Journal: Advanced Science

Article Title: PLAUR + Neutrophils Drive Anti‐PD‐1 Therapy Resistance in Patients with Hepatocellular Carcinoma by Shaping an Immunosuppressive Microenvironment

doi: 10.1002/advs.202507167

Figure Lengend Snippet: PLAUR inhibitor reverses the immunosuppressive phenotype of neutrophils and attenuates tumor progression. A) Flowchart depicting the screening strategy for small‐molecule compounds targeting PLAUR. B) The affinity of 40 candidate small‐molecule compounds targeting PLAUR detected by SPR analysis. C) Schematic diagram of the predicted docking structure of DAPTA and PLAUR. D) Cell viability of DAPTA detected in human neutrophils. E) Western blot analysis of PLAUR, phosphorylated and non‐phosphorylated NF‐κB expression in human neutrophils treated with DMSO or DAPTA (5 µ m ). F) quantitative PCR analysis of the indicated genes in DMSO and DAPTA treatment groups ( n = 3 per group). G) Flow cytometry analysis of CD206 and CD95 expression in DMSO and DAPTA treatment groups (n = 3 per group). H) Schematic showing the treatment plan and establishment of spontaneous HCC models in mice. I) Representative images of the spontaneous tumors at the study endpoint (5 mice per group). Scale bar: 1 cm. J) The maximum tumor volume of each group at the study endpoint ( n = 5 per group). K) Kaplan‐Meier survival curves for mice ( n = 5 per group). L) Immunofluorescence staining and statistical analysis of PLAUR, F4/80 and CD8 in the indicated groups ( n = 5 per group). Scale bars: 100 µm. M,N) Flow cytometry analysis of Ly6G + CD206 + neutrophils, CD11b + F4/80 + macrophages and CD3 + CD8 + T cells in the indicated groups ( n = 5 per group). The data are presented as the means ± SDs. * P < 0.05, ** P < 0.01, and *** P < 0.001, Student's t test.

Article Snippet: For PLAUR inhibitor treatment, mice were treated intraperitoneally with D‐Ala‐peptide T‐amide (DAPTA) (MedChemExpress, 100 μg per mouse) following the schedule shown in Figures and .

Techniques: Western Blot, Expressing, Real-time Polymerase Chain Reaction, Flow Cytometry, Immunofluorescence, Staining

Journal: Journal of Translational Medicine

Article Title: Glucagon-like peptide-1 receptor agonists inhibit the progression of malignant pleural effusion in obese mice by regulating the metabolism of pleural effusion

doi: 10.1186/s12967-025-06875-8

Figure Lengend Snippet: GLP-1RA inhibited MPE formation in obese mice. A . Schematic depiction of the experimental timeline. B . Plot of the mice’s body weight. LCT, chow diet + normal saline injection ( n = 6); LGP, chow diet + GLP-1RA injection ( n = 6); HCT, high-fat diet + normal saline injection ( n = 6); HGP, high-fat diet + GLP-1RA injection ( n = 6). * P < 0.05 of Wilcoxon signed-rank test with Bonferroni correction. C . Blood glucose before and after GLP-1RA treatment in each mice group. Before, at week 20; after, at week 21. *** P < 0.001 of Wilcoxon signed-rank test with Bonferroni correction. D . Anatomical images (left panel) and comparisons (right panel) of MPE from different groups of mice. * P < 0.05, *** P < 0.001 of Wilcoxon signed-rank test with Bonferroni correction. Data were presented as means ± SD. E. Life span analysis of mice receiving different treatments. Overall survival was analyzed using Kaplan-Meier method and a pair-wise log-rank test (each n = 15). *** P < 0.001

Article Snippet: For the subsequent GLP-1RA (T3984, TargetMol, Boston, MA, USA) treatment experiment, both the high-fat diet and the standard chow diet group were further randomly divided into two subgroups, totaling four subgroups.

Techniques: Saline, Injection, Analysis

Journal: Journal of Translational Medicine

Article Title: Glucagon-like peptide-1 receptor agonists inhibit the progression of malignant pleural effusion in obese mice by regulating the metabolism of pleural effusion

doi: 10.1186/s12967-025-06875-8

Figure Lengend Snippet: Metabolomics of MPE in obese mice with or without GLP-1RA treatment. A . Orthogonal PLS-DA (OPLS-DA) of metabolomics profile in HCT and HGP groups. B . Heat map of differential metabolites ( P < 0.05, VIP > 1 and fold-change > 1). C . Lollipop plot of the ten differential metabolites with the largest VIP values among the up-regulated and down-regulated differential metabolites. Red indicates upregulation, blue indicates downregulation, asterisks indicate significance of differential metabolism, and dot size is determined by VIP value. D . Box plot of the metabolic intensity of the corresponding metabolite. * P < 0.05, ** P < 0.01, *** P < 0.001 of Student’s t test

Article Snippet: For the subsequent GLP-1RA (T3984, TargetMol, Boston, MA, USA) treatment experiment, both the high-fat diet and the standard chow diet group were further randomly divided into two subgroups, totaling four subgroups.

Techniques:

Journal: Journal of Translational Medicine

Article Title: Glucagon-like peptide-1 receptor agonists inhibit the progression of malignant pleural effusion in obese mice by regulating the metabolism of pleural effusion

doi: 10.1186/s12967-025-06875-8

Figure Lengend Snippet: Pathway enrichment analysis of differential metabolites in MPE from obese mice with or without GLP-1RA treatment. A . KEGG analysis of the differential metabolites. B . Reactome pathway analysis of the differential metabolites. C . Heat map of the intensity of the corresponding metabolites in the purine metabolism pathway. D . Heat map of the intensity of the corresponding metabolites in the amino sugar and nucleotide sugar metabolism

Article Snippet: For the subsequent GLP-1RA (T3984, TargetMol, Boston, MA, USA) treatment experiment, both the high-fat diet and the standard chow diet group were further randomly divided into two subgroups, totaling four subgroups.

Techniques: Analysis

Journal: Journal of Translational Medicine

Article Title: Glucagon-like peptide-1 receptor agonists inhibit the progression of malignant pleural effusion in obese mice by regulating the metabolism of pleural effusion

doi: 10.1186/s12967-025-06875-8

Figure Lengend Snippet: Pathway enrichment analysis of differential metabolites in MPE after treatment with GLP-1RA in normal-weight and obese mice. ( A , B ). Gene Set Enrichment Analysis (GSEA) of differential metabolites between HGP and LGP group in the corresponding pathway set

Article Snippet: For the subsequent GLP-1RA (T3984, TargetMol, Boston, MA, USA) treatment experiment, both the high-fat diet and the standard chow diet group were further randomly divided into two subgroups, totaling four subgroups.

Techniques: Analysis

Journal: JCI Insight

Article Title: Platelets impair the resolution of inflammation in atherosclerotic plaques in insulin-resistant mice after lipid lowering

doi: 10.1172/jci.insight.193593

Figure Lengend Snippet: ( A ) Study design. Eight-week-old Ldlr –/– male mice fed a high-fat, high-cholesterol (HFHC) diet for the whole duration of the study (23 weeks). After the atherosclerosis progression period (obese baseline, Ob), mice were injected with ApoB ASO to lower lipids (lipid-lowering period). All lipid-lowered mice were split into 2 groups, injected either with isotype control antibody (IgG) or platelet depletion antibody (αCD42b) every 3 days for a total of 3 weeks. ( B ) Platelet counts in circulating blood of Ob, IgG, and αCD42b 3 days before harvest. ( C ) Blood glucose measurements (lean n = 16, Ob n = 47) and ( D ) area of curve (AOC) quantification of glucose tolerance tests (GTTs) from lean, Ob, IgG, and αCD42b mice after 16 weeks of HFHC diet during atherosclerosis progression. ( E ) Blood glucose measurements (Ob n = 3, IgG n = 4, αCD42b n = 4) and ( F ) AOC quantification of GTTs from Ob, IgG, and αCD42b mice after 22 weeks of HFHC diet during atherosclerosis resolution. Mean fluorescent intensity (MFI) of platelet ( G ) JonA and ( H ) P-selectin in nonstimulated (NS) samples and upon 100 μM PAR4-AP agonist stimulation of lean and Ob circulating blood samples. ( I ) Mean platelet volume (MPV) from circulating blood of lean, Ob, and IgG-treated mice, 3 days before harvest. In C and E , error bars represent SD. Data were analyzed by Kruskal-Wallis with Dunn’s post hoc test ( B and F ), unpaired Mann-Whitney test ( C , D , and H ), unpaired Student’s t test ( G ), or ordinary 1-way ANOVA with Tukey’s multiple-comparison test ( I ). P values are shown in graphs.

Article Snippet: The whole blood was stained with anti–mouse JonA-PE (M023-2, Emfret Analytics) and anti–mouse P-selectin Alexa Fluor 647 (563674, BD Biosciences) and then treated with PAR4-AP platelet agonist (100 μM; MedChemExpress) for 15 minutes at room temperature.

Techniques: Injection, Control, MANN-WHITNEY, Comparison

Journal: Molecular Biology Reports

Article Title: GLP-1(7–36) protected against oxidative damage and neuronal apoptosis in the hippocampal CA region after traumatic brain injury by regulating ERK5/CREB

doi: 10.1007/s11033-024-09244-8

Figure Lengend Snippet: GLP-1 (7–36) improved neurologic deficits and cognitive dysfunction. A Experimental timeline. B Neurological functional outcomes were determined by the mNSS score. The rat’s responsiveness to vibrissae stimulation and motor coordination and balance were assessed by the C forelimb placement test and D rotarod performance test. The recovery of cognitive functions on days E–J 1–5 and G–J 26–30 was determined by the MWM test. Values are expressed as the means ± standard deviations. These behavioral assays were repeated in three to five biological and three technical replications. TBI, traumatic brain injury; GLP-1, glucagon-like peptide-1. (# P  < 0.05, ## P  < 0.01 compared with the Sham group; * P  < 0.05, ** P  < 0.01 compared with the TBI group; & P  < 0.05, && P  < 0.01 compared with the GLP-1 (7–36)-L group)

Article Snippet: GLP-1(7–36) was purchased from MCE (cat. no. HY-P0054A, CAS: 1119517-19-9, China).

Techniques: Functional Assay

Journal: Molecular Biology Reports

Article Title: GLP-1(7–36) protected against oxidative damage and neuronal apoptosis in the hippocampal CA region after traumatic brain injury by regulating ERK5/CREB

doi: 10.1007/s11033-024-09244-8

Figure Lengend Snippet: GLP-1(7–36) reduced brain oedema and pathological injury caused by TBI. A Brain water content was determined. B Quantification of the number of viable neurons per 250-lm length in each group. C H&E staining (scale bar, 100 μm). Values are expressed as the means ± standard deviations ( n = 3 per group). TBI, traumatic brain injury; GLP-1, glucagon-like peptide-1. (# P < 0.05, ## P < 0.01 compared with the Sham group; * P < 0.05, ** P < 0.01 compared with the TBI group; & P < 0.05, && P < 0.01 compared with the GLP-1 (7–36)-L group)

Article Snippet: GLP-1(7–36) was purchased from MCE (cat. no. HY-P0054A, CAS: 1119517-19-9, China).

Techniques: Staining

Journal: Molecular Biology Reports

Article Title: GLP-1(7–36) protected against oxidative damage and neuronal apoptosis in the hippocampal CA region after traumatic brain injury by regulating ERK5/CREB

doi: 10.1007/s11033-024-09244-8

Figure Lengend Snippet: GLP-1(7–36) decreased the contents of H2O2 and intracellular ROS and increased cellular antioxidant factors. A The results show the release of H2O2 in the different groups. B Fluorescence images show DCF-stained hippocampal tissues. C Bar graphs showing the relative DCF fluorescence intensity in the hippocampal tissues. D CAT activity, E GSH levels and F SOD activity were detected to determine the antioxidant capacity. Values are expressed as the means ± standard deviations ( n = 3 per group). TBI, traumatic brain injury; GLP-1, glucagon-like peptide-1; catalase, CAT; glutathione, GSH; superoxide dismutase, SOD. (# P < 0.05, ## P < 0.01 compared with the Sham group; * P < 0.05, ** P < 0.01 compared with the TBI group; & P < 0.05, && P < 0.01 compared with the GLP-1 (7–36)-L group)

Article Snippet: GLP-1(7–36) was purchased from MCE (cat. no. HY-P0054A, CAS: 1119517-19-9, China).

Techniques: Fluorescence, Staining, Activity Assay

Journal: Molecular Biology Reports

Article Title: GLP-1(7–36) protected against oxidative damage and neuronal apoptosis in the hippocampal CA region after traumatic brain injury by regulating ERK5/CREB

doi: 10.1007/s11033-024-09244-8

Figure Lengend Snippet: GLP-1(7–36) promoted the activation of the ERK5/CREB signalling pathways. A Representative western blots of proteins examined. The expression of ( B and D ) p-ERK5 and ( C and E ) CREB was determined by western blot analysis and reverse transcription-quantitative PCR. β-Actin was used as an internal control. F Representative double immunofluorescence staining of p-ERK5-positive cells (green) and NeuN-positive cells (red) in brain sections is displayed. G Statistical analysis of the p-ERK5-positive cell numbers in the observed area. Values are expressed as the means ± standard deviations ( n = 3 per group). TBI, traumatic brain injury; GLP-1, glucagon-like peptide-1; ERK5, extracellular signal-regulated kinase; CREB, cAMP response element binding. (# P < 0.05, ## P < 0.01 compared with the Sham group; * P < 0.05, ** P < 0.01 compared with the TBI group; & P < 0.05, && P < 0.01 compared with the GLP-1 (7–36)-L group). (Color figure online)

Article Snippet: GLP-1(7–36) was purchased from MCE (cat. no. HY-P0054A, CAS: 1119517-19-9, China).

Techniques: Activation Assay, Western Blot, Expressing, Reverse Transcription, Real-time Polymerase Chain Reaction, Control, Double Immunofluorescence Staining, Binding Assay

Journal: Molecular Biology Reports

Article Title: GLP-1(7–36) protected against oxidative damage and neuronal apoptosis in the hippocampal CA region after traumatic brain injury by regulating ERK5/CREB

doi: 10.1007/s11033-024-09244-8

Figure Lengend Snippet: GLP-1(7–36) suppressed apoptosis caused by TBI. A Representative western blots of proteins examined. The expression of ( B and D ) CC-3 and ( C and E ) Bax/Bcl-2 was determined by western blot analysis and reverse transcription-quantitative PCR. β-Actin was used as an internal control. ( F ) Representative confocal images (scale bar, 50 μm) show neuronal apoptosis in hippocampal tissues based on TUNEL (green) and DAPI (blue) staining. ( G ) Bar graph shows the relative percentage of apoptotic neuronal cells in hippocampal tissues based on TUNEL staining. Values are expressed as the means ± standard deviations ( n = 3 per group). TBI, traumatic brain injury; GLP-1, glucagon-like peptide-1; CC-3, cleaved caspase-3; Bcl-2, B-cell lymphoma-2. (# P < 0.05, ## P < 0.01 compared with the Sham group; * P < 0.05, ** P < 0.01 compared with the TBI group; & P < 0.05, && P < 0.01 compared with the GLP-1 (7–36)-L group). (Color figure online)

Article Snippet: GLP-1(7–36) was purchased from MCE (cat. no. HY-P0054A, CAS: 1119517-19-9, China).

Techniques: Western Blot, Expressing, Reverse Transcription, Real-time Polymerase Chain Reaction, Control, TUNEL Assay, Staining

Journal: Molecular Biology Reports

Article Title: GLP-1(7–36) protected against oxidative damage and neuronal apoptosis in the hippocampal CA region after traumatic brain injury by regulating ERK5/CREB

doi: 10.1007/s11033-024-09244-8

Figure Lengend Snippet: GLP-1 (7–36) increased cellular antioxidant capacity and inhibited apoptosis by activating ERK5/CREB signalling. A Cellular viability was detected using a CCK-8 assay. B The results show the release of H2O2 in the different groups. C Bar graphs showing the relative DCF fluorescence intensity in hippocampal neurons. D CAT activity, E GSH levels and F SOD activity were detected to determine the antioxidant capacity. G Representative western blots of proteins examined. The expression of ( H and J ) CC-3 and (I and K) Bax/Bcl-2 was determined by western blot analysis and reverse transcription-quantitative PCR. β-Actin was used as an internal control. L Bar graph shows the relative percentage of apoptotic neuronal cells in primary hippocampal neurons based on TUNEL staining. M Representative confocal images (scale bar, 50 μm) show neuronal apoptosis in primary hippocampal neurons based on TUNEL (green) and DAPI (blue) staining. Values are expressed as the means ± standard deviations. These experiments were repeated three times with five samples for each group. TBI, traumatic brain injury; GLP-1, glucagon-like peptide-1; catalase, CAT; glutathione, GSH; superoxide dismutase, SOD; CC-3, cleaved caspase-3; Bcl-2, B-cell lymphoma-2. (# P  < 0.05, ## P  < 0.01 compared with the Sham group; * P  < 0.05, ** P  < 0.01 compared with the TBI group; & P  < 0.05, && P  < 0.01 compared with the TBI + GLP-1 (7–36) group). (Color figure online)

Article Snippet: GLP-1(7–36) was purchased from MCE (cat. no. HY-P0054A, CAS: 1119517-19-9, China).

Techniques: CCK-8 Assay, Fluorescence, Activity Assay, Western Blot, Expressing, Reverse Transcription, Real-time Polymerase Chain Reaction, Control, TUNEL Assay, Staining

Journal: Molecular Biology Reports

Article Title: GLP-1(7–36) protected against oxidative damage and neuronal apoptosis in the hippocampal CA region after traumatic brain injury by regulating ERK5/CREB

doi: 10.1007/s11033-024-09244-8

Figure Lengend Snippet: The mechanism’s diagram. GLP-1(7-36) mitigated neuronal damage following traumatic brain injury. The underlying mechanisms likely involve reducing oxidative stress by modulating the ERK5/CREB pathway, which includes decreasing ROS accumulation and enhancing the expression of antioxidant genes. Simultaneously, this pathway facilitates neuronal cell survival by inhibiting the activation of caspase family members and suppressing the proapoptotic Bcl-2 family members Bax or Bak

Article Snippet: GLP-1(7–36) was purchased from MCE (cat. no. HY-P0054A, CAS: 1119517-19-9, China).

Techniques: Expressing, Activation Assay