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Figure 5. OPA1 overexpression or activation improved Aβ clearance of microglia and synaptic plasticity (A) Representative images showing the Aβ (red) deposition in the hippocampus of APP/PS1 and APP/PS1-OPA1-OE mice. (B-C) Aβ plaque counts and areas in hippocampus were low in APP/PS1-OPA1-OE mice compared with APP/PS1 mice. n = 3 for each group. t(4) = 4.621 p=0.0099 in (B), t(4) = 4.376 p=0.0119 in (C). (D) Representative images showing the Aβ (green) deposition in the hippocampus of APP/PS1 <t>and</t> <t>BGP-15‐treated</t> APP/PS1 mice. (E-F) Aβ plaque counts and areas in hippocampus were low in BGP-15‐treated APP/PS1 mice compared with APP/PS1 mice treated with <t>DMSO.</t> n = 3 for each group. t(4) = 4.330 p=0.0123 in (E), t(4) = 4.167, p=0.0141 in (F). (G) Representative pictures showing colocalization of Aβ (magenta) with IBA-1 (red) and CD68 (green) in the hippocampus of WT, APP/PS1 and APP/PS1-OPA1-OE mice. (H) The number of microglia surrounding Aβ was higher in APP/PS1- OPA1-OE mice compared with APP/PS1 mice. n = 4 for each group. p=0.0286 (I)Representative pictures showing colocalization of Aβ (green) with IBA-1 (red) and CD68 (magenta) in the hippocampus of WT, APP/PS1 and BGP-15‐treated APP/PS1 mice. (J) The number of microglia surrounding Aβ was higher in BGP-15‐treated APP/PS1 mice compared with APP/PS1 mice. n = 3 for each group. t(4) = 5.483, p=0.0054 (K) The input–output response increased in APP/PS1-OPA1-OE mice (n=3 slices/mouse, N=3 mice/group) compared with APP/PS1 mice (n=3 slices/mouse, N=3 mice/group). F(2,22)=2.035, APP/PS1 versus WT group: p < 0.0001, APP/PS1 versus APP/PS1-OPA1-OE group: p=0.0399. (L and M) The slope of the evoked fEPSP increased in APP/PS1- OPA1-OE mice (n=3slices/mouse, N=3mice/group) compared with APP/PS1 mice during LTP induction (n=3slices/mouse, N=3mice/group). APP/PS1 versus WT group: p=0.0262, APP/PS1 versus APP/PS1-OPA1-OE group: p=0.416. (N) The input–output response increased in BGP-15‐treated APP/PS1 mice (n=2-4 slices/mouse, N=3 mice/group) compared with APP/PS1 mice treated with DMSO (n=2-4 slices/mouse, N=3 mice/group). F(2,20)=4.289, APP/PS1 versus WT group: p =0.0260, APP/PS1 versus APP/PS1+BGP15 group: p<0.0001. (O and P) The slope of the evoked fEPSP increased in BGP-15‐treated APP/PS1 mice (n=3slices/mouse, N=3mice/group) compared with APP/PS1 mice treated with DMSO during LTP induction (n=3slices/mouse, N=3mice/group). APP/PS1 versus WT group: p =0.0103, APP/PS1 versus APP/PS1+BGP15 group: p=0.0063. Unpaired two-tailed test for (B), (C), (E), (F)and(J). Mann-Whitney U test for (H), Two-way ANOVA followed by Tukey’s post hoc test for (K) and (N). Kruskal-Wallis followed by Dunn's post-hoc test for (M)and (P). *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001
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Figure 5. OPA1 overexpression or activation improved Aβ clearance of microglia and synaptic plasticity (A) Representative images showing the Aβ (red) deposition in the hippocampus of APP/PS1 and APP/PS1-OPA1-OE mice. (B-C) Aβ plaque counts and areas in hippocampus were low in APP/PS1-OPA1-OE mice compared with APP/PS1 mice. n = 3 for each group. t(4) = 4.621 p=0.0099 in (B), t(4) = 4.376 p=0.0119 in (C). (D) Representative images showing the Aβ (green) deposition in the hippocampus of APP/PS1 <t>and</t> <t>BGP-15‐treated</t> APP/PS1 mice. (E-F) Aβ plaque counts and areas in hippocampus were low in BGP-15‐treated APP/PS1 mice compared with APP/PS1 mice treated with <t>DMSO.</t> n = 3 for each group. t(4) = 4.330 p=0.0123 in (E), t(4) = 4.167, p=0.0141 in (F). (G) Representative pictures showing colocalization of Aβ (magenta) with IBA-1 (red) and CD68 (green) in the hippocampus of WT, APP/PS1 and APP/PS1-OPA1-OE mice. (H) The number of microglia surrounding Aβ was higher in APP/PS1- OPA1-OE mice compared with APP/PS1 mice. n = 4 for each group. p=0.0286 (I)Representative pictures showing colocalization of Aβ (green) with IBA-1 (red) and CD68 (magenta) in the hippocampus of WT, APP/PS1 and BGP-15‐treated APP/PS1 mice. (J) The number of microglia surrounding Aβ was higher in BGP-15‐treated APP/PS1 mice compared with APP/PS1 mice. n = 3 for each group. t(4) = 5.483, p=0.0054 (K) The input–output response increased in APP/PS1-OPA1-OE mice (n=3 slices/mouse, N=3 mice/group) compared with APP/PS1 mice (n=3 slices/mouse, N=3 mice/group). F(2,22)=2.035, APP/PS1 versus WT group: p < 0.0001, APP/PS1 versus APP/PS1-OPA1-OE group: p=0.0399. (L and M) The slope of the evoked fEPSP increased in APP/PS1- OPA1-OE mice (n=3slices/mouse, N=3mice/group) compared with APP/PS1 mice during LTP induction (n=3slices/mouse, N=3mice/group). APP/PS1 versus WT group: p=0.0262, APP/PS1 versus APP/PS1-OPA1-OE group: p=0.416. (N) The input–output response increased in BGP-15‐treated APP/PS1 mice (n=2-4 slices/mouse, N=3 mice/group) compared with APP/PS1 mice treated with DMSO (n=2-4 slices/mouse, N=3 mice/group). F(2,20)=4.289, APP/PS1 versus WT group: p =0.0260, APP/PS1 versus APP/PS1+BGP15 group: p<0.0001. (O and P) The slope of the evoked fEPSP increased in BGP-15‐treated APP/PS1 mice (n=3slices/mouse, N=3mice/group) compared with APP/PS1 mice treated with DMSO during LTP induction (n=3slices/mouse, N=3mice/group). APP/PS1 versus WT group: p =0.0103, APP/PS1 versus APP/PS1+BGP15 group: p=0.0063. Unpaired two-tailed test for (B), (C), (E), (F)and(J). Mann-Whitney U test for (H), Two-way ANOVA followed by Tukey’s post hoc test for (K) and (N). Kruskal-Wallis followed by Dunn's post-hoc test for (M)and (P). *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001
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Figure 5. OPA1 overexpression or activation improved Aβ clearance of microglia and synaptic plasticity (A) Representative images showing the Aβ (red) deposition in the hippocampus of APP/PS1 and APP/PS1-OPA1-OE mice. (B-C) Aβ plaque counts and areas in hippocampus were low in APP/PS1-OPA1-OE mice compared with APP/PS1 mice. n = 3 for each group. t(4) = 4.621 p=0.0099 in (B), t(4) = 4.376 p=0.0119 in (C). (D) Representative images showing the Aβ (green) deposition in the hippocampus of APP/PS1 <t>and</t> <t>BGP-15‐treated</t> APP/PS1 mice. (E-F) Aβ plaque counts and areas in hippocampus were low in BGP-15‐treated APP/PS1 mice compared with APP/PS1 mice treated with <t>DMSO.</t> n = 3 for each group. t(4) = 4.330 p=0.0123 in (E), t(4) = 4.167, p=0.0141 in (F). (G) Representative pictures showing colocalization of Aβ (magenta) with IBA-1 (red) and CD68 (green) in the hippocampus of WT, APP/PS1 and APP/PS1-OPA1-OE mice. (H) The number of microglia surrounding Aβ was higher in APP/PS1- OPA1-OE mice compared with APP/PS1 mice. n = 4 for each group. p=0.0286 (I)Representative pictures showing colocalization of Aβ (green) with IBA-1 (red) and CD68 (magenta) in the hippocampus of WT, APP/PS1 and BGP-15‐treated APP/PS1 mice. (J) The number of microglia surrounding Aβ was higher in BGP-15‐treated APP/PS1 mice compared with APP/PS1 mice. n = 3 for each group. t(4) = 5.483, p=0.0054 (K) The input–output response increased in APP/PS1-OPA1-OE mice (n=3 slices/mouse, N=3 mice/group) compared with APP/PS1 mice (n=3 slices/mouse, N=3 mice/group). F(2,22)=2.035, APP/PS1 versus WT group: p < 0.0001, APP/PS1 versus APP/PS1-OPA1-OE group: p=0.0399. (L and M) The slope of the evoked fEPSP increased in APP/PS1- OPA1-OE mice (n=3slices/mouse, N=3mice/group) compared with APP/PS1 mice during LTP induction (n=3slices/mouse, N=3mice/group). APP/PS1 versus WT group: p=0.0262, APP/PS1 versus APP/PS1-OPA1-OE group: p=0.416. (N) The input–output response increased in BGP-15‐treated APP/PS1 mice (n=2-4 slices/mouse, N=3 mice/group) compared with APP/PS1 mice treated with DMSO (n=2-4 slices/mouse, N=3 mice/group). F(2,20)=4.289, APP/PS1 versus WT group: p =0.0260, APP/PS1 versus APP/PS1+BGP15 group: p<0.0001. (O and P) The slope of the evoked fEPSP increased in BGP-15‐treated APP/PS1 mice (n=3slices/mouse, N=3mice/group) compared with APP/PS1 mice treated with DMSO during LTP induction (n=3slices/mouse, N=3mice/group). APP/PS1 versus WT group: p =0.0103, APP/PS1 versus APP/PS1+BGP15 group: p=0.0063. Unpaired two-tailed test for (B), (C), (E), (F)and(J). Mann-Whitney U test for (H), Two-way ANOVA followed by Tukey’s post hoc test for (K) and (N). Kruskal-Wallis followed by Dunn's post-hoc test for (M)and (P). *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001
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Figure 5. OPA1 overexpression or activation improved Aβ clearance of microglia and synaptic plasticity (A) Representative images showing the Aβ (red) deposition in the hippocampus of APP/PS1 and APP/PS1-OPA1-OE mice. (B-C) Aβ plaque counts and areas in hippocampus were low in APP/PS1-OPA1-OE mice compared with APP/PS1 mice. n = 3 for each group. t(4) = 4.621 p=0.0099 in (B), t(4) = 4.376 p=0.0119 in (C). (D) Representative images showing the Aβ (green) deposition in the hippocampus of APP/PS1 <t>and</t> <t>BGP-15‐treated</t> APP/PS1 mice. (E-F) Aβ plaque counts and areas in hippocampus were low in BGP-15‐treated APP/PS1 mice compared with APP/PS1 mice treated with <t>DMSO.</t> n = 3 for each group. t(4) = 4.330 p=0.0123 in (E), t(4) = 4.167, p=0.0141 in (F). (G) Representative pictures showing colocalization of Aβ (magenta) with IBA-1 (red) and CD68 (green) in the hippocampus of WT, APP/PS1 and APP/PS1-OPA1-OE mice. (H) The number of microglia surrounding Aβ was higher in APP/PS1- OPA1-OE mice compared with APP/PS1 mice. n = 4 for each group. p=0.0286 (I)Representative pictures showing colocalization of Aβ (green) with IBA-1 (red) and CD68 (magenta) in the hippocampus of WT, APP/PS1 and BGP-15‐treated APP/PS1 mice. (J) The number of microglia surrounding Aβ was higher in BGP-15‐treated APP/PS1 mice compared with APP/PS1 mice. n = 3 for each group. t(4) = 5.483, p=0.0054 (K) The input–output response increased in APP/PS1-OPA1-OE mice (n=3 slices/mouse, N=3 mice/group) compared with APP/PS1 mice (n=3 slices/mouse, N=3 mice/group). F(2,22)=2.035, APP/PS1 versus WT group: p < 0.0001, APP/PS1 versus APP/PS1-OPA1-OE group: p=0.0399. (L and M) The slope of the evoked fEPSP increased in APP/PS1- OPA1-OE mice (n=3slices/mouse, N=3mice/group) compared with APP/PS1 mice during LTP induction (n=3slices/mouse, N=3mice/group). APP/PS1 versus WT group: p=0.0262, APP/PS1 versus APP/PS1-OPA1-OE group: p=0.416. (N) The input–output response increased in BGP-15‐treated APP/PS1 mice (n=2-4 slices/mouse, N=3 mice/group) compared with APP/PS1 mice treated with DMSO (n=2-4 slices/mouse, N=3 mice/group). F(2,20)=4.289, APP/PS1 versus WT group: p =0.0260, APP/PS1 versus APP/PS1+BGP15 group: p<0.0001. (O and P) The slope of the evoked fEPSP increased in BGP-15‐treated APP/PS1 mice (n=3slices/mouse, N=3mice/group) compared with APP/PS1 mice treated with DMSO during LTP induction (n=3slices/mouse, N=3mice/group). APP/PS1 versus WT group: p =0.0103, APP/PS1 versus APP/PS1+BGP15 group: p=0.0063. Unpaired two-tailed test for (B), (C), (E), (F)and(J). Mann-Whitney U test for (H), Two-way ANOVA followed by Tukey’s post hoc test for (K) and (N). Kruskal-Wallis followed by Dunn's post-hoc test for (M)and (P). *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001
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Figure 5. OPA1 overexpression or activation improved Aβ clearance of microglia and synaptic plasticity (A) Representative images showing the Aβ (red) deposition in the hippocampus of APP/PS1 and APP/PS1-OPA1-OE mice. (B-C) Aβ plaque counts and areas in hippocampus were low in APP/PS1-OPA1-OE mice compared with APP/PS1 mice. n = 3 for each group. t(4) = 4.621 p=0.0099 in (B), t(4) = 4.376 p=0.0119 in (C). (D) Representative images showing the Aβ (green) deposition in the hippocampus of APP/PS1 and BGP-15‐treated APP/PS1 mice. (E-F) Aβ plaque counts and areas in hippocampus were low in BGP-15‐treated APP/PS1 mice compared with APP/PS1 mice treated with DMSO. n = 3 for each group. t(4) = 4.330 p=0.0123 in (E), t(4) = 4.167, p=0.0141 in (F). (G) Representative pictures showing colocalization of Aβ (magenta) with IBA-1 (red) and CD68 (green) in the hippocampus of WT, APP/PS1 and APP/PS1-OPA1-OE mice. (H) The number of microglia surrounding Aβ was higher in APP/PS1- OPA1-OE mice compared with APP/PS1 mice. n = 4 for each group. p=0.0286 (I)Representative pictures showing colocalization of Aβ (green) with IBA-1 (red) and CD68 (magenta) in the hippocampus of WT, APP/PS1 and BGP-15‐treated APP/PS1 mice. (J) The number of microglia surrounding Aβ was higher in BGP-15‐treated APP/PS1 mice compared with APP/PS1 mice. n = 3 for each group. t(4) = 5.483, p=0.0054 (K) The input–output response increased in APP/PS1-OPA1-OE mice (n=3 slices/mouse, N=3 mice/group) compared with APP/PS1 mice (n=3 slices/mouse, N=3 mice/group). F(2,22)=2.035, APP/PS1 versus WT group: p < 0.0001, APP/PS1 versus APP/PS1-OPA1-OE group: p=0.0399. (L and M) The slope of the evoked fEPSP increased in APP/PS1- OPA1-OE mice (n=3slices/mouse, N=3mice/group) compared with APP/PS1 mice during LTP induction (n=3slices/mouse, N=3mice/group). APP/PS1 versus WT group: p=0.0262, APP/PS1 versus APP/PS1-OPA1-OE group: p=0.416. (N) The input–output response increased in BGP-15‐treated APP/PS1 mice (n=2-4 slices/mouse, N=3 mice/group) compared with APP/PS1 mice treated with DMSO (n=2-4 slices/mouse, N=3 mice/group). F(2,20)=4.289, APP/PS1 versus WT group: p =0.0260, APP/PS1 versus APP/PS1+BGP15 group: p<0.0001. (O and P) The slope of the evoked fEPSP increased in BGP-15‐treated APP/PS1 mice (n=3slices/mouse, N=3mice/group) compared with APP/PS1 mice treated with DMSO during LTP induction (n=3slices/mouse, N=3mice/group). APP/PS1 versus WT group: p =0.0103, APP/PS1 versus APP/PS1+BGP15 group: p=0.0063. Unpaired two-tailed test for (B), (C), (E), (F)and(J). Mann-Whitney U test for (H), Two-way ANOVA followed by Tukey’s post hoc test for (K) and (N). Kruskal-Wallis followed by Dunn's post-hoc test for (M)and (P). *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001

Journal: aging and disease

Article Title: OPA1 Enhances Microglial Amyloid-β Clearance and Alleviates Cognitive Impairments in an Alzheimer’s Disease Model

doi: 10.14336/ad.2025.0082

Figure Lengend Snippet: Figure 5. OPA1 overexpression or activation improved Aβ clearance of microglia and synaptic plasticity (A) Representative images showing the Aβ (red) deposition in the hippocampus of APP/PS1 and APP/PS1-OPA1-OE mice. (B-C) Aβ plaque counts and areas in hippocampus were low in APP/PS1-OPA1-OE mice compared with APP/PS1 mice. n = 3 for each group. t(4) = 4.621 p=0.0099 in (B), t(4) = 4.376 p=0.0119 in (C). (D) Representative images showing the Aβ (green) deposition in the hippocampus of APP/PS1 and BGP-15‐treated APP/PS1 mice. (E-F) Aβ plaque counts and areas in hippocampus were low in BGP-15‐treated APP/PS1 mice compared with APP/PS1 mice treated with DMSO. n = 3 for each group. t(4) = 4.330 p=0.0123 in (E), t(4) = 4.167, p=0.0141 in (F). (G) Representative pictures showing colocalization of Aβ (magenta) with IBA-1 (red) and CD68 (green) in the hippocampus of WT, APP/PS1 and APP/PS1-OPA1-OE mice. (H) The number of microglia surrounding Aβ was higher in APP/PS1- OPA1-OE mice compared with APP/PS1 mice. n = 4 for each group. p=0.0286 (I)Representative pictures showing colocalization of Aβ (green) with IBA-1 (red) and CD68 (magenta) in the hippocampus of WT, APP/PS1 and BGP-15‐treated APP/PS1 mice. (J) The number of microglia surrounding Aβ was higher in BGP-15‐treated APP/PS1 mice compared with APP/PS1 mice. n = 3 for each group. t(4) = 5.483, p=0.0054 (K) The input–output response increased in APP/PS1-OPA1-OE mice (n=3 slices/mouse, N=3 mice/group) compared with APP/PS1 mice (n=3 slices/mouse, N=3 mice/group). F(2,22)=2.035, APP/PS1 versus WT group: p < 0.0001, APP/PS1 versus APP/PS1-OPA1-OE group: p=0.0399. (L and M) The slope of the evoked fEPSP increased in APP/PS1- OPA1-OE mice (n=3slices/mouse, N=3mice/group) compared with APP/PS1 mice during LTP induction (n=3slices/mouse, N=3mice/group). APP/PS1 versus WT group: p=0.0262, APP/PS1 versus APP/PS1-OPA1-OE group: p=0.416. (N) The input–output response increased in BGP-15‐treated APP/PS1 mice (n=2-4 slices/mouse, N=3 mice/group) compared with APP/PS1 mice treated with DMSO (n=2-4 slices/mouse, N=3 mice/group). F(2,20)=4.289, APP/PS1 versus WT group: p =0.0260, APP/PS1 versus APP/PS1+BGP15 group: p<0.0001. (O and P) The slope of the evoked fEPSP increased in BGP-15‐treated APP/PS1 mice (n=3slices/mouse, N=3mice/group) compared with APP/PS1 mice treated with DMSO during LTP induction (n=3slices/mouse, N=3mice/group). APP/PS1 versus WT group: p =0.0103, APP/PS1 versus APP/PS1+BGP15 group: p=0.0063. Unpaired two-tailed test for (B), (C), (E), (F)and(J). Mann-Whitney U test for (H), Two-way ANOVA followed by Tukey’s post hoc test for (K) and (N). Kruskal-Wallis followed by Dunn's post-hoc test for (M)and (P). *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001

Article Snippet: Mice were treated daily with 20mg/kg BGP-15 dissolved in 10% dimethyl sulfoxide (DMSO) or vehicle 10% DMSO (S8370, Selleck, Shanghai, China) for 15 censecutive days by oral gavage.

Techniques: Over Expression, Activation Assay, Two Tailed Test, MANN-WHITNEY