Journal: Nature

Article Title: Adenosine signalling drives antidepressant actions of ketamine and ECT

doi: 10.1038/s41586-025-09755-9

Figure Lengend Snippet: a , Schematic of ketamine metabolism pathways. b , c , Time course of extracellular adenosine levels in the mPFC (b) and and corresponding AUC ( c ) following administration of ketamine, norketamine (NK), (2 R,6 R)-HNK (all at 10 mg·kg −1 , i.p.), or saline. Area under the curve (AUC, normalized to saline) ( c ) was calculated post-administration. d , e , Effect of ritonavir pretreatment (50 mg·kg −1 , i.p.) on ketamine-induced adenosine release. d, Adenosine time course with and without ritonavir. e, Quantification of adenosine peak ( ΔF/F %), time to peak, and AUC (normalized to vehicle). Recordings were performed on separate days in the same cohort of mice. f , g , Effect of ketoconazole pretreatment (50 mg·kg −1 , i.p.) on ketamine-induced adenosine signals. Same conventions as in ( d , e ). h , i , Effects of ticlopidine pretreatment (20 mg·kg −1 , i.p.) on ketamine-induced adenosine signals, displayed as in d , e . j - l , Time course and AUC of extracellular adenosine in the mPFC after administration of ritonavir ( j ), ketoconazole ( k ), or ticlopidine ( l ) alone, compared to vehicle. Data are mean ± s.e.m. (shading in b, d, f, h, j-l ; error bars in c, j-l ). Statistical analyses used a two-tailed paired t-test ( e, g, i ) and two-tailed unpaired t-tests ( c, j-l ) (** P < 0.01, *** P < 0.001). See Supplementary Table for detailed statistics.

Article Snippet: Additional key chemicals were purchased from commercial sources, including norketamine hydrochloride (Tocris, 1970), (2 R ,6 R )-HNK (Tocris, 6094), ticlopidine (Selleck, S0721), ketoconazole (Selleck, S1353), ritonavir (Selleck, S1185), dipyridamole (Selleck, S1895), LPS from Escherichia coli O127:B8 (LPS; Sigma, L3129), PSB36 (MCE, HY-103175), ZM241385 (Selleck, S8105), CHA (MCE, HY-18939), CGS21680 hydrochloride (MCE, HY-13201A), adenosine (MCE, HY-B0228), sodium [ 13 C 3 ]pyruvate (MCE, HY-W015913S), ADP (MCE, HY-W010918) and wheat germ agglutinin (Alexa Fluor 555; Thermo Scientific, W32464 ).

Techniques: Saline, Two Tailed Test

Journal: Cancers

Article Title: STAT3 Enhances Sensitivity of Glioblastoma to Drug-Induced Autophagy-Dependent Cell Death

doi: 10.3390/cancers14020339

Figure Lengend Snippet: Depletion of STAT3 protects GBM cells from autophagy-dependent cell death. ( A ) Western Blot of STAT3 after Crispr/Cas9-mediated knockout (KO) of STAT3 in MZ-54 human GBM cells showing complete absence of detectable STAT3 in the KO cell lines. GAPDH served as a housekeeping protein. ( B ) MTT cell proliferation assay showing reduced growth rate of STAT3-KO cell lines compared to WT. ( C – E ) ADCD inducers triggered non-apoptotic cell death that could be reversed by complete loss of STAT3. MZ-54 WT and STAT3-KO cells were treated with ( C ) 20 μM imipramine (IM) and 100 μM ticlopidine (TIC), ( D ) 12.5 μM pimozide (Pimo) and ( E ) 40 μM STF-62247 (STF) for 40 h. DMSO was used as vehicle control treatment. Total cell death was determined by subsequent Annexin-V-APC/PI staining and FACS analysis. ( F ) Western Blot of Cripsr/Cas9-mediated KO of Stat3 of the murine GBM cell line Tu9648. ( G ) Tu9648 WT and Stat3-KO cells were treated with 7.5 µM Pimo for 40 h and cell death was determined. ( H ) Western Blot of LN-299 human GBM cells after stable depletion of STAT3 using shRNA. ( I ) LN-229 Ctrl and STAT3-KD cells were treated with 12.5 µM Pimo for 40 h and cell death was determined. The data are presented as point plots of at least three experiments performed with 4 replicates. ** p < 0.01; **** p > 0.0001; Two-Way ANOVA with Tukey’s multiple comparison test (GraphPad Prism 9).

Article Snippet: The following compounds were dissolved in dimethyl-sulfoxide (DMSO; Carl Roth, Karlsruhe, Germany): imipramine hydrochloride (IM; Sigma-Aldrich), ticlopidine hydrochloride (TIC; Sigma-Aldrich), Pimozide (Pimo; Sigma-Aldrich), STF-62247 (STF, Santa Cruz), ABT-737 (ABT, Santa Cruz), Etoposide (Etopo, Enzo Life Sciences, Lörrach, Germany), Fillipin III (Abcam Biochemicals, Cambridge, UK), U18666A (Abcam Biochemicals), Digitonin (Sigma-Aldrich) E64D (Biomol, Hamburg, Germany), Pepstatin A (PepA, Applichem, Darmstadt, Germany).

Techniques: Western Blot, CRISPR, Knock-Out, MTT Cell Proliferation, Control, Staining, shRNA, Comparison

Journal: Cancers

Article Title: STAT3 Enhances Sensitivity of Glioblastoma to Drug-Induced Autophagy-Dependent Cell Death

doi: 10.3390/cancers14020339

Figure Lengend Snippet: Depletion of STAT3 does not affect autophagy induction or autophagic flux. ( A – C ) Representative Western Blots of MAP1LC3B-I and II of MZ-54 WT cells and STAT3-KO-cells after treatment with ( A ) 12.5 µM Pimozide (Pimo), ( B ) 20 µM imipramine (IM) and 100 µM ticlopidine (TIC) and ( C ) 40 µM STF-62247 (STF) for 6 h. GAPDH served as a housekeeping protein. ( D , E ) Representative pictures of ( D ) MZ-54 WT cells and ( E ) STAT3-KO#1 cells stably transfected with ptf-LC3 for the expression of mRFP-GFP-MAP1LC3B and treated with 15 µM Pimo, 40 µM STF, 20 µM IM and 100 µM TIC or vehicle (DMSO) for 24 h. Note that the presence of red-only punctae indicating active flux is unchanged between WT and STAT3-KO cells (arrow heads). Scale bar: 25 µm. ( F , G ) Flow cytometric quantification of the autophagic flux using stably transfection of pMRX-IP-GFP-LC3-RFP-LC3ΔG of MZ-54 WT and STAT3-KO cells. ** p < 0.01; **** p > 0.0001; Two-Way ANOVA with Tukey’s multiple comparison test (GraphPad Prism 7).

Article Snippet: The following compounds were dissolved in dimethyl-sulfoxide (DMSO; Carl Roth, Karlsruhe, Germany): imipramine hydrochloride (IM; Sigma-Aldrich), ticlopidine hydrochloride (TIC; Sigma-Aldrich), Pimozide (Pimo; Sigma-Aldrich), STF-62247 (STF, Santa Cruz), ABT-737 (ABT, Santa Cruz), Etoposide (Etopo, Enzo Life Sciences, Lörrach, Germany), Fillipin III (Abcam Biochemicals, Cambridge, UK), U18666A (Abcam Biochemicals), Digitonin (Sigma-Aldrich) E64D (Biomol, Hamburg, Germany), Pepstatin A (PepA, Applichem, Darmstadt, Germany).

Techniques: Western Blot, Stable Transfection, Transfection, Expressing, Comparison

Journal: Cancers

Article Title: A Potential New Treatment for High-Grade Glioma: A Study Assessing Repurposed Drug Combinations against Patient-Derived High-Grade Glioma Cells

doi: 10.3390/cancers14112602

Figure Lengend Snippet: The mechanisms of action of each drug against high-grade gliomas.

Article Snippet: Irinotecan, pitavastatin calcium, captopril, celecoxib, itraconazole and ticlopidine were supplied by LGM pharma, Florida, USA.

Techniques: Inhibition, Expressing, Activation Assay, Activity Assay, Migration

Journal: Cancers

Article Title: A Potential New Treatment for High-Grade Glioma: A Study Assessing Repurposed Drug Combinations against Patient-Derived High-Grade Glioma Cells

doi: 10.3390/cancers14112602

Figure Lengend Snippet: Mechanisms of action and growth-promoting pathway targeted by each drug in the combinations.

Article Snippet: Irinotecan, pitavastatin calcium, captopril, celecoxib, itraconazole and ticlopidine were supplied by LGM pharma, Florida, USA.

Techniques: Activity Assay, Inhibition, Clone Assay, Expressing

Journal: Cancers

Article Title: A Potential New Treatment for High-Grade Glioma: A Study Assessing Repurposed Drug Combinations against Patient-Derived High-Grade Glioma Cells

doi: 10.3390/cancers14112602

Figure Lengend Snippet: Three-day incubation average ( n = 9) drug cytotoxicity data for TMZ and drug combinations against patient-derived tumour core samples. ( A ) Average ( n = 9) cytotoxicity curves and ( B ) average ( n = 9) LogIC 50 data for nine tumour core samples treated with TMZ, C1, C2, C3 or C4. Significance between the groups is denoted by *** p < 0.001, if no line is drawn p > 0.05 within the bar charts. Abbreviations for drug treatments: TMZ, Temozolomide; C1, Irinotecan–Pitavastatin–Disulfiram–Copper Gluconate; C2, Irinotecan–Captopril–Celecoxib–Itraconazole; C3, Irinotecan–Captopril–Disulfiram; C4, Irinotecan–Pitavastatin–Captopril–Ticlopidine.

Article Snippet: Irinotecan, pitavastatin calcium, captopril, celecoxib, itraconazole and ticlopidine were supplied by LGM pharma, Florida, USA.

Techniques: Incubation, Derivative Assay

Journal: Cancers

Article Title: A Potential New Treatment for High-Grade Glioma: A Study Assessing Repurposed Drug Combinations against Patient-Derived High-Grade Glioma Cells

doi: 10.3390/cancers14112602

Figure Lengend Snippet: Days 3, 6, 8, 10 and 14 of incubation drug cytotoxicity data for TMZ and each drug combinations tested against patient-derived tumour margin samples using MTT assay. ( A ) Average ( n = 5) cytotoxicity curves and ( B ) average ( n = 5) LogIC 50 data for the tumour margin samples treated with TMZ, C1, C2, C3 and C4. Significance between groups is denoted by * p < 0.05 and ** p < 0.01 if no line is drawn, p > 0.05 within the bar charts. Abbreviations for drug treatments: TMZ, Temozolomide; C1, Irinotecan–Pitavastatin–Disulfiram–Copper Gluconate; C2, Irinotecan–Captopril–Celecoxib–Itraconazole; C3, Irinotecan–Captopril–Disulfiram; C4, Irinotecan–Pitavastatin–Captopril–Ticlopidine.

Article Snippet: Irinotecan, pitavastatin calcium, captopril, celecoxib, itraconazole and ticlopidine were supplied by LGM pharma, Florida, USA.

Techniques: Incubation, Derivative Assay, MTT Assay

Journal: Cancers

Article Title: A Potential New Treatment for High-Grade Glioma: A Study Assessing Repurposed Drug Combinations against Patient-Derived High-Grade Glioma Cells

doi: 10.3390/cancers14112602

Figure Lengend Snippet: Dose evaluation study of patient-derived primary cells tested at Log 2.4, 2.7, 3, 4 and 5 nM drug concentrations using MTT assay. ( A ) Average ( n = 9) cell viability data for the tumour core samples are 3 days of treatment with very low (Log 2.4 nM), low (Log 2.7 nM), medium (Log 3 nM), high (Log 4 nM) and very high (Log 5 nM) doses. ( B ) Average ( n = 5) cell viability data tumour margin samples after 3, 6, 8, 10 and 14 days of treatment with very low (Log 2.4 nM), low (Log 2.7 nM), medium (Log 3 nM), high (Log 4 nM) and very high (Log 5 nM) doses. Abbreviations for drug treatments: TMZ, Temozolomide; C1, Irinotecan–Pitavastatin–Disulfiram–Copper Gluconate; C2, Irinotecan–Captopril–Celecoxib–Itraconazole; C3, Irinotecan–Captopril–Disulfiram; C4, Irinotecan–Pitavastatin–Captopril–Ticlopidine.

Article Snippet: Irinotecan, pitavastatin calcium, captopril, celecoxib, itraconazole and ticlopidine were supplied by LGM pharma, Florida, USA.

Techniques: Derivative Assay, MTT Assay

Journal: Cancers

Article Title: A Potential New Treatment for High-Grade Glioma: A Study Assessing Repurposed Drug Combinations against Patient-Derived High-Grade Glioma Cells

doi: 10.3390/cancers14112602

Figure Lengend Snippet: Patient-3-derived TC average ( n = 3) drug cytotoxicity and contrast phase image data. ( A ) MTT vs. IncuCyte assay 3-day treatment cell viability data. ( B ) Control vs. Log 5 nM drug treatment phase contrast image data at day 3. Abbreviations for drug treatments: TMZ, Temozolomide; C1, Irinotecan–Pitavastatin–Disulfiram–Copper Gluconate; C2, Irinotecan–Captopril–Celecoxib–Itraconazole; C3, Irinotecan–Captopril–Disulfiram; C4, Irinotecan–Pitavastatin–Captopril–Ticlopidine.

Article Snippet: Irinotecan, pitavastatin calcium, captopril, celecoxib, itraconazole and ticlopidine were supplied by LGM pharma, Florida, USA.

Techniques: Derivative Assay

Journal: Molecules

Article Title: Antiplatelet, Anticoagulant, and Fibrinolytic Activity of Orchids: A Review

doi: 10.3390/molecules29235706

Figure Lengend Snippet: Orchids with antithrombotic activity.

Article Snippet: Dendrobium longicornu Lindl. , Longicornuol A (threo-1-{9-hydroxy-3-[2-(3-hydroxyphenyl)-ethyl]-1,8,10-trimethoxy- 6H-benzo[c]chromen-6-yl}-ethane-1,2-diol) , Bibenzyl , In vitro; rabbit platelets , 1525.6 μM: inhibits PA with ADP in 73.59% vs. 100% of the positive control (1088.4 μM Ticlopidine). Ticlopidine (TCP). , , [ ] .

Techniques: Activity Assay, In Vitro, Control, Inhibition, Positive Control, Binding Assay, Concentration Assay, Lysis, Saline, In Vivo, Ex Vivo, Clinical Proteomics