antibody; NOS2, nitric oxide synthase 2; ns, not significant; PE, phycoerythrin; SIRPα, signal regulatory protein-α; SSCA, side scatter area; TC, tumor core.

    Article Snippet: Human IFN-γ, IL-1β, IL-6, IL-10, TGF-β and TNF-α levels were quantified using commercial ELISA kits (Human IFN-γ ELISA kit, cat. no. E-EL-H0108; Human IL-1β ELISA kit, cat. no. E-EL-H0149; Human IL-6 ELISA kit, cat. no. E-EL-H0102; Human IL-10 ELISA kit, cat. no. E-EL-H0103; Human TGF-β ELISA kit, cat. no. E-EL-H0110; Human TNF-α ELISA kit, cat. no. E-EL-H0109; Wuhan Elabscience Biotechnology Co., Ltd.).

    Techniques: Immunofluorescence, Staining, Comparison, Fluorescence, Real-time Polymerase Chain Reaction, Activation Assay, EdU Assay, Co-Culture Assay, Microscopy, Flow Cytometry, Labeling, Two Tailed Test

    Summary graphic illustration. This illustration summarizes the proposed model during pituitary adenoma invasion. The tumor invasive front abuts an intact sphenoid sinus mucosa, forming a distinct boundary. The mucosal compartment is enriched for ionised calcium binding adaptor molecule 1-positive macrophages with an M1-like predominance and IgG-high B cells. B cell-derived IgG promotes M2-to-M1 macrophage reprogramming, while coordinated IFN-γ and IL-6 production establishes a tumor-suppressive cytokine gradient that decreases from mucosa toward the tumor core, constraining proliferation and migration via JAK-STAT1 activation. Therapeutically, anti-CD47 monoclonal antibody blocks the CD47-SIRPα ‘don't-eat-me’ axis and augments antibody-dependent cellular phagocytosis, highlighting a strategy for immune checkpoint-targeted therapy that may complement surgical management. FcR, Fc receptor; JAK, Janus kinase; mAb, monoclonal antibody; p-, phosphorylated; SIRPα, signal regulatory protein-α.

    Journal: Molecular Medicine Reports

    Article Title: Elevated IgG levels induce an M2-to-M1 phenotypic shift in mucosal macrophages and restrict the growth of invasive sphenoid sinus pituitary adenomas

    doi: 10.3892/mmr.2026.13878

    Figure Lengend Snippet: Summary graphic illustration. This illustration summarizes the proposed model during pituitary adenoma invasion. The tumor invasive front abuts an intact sphenoid sinus mucosa, forming a distinct boundary. The mucosal compartment is enriched for ionised calcium binding adaptor molecule 1-positive macrophages with an M1-like predominance and IgG-high B cells. B cell-derived IgG promotes M2-to-M1 macrophage reprogramming, while coordinated IFN-γ and IL-6 production establishes a tumor-suppressive cytokine gradient that decreases from mucosa toward the tumor core, constraining proliferation and migration via JAK-STAT1 activation. Therapeutically, anti-CD47 monoclonal antibody blocks the CD47-SIRPα ‘don't-eat-me’ axis and augments antibody-dependent cellular phagocytosis, highlighting a strategy for immune checkpoint-targeted therapy that may complement surgical management. FcR, Fc receptor; JAK, Janus kinase; mAb, monoclonal antibody; p-, phosphorylated; SIRPα, signal regulatory protein-α.

    Article Snippet: Human IFN-γ, IL-1β, IL-6, IL-10, TGF-β and TNF-α levels were quantified using commercial ELISA kits (Human IFN-γ ELISA kit, cat. no. E-EL-H0108; Human IL-1β ELISA kit, cat. no. E-EL-H0149; Human IL-6 ELISA kit, cat. no. E-EL-H0102; Human IL-10 ELISA kit, cat. no. E-EL-H0103; Human TGF-β ELISA kit, cat. no. E-EL-H0110; Human TNF-α ELISA kit, cat. no. E-EL-H0109; Wuhan Elabscience Biotechnology Co., Ltd.).

    Techniques: Binding Assay, Derivative Assay, Migration, Activation Assay