Journal: Oncology Reports

Article Title: SNX10 regulates the proliferation, apoptosis and cell cycle of acute B lymphoblastic leukemia cells via the PI3K/Akt signaling pathway

doi: 10.3892/or.2025.8911

Figure Lengend Snippet: SNX10 promotes B-ALL cellular behaviors via the PI3K/Akt signaling pathway. (A) Venn diagram showing the 211 significantly differentially expressed proteins identified between SNX10-OE Rs4;11 and EV cells. (B) Volcano plot of the differentially expressed proteins showed 76 downregulated and 135 upregulated proteins. (C) KEGG pathway enrichment analysis of the differentially expressed proteins. SNX10, sorting nexin 10; B-ALL, B-cell acute lymphoblastic leukemia; OE, overexpression; EV, empty vector; KEGG, Kyoto Encyclopedia of Genes and Genomes.

Article Snippet: Idelalisib (IDEL, TargetMoi, Cas: 870281-82-6) is a small molecule inhibitor that targets the PI3K catalytic subunit p110δ.

Techniques: Analysis, Over Expression, Plasmid Preparation, Significance Assay

Journal: Oncology Reports

Article Title: SNX10 regulates the proliferation, apoptosis and cell cycle of acute B lymphoblastic leukemia cells via the PI3K/Akt signaling pathway

doi: 10.3892/or.2025.8911

Figure Lengend Snippet: SNX10 influences the activity of the PI3K/Akt signaling pathway in B-ALL cells. The protein expression levels of PI3K, p-PI3K, Akt and p-Akt proteins in SNX10-OE and knockdown (A) Rs4;11 and (B) Nalm-6 cells were detected. After treating SNX10-OE B-ALL cells with 10 µM IDEL (a PI3K inhibitor) for 24 h, the protein expression levels of PI3K, p-PI3K, Akt and p-Akt proteins in SNX10-OE and knockdown (C) Rs4;11 and (D) Nalm-6 cells were detected. Data are presented as the mean ± SD of three independent repeats and compared using a one-way or two-way ANOVA. *P<0.05, **P<0.01, ***P<0.001 and ****P<0.0001 vs. EV group or shNC group. SNX10, sorting nexin 10; B-ALL, B-cell acute lymphoblastic leukemia; OE, overexpression; EV, empty vector; shRNA, short hairpin RNA; NC, negative control; IDEL, Idelalisib; p-, phosphorylated.

Article Snippet: Idelalisib (IDEL, TargetMoi, Cas: 870281-82-6) is a small molecule inhibitor that targets the PI3K catalytic subunit p110δ.

Techniques: Activity Assay, Expressing, Knockdown, Over Expression, Plasmid Preparation, shRNA, Negative Control, Western Blot

Journal: Oncology Reports

Article Title: SNX10 regulates the proliferation, apoptosis and cell cycle of acute B lymphoblastic leukemia cells via the PI3K/Akt signaling pathway

doi: 10.3892/or.2025.8911

Figure Lengend Snippet: SNX10 affects the activity of B-ALL cells through the PI3K/Akt signaling pathway. After treating (A) Rs4;11 cells and (B) Nalm-6 cells with 10 µM IDEL (a PI3K inhibitor) for 24 h, cell proliferation was analyzed using a Cell Counting Kit-8 assay. Apoptosis of (C) Rs4;11 cells and (D) Nalm-6 cells (annexin V/7-AAD staining) was analyzed by flow cytometry. Cell cycle distribution in (E) Rs4;11 cells and (F) Nalm-6 cells was analyzed by flow cytometry. Data are presented as the mean ± SD of three independent repeats and compared using a one-way or two-way ANOVA. ***P<0.001 and ****P<0.0001 vs. EV group. SNX10, sorting nexin 10; B-ALL, B-cell acute lymphoblastic leukemia; OE, overexpression; EV, empty vector; IDEL, Idelalisib; ns, not significant.

Article Snippet: Idelalisib (IDEL, TargetMoi, Cas: 870281-82-6) is a small molecule inhibitor that targets the PI3K catalytic subunit p110δ.

Techniques: Activity Assay, Cell Counting, Staining, Flow Cytometry, Over Expression, Plasmid Preparation, FACS

Journal: Acta Neuropathologica Communications

Article Title: Calcineurin depletion coincides with phosphorylated TDP-43 deposition in a mouse model of ALS/FTLD-TDP

doi: 10.1186/s40478-025-02192-9

Figure Lengend Snippet: Reduced calcineurin in rNLS8 mouse brain at symptomatic timepoints. Representative images of calcineurin immunostaining in control animals, and rNLS8 animals at 1 week, 4 weeks, and 7 weeks post-induction. a – d hippocampus, h – k motor cortex, o – r dorsal striatum. Scale bars: 100 µm. Insets show higher magnification detail. Immunoreactivity quantification at 1 week, 4 weeks, and 7 weeks post-induction in hippocampus ( e – g ), motor cortex ( l – n ), and dorsal striatum ( s – u ). Statistical analysis is by unpaired t -test, two-tailed [ n = 8 control, 15 rNLS8 animals (1 week); 8 control, 16 rNLS8 animals (4 weeks); 15 control, 15 rNLS8 animals (7 weeks); ns: p > 0.05, *: p ≤ 0.05, and ****: p ≤ 0.0001]. All bar graphs represent mean ± SEM

Article Snippet: Sections were treated for endogenous peroxidases with 3% hydrogen peroxide in PBS (pH 7.4) for 30 min at room temperature, blocked in 5% non-fat milk in PBS for one hour at room temperature, and incubated with one of the following primary antibodies overnight at 4 °C: calcineurin (CN-A1 mAb, Rockland 200-301-P23, 1:500), NeuN (A60 mAb, MilliporeSigma MAB377, 1:2000) and pTDP-43 (S409/410, clone 1D3, gift from Dr. Manuela Neumann, 1:400) [ ].

Techniques: Immunostaining, Control, Two Tailed Test

Journal: Acta Neuropathologica Communications

Article Title: Calcineurin depletion coincides with phosphorylated TDP-43 deposition in a mouse model of ALS/FTLD-TDP

doi: 10.1186/s40478-025-02192-9

Figure Lengend Snippet: Calcineurin and CDC7 protein level changes correspond to onset of TDP-43 phosphorylation in rNLS8 mouse brain. Representative immunoblots and densitometry analysis of chemiluminescence signals for total TDP-43, phosphorylated TDP-43 (pTDP-43), calcineurin, CDC7, and actin for control animals, and rNLS8 animals at 1 week, 4 weeks, and 7 weeks post-induction. Quantification is normalized to actin. a – e hippocampus, f – j cortex, and k – o striatum. Statistical analysis is by one-way ANOVA, followed by Tukey’s post-test ( n = 4–6 control animals and 4–6 rNLS8 animals for 1 week, 4 weeks, and 7 weeks post-transduction; ns: p > 0.05, *: p ≤ 0.05, **: p ≤ 0.01, ***: p ≤ 0.001, and ****: p ≤ 0.0001). All bar graphs represent mean ± SEM

Article Snippet: Sections were treated for endogenous peroxidases with 3% hydrogen peroxide in PBS (pH 7.4) for 30 min at room temperature, blocked in 5% non-fat milk in PBS for one hour at room temperature, and incubated with one of the following primary antibodies overnight at 4 °C: calcineurin (CN-A1 mAb, Rockland 200-301-P23, 1:500), NeuN (A60 mAb, MilliporeSigma MAB377, 1:2000) and pTDP-43 (S409/410, clone 1D3, gift from Dr. Manuela Neumann, 1:400) [ ].

Techniques: Phospho-proteomics, Western Blot, Control, Transduction

Journal: Acta Neuropathologica Communications

Article Title: Calcineurin depletion coincides with phosphorylated TDP-43 deposition in a mouse model of ALS/FTLD-TDP

doi: 10.1186/s40478-025-02192-9

Figure Lengend Snippet: Reduced calcineurin transcription in symptomatic rNLS8 mouse brain. a UMAP showing cluster distribution of single nucleus RNA sequencing(snRNAseq) combined from 5 control animals and 5 rNLS8 animals at 4 weeks post-induction. b Average expression of calcineurin heterodimer catalytic and regulatory genes (Ppp3ca, Ppp3cb, Ppp3cc, Ppp3r1, Ppp3r2) throughout UMAP space. c Log-normalized expression of the calcineurin catalytic subunit Ppp3ca in control (WT) and rNLS8 animals in cortical layer 6 intratelencephalic-projecting glutamatergic neurons (L6 IT), cortical layer 4/5 intratelencephalic-projecting glutamatergic neurons (L4/5 IT), cortical layer 2/3 intratelencephalic-projecting glutamatergic neurons (L2/3 IT), hippocampal CA1 glutamatergic neurons (CA1-Pros), cortical layer 6 corticothalamicprojecting glutamatergic neurons (L6 CT), and cerebellar granule glutamatergic neurons (CB Gran). Significance values are p adj values generated from cluster level pseudobulk analysis with DESeq2. d–f qRT-PCR of the calcineurin catalytic subunit Ppp3ca mRNA levels in d hippocampus, e cortex, and f striatum. Statistical analysis is by unpaired t-test, two-tailed (n = 4 animals; N = 3 technical replicates; ns: p > 0.05, **: p ≤ 0.01). All bar graphs represent mean ± SEM

Article Snippet: Sections were treated for endogenous peroxidases with 3% hydrogen peroxide in PBS (pH 7.4) for 30 min at room temperature, blocked in 5% non-fat milk in PBS for one hour at room temperature, and incubated with one of the following primary antibodies overnight at 4 °C: calcineurin (CN-A1 mAb, Rockland 200-301-P23, 1:500), NeuN (A60 mAb, MilliporeSigma MAB377, 1:2000) and pTDP-43 (S409/410, clone 1D3, gift from Dr. Manuela Neumann, 1:400) [ ].

Techniques: RNA Sequencing, Control, Expressing, Generated, Quantitative RT-PCR, Two Tailed Test

Journal: Acta Neuropathologica Communications

Article Title: Calcineurin depletion coincides with phosphorylated TDP-43 deposition in a mouse model of ALS/FTLD-TDP

doi: 10.1186/s40478-025-02192-9

Figure Lengend Snippet: Activation of calcineurin protects against TDP-43 phosphorylation in mouse primary neurons. C57BL/6 mouse primary cortical neurons were cultured for 7 days and pretreated with either 0 µM or 250 µM nickel chloride (NiCl 2 ) for 3 h to activate calcineurin. Cells were then exposed to 75 µM ethacrynic acid (EA) for 3 h to induce TDP-43 phosphorylation. a Representative immunoblots for total TDP-43, phosphorylated TDP-43 (pTDP-43), and actin. b – c Densitometry analysis of b total TDP-43 and c phosphorylated TDP-43 chemiluminescence signals normalized to actin and to control samples within each set. Statistical analysis is by paired t -test, two-tailed ( n = 4 independent experiments; ns: p > 0.05 and **: p ≤ 0.01). All bar graphs represent mean ± SEM

Article Snippet: Sections were treated for endogenous peroxidases with 3% hydrogen peroxide in PBS (pH 7.4) for 30 min at room temperature, blocked in 5% non-fat milk in PBS for one hour at room temperature, and incubated with one of the following primary antibodies overnight at 4 °C: calcineurin (CN-A1 mAb, Rockland 200-301-P23, 1:500), NeuN (A60 mAb, MilliporeSigma MAB377, 1:2000) and pTDP-43 (S409/410, clone 1D3, gift from Dr. Manuela Neumann, 1:400) [ ].

Techniques: Activation Assay, Phospho-proteomics, Cell Culture, Western Blot, Control, Two Tailed Test

Journal: Acta Neuropathologica Communications

Article Title: Calcineurin depletion coincides with phosphorylated TDP-43 deposition in a mouse model of ALS/FTLD-TDP

doi: 10.1186/s40478-025-02192-9

Figure Lengend Snippet: Activation of calcineurin protects against TDP-43 neurotoxicity in C. elegans . a A gain-of-function mutation in the C. elegans calcineurin homolog [ tax-6(jh107) ] improves TDP-43 transgenic C. elegans (TDP-43 Tg) motor dysfunction. Dispersal velocity of developmentally staged L4 larvae was measured by calculating the linear distance traveled from a designated central starting point over time. Statistical analysis is by unpaired t -test, two-tailed ( n > 100 animals; N = 3 independent experiments; ****: p ≤ 0.0001). b A transgene overexpressing wildtype TAX-6 ( tax-6 o/ex ) improves TDP-43 Tg motor dysfunction, as measured by dispersal velocity. Statistical analysis is by unpaired t -test, two-tailed ( n > 90 animals; N = 3 independent experiments, **: p ≤ 0.01). c Representative electropharyngeogram (EPG) recording traces from non-Tg, TDP-43 Tg, and TDP-43 Tg; tax-6(jh107) animals. Traces are 2 s; bar is 0.4 s. Frequency ( d ) and duration ( e ) of C. elegans pharyngeal pumping was evaluated using EPG recordings of neuron and muscle electrical signaling. tax-6(jh107) partially restores pharyngeal pumping frequency and restores pharyngeal pumping duration in TDP-43 Tg animals. Statistical analysis is by one-way ANOVA, followed by Tukey’s post-test ( n ≥ 29 animals; N = 3 independent experiments; ns: p > 0.05, *: p ≤ 0.05, **: p ≤ 0.01, ****: p ≤ 0.0001). f GFP-labeled D-type GABAergic motor neurons were counted during late day 1 of adulthood in vivo in living animals. TDP-43 Tg animals had an average of 14.6 out of 19 total neurons (13 VD + 6 DD type neurons). TDP-43 Tg; tax-6(jh107) gain-of-function animals averaged 16.1 neurons per animal. Statistical analysis is by unpaired t -test, two-tailed ( n ≥ 25 animals; ****: p ≤ 0.0001). All bar graphs represent mean ± SEM

Article Snippet: Sections were treated for endogenous peroxidases with 3% hydrogen peroxide in PBS (pH 7.4) for 30 min at room temperature, blocked in 5% non-fat milk in PBS for one hour at room temperature, and incubated with one of the following primary antibodies overnight at 4 °C: calcineurin (CN-A1 mAb, Rockland 200-301-P23, 1:500), NeuN (A60 mAb, MilliporeSigma MAB377, 1:2000) and pTDP-43 (S409/410, clone 1D3, gift from Dr. Manuela Neumann, 1:400) [ ].

Techniques: Activation Assay, Mutagenesis, Transgenic Assay, Two Tailed Test, Labeling, In Vivo