Journal: Theranostics

Article Title: A novel ferroptosis inhibitor, Thonningianin A, improves Alzheimer's disease by activating GPX4

doi: 10.7150/thno.98172

Figure Lengend Snippet: Identification of ThA as a potent inhibitor of ferroptosis. (A) Screening for inhibitors of ferroptosis in PC-12 cells exposed to RSL-3; green indicates the lowest cell viability and red represents the highest cell viability. (B) Molecular structure of ThA. (C-F) Bar charts show PC-12 and SH-SY5Y cell viability treated with 0.5 μM RSL-3 or 20 μM erastin in the presence or absence of ThA and Lip-1 at specified concentrations. (G) Bar chart indicates PC-12 cell viability treated with 10 ng/mL TNF-α and 10 nM SM-164. (T/S) with or without 8 μM ThA and 2 μM ZVF. (H) Bar chart indicates PC-12 cell viability treated with 1 μg/mL LPS and 5 μM nigericin. (L/N) in the presence or absence of 8 μM ThA, 20 μM MCC, and 10 μM NSA. (I) Bar chart indicates the viability of PC-12 cells treated with 5 ng/mL TNF-α, 1 μM SM-164, and 10 μM ZVF. (T/S/Z) with or without 8 μM ThA and 10 μM Nec-1. (J) LifeAct-GFP-transfected PC-12 cells were treated with 0.5 μM RSL-3 with or without 8 μM ThA. Mitochondrial morphology was then assessed through Mito-Tracker staining, and representative images captured. Magnification: 40×; Scale bars: 200 μm. (K) Representative images of PC-12 cells stained with JC-1-, DCFDA-, or C11 BODIPY after treatment with 0.5 μM RSL-3 with or without 8 μM ThA. Magnification: 10×; Scale bars: 200 μm. (L-N) Bar charts indicate the relative JC-1 RFP/GFP ratio, DCFDA intensity, and C11 GFP/RFP ratio. (O) Bar chart indicates the relative MDA content in PC-12 cells treated with 0.5 μM RSL-3 in the presence or absence of 8 μM ThA and 0.2 μM Lip-1. (P) Representative Western blotting images of 4-HNE and β-actin in PC-12 cells treated with 0.5 μM RSL-3 with or without 8 μM ThA. Full-length Western blot images are available in . (Q) Bar chart indicates the ratio of 4-NHE to β-actin. Bar, SD. *, p < 0.05; **, p < 0.01; ***, p < 0.001.

Article Snippet: In brief, cells were lysed in 1× RIPA buffer containing Tris-HCl, NaCl, EDTA, Triton X-100, sodium dodecyl sulfate (SDS), sodium deoxycholate, and phosphatase and protease inhibitors (Topscience, Shanghai, China).

Techniques: Transfection, Staining, Western Blot

Journal: Acta Pharmaceutica Sinica. B

Article Title: USP51/GRP78/ABCB1 axis confers chemoresistance through decreasing doxorubicin accumulation in triple-negative breast cancer cells

doi: 10.1016/j.apsb.2025.03.004

Figure Lengend Snippet: GRP78 promotes TNBC chemoresistance by regulating ATP binding cassette subfamily B member 1 (ABCB1)-mediated DOX efflux. (A) Fluorescence detection of DOX in Cal51 and Cal51 R cells. (B) Western blotting of GRP78 and fluorescence detection of DOX in GRP78-treated Cal51 R cells treated with DOX (1 μmol/L) in the presence or absence of Encequidar (100 nmol/L). (C) Co-IP assay of GRP78 and ABCB1 in Cal51 R cells. (D) Immunofluorescence staining of GRP78 and ABCB1 in ABCB1-Myc/Cal51 R . (E) Analysis of ABCB1 nanodiscs via electron microscopy. (F) Western blotting of ABCB1 expression in nanodiscs derived from Ctrl/HeLa and ABCB1/HeLa cells. (G) ATPase activity assay of ABCB1 nanodiscs with purified GST or GST-GRP78 proteins. (H–M) Cell viability (H), colony formation (I), cell apoptosis (J, K) and γ H2AX foci formation (L, M) were examined in shGRP78/Cal51 R cells treated with DOX alone or in combination with Encequidar (100 nmol/L). ∗∗∗ P < 0.001; ns represents no significant difference; the data in A, B, I, J and M were assessed via unpaired Student's t -test. The data are presented as the mean ± SD in (A, B, G–J, M). The data are representative of three (A, B, G, I, J, M) or four (H) independent experiments.

Article Snippet: The dose of the ABCB1 inhibitor Encequidar (TOPSCIENCE, Shanghai, China) was 100 nmol/L.

Techniques: Binding Assay, Fluorescence, Western Blot, Co-Immunoprecipitation Assay, Immunofluorescence, Staining, Electron Microscopy, Expressing, Derivative Assay, Activity Assay, Purification

Journal: Acta Pharmaceutica Sinica. B

Article Title: USP51/GRP78/ABCB1 axis confers chemoresistance through decreasing doxorubicin accumulation in triple-negative breast cancer cells

doi: 10.1016/j.apsb.2025.03.004

Figure Lengend Snippet: Increased expression of USP51, GRP78 and ABCB1 is correlated with chemoresistance in TNBC. (A) Representative image of immunohistochemical staining of USP51, GRP78 and ABCB1 in serial sections from chemoresistant and nonresistant tumors is shown. (B–D) Direct associations of USP51, GRP78 and ABCB1 expression with chemoresistance were observed in human breast cancer samples. (E) Positive correlation between USP51 and GRP78 expression was observed in human breast cancer samples. (F, G) A positive correlation between the USP51 and GRP78 contents and pathological grade was observed in human breast cancer samples. (H, I) Direct associations between USP51 and GRP78 expression levels and advanced TNM stage were observed in human breast cancer samples. (J–L) Direct associations of USP51, GRP78 and ABCB1 expression with chemoresistance were observed in human TNBC samples. (M) A positive correlation between USP51 expression and GRP78 expression was observed in human TNBC samples. (N, O) A positive association between USP51 and GRP78 expression levels and pathological grade was observed in human TNBC samples. (P, Q) Direct associations between USP51 and GRP78 contents and advanced TNM stage were observed in human TNBC samples. (R–U) Kaplan–Meier curves of overall survival in TNBC patients with high or low expression of USP51, GRP78 and ABCB1 in their breast tumors. The data in B–U were assessed via Spearman's rank correction test.

Article Snippet: The dose of the ABCB1 inhibitor Encequidar (TOPSCIENCE, Shanghai, China) was 100 nmol/L.

Techniques: Expressing, Immunohistochemical staining, Staining

Journal: Acta Pharmaceutica Sinica. B

Article Title: USP51/GRP78/ABCB1 axis confers chemoresistance through decreasing doxorubicin accumulation in triple-negative breast cancer cells

doi: 10.1016/j.apsb.2025.03.004

Figure Lengend Snippet: Working model concerning the mechanism of the USP51/GRP78/ABCB1 network in TNBC chemoresistance.

Article Snippet: The dose of the ABCB1 inhibitor Encequidar (TOPSCIENCE, Shanghai, China) was 100 nmol/L.

Techniques: