Journal: Frontiers in Endocrinology

Article Title: Unveiling the TrkA-p35/CDK5 axis: a novel therapeutic target in diabetic kidney disease

doi: 10.3389/fendo.2026.1791283

Figure Lengend Snippet: Identification of NGFR as a potential upstream regulator in podocyte injury. (A) Volcano plot of differentially expressed genes (|log2FC| ≥ 1; padj < 0.05) in renal tissues of db/db mice compared to controls. (B) Heatmap of gene expression profiles in renal tissues from control (n = 5) and db/db (n = 5) mice. Notably, NGFR expression was significantly upregulated (log2FoldChange = 1.53; padj = 4.75 × 10 -6 ). (C) PCA score plot demonstrating the distinct separation between control and db/db groups. (D, E) AlphaFold3 modeling predicting the molecular interface between CDK5 and the kinase domain of TrkA.

Article Snippet: Antibodies against TrkA (Cat. No. 2505), Cdk5 (Cat. No. 2506), and p35/25 (Cat. No. 2680) were purchased from Cell Signaling Technology (Danvers, MA, USA).

Techniques: Gene Expression, Control, Expressing

Journal: Frontiers in Endocrinology

Article Title: Unveiling the TrkA-p35/CDK5 axis: a novel therapeutic target in diabetic kidney disease

doi: 10.3389/fendo.2026.1791283

Figure Lengend Snippet: HG-induced TrkA phosphorylation is associated with podocyte inflammation and injury. (A–D) Representative western blots show the levels of (A) TrkA and phospho-TrkA (Tyr490); (B) ERK, phospho-ERK and EGR1; (C) p35 and CDK5; and (D) IL-1β and TNF-α in MPC5 cells from the LG, HG, and LG + Man groups at 24 h (E) Representative immunofluorescence double staining shows the expression of phospho-TrkA (Tyr490) and synaptopodin in MPC5 cells from the LG, HG, and LG + Man groups. ****p < 0.0001. p < 0.05 was considered statistically significant; ns indicates not significant.

Article Snippet: Antibodies against TrkA (Cat. No. 2505), Cdk5 (Cat. No. 2506), and p35/25 (Cat. No. 2680) were purchased from Cell Signaling Technology (Danvers, MA, USA).

Techniques: Phospho-proteomics, Western Blot, Immunofluorescence, Double Staining, Expressing

Journal: Frontiers in Endocrinology

Article Title: Unveiling the TrkA-p35/CDK5 axis: a novel therapeutic target in diabetic kidney disease

doi: 10.3389/fendo.2026.1791283

Figure Lengend Snippet: TrkA inhibitor suppresses p-TrkA-mediated upregulation of ERK, EGR1, and p35 in the MPC5 cells grown under HG conditions. Representative western blots show the levels of (A) TrkA and phospho-TrkA (Tyr490), (C) ERK, phospho-ERK, and EGR1, and (E) CDK5 and p35 in the LG, HG+Vehicle (0.1% DMSO), HG + Inh-TrkA, HG + empty vector, HG + TrkA OE, and HG + TrkA OE + PD98059 groups. Representative western blots show the levels of (B) TrkA and phospho-TrkA (Tyr490), (D) ERK, phospho-ERK, and EGR1, and (F) CDK5 and p35 in the LG, HG+si-NC, HG+si-TrkA, HG + TrkA OE+Ctrl, and HG + TrkA OE + GW441756 groups. *p < 0.05, **p < 0.01, ***p < 0.001, and ****p < 0.0001. p < 0.05 was considered statistically significant.

Article Snippet: Antibodies against TrkA (Cat. No. 2505), Cdk5 (Cat. No. 2506), and p35/25 (Cat. No. 2680) were purchased from Cell Signaling Technology (Danvers, MA, USA).

Techniques: Western Blot, Plasmid Preparation

Journal: Frontiers in Endocrinology

Article Title: Unveiling the TrkA-p35/CDK5 axis: a novel therapeutic target in diabetic kidney disease

doi: 10.3389/fendo.2026.1791283

Figure Lengend Snippet: TrkA inhibition reduces the levels of p-TrkA, p-ERK, EGR1, p35, and CDK5 in the kidneys of db/db mice. (A–C) Representative western blots show the protein expression levels of (A) TrkA and phospho-TrkA (Tyr490), (B) ERK, p-ERK and EGR1, and (C) p35 and CDK5 in the kidney samples from the control, db/db, Inh-NC, and Inh-TrkA groups of mice. (D) Representative IF images show the expression of Synaptopodin (red) in the glomeruli of control, db/db, Inh-NC, and Inh-TrkA groups of mice (400X). ***p < 0.001. p < 0.05 was considered statistically significant; ns indicates not significant.

Article Snippet: Antibodies against TrkA (Cat. No. 2505), Cdk5 (Cat. No. 2506), and p35/25 (Cat. No. 2680) were purchased from Cell Signaling Technology (Danvers, MA, USA).

Techniques: Inhibition, Western Blot, Expressing, Control

Journal: Frontiers in Endocrinology

Article Title: Unveiling the TrkA-p35/CDK5 axis: a novel therapeutic target in diabetic kidney disease

doi: 10.3389/fendo.2026.1791283

Figure Lengend Snippet: Schematic diagram shows the TrkA/ERK/p35/CDK5 regulatory axis and the site of action for the TrkA inhibitor GW441756 in the murine renal podocytes.

Article Snippet: Antibodies against TrkA (Cat. No. 2505), Cdk5 (Cat. No. 2506), and p35/25 (Cat. No. 2680) were purchased from Cell Signaling Technology (Danvers, MA, USA).

Techniques:

Journal: Science translational medicine

Article Title: Lipid nanoparticles and siRNA targeting plasminogen provide lasting inhibition of fibrinolysis in mouse and dog models of hemophilia A

doi: 10.1126/scitranslmed.adh0027

Figure Lengend Snippet: (A) Mice were injected with a single dose of siLuc (gray) or siPlg (teal blue). Plg mRNA in liver tissue was measured using qPCR, normalized against the housekeeping gene, Ppia. (B) Representative Western blot against plasminogen, where each lane contains the plasma from an individual mouse in either treatment group. The triangular marker indicates the expected molecular weight of plasminogen (92 kDa). (C) Plasminogen protein in plasma measured in a portion of the mice enrolled at each time point using densitometry, normalized to a loading control, and graphed relative to untreated mice. (D) Plasminogen protein in plasma quantified after administration of siPlg to dogs at 0.027 (purple, n = 3), 0.054 (green, n = 2), or 0.54 (teal blue, n = 1) mg siRNA/kg body weight. (E) Representative Western blot against plasminogen, where each lane contains plasma collected from a single WT dog at a different time point before or after siPlg administration at 0.054 mg/kg. Data are presented as mean ± SEM and were analyzed by two-tailed unpaired Student’s t test (A) or by two-way ANOVA (C); *P < 0.05.

Article Snippet: The membranes were treated with a primary antibody against plasminogen (1:1000; SAPG-AP; confirmed cross-reactivity: human, rat, mouse, rabbit, canine, and pig; Affinity Biologicals), washed, and treated with horseradish peroxidase–labeled anti-host secondary antibody (1:15,000; Abcam).

Techniques: Injection, Western Blot, Clinical Proteomics, Marker, Molecular Weight, Control, Two Tailed Test

Journal: Science translational medicine

Article Title: Lipid nanoparticles and siRNA targeting plasminogen provide lasting inhibition of fibrinolysis in mouse and dog models of hemophilia A

doi: 10.1126/scitranslmed.adh0027

Figure Lengend Snippet: Samples were collected from two HA dogs at baseline (green), within 4 hours of TXA (10 mg/kg iv, orange), within 3 weeks of siPlg administration without TXA (teal), or after administration of both siPlg and TXA (purple). (A) Representative TEG curve tracings using plasma from two HA dogs (top and bottom graphs) with added tPA. (B) Clot lysis time within 180-min monitoring period, values represent mean, and error bars represent ± SEM. (C) Thrombin generation in plasma collected weekly from two HA dogs or pooled plasma from WT dogs (WT, gray). (D) Correlation between plasminogen protein in plasma and thrombin generation peak (open and closed markers distinguish the two siPlg-treated dogs). (E) Plasmin generation in plasma collected weekly from two HA dogs or pooled plasma from WT dogs. (F) Correlation between plasma plasminogen and plasmin generation peak.

Article Snippet: The membranes were treated with a primary antibody against plasminogen (1:1000; SAPG-AP; confirmed cross-reactivity: human, rat, mouse, rabbit, canine, and pig; Affinity Biologicals), washed, and treated with horseradish peroxidase–labeled anti-host secondary antibody (1:15,000; Abcam).

Techniques: Clinical Proteomics, Lysis

Journal: Science translational medicine

Article Title: Lipid nanoparticles and siRNA targeting plasminogen provide lasting inhibition of fibrinolysis in mouse and dog models of hemophilia A

doi: 10.1126/scitranslmed.adh0027

Figure Lengend Snippet: (A) Plasma plasminogen (left y axis) quantified during 9 months of repeat administration of siPlg. The weight of mice (right y axis) was tracked over this period during administration of siLuc (gray) and siPlg (orange). (B) Periodontal bone loss measured by the distance between the cementoenamel junction and the alveolar bone crest (orange lines) in samples stained with methylene blue from mice administered siLuc (n = 6) or siPlg (n = 7) for 9 months compared to untreated (Unt WT) age-matched WT controls (purple line). Scale bar, 2 mm. (C to F) Inflammatory markers IL-6 (C and D) and TNF-α (E and F) were measured using qPCR in liver tissue or enzyme-linked immunosorbent assay in plasma from siLuc-treated (n = 8) or siPlg-treated (n = 10) mice compared to untreated (Unt) controls (purple line). (G) Immunohistochemistry against fibrin(ogen) in microscopy images of liver tissue of siPlg-treated mice showed inflammatory infiltrates but no fibrinous lesions. Scale bar, 100 μm. (H) Immunohistochemistry against fibrin(ogen) in clots formed ex vivo in whole blood from mice treated with siLuc (left) or siPlg (right). Scale bar, 25 μm. For all graphs, values represent mean ± SEM, ns indicates difference not statistically significant (P > 0.05), analyzed by two-tailed unpaired Student’s t test.

Article Snippet: The membranes were treated with a primary antibody against plasminogen (1:1000; SAPG-AP; confirmed cross-reactivity: human, rat, mouse, rabbit, canine, and pig; Affinity Biologicals), washed, and treated with horseradish peroxidase–labeled anti-host secondary antibody (1:15,000; Abcam).

Techniques: Clinical Proteomics, Staining, Enzyme-linked Immunosorbent Assay, Immunohistochemistry, Microscopy, Ex Vivo, Two Tailed Test

Journal: Science translational medicine

Article Title: Lipid nanoparticles and siRNA targeting plasminogen provide lasting inhibition of fibrinolysis in mouse and dog models of hemophilia A

doi: 10.1126/scitranslmed.adh0027

Figure Lengend Snippet: (A) Schematic showing SVP and TVT injury models. (B) Plasminogen in HA mice at the time of TVT bleed. (C and D) Blood loss in microliters of blood per gram of body weight (C) and bleeding time (D) after TVT in WT, untreated HA, and treated HA mice (n = 5 to 7). (E and F) Blood loss in microliters of blood per gram of body weight (E) and bleeding time (F) to end of observation period at 40 min (gray dashed line) after SVP (n = 7 to 10). Values represent mean ± SEM; *P < 0.05, **P < 0.01, and ns indicates not significant (P > 0.05), analyzed by one-way ANOVA.

Article Snippet: The membranes were treated with a primary antibody against plasminogen (1:1000; SAPG-AP; confirmed cross-reactivity: human, rat, mouse, rabbit, canine, and pig; Affinity Biologicals), washed, and treated with horseradish peroxidase–labeled anti-host secondary antibody (1:15,000; Abcam).

Techniques:

Journal: Science translational medicine

Article Title: Lipid nanoparticles and siRNA targeting plasminogen provide lasting inhibition of fibrinolysis in mouse and dog models of hemophilia A

doi: 10.1126/scitranslmed.adh0027

Figure Lengend Snippet: HA dogs were administered five doses of siPlg over 15 weeks. Vertical dashed lines indicate days of an administration. (A) Plasminogen in plasma quantified using densitometry of Western blots. Values represent mean ± SEM. (B) Annualized bleeding rate extrapolated from 10 months before treatment and the 4-month period of siPlg treatment in two HA dogs (circle and diamond each indicate an individual dog).

Article Snippet: The membranes were treated with a primary antibody against plasminogen (1:1000; SAPG-AP; confirmed cross-reactivity: human, rat, mouse, rabbit, canine, and pig; Affinity Biologicals), washed, and treated with horseradish peroxidase–labeled anti-host secondary antibody (1:15,000; Abcam).

Techniques: Clinical Proteomics, Western Blot

Journal: Journal of Inflammation Research

Article Title: Augmented Cornus officinalis Levels in Liuwei Dihuang Decoction Inhibits Nucleus Pulposus Cell Pyroptosis to Enhance Therapeutic Efficacy Against Intervertebral Disc Degeneration

doi: 10.2147/JIR.S465690

Figure Lengend Snippet: LWDHD formulations activate the NRF2 antioxidant pathway in IVDs of IVDD mice. ( A and B ) IF staining and corresponding qualification of NRF2 (S40) in IVDs of IVDD mice after treatment with LWDHD formulation for 1 week. White arrows indicate high expression of NRF2 (S40) in NP tissues. ( C and D ) IHC staining and corresponding qualification of KEAP1 in IVDs of IVDD mice. Black arrows indicate high expression of KEAP1 in NP tissues. ( E – H ) IF staining and corresponding qualification of p-I-κB ( E and F ) and p-P65 ( G and H ) in IVDs of IVDD mice. Data are shown as mean ± SEM (n = 6). *Denotes a significant difference compared with the Sham group (** p < 0.01), # Means a significant difference compared with the Vehicle group ( # p < 0.05, ## p < 0.01), + Indicates a significant difference compared with the LWDHD group ( ++ p < 0.01), & Means a significant difference compared with the 5 × CO group ( && p < 0.01).

Article Snippet: Primary antibodies against Tyrosine kinase A (TrkA), and NRF2 (S40) were obtained from HuaBio (Hangzhou, China).

Techniques: Staining, Formulation, Expressing, Immunohistochemistry

Journal: Journal of Inflammation Research

Article Title: Augmented Cornus officinalis Levels in Liuwei Dihuang Decoction Inhibits Nucleus Pulposus Cell Pyroptosis to Enhance Therapeutic Efficacy Against Intervertebral Disc Degeneration

doi: 10.2147/JIR.S465690

Figure Lengend Snippet: Combined Score of Modified Formulations of LWDHD in Delaying IVDD

Article Snippet: Primary antibodies against Tyrosine kinase A (TrkA), and NRF2 (S40) were obtained from HuaBio (Hangzhou, China).

Techniques: Modification, TUNEL Assay

Journal: Journal of Inflammation Research

Article Title: Augmented Cornus officinalis Levels in Liuwei Dihuang Decoction Inhibits Nucleus Pulposus Cell Pyroptosis to Enhance Therapeutic Efficacy Against Intervertebral Disc Degeneration

doi: 10.2147/JIR.S465690

Figure Lengend Snippet: Schematic illustration of the mechanism by which LWDHD formulation, containing varying dosages of CO, protects against IVDD progression through the inhibition of NP pyroptosis by activating the NRF2 pathway. The schematic illustration is drawn by Figdraw.

Article Snippet: Primary antibodies against Tyrosine kinase A (TrkA), and NRF2 (S40) were obtained from HuaBio (Hangzhou, China).

Techniques: Formulation, Inhibition