Journal: CNS Neuroscience & Therapeutics

Article Title: Aerobic Exercise Promotes Hippocampal Neurogenesis and Ameliorates Cognitive Dysfunction Induced by Unilateral Labyrinthectomy

doi: 10.1002/cns.70773

Figure Lengend Snippet: AZD1480 ameliorates UL‐induced cognitive dysfunction, whereas LPS significantly counteracts the cognitive improvements conferred by running. (A) Schematic of the experimental design showing AZD1480 and LPS interventions in UL mice. (B, C) In the open field test, there were no significant differences in total movement distance and average speed among the four groups of mice: UL + Static + VH, UL + Static + AZD1480, UL + Run + VH, UL + Run + LPS (One‐way ANOVA: F (3,36) = 1.236, p = 0.3110, and F (3,36) = 1.257, p = 0.3037). (D, E) There were no significant intergroup differences in terms of total immobility time and the duration spent in the central zone of the open field for the UL + Static + VH, UL + Static + AZD1480, UL + Run + VH, UL + Run + LPS groups (One‐way ANOVA: F (3,36) = 1.780, p = 0.1684 and F (3,36) = 0.7831, p = 0.5112, n = 10/group in OFT). (F, G) AZD1480 ameliorated the UL‐induced working memory impairment, whereas LPS counteracts the cognitive improvements conferred by running, manifested by the total entry to and time spent in the novel arm. Right arm (F) was set as the novel arm (One‐way ANOVA: F (3,36) = 9.760, p < 0.0001), Tukey's multiple comparisons test: UL + Static + VH vs. UL + Static + AZD1480: p = 0.0011, UL + Static + VH vs. UL + Run + VH: p = 0.0036, UL + AZD1480 vs. UL + Run + LPS: p = 0.0022, UL + Run + VH vs. UL + Run + LPS: p = 0.0068 for the percentage of novel arms; One‐way ANOVA: F (3,36) = 15.93, p < 0.0001, Tukey's multiple comparisons test: UL + Static + VH vs. UL + Static + AZD1480: p < 0.0001, UL + AZD1480 vs. UL + Run + VH: p = 0.0056, UL + Static + AZD1480 vs. UL + Run + LPS: p < 0.0001 for the total time of the novel arms, Left arm (G) was set as the novel arms (One‐way ANOVA: F (3,36) = 2.814, p = 0.0529, Tukey's multiple comparisons test: UL + Static + VH vs. UL + Run + VH p = 0.0488, for the percentage of novel arms; One‐way ANOVA: F (3,36) = 7.771, p = 0.0004, Tukey's multiple comparisons test: UL + Static + VH vs. UL + Static + AZD1480: p = 0.0036, UL + Static + VH vs. UL + Run+ VH: p = 0.0005 for the total time of the novel arms, n = 10/group in T maze). (H) AZD1480 significantly improves the number of errors in UL‐induced reference memory, whereas LPS counteracts the cognitive improvements conferred by running (two‐way ANOVA: F (27,324) = 2.115, p = 0.0013, Tukey's multiple comparisons test: UL + Static + VH vs. UL + Static + AZD1480: p < 0.0001, UL + Static + VH vs. UL + Run + VH: p < 0.0001, UL + Static + AZD1480 vs. UL + Run + LPS: p < 0.0001, UL + Run + VH vs. UL + Run + LPS: p < 0.0001). (I) AZD1480 significantly reduces the number of errors in working memory induced by UL (two‐way ANOVA: F (27,324) = 1.623, p = 0.0283, Tukey's multiple comparisons test: UL + Static + VH vs. UL + Static + AZD1480: p < 0.0001, UL + Static + VH vs. UL + Run + VH: p = 0.0273, UL + Static + AZD1480 vs. UL + Run + LPS: p = 0.0006). (J) Total time to complete tasks decreased by aerobic exercise (two‐way ANOVA: F (27,324) = 3.394, p < 0.0001), Tukey's multiple comparisons test: UL + Static + VH vs. UL + Static + AZD1480: p = 0.0003, UL + Static + VH vs. UL + Run + VH: p = 0.0003, UL + Static + AZD1480 vs. UL + Run + LPS: p = 0.0001, UL + Run + VH vs. UL + Run + LPS: p = 0.0001, n = 10/group, data are presented as mean ± standard error of the mean (SEM). (K) Throughout the training, UL + Static + VH, UL + Static + AZD1480, UL + Run + VH and UL + Run + LPS mice froze at comparable level during the trace interval (two‐way ANOVA, F (3,72) = 0.5261, p = 0.6658). (L, M) AZD1480 and running resulted in improved contextual and tone‐cued fear conditioning, but LPS prevented the running‐induced improvement (One‐way ANOVA: F (3,36) = 17.34, p < 0.0001, Tukey's multiple comparisons test: UL + Static + VH vs. UL + Static + AZD1480: p < 0.0001, UL + Static + VH vs. UL + Run + VH: p = 0.0017, UL + Static + AZD1480 vs. UL + Run + LPS: p < 0.0001, UL + Run + VH vs. UL + Run + LPS: p < 0.0001. One‐way ANOVA: F (3,36) = 8.139, p = 0.0003, Tukey's multiple comparisons test: UL + Static + VH vs. UL + Static + AZD1480: p = 0.0007, UL + Static + VH vs. UL + Run + VH: p = 0.0462, UL + Static + AZD1480 vs. UL + Run + LPS: p = 0.0023, n = 10/group in fear conditioning). * p < 0.05, ** p < 0.01, *** p < 0.001, **** p < 0.0001.

Article Snippet: At 2 weeks after UL induction, mice received daily oral gavage of either AZD1480 (HY‐10193, MCE) at 25 mg/kg or a vehicle (VH) control consisting of 0.1% dimethyl sulfoxide (DMSO; HY‐Y0320, MCE) [ ].

Techniques:

Journal: CNS Neuroscience & Therapeutics

Article Title: Aerobic Exercise Promotes Hippocampal Neurogenesis and Ameliorates Cognitive Dysfunction Induced by Unilateral Labyrinthectomy

doi: 10.1002/cns.70773

Figure Lengend Snippet: AZD1480 rescues the UL‐mediated suppression of hippocampal neurogenesis, while LPS markedly attenuates the pro‐proliferative effects of running. (A) Representative images showing BrdU+ and DAPI+ cells in the DG. (B) AZD1480 increases the number of BrdU+ cells induced by UL, while LPS counteracts the neuroproliferative effects induced by running. (One‐way ANOVA: F (3,36) = 21.29, p < 0.0001, Tukey's multiple comparisons test: UL + Static + VH vs. UL + Static + AZD1480: p = 0.0001, UL + Static + VH vs. UL + Run + VH: p < 0.0001, UL + Static + AZD1480 vs. UL + Run + LPS: p = 0.0094, UL + Run + VH vs. UL + Run + LPS: p < 0.0001). (C) Representative images showing Ki67+ and DAPI+ cells in the DG. (D) Running increases the number of UL‐induced Ki67+ cells, while AZD1480 and LPS have no significant effect on Ki67+ cell counts. (One‐way ANOVA: F (3,36) = 4.058, p = 0.0139, Tukey's multiple comparisons test: UL + Static + VH vs. UL + Run + VH: p = 0.0092). (E) Representative images showing DCX+ and DAPI+ cells in the DG. (F) AZD1480 increases the number of DCX+ cells induced by UL, while LPS counteracts the neuroproliferative effects induced by running. (One‐way ANOVA: F (3,36) = 10.35, p < 0.0001, Tukey's multiple comparisons test: UL + Static + VH vs. UL + Static + AZD1480: p = 0.0007, UL + Static + VH vs. UL + Run + VH: p < 0.0001, UL + Run + VH vs. UL + Run + LPS: p = 0.0490). (G) Representative photomicrographs of the dendritic branches of GFP+ cells in the DG. GFP+ cells were labeled with retrovirus pROVEF1a‐EGFP, which was injected in the DG. (H) AZD1480 significantly increases the total number of dendritic branches in individual GFP + newborn neurons induced by UL. (One‐way ANOVA: F (3,28) = 12.20, p < 0.0001, Tukey's multiple comparisons test: UL + Static + VH vs. UL + Static + AZD1480: p = 0.0012, UL + Static + VH vs. UL + Run + VH < 0.0001, UL + Static + VH vs. UL + RUN + LPS: p = 0.0020).

Article Snippet: At 2 weeks after UL induction, mice received daily oral gavage of either AZD1480 (HY‐10193, MCE) at 25 mg/kg or a vehicle (VH) control consisting of 0.1% dimethyl sulfoxide (DMSO; HY‐Y0320, MCE) [ ].

Techniques: Labeling, Injection

Journal: iScience

Article Title: NF-κB and STAT3 signaling uniquely stratify survival in female glioblastoma patients

doi: 10.1016/j.isci.2026.114761

Figure Lengend Snippet: Female murine transformed astrocytes are more sensitive to regulation and inhibition of STAT3 signaling than male cells (A) Correlation between IL-6 expression and p-STAT3 (Y705) expression in full serum conditions ( n = 5 lots). Male: r = 0.51, R 2 = 0.26, ns; female: r = 0.96, R 2 = 0.93, ∗∗, p < 0.01 (Pearson’s correlation). (B and C) Western blot (B) and quantification (C) of p-STAT3 (Y705) levels in serum-starved conditions following TNF-α treatment (10 ng/mL) with blocking using 10 μg/mL of either α-IgG control or α-IL-6 for 24 h in female cells ( n = 3 lots). Western blot representative of n = 3 independent experiments. (D) Western blot of p-STAT3 (Y705) levels in serum-starved conditions with or without supplemental 10 ng/mL epidermal growth factor (EGF) in male and female cells ( n = 5 lots). Replicate lot 6 results serve for normalization between blots. (E and F) Quantification of p-STAT3 Y705 levels from (D), segregated by sex ( n = 5 lots; E) or strength of NF-κB gene signature ( n = 6 weak, n = 4 strong; F); 6F is the abbreviation for lot 6 females. (G) Correlation between p-STAT3 (Y705) levels and IC 50 of AZD1480 in serum-starved conditions in murine transformed astrocytes ( n = 5 lots per sex with or without supplemental EGF). Male: r = −0.26, R 2 = 0.25, ns; female: r = −0.79, R 2 = 0.53, ∗∗, p < 0.01 (Spearman’s correlation). (H and I) Western blot (H) and quantification (I) of p-STAT3 (Y705) and p-p65 (S536) levels in serum-starved conditions following treatment with vehicle-control (DMSO) or H-89 (10 μM) for 18 h in lot 6 male and female cells. Western blot representative of n = 3 independent experiments. Expression levels normalized to vehicle-treated (DMSO) female cells. (J) Hazard ratios from univariate survival analysis of wild-type (WT) or altered (alt) EGFR tumors in all ( N = 164 WT, N = 198 alt), male-only ( N = 94 WT, N = 125 alt), or female-only ( N = 70 WT, N = 73 alt) patients of IL-6/JAK/STAT3 genes from the Human Molecular Signatures Database. Data are presented as the median ± interquartile range. In (C), (E), (F), and (I), data are presented as the mean ± SD. In (C), (E), (F), (I), and (J), ∗, p < 0.05; ∗∗, p < 0.01; ∗∗∗, p < 0.001; ∗∗∗∗; p < 0.0001; ns, not significant as determined by Tukey’s post hoc pairwise comparison following two-way ANOVA test (C, E, F, and I) or Kruskal-Wallis test followed by a Dunn’s test for post-hoc pairwise comparisons with multiplicity corrections (J). (C) Lot 6: α-IL-6 (∗, p < 0.05); TNF-α (∗∗∗, p < 0.001); interaction (ns, not significant). Lot 8: α-IL-6 (∗, p < 0.05); TNF-α (∗, p < 0.05); and interaction (ns, not significant). Lot 12: α-IL-6 (∗∗∗, p < 0.001); TNF-α (ns, not significant); and interaction (∗∗, p < 0.01) by two-way ANOVA. (E) Sex (ns, not significant); EGF (∗, p < 0.05); and interaction (ns, not significant) by two-way ANOVA. (F) NF-κB (∗, p < 0.05); EGF (∗∗, p < 0.01); and interaction (ns, not significant) by two-way ANOVA. (I) p-p65 (S536): sex (ns, not significant); H-89 (ns, not significant); and interaction (ns, not significant). P-STAT3 (Y705): sex (∗∗∗∗; p < 0.0001); H-89 (∗∗, p < 0.01), and interaction (∗∗, p < 0.01) by two-way ANOVA. Blue and red boxes in (D) and (H) indicate male and female murine transformed astrocytes, respectively. All data in (A)–(I) are compiled from n = 3 independent experiments (technical replication). In (A), (D), (E), (F), and (G), all data are compiled from each of the 5 lots (biological replication). See also and .

Article Snippet: AZD1480 (S2162) or H-89 2-HCl (S1582) was purchased from Selleckchem, and dissolved in DMSO to make stock concentrations.

Techniques: Transformation Assay, Inhibition, Expressing, Western Blot, Blocking Assay, Control, Comparison

Journal: iScience

Article Title: NF-κB and STAT3 signaling uniquely stratify survival in female glioblastoma patients

doi: 10.1016/j.isci.2026.114761

Figure Lengend Snippet: Female murine transformed astrocytes are more sensitive to regulation and inhibition of STAT3 signaling than male cells (A) Correlation between IL-6 expression and p-STAT3 (Y705) expression in full serum conditions ( n = 5 lots). Male: r = 0.51, R 2 = 0.26, ns; female: r = 0.96, R 2 = 0.93, ∗∗, p < 0.01 (Pearson’s correlation). (B and C) Western blot (B) and quantification (C) of p-STAT3 (Y705) levels in serum-starved conditions following TNF-α treatment (10 ng/mL) with blocking using 10 μg/mL of either α-IgG control or α-IL-6 for 24 h in female cells ( n = 3 lots). Western blot representative of n = 3 independent experiments. (D) Western blot of p-STAT3 (Y705) levels in serum-starved conditions with or without supplemental 10 ng/mL epidermal growth factor (EGF) in male and female cells ( n = 5 lots). Replicate lot 6 results serve for normalization between blots. (E and F) Quantification of p-STAT3 Y705 levels from (D), segregated by sex ( n = 5 lots; E) or strength of NF-κB gene signature ( n = 6 weak, n = 4 strong; F); 6F is the abbreviation for lot 6 females. (G) Correlation between p-STAT3 (Y705) levels and IC 50 of AZD1480 in serum-starved conditions in murine transformed astrocytes ( n = 5 lots per sex with or without supplemental EGF). Male: r = −0.26, R 2 = 0.25, ns; female: r = −0.79, R 2 = 0.53, ∗∗, p < 0.01 (Spearman’s correlation). (H and I) Western blot (H) and quantification (I) of p-STAT3 (Y705) and p-p65 (S536) levels in serum-starved conditions following treatment with vehicle-control (DMSO) or H-89 (10 μM) for 18 h in lot 6 male and female cells. Western blot representative of n = 3 independent experiments. Expression levels normalized to vehicle-treated (DMSO) female cells. (J) Hazard ratios from univariate survival analysis of wild-type (WT) or altered (alt) EGFR tumors in all ( N = 164 WT, N = 198 alt), male-only ( N = 94 WT, N = 125 alt), or female-only ( N = 70 WT, N = 73 alt) patients of IL-6/JAK/STAT3 genes from the Human Molecular Signatures Database. Data are presented as the median ± interquartile range. In (C), (E), (F), and (I), data are presented as the mean ± SD. In (C), (E), (F), (I), and (J), ∗, p < 0.05; ∗∗, p < 0.01; ∗∗∗, p < 0.001; ∗∗∗∗; p < 0.0001; ns, not significant as determined by Tukey’s post hoc pairwise comparison following two-way ANOVA test (C, E, F, and I) or Kruskal-Wallis test followed by a Dunn’s test for post-hoc pairwise comparisons with multiplicity corrections (J). (C) Lot 6: α-IL-6 (∗, p < 0.05); TNF-α (∗∗∗, p < 0.001); interaction (ns, not significant). Lot 8: α-IL-6 (∗, p < 0.05); TNF-α (∗, p < 0.05); and interaction (ns, not significant). Lot 12: α-IL-6 (∗∗∗, p < 0.001); TNF-α (ns, not significant); and interaction (∗∗, p < 0.01) by two-way ANOVA. (E) Sex (ns, not significant); EGF (∗, p < 0.05); and interaction (ns, not significant) by two-way ANOVA. (F) NF-κB (∗, p < 0.05); EGF (∗∗, p < 0.01); and interaction (ns, not significant) by two-way ANOVA. (I) p-p65 (S536): sex (ns, not significant); H-89 (ns, not significant); and interaction (ns, not significant). P-STAT3 (Y705): sex (∗∗∗∗; p < 0.0001); H-89 (∗∗, p < 0.01), and interaction (∗∗, p < 0.01) by two-way ANOVA. Blue and red boxes in (D) and (H) indicate male and female murine transformed astrocytes, respectively. All data in (A)–(I) are compiled from n = 3 independent experiments (technical replication). In (A), (D), (E), (F), and (G), all data are compiled from each of the 5 lots (biological replication). See also and .

Article Snippet: AZD1480 , Selleckchem , Cat#S2162.

Techniques: Transformation Assay, Inhibition, Expressing, Western Blot, Blocking Assay, Control, Comparison