Journal: Frontiers in Pharmacology

Article Title: Enhanced therapeutic potential of paeoniflorin and vitamin B12 in intracerebropeduncle ethidium bromide-induced multiple sclerosis-like pathology

doi: 10.3389/fphar.2026.1792674

Figure Lengend Snippet: The figures illustrate the docking interaction of paeoniflorin with the GDNF receptor (PDB ID: 1AGQ). (A) Shows a surface representation of the GDNF receptor, with the active site highlighted in yellow, where the ligand paeoniflorin (red) is bound. (B) 2D interaction diagram displays key interactions between paeoniflorin and the receptor, with hydrogen bonds and hydrophobic interactions clearly indicated. (C) Provides a 3D view of the docking, showing paeoniflorin (blue) interacting with GDNF, with hydrogen bonds represented by green dashed lines and key regions labeled. (D) Offers a zoomed-in view of the binding site, emphasizing hydrogen bonds and hydrophobic contacts, depicted within a ribbon structure for clarity.

Article Snippet: The ELISA kits for evaluating cellular and molecular targets included GDNF [E-EL-H1495; Elabscience GFRA1 [PKSH033670; Elabscience]; RET [AN00810P; Elabscience], AKT [E-EL-R0807 98T, Elabscience, Wuhan, China] ( ); ERK1/2 [E-AB-70292; Elabscience] ( ); and GSK3-Beta [KLR0989, KRISHGEN, Maharashtra, India] ( ).

Techniques: Labeling, Binding Assay

Journal: Frontiers in Pharmacology

Article Title: Enhanced therapeutic potential of paeoniflorin and vitamin B12 in intracerebropeduncle ethidium bromide-induced multiple sclerosis-like pathology

doi: 10.3389/fphar.2026.1792674

Figure Lengend Snippet: (A–H) PNN neuroprotective role in mitigating EBRO-induced alterations in levels of cellular and molecular targets in MS rat model: GDNF (A) , GFRA1 (B) , AKT (C) , ERK1/2 (D) , GSK3-Beta (E) , in brain homogenates, and GDNF, GFRA1, AKT, ERK1/2, GSK3-Beta in CSF levels (F–H) . Statistical analysis was performed using a one-way ANOVA followed by Tukey’s post hoc test to determine significant differences among groups (A–H) . Data were presented as mean ± standard deviation (SD), with statistical significance set at p < 0.01. Each experimental group consisted of eight wistar rats (n = 8). β v/s Sham Control, Vehicle Control, and PNN Perse; δ v/s EBRO; δα1 v/s EBRO + PNN50; δα2 v/s EBRO + PNN100, EBRO + PNN50; and δα3 v/s EBRO + VB12 (30), EBRO + PNN100, EBRO + PNN50. To identify significant differences between groups, a one-way ANOVA and Tukey’s post hoc test were used for statistical analysis (A–H) . The statistical significance level was set at p < 0.01, and the data were displayed as mean ± standard deviation (SD). There were eight wistar rats (n = 8) in each experimental group. β v/s Sham Control, Vehicle Control, and PNN Perse; δ v/s EBRO; δα1 v/s EBRO + PNN50; δα2 v/s EBRO + PNN100, EBRO + PNN50; and δα3 v/s EBRO + VB12 (30), EBRO + PNN100, EBRO + PNN50.

Article Snippet: The ELISA kits for evaluating cellular and molecular targets included GDNF [E-EL-H1495; Elabscience GFRA1 [PKSH033670; Elabscience]; RET [AN00810P; Elabscience], AKT [E-EL-R0807 98T, Elabscience, Wuhan, China] ( ); ERK1/2 [E-AB-70292; Elabscience] ( ); and GSK3-Beta [KLR0989, KRISHGEN, Maharashtra, India] ( ).

Techniques: Standard Deviation, Control

Journal: bioRxiv

Article Title: Synthetic budding morphogenesis by optogenetic receptor tyrosine kinase signaling

doi: 10.64898/2026.03.31.715459

Figure Lengend Snippet: GDNF-RET signaling tunes branching in mouse and human ureteric bud tissues. A. GDNF-RET signaling interactions involved in kidney branching. B. Immunofluorescence of cleared E14 mouse kidney. Top left , ECAD and SIX2. Bottom left, RET and GFRA1. Top right , isolated RET. Bottom right , isolated GFRA1 signal. C. Air-liquid interface (ALI) culture of mouse embryonic kidney explants. D. Design of GDNF-RET signaling perturbation experiments in ALI culture. E. Immunofluorescence of E13 kidneys grown in ALI culture for 4 days in 100 nM Selpercatinib (+RETi), 100 ng ml -1 GDNF (+GDNF), or control media. Inset , close-up of tip domains. Explants are immunostained for EpCAM (epithelium), RET (tip cells), and JAG1 (early nephrons). F. Tip number on days 1-4 across all conditions, N = 4 kidneys per condition. P -values by one-way Kruskal-Wallis test with Dunn’s post hoc test. G. Differentiation of iUB organoids from hiPSCs H. Immunofluorescence of epithelial (ECAD) and tip (RET) markers in a day 12 iUB organoid. I. Design of GDNF-RET signaling perturbations for iUB organoids. J. Merged brightfield and GATA3:mCherry images of iUB organoids at days 9 and 12. Organoids were cultured in control (-GDNF) or complete branching medium (+GDNF, 50 ng ml -1 ), excess GDNF (++GDNF, 250 ng ml -1 ), or complete branching medium with 100 nM Selpercatinib (+RETi). See: Fig. S4F . K. Projected area (x10 4 µm 2 ) on days 9 and 12 for all conditions, n = 47, 56, 40, 46 iUB organoids (-GDNF, +RETi, +GDNF, ++GDNF) from 2 independent biological replicates. L. Circularity (a.u.) on days 9 and 12. M. Bud number on days 9 and 12. P -values in panels K, L, M by one-way ANOVA with Dunnett’s post hoc test using +GDNF as reference group.

Article Snippet: MDCK cells were not starved and were treated with 50 ng ml -1 GDNF (#212-GD-050, R&D Systems) and 100 ng ml -1 recombinant human Gfrɑ1 (#714-GR-100, R&D Systems) at defined time points.

Techniques: Immunofluorescence, Isolation, Control, Cell Culture

Journal: bioRxiv

Article Title: Synthetic budding morphogenesis by optogenetic receptor tyrosine kinase signaling

doi: 10.64898/2026.03.31.715459

Figure Lengend Snippet: Blue light stimulation of optoRET drives ERK signaling and ligand-independent budding in iUB organoids. C. Schematic of hiPSC-optoRET generation using piggyBac transposase and differentiation into iUB-optoRET organoids. D. Immunofluorescence of iUB-optoRET monolayers stimulated for 2 hr under the indicated conditions (±light). Blue light stimulation was provided by an optoPlate-96 (470 nm, 50 mW cm -2 , 1 s every 10 s) for 2 hrs. Top , optoRET (detected by anti-GFP) and nuclei (DAPI). Bottom , intensity-coded ppERK (a.u.). E. Violin plot of ppERK (a.u.) for iUB-optoRET cells under -light and +light conditions, n = 2458, 2030 cells (control, +light) pooled from 2 independent biological replicates. P -value by Welch’s t-test. F. Immunofluorescence density plot of ppERK (a.u.) as a function of optoRET(eGFP) intensity (a.u.) for cells shown in B. n = 2458, 2030 cells (control, +light) pooled from two independent biological replicates. G. Stimulation conditions for iUB-optoRET organoids: control (−light/−GDNF), +light, +GDNF, and combined (+light/+GDNF) treatments. H. Live fluorescence images of GATA3 mCherry iUB-optoRET organoids under optogenetic and ligand-based stimulation conditions. Blue light stimulation was provided by an optoPlate-96 (320 mW cm -2 , 0.5 s every 4 min) between days 7-11 and the +GDNF and +light/+GDNF groups received 50 ng ml -1 GDNF. I. Bud number on day 11 across all conditions, n = 50, 50, 51, 50 organoids (control, +light, +GDNF, +light/+GDNF) from 2 independent biological replicates. P -values by one-way Kruskal-Wallis test with Dunn’s post hoc test. J. Differential expression analysis from bulk RNA-seq of iUB-optoRET organoids grown in ±light stimulation conditions (see also: Fig. S14 ). Top , relative density of tip and trunk marker genes. Bottom , volcano plot of all genes organized by significance (-log 10 ( p )) and log 2 (fold-change) with tip and trunk-specific markers highlighted. Data are derived from 3 biological replicates. K. Gene Set Enrichment Analysis (GSEA) as a function of normalized enrichment score (NES). Hallmark gene sets are color coded by false discovery rate (FDR), size coded by the size of the gene set.

Article Snippet: MDCK cells were not starved and were treated with 50 ng ml -1 GDNF (#212-GD-050, R&D Systems) and 100 ng ml -1 recombinant human Gfrɑ1 (#714-GR-100, R&D Systems) at defined time points.

Techniques: Immunofluorescence, Control, Fluorescence, Quantitative Proteomics, RNA Sequencing, Marker, Derivative Assay

Journal: bioRxiv

Article Title: Synthetic budding morphogenesis by optogenetic receptor tyrosine kinase signaling

doi: 10.64898/2026.03.31.715459

Figure Lengend Snippet: Spatially patterned optoRET stimulation drives asymmetric budding in iUB organoids. A. Strategy for targeted optogenetic stimulation of iUB-optoRET organoids. B. Average projections of GATA3:mCherry for small ( top panels ) and large ( bottom panels ) iUB-optoRET organoids under control, +GDNF, +light whole, and +light half conditions. Light stimulation was provided by 488 nm DMD-based light projection (0.5 s every 4 mins) for 4 days. Organoids in the +GDNF group received 50 ng ml -1 GDNF. Top row , average projections across individual organoids at day 7. Middle row , average projections across individual organoids at day 11. Bottom row , normalized average projections for individual organoids at day 11. C. Representative average projections of individual small ( top ) and large ( bottom ) iUB-optoRET organoids on day 11. The cyan dashed line divides the non-illuminated side ( left , -light half) from the illuminated side ( right , +light half). Magenta dots indicate bud locations. D. Confocal immunofluorescence images of optoRET+ and RET+ cells within iUB-optoRET bud tips in +light whole condition. Endogenous RET was visualized with an antibody against the extracellular domain (ECD). Left , ECAD, optoRET, and RET(ECD). Middle , optoRET and tip outline. Right , RET(ECD) and tip outline. E. Radial histograms of bud orientation angle (°) for small organoids across all conditions, n = 19, 20, 19, 20 organoids (control, +GDNF, +light whole, and +light half) pooled from 2 biological replicates. P -values by Kolmogorov-Smirnov test against a uniform reference distribution.

Article Snippet: MDCK cells were not starved and were treated with 50 ng ml -1 GDNF (#212-GD-050, R&D Systems) and 100 ng ml -1 recombinant human Gfrɑ1 (#714-GR-100, R&D Systems) at defined time points.

Techniques: Control, Immunofluorescence