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: Total distance traveled by 5 dpf cdkl5 -/- zebrafish larvae following treatment with 149 compounds from the MAPK Inhibitor Library (10 μM). Each dot represents the mean ± SEM distance traveled by 48 cdkl5 -/- larvae per compound, normalized to DMSO-treated WT controls. The green and grey horizontal lines indicate the mean ± SEM distance traveled by DMSO-treated WT and DMSO-treated cdkl5 -/- larvae, respectively. Statistical analysis was performed using one-way ANOVA followed by Dunnett’s post hoc test. Compounds classified as great candidates (green dots) significantly increased ( p <0.05) the distance traveled by cdkl5 ⁻/⁻ larvae to levels not significantly different from those of DMSO-treated WT controls ( p >0.05). Compounds classified as good candidates (blue dots) significantly increased ( p <0.05) the distance traveled by cdkl5 ⁻/⁻ larvae but remained significantly lower than that of DMSO-treated WT controls ( p <0.05). The compound classified as overabundant candidate (red dot) resulted in a significantly greater distance traveled by cdkl5 ⁻/⁻ larvae compared to both DMSO-treated cdkl5 ⁻/⁻ and WT control larvae ( p <0.05).

Article Snippet: Two compound libraries were used in this study: the MAPK Inhibitor Library (258 compounds, catalog no. L3400) and the Histone Modification Library (347 compounds, catalog no. L4900), both purchased from Selleckchem (Houston, USA).

Techniques: Control

Journal: Drug Design, Development and Therapy

Article Title: Knee Osteoarthritis Therapy: Recent Advances in Intra-Articular Drug Delivery Systems

doi: 10.2147/DDDT.S357386

Figure Lengend Snippet: Summary of Nanoparticles Drug Loading System

Article Snippet: Phase 3 , FX005 , Polymeric microsphere , p38 MAPK inhibitor , Flexion Therapeutics.

Techniques: Liposomes, In Vitro, Incubation, Injection, Immunohistochemistry, In Vivo, Expressing, Quantitative Proteomics, Translocation Assay, Modification, Molecular Weight, Blocking Assay, Binding Assay, Drug discovery, Polymer, Protein-Protein interactions, Labeling, Fluorescence, Activity Assay, Cell Culture, DPPH Assay, Ex Vivo, Concentration Assay, Membrane

Journal: Drug Design, Development and Therapy

Article Title: Knee Osteoarthritis Therapy: Recent Advances in Intra-Articular Drug Delivery Systems

doi: 10.2147/DDDT.S357386

Figure Lengend Snippet: Summary of Previous Studies on Signaling Pathway in IA DDSs

Article Snippet: Phase 3 , FX005 , Polymeric microsphere , p38 MAPK inhibitor , Flexion Therapeutics.

Techniques: Protein-Protein interactions, Activation Assay, Solubility, Expressing, Membrane

Journal: Drug Design, Development and Therapy

Article Title: Knee Osteoarthritis Therapy: Recent Advances in Intra-Articular Drug Delivery Systems

doi: 10.2147/DDDT.S357386

Figure Lengend Snippet: Recent IA DDSs Reported in Preclinical and Clinical Trials

Article Snippet: Phase 3 , FX005 , Polymeric microsphere , p38 MAPK inhibitor , Flexion Therapeutics.

Techniques: Formulation

Journal: Bioengineered

Article Title: Coordination of PRKCA/PRKCA-AS1 interplay facilitates DNA methyltransferase 1 recruitment on DNA methylation to affect protein kinase C alpha transcription in mitral valve of rheumatic heart disease

doi: 10.1080/21655979.2021.1971482

Figure Lengend Snippet: The role of p38/MAPK in regulating PRKCA-AS1 expression in RHD. (a) the RNA levels of PRKCA-AS1 and PRKCA in TNF-α-induced AC16 cells treated with inhibition of different signaling pathways. (b) Smad2 occupancy on PRKCA-AS1 in TNF-α-induced AC16 cells treated with inhibition of different signaling pathways. (c) Smad2 occupancy on PRKCA-AS1 in mitral valve of RHD. the given data from triplicate experiments was processed as mean ± standard error and compared by student’s t-test. ‘FC’: fold change; ‘BK’: blocking

Article Snippet: The conditions of 100 ng/mL tumor necrosis factor-α (TNF-α) (APExBIO, Houston, TX, USA) for 16 h [ ], 20 ng/mL 5-Azacytidine (APExBIO) for 24 h [ ], 1 μM p38/MAPK inhibitor (2-(4-chlorophenyl)-4-(4-fluorophenyl)-5-(pyridin-4-yl)-1H-pyrazol-3(2 H)-one) (APExBIO) for 4 h, 50 mM transforming growth factor β1 (TGFB1) inhibitor (4-[2-(6-methylpyridin-2-yl)-5,6-dihydro-4 H-yrrolo[1,2-b]pyrazol-3-yl]quinoline-6-carboxamide) (APExBIO) for 4 h, 0.1 μM Rho associated coiled-coil containing protein kinase 1/2 (ROCK1/2) (4-[(1 R)-1-aminoethyl]-N-pyridin-4-ylcyclohexane-1-carboxamide) (APExBIO) for 6 h, 10 μM peroxisome proliferator activated receptor gamma/delta (PPARγ/δ) (2,5-dichloro-N-(2-methyl-4-nitrophenyl) benzenesulfonamide) (APExBIO) for 4 h, and 100 μM signal transducer and activator of transcription 3 (STAT3) (5,15-diphenyl-21 H,23 H-porphine) (APExBIO) for 6 h were adopted.

Techniques: Expressing, Inhibition, Blocking Assay

Journal: Annals of the rheumatic diseases

Article Title: MicroRNA-199a* regulates the expression of cyclooxygenase-2 in human chondrocytes

doi: 10.1136/annrheumdis-2011-200519

Figure Lengend Snippet: miR-199a* directly inhibits the expression of cyclooxygenase-2 (COX-2) in osteoarthritis chondrocytes. (A) Luciferase activity in chondrocytes transfected with the reporter vector and premiR-199a* (*p<0.05). (B, C) Expression of COX-2 protein in premiR-199a* or antimiR-199a* transfected chondrocytes after 72 h of stimulation with interleukin-1β (IL-1β). (D, E) Expression of COX-2 protein in negative control premiRNA or negative control-antimiRNA-transfected chondrocytes after 72 h of stimulation with IL-1β. (F, G) Expression levels of miR-199a* and COX-2 in chondrocytes treated with the p38-MAPK inhibitor (SB202190) and stimulated with IL-1β were determined by TaqMan assays. Gene expression in unstimulated chondrocytes was used as a control and expression of RNU6B/glyceraldehyde 3-phosphate dehydrogenase was used as an endogenous control. COX-2 protein expression was determined by western immunoblotting. Each experiment was performed in duplicate with samples from the indicated number of patients. *p<0.05 vs control; #p<0.05 vs IL-1β-stimulated chondrocytes.

Article Snippet: OA chondrocytes were serum-starved overnight and then stimulated with IL-1β (5 ng/ml; R&D Systems, St Paul, Minnesota, USA) or p38-MAPK inhibitor (SB202190 100 μM; A G Scientific Inc, San Diego, California, USA) for the indicated time and total RNA was prepared using the TRIZOL reagent (Invitrogen, Carlsbad, California, USA).

Techniques: Expressing, Luciferase, Activity Assay, Transfection, Plasmid Preparation, Negative Control, Gene Expression, Control, Western Blot

Journal: Frontiers in Immunology

Article Title: Inhibition of NKCC1 Modulates Alveolar Fluid Clearance and Inflammation in Ischemia-Reperfusion Lung Injury via TRAF6-Mediated Pathways

doi: 10.3389/fimmu.2018.02049

Figure Lengend Snippet: Expressions of MAPKs and α-ENaC in MLE-12 cells. (A) Total Erk MAPK (T-Erk) and phosphorylated Erk MAPK (p-Erk), (B) total JNK MAPK (T-JNK) and phosphorylated JNK MAPK (p-JNK), (C) total p38 MAPK (T-p38) and phosphorylated p38 MAPK (p-p38) after HR treated with BMT. (D) α-ENaC expression after HR treated by p38 MAPK inhibitor, BIRB-796 10 μM. BMT, bumetanide 20-μM; CTRL, control. Data are expressed as the mean ± SD ( n = 5 per group). * P < 0.05 compared with the control group; # P < 0.05 compared with the HR group.

Article Snippet: After 24 h of incubation, the cells were pretreated with vehicle, bumetanide (10, 20, 40-μM), or p38 MAPK inhibitor BIRB-796 (10-μM; Enzo Life Sciences, Inc., San Diego, CA, USA).

Techniques: Expressing

Journal: Frontiers in Immunology

Article Title: Inhibition of NKCC1 Modulates Alveolar Fluid Clearance and Inflammation in Ischemia-Reperfusion Lung Injury via TRAF6-Mediated Pathways

doi: 10.3389/fimmu.2018.02049

Figure Lengend Snippet: The mechanisms of NKCC1 modulating alveolar fluid clearance and inflammation in IR-ALI. IR stress causes phosphorylation of NKCC1 and activation of TRAF6, which result in cell swelling and inflammation of alveolar epithelium. Inhibition of NKCC1 by bumetanide reciprocally modulates epithelial TRAF6 expression. This interaction suppresses downstream p38 MAPK and NF-κB pathways, which attenuates the reduction of AFC via upregulating α-ENaC expression and reduces the alveolar inflammation.

Article Snippet: After 24 h of incubation, the cells were pretreated with vehicle, bumetanide (10, 20, 40-μM), or p38 MAPK inhibitor BIRB-796 (10-μM; Enzo Life Sciences, Inc., San Diego, CA, USA).

Techniques: Activation Assay, Inhibition, Expressing

Journal: EXS

Article Title: Targeting AMPK for the Alleviation of Pathological Pain

doi: 10.1007/978-3-319-43589-3_11

Figure Lengend Snippet: Impact of AMPK activation on pathological pain-related signaling cascades. Factors associated with pathological pain employ signaling mechanisms that converge onto the mTORC1 and MAPK pathways to induce and maintain pain plasticity in nociceptors. Activation of AMPK abrogates these effects by negatively regulating these signaling events via phosphorylation of key effector molecules. AMPK activation phosphorylates IRS, an adaptor protein of the Trk receptor, at Ser789 to inhibit signaling via Trk and Insulin/IGF1 receptors. AMPK activation dampens mTORC1 signaling by phosphorylating TSC1/2 at Ser 1227 and 1345. The phosphorylation of Braf (Raf), a small GTPase linking receptors to MAPK signaling, by AMPK attenuates downstream ERK signaling. These signaling events produce several pathological pain attenuation outcomes such as: (1) a decrease in the phosphorylation of voltage-gated sodium channels such as Nav1.7 leading to blunted neuronal excitability, (2) a reduction in microglial activation and microglia-related release of pro-inflammatory factors potentially resulting in reduced neuropathic pain, opioid-induced hypersensitivity, and diminished opioid tolerance, and (3) AMPK activation also normalizes dysregulation in mitochondrial and neuronal bioenergetics that is likely associated with diabetic neuropathic pain

Article Snippet: MAPK inhibitors have been widely investigated as pain therapeutics ( Ji et al. 2009b ) including some clinical trials for p38 inhibitors that have had mixed success ( Anand et al. 2011 ).

Techniques: Activation Assay, Phospho-proteomics

Journal: Science Advances

Article Title: Synthetic dysmobility screen unveils an integrated STK40-YAP-MAPK system driving cell migration

doi: 10.1126/sciadv.abg2106

Figure Lengend Snippet: ( A ) Scheme for the two-hit sheet migration screen. ( B ) Representative images showing sheet migration of HUVECs treated with shRNAs: shCTRL, shCTNNA1, and shRAC1; and drug inhibitors: ND [no drug; i.e., dimethyl sulfoxide (DMSO)], 2 μM Ca 2+ inhibitor BTP2, 5 μM ROCK inhibitor Y27632, and 10 μM MAPK inhibitor PD98059. Hoechst stain marked cell nucleus. ( C ) Quantification of the sheet migration effects by shRNAs and drugs in (B). ( D ) Dot plot demonstrates sheet migration effects by individual shRNAs. Red circles resemble shSTK40s, while gray circles resemble other individual shRNAs. ( E ) Black bars resemble average sheet migration of all shRNAs ( n = 1890), while gray bars resemble average sheet migration of shSTK40 ( n = 15) upon specific drug treatments. Notice that shSTK40 markedly decreased sheet migration under PD98059. ( F ) Representative images of shSTK40- and/or PD98059-treated sheet migration in our HUVEC screen. ( G ) SAS cells treated with shSTK40 and another MAPK inhibitor trametinib (TRA) also revealed synergistic suppression in sheet migration. Left: Representative images. Right: Quantification. Error bars denote means ± SEM. n = 6 biological repeats for each group.

Article Snippet: The MAPK kinase (MEK) inhibitor trametinib enhanced FA in SAS cells similarly to shSTK40 ( ).

Techniques: Migration, Staining

Journal: Science Advances

Article Title: Synthetic dysmobility screen unveils an integrated STK40-YAP-MAPK system driving cell migration

doi: 10.1126/sciadv.abg2106

Figure Lengend Snippet: ( A ) Top: Diagram of FL STK40, STK40 with KD only, and ΔKD constructs expressed in SAS cells. Bottom: Quantification of integrated FA intensity in SAS cells overexpressing above vectors. YFP, control vector. ( B ) Representative images of FAs of (A). ( C ) Top: Diagram of STK40-EYFP and STK40-EYFP-NES constructs expressed in SAS cells. Bottom: Quantification of integrated FA intensity in SAS cells overexpressing above vectors. ( D ) Representative images of FA of (C). 4of (Diamidino-2-phenylindole (DAPI) channel revealed locations of cell nuclei. YFP channel denotes subcellular distribution of above vectors. Note the distinct cytosolic translocation of STK40 by the NES. ( E ) Representative images and quantification of FA in SAS cells without or with shSTK40 treated with 100 nM trametinib overnight. Note that the trametinib effect was masked by STK40 knockdown in high efficiency. ( F ) Representative images of α-SMA in fibroblast HS68 cells without or with shSTK40 treated with 100 nM trametinib overnight. Note that the lower knockdown efficiency of STK40 in HS68 cells than in SAS cells resulted in marked synergistic enrichment of α-SMA on stress fibers of HS68 cells under combination treatment. ( G ) YAP activity [labeled by connective tissue growth factor (CTGF) expression] was decreased in SAS cells treated with (top) verteporfin (VP) and (bottom) trametinib, shRNA targeting cyclic adenosine 3′,5′-monophosphate response element–binding protein (shCREB), or shSTK40. HPRT, hypoxanthine-guanine phosphoribosyltransferase. ( H ) Representative images and quantification of FA in SAS cells without or with VP treated with shCTRL or shSTK40. ( I ) Representative images and quantification of FA in SAS cells with shSTK40 and treated with VP and/or trametinib. Note that shSTK40 and VP abolished effects of trametinib. Error bars denote means ± SEM. * P < 0.05. ns, not significant.

Article Snippet: The MAPK kinase (MEK) inhibitor trametinib enhanced FA in SAS cells similarly to shSTK40 ( ).

Techniques: Construct, Control, Plasmid Preparation, Translocation Assay, Knockdown, Activity Assay, Labeling, Expressing, shRNA, Binding Assay

Journal: Science Advances

Article Title: Synthetic dysmobility screen unveils an integrated STK40-YAP-MAPK system driving cell migration

doi: 10.1126/sciadv.abg2106

Figure Lengend Snippet: ( A ) Representative images and quantification of subcellular YAP distribution. Notice the decreased N/C ratio of YAP by shSTK40. A.U., arbitrary units. ( B ) Representative images and quantification of FA in SAS cells without or with leptomycin B (LMB) treated with shCTRL or shSTK40. Note the vanishment of STK40 effect under leptomycin B. ( C ) SAS cells received STK40 knockdown (shSTK40) followed by rescue experiments using STK40 of FL, KD, and ΔKD constructs. Their cytosolic YAP levels were measured using immunofluorescence. Notice that FL and ΔKD rescued YAP levels that were reduced by shSTK40. shCTRL, control shRNA; YFP, control vector. ( D ) Top: SAS cells with STK40 knockdown (shSTK40) were treated with cycloheximide. Their YAP protein was collected at different time points after cycloheximide treatment and measured using Western blots. Bottom: Quantification of the above results. Note that shSTK40 facilitated YAP degradation. ( E ) Representative images and quantification of FA in SAS cells with shSTK40 and treated with VP and/or shCREB. Note that shSTK40 and VP abolished effects of shCREB. Error bars denote means ± SEM. * P < 0.05. ( F ) Working models depict how STK40 and MAPK collaboratively regulate YAP activities (left) and how STK40 plus MAPK suppression causes synthetic dysmobility (right).

Article Snippet: The MAPK kinase (MEK) inhibitor trametinib enhanced FA in SAS cells similarly to shSTK40 ( ).

Techniques: Knockdown, Construct, Immunofluorescence, Control, shRNA, Plasmid Preparation, Western Blot

Journal: International Journal of Molecular Sciences

Article Title: Recent Advances in Fragment-Based QSAR and Multi-Dimensional QSAR Methods

doi: 10.3390/ijms11103846

Figure Lengend Snippet: Summary of different QSAR methods and source information.

Article Snippet: 4D-QSAR , 4D , 20 DHFR inhibitors; 42 PGF 2 a analogs; 40 2-substituted dipyridodiazepione inhibitors 33 p38-MAPK inhibitors , PLS GL-PLS , r 2 = [0.90, 0.95]; r 2 = [0.73, 0.86]; r 2 = [0.67, 0.76] [ ] q 2 = [0.67, 0.85] [64] , [ ] http://www.seascapelearning.com/4DsgiSW/ [64] .

Techniques: Pesticides, Standard Deviation