tti 101  (MedChemExpress)

Journal: Cell Death & Disease

Article Title: BRUCE liver-KO enhances MASLD/MASH development in the steatotic PTEN-KO background by impairing mitochondrial metabolism and activating STAT3

doi: 10.1038/s41419-025-08294-5

Figure Lengend Snippet: A WB of liver lysates from 2-month-old mice (upper) and IHC of pSTAT3-Y705 with WT and DKO liver sections showing nuclear positivity of pSTAT3-Y705 both in hepatocytes and NPCs in DKO (lower); scale bar 50 µm. B Liver images of WT and DKO mice treated with TTI-101 (100 mg/kg/bw, daily i.p.) for 3 weeks or left untreated with liver-to-body weight ratio quantified; scale bar 1 cm. These mice were analyzed by WB for indicated proteins ( C ), ORO ( D ), H&E ( E ), Sirius Red ( F ) and IHC for α-SMA, scale bar 50 µm ( G ) with quantification below. n.s.: not significant, ** p < 0.01, *** p < 0.001 by 2-way ANOVA. Mice per genotype ( n = 3) with representative images quantified ( n = 4–11).

Article Snippet: For STAT3 inhibition, 2-month-old WT and DKO mice received daily intraperitoneal injection of TTI-101 (MedChemExpress HY-112288; 100 mg/kg) for three weeks.

Techniques:

Journal: Cell Death & Disease

Article Title: BRUCE liver-KO enhances MASLD/MASH development in the steatotic PTEN-KO background by impairing mitochondrial metabolism and activating STAT3

doi: 10.1038/s41419-025-08294-5

Figure Lengend Snippet: IHC of BRUCE, PTEN and pSTAT3-Y705 in consecutive liver sections from healthy individuals and MASH specimens at 40x ( A , scale bar 400 µm) and 200x magnification ( B , scale bar 100 µm) shows nuclear pSTAT3-Y705 positivity only in MASH livers, with quantification shown ( C ). Birc6 ( D ) and Pten ( E ) expression across normal livers and MASH fibrosis stages F0-F4 were analyzed using GEO2R, with Birc6 and Pten co-expression ( F ) and Stat3 expression ( G ) shown. Birc6 ( H ) and Pten ( I ) expression in normal and MASH livers with varying NAS scores were also analyzed. All data were from the GSE162694 dataset. ( J ) A model illustrating BRUCE/PTEN-STAT3 axis in MASLD/MASH regulation: The combined loss of BRUCE (BRUCE→mt→FAO) and PTEN (PTEN┫AKT → DNL) creates a ‘double hit’ that exacerbates MASLD. BRUCE deficiency impairs mitochondrial metabolism (specifically, fatty acid oxidation, respiration, and bioenergetics), while PTEN loss activates the AKT pathway, promoting de novo lipogenesis. Together, these defects intensify hepatic lipid accumulation, driving MASLD. Additionally, BRUCE loss increases DNA damage, apoptosis, and compensatory hepatocyte proliferation, further elevating oxidative stress. This cumulative oxidative stress, amplified by AKT-driven oxidative stress signals, triggers STAT3 activation in both hepatocytes and non-parenchymal cells, driving progression to MASH with fibrosis, which can be mitigated by STAT3 inhibitor TTI-101. Yellow-highlighted areas represent steatosis-promoting events. mt: mitochondria. *** p < 0.001 by student’s t test. Normal ( n = 5), MASH ( n = 4), with representative images quantified ( n = 8). Normal histology ( n = 33), F0 ( n = 33), F1 ( n = 30), F2 ( n = 27), F3 ( n = 8), F4 ( n = 12).

Article Snippet: For STAT3 inhibition, 2-month-old WT and DKO mice received daily intraperitoneal injection of TTI-101 (MedChemExpress HY-112288; 100 mg/kg) for three weeks.

Techniques: Expressing, Amplification, Activation Assay

Journal: Cell Death & Disease

Article Title: IGFBP2/ITGA5 promotes gefitinib resistance via activating STAT3/CXCL1 axis in non-small cell lung cancer

doi: 10.1038/s41419-024-06843-y

Figure Lengend Snippet: RT-qPCR primers.

Article Snippet: 20 mg/kg gefitinib was administrated by gavage for 10 days after inoculation, followed by the injection of adenoviral sh-IGFBP2 (10 μL) or STAT3 inhibitor TTI-101 (10 mg, Sigma-Aldrich, St Louis, MO, USA) for 20 days.

Techniques:

Journal: Cell Death & Disease

Article Title: IGFBP2/ITGA5 promotes gefitinib resistance via activating STAT3/CXCL1 axis in non-small cell lung cancer

doi: 10.1038/s41419-024-06843-y

Figure Lengend Snippet: A The putative binding sites between STAT3 and CXCL1 promoter were predicted by JASPAR, a database of transcription factor binding profiles (genereg.net). B The protein levels of STAT3 and p-STAT3 were detected by western blot with quantitative analysis. C The luciferase activity was assessed using dual luciferase reporter assay. (D-F) The interactions among STAT3, H3K27Ac, RNA pol II and CXCL1 promoter in tumor tissues and NSCLC cells were detected by ChIP assay. G , H The mRNA and protein levels of CXCL1 were detected by qRT-PCR and western blot, respectively. In B , C , G , H Dunnett’s test of one-way ANOVA. In D – F , Student’s t -test. * P < 0.05, ** P < 0.01, *** P < 0.001. IgG, normal IgG control; Input, total chromatin, IP immunoprecipitation; MUT mutant; OE-NC overexpression vector alone; sh-NC negative control shRNA; WT wild type.

Article Snippet: 20 mg/kg gefitinib was administrated by gavage for 10 days after inoculation, followed by the injection of adenoviral sh-IGFBP2 (10 μL) or STAT3 inhibitor TTI-101 (10 mg, Sigma-Aldrich, St Louis, MO, USA) for 20 days.

Techniques: Binding Assay, Western Blot, Luciferase, Activity Assay, Reporter Assay, Quantitative RT-PCR, Control, Chromatin Immunoprecipitation, Immunoprecipitation, Mutagenesis, Over Expression, Plasmid Preparation, Negative Control, shRNA

Journal: Cell Death & Disease

Article Title: IGFBP2/ITGA5 promotes gefitinib resistance via activating STAT3/CXCL1 axis in non-small cell lung cancer

doi: 10.1038/s41419-024-06843-y

Figure Lengend Snippet: A The association between STAT3 and CXCL1 promoter was detected by ChIP assay. B The protein levels of VEGFR, STAT3 and p-STAT3 in the nucleus and cytoplasm were detected by western blot. C The protein level of CXCL1 was detected by western blot. D The immunoreactivities of STAT3 and CXCL1 in lung metastases were detected by IHC analysis.

Article Snippet: 20 mg/kg gefitinib was administrated by gavage for 10 days after inoculation, followed by the injection of adenoviral sh-IGFBP2 (10 μL) or STAT3 inhibitor TTI-101 (10 mg, Sigma-Aldrich, St Louis, MO, USA) for 20 days.

Techniques: Western Blot

Journal: Cell Death & Disease

Article Title: IGFBP2/ITGA5 promotes gefitinib resistance via activating STAT3/CXCL1 axis in non-small cell lung cancer

doi: 10.1038/s41419-024-06843-y

Figure Lengend Snippet: The interaction relation between IGFBP2 and ITGA5 through A BioGRID and B String databases. C , D The protein levels of ITGA5, STAT3, p-STAT3 and CXCL1 were detected by western blot.

Article Snippet: 20 mg/kg gefitinib was administrated by gavage for 10 days after inoculation, followed by the injection of adenoviral sh-IGFBP2 (10 μL) or STAT3 inhibitor TTI-101 (10 mg, Sigma-Aldrich, St Louis, MO, USA) for 20 days.

Techniques: Western Blot

Journal: Cell Death & Disease

Article Title: IGFBP2/ITGA5 promotes gefitinib resistance via activating STAT3/CXCL1 axis in non-small cell lung cancer

doi: 10.1038/s41419-024-06843-y

Figure Lengend Snippet: A The scheme of the in vivo experiment design. Representative photos of lung metastases with quantitative analysis and in vivo imaging of lung tissues. The immunoreactivities of IGFBP2, STAT3 and CXCL1 in lung metastases were detected by IHC analysis. Dunnett’s test of one-way ANOVA. * P < 0.05; ** P < 0.01; *** P < 0.001.

Article Snippet: 20 mg/kg gefitinib was administrated by gavage for 10 days after inoculation, followed by the injection of adenoviral sh-IGFBP2 (10 μL) or STAT3 inhibitor TTI-101 (10 mg, Sigma-Aldrich, St Louis, MO, USA) for 20 days.

Techniques: In Vivo, In Vivo Imaging

Journal: Cell Death & Disease

Article Title: IGFBP2/ITGA5 promotes gefitinib resistance via activating STAT3/CXCL1 axis in non-small cell lung cancer

doi: 10.1038/s41419-024-06843-y

Figure Lengend Snippet: IGFBP2/ITGA5 promoted gefitinib resistance via activating STAT3/CXCL1 axis.

Article Snippet: 20 mg/kg gefitinib was administrated by gavage for 10 days after inoculation, followed by the injection of adenoviral sh-IGFBP2 (10 μL) or STAT3 inhibitor TTI-101 (10 mg, Sigma-Aldrich, St Louis, MO, USA) for 20 days.

Techniques: