Journal: Biochemistry and biophysics reports

Article Title: NanoLuciferase technology-based detection of TMPRSS2 as attempt to develop anti-coronavirus agents.

doi: 10.1016/j.bbrep.2024.101783

Figure Lengend Snippet: Fig. 1. Normalized TMPRSS2-HiBiT signal under treatment of compounds from (A) diversified building block library, (B) bioactive compound library, or (C) human endogenous metabolite library, at concentration of 10 μM and adjusted to corresponding ATP-Glo signal.

Article Snippet: Diversified building block compound library, bioactive compound library and endogenous metabolite compound library were from TargetMol.

Techniques: Blocking Assay, Drug discovery, Concentration Assay

Journal: Frontiers in Neurology

Article Title: Exosomal circ_0093708 as a potential ferroptosis biomarker in cerebral ischemia–reperfusion injury

doi: 10.3389/fneur.2025.1633393

Figure Lengend Snippet: Mining of key genes for ferroptosis and verification in external databases. (A) The 5-set Venn diagram showing the comprehensive strategy among suppressor ferroptosis-associated genes (green circle), unclassified ferroptosis-associated genes (orange circle), marker ferroptosis-associated genes (blue circle), driver ferroptosis-associated genes (pink circle), and differentially expressed genes (DEGs) (purple circle). (B) ROC analysis for DUSP1 in the discovery dataset. (C) ROC analysis for PTGS2 in the discovery dataset. (D) ROC analysis for DUSP1 in the validation dataset. (E) ROC analysis for PTGS2 in the validation dataset. ROC, receiver operating characteristic.

Article Snippet: We chose CIL56 (T4309, TargetMol, America) to construct the ferroptosis model under the condition of 0.7 μM for 24 h. (E)-2-benzylidene-3-(cyclohexylamino)-2,3-dihydro-1H-inden-1-one (BCI) is a commonly used inhibitor of MKP-1.

Techniques: Marker, Biomarker Discovery

Journal: Frontiers in Neurology

Article Title: Exosomal circ_0093708 as a potential ferroptosis biomarker in cerebral ischemia–reperfusion injury

doi: 10.3389/fneur.2025.1633393

Figure Lengend Snippet: Inhibition of DUSP1 exacerbates ferroptosis in PC12 cells. (A) Cell viability after CIL56 treatment. (B) Intracellular MDA levels. (C) Effect of BCI on DUSP1 inhibition in the ferroptosis model. (D) Intracellular ROS levels (scale bar: 20 μm). (E) Protein expression of DUSP1, GPX4, and TFRC. (F) Quantification of GPX4 levels. (G) Quantification of TFRC levels. Data were analyzed by one-way ANOVA with Tukey’s post hoc test and presented as mean ± SD. Con, control.

Article Snippet: We chose CIL56 (T4309, TargetMol, America) to construct the ferroptosis model under the condition of 0.7 μM for 24 h. (E)-2-benzylidene-3-(cyclohexylamino)-2,3-dihydro-1H-inden-1-one (BCI) is a commonly used inhibitor of MKP-1.

Techniques: Inhibition, Expressing, Control

Journal: EBioMedicine

Article Title: Ketogenesis acts as an endogenous protective programme to restrain inflammatory macrophage activation during acute pancreatitis

doi: 10.1016/j.ebiom.2022.103959

Figure Lengend Snippet: βOHB limits proinflammatory macrophage activation via class I HDACs, (a, b) Gene set enrichment analysis (GSEA) of gene expression in murine BMDMs are depicted. (a) Enrichment of TSA-upregulated signature genes (GSE22049) in βOHB-treated BMDMs. (b) Enrichment of HDAC3 depletion related signature genes (GES33162) in βOHB-treated BMDMs. (c, d) BMDMs treated with LPS (100 ng/ml) together with βOHB (10 mM), TSA (1 μΜ), or MS-275 (20 μM) for 4 h. (c) Flow cytometry analysis of intracellular TNFα levels. (d) Quantitative PCR analysis of Nos2, Il6, Il12b , and Tnfa mRNA expression. (e) ChIP-qPCR analysis of H3Ac and H4Ac occupancy in Edn1, Il12a , and Nos2 loci in the indicated group, with IgG as the control. (f) Ingenuity Pathway Analysis (IPA) of genes in cluster A. (g) BMDMs were pretreated with βOHB (10 mM) or TSA (1 μΜ) 1 h prior to LPS (100 ng/ml) stimulation for 15 min. Acylated p65 levels were determined by immunoprecipitation, while p-p65 and total p65 were determined by immunoblotting. (h) Mice were i.p. injected with TSA (0.1 mg/kg), MS-275 (20 mg/kg) or DMSO as a control 1 h prior to the CER-AP (Cer*7) induction and were harvested at 24 h thereafter (n = 5 / group). Frequency of TNFα + macrophagess (F4/80 + CD11b + ) in pancreatic leukocytes from the indicated groups. Data are presented as the mean ± SD in bar graphs (c–e) or the mean ± SEM in dot plots (h). *p < 0.05, **p < 0.01, ***p < 0.001

Article Snippet: For treatments, the Balb/c mice were (1) fed with 1,3-butanediol (5.72% (w/v); Sigma-Aldrich) or normal water (control) one week before disease induction; received a single intraperitoneal injection of βOHB (3 mmol/kg; Sigma-Aldrich) or normal saline at the indicated time; and (3) the CPT1α inhibitor etomoxir (20 mg/kg, Sigma-Aldrich), histone deacetylase (HDAC) pan inhibitor TSA (0.1 mg/kg; Targetmol), HDAC1/3 inhibitor MS-275 (20 mg/kg; Targetmol), or dimethyl sulfoxide (DMSO) as a control 1 h before disease induction.

Techniques: Activation Assay, Gene Expression, Flow Cytometry, Real-time Polymerase Chain Reaction, Expressing, ChIP-qPCR, Control, Immunoprecipitation, Western Blot, Injection

Journal: Biomedicines

Article Title: Ivosidenib Confers BRCAness Phenotype and Synthetic Lethality to Poly (ADP-Ribose) Polymerase Inhibition in BRCA1/2-Proficient Cancer Cells

doi: 10.3390/biomedicines13040958

Figure Lengend Snippet: Figure 1. High-throughput screening shows that IDH1 inhibitor ivosidenib greatly sensitizes BRCA1/2-proficient cancer cells to PARPi. (A) The workflow for screening sensitizer drugs for the PARP inhibitor Olaparib in A2780 cells using an FDA-approved drug library (TargetMol, #L1000) that contains 2040 approved small molecule drugs. (B) The relative cell viability of A2780 cells grown in the presence of 10 µM of FDA-approved drugs alone (upper) or FDA-approved drugs plus 10 µM of Olaparib for 72 h; cell viability was analyzed through CCK-8 assay. (C) Ivosidenib increases Olaparib sensitivity in BRCA1/2-WT breast and ovarian cancer cells. Indicated cells were treated with increasing concentrations of Olaparib (ola) in the presence or absence of 5 µM of ivosidenib (Ivo) for 72 h, followed by cell viability analysis. (D) Ivosidenib and Olaparib synergistically suppress cancer cell growth. Indicated cells were co-treated with serial dosages of Olaparib and ivosidenib for 72 h, followed by Bliss synergy analysis. (E) Ivosidenib and Olaparib synergistically inhibit clonogenic survival in BRCA1/2-WT cancer cells. The colony formation analysis indicated cells treated with 2 µM of ivosidenib, 2 µM of Olaparib, or their combination. Data are presented as means ± SD, n = 6. * p < 0.05 and *** p < 0.001 based on the two-tailed t-test.

Article Snippet: High-throughput screening shows that IDH1 inhibi r ivosidenib greatly sensitizes BRCA1/2-proficient cancer cells to PARPi. (A) The workflow for screening sensitizer drugs for the PARP inhibitor Olaparib in A2780 cells using an FDA-approved drug library (TargetMol, #L1000) that contains 2040 approved small molecule drugs. (B) The relative cell viability of A2780 cells grown in the presence of 10 μM of FDA-app oved drugs alone (upper) o FDA-approved drugs plus 10 μM of Olaparib for 72 h; cell viability was analyzed through CCK-8 assay. (C) Ivosidenib increases Olaparib sensitivity in BRCA1/2-WT breast and ovarian cancer cells.

Techniques: High Throughput Screening Assay, Drug discovery, CCK-8 Assay, Two Tailed Test

Journal: Biomedicines

Article Title: Ivosidenib Confers BRCAness Phenotype and Synthetic Lethality to Poly (ADP-Ribose) Polymerase Inhibition in BRCA1/2-Proficient Cancer Cells

doi: 10.3390/biomedicines13040958

Figure Lengend Snippet: Figure 2. Ivosidenib (Ivo) greatly potentiates Olaparib (Ola)-induced DNA damage in BRCA1/2- proficient cells. (A) Ivosidenib enhances Olaparib-induced γH2AX formation in BRCA1/2-WT cancer cells. Indicated cells were treated with 50 µM of Ola, 10 µM of Ivo, or their combination for 48 h, followed by Western blot analysis of γH2AX. (B) Ivosidenib delayed the reduction of γH2AX after Olaparib treatment. A2780 cells were treated with 100 µM for 48 h and then released into normal culture medium in the presence or absence of Ivo for indicated time points, followed by Western blot analysis of γH2AX. (C) Ivosidenib increases Olaparib-caused DNA damage. A2780 cells were treated with 50 µM of Ola, 10 µM of Ivo, or their combination for 48 h, followed by measuring the DNA damage through comet assay. Data are presented as means ± SD.

Article Snippet: High-throughput screening shows that IDH1 inhibi r ivosidenib greatly sensitizes BRCA1/2-proficient cancer cells to PARPi. (A) The workflow for screening sensitizer drugs for the PARP inhibitor Olaparib in A2780 cells using an FDA-approved drug library (TargetMol, #L1000) that contains 2040 approved small molecule drugs. (B) The relative cell viability of A2780 cells grown in the presence of 10 μM of FDA-app oved drugs alone (upper) o FDA-approved drugs plus 10 μM of Olaparib for 72 h; cell viability was analyzed through CCK-8 assay. (C) Ivosidenib increases Olaparib sensitivity in BRCA1/2-WT breast and ovarian cancer cells.

Techniques: Western Blot, Single Cell Gel Electrophoresis

Journal: Biomedicines

Article Title: Ivosidenib Confers BRCAness Phenotype and Synthetic Lethality to Poly (ADP-Ribose) Polymerase Inhibition in BRCA1/2-Proficient Cancer Cells

doi: 10.3390/biomedicines13040958

Figure Lengend Snippet: Figure 3. Ivosidenib (Ivo) treatment suppresses the repair of Olaparib (Ola)-induced DSBs. Ivosidenib inhibits HR repair. (A,B) Ivosidenib A2780 cells were treated with 50 of µM Ola, 10 µM of Ivo, or their combination for 48 h, followed by immunofluorescence analysis of Rad51/γH2AX (A) or RPA2/γH2AX (B). (C) Cells were treated as indicated for 48 h, followed by Western blot analysis of pRPA2 S4/8. Data were are presented as means ± SD. ** p < 0.01 and *** p < 0.001 according to the two2-tailed t-test.

Article Snippet: High-throughput screening shows that IDH1 inhibi r ivosidenib greatly sensitizes BRCA1/2-proficient cancer cells to PARPi. (A) The workflow for screening sensitizer drugs for the PARP inhibitor Olaparib in A2780 cells using an FDA-approved drug library (TargetMol, #L1000) that contains 2040 approved small molecule drugs. (B) The relative cell viability of A2780 cells grown in the presence of 10 μM of FDA-app oved drugs alone (upper) o FDA-approved drugs plus 10 μM of Olaparib for 72 h; cell viability was analyzed through CCK-8 assay. (C) Ivosidenib increases Olaparib sensitivity in BRCA1/2-WT breast and ovarian cancer cells.

Techniques: Immunofluorescence, Western Blot

Journal: Biomedicines

Article Title: Ivosidenib Confers BRCAness Phenotype and Synthetic Lethality to Poly (ADP-Ribose) Polymerase Inhibition in BRCA1/2-Proficient Cancer Cells

doi: 10.3390/biomedicines13040958

Figure Lengend Snippet: Figure 5. YTHDC2 knockdown suppresses HR repair. (A) Schematic diagram of HR repair reporter system (DR-GFP). (B,C) Silencing of YTHDC2 decreases HR repair. QU20S-DRGFP cells were transfected with control (ctrl) or YTHDC2 siRNA and, 24 h later, cells were transfected with pCBASceI plasmid to induce endonuclease-induced DSB, followed by flow cytometry analysis of GFP expression 48 h after pCBASceI expression (B). A2780 cells were transfected with control (Ctrl) or YTHDC2 siRNA; cells were then treated with 50 µM of Olaparib for 48 h, followed by immunofluorescence analysis of Rad51/γH2AX (C). Data are presented as means ± SD. *** p < 0.001 according to the two-tailed t-test.

Article Snippet: High-throughput screening shows that IDH1 inhibi r ivosidenib greatly sensitizes BRCA1/2-proficient cancer cells to PARPi. (A) The workflow for screening sensitizer drugs for the PARP inhibitor Olaparib in A2780 cells using an FDA-approved drug library (TargetMol, #L1000) that contains 2040 approved small molecule drugs. (B) The relative cell viability of A2780 cells grown in the presence of 10 μM of FDA-app oved drugs alone (upper) o FDA-approved drugs plus 10 μM of Olaparib for 72 h; cell viability was analyzed through CCK-8 assay. (C) Ivosidenib increases Olaparib sensitivity in BRCA1/2-WT breast and ovarian cancer cells.

Techniques: Knockdown, Transfection, Control, Plasmid Preparation, Flow Cytometry, Expressing, Immunofluorescence, Two Tailed Test

Journal: Biomedicines

Article Title: Ivosidenib Confers BRCAness Phenotype and Synthetic Lethality to Poly (ADP-Ribose) Polymerase Inhibition in BRCA1/2-Proficient Cancer Cells

doi: 10.3390/biomedicines13040958

Figure Lengend Snippet: Figure 7. Combination treatment of ivosidenib (Ivo) and Olaparib (Ola) produces synergistic anti- tumor efficacy in BRCA1/2-proficient ovarian cancers. (A–C) Ivosidenib and Olaparib synergistically suppress tumor growth. A2780 xenograft bearing mice treated with Ola (100 mg/kg, orally) and Ivo (100 mg/kg, orally) and tumor growth curve (A), tumor image (B), and tumor weights (C) are shown. (D,E) Co-treatment with ivosidenib and Olaparib greatly induces DSBs and reduces proliferation in A2780 xenograft tumors. Immunohistochemistry analysis of γH2AX (D) and Ki67 (E) in tumors treated as indicated. Data are presented as means ± SD. *** p < 0.001 according to the two-tailed t-test.

Article Snippet: High-throughput screening shows that IDH1 inhibi r ivosidenib greatly sensitizes BRCA1/2-proficient cancer cells to PARPi. (A) The workflow for screening sensitizer drugs for the PARP inhibitor Olaparib in A2780 cells using an FDA-approved drug library (TargetMol, #L1000) that contains 2040 approved small molecule drugs. (B) The relative cell viability of A2780 cells grown in the presence of 10 μM of FDA-app oved drugs alone (upper) o FDA-approved drugs plus 10 μM of Olaparib for 72 h; cell viability was analyzed through CCK-8 assay. (C) Ivosidenib increases Olaparib sensitivity in BRCA1/2-WT breast and ovarian cancer cells.

Techniques: Immunohistochemistry, Two Tailed Test