Journal: Advanced Science

Article Title: Cuproptosis and Mitophagy Mediated by the THUMPD1/IGF2R‐Dependent Suppression of AKT and Activation of AMPK Signaling Suppress Lung Adenocarcinoma Progression

doi: 10.1002/advs.202521238

Figure Lengend Snippet: Cu + overload and cuproptosis‐associated metabolic stress promote excessive mitophagy in LUAD. (a) Transmission electron microscopy (TEM) images. Top row: overview (scale bar: 50 µm); bottom row: magnified views (scale bar: 20 µm) showing progressive mitochondrial damage and mitophagosome formation (red arrows) in THUMPD1‐overexpressing (OE) cells compared to vector control (Vec), with partial rescue upon IGF2R knockdown (OE + IGF2R sh). Images B–E (OE group) are all from the same OE sample, representing different stages of mitochondrial damage. (b) Validation of central‐carbon metabolites changes in A549 and PC9 cells by assay kits. (c) Western blot of SLC31A1, FDX1, and lipoylated DLAT/DLST. (d‐e) Intracellular Cu + measurements in A549 (d) and PC‐9 (e) cells across the indicated groups. Left: quantitative Cu + levels measured by assay kit. Right: representative CopperSensor‐1 (CS1) fluorescence images. Values are mean ± s.d. of n = 3 biological replicates in b‐e. One‐way ANOVA was used for comparisons among multiple groups. Significance: *p < 0.05; **p < 0.01; ****p < 0.0001. Original unprocessed blots are shown in Figure .

Article Snippet: Antibodies against THUMPD1 (Proteintech, 14921‐1‐AP), anti‐puromycin (Abcam, ab315887), IGF2R (Proteintech, 20253‐1‐AP), SLC31A1 (ABclonal, A10109), FDX1 (Proteintech, 12592‐1‐AP), Lipoic acid antibody (Abcam, ab58724), PINK1 (Abcam, ab216144), Parkin (Servicebio, GB15596), LC3 (Abmart, T55992 ), p‐AKT (Abmart, T40067 ), AKT (Abmart, T55561 ), p‐AMPK (CST, #2535), AMPK (CST, #5831), PPP2R1A (HUABIO, HA500160 ) and β‐actin (Servicebio, GB15003) were used.

Techniques: Transmission Assay, Electron Microscopy, Plasmid Preparation, Control, Knockdown, Biomarker Discovery, Western Blot, Measured Assay, Fluorescence

Journal: Advanced Science

Article Title: Cuproptosis and Mitophagy Mediated by the THUMPD1/IGF2R‐Dependent Suppression of AKT and Activation of AMPK Signaling Suppress Lung Adenocarcinoma Progression

doi: 10.1002/advs.202521238

Figure Lengend Snippet: Proposed schematic model of the tumor‐suppressive mechanism mediated by the THUMPD1/IGF2R signaling axis in LUAD. THUMPD1 binds to IGF2R mRNA in the nucleus and promotes its export to the cytoplasm, thereby enhancing IGF2R translation. The increased IGF2R protein suppresses AKT signaling, at least in part through interaction with PPP2R1A, which may facilitate PP2A‐associated dephosphorylation of AKT, leading to activation of AMPK. Activated AMPK stabilizes and upregulates the copper transporter SLC31A1, resulting in elevated intracellular Cu + accumulation. Excess Cu + induces cuproptosis by disrupting lipoylated TCA cycle proteins and mitochondrial metabolism, while simultaneously triggering excessive mitophagy. The combined effects of copper‐dependent cell death and uncontrolled mitophagy ultimately suppress LUAD cell proliferation and metastasis. Created with BioRender.com.

Article Snippet: Antibodies against THUMPD1 (Proteintech, 14921‐1‐AP), anti‐puromycin (Abcam, ab315887), IGF2R (Proteintech, 20253‐1‐AP), SLC31A1 (ABclonal, A10109), FDX1 (Proteintech, 12592‐1‐AP), Lipoic acid antibody (Abcam, ab58724), PINK1 (Abcam, ab216144), Parkin (Servicebio, GB15596), LC3 (Abmart, T55992 ), p‐AKT (Abmart, T40067 ), AKT (Abmart, T55561 ), p‐AMPK (CST, #2535), AMPK (CST, #5831), PPP2R1A (HUABIO, HA500160 ) and β‐actin (Servicebio, GB15003) were used.

Techniques: De-Phosphorylation Assay, Activation Assay

Journal: Materials Today Bio

Article Title: PKA activation rescues myocardial injury elicited by silica nanoparticles through improving oxidative stress, mitochondrial health, and copper homeostasis

doi: 10.1016/j.mtbio.2026.103021

Figure Lengend Snippet: PKA mitigated copper overload triggered by SiNPs. (A) In the SiNPs-instilled rats, enhanced copper contents in both serum (a) and myocardial tissues (b) were detected, but PKA agonist Forskolin reversed it. n = 9-10 per group. (B) The dose-dependent elevation of intracellular Cu 2+ content by SiNPs treatment in the in vitro cultured AC16 cardiomyocytes (a), which could be greatly reduced by PKA stimulator 8-Br-cAMP but increased by PKA inhibitor H89 (b). (C) The expressions of copper metabolism-related protein (FDX1, SLC31A1, and ATP7B) in AC16 cells were measured (C-a, protein bands; C-b, bands analysis). Also, the expression of ATP7B was measured in rat myocardial tissue (D). n = 3. ∗ p < 0.05 vs control, # p < 0.05 vs SiNPs or SiNPs + Forskolin.

Article Snippet: Primary antibodies for PKA, p -PKA, p -DRP1 s637 , SLC31A1, and ATP7B were purchased from ABclonal, China; FDX1 from Proteintech, USA; and DRP1 and GAPDH from CST, USA.

Techniques: In Vitro, Cell Culture, Expressing, Control

Journal: Investigative Ophthalmology & Visual Science

Article Title: Tannic Acid Achieves Rapid Scar-Free Corneal Healing by Chelating Excess Copper to Suppress Aberrant LOX-Mediated Fibrosis

doi: 10.1167/iovs.67.3.13

Figure Lengend Snippet: Transcriptomic analysis reveals tannic acid's anti-fibrotic mechanisms in injured rabbit corneas. ( A ) Volcano plot showing differentially expressed genes (DEGs) between TA-treated and control groups ( n = 3). ( B ) Gene Ontology (GO) enrichment analysis of DEGs, categorized into biological process (BP), cellular component (CC), and molecular function (MF). ( C ) Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of DEGs. ( D ) Gene Set Enrichment Analysis (GSEA) based on REACTOME gene sets. ( E ) Heatmap displaying key DEGs associated with inflammatory response, redox homeostasis, and corneal scarring. ( F – K ) RT-qPCR validation of mRNA expression levels of representative genes in rabbit corneas at day 28 following different treatments ( n = 3), including F SOD2 , G ACTA2 , H IL1B , I LOX , J LOXL2 , and K SLC31A1 . * P < 0.05, ** P < 0.01, *** P < 0.001, **** P < 0.0001. Mean ± SD, 1-way ANOVA.

Article Snippet: After blocking, membranes were incubated with primary antibodies against LOX (1:1000, 17958-1-AP; Proteintech), LOXL2 (1:1000, GTX105085; GeneTex), CTR1 (1:5000, 67221-1-Ig; Proteintech), VIM (1:20000, 60330-1-Ig; Proteintech), α-SMA (1:5000, 14395-1-AP; Proteintech), IL-1β (1:1000, ab234437; Abcam), and β-actin (1:10000, AC026; ABclonal), followed by HRP-conjugated secondary antibodies (1:10000, SA00001-2; Proteintech).

Techniques: Control, Quantitative RT-PCR, Biomarker Discovery, Expressing

Journal: Investigative Ophthalmology & Visual Science

Article Title: Tannic Acid Achieves Rapid Scar-Free Corneal Healing by Chelating Excess Copper to Suppress Aberrant LOX-Mediated Fibrosis

doi: 10.1167/iovs.67.3.13

Figure Lengend Snippet: Tannic acid reduces fibrosis by chelating excess copper to inhibit lox expression and activity. ( A ) Quantitative analysis of copper concentration in corneal tissues following different treatments (FK = fungal keratitis; CED = corneal epithelial defect; n = 3). ( B ) Quantitative analysis of LOX enzymatic activity in corneal tissues following different treatments ( n = 3). ( C ) Quantitative analysis of central corneal thickness in TA-treated ALK model at day 56 compared with healthy controls ( n = 3). ( D ) Representative Western blot images of LOX, LOXL2, CTR1, VIM, α-SMA, IL-1β, and β-actin protein expression in rabbit corneas at day 28 and ( E – J ) corresponding quantitative analyses of E LOX, F LOXL2, G CTR1, H VIM, I α-SMA, and J IL-1β protein levels ( n = 3). ns, not significant, * P < 0.05, ** P < 0.01, *** P < 0.001, **** P < 0.0001. Mean ± SD, 1-way ANOVA.

Article Snippet: After blocking, membranes were incubated with primary antibodies against LOX (1:1000, 17958-1-AP; Proteintech), LOXL2 (1:1000, GTX105085; GeneTex), CTR1 (1:5000, 67221-1-Ig; Proteintech), VIM (1:20000, 60330-1-Ig; Proteintech), α-SMA (1:5000, 14395-1-AP; Proteintech), IL-1β (1:1000, ab234437; Abcam), and β-actin (1:10000, AC026; ABclonal), followed by HRP-conjugated secondary antibodies (1:10000, SA00001-2; Proteintech).

Techniques: Expressing, Activity Assay, Concentration Assay, Western Blot

Journal: Investigative Ophthalmology & Visual Science

Article Title: Tannic Acid Achieves Rapid Scar-Free Corneal Healing by Chelating Excess Copper to Suppress Aberrant LOX-Mediated Fibrosis

doi: 10.1167/iovs.67.3.13

Figure Lengend Snippet: Exogenous copper supplementation reverses tannic acid's anti-fibrotic effects. ( A ) Representative Western blot images of LOX, LOXL2, CTR1, VIM, α-SMA, and β-actin protein expression in rabbit corneas at day 28 following different treatments and ( B – F ) corresponding quantitative analyses of B LOX, C LOXL2, D CTR1, E VIM, and F α-SMA protein levels ( n = 3). * P < 0.05, ** P < 0.01, *** P < 0.001, **** P < 0.0001. Mean ± SD, n = 3; 1-way ANOVA.

Article Snippet: After blocking, membranes were incubated with primary antibodies against LOX (1:1000, 17958-1-AP; Proteintech), LOXL2 (1:1000, GTX105085; GeneTex), CTR1 (1:5000, 67221-1-Ig; Proteintech), VIM (1:20000, 60330-1-Ig; Proteintech), α-SMA (1:5000, 14395-1-AP; Proteintech), IL-1β (1:1000, ab234437; Abcam), and β-actin (1:10000, AC026; ABclonal), followed by HRP-conjugated secondary antibodies (1:10000, SA00001-2; Proteintech).

Techniques: Western Blot, Expressing