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MedChemExpress skf 86002
Skf 86002, supplied by MedChemExpress, used in various techniques. Bioz Stars score: 92/100, based on 4 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
https://www.bioz.com/product/skf+86002/SKF-86002/pm39393507-96-12-15
Average 92 stars, based on 4 article reviews

skf 86002 - by Bioz Stars, 2026-11

92/100 stars

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Injection:

Article Title: Blockage of p38MAPK in astrocytes alleviates brain damage in a mouse model of embolic stroke through the CX43/AQP4 axis.
Article Snippet: Background: Cerebral edema, a significant complication arising from acute ischemic stroke (IS), has a critical influence on morbidity and mortality. p38MAPK has been shown to promote neuronal apoptosis and brain damage.. However, the role of the p38MAPK inhibitor SKF-86002 in protecting against ischemic injury and cerebral edema remains unclear.. Methods: Infarct area was examined by TTC staining in middle cerebral artery occlusion (MCAO) mice.

Article Title: Inhibition of p38α MAPK restores neuronal p38γ MAPK and ameliorates synaptic degeneration in a mouse model of DLB/PD
Article Snippet: .. Both non-tg and α-syn tg mice were treated with SKF-86002 (20 mg/kg; MedChemExpress, Monmouth Junction, NJ), which was dissolved in 10% dimethyl sulfoxide (DMSO) (non-tg, n = 6; α-syn tg, n = 5 for cohort 1; non-tg, n = 10; α-syn tg, n = 8 for cohort 2) or vehicle control 10% DMSO (vehicle) (non-tg, n = 7; α-syn tg, n = 6 for cohort 1; non-tg, n = 9; α-syn tg, n = 9 for cohort 2) and administered five times per week for 12 weeks by intraperitoneal injection. ..

Control:

Image Search Results

A Schematic illustration of drug administration during ligature. B Representative 3D micro-CT images of murine upper molars and alveolar bone in the vehicle, Lip-1, and erastin groups. Scale bar, 1 mm. C Quantification of the distance between the cementum enamel junction and alveolar bone crest (CEJ-ABC distance). D The bone volume over total volume (BV/TV), trabecular number (Tb.N), trabecular thickness (Tb.Th), and trabecular spacing (Tb.Sp) of the ROIs in the maxillary alveolar bone on the ligature side. E Representative images of H&E-stained sagittal sections of the upper first molars on the ligature side and magnified views of the gingiva and alveolar bone distal to the upper first molar. The green arrows indicate inflammatory cells. The blue arrows indicate empty osteocyte lacunae. Scale bar, 200 μm (panoramic view)/50 μm (magnified view). F Representative TUNEL staining of dead cells in distal regions of upper first molars. Magnified views of the gingiva or alveolar bone are shown in the yellow or orange frames, respectively. Scale bar, 100 μm (panoramic view)/10 μm (magnified view). G Representative immunofluorescence images of 4-HNE, GPX4, and TfR1 expression in distal regions of the upper first molars. Scale bar, 100 μm. H The percentage of TUNEL-positive cells was quantified. I Quantification of the mean fluorescence intensity of 4-HNE, GPX4, and TfR1 in the alveolar bone of the vehicle, Lip-1, and erastin groups. G gingiva, AB alveolar bone, P periodontal ligament, D dentin, DP dental pulp. The data are shown as the means ± SDs; n = 3 mice; ns not significant; * P < 0.05; ** P < 0.01; *** P < 0.001; **** P < 0.0001.

Journal: Cell Death Discovery

Article Title: Unraveling ferroptosis in osteogenic lineages: implications for dysregulated bone remodeling during periodontitis progression

doi: 10.1038/s41420-024-01969-6

Figure Lengend Snippet: A Schematic illustration of drug administration during ligature. B Representative 3D micro-CT images of murine upper molars and alveolar bone in the vehicle, Lip-1, and erastin groups. Scale bar, 1 mm. C Quantification of the distance between the cementum enamel junction and alveolar bone crest (CEJ-ABC distance). D The bone volume over total volume (BV/TV), trabecular number (Tb.N), trabecular thickness (Tb.Th), and trabecular spacing (Tb.Sp) of the ROIs in the maxillary alveolar bone on the ligature side. E Representative images of H&E-stained sagittal sections of the upper first molars on the ligature side and magnified views of the gingiva and alveolar bone distal to the upper first molar. The green arrows indicate inflammatory cells. The blue arrows indicate empty osteocyte lacunae. Scale bar, 200 μm (panoramic view)/50 μm (magnified view). F Representative TUNEL staining of dead cells in distal regions of upper first molars. Magnified views of the gingiva or alveolar bone are shown in the yellow or orange frames, respectively. Scale bar, 100 μm (panoramic view)/10 μm (magnified view). G Representative immunofluorescence images of 4-HNE, GPX4, and TfR1 expression in distal regions of the upper first molars. Scale bar, 100 μm. H The percentage of TUNEL-positive cells was quantified. I Quantification of the mean fluorescence intensity of 4-HNE, GPX4, and TfR1 in the alveolar bone of the vehicle, Lip-1, and erastin groups. G gingiva, AB alveolar bone, P periodontal ligament, D dentin, DP dental pulp. The data are shown as the means ± SDs; n = 3 mice; ns not significant; * P < 0.05; ** P < 0.01; *** P < 0.001; **** P < 0.0001.

Article Snippet: Once the ligature was placed (Day 0), 10 mg/kg Lip-1 (T2367, TargetMOI), 30 mg/kg Erastin (T1765, TargetMOI), or an equal volume of vehicle was injected intraperitoneally once every other day over the 10-day period.

Techniques: Micro-CT, Staining, TUNEL Assay, Immunofluorescence, Expressing, Fluorescence

A Representative immunofluorescence images showing RANKL expression in distal regions of upper first molars in the vehicle, Lip-1, and erastin groups. The lower panel shows magnified views of the boxed areas in the upper panel. Scale bar, 50 μm. B Quantification of the mean fluorescence intensity of RANKL in the alveolar bone. C Representative immunofluorescence images of RUNX2 expression in distal regions of upper first molars. The lower panel shows magnified views of the boxed areas in the upper panel. Scale bar, 50 μm (panoramic view)/10 μm (magnified view). D Quantification of the mean fluorescence intensity of RUNX2 in alveolar bone. E Representative images of TRAP staining in the vehicle, Lip-1, and erastin groups. Magnified views of alveolar bone in the interradicular region or distal alveolar bone are shown in the blue or red frames, respectively. The white arrows indicate TRAP-positive cells. Scale bar, 200 μm (panoramic view)/40 μm (magnified view). F Quantification of TRAP-positive cells per mm of bone surface. G gingiva, AB alveolar bone. The data are shown as the means ± SDs; n = 3 mice; * P < 0.05; ** P < 0.01; *** P < 0.001; **** P < 0.0001.

Journal: Cell Death Discovery

Article Title: Unraveling ferroptosis in osteogenic lineages: implications for dysregulated bone remodeling during periodontitis progression

doi: 10.1038/s41420-024-01969-6

Figure Lengend Snippet: A Representative immunofluorescence images showing RANKL expression in distal regions of upper first molars in the vehicle, Lip-1, and erastin groups. The lower panel shows magnified views of the boxed areas in the upper panel. Scale bar, 50 μm. B Quantification of the mean fluorescence intensity of RANKL in the alveolar bone. C Representative immunofluorescence images of RUNX2 expression in distal regions of upper first molars. The lower panel shows magnified views of the boxed areas in the upper panel. Scale bar, 50 μm (panoramic view)/10 μm (magnified view). D Quantification of the mean fluorescence intensity of RUNX2 in alveolar bone. E Representative images of TRAP staining in the vehicle, Lip-1, and erastin groups. Magnified views of alveolar bone in the interradicular region or distal alveolar bone are shown in the blue or red frames, respectively. The white arrows indicate TRAP-positive cells. Scale bar, 200 μm (panoramic view)/40 μm (magnified view). F Quantification of TRAP-positive cells per mm of bone surface. G gingiva, AB alveolar bone. The data are shown as the means ± SDs; n = 3 mice; * P < 0.05; ** P < 0.01; *** P < 0.001; **** P < 0.0001.

Techniques: Immunofluorescence, Expressing, Fluorescence, Staining

A TUNEL assay showing dead MLO-Y4 cells after treatment with vehicle, LPS, or LPS + Lip-1. Scale bar, 50 μm (panoramic view)/10 μm (magnified view). B Statistics of the percentage of TUNEL-positive osteocytes. C CCK-8 assay of treated MLO-Y4 cells. D C11-BODIPY staining showing nonoxidized lipids (red) and oxidized lipids (green) in treated MLO-Y4 cells. Scale bar, 10 μm. E Quantification of the mean fluorescence intensity of C11-BODIPY (green/red ratio). F Measurement of intracellular ROS levels in treated MLO-Y4 cells. G Relative mRNA expression of Slc7a11 and Ncoa4 in treated MLO-Y4 cells. H – K Western blot analysis of TfR1, RANKL, OPG, GPX4, and IL-6 expression in treated MLO-Y4 cells. L Quantification of the relative RANKL and OPG protein expression and the RANKL/OPG ratio. The data are shown as the means ± SDs; n = 3 biological replicates; ns not significant; * P < 0.05; ** P < 0.01; *** P < 0.001; **** P < 0.0001.

Journal: Cell Death Discovery

Article Title: Unraveling ferroptosis in osteogenic lineages: implications for dysregulated bone remodeling during periodontitis progression

doi: 10.1038/s41420-024-01969-6

Figure Lengend Snippet: A TUNEL assay showing dead MLO-Y4 cells after treatment with vehicle, LPS, or LPS + Lip-1. Scale bar, 50 μm (panoramic view)/10 μm (magnified view). B Statistics of the percentage of TUNEL-positive osteocytes. C CCK-8 assay of treated MLO-Y4 cells. D C11-BODIPY staining showing nonoxidized lipids (red) and oxidized lipids (green) in treated MLO-Y4 cells. Scale bar, 10 μm. E Quantification of the mean fluorescence intensity of C11-BODIPY (green/red ratio). F Measurement of intracellular ROS levels in treated MLO-Y4 cells. G Relative mRNA expression of Slc7a11 and Ncoa4 in treated MLO-Y4 cells. H – K Western blot analysis of TfR1, RANKL, OPG, GPX4, and IL-6 expression in treated MLO-Y4 cells. L Quantification of the relative RANKL and OPG protein expression and the RANKL/OPG ratio. The data are shown as the means ± SDs; n = 3 biological replicates; ns not significant; * P < 0.05; ** P < 0.01; *** P < 0.001; **** P < 0.0001.

Techniques: TUNEL Assay, CCK-8 Assay, Staining, Fluorescence, Expressing, Western Blot

$( A ) Concentration of SKF in the blood and brain of the non-tg mouse was determined by pharmacokinetic analysis ( n = 3 per group). ( B to D ) Immunoblot analysis of non-tg mice brain homogenates administrated with indicated amounts of SKF is shown. Cytosolic (B) and particulate (C) fractions were probed with phosphor-Atf2 (p-Atf2), total Atf2, and β-actin. Whole brain lysates (D) were probed with phosphor-p38 (p-p38), total p38, and β-actin. Phosphor-Atf2 and phosphor-p38 band intensities were determined by densitometric quantification and normalized to total Atf2 and p38, respectively. Data are means ± SEM. * P < 0.05, ** P < 0.01, and **** P < 0.0001 (one-way ANOVA with Tukey’s multiple comparison post hoc test). n = 3 per group. ( E ) Immunoblot analysis of p38 kinase assay is shown. Human recombinant ATF2 was incubated with non-tg mouse brain homogenate in the presence and absence of ATP and SKF. The blot was probed with phosphor-ATF2 and total ATF2. ( F to J ) Immunoblot analysis of non-tg and α-syn tg mice administrated with either vehicle (Veh) or SKF. Whole brain lysates (F) and cytosolic/particulate fractions (G) were probed with phosphor-Atf2, total Atf2, phosphor-p38, and β-actin. Phosphor-Atf2 (H) and phosphor-p38 (I and J) band intensities were determined by densitometric quantification. Phosphor-Atf2 and phosphor-p38 were normalized to total Atf2 and β-actin, respectively. Data are means ± SEM. * P < 0.05 (two-way ANOVAwith Tukey’s multiple comparison post hoc test). n = 4 per group. ( K ) Representative images from immunohistochemical analysis for phosphor-Atf2 in the neocortices of injected mice are shown. Scale bar, 10 μm.$

Journal: Science translational medicine

Article Title: Inhibition of p38α MAPK restores neuronal p38γ MAPK and ameliorates synaptic degeneration in a mouse model of DLB/PD

doi: 10.1126/scitranslmed.abq6089

Figure Lengend Snippet: ( A ) Concentration of SKF in the blood and brain of the non-tg mouse was determined by pharmacokinetic analysis ( n = 3 per group). ( B to D ) Immunoblot analysis of non-tg mice brain homogenates administrated with indicated amounts of SKF is shown. Cytosolic (B) and particulate (C) fractions were probed with phosphor-Atf2 (p-Atf2), total Atf2, and β-actin. Whole brain lysates (D) were probed with phosphor-p38 (p-p38), total p38, and β-actin. Phosphor-Atf2 and phosphor-p38 band intensities were determined by densitometric quantification and normalized to total Atf2 and p38, respectively. Data are means ± SEM. * P < 0.05, ** P < 0.01, and **** P < 0.0001 (one-way ANOVA with Tukey’s multiple comparison post hoc test). n = 3 per group. ( E ) Immunoblot analysis of p38 kinase assay is shown. Human recombinant ATF2 was incubated with non-tg mouse brain homogenate in the presence and absence of ATP and SKF. The blot was probed with phosphor-ATF2 and total ATF2. ( F to J ) Immunoblot analysis of non-tg and α-syn tg mice administrated with either vehicle (Veh) or SKF. Whole brain lysates (F) and cytosolic/particulate fractions (G) were probed with phosphor-Atf2, total Atf2, phosphor-p38, and β-actin. Phosphor-Atf2 (H) and phosphor-p38 (I and J) band intensities were determined by densitometric quantification. Phosphor-Atf2 and phosphor-p38 were normalized to total Atf2 and β-actin, respectively. Data are means ± SEM. * P < 0.05 (two-way ANOVAwith Tukey’s multiple comparison post hoc test). n = 4 per group. ( K ) Representative images from immunohistochemical analysis for phosphor-Atf2 in the neocortices of injected mice are shown. Scale bar, 10 μm.

Article Snippet: Both non-tg and α-syn tg mice were treated with SKF-86002 (20 mg/kg; MedChemExpress, Monmouth Junction, NJ), which was dissolved in 10% dimethyl sulfoxide (DMSO) (non-tg, n = 6; α-syn tg, n = 5 for cohort 1; non-tg, n = 10; α-syn tg, n = 8 for cohort 2) or vehicle control 10% DMSO (vehicle) (non-tg, n = 7; α-syn tg, n = 6 for cohort 1; non-tg, n = 9; α-syn tg, n = 9 for cohort 2) and administered five times per week for 12 weeks by intraperitoneal injection.

Techniques: Drug discovery, Concentration Assay, Western Blot, Comparison, Kinase Assay, Recombinant, Incubation, Immunohistochemical staining, Injection

Non-tg and α-syn tg mice were injected with vehicle or SKF (20 mg/kg) five times weekly for 12 weeks. ( A ) Representative images from immunohistochemical stainings for p38α in the neocortices, hippocampi, and striata of injected mice are shown. Scale bars, 250 μm (low magnification) and 25 μm (high magnification). ( B to D ) Percentage of p38α-positive cell area was analyzed in the neocortices (Ctx) (B), hippocampi (HP) (C), and striata (ST) (D) of the mice. Data are means ± SEM. *** P < 0.001 and **** P < 0.0001 (two-way ANOVA with Tukey’s multiple comparison post hoc test). n = 6 for non-tg + Veh, n = 7 for non-tg + SKF, n = 5 for α-syn tg + Veh, and n = 6 for α-syn tg + SKF. ( E ) Representative images from immunohistochemical analysis for Gfap in the neocortices, hippocampi, and striata of injected mice are shown. Scale bars, 250 μm (low magnification) and 25 μm (high magnification). ( F to H ) Optical density of Gfap immunoreactivity was analyzed in the neocortices (F), hippocampi (G), and striata (H) of the mice. Data are means ± SEM. * P < 0.05, ** P < 0.01, and **** P < 0.0001 (two-way ANOVA with Tukey’s multiple comparison post hoc test). n = 6 for non-tg + Veh, n = 7 for non-tg + SKF, n = 5 for α-syn tg + Veh, and n = 6 for α-syn tg + SKF. ( I ) Representative images from immunohistochemical stainings for Iba-1 in the neocortices, hippocampi, and striata of injected mice are shown. Scale bars, 250 μm (low magnification) and 25 μm (high magnification). ( J to L ) Number of Iba-1–positive cells was analyzed in the neocortices (J), hippocampi (K), and striata (L) of the mice. Data are means ± SEM. * P < 0.05 and ** P < 0.01 (two-way ANOVA with Tukey’s multiple comparison post hoc test). n = 6 for non-tg + Veh, n = 7 for non-tg + SKF, n = 5 for α-syn tg + Veh, and n = 6 for α-syn tg–SKF. ( M to Q ) Quantitative gene expression analysis from the brains of mice injected with vehicle or SKF. Expressions of Tnf (M), Il-6 (N), Il-13 (O), Cxcl1 (P), and Ccl2 (Q) were analyzed by quantitative PCR. Data are means ± SEM. * P < 0.05, ** P < 0.01, *** P < 0.001, and **** P < 0.0001 (two-way ANOVA with Tukey’s multiple comparison post hoc test). n = 7 for non-tg + Veh, n = 6 for non-tg + SKF, n = 5 for α-syn tg + Veh, and n = 6 for α-syn tg + SKF.

Journal: Science translational medicine

Article Title: Inhibition of p38α MAPK restores neuronal p38γ MAPK and ameliorates synaptic degeneration in a mouse model of DLB/PD

doi: 10.1126/scitranslmed.abq6089

Figure Lengend Snippet: Non-tg and α-syn tg mice were injected with vehicle or SKF (20 mg/kg) five times weekly for 12 weeks. ( A ) Representative images from immunohistochemical stainings for p38α in the neocortices, hippocampi, and striata of injected mice are shown. Scale bars, 250 μm (low magnification) and 25 μm (high magnification). ( B to D ) Percentage of p38α-positive cell area was analyzed in the neocortices (Ctx) (B), hippocampi (HP) (C), and striata (ST) (D) of the mice. Data are means ± SEM. *** P < 0.001 and **** P < 0.0001 (two-way ANOVA with Tukey’s multiple comparison post hoc test). n = 6 for non-tg + Veh, n = 7 for non-tg + SKF, n = 5 for α-syn tg + Veh, and n = 6 for α-syn tg + SKF. ( E ) Representative images from immunohistochemical analysis for Gfap in the neocortices, hippocampi, and striata of injected mice are shown. Scale bars, 250 μm (low magnification) and 25 μm (high magnification). ( F to H ) Optical density of Gfap immunoreactivity was analyzed in the neocortices (F), hippocampi (G), and striata (H) of the mice. Data are means ± SEM. * P < 0.05, ** P < 0.01, and **** P < 0.0001 (two-way ANOVA with Tukey’s multiple comparison post hoc test). n = 6 for non-tg + Veh, n = 7 for non-tg + SKF, n = 5 for α-syn tg + Veh, and n = 6 for α-syn tg + SKF. ( I ) Representative images from immunohistochemical stainings for Iba-1 in the neocortices, hippocampi, and striata of injected mice are shown. Scale bars, 250 μm (low magnification) and 25 μm (high magnification). ( J to L ) Number of Iba-1–positive cells was analyzed in the neocortices (J), hippocampi (K), and striata (L) of the mice. Data are means ± SEM. * P < 0.05 and ** P < 0.01 (two-way ANOVA with Tukey’s multiple comparison post hoc test). n = 6 for non-tg + Veh, n = 7 for non-tg + SKF, n = 5 for α-syn tg + Veh, and n = 6 for α-syn tg–SKF. ( M to Q ) Quantitative gene expression analysis from the brains of mice injected with vehicle or SKF. Expressions of Tnf (M), Il-6 (N), Il-13 (O), Cxcl1 (P), and Ccl2 (Q) were analyzed by quantitative PCR. Data are means ± SEM. * P < 0.05, ** P < 0.01, *** P < 0.001, and **** P < 0.0001 (two-way ANOVA with Tukey’s multiple comparison post hoc test). n = 7 for non-tg + Veh, n = 6 for non-tg + SKF, n = 5 for α-syn tg + Veh, and n = 6 for α-syn tg + SKF.

Techniques: Injection, Immunohistochemical staining, Comparison, Gene Expression, Real-time Polymerase Chain Reaction

Primary microglia from WT mice were pretreated with control, SKF, p38 MAPK inhibitor IV (IV), VX-745 (VX), SB 706504 (SB), or DBM 1285 (DBM) for 30 min, followed by challenge with LZCM (control) or αSCM for 2 hours. Microglial cytokine gene expression was determined by quantitative PCR. ( A ) Schematic illustration of experiment procedure. ( B to D ) Expressions of Il-1 β (B), Il-6 (C), and Il-10 (D) were analyzed by quantitative PCR. Data are means ± SEM. **** P < 0.0001 (two-way ANOVA with Tukey’s multiple comparison post hoc test). n = 6 per group.

Journal: Science translational medicine

Article Title: Inhibition of p38α MAPK restores neuronal p38γ MAPK and ameliorates synaptic degeneration in a mouse model of DLB/PD

doi: 10.1126/scitranslmed.abq6089

Figure Lengend Snippet: Primary microglia from WT mice were pretreated with control, SKF, p38 MAPK inhibitor IV (IV), VX-745 (VX), SB 706504 (SB), or DBM 1285 (DBM) for 30 min, followed by challenge with LZCM (control) or αSCM for 2 hours. Microglial cytokine gene expression was determined by quantitative PCR. ( A ) Schematic illustration of experiment procedure. ( B to D ) Expressions of Il-1 β (B), Il-6 (C), and Il-10 (D) were analyzed by quantitative PCR. Data are means ± SEM. **** P < 0.0001 (two-way ANOVA with Tukey’s multiple comparison post hoc test). n = 6 per group.

Techniques: Gene Expression, Control, Real-time Polymerase Chain Reaction, Comparison

$Non-tg and α-syn tg mice were injected with vehicle or SKF (20 mg/kg) five times weekly for 12 weeks. ( A ) Representative images from immunohistochemical stainings for p38γ in the neocortices, hippocampi, and striata of injected mice. Scale bars, 250 μm (low magnification) and 25 μm (high magnification). ( B to D ) Percentage of p38γ-positive neuropil area analyzed in the neocortices (B), hippocampi (C), and striata (D) of injected mice. ( E to G ) Percentage of p38γ-positive cell area analyzed in the neocortices (E), hippocampi (F), and striata (G) of injected mice. Data are means ± SEM. * P < 0.05, ** P < 0.01, *** P < 0.001, and **** P < 0.0001 (two-way ANOVAwith Tukey’s multiple comparison post hoc test). n = 6 for non-tg + Veh, n = 7 for non-tg + SKF, n = 5 for α-syn tg + Veh, and n = 6 for α-syn tg + SKF. ( H to J ) Immunoblot analysis of injected mice. Cytosolic and particulate fractions were probed with total p38γ and β-actin (H). Cytosolic (I) and particulate (J) total p38γ band intensity was determined by densitometric quantification and normalized to β-actin. Data are means ± SEM. * P < 0.05 and ** P < 0.01 (two-way ANOVA with Tukey’s multiple comparison post hoc test). n = 4 per group.$

Journal: Science translational medicine

Article Title: Inhibition of p38α MAPK restores neuronal p38γ MAPK and ameliorates synaptic degeneration in a mouse model of DLB/PD

doi: 10.1126/scitranslmed.abq6089

Techniques: Expressing, Injection, Immunohistochemical staining, Comparison, Western Blot

$Non-tg and α-syn tg mice were injected with vehicle or SKF (20 mg/kg) five times weekly for 12 weeks. ( A ) Representative images from immunohistochemical stainings for α-syn in the neocortices, hippocampi, and striata of injected mice are shown. Scale bars, 250 μm (low magnification) and 25 μm (high magnification). ( B to D ) Percentage of α-syn–positive neuropil area analyzed in the neocortices (B), hippocampi (C), and striata (D) of injected mice. ( E to G ) Number of α-syn–positive cells analyzed in the neocortices (E), hippocampi (F), and striata (G) of injected mice. Data are means ± SEM. * P < 0.05, ** P < 0.01, *** P < 0.001, and **** P < 0.0001 (two-way ANOVA with Tukey’s multiple comparison post hoc test). n = 6 for non-tg + Veh, n = 7 for non-tg + SKF, n = 5 for α-syn tg + Veh, and n = 6 for α-syn tg + SKF. ( H to J ) Immunoblot analysis of injected mice. (H) Whole brain lysates were probed with α-syn and β-actin. Band intensities of monomeric (I) and oligomeric (J) α-syn were determined by densitometric quantification and normalized to β-actin. Data are means ± SEM. ** P < 0.01 and **** P < 0.0001 (two-way ANOVA with Tukey’s multiple comparison post hoc test). n = 4 per group. ( K and L ) Amounts of human α-syn in cytosolic (K) and particulate (L) fractions were determined by ELISA. Data are means ± SEM. ** P < 0.01 (unpaired two-tailed Student’s t test). n = 6 per group. ( M and N ) Representative images from double immunostaining analysis for p38γ with synaptophysin (M) and p38γ with α-syn (N) in the neocortices of injected mice. Scale bars, 10 μm (low magnification) and 5 μm (high magnification). ( O and P ) Percentages of p38γ/synaptophysin– (O) and p38γ/α-syn (P)–positive cells were analyzed in the neocortices of the injected mice. Data are means ± SEM. * P < 0.05, *** P < 0.001, and **** P < 0.0001 (two-way ANOVA with Tukey’s multiple comparison post hoc test). n = 4 per group.$

Journal: Science translational medicine

Article Title: Inhibition of p38α MAPK restores neuronal p38γ MAPK and ameliorates synaptic degeneration in a mouse model of DLB/PD

doi: 10.1126/scitranslmed.abq6089

Figure Lengend Snippet: Non-tg and α-syn tg mice were injected with vehicle or SKF (20 mg/kg) five times weekly for 12 weeks. ( A ) Representative images from immunohistochemical stainings for α-syn in the neocortices, hippocampi, and striata of injected mice are shown. Scale bars, 250 μm (low magnification) and 25 μm (high magnification). ( B to D ) Percentage of α-syn–positive neuropil area analyzed in the neocortices (B), hippocampi (C), and striata (D) of injected mice. ( E to G ) Number of α-syn–positive cells analyzed in the neocortices (E), hippocampi (F), and striata (G) of injected mice. Data are means ± SEM. * P < 0.05, ** P < 0.01, *** P < 0.001, and **** P < 0.0001 (two-way ANOVA with Tukey’s multiple comparison post hoc test). n = 6 for non-tg + Veh, n = 7 for non-tg + SKF, n = 5 for α-syn tg + Veh, and n = 6 for α-syn tg + SKF. ( H to J ) Immunoblot analysis of injected mice. (H) Whole brain lysates were probed with α-syn and β-actin. Band intensities of monomeric (I) and oligomeric (J) α-syn were determined by densitometric quantification and normalized to β-actin. Data are means ± SEM. ** P < 0.01 and **** P < 0.0001 (two-way ANOVA with Tukey’s multiple comparison post hoc test). n = 4 per group. ( K and L ) Amounts of human α-syn in cytosolic (K) and particulate (L) fractions were determined by ELISA. Data are means ± SEM. ** P < 0.01 (unpaired two-tailed Student’s t test). n = 6 per group. ( M and N ) Representative images from double immunostaining analysis for p38γ with synaptophysin (M) and p38γ with α-syn (N) in the neocortices of injected mice. Scale bars, 10 μm (low magnification) and 5 μm (high magnification). ( O and P ) Percentages of p38γ/synaptophysin– (O) and p38γ/α-syn (P)–positive cells were analyzed in the neocortices of the injected mice. Data are means ± SEM. * P < 0.05, *** P < 0.001, and **** P < 0.0001 (two-way ANOVA with Tukey’s multiple comparison post hoc test). n = 4 per group.

Techniques: Injection, Immunohistochemical staining, Comparison, Western Blot, Enzyme-linked Immunosorbent Assay, Two Tailed Test, Double Immunostaining

Journal: Science translational medicine

Article Title: Inhibition of p38α MAPK restores neuronal p38γ MAPK and ameliorates synaptic degeneration in a mouse model of DLB/PD

doi: 10.1126/scitranslmed.abq6089

Techniques: Injection, Immunohistochemical staining, Comparison

Healthy control and A53T-mutant patient–derived human iPSC neurons and glia mixed cultures were treated with low (1 μM) or high (50 μM) concentrations of SKF. After 1 or 18 hours of incubation, the cells were analyzed by double immunostaining analysis. ( A and B ) Representative images from double immunostaining analysis of p38γ and α-syn in SKF-treated cells after 1 hour (A) and 18 hours (B) of incubations. Arrows indicate neurites. Scale bars, 50 μm (low magnification) and 25 μm (high magnification). ( C and D ) Pixel intensity of p38γ in the cell body (C) and percentage of α-syn–positive neurite area (D) were analyzed. **** P < 0.0001 (unpaired two-tailed Student’s t test). n = 8 per group. ( E and F ) Representative images from double immunostaining of synaptophysin and Map2 in SKF-treated cells after 1 hour (E) and 18 hours (F) of incubations. Scale bars, 50 μm (low magnification) and 25 μm (high magnification). ( G and H ) Percentages of synaptophysin-positive (G) and Map2-positive (H) area are analyzed. * P < 0.05 and ** P < 0.01 (unpaired two-tailed Student’s t test). n = 8 per group.

Journal: Science translational medicine

Article Title: Inhibition of p38α MAPK restores neuronal p38γ MAPK and ameliorates synaptic degeneration in a mouse model of DLB/PD

doi: 10.1126/scitranslmed.abq6089

Figure Lengend Snippet: Healthy control and A53T-mutant patient–derived human iPSC neurons and glia mixed cultures were treated with low (1 μM) or high (50 μM) concentrations of SKF. After 1 or 18 hours of incubation, the cells were analyzed by double immunostaining analysis. ( A and B ) Representative images from double immunostaining analysis of p38γ and α-syn in SKF-treated cells after 1 hour (A) and 18 hours (B) of incubations. Arrows indicate neurites. Scale bars, 50 μm (low magnification) and 25 μm (high magnification). ( C and D ) Pixel intensity of p38γ in the cell body (C) and percentage of α-syn–positive neurite area (D) were analyzed. **** P < 0.0001 (unpaired two-tailed Student’s t test). n = 8 per group. ( E and F ) Representative images from double immunostaining of synaptophysin and Map2 in SKF-treated cells after 1 hour (E) and 18 hours (F) of incubations. Scale bars, 50 μm (low magnification) and 25 μm (high magnification). ( G and H ) Percentages of synaptophysin-positive (G) and Map2-positive (H) area are analyzed. * P < 0.05 and ** P < 0.01 (unpaired two-tailed Student’s t test). n = 8 per group.

Techniques: Control, Mutagenesis, Derivative Assay, Incubation, Double Immunostaining, Two Tailed Test

( A ) Illustrated is the experimental design to obtain MgCM and to test microglial neurotoxicity. Non-tg mouse primary microglia were pretreated with either control or SKF for 30 min, followed by challenge with LZCM (control) or αSCM. After 1-hour incubation, cells were incubated with fresh neurobasal media for additional 6 hours, and cultured media were collected. ( B ) Non-tg mouse primary neurons were treated with MgCM-control, MgCM-SKF, MgCM-αSCM, or MgCM-SKF-αSCM for 18 hours. The neuronal viability was determined by CyQUANT assay. Data are means ± SEM. ** P < 0.01 and *** P < 0.001 (two-way ANOVA with Tukey’s multiple comparison post hoc test). n = 4 per group. ( C ) Non-tg mouse primary neurons were incubated with either MgCM-control or MgCM-αSCM in the presence and absence of SKF. ( D ) Neuronal viability was determined by cyquant assay. Data are means ± SEM. *** P < 0.001 (two-way ANOVA with Tukey’s multiple comparison post hoc test). n = 4 per group.

Journal: Science translational medicine

Article Title: Inhibition of p38α MAPK restores neuronal p38γ MAPK and ameliorates synaptic degeneration in a mouse model of DLB/PD

doi: 10.1126/scitranslmed.abq6089

Figure Lengend Snippet: ( A ) Illustrated is the experimental design to obtain MgCM and to test microglial neurotoxicity. Non-tg mouse primary microglia were pretreated with either control or SKF for 30 min, followed by challenge with LZCM (control) or αSCM. After 1-hour incubation, cells were incubated with fresh neurobasal media for additional 6 hours, and cultured media were collected. ( B ) Non-tg mouse primary neurons were treated with MgCM-control, MgCM-SKF, MgCM-αSCM, or MgCM-SKF-αSCM for 18 hours. The neuronal viability was determined by CyQUANT assay. Data are means ± SEM. ** P < 0.01 and *** P < 0.001 (two-way ANOVA with Tukey’s multiple comparison post hoc test). n = 4 per group. ( C ) Non-tg mouse primary neurons were incubated with either MgCM-control or MgCM-αSCM in the presence and absence of SKF. ( D ) Neuronal viability was determined by cyquant assay. Data are means ± SEM. *** P < 0.001 (two-way ANOVA with Tukey’s multiple comparison post hoc test). n = 4 per group.

Techniques: Control, Incubation, Cell Culture, CyQUANT Assay, Comparison

Figure 3. p38 MAPK functioned as the downstream of β-arrestin 2. (A) Protein levels of phosphorylated p38 MAPK in WT and β-arrestin 2 KO cells after SKF83566 treatment in 3L NSC. (B) Statistic of protein bands in different times. (C) Protein levels of phosphorylated JNK in WT and β-arrestin 2 KO cells after SKF83566 treatment. (D) Statistic of protein bands in different times. (E) Protein levels of phosphorylated ERK1/2 in WT and β-arrestin 2 KO cells after SKF83566 treatment. (F) Statistic of protein bands in different times. (G, H) The effect of SKF83566 on human NSCs proliferation in the presence of p38 MAPK inhibitors (SB203580, SKF86002). (I) The effect of SKF83566 on human NSCs proliferation in the presence of JNK inhibitor SP600125. (J) The effect of SKF83566 on human NSCs proliferation in the presence of ERK inhibitor PD98059. (K, L) The number of secondary neurospheres formed from SKF83566-treated control or p38 MAPK-knockdown NSCs. For B, D, F-J, N = 3 independent experiments. Data are mean ± SEM. ***P < .001, **P < .01, *P < .05, 2-way ANOVA, followed by Tukey’s multiple comparisons test.

Journal: Stem cells (Dayton, Ohio)

Article Title: β-Arrestin 2 and Epac2 Cooperatively Mediate DRD1-Stimulated Proliferation of Human Neural Stem Cells and Growth of Human Cerebral Organoids.

doi: 10.1093/stmcls/sxac046

Figure Lengend Snippet: Figure 3. p38 MAPK functioned as the downstream of β-arrestin 2. (A) Protein levels of phosphorylated p38 MAPK in WT and β-arrestin 2 KO cells after SKF83566 treatment in 3L NSC. (B) Statistic of protein bands in different times. (C) Protein levels of phosphorylated JNK in WT and β-arrestin 2 KO cells after SKF83566 treatment. (D) Statistic of protein bands in different times. (E) Protein levels of phosphorylated ERK1/2 in WT and β-arrestin 2 KO cells after SKF83566 treatment. (F) Statistic of protein bands in different times. (G, H) The effect of SKF83566 on human NSCs proliferation in the presence of p38 MAPK inhibitors (SB203580, SKF86002). (I) The effect of SKF83566 on human NSCs proliferation in the presence of JNK inhibitor SP600125. (J) The effect of SKF83566 on human NSCs proliferation in the presence of ERK inhibitor PD98059. (K, L) The number of secondary neurospheres formed from SKF83566-treated control or p38 MAPK-knockdown NSCs. For B, D, F-J, N = 3 independent experiments. Data are mean ± SEM. ***P < .001, **P < .01, *P < .05, 2-way ANOVA, followed by Tukey’s multiple comparisons test.

Article Snippet: SKF83566 was purchased from Tocris Bioscience; ESI-05, HJC0350, SB203580, SKF86002, PD98059, SP600125 were purchased from MedChemExpress; Cell CountingLite 2.0 Luminescent cell viability assay was purchased from Vazyme.

Techniques: Control, Knockdown

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