Journal: Biomedical Engineering and Computational Biology

Article Title: Automated High-Throughput Live Cell Monitoring of Scratch Wound Closure

doi: 10.1177/11795972241295619

Figure Lengend Snippet: Nintedanib reduces endothelial cell migration. (a, c, e) Graphs show relative areas covered (RAC) or cell density in wounds over time in scratch assays with human umbilical vein endothelial cells treated with nintedanib in different concentrations with or without growth factors (GFs). Colored dotted lines demarcate upper and lower limits of respective 95% CIs. Analysis was performed with Migration Assay Analysis Macro (a) and the python pipeline either without (c) or with scaling (e). (b, d, f) Area under curve (AUC) calculated from respective RAC or cell density graphs in dependence of the applied nintedanib concentration. Dashed and dotted lines represent respective control means and 95% CIs. Solid lines show fitted 4-parameter logistic model. Abbreviations: Ctrl, control; veh, vehicle.

Article Snippet: Nintedanib (Selleckchem, Planegg, Germany) treatment was applied either alone or in combination with growth factors following the wound infliction.

Techniques: Migration, Concentration Assay, Control

Journal: Nano today

Article Title: Reprogramming the pancreatic cancer stroma and immune landscape by a silicasome nanocarrier delivering nintedanib, a protein tyrosine kinase inhibitor

doi: 10.1016/j.nantod.2023.102058

Figure Lengend Snippet: Silicasome nanocarrier development for Nintedanib delivery in PDAC. (a) Schematic to outline the synthesis steps for constructing the Silicasome-Nintedanib (Si-Ninte) carrier. (b) Schematic delineating the chemical structure and medicinal chemical properties of Nintedanib esylate, required for remote loading into mesoporous silica nanoparticles (MSNP) pores. Remote loading was accomplished by the use of soaking MSNPs in a trapping agent, TEA 8 SOS. (c) CryoEM visualization and physicochemical properties of Si-Ninte (hydrodynamic size, polydispersity index (PDI), zeta potential, and drug loading capacity). Bar is 100 μm. The schematic depicts the supported lipid bilayer.

Article Snippet: Nintedanib esylate, (2-Hydroxypropyl)-β-cyclodextrin (HP-β-CD) and IFN-γ were purchased from MedChem Express, USA.

Techniques: Zeta Potential Analyzer

Journal: Nano today

Article Title: Reprogramming the pancreatic cancer stroma and immune landscape by a silicasome nanocarrier delivering nintedanib, a protein tyrosine kinase inhibitor

doi: 10.1016/j.nantod.2023.102058

Figure Lengend Snippet: Improved pharmacokinetics and Nintedanib biodistribution in an orthotopic KPC model. (a and b) Experimental timeline for assessing blood levels and drug biodistribution by Si-Ninte compared to free drug in orthotopic tumor-bearing mice. The orthotopic implant involves injection of KPC-luc cells into the pancreas tail. Tumor-bearing animals were treated with single drug administration, involving oral gavage or IV injection of Si-Ninte to deliver 50 mg/kg Nintedanib (n = 3). (c) Physicochemical properties of DiR-labeled Si-Ninte. (d) Measurement of Nintedanib t plasma concentrations by HPLC, blood withdrawal on 6 occasions over 24 h. (e) In a separate experiment, using the same treatment regimen, in vivo DiR imaging was performed at 24, 48 and 72 hs (left-side panel). This was followed by animal sacrifice and ex vivo organ explantation and imaging (right-side panel). Fluorescence was expressed as radiant intensity. (f) Normalized fluorescence intensity of explanted organs. (g) The Nintedanib concentrations at the tumor sites were determined at different time points by HPLC. Data represent mean ± SEM. *p < 0.05, **p < 0.01.

Article Snippet: Nintedanib esylate, (2-Hydroxypropyl)-β-cyclodextrin (HP-β-CD) and IFN-γ were purchased from MedChem Express, USA.

Techniques: Drug discovery, Injection, IV Injection, Labeling, Clinical Proteomics, In Vivo, Imaging, Ex Vivo, Fluorescence

Journal: Nano today

Article Title: Reprogramming the pancreatic cancer stroma and immune landscape by a silicasome nanocarrier delivering nintedanib, a protein tyrosine kinase inhibitor

doi: 10.1016/j.nantod.2023.102058

Figure Lengend Snippet: Nintedanib therapeutic impact on orthotopic tumor growth. (a) Experimental timeline to assess the therapeutic impact of oral-administered free Nintedanib vs. IV injected Si-Ninte in orthotopic KPC-luc tumor-bearing mice. (b) IVIS images tracking luminescence in KPC mice, following IV injection of saline, oral administration of free Nintedanib (50 mg/kg), or IV injection of Si-Ninte (10 mg/kg) twice a week for 2 weeks. (c) Average tumor bioluminescence intensity for each group (n=6) on days 12 and 16. Tumor growth inhibition by Si-Ninte was statistically significant (p < 0.05) compared to the saline control or free drug on day 16. (d) Comparison of average primary tumor weights in each group on day 21. (e) Photographic images of primary tumors, obtained on day 21. Body weight monitoring did not show any significant differences among all groups ( Fig. S3 ). Data represent mean ± SEM. *p < 0.05, **p < 0.01, # p < 0.05, ## p < 0.01.

Article Snippet: Nintedanib esylate, (2-Hydroxypropyl)-β-cyclodextrin (HP-β-CD) and IFN-γ were purchased from MedChem Express, USA.

Techniques: Injection, IV Injection, Saline, Inhibition, Control, Comparison

Journal: Nano today

Article Title: Reprogramming the pancreatic cancer stroma and immune landscape by a silicasome nanocarrier delivering nintedanib, a protein tyrosine kinase inhibitor

doi: 10.1016/j.nantod.2023.102058

Figure Lengend Snippet: Nintedanib impact on PD-L1 expression in vitro and in vivo . (a) Representative IHC images, with quantification of PD-L1 intensity in tumors obtained from the orthotopic experiment in Fig. 3 . (b) Flow cytometry analysis to quantify PD-L1 expression in the KPC cell line in response to different in vitro exposures. PD-L1 expression levels were evaluated by calculating MFI. (c) Schematic illustration of signaling pathways involved in transcriptional activation of the PD-L1 promotor in response to biological stimuli, including cytokines, hypoxia, toll-like receptor ligands and growth factors. The net result is determined by linear as well as interactive pathway connections, which depends on the contribution of each pathway in the TME. (d) Western blot analysis to access phosphorylation of ERK1/2 in KPC cells after treatment with free or encapsulated drug. Vinculin served as a stable-expressed household protein for comparative analysis. (e, f) Tumor slices and protein extracts obtained from tumor tissues in Fig. 3 were used for IHC and western blot analyses. Panel e shows representative IHC images and quantification of pERK intensity in each group, while panel f shows the immunoblotting results and quantification of pERK1/2 expression. Bars are 50 μm. Data represent mean ± SEM. *p < 0.05, **p < 0.01, # p < 0.05, ## p < 0.01. The study of STAT3 phosphorylation appears in Fig. S5 .

Article Snippet: Nintedanib esylate, (2-Hydroxypropyl)-β-cyclodextrin (HP-β-CD) and IFN-γ were purchased from MedChem Express, USA.

Techniques: Expressing, In Vitro, In Vivo, Flow Cytometry, Protein-Protein interactions, Activation Assay, Western Blot, Phospho-proteomics

Journal: bioRxiv

Article Title: Hydrogel-Embedded Precision-Cut Lung Slices Recapitulate Fibrotic Gene Expression and Enable Therapeutic Response Evaluation

doi: 10.64898/2026.03.24.714004

Figure Lengend Snippet: Nintedanib was administered to stiffened hydrogel-embedded PCLS from days 16 to day 22 (one to two weeks post-stiffening) to assess its ability to mitigate ongoing fibrotic progression. (A) Relative gene expression of epithelial cell markers in stiffened hydrogels following Nintedanib treatment on day 22, normalized to the FC-only controls. (B) Relative gene expression of fibroblast activation markers in stiffened hydrogels following Nintedanib treatment on day 22 (two-weeks post-stiffening), normalized to the FC-only controls. All statistical analyses assessed significance by unpaired t-tests with Welch comparison. Bars represent mean ± SEM, n=4. Symbols indicate experimental replicates (pooled hydrogel-embedded PCLS samples from each embedding round).

Article Snippet: The FDA-approved anti-fibrotic drug Nintedanib (10 μM, Tocris, cat. #7049) was dissolved in dimethyl sulfoxide.

Techniques: Gene Expression, Activation Assay, Comparison

Journal: iScience

Article Title: Multiphase micro-computed tomography reconstructions provide dynamic respiratory function in a mouse lung fibrosis model

doi: 10.1016/j.isci.2024.109262

Figure Lengend Snippet: Representative multiphase images reconstructed at end inspiration and end expiration Representative mid-thorax coronal slices at end-expiration and end-inspiration in a representative saline (SAL, first column), bleomycin (BLM, second column) and nintedanib-treated mouse (NINT, third column), acquired on day 7 and 21. From end-expiration to end-inspiration, images show reduced parenchymal density, due to increased gas fraction. The bleomycin and the nintedanib-treated mice display heterogeneously distributed ground glass opacities on day 7, and consolidations on day 21.

Article Snippet: Nintedanib Ethanesulfonate Salt , Carbosynth Limited, Compton, UK , FD71497.

Techniques: Saline

Journal: iScience

Article Title: Multiphase micro-computed tomography reconstructions provide dynamic respiratory function in a mouse lung fibrosis model

doi: 10.1016/j.isci.2024.109262

Figure Lengend Snippet: Breathing pattern derived from multiphase micro-CT (A) Relationship between the median values (25 th -75 th percentile) of tidal volume (V T , x axis) and respiratory rate (RR, y axis) in saline (SAL, black), bleomycin (BLM, red) and nintedanib-treated (NINT, green) groups on day 7 (filled circles) and day 21 (open circles). Lines represent the isopleths of different levels of minute ventilation ( V ˙ ) from 10 to 50 mm 3 /min, according to the relation V ˙ = V T ∗ R R . (B) Relationship between the median values (25 th -75 th percentile) of inspiratory flow (V T /t I, x axis) and duty cycle (t I /T TOT , y axis) in saline (SAL, black), bleomycin (BLM, red) and nintedanib-treated (NINT, green) groups on day 7 (filled circles) and day 21 (open circles).). Lines represent the isopleths of different levels of minute ventilation ( V ˙ ) from 10 to 50 cm 3 /min, according to the relation V ˙ = V T t I ∗ t I t T O T .

Article Snippet: Nintedanib Ethanesulfonate Salt , Carbosynth Limited, Compton, UK , FD71497.

Techniques: Derivative Assay, Micro-CT, Saline

Journal: iScience

Article Title: Multiphase micro-computed tomography reconstructions provide dynamic respiratory function in a mouse lung fibrosis model

doi: 10.1016/j.isci.2024.109262

Figure Lengend Snippet: Flow-volume loops derived from multiphase micro-CT Individual (thin line) and overall group (solid line) flow-volume loops in saline (SAL, left), bleomycin (BLM, middle) and nintedanib-treated (NINT, right) groups, on day 7 (top row) and 21 (bottom row).

Article Snippet: Nintedanib Ethanesulfonate Salt , Carbosynth Limited, Compton, UK , FD71497.

Techniques: Derivative Assay, Micro-CT, Saline

Journal: iScience

Article Title: Multiphase micro-computed tomography reconstructions provide dynamic respiratory function in a mouse lung fibrosis model

doi: 10.1016/j.isci.2024.109262

Figure Lengend Snippet: Lung function measurements by micro-CT imaging and by pulmonary function tests Pulmonary function tests performed on day 21 in saline (SAL), bleomycin (BLM) and nintedanib-treated (NINT) animals. Inspiratory capacity (A) and static compliance (B) were significantly lower in BLM compared to SAL (respectively p = 0.02 and p = 0.008). Data are expressed as mean ± SD. One-way analysis of variance and Dunnett’s multiple comparison post hoc test was applied to compare PFT outcome measures between groups. (C) micro-CT and flexiVent data were correlated using a Spearman matrix. The color bar evidence high positive correlations in red, whereas negative trends are shown in blue. For each correlation the R Spearman has been reported in each box if significant. IC, inspiratory capacity; G, lung tissue damping; H, lung tissue elastance; Cst, static compliance; Crs, dynamic compliance.

Article Snippet: Nintedanib Ethanesulfonate Salt , Carbosynth Limited, Compton, UK , FD71497.

Techniques: Micro-CT, Imaging, Saline, Comparison

Journal: iScience

Article Title: Multiphase micro-computed tomography reconstructions provide dynamic respiratory function in a mouse lung fibrosis model

doi: 10.1016/j.isci.2024.109262

Figure Lengend Snippet: Histomorphometric analysis of lung fibrosis progression (A) Histological assessment of fibrosis progression in the BLM model and nintedanib effect. a) Representative images (20X magnification, bar scale corresponds to 100μm) of Hematoxylin and eosin (H&E) and Masson’s trichrome (TM) stained histological sections from representative saline control (SAL, black), bleomycin (BLM, red) and nintedanib-treated (NINT, green) mice. (B) White blood cells (WBC) pulmonary infiltrate quantification for the three groups on the whole lungs, on day 7 and 21, with significantly lower values in the saline compared to the BLM group. (C) Ashcroft score quantification for the three groups on the whole lungs, on day 7 and 21, with both saline and NINT groups showing lower values compared to BLM. Statistical significance of the differences between groups were calculated by One-way ANOVA followed by Tukey’s test for multiple comparison (∗p < 0.05; ∗∗∗p < 0.001 vs. BLM group), separately at the two timepoints.

Article Snippet: Nintedanib Ethanesulfonate Salt , Carbosynth Limited, Compton, UK , FD71497.

Techniques: Staining, Saline, Control, Comparison

Journal: iScience

Article Title: Multiphase micro-computed tomography reconstructions provide dynamic respiratory function in a mouse lung fibrosis model

doi: 10.1016/j.isci.2024.109262

Figure Lengend Snippet:

Article Snippet: Nintedanib Ethanesulfonate Salt , Carbosynth Limited, Compton, UK , FD71497.

Techniques: Recombinant, Software

Journal: International Journal of Molecular Sciences

Article Title: Proteomic Fingerprint of Lung Fibrosis Progression and Response to Therapy in Bleomycin-Induced Mouse Model

doi: 10.3390/ijms24054410

Figure Lengend Snippet: ( a ) For each treatment group, representative coronal 2D micro-CT lung slices are followed by their relative 3D renderings (on the left) and representative whole lung sections are stained with Masson’s trichrome (on the right). In micro-CT renderings, cyan represents the normally aerated tissue while purple regions correspond to poorly aerated tissue; ( b ) Side-by-side comparison between micro-CT and histomorphometric readouts with the identification of different degrees of severity by Ashcroft score. ( c ) A simple linear regression comparing the average Ashcroft score with the % of poorly aerated tissue for each mouse ( p < 0.0001). Green, orange, and red colors represent the three categories (mild, moderate and severe) defined by the average Ashcroft score value. NINT—nintedanib; BLM—bleomycin; and AS—Ashcroft score.

Article Snippet: At day 7, BLM-treated mice were randomly divided into 2 subgroups, receiving either nintedanib (60 mg/kg/day, Carbosynth Limited, Compton, UK) dissolved in Tween80 0.05% in saline (NINT group) or vehicle (Tween80 0.05% in saline), by gavage, daily for 2 weeks ( a).

Techniques: Micro-CT, Staining, Comparison

Journal: International Journal of Molecular Sciences

Article Title: Proteomic Fingerprint of Lung Fibrosis Progression and Response to Therapy in Bleomycin-Induced Mouse Model

doi: 10.3390/ijms24054410

Figure Lengend Snippet: Summary of proteomics results. ( a ) Total numbers of identified and quantified proteins and further data elaboration steps. ( b ) Results of the statistical analysis following pairwise comparisons. PCA—principal component analysis; NINT: nintedanib; and BLM: bleomycin.

Article Snippet: At day 7, BLM-treated mice were randomly divided into 2 subgroups, receiving either nintedanib (60 mg/kg/day, Carbosynth Limited, Compton, UK) dissolved in Tween80 0.05% in saline (NINT group) or vehicle (Tween80 0.05% in saline), by gavage, daily for 2 weeks ( a).

Techniques:

Journal: International Journal of Molecular Sciences

Article Title: Proteomic Fingerprint of Lung Fibrosis Progression and Response to Therapy in Bleomycin-Induced Mouse Model

doi: 10.3390/ijms24054410

Figure Lengend Snippet: Multivariate Analysis. Principal Component Analysis (PCA): ( a ) 2D score plot between the following PCs, left-to-right: PC1-PC2, PC1-PC3, PC1-PC4, and PC1-PC5. The explained variances are shown in brackets. Pareto scaling is applied to rows, and singular value decomposition (SVD) with imputation is used to calculate principal components. Prediction ellipses are such that, with a probability of 0.95, a new observation from the same group will fall inside the ellipse. n = 19 data points; 2D score plots were created with Clustvis. ( b ) Loadings plots; loading plots were created with MetaboAnalyst 5.0. Hierarchical cluster analysis (HCA) with heatmap visualization based on ( c ) sample treatment and ( d ) the average histological grade. Heatmaps were created with MetaboAnalyst 5.0. The data were autoscaled; Pearson was used as a distance measure, and Ward as a clustering method. Heatmaps showed the top 50 features selected by t -test/analysis of variance (ANOVA). BLM—bleomycin; NINT—nintedanib; and d—days.

Article Snippet: At day 7, BLM-treated mice were randomly divided into 2 subgroups, receiving either nintedanib (60 mg/kg/day, Carbosynth Limited, Compton, UK) dissolved in Tween80 0.05% in saline (NINT group) or vehicle (Tween80 0.05% in saline), by gavage, daily for 2 weeks ( a).

Techniques:

Journal: International Journal of Molecular Sciences

Article Title: Proteomic Fingerprint of Lung Fibrosis Progression and Response to Therapy in Bleomycin-Induced Mouse Model

doi: 10.3390/ijms24054410

Figure Lengend Snippet: List of analyzed mice with their ID and treatment, average Ashcroft, Ashcroft frequencies, and fibrosis severity. Fibrosis severity was evaluated based on the average Ashcroft score: mild ( ≤ 3.5), moderate ( > 3.5 or ≤4.5), severe (> 4.5). * FFPE lung tissue blocks of these samples were prepared from both left and right lungs. SAL—saline; NINT—nintedanib; and BLM—bleomycin.

Article Snippet: At day 7, BLM-treated mice were randomly divided into 2 subgroups, receiving either nintedanib (60 mg/kg/day, Carbosynth Limited, Compton, UK) dissolved in Tween80 0.05% in saline (NINT group) or vehicle (Tween80 0.05% in saline), by gavage, daily for 2 weeks ( a).

Techniques:

Journal: International Journal of Molecular Sciences

Article Title: Proteomic Fingerprint of Lung Fibrosis Progression and Response to Therapy in Bleomycin-Induced Mouse Model

doi: 10.3390/ijms24054410

Figure Lengend Snippet: Nintedanib-mediated fibrosis slowdown. ( a ) Venn diagram comparing statistically significant proteins ( p -value adj ≤ 0.05, Fold Change ≥ 2 or ≤−2) in the comparisons of moderate BLM vs. mild/ severe BLM vs. mild/moderate NINT 21d vs. moderate BLM 21d; the two proteins common to all pairwise comparison are circled in red; and the even proteins are statistically significant ( p -value adj ≤ 0.05, fold change ≥ 2 or ≤−2) only in the comparison moderate NINT 21d vs. moderate BLM 21d are listed in a table. ( b ) Pattern search analysis of the proteins with a statistically significant ( p -value ≤ 0.05) correlation pattern and modulated (increased or decreased) by NINT treatment in the comparison between mild (green), moderate BLM 21d (orange), and moderate NINT 21d (blue), the correlation distance value in the bar chart is expressed based on the pattern search 1-2-1. ( c ) Cytoscape network of KEGG pathways obtained including the analysis of all 22 proteins with a statistically significant correlation. ( d ) Ten proteins with a reversing fold change in the comparison between moderate-BLM 21d vs. mild and moderate-NINT 21d vs. moderate-BLM 21d ( p -value adj ≤ 0.05, FC ≥ 1.5 or ≤−1.5). ( e ) Boxplots of the ten proteins. In all boxplots, mild/saline boxes are colored in green, moderate BLM 21d in orange, and moderate NINT 21d in blue. BLM—bleomycin; NINT—nintedanib; and d—days. In all Boxplots, black dots represent the abundance of the selected features in all samples, yellow diamond represents the mean abundance.

Article Snippet: At day 7, BLM-treated mice were randomly divided into 2 subgroups, receiving either nintedanib (60 mg/kg/day, Carbosynth Limited, Compton, UK) dissolved in Tween80 0.05% in saline (NINT group) or vehicle (Tween80 0.05% in saline), by gavage, daily for 2 weeks ( a).

Techniques: Comparison, Saline

Journal: International Journal of Molecular Sciences

Article Title: Proteomic Fingerprint of Lung Fibrosis Progression and Response to Therapy in Bleomycin-Induced Mouse Model

doi: 10.3390/ijms24054410

Figure Lengend Snippet: ( a ) Boxplots of lactate dehydrogenase A (Ldha) and lactate dehydrogenase B (Ldhb) in mild (green), moderate BLM (orange), moderate NINT (blue), and severe BLM (dark orange). Black dots represent the abundance of the selected features in all samples, yellow diamond represents the mean abundance. ( b ) Map of the pathways altered in moderate fibrosis and proteins modulated by nintedanib action ( p -value adj ≤ 0.05, FC ≥ 1.5 or ≤−1.5). The proteins upregulated and those downregulated in moderate fibrosis compared to mild are colored in red and green, respectively. BLM—bleomycin; NINT—nintedanib.

Article Snippet: At day 7, BLM-treated mice were randomly divided into 2 subgroups, receiving either nintedanib (60 mg/kg/day, Carbosynth Limited, Compton, UK) dissolved in Tween80 0.05% in saline (NINT group) or vehicle (Tween80 0.05% in saline), by gavage, daily for 2 weeks ( a).

Techniques:

Journal: International Journal of Molecular Sciences

Article Title: Proteomic Fingerprint of Lung Fibrosis Progression and Response to Therapy in Bleomycin-Induced Mouse Model

doi: 10.3390/ijms24054410

Figure Lengend Snippet: Experimental workflow of all the processes involved in sample collection, preparation, and data analysis. ( a ) Study design for control, BLM, and NINT treatment groups in C57BL6 mice. ( b ) Tissue sample selection and mass spectrometry analysis: (1) lung tissue histological evaluation, (2) sample preparation, (3) sample analysis, and (4) data analysis. BLM—bleomycin; OA—oropharyngeal aspiration; NINT—nintedanib; CT—computed tomography; nLC-ESI-MS/MS—nano-scale liquid chromatographic tandem mass spectrometry; and FFPE—formalin-fixed paraffin-embedded.

Article Snippet: At day 7, BLM-treated mice were randomly divided into 2 subgroups, receiving either nintedanib (60 mg/kg/day, Carbosynth Limited, Compton, UK) dissolved in Tween80 0.05% in saline (NINT group) or vehicle (Tween80 0.05% in saline), by gavage, daily for 2 weeks ( a).

Techniques: Control, Selection, Mass Spectrometry, Sample Prep, Computed Tomography, Tandem Mass Spectroscopy, Formalin-fixed Paraffin-Embedded

Journal: Cells

Article Title: Exploring the Therapeutic Potential of Elastase Inhibition in Age-Related Macular Degeneration in Mouse and Human.

doi: 10.3390/cells12091308

Figure Lengend Snippet: Figure 3. A1AT prevents increase in VEGF levels induced by elastase. (A) ELISA-based detection of extracellular VEGF protein levels in the apical and the basal supernatants collected from ARPE-19 monolayers treated with neutrophil elastase (NE) and A1AT for 24 h (n = 3–4). (B) VEGFA mRNA expression in ARPE-19 monolayers treated with NE for 3 h (n = 4) (C) Western blot detection of VEGFA protein and its quantification (D) in the retinas of WT, JR5558 and A1AT injected JR5558 mice (n = 4 retinas per group). (E) FITC dextran permeability assay in NE- and A1AT-treated ARPE-19 monolayers (n = 4) (F) ELISA-based VEGF protein level analysis in the basal supernatants collected from NE and VEGF receptor inhibitor ND (Nintedanib) treated ARPE-19 cells (n = 3–4). (G) ELISA- based VEGF protein level analysis in the basal supernatants collected from NE and PAR 2 antagonist (ENMD 1068) treated ARPE-19 cells. Extracellular C3a (H) and C5a (I) protein levels in NE and A1AT treated ARPE-19 cells (n = 3–4). Statistics used: (A–G) t-test for single comparison, one-way ANOVA, Dunnett’s MC; (H,I) Mann-Whitney non-parametric test. * p < 0.05, ** p < 0.01, **** p < 0.0001, ns: not significant. Data represent the mean ± SEM.

Article Snippet: Nintedanib (Tocris Bioscience, Bristol, UK), an anti-angiogenic drug targeting the receptor tyrosine kinases VEGFR, was used at 1 μM.

Techniques: Enzyme-linked Immunosorbent Assay, Expressing, Western Blot, Injection, FITC-Dextran Permeability Assay, Comparison, MANN-WHITNEY

Journal: Pharmaceutics

Article Title: Pharmacological Treatment of Interstitial Lung Diseases: A Novel Landscape for Inhaled Agents

doi: 10.3390/pharmaceutics16111391

Figure Lengend Snippet: Inhaling molecules under investigation in pulmonary fibrosis treatment. Smoking, air pollution, and dust represent the main noxae involved in ROS production and inflammation ignited within the lungs. This eventually may lead to a sustained aberrant response of alveolar epithelial cells leading EMT to progress and, finally, to fibrosis and lung parenchyma destruction. Several inhaling molecules are currently under investigation for future employment in pulmonary fibrosis treatment. *: PLGA–nintedanib has currently only been tested in vitro, by Wang et al. . α-SMA: alpha-smooth muscle actin; DMF: dimethyl fumarate; Gal-3: galectin 3; Gly: glycine; EMT: epithelial–mesenchymal transition; HO-1: heme oxygenase 1; Leu: leucine; Lip@VP: Liposome@verteporfin/pirfenidone; LUT@CDMOFs: Luteolin into γ-cyclodextrin metal–organic frameworks; MMP-9: matrix metalloproteinase-9; NAC: N-acetyl cysteine; NF-κB: nuclear factor kappa B; NLRP3: NLR family pyrin domain-containing 3; Nrf2: nuclear factor erythroid factor 2-related factor 2; NS: nanosuspension; PI3Ks: phosphoinositide 3-kinases; PKB: protein kinase B; PLGA: poly lactic-co-glycolic acid; ROS: reactive oxygen species; TD139: thiodigalactoside galectin-3 inhibitor; TGF-β1: transforming growth factor beta 1.

Article Snippet: Conversely, the idea of a multitarget intervention in ILDs has led to the development of the co-suspension of NAC and nintedanib.

Techniques: In Vitro

Journal: Pharmaceutics

Article Title: Pharmacological Treatment of Interstitial Lung Diseases: A Novel Landscape for Inhaled Agents

doi: 10.3390/pharmaceutics16111391

Figure Lengend Snippet: Pharmacological inhaled agents with antifibrotic properties: in vitro and murine models.

Article Snippet: Conversely, the idea of a multitarget intervention in ILDs has led to the development of the co-suspension of NAC and nintedanib.

Techniques: In Vitro, Drug discovery, Cell Culture, Expressing, Suspension, Formulation, Produced, Functional Assay

Journal: Pharmaceutics

Article Title: Pharmacological Treatment of Interstitial Lung Diseases: A Novel Landscape for Inhaled Agents

doi: 10.3390/pharmaceutics16111391

Figure Lengend Snippet: Inhaled antioxidant agents in pulmonary fibrosis: murine models.

Article Snippet: Conversely, the idea of a multitarget intervention in ILDs has led to the development of the co-suspension of NAC and nintedanib.

Techniques: Liposomes, Expressing, Formulation

Journal: Journal of Thoracic Disease

Article Title: Experimental study of the effects of pirfenidone and nintedanib on joint inflammation and pulmonary fibrosis in a rheumatoid arthritis-associated interstitial lung disease mouse model

doi: 10.21037/jtd-24-882

Figure Lengend Snippet: Body weights and arthritis scores of the mice. (A) Body weight changes of mice in each group; compared with those in the RA-ILD group (n≥3; a, P<0.05; b, P<0.01; c, P<0.001). (B) Arthritis scores change of mice in each group; compared with those in the RA-ILD group (n≥3; a, P<0.05; c, P<0.001). (C) Joint manifestations of the mice in each group: representative images of the left foot joints of the mice in the control, RA-ILD, pirfenidone and nintedanib groups. In the RA-ILD group, obvious swelling, stiffness and deformation of the ankle joint and toe joint were observed. RA-ILD, rheumatoid arthritis-associated interstitial lung disease.

Article Snippet: Pirfenidone was nintedanib were purchased from MedChemExpress (Cat No. HY-B0673; Shanghai, China) and nintedanib was purchased from Adooq (Cat No. A10137; Nanjing, China).

Techniques: Control

Journal: Journal of Thoracic Disease

Article Title: Experimental study of the effects of pirfenidone and nintedanib on joint inflammation and pulmonary fibrosis in a rheumatoid arthritis-associated interstitial lung disease mouse model

doi: 10.21037/jtd-24-882

Figure Lengend Snippet: Pirfenidone and nintedanib alleviate lung inflammation and fibrosis in a collagen-induced RA-ILD mouse model. (A) H&E staining and Masson staining of lung tissue. H&E staining revealed thickening of the alveolar septa and inflammatory cell infiltration in the lungs of the mice in the model group and the intervention group. Masson staining revealed a large area of blue staining in the alveolar septa of the mice in the RA-ILD group, indicating increased collagen deposition in the alveolar septa. (B) Mouse pulmonary inflammation scores. (C) Mouse pulmonary fibrosis scores. n≥3. *, P<0.05; **, P<0.01. RA-ILD, rheumatoid arthritis-associated interstitial lung disease; H&E, hematoxylin-eosin.

Article Snippet: Pirfenidone was nintedanib were purchased from MedChemExpress (Cat No. HY-B0673; Shanghai, China) and nintedanib was purchased from Adooq (Cat No. A10137; Nanjing, China).

Techniques: Staining

Journal: Journal of Thoracic Disease

Article Title: Experimental study of the effects of pirfenidone and nintedanib on joint inflammation and pulmonary fibrosis in a rheumatoid arthritis-associated interstitial lung disease mouse model

doi: 10.21037/jtd-24-882

Figure Lengend Snippet: H&E staining and synovitis scores for the knee joint. (A) H&E staining showed substantial hyperplasia of the synovial layer, inflammatory cell infiltration, collagen deposition and angiogenesis in the knee joints of the mice; bone destruction was observed in the RA-ILD group. These symptoms were alleviated in the pirfenidone and nintedanib groups. (B) Synovitis scores for the knee joints of the mice. n≥3. *, P<0.05. RA-ILD, rheumatoid arthritis-associated interstitial lung disease; H&E, hematoxylin-eosin.

Article Snippet: Pirfenidone was nintedanib were purchased from MedChemExpress (Cat No. HY-B0673; Shanghai, China) and nintedanib was purchased from Adooq (Cat No. A10137; Nanjing, China).

Techniques: Staining

Journal: Journal of Thoracic Disease

Article Title: Experimental study of the effects of pirfenidone and nintedanib on joint inflammation and pulmonary fibrosis in a rheumatoid arthritis-associated interstitial lung disease mouse model

doi: 10.21037/jtd-24-882

Figure Lengend Snippet: mRNA levels of Jak2, Stat3 and Col-IV in lung tissues. Both pirfenidone and nintedanib inhibited the expression of the Jak2, Stat3 and Col-IV genes. n=3. *, P<0.05; ***, P<0.005; ****, P<0.0001. RA-ILD, rheumatoid arthritis-associated interstitial lung disease; GAPDH, glyceraldehyde-3-phosphate dehydrogenase; Col-IV, collagen-IV.

Article Snippet: Pirfenidone was nintedanib were purchased from MedChemExpress (Cat No. HY-B0673; Shanghai, China) and nintedanib was purchased from Adooq (Cat No. A10137; Nanjing, China).

Techniques: Expressing

Journal: Journal of Thoracic Disease

Article Title: Experimental study of the effects of pirfenidone and nintedanib on joint inflammation and pulmonary fibrosis in a rheumatoid arthritis-associated interstitial lung disease mouse model

doi: 10.21037/jtd-24-882

Figure Lengend Snippet: Effects of pirfenidone and nintedanib on the expression of ECM-related proteins and the Jak2/Stat3 and TGF-β1/Smad3 signaling pathways in the lungs of mice. (A) Western blot detected Col-IV, fibronectin, p-Jak2/Jak2, p-Stat 3/Stat3, p-Smad3/Smad3, and TGF-βR2 protein expression levels in lung tissues. Pirfenidone and nintedanib inhibited the TGF-β1/Smad3 signaling pathway and down-regulated the Jak2/Stat3 signaling pathway. (B) Relative expression levels of fibronectin, Col-IV, p-Jak2, Jak2, p-Stat3, Stat3, TGF-βR2, p-Smad3 and Smad3. The grayscale values were measured three times. n=3. *, P<0.05; **, P<0.01; ***, P<0.005; ****, P<0.0001. RA-ILD, rheumatoid arthritis-associated interstitial lung disease; Col-IV, collagen-IV; GAPDH, glyceraldehyde-3-phosphate dehydrogenase; ECM, extracellular matrix.

Article Snippet: Pirfenidone was nintedanib were purchased from MedChemExpress (Cat No. HY-B0673; Shanghai, China) and nintedanib was purchased from Adooq (Cat No. A10137; Nanjing, China).

Techniques: Expressing, Protein-Protein interactions, Western Blot

Journal: Journal of Thoracic Disease

Article Title: Experimental study of the effects of pirfenidone and nintedanib on joint inflammation and pulmonary fibrosis in a rheumatoid arthritis-associated interstitial lung disease mouse model

doi: 10.21037/jtd-24-882

Figure Lengend Snippet: Effects of different concentrations of pirfenidone and nintedanib on p-Jak2/Jak2, p-Stat3/Stat3, TGF-βR2, CD206, and ARG-1 expression in RAW264.7 cells. (A) Protein expression in RAW264.7 cells (western blot). (B) Relative expression levels of the M2 macrophage markers ARG-1 and CD206. (C) Relative expression levels of p-Jak2, Jak2, p-Stat3, Stat3, and TGF-βR2. The grayscale values were measured three times. n=3. ns, no statistical significance; *, P<0.05; **, P<0.01; ***, P<0.005; ****, P<0.0001. CD206, cluster of differentiation 206; TGF-βR2, TGF-β receptor 2; ARG-1, arginase-1.

Article Snippet: Pirfenidone was nintedanib were purchased from MedChemExpress (Cat No. HY-B0673; Shanghai, China) and nintedanib was purchased from Adooq (Cat No. A10137; Nanjing, China).

Techniques: Expressing, Western Blot

Journal: Journal of Thoracic Disease

Article Title: Experimental study of the effects of pirfenidone and nintedanib on joint inflammation and pulmonary fibrosis in a rheumatoid arthritis-associated interstitial lung disease mouse model

doi: 10.21037/jtd-24-882

Figure Lengend Snippet: Effects of different concentrations of pirfenidone and nintedanib on p-Jak2/Jak2, p-Stat3/Stat3, and TGF-βR2 expression in FLS cells. (A) Protein expression in FLS cells (western blot). (B) Relative expression levels of p-Jak2, Jak2, p-Stat3, Stat3, and TGF-βR2. The expression of these proteins was greater in the FLS + TGF-β1 group than in the pirfenidone and nintedanib groups. Pirfenidone and nintedanib block the Jak2/Stat3 pathway through inhibition of the TGF-β1 signaling pathway. The grayscale values were measured three times. n=3. **, P<0.01; ***, P<0.005; ****, P<0.0001. FLS, fibroblast-like synovial; TGF-β1, transforming growth factor-β1; TGF-βR2, TGF-β receptor 2.

Article Snippet: Pirfenidone was nintedanib were purchased from MedChemExpress (Cat No. HY-B0673; Shanghai, China) and nintedanib was purchased from Adooq (Cat No. A10137; Nanjing, China).

Techniques: Expressing, Western Blot, Blocking Assay, Inhibition