Journal: Blood Cancer Journal

Article Title: Bruton’s tyrosine kinase inhibition re-sensitizes multidrug-resistant DLBCL tumors driven by BCL10 gain-of-function mutants to venetoclax

doi: 10.1038/s41408-025-01214-y

Figure Lengend Snippet: A Heatmap of differentially expressed genes in RIVA cells containing vector or BCL10 mutants, (FC ≥ 1.5x up or down) . B Venn diagram of the number of differentially expressed genes in BCL10 mutants compared to vector. C Top 10 upregulated (adjusted p value ≤ 0.001) Jensen compartment complexes using genes upregulated with a FC ≥ 2. D The top overlapping Hallmark gene set pathways upregulated (FDR q-value ≤ 0.25) in BCL10 mutants. E Western blot of RIVA and HBL1 cells induced with doxycycline for 24 h and probed as indicated. F TNFα ELISA assay on cell supernatant from RIVA, HBL1, and U2932 cells containing vector or BCL10 mutants. G Boxplot of gene expression levels of TNFRSF13B and USP2 of untreated DLBCL cases comparing mutant versus wildtype BCL10 cases.

Article Snippet: To more fully assess impact of BCL10 mutations on treatment resistance, we interrogated the 960-compound TargetMol Epigenetic Library.

Techniques: Plasmid Preparation, Western Blot, Enzyme-linked Immunosorbent Assay, Gene Expression, Mutagenesis

Journal: Blood Cancer Journal

Article Title: Bruton’s tyrosine kinase inhibition re-sensitizes multidrug-resistant DLBCL tumors driven by BCL10 gain-of-function mutants to venetoclax

doi: 10.1038/s41408-025-01214-y

Figure Lengend Snippet: A Gene ontology analysis of genes upregulated in BCL10 mutant RIVA cells showing top 10 of 49 significantly upregulated ontologies (adjusted p < 0.001). Ontologies that were completely overlapping in genes were combined. B GSEA “BIOCARTA_CYTOKINE_PATHWAY” for BCL10 mutants (q = 0.082 S136X, q = 0.176 for R58Q). C Venn diagram of cytokine genes upregulated in BCL10 mutants with array validations indicated. D Boxplot of gene expression levels of CCL22 and IL7 of untreated DLBCL cases comparing mutant versus wildtype BCL10 cases. E ELISA assays of IL6, IL7 and TNFβ on cells supernatant of RIVA and HBL1 cells induced for 24 (IL7 and TNFβ) or 72 h (IL6) with doxycycline, ** p < 0.01; *** p < 0.001; **** p < 0.0001.

Article Snippet: To more fully assess impact of BCL10 mutations on treatment resistance, we interrogated the 960-compound TargetMol Epigenetic Library.

Techniques: Mutagenesis, Gene Expression, Enzyme-linked Immunosorbent Assay

Journal: Blood Cancer Journal

Article Title: Bruton’s tyrosine kinase inhibition re-sensitizes multidrug-resistant DLBCL tumors driven by BCL10 gain-of-function mutants to venetoclax

doi: 10.1038/s41408-025-01214-y

Figure Lengend Snippet: A Genes that were upregulated (FC ≥ 2) in both mutants were analyzed for enrichment in regulation by transcription factors from the ENCODE project through the online transcription factor analysis tool ChIP-X Enrichment Analysis Version 3 (ChEA3). Sixteen transcription factors were significantly upregulated in BCL10 mutants (FDR ≤ 0.05). B Schematic of transcription factors identified to be upregulated in ( A ). C Boxplot of gene expression levels of BATF and IRF4 of untreated DLBCL cases comparing mutant versus wildtype BCL10 cases. D Western blot of RIVA and HBL1 cells induced with doxycycline for 24 h and probed as indicated. E Western blot of RIVA and U2932 cells induced with doxycycline for 24 h and probed as indicated. F ELISA assays in RIVA AND U2932 cell supernatant probing for CXCL10 (RIVA - S136X: p = 0.0046, R58Q: p = 0.0003, U2932- S136X: p = 0.0003, R58Q: p = 0.0028).

Article Snippet: To more fully assess impact of BCL10 mutations on treatment resistance, we interrogated the 960-compound TargetMol Epigenetic Library.

Techniques: Gene Expression, Mutagenesis, Western Blot, Enzyme-linked Immunosorbent Assay

Journal: Blood Cancer Journal

Article Title: Bruton’s tyrosine kinase inhibition re-sensitizes multidrug-resistant DLBCL tumors driven by BCL10 gain-of-function mutants to venetoclax

doi: 10.1038/s41408-025-01214-y

Figure Lengend Snippet: A Dose response viability assays of RIVA cells treated with pirtobrutinib (S136X: p = 0.033, R58Q: p = 0.019), acalabrutinib (S136X: p = 0.07, R58Q: p = 0.07), and ibrutinib (S136X: p = 0.023, R58Q: p = < 0.0001). B Epigenetic Library (TargetMol) on doxycycline induced RIVA cells. Hits are compounds that significantly inhibited cell viability and compounds that had an increase or decrease in viability two standard deviations from the mean of the difference between BCL10 S136X and vector after 72 h of 10 μM drug treatment. Targets in red highlight mutant-driven resistance, mutant-sensitive targets are in blue, and compounds that sensitized both vector and BCL10 S136X are in purple. C Schematic of hits from 4B. D Dose response viability assays of RIVA cells treated with selcidemstat (p=ns), tovorafenib (p = ns), ulixertinib (S136X: p = 0.0125, R58Q: p = 0.0103), JNKi (p = ns), duvelisib (S136X: p = 0.126, R58Q: p = 0.0264), idelalisib (S136X: p = ns, R58Q: p = 0.004), capivasertib (S136X: p = 0.0002, R58Q: p = 0.005), venetoclax (S136X: p = 0.008, R58Q: p = 0. 0.046), and AZD1208 (PIMi) (S136X: p = 0.019, R58Q: p = 0.040).

Article Snippet: To more fully assess impact of BCL10 mutations on treatment resistance, we interrogated the 960-compound TargetMol Epigenetic Library.

Techniques: Plasmid Preparation, Mutagenesis

Journal: Blood Cancer Journal

Article Title: Bruton’s tyrosine kinase inhibition re-sensitizes multidrug-resistant DLBCL tumors driven by BCL10 gain-of-function mutants to venetoclax

doi: 10.1038/s41408-025-01214-y

Figure Lengend Snippet: A Normalized counts from gene expression data for BCL2 family genes BCL2, BCL2L1 , and BCL2A1 in the BCL10 mutants. B Western blot of proteins implicated in venetoclax resistance including BCL-xL, BFL1, and BCL2 in doxycycline induced RIVA cells. C Transcript levels of doxycycline induced RIVA cells treated with DMSO or 5uM pirtobrutinib for 24 h: BCL2 (vector: p = 0.0325, R58Q: p = 0.005, S136X: p = 0.0006), BCL2L1 (vector: p=ns, R58Q: p = 0.0484, S136X: p = 0.0007), BCL2A1 (vector: p = 0.0087, R58Q: p = 0.0121, S136X: p = 0.0005). D Mitochondrial membrane potential flow cytometry assay in RIVA vector compared to RIVA R58Q and S136X at baseline. E Time course for BCL-xL, BFL1, and BCL2 in 5 μM pirtobrutinib treated RIVA cells. F Transcript levels of VDACs and TOMM22 after 24-h treatment with pirtobrutinib in RIVA cells. G Mitochondrial membrane potential flow cytometry assay in RIVA vector compared to RIVA R58Q and S136X after treatment with DMSO, pirtobrutinib, venetoclax or the combination for 2, 6 or 20 h. H Western blot of doxycycline induced RIVA cells treated with DMSO, venetoclax, pirtobrutinib or the combination for 24 h.

Article Snippet: To more fully assess impact of BCL10 mutations on treatment resistance, we interrogated the 960-compound TargetMol Epigenetic Library.

Techniques: Gene Expression, Western Blot, Plasmid Preparation, Membrane, Flow Cytometry

Journal: Blood Cancer Journal

Article Title: Bruton’s tyrosine kinase inhibition re-sensitizes multidrug-resistant DLBCL tumors driven by BCL10 gain-of-function mutants to venetoclax

doi: 10.1038/s41408-025-01214-y

Figure Lengend Snippet: A Upregulated transcription factor protein-protein interactions in genes upregulated by the BCL10 mutants probed through the Enrichr website ( p < 0.05). B Western blot showing phosphorylated STAT3 and total STAT3 in HBL1 and RIVA cells containing BCL10 mutants. C IL6 transcript levels of RIVA vector and mutants treated with pirtobrutinib for 24 h ( p < 0.0001). D IL6 cytokine levels in RIVA vector and mutants supernatant treated/untreated with 10uM pirtobrutinib for 24 h. E , F Western blot of doxycycline induced RIVA cells treated with DMSO, venetoclax, pirtobrutinib or the combination for 24 h. G Western Blot analysis of RIVA S136X cells treated with increasing concentrations of ruxolitinib with or without tocilizumab (IL6 inhibitor). H Western Blot analysis of RIVA S136X cells treated with increasing concentrations of ruxolitinib with or without the addition of TNFa. I IL6 transcript levels of RIVA S136X cells treated with TNFa alone or with ruxolitinib. J Schematic of TNFa / IL6/JAK/STAT signaling in BCL10 mutant cells. K Dose response viability assays of RIVA and HBL1 cells treated with pirtobrutinib (HBL1 clone1: p = 0.0027, HBL1 clone2: p = 0.0013, RIVA clone1: p = 0.0029, RIVA clone2: p < 0001) and ibrutinib (HBL1 clone1: p = 0.0401, HBL1 clone2: p = 0.0028, RIVA clone1: p = 0.3089, RIVA clone2: p < 0001), clones1 and 2 are the mutation (S136X) engineered at BCL10 gene locus. L Synergy assessments of venetoclax plus pirtobrutinib in endogenous BCL10 mutants (S136X) with reported synergy score.

Article Snippet: To more fully assess impact of BCL10 mutations on treatment resistance, we interrogated the 960-compound TargetMol Epigenetic Library.

Techniques: Protein-Protein interactions, Western Blot, Plasmid Preparation, Mutagenesis

Journal: The Journal of Cell Biology

Article Title: Microglia control the glycinergic but not the GABAergic synapses via prostaglandin E2 in the spinal cord

doi: 10.1083/jcb.201607048

Figure Lengend Snippet: PGE2 mediates microglial regulation of synaptic GlyR accumulation via EP2 receptors. (A) Double labeling of organotypic slices showing Cox-2 and Iba1 IRs in control condition and after 30-min LPS application or 15-min 4AP application. Cox-2 IR is restricted to microglia. Bar, 20 µm. (B) Quantification (mean ± SEM) of Cox-2 fluorescence intensities over the corresponding Iba1 profiles in control (CT), LPS, and 4AP conditions. Circles represent single experiments. (C and D) The modulation of GlyR α1 QD synaptic dwell time (C) and stability (D) in control (CT), after LPS application (LPS), and after LPS and PF04418948 treatment (LPS + PF044). (C) Synaptic dwell time distributions indicating 25, 50 (black bar), and 75% of all trajectories. *, P < 0.05; **, P < 0.01; ***, P < 0.001; Kolmogorov-Smirnov test. (D) Percentage of stable synaptic trajectories detected during the imaging session ( n = 3 independent experiments; mean ± SEM; ns, P > 0.05; *, P < 0.05; t test). (E and F) Fluorescence intensities relative to control of synaptic GlyR α1 IR after application of LPS or 4AP in the presence of EP2 receptor antagonist PF04418948 (E) or the PKA antagonist H-89 (F) in organotypic slices. Mean ± SEM; circles represent single experiments.

Article Snippet: Slices were permeabilized and blocked in PBS 0.1% Triton X-100 and 0.25% fish gelatin and incubated with primary antibodies (anti-GlyR α1 [1:400; rabbit]; anti-GABA A R γ2 [1:50; Alomone Labs], anti-gephyrin [1:400; mAb7a; Synaptic Systems], anti-Cox-2 [1:200; M-19; Santa Cruz Biotechnology], anti-Iba1 [1:400; Wako], and anti-EP2R [Alomone Labs]).

Techniques: Labeling, Fluorescence, Imaging

Journal: Frontiers in Pharmacology

Article Title: Achyranthes bidentata Polysaccharide Activates Nuclear Factor-Kappa B and Promotes Cytokine Production in J774A.1 Cells Through TLR4/MyD88 Signaling Pathway

doi: 10.3389/fphar.2021.753599

Figure Lengend Snippet: Primer sequences for PCR.

Article Snippet: Antibodies against Toll-like receptor 2 (TLR2), cluster of differentiation 14 (CD14), and TRIF-related adaptor molecule (TRAM) were purchased from Proteintech (IL, United States).

Techniques:

Journal: Frontiers in Pharmacology

Article Title: Achyranthes bidentata Polysaccharide Activates Nuclear Factor-Kappa B and Promotes Cytokine Production in J774A.1 Cells Through TLR4/MyD88 Signaling Pathway

doi: 10.3389/fphar.2021.753599

Figure Lengend Snippet: ABPS increased the expression of TLR4 and MyD88 in J774 A.1 cells. (A) The mRNA expression of TLR2, TLR4, TRAM, and MyD88. (B) The protein expression of TLR2, TLR4, TRAM, and MyD88. The blot shown is representative of one of the three similar experiments. Cells were treated 500 μg/ml ABPS for 24 h. NC: normal control; ABPS500: 500 μg/ml ABPS treated. * p < 0.05, ** p < 0.01 vs. NC. The values are presented as means ± SD.

Article Snippet: Antibodies against Toll-like receptor 2 (TLR2), cluster of differentiation 14 (CD14), and TRIF-related adaptor molecule (TRAM) were purchased from Proteintech (IL, United States).

Techniques: Expressing

Journal: Pharmacological Research - Modern Chinese Medicine

Article Title: The pharmaceutical applications of total flavonoids extract from Isatis tinctoria L. leaves

doi: 10.1016/j.prmcm.2022.100122

Figure Lengend Snippet: Fig. 8. Effects of TFE from Folium isatidis on the genes expression of TLR4 (a), TRAF6 (b), TRIF (c), I 𝜅B (d) and p65 (e) in lungs tissues of LPS induced ALI mice ( # compared with the control, ∗ compared with LPS, ∗ P < 0.05, ∗ ∗ / ## P < 0.01).

Article Snippet: Antibodies against TLR4, RAF6, TRIF, NF- κB p65, p-NF- κB p65, I κB α, p-I κB α and β-actin were urchased from Santa Cruz Biotechnology (Santa Cruz, CA, USA), and econdary antibodies were obtained from Wuhan Boster Biological Techology., Ltd (Wuhan, China).

Techniques: Expressing, Control

Journal: Pharmacological Research - Modern Chinese Medicine

Article Title: The pharmaceutical applications of total flavonoids extract from Isatis tinctoria L. leaves

doi: 10.1016/j.prmcm.2022.100122

Figure Lengend Snippet: Fig. 9. Effects of TFE from Folium isatidis on the proteins expression of TLR4 (a), TRAF6 (b), TRIF (c), I 𝜅B (d), p-I 𝜅B (e), p65 (f) and p-p65 (g) in lungs tissues of LPS induced ALI mice ( # compared with the cntrol, ∗ compared with LPS, ∗ P < 0.05, ∗ ∗ / ## P < 0.01).

Article Snippet: Antibodies against TLR4, RAF6, TRIF, NF- κB p65, p-NF- κB p65, I κB α, p-I κB α and β-actin were urchased from Santa Cruz Biotechnology (Santa Cruz, CA, USA), and econdary antibodies were obtained from Wuhan Boster Biological Techology., Ltd (Wuhan, China).

Techniques: Expressing

Journal: Pharmacological Research - Modern Chinese Medicine

Article Title: The pharmaceutical applications of total flavonoids extract from Isatis tinctoria L. leaves

doi: 10.1016/j.prmcm.2022.100122

Figure Lengend Snippet: Fig. 10. Regulation of TFE from Folium isatidis on TLR4-TRIF-NF- 𝜅B signaling pathway in LPS induced ALI mice.

Article Snippet: Antibodies against TLR4, RAF6, TRIF, NF- κB p65, p-NF- κB p65, I κB α, p-I κB α and β-actin were urchased from Santa Cruz Biotechnology (Santa Cruz, CA, USA), and econdary antibodies were obtained from Wuhan Boster Biological Techology., Ltd (Wuhan, China).

Techniques: