Journal: Cell Death & Disease

Article Title: Unveiling DEFB1 as a novel driver and promising therapeutic target in lung adenocarcinoma

doi: 10.1038/s41419-026-08748-4

Figure Lengend Snippet: A Infiltrating status of M1 (marked by F4/80 and INOS) and M2 (marked by F4/80 and CD206) macrophages in nude-mouse xenografts derived from A549 DEFB1-NC/KO/ROE cells (scale bar: 200 μm); B CoIP verification of the interaction between DEFB1 and MIF in A549/PC-9 cells treated with exogenously added 3× Flag-tagged DEFB1 (200 pg/mL); C AlphaFold 3 prediction of the interaction mode between DEFB1 and MIF; D Schematic diagram of an in vitro co-culture model of lung adenocarcinoma cells and THP-1 derived macrophages; E , F Flow Cytometry and qRT-PCR for evaluating the effects of DEFB1 and/or MIF inhibitor (ISO-1) on M1 polarization of THP-1 M0 cells co-cultured with A549 cells; G , H Flow Cytometry and qRT-PCR for evaluating the effects of DEFB1 and/or ISO-1 on M2 polarization of THP-1 M0 cells co-cultured with A549 cells; I , J Effects of DEFB1-KO, PPL-KO, and/or ISO-1 on the in vivo proliferative capacity in nude-mouse CDX model. Statistical analysis: ( F , H , and G ) One-way ANOVA test and Bonferroni correction.

Article Snippet: ISO-1 (#T3680) was obtained from TargetMol (Boston, Massachusetts, USA).

Techniques: Derivative Assay, In Vitro, Co-culture Assay, Flow Cytometry, Quantitative RT-PCR, Cell Culture, In Vivo, Analysis, Immunofluorescence, Co-Immunoprecipitation Assay, Real-time Polymerase Chain Reaction, Xenograft Assay

Journal: Aging Cell

Article Title: Characterizing the SASP ‐Dependent Paracrine Spreading of Senescence Between Human Brain Cell Types

doi: 10.1111/acel.70673

Figure Lengend Snippet: Analysis of ligands and receptors in senescent and receiving cells. (A) Schematic depicting BulkSignalR pipeline which uses known ligand‐receptor interactions and affected downstream pathways to analyze their activation based on our bulk RNAseq data from DMSO and BrdU treated human cell lines (created with BioRender). (B) Venn diagram showing the number of receptors inferred from BulkSignalR to be activated across each of the five human cell types. Three receptors were identified in common between astrocytes (purple), endothelial cells (pink), and microglia (yellow) which were the cell types shown (Figure ) to be capable of receiving senescence signals and becoming SA β‐gal positive: CXCR7, KREMEN2, and GIPR. Only CXCR7 was expressed in the cell types capable of entering secondary senescence (astrocytes, endothelial cells, microglia) (Figure , Figure ). (C) TPM expression values of CXCR7 , its ligand CXCL12 , and DPP4 which cleaves and inactivates CXCL12 in DMSO (gray) and BrdU (red) treated cell lines ( n = 3 replicates). (D) Schematic of the four selected SASP inhibitors mechanisms of action: Bindarit is a CCL2 synthesis inhibitor which prevents p65 activation of the CCL2 gene at the promoter region, ISO‐1 is a MIF antagonist, ACT‐1004‐1239 is a CXCR7 antagonist, and Sitagliptin inhibits DPP4 preventing its action of cleaving and inactivating CXCL12 (created with BioRender). Data were analyzed by two‐way ANOVA with Tukey's multiple comparisons test (C). All graphs show mean with error bars depicting standard deviation (ns, p > 0.05, ** p < 0.01, *** p < 0.001).

Article Snippet: Treatment with migration inhibitor factor (MIF) antagonist ISO‐1 (MedChemExpress, Catalog No. HY‐16692) (Kok et al. ) was utilized to prevent MIF‐associated communication between senescence inducers and receiving cells.

Techniques: Activation Assay, RNA sequencing, Expressing, Standard Deviation

Journal: Aging Cell

Article Title: Characterizing the SASP ‐Dependent Paracrine Spreading of Senescence Between Human Brain Cell Types

doi: 10.1111/acel.70673

Figure Lengend Snippet: Targeting SASP ligands and receptors to prevent the spreading of senescence. (A) Quantification of percentage of SA β‐gal positive astrocytes following 7‐day treatment with 100 μM BrdU (red) along with 200 μM Bindarit (pink), 50 μM ISO‐1 (blue), 200 μM ACT‐1004‐1239 (orange), or 2 μM Sitagliptin (green) ( n = 6 replicates). (B) Quantification of percentage of SA β‐gal positive microglia following 7‐day treatment with 100 μM BrdU (red) along with 200 μM Bindarit (pink), 50 μM ISO‐1 (blue), 200 μM ACT‐1004‐1239 (orange), or 2 μM Sitagliptin (green) ( n = 6 replicates). (C) Timeline showing treatment with DMSO + Bindarit CM or BrdU + Bindarit CM for 7 days. Timeline showing treatment with DMSO or 100 μM BrdU along with SASP inhibitors (ISO‐1, ACT‐1004‐1239, or Sitagliptin) for 7 days. Features of senescence were analyzed 8 days after the initial plating of cells (created with BioRender). (D) Quantification of percentage of SA β‐gal positive astrocytes following 7‐day treatment with DMSO + Bindarit CM from astrocytes (gray), BrdU + Bindarit CM from astrocytes (red), DMSO CM from astrocytes + SASP inhibitor (gray), or BrdU CM from astrocytes + SASP inhibitor (red) ( n = 4 replicates). Quantification of percentage of SA β‐gal positive astrocytes following 7‐day treatment with DMSO CM from astrocytes + Bindarit (gray) or BrdU CM from astrocytes + Bindarit (red) ( n = 4 replicates). (E) Quantification of percentage of SA β‐gal positive astrocytes following 7‐day treatment with DMSO + Bindarit CM from microglia (gray), BrdU + Bindarit CM from microglia (red), DMSO CM from microglia + SASP inhibitor (gray), or BrdU CM from microglia + SASP inhibitor (red) ( n = 4 replicates). Quantification of percentage of SA β‐gal positive astrocytes following 7‐day treatment with DMSO CM from microglia + Bindarit (gray) or BrdU CM from microglia + Bindarit (red) ( n = 4 replicates). (F) Quantification of percentage of SA β‐gal positive microglia following 7‐day treatment with DMSO + Bindarit CM from microglia (gray), BrdU + Bindarit CM from microglia (red), DMSO CM from microglia + SASP inhibitor (gray), or BrdU CM from microglia + SASP inhibitor (red) ( n = 4 replicates). Quantification of percentage of SA β‐gal positive astrocytes following 7‐day treatment with DMSO CM from microglia + Bindarit (gray) or BrdU CM from microglia + Bindarit (red) ( n = 4 replicates). (G) Quantification of percentage of SA β‐gal positive microglia following 7‐day treatment with DMSO + Bindarit CM from astrocytes (gray), BrdU + Bindarit CM from astrocytes (red), DMSO CM from astrocytes + SASP inhibitor (gray), or BrdU CM from astrocytes + SASP inhibitor (red) ( n = 4 replicates). Quantification of percentage of SA β‐gal positive astrocytes following 7‐day treatment with DMSO CM from astrocytes + Bindarit (gray) or BrdU CM from astrocytes + Bindarit (red) ( n = 4 replicates). Data analyzed by unpaired t ‐test (A, B) and two‐way ANOVA with Tukey's or Šídák's multiple comparisons test (D–G). All graphs show mean with error bars depicting standard deviation (ns, p > 0.05, * p < 0.05, ** p < 0.01, *** p < 0.001).

Article Snippet: Treatment with migration inhibitor factor (MIF) antagonist ISO‐1 (MedChemExpress, Catalog No. HY‐16692) (Kok et al. ) was utilized to prevent MIF‐associated communication between senescence inducers and receiving cells.

Techniques: Standard Deviation

Journal: Acta Physiologica (Oxford, England)

Article Title: Angiotensin‐(1–7) Alleviates Isoproterenol‐Induced Cardiac Hypertrophy by Suppressing Autophagy and Apoptosis Through the Synergistic Action of Mas Receptor and Angiotensin II Type 2 Receptor

doi: 10.1111/apha.70200

Figure Lengend Snippet: Physical and chemical properties and biosafety assessment of Ang‐(1–7). (A) Key molecular properties: molecular weight (MW), net charge, isoelectric point (pI), hydrophobicity (GRAVY index), and aromaticity. (B, C) Topological structure predicted by Deep TMHMM, showing a spherical soluble conformation (no transmembrane helices) and predicted functional sites (red‐intracellular; blue‐extracellular). (D) Hemolytic activity ( n = 6). (E) Cytotoxicity assessment in H9c2, HepG2, and NRK‐52E cell lines ( n = 6). Cell viability was determined using the Cell Counting Kit‐8 (CCK‐8) assay. The data is expressed as an mean ± standard deviation (SD).

Article Snippet: After 7 days' acclimatization, animals were randomized (blinded assessment) into five groups ( n = 6 per group) receiving daily Subcutaneous injection for 7 days [ , , ]:Ctrl: saline (Sanlian, Harbin, China); ISO: isoproterenol 5 mg/kg/day (Solarbio, II0200, Beijing, China; dissolved in DMSO); ISO + Ang‐(1–7): Ang‐(1–7) 576 μg/kg/day (MCE, HY‐12403, USA; in distilled water); ISO + Ang‐(1–7) + A‐779: A‐7791148 μg/kg/day (MCE, HY‐P0216, USA); ISO + Ang‐(1–7) + PD123319 : PD123319 5 mg/kg/day (MCE, HY‐10259A, USA); ISO + Ang‐(1–7) + PD123319 + A779.

Techniques: Molecular Weight, Functional Assay, Activity Assay, Cell Counting, CCK-8 Assay, Standard Deviation

Journal: Acta Physiologica (Oxford, England)

Article Title: Angiotensin‐(1–7) Alleviates Isoproterenol‐Induced Cardiac Hypertrophy by Suppressing Autophagy and Apoptosis Through the Synergistic Action of Mas Receptor and Angiotensin II Type 2 Receptor

doi: 10.1111/apha.70200

Figure Lengend Snippet: Effects of Ang‐(1–7) on isoproterenol (ISO)‐induced cardiac hypertrophy and fibrosis. (A) HE staining and Masson staining of myocardial sections (scale bar = 20 μm). (B, C) Quantitative analysis of myocardial cell cross‐sectional area and collagen volume fraction. (D, E) Macroscopic morphology and cross‐sectional observation of the heart, with measurement of heart weight/body weight ratio (HW/BW) (scale bar = 2 mm). (F) Western blot analysis of ANP, BNP, and β‐MHC expression. (G–I) Quantitative analysis of band intensity normalized to GAPDH. The data is expressed as an mean ± standard deviation (SD) ( n = 5). A + I, Ang‐(1–7) + ISO; AntM+A + I, A‐779 + Ang‐(1–7) + ISO; AntA+A + I, PD123319 + Ang‐(1–7) + ISO. *** p < 0.001 versus Ctrl; ### p < 0.001 versus ISO; &&& p < 0.001, && p < 0.01, & p < 0.05 versus Ang‐(1–7) + ISO.

Article Snippet: After 7 days' acclimatization, animals were randomized (blinded assessment) into five groups ( n = 6 per group) receiving daily Subcutaneous injection for 7 days [ , , ]:Ctrl: saline (Sanlian, Harbin, China); ISO: isoproterenol 5 mg/kg/day (Solarbio, II0200, Beijing, China; dissolved in DMSO); ISO + Ang‐(1–7): Ang‐(1–7) 576 μg/kg/day (MCE, HY‐12403, USA; in distilled water); ISO + Ang‐(1–7) + A‐779: A‐7791148 μg/kg/day (MCE, HY‐P0216, USA); ISO + Ang‐(1–7) + PD123319 : PD123319 5 mg/kg/day (MCE, HY‐10259A, USA); ISO + Ang‐(1–7) + PD123319 + A779.

Techniques: Staining, Western Blot, Expressing, Standard Deviation

Journal: Acta Physiologica (Oxford, England)

Article Title: Angiotensin‐(1–7) Alleviates Isoproterenol‐Induced Cardiac Hypertrophy by Suppressing Autophagy and Apoptosis Through the Synergistic Action of Mas Receptor and Angiotensin II Type 2 Receptor

doi: 10.1111/apha.70200

Figure Lengend Snippet: Ang‐(1–7) improves ISO‐induced ventricular remodeling and dysfunction via MasR and AT 2 R. (A) Representative M‐mode echocardiograms from each group (scale bar = 2 mm). (B, C) Quantification of left ventricular internal diameters at systole (LVIDs) and diastole (LVIDd). (D, E) Left ventricular ejection fraction (LVEF%) and fractional shortening (LVFS%). (F, G) Left ventricular posterior wall thickness at systole (LVPWs) and diastole (LVPWd). (H) Representative immunofluorescence images of cardiomyocytes (green, α‐actinin; blue, nuclei; scale bar = 10 μm). (I) Relative mRNA expression of ANP, BNP, and β‐MHC ( n = 6). The data is expressed as an mean ± standard deviation (SD) ( n = 5). A + I, Ang‐(1–7) + ISO; AntM + A + I, A‐779 + Ang‐(1–7) + ISO; AntA + A + I, PD123319 + Ang‐(1–7) + ISO; AntM + AntA + A + I, A‐779 + PD123319 + Ang‐(1–7) + ISO. *** p < 0.001, ** p < 0.01 versus Ctrl; ### p < 0.001, ## p < 0.01 versus ISO; &&& p < 0.001, && p < 0.01, & p < 0.05 versus Ang‐(1–7) + ISO, & p < 0.05 versus ISO.

Article Snippet: After 7 days' acclimatization, animals were randomized (blinded assessment) into five groups ( n = 6 per group) receiving daily Subcutaneous injection for 7 days [ , , ]:Ctrl: saline (Sanlian, Harbin, China); ISO: isoproterenol 5 mg/kg/day (Solarbio, II0200, Beijing, China; dissolved in DMSO); ISO + Ang‐(1–7): Ang‐(1–7) 576 μg/kg/day (MCE, HY‐12403, USA; in distilled water); ISO + Ang‐(1–7) + A‐779: A‐7791148 μg/kg/day (MCE, HY‐P0216, USA); ISO + Ang‐(1–7) + PD123319 : PD123319 5 mg/kg/day (MCE, HY‐10259A, USA); ISO + Ang‐(1–7) + PD123319 + A779.

Techniques: Immunofluorescence, Expressing, Standard Deviation

Journal: Acta Physiologica (Oxford, England)

Article Title: Angiotensin‐(1–7) Alleviates Isoproterenol‐Induced Cardiac Hypertrophy by Suppressing Autophagy and Apoptosis Through the Synergistic Action of Mas Receptor and Angiotensin II Type 2 Receptor

doi: 10.1111/apha.70200

Figure Lengend Snippet: Ang‐(1–7) regulates the expression of MasR and AT 2 R in H9c2 cardiomyocytes and exhibits cross‐inhibition with receptor antagonists. (A) Immunofluorescence images and immunofluorescence intensity of MasR (green), AT 2 R (red), and DAPI (blue) in H9c2 cells from different treatment groups, reflecting receptor expression levels (scale bar = 80 μm) ( n = 5). (B) Shows the expression of AT 2 R and MasR mRNA in H9c2 cells ( n = 6). (C) Analyzes MasR expression and relative thermal stability in cardiomyocytes at different temperatures (37°C–58°C). The data is expressed as an mean ± standard deviation (SD) ( n = 5). A + I, Ang‐(1–7) + ISO; AntM + A + I, A‐779 + Ang‐(1–7) + ISO; AntA + A + I, PD123319 + Ang‐(1–7) + ISO; AntM + AntA + A + I, A‐779 + PD123319 + Ang‐(1–7) + ISO. *** p < 0.001, * p < 0.05 versus Ctrl; #### p < 0.0001, ### p < 0.001 versus ISO; &&& p < 0.001, && p < 0.01, & p < 0.05 versus Ang‐(1–7) + ISO.

Article Snippet: After 7 days' acclimatization, animals were randomized (blinded assessment) into five groups ( n = 6 per group) receiving daily Subcutaneous injection for 7 days [ , , ]:Ctrl: saline (Sanlian, Harbin, China); ISO: isoproterenol 5 mg/kg/day (Solarbio, II0200, Beijing, China; dissolved in DMSO); ISO + Ang‐(1–7): Ang‐(1–7) 576 μg/kg/day (MCE, HY‐12403, USA; in distilled water); ISO + Ang‐(1–7) + A‐779: A‐7791148 μg/kg/day (MCE, HY‐P0216, USA); ISO + Ang‐(1–7) + PD123319 : PD123319 5 mg/kg/day (MCE, HY‐10259A, USA); ISO + Ang‐(1–7) + PD123319 + A779.

Techniques: Expressing, Inhibition, Immunofluorescence, Standard Deviation

Journal: Acta Physiologica (Oxford, England)

Article Title: Angiotensin‐(1–7) Alleviates Isoproterenol‐Induced Cardiac Hypertrophy by Suppressing Autophagy and Apoptosis Through the Synergistic Action of Mas Receptor and Angiotensin II Type 2 Receptor

doi: 10.1111/apha.70200

Figure Lengend Snippet: Ang‐(1–7) regulates the expression of MasR and AT 2 R and their heterodimer formation. (A) Immunofluorescence staining images of MasR (green), AT 2 R (red), and DAPI (blue) in myocardial tissue from mice in each treatment group. Arrows indicate the localization of receptors in the myocardium (scale bar = 20 μm) ( n = 5). (B) Protein expression and quantitative analysis of MasR and AT 2 R in myocardial tissue ( n = 6). (C) Molecular docking simulations showing the interactions between MasR and AT 2 R, as well as between Ang‐(1–7) and the receptors, along with the binding energies (ΔG) for each interaction. (D) Immunoprecipitation (Co‐IP): Interaction between MasR and AT 2 R in cardiac muscle tissue. The data is expressed as an mean ± standard deviation (SD). A + I, Ang‐(1–7) + ISO; AntM + A + I, A‐779 + Ang‐(1–7) + ISO; Ant A + A + I, PD123319 + Ang‐(1–7) + ISO. * p < 0.05 versus Ctrl; ### p < 0.001 versus ISO; &&& p < 0.001, & p < 0.05 versus Ang‐(1–7) + ISO.

Article Snippet: After 7 days' acclimatization, animals were randomized (blinded assessment) into five groups ( n = 6 per group) receiving daily Subcutaneous injection for 7 days [ , , ]:Ctrl: saline (Sanlian, Harbin, China); ISO: isoproterenol 5 mg/kg/day (Solarbio, II0200, Beijing, China; dissolved in DMSO); ISO + Ang‐(1–7): Ang‐(1–7) 576 μg/kg/day (MCE, HY‐12403, USA; in distilled water); ISO + Ang‐(1–7) + A‐779: A‐7791148 μg/kg/day (MCE, HY‐P0216, USA); ISO + Ang‐(1–7) + PD123319 : PD123319 5 mg/kg/day (MCE, HY‐10259A, USA); ISO + Ang‐(1–7) + PD123319 + A779.

Techniques: Expressing, Immunofluorescence, Staining, Binding Assay, Immunoprecipitation, Co-Immunoprecipitation Assay, Standard Deviation

Journal: Acta Physiologica (Oxford, England)

Article Title: Angiotensin‐(1–7) Alleviates Isoproterenol‐Induced Cardiac Hypertrophy by Suppressing Autophagy and Apoptosis Through the Synergistic Action of Mas Receptor and Angiotensin II Type 2 Receptor

doi: 10.1111/apha.70200

Figure Lengend Snippet: Ang‐(1–7) attenuates ISO‐induced excessive autophagy and apoptosis in vivo by regulating MasR and AT 2 R. (A) Transmission electron microscopy (TEM) images showing autophagosomes, lysosomes, and damaged mitochondria in cardiomyocytes; quantification of damaged mitochondria is shown (scale bar = 5 μm, 2 μm n = 4). (B) Western blot analysis of autophagy‐related proteins LC3‐II/I, Beclin1, and P62 ( n = 5). (C) Western blot analysis of apoptosis‐related proteins Bcl‐2, Bax, and cleaved caspase‐3 ( n = 5). (D, E) Quantitative densitometry analysis of autophagy‐ and apoptosis‐related proteins normalized to GAPDH. The data is expressed as an mean ± standard deviation (SD). A + I, Ang‐(1–7) + ISO; AntM + A + I, A‐779 + Ang‐(1–7) + ISO; Ant A + A + I, PD123319 + Ang‐(1–7) + ISO. *** p < 0.001 versus Ctrl; ### p < 0.001, # p < 0.05 versus ISO; &&& p < 0.001, && p < 0.01, & p < 0.05 versus Ang‐(1–7) + ISO.

Article Snippet: After 7 days' acclimatization, animals were randomized (blinded assessment) into five groups ( n = 6 per group) receiving daily Subcutaneous injection for 7 days [ , , ]:Ctrl: saline (Sanlian, Harbin, China); ISO: isoproterenol 5 mg/kg/day (Solarbio, II0200, Beijing, China; dissolved in DMSO); ISO + Ang‐(1–7): Ang‐(1–7) 576 μg/kg/day (MCE, HY‐12403, USA; in distilled water); ISO + Ang‐(1–7) + A‐779: A‐7791148 μg/kg/day (MCE, HY‐P0216, USA); ISO + Ang‐(1–7) + PD123319 : PD123319 5 mg/kg/day (MCE, HY‐10259A, USA); ISO + Ang‐(1–7) + PD123319 + A779.

Techniques: In Vivo, Transmission Assay, Electron Microscopy, Western Blot, Standard Deviation

Journal: Acta Physiologica (Oxford, England)

Article Title: Angiotensin‐(1–7) Alleviates Isoproterenol‐Induced Cardiac Hypertrophy by Suppressing Autophagy and Apoptosis Through the Synergistic Action of Mas Receptor and Angiotensin II Type 2 Receptor

doi: 10.1111/apha.70200

Figure Lengend Snippet: Ang‐(1–7) regulates autophagic flux and apoptosis in H9c2 cardiomyocytes through MasR and AT 2 R. (A) Representative images of TUNEL immunofluorescence staining (green fluorescence labels apoptotic cells) and Hoechst nuclear staining (blue) ( n = 6), with the Merge panel showing their overlay. (B) Western blot analysis of apoptosis related proteins (Bax, Bcl 2 , Cleaved caspase‐3) expression levels, with GAPDH as the internal control protein ( n = 3). (C) Western blot analysis of autophagy‐related proteins (LC3‐II, Beclin1, P62) expression levels, with GAPDH as the internal control protein ( n = 3). The data is expressed as an mean ± standard deviation (SD). A + I, Ang‐(1–7) + ISO; AntM + A + I, A‐779 + Ang‐(1–7) + ISO; Ant A + A + I, PD123319 + Ang‐(1–7) + ISO; AntM + AntA + A + I, A‐779 + PD123319 + Ang‐(1–7) + ISO.

Article Snippet: After 7 days' acclimatization, animals were randomized (blinded assessment) into five groups ( n = 6 per group) receiving daily Subcutaneous injection for 7 days [ , , ]:Ctrl: saline (Sanlian, Harbin, China); ISO: isoproterenol 5 mg/kg/day (Solarbio, II0200, Beijing, China; dissolved in DMSO); ISO + Ang‐(1–7): Ang‐(1–7) 576 μg/kg/day (MCE, HY‐12403, USA; in distilled water); ISO + Ang‐(1–7) + A‐779: A‐7791148 μg/kg/day (MCE, HY‐P0216, USA); ISO + Ang‐(1–7) + PD123319 : PD123319 5 mg/kg/day (MCE, HY‐10259A, USA); ISO + Ang‐(1–7) + PD123319 + A779.

Techniques: TUNEL Assay, Immunofluorescence, Staining, Fluorescence, Western Blot, Expressing, Control, Standard Deviation

Journal: Acta Physiologica (Oxford, England)

Article Title: Angiotensin‐(1–7) Alleviates Isoproterenol‐Induced Cardiac Hypertrophy by Suppressing Autophagy and Apoptosis Through the Synergistic Action of Mas Receptor and Angiotensin II Type 2 Receptor

doi: 10.1111/apha.70200

Figure Lengend Snippet: Physical and chemical properties and biosafety assessment of Ang‐(1–7). (A) Key molecular properties: molecular weight (MW), net charge, isoelectric point (pI), hydrophobicity (GRAVY index), and aromaticity. (B, C) Topological structure predicted by Deep TMHMM, showing a spherical soluble conformation (no transmembrane helices) and predicted functional sites (red‐intracellular; blue‐extracellular). (D) Hemolytic activity ( n = 6). (E) Cytotoxicity assessment in H9c2, HepG2, and NRK‐52E cell lines ( n = 6). Cell viability was determined using the Cell Counting Kit‐8 (CCK‐8) assay. The data is expressed as an mean ± standard deviation (SD).

Article Snippet: After 7 days' acclimatization, animals were randomized (blinded assessment) into five groups ( n = 6 per group) receiving daily Subcutaneous injection for 7 days [ , , ]:Ctrl: saline (Sanlian, Harbin, China); ISO: isoproterenol 5 mg/kg/day (Solarbio, II0200, Beijing, China; dissolved in DMSO); ISO + Ang‐(1–7): Ang‐(1–7) 576 μg/kg/day (MCE, HY‐12403, USA; in distilled water); ISO + Ang‐(1–7) + A‐779: A‐7791148 μg/kg/day (MCE, HY‐P0216, USA); ISO + Ang‐(1–7) + PD123319 : PD123319 5 mg/kg/day (MCE, HY‐10259A, USA); ISO + Ang‐(1–7) + PD123319 + A779.

Techniques: Molecular Weight, Functional Assay, Activity Assay, Cell Counting, CCK-8 Assay, Standard Deviation

Journal: Acta Physiologica (Oxford, England)

Article Title: Angiotensin‐(1–7) Alleviates Isoproterenol‐Induced Cardiac Hypertrophy by Suppressing Autophagy and Apoptosis Through the Synergistic Action of Mas Receptor and Angiotensin II Type 2 Receptor

doi: 10.1111/apha.70200

Figure Lengend Snippet: Effects of Ang‐(1–7) on isoproterenol (ISO)‐induced cardiac hypertrophy and fibrosis. (A) HE staining and Masson staining of myocardial sections (scale bar = 20 μm). (B, C) Quantitative analysis of myocardial cell cross‐sectional area and collagen volume fraction. (D, E) Macroscopic morphology and cross‐sectional observation of the heart, with measurement of heart weight/body weight ratio (HW/BW) (scale bar = 2 mm). (F) Western blot analysis of ANP, BNP, and β‐MHC expression. (G–I) Quantitative analysis of band intensity normalized to GAPDH. The data is expressed as an mean ± standard deviation (SD) ( n = 5). A + I, Ang‐(1–7) + ISO; AntM+A + I, A‐779 + Ang‐(1–7) + ISO; AntA+A + I, PD123319 + Ang‐(1–7) + ISO. *** p < 0.001 versus Ctrl; ### p < 0.001 versus ISO; &&& p < 0.001, && p < 0.01, & p < 0.05 versus Ang‐(1–7) + ISO.

Article Snippet: After 7 days' acclimatization, animals were randomized (blinded assessment) into five groups ( n = 6 per group) receiving daily Subcutaneous injection for 7 days [ , , ]:Ctrl: saline (Sanlian, Harbin, China); ISO: isoproterenol 5 mg/kg/day (Solarbio, II0200, Beijing, China; dissolved in DMSO); ISO + Ang‐(1–7): Ang‐(1–7) 576 μg/kg/day (MCE, HY‐12403, USA; in distilled water); ISO + Ang‐(1–7) + A‐779: A‐7791148 μg/kg/day (MCE, HY‐P0216, USA); ISO + Ang‐(1–7) + PD123319 : PD123319 5 mg/kg/day (MCE, HY‐10259A, USA); ISO + Ang‐(1–7) + PD123319 + A779.

Techniques: Staining, Western Blot, Expressing, Standard Deviation

Journal: Acta Physiologica (Oxford, England)

Article Title: Angiotensin‐(1–7) Alleviates Isoproterenol‐Induced Cardiac Hypertrophy by Suppressing Autophagy and Apoptosis Through the Synergistic Action of Mas Receptor and Angiotensin II Type 2 Receptor

doi: 10.1111/apha.70200

Figure Lengend Snippet: Ang‐(1–7) improves ISO‐induced ventricular remodeling and dysfunction via MasR and AT 2 R. (A) Representative M‐mode echocardiograms from each group (scale bar = 2 mm). (B, C) Quantification of left ventricular internal diameters at systole (LVIDs) and diastole (LVIDd). (D, E) Left ventricular ejection fraction (LVEF%) and fractional shortening (LVFS%). (F, G) Left ventricular posterior wall thickness at systole (LVPWs) and diastole (LVPWd). (H) Representative immunofluorescence images of cardiomyocytes (green, α‐actinin; blue, nuclei; scale bar = 10 μm). (I) Relative mRNA expression of ANP, BNP, and β‐MHC ( n = 6). The data is expressed as an mean ± standard deviation (SD) ( n = 5). A + I, Ang‐(1–7) + ISO; AntM + A + I, A‐779 + Ang‐(1–7) + ISO; AntA + A + I, PD123319 + Ang‐(1–7) + ISO; AntM + AntA + A + I, A‐779 + PD123319 + Ang‐(1–7) + ISO. *** p < 0.001, ** p < 0.01 versus Ctrl; ### p < 0.001, ## p < 0.01 versus ISO; &&& p < 0.001, && p < 0.01, & p < 0.05 versus Ang‐(1–7) + ISO, & p < 0.05 versus ISO.

Article Snippet: After 7 days' acclimatization, animals were randomized (blinded assessment) into five groups ( n = 6 per group) receiving daily Subcutaneous injection for 7 days [ , , ]:Ctrl: saline (Sanlian, Harbin, China); ISO: isoproterenol 5 mg/kg/day (Solarbio, II0200, Beijing, China; dissolved in DMSO); ISO + Ang‐(1–7): Ang‐(1–7) 576 μg/kg/day (MCE, HY‐12403, USA; in distilled water); ISO + Ang‐(1–7) + A‐779: A‐7791148 μg/kg/day (MCE, HY‐P0216, USA); ISO + Ang‐(1–7) + PD123319 : PD123319 5 mg/kg/day (MCE, HY‐10259A, USA); ISO + Ang‐(1–7) + PD123319 + A779.

Techniques: Immunofluorescence, Expressing, Standard Deviation

Journal: Acta Physiologica (Oxford, England)

Article Title: Angiotensin‐(1–7) Alleviates Isoproterenol‐Induced Cardiac Hypertrophy by Suppressing Autophagy and Apoptosis Through the Synergistic Action of Mas Receptor and Angiotensin II Type 2 Receptor

doi: 10.1111/apha.70200

Figure Lengend Snippet: Ang‐(1–7) regulates the expression of MasR and AT 2 R in H9c2 cardiomyocytes and exhibits cross‐inhibition with receptor antagonists. (A) Immunofluorescence images and immunofluorescence intensity of MasR (green), AT 2 R (red), and DAPI (blue) in H9c2 cells from different treatment groups, reflecting receptor expression levels (scale bar = 80 μm) ( n = 5). (B) Shows the expression of AT 2 R and MasR mRNA in H9c2 cells ( n = 6). (C) Analyzes MasR expression and relative thermal stability in cardiomyocytes at different temperatures (37°C–58°C). The data is expressed as an mean ± standard deviation (SD) ( n = 5). A + I, Ang‐(1–7) + ISO; AntM + A + I, A‐779 + Ang‐(1–7) + ISO; AntA + A + I, PD123319 + Ang‐(1–7) + ISO; AntM + AntA + A + I, A‐779 + PD123319 + Ang‐(1–7) + ISO. *** p < 0.001, * p < 0.05 versus Ctrl; #### p < 0.0001, ### p < 0.001 versus ISO; &&& p < 0.001, && p < 0.01, & p < 0.05 versus Ang‐(1–7) + ISO.

Article Snippet: After 7 days' acclimatization, animals were randomized (blinded assessment) into five groups ( n = 6 per group) receiving daily Subcutaneous injection for 7 days [ , , ]:Ctrl: saline (Sanlian, Harbin, China); ISO: isoproterenol 5 mg/kg/day (Solarbio, II0200, Beijing, China; dissolved in DMSO); ISO + Ang‐(1–7): Ang‐(1–7) 576 μg/kg/day (MCE, HY‐12403, USA; in distilled water); ISO + Ang‐(1–7) + A‐779: A‐7791148 μg/kg/day (MCE, HY‐P0216, USA); ISO + Ang‐(1–7) + PD123319 : PD123319 5 mg/kg/day (MCE, HY‐10259A, USA); ISO + Ang‐(1–7) + PD123319 + A779.

Techniques: Expressing, Inhibition, Immunofluorescence, Standard Deviation

Journal: Acta Physiologica (Oxford, England)

Article Title: Angiotensin‐(1–7) Alleviates Isoproterenol‐Induced Cardiac Hypertrophy by Suppressing Autophagy and Apoptosis Through the Synergistic Action of Mas Receptor and Angiotensin II Type 2 Receptor

doi: 10.1111/apha.70200

Figure Lengend Snippet: Ang‐(1–7) regulates the expression of MasR and AT 2 R and their heterodimer formation. (A) Immunofluorescence staining images of MasR (green), AT 2 R (red), and DAPI (blue) in myocardial tissue from mice in each treatment group. Arrows indicate the localization of receptors in the myocardium (scale bar = 20 μm) ( n = 5). (B) Protein expression and quantitative analysis of MasR and AT 2 R in myocardial tissue ( n = 6). (C) Molecular docking simulations showing the interactions between MasR and AT 2 R, as well as between Ang‐(1–7) and the receptors, along with the binding energies (ΔG) for each interaction. (D) Immunoprecipitation (Co‐IP): Interaction between MasR and AT 2 R in cardiac muscle tissue. The data is expressed as an mean ± standard deviation (SD). A + I, Ang‐(1–7) + ISO; AntM + A + I, A‐779 + Ang‐(1–7) + ISO; Ant A + A + I, PD123319 + Ang‐(1–7) + ISO. * p < 0.05 versus Ctrl; ### p < 0.001 versus ISO; &&& p < 0.001, & p < 0.05 versus Ang‐(1–7) + ISO.

Article Snippet: After 7 days' acclimatization, animals were randomized (blinded assessment) into five groups ( n = 6 per group) receiving daily Subcutaneous injection for 7 days [ , , ]:Ctrl: saline (Sanlian, Harbin, China); ISO: isoproterenol 5 mg/kg/day (Solarbio, II0200, Beijing, China; dissolved in DMSO); ISO + Ang‐(1–7): Ang‐(1–7) 576 μg/kg/day (MCE, HY‐12403, USA; in distilled water); ISO + Ang‐(1–7) + A‐779: A‐7791148 μg/kg/day (MCE, HY‐P0216, USA); ISO + Ang‐(1–7) + PD123319 : PD123319 5 mg/kg/day (MCE, HY‐10259A, USA); ISO + Ang‐(1–7) + PD123319 + A779.

Techniques: Expressing, Immunofluorescence, Staining, Binding Assay, Immunoprecipitation, Co-Immunoprecipitation Assay, Standard Deviation

Journal: Acta Physiologica (Oxford, England)

Article Title: Angiotensin‐(1–7) Alleviates Isoproterenol‐Induced Cardiac Hypertrophy by Suppressing Autophagy and Apoptosis Through the Synergistic Action of Mas Receptor and Angiotensin II Type 2 Receptor

doi: 10.1111/apha.70200

Figure Lengend Snippet: Ang‐(1–7) attenuates ISO‐induced excessive autophagy and apoptosis in vivo by regulating MasR and AT 2 R. (A) Transmission electron microscopy (TEM) images showing autophagosomes, lysosomes, and damaged mitochondria in cardiomyocytes; quantification of damaged mitochondria is shown (scale bar = 5 μm, 2 μm n = 4). (B) Western blot analysis of autophagy‐related proteins LC3‐II/I, Beclin1, and P62 ( n = 5). (C) Western blot analysis of apoptosis‐related proteins Bcl‐2, Bax, and cleaved caspase‐3 ( n = 5). (D, E) Quantitative densitometry analysis of autophagy‐ and apoptosis‐related proteins normalized to GAPDH. The data is expressed as an mean ± standard deviation (SD). A + I, Ang‐(1–7) + ISO; AntM + A + I, A‐779 + Ang‐(1–7) + ISO; Ant A + A + I, PD123319 + Ang‐(1–7) + ISO. *** p < 0.001 versus Ctrl; ### p < 0.001, # p < 0.05 versus ISO; &&& p < 0.001, && p < 0.01, & p < 0.05 versus Ang‐(1–7) + ISO.

Article Snippet: After 7 days' acclimatization, animals were randomized (blinded assessment) into five groups ( n = 6 per group) receiving daily Subcutaneous injection for 7 days [ , , ]:Ctrl: saline (Sanlian, Harbin, China); ISO: isoproterenol 5 mg/kg/day (Solarbio, II0200, Beijing, China; dissolved in DMSO); ISO + Ang‐(1–7): Ang‐(1–7) 576 μg/kg/day (MCE, HY‐12403, USA; in distilled water); ISO + Ang‐(1–7) + A‐779: A‐7791148 μg/kg/day (MCE, HY‐P0216, USA); ISO + Ang‐(1–7) + PD123319 : PD123319 5 mg/kg/day (MCE, HY‐10259A, USA); ISO + Ang‐(1–7) + PD123319 + A779.

Techniques: In Vivo, Transmission Assay, Electron Microscopy, Western Blot, Standard Deviation

Journal: Acta Physiologica (Oxford, England)

Article Title: Angiotensin‐(1–7) Alleviates Isoproterenol‐Induced Cardiac Hypertrophy by Suppressing Autophagy and Apoptosis Through the Synergistic Action of Mas Receptor and Angiotensin II Type 2 Receptor

doi: 10.1111/apha.70200

Figure Lengend Snippet: Ang‐(1–7) regulates autophagic flux and apoptosis in H9c2 cardiomyocytes through MasR and AT 2 R. (A) Representative images of TUNEL immunofluorescence staining (green fluorescence labels apoptotic cells) and Hoechst nuclear staining (blue) ( n = 6), with the Merge panel showing their overlay. (B) Western blot analysis of apoptosis related proteins (Bax, Bcl 2 , Cleaved caspase‐3) expression levels, with GAPDH as the internal control protein ( n = 3). (C) Western blot analysis of autophagy‐related proteins (LC3‐II, Beclin1, P62) expression levels, with GAPDH as the internal control protein ( n = 3). The data is expressed as an mean ± standard deviation (SD). A + I, Ang‐(1–7) + ISO; AntM + A + I, A‐779 + Ang‐(1–7) + ISO; Ant A + A + I, PD123319 + Ang‐(1–7) + ISO; AntM + AntA + A + I, A‐779 + PD123319 + Ang‐(1–7) + ISO.

Article Snippet: After 7 days' acclimatization, animals were randomized (blinded assessment) into five groups ( n = 6 per group) receiving daily Subcutaneous injection for 7 days [ , , ]:Ctrl: saline (Sanlian, Harbin, China); ISO: isoproterenol 5 mg/kg/day (Solarbio, II0200, Beijing, China; dissolved in DMSO); ISO + Ang‐(1–7): Ang‐(1–7) 576 μg/kg/day (MCE, HY‐12403, USA; in distilled water); ISO + Ang‐(1–7) + A‐779: A‐7791148 μg/kg/day (MCE, HY‐P0216, USA); ISO + Ang‐(1–7) + PD123319 : PD123319 5 mg/kg/day (MCE, HY‐10259A, USA); ISO + Ang‐(1–7) + PD123319 + A779.

Techniques: TUNEL Assay, Immunofluorescence, Staining, Fluorescence, Western Blot, Expressing, Control, Standard Deviation