Journal: bioRxiv

Article Title: Rescuing functional defects in a zebrafish model of CDKL5 deficiency disorder: Contribution to the identification of new therapeutic compounds

doi: 10.64898/2026.03.12.711124

Figure Lengend Snippet: A) Representative images of the WT, DMSO-treated cdkl5 ⁻/⁻ larvae and cdkl5 -/- larvae following drug treatment with fisetin, divalproex, resveratrol and VX-702, stained with Alcian blue. B) Schematic illustration of the analyzed craniofacial cartilage parameters, adapted from Raterman et al. C) Quantification of craniofacial cartilage parameters, including ceratohyal cartilage length (Ch-l), palatoquadrate length (Pq-l), and ceratohyal cartilage width (Ch-w). Data are presented as median with interquartile range (n=29). Statistical analysis was performed using one-way ANOVA followed by Tukey’s multiple comparisons test. Significant differences are indicated by distinct lowercase letters.

Article Snippet: Resveratrol was order from MedChemExpress (HY-16561/CS-1050), fisetin from Biorbyt (orb593928), divalproex sodium from MyBioSource (MBS579016) and VX-702 from MedChemExpress (HY-10401/CS-0074).

Techniques: Staining

Journal: bioRxiv

Article Title: Rescuing functional defects in a zebrafish model of CDKL5 deficiency disorder: Contribution to the identification of new therapeutic compounds

doi: 10.64898/2026.03.12.711124

Figure Lengend Snippet: RT-qPCR analysis was performed on larvae treated with 10 µM of fisetin, divalproex, resveratrol or VX-702 for 48h. WT and cdkl5 -/- control groups were treated with 0.1% DMSO as vehicle. Relative gene expression levels are presented as mean±SD of three biological replicates, except for the resveratrol group, which included two biological replicates. Each replicate consisted of a pool of 15 larvae. Statistical analysis was performed using one-way ANOVA followed by Tukey’s multiple comparisons test. Statistically significant differences are indicated by distinct lowercase letters.

Article Snippet: Resveratrol was order from MedChemExpress (HY-16561/CS-1050), fisetin from Biorbyt (orb593928), divalproex sodium from MyBioSource (MBS579016) and VX-702 from MedChemExpress (HY-10401/CS-0074).

Techniques: Quantitative RT-PCR, Control, Gene Expression

Journal: The FASEB Journal

Article Title: Distinct cAMP Regulation in Scleroderma Lung and Skin Myofibroblasts Governs Their Dedifferentiation via p38α Inhibition

doi: 10.1096/fj.202500694RR

Figure Lengend Snippet: cAMP‐mediated p38 inhibition promotes dedifferentiation of lung and skin MFs. (A, B) Western blot and densitometric analysis of the phosphorylated proteins p‐p38, p‐ERK, and p‐JNK following SSc lung (A) and skin (B) MF treatment with forskolin (20 μM) for 6 h. Phosphorylated proteins were normalized to total levels of their respective proteins. (C) Western blot and densitometric analysis of the fibrosis‐associated genes Col1A1 and αSMA following SSc lung and skin MF treatment with SB203580 (20 μM) for 96 h. (D) αSMA stress fibers were identified by immunofluorescence microscopy using an anti‐αSMA‐FITC‐conjugated antibody (using the same protocol in C). Nuclei were stained with DAPI. Data points represent distinct patient‐derived cell lines. Significance for densitometric data ( n = 5–7) in (A and B) was determined by a 2‐tailed paired t‐test and by one‐way ANOVA in (C). * p < 0.05, ** p < 0.01, *** p < 0.001, and **** p < 0.0001.

Article Snippet: The pan‐p38 inhibitor SB203580 (20 μM) and p38α inhibitor VX‐702 (50 μM) were purchased from Cayman Chemicals (13067) and Selleckchem (HY‐10401), respectively.

Techniques: Inhibition, Western Blot, Immunofluorescence, Microscopy, Staining, Derivative Assay

Journal: The FASEB Journal

Article Title: Distinct cAMP Regulation in Scleroderma Lung and Skin Myofibroblasts Governs Their Dedifferentiation via p38α Inhibition

doi: 10.1096/fj.202500694RR

Figure Lengend Snippet: p38α inhibition promotes SSc lung and skin MF dedifferentiation. (A) qPCR data representing the relative expression of the genes encoding p38α, p38β, p38γ and p38δ in SSc lung and skin MFs. (B) Western blot and densitometric analysis of the fibrosis‐associated genes Col1A1 and αSMA following SSc lung and skin MF treatment with the isoform‐specific p38α inhibitor VX‐702 (50 μM) for 96 h. (C) αSMA stress fibers were identified by immunofluorescence microscopy using an anti‐αSMA‐FITC‐conjugated antibody (using the same protocol in B). Nuclei were stained with DAPI. Data points represent distinct patient‐derived cell lines. Significance for data in (A) ( n = 8) was determined by two‐tailed unpaired or paired t ‐test where appropriate and by one‐way ANOVA in (B) ( n = 6). * p < 0.05, ** p < 0.01, *** p < 0.001, and **** p < 0.0001.

Article Snippet: The pan‐p38 inhibitor SB203580 (20 μM) and p38α inhibitor VX‐702 (50 μM) were purchased from Cayman Chemicals (13067) and Selleckchem (HY‐10401), respectively.

Techniques: Inhibition, Expressing, Western Blot, Immunofluorescence, Microscopy, Staining, Derivative Assay, Two Tailed Test

Journal: Nature Communications

Article Title: MNKs act as a regulatory switch for eIF4E1 and eIF4E3 driven mRNA translation in DLBCL

doi: 10.1038/ncomms6413

Figure Lengend Snippet: ( a ) Western blot analysis of total and phospho-eIF4E1(S209) as well as total and phospho-ERK after 24 h treatment with an MEK inhibitor AZD6244 (AZD 200 nM), compared with untreated and vehicle controls in HLY-1, GM02184 and Pfeiffer cell lines. Densitometry analysis is shown in . ( b ) Western blot analysis of phospho-MNKs (antibody detects p-MNK1 and p-MNK2), total MNK1, total MNK2, total and phospho-eIF4E1(S209) after 1 h treatment with a p38 inhibitor VX702 (200 nM). Densitometry analysis is shown in . ( c ) Western blot analysis of total and phospho-eIF4E1 and MCL-1 post 4 h treatment with a p38 inhibitor VX702. ( d ) Densitometry analysis of phospho-eIF4E1(S209) and ( e ) MCL-1 band intensity of western blot in , relative to GAPDH following 4 h treatment with vehicle (black bar) or 200 nM VX702 (white bar). Mean±s.d., n =3, * P -value of Student’s t -test <0.05. ( f ) Trypan blue exclusion assay of HLY-1, GM02184 and Pfeiffer cells after 72 h treatment with vehicle (black bar) or 200 nM VX702 (white bar). Mean±s.d., n =3, * P -value of Student’s t -test <0.001. ( g ) Representative CFSE analysis of HLY-1 cells 48 and 72 h post treatment with 200 nM VX702 (blue line) or vehicle (DMSO; red line). P0 denotes initial population, while P1, P2 and P3 denote subsequent daughter cell populations. Three independent experiments are shown in . ( h ) Western blot showing total and phospho-eIF4E1(S209) as well as MCL-1 with or without 4 h treatment with 200 nM VX702 in HLY-1 cells expressing empty vector (EV), MNK1-wildtype (M1WT), MNK1-phosphomimetic (M1TD), MNK1-phosphonull (M1 AA), and MNK2-wildtype (M2WT). ( i , j ) Densitometry analysis showing relative band intensity of ( i ) phospho-eIF4E1(S209) or ( j ) MCL-1 to GAPDH in HLY-1 cells treated with vehicle (black bar) or 200 nM VX702 (white bar) for 4 h of immunoblot in (mean±s.d., n =3, * P -value of Student’s t -test <0.05). ( k ) Summarizing figure illustrating the p38-regulated MNK-dependent eIF4E1 phosphorylation in DLBCL cells. Cartoon depicts two potential modes of disrupting the p38-MNK-eIF4E1 axis in DLBCL, that are, via the use of p38 or MNK inhibitors. Full immunoblots are shown in .

Article Snippet: VX702 (p38 inhibitor) was purchased from Cayman Chemical, and MEK inhibitor AZD6244 was purchased from CalBiochem.

Techniques: Western Blot, Trypan Blue Exclusion Assay, Expressing, Plasmid Preparation, Phospho-proteomics

Journal: Nature Communications

Article Title: MNKs act as a regulatory switch for eIF4E1 and eIF4E3 driven mRNA translation in DLBCL

doi: 10.1038/ncomms6413

Figure Lengend Snippet: ( a ) On activation by p38, MNKs phosphorylate eIF4E1 at S209. ( b ) In the absence of MNK kinase activity, eIF4E1 cannot be phosphorylated, while in the ( c ) absence of MNK protein expression or its physical suppression, eIF4E1 protein expression is downregulated. ( d ) The unphosphorylated eIF4E1 (at S209) form is stimulatory for eIF4E3 protein upregulation. Increased abundance of eIF4E3 in a cellular context enhances the ability for eIF4E3 to bind cap. The relative abundance of either eIF4E1 or eIF4E3 is determined by MNKs. The accessibility to mRNA cap structure by both eIF4Es mandates a distinct cellular translatome that dictates pro- or anti-oncogenic phenotype.

Article Snippet: VX702 (p38 inhibitor) was purchased from Cayman Chemical, and MEK inhibitor AZD6244 was purchased from CalBiochem.

Techniques: Activation Assay, Activity Assay, Expressing