Journal: Frontiers in Immunology

Article Title: Lipoprotein (a) fuels EV71 replication by activating p38 MAPK-autophagy axis

doi: 10.3389/fimmu.2026.1865808

Figure Lengend Snippet: Modulation of Lp(a)-induced autophagy alters EV71 replication. (A) Cells were treated with 40 mg/L Lp(a) and/or the autophagy inhibitor Chloroquine (CQ). Co-treatment with CQ and Lp(a) further decreased LC3-II and VP1 levels compared to EV71 infection alone or with Lp(a). Quantification (bottom) showed that Lp(a) increases LC3-II and VP1 levels during EV71 infection, and CQ decreases LC3-II accumulation and VP1 expression. (B) The combination of EV71, Lp(a), and CQ shows a marked decrease in LC3-positive puncta. (C) Cells were treated with 40 mg/L Lp(a) and/or the autophagy inhibitor 3-Methyladenine (3-MA). 3-MA treatment suppresses Lp(a)-induced LC3-II accumulation and reduced VP1 protein levels. Quantification (bottom) shows significant suppression of Lp(a)-enhanced EV71 replication by 3-MA. (D) 3-MA treatment reduces the formation of LC3-positive puncta induced by EV71 and Lp(a). (E) Cells were treated with 40 mg/L Lp(a) and/or the autophagy inducer Rapamycin (Rapa). Rapamycin enhances the LC3-II accumulation induced by Lp(a) and further increased VP1 protein levels. Quantification (bottom) shows significant upregulation of LC3-II and VP1 following autophagy activation. (F) Rapamycin treatment enhances the formation of LC3-positive puncta induced by EV71 and Lp(a). Cells were stained for LC3 (red) to visualize autophagosomes and with DAPI (blue) for nuclei. Scale bar, 10 µm. Data are presented as mean ± SD; * P < 0.05, ** P < 0.01, *** P < 0.001, **** P < 0.0001.

Article Snippet: The autophagy inhibitor 3-methyladenine (3-MA) (MCE, MedChemExpress), chloroquine (CQ) (MCE, MedChemExpress) and the autophagy activator rapamycin (MCE, MedChemExpress), were freshly dissolved in DMSO at stock concentrations of 20 mM, 100 mM, 100 mM, respectively.

Techniques: Infection, Expressing, Activation Assay, Staining

Journal: Aging Cell

Article Title: Unveiling the AcSirt2 ‐ FOXO ‐Mitophagy Axis: Insights Into Mitochondrial Quality Control and Delayed Aging in Apis cerana

doi: 10.1111/acel.70645

Figure Lengend Snippet: In vivo modulation of AcSirt2 influences aging, motor function, and brain ultrastructure in A. cerana . (A) Relative mRNA expression levels of AcSirt2 in the brains of worker bees at 24, 48, and 72 h after dsAcSirt2 or dsEGFP (control) treatment, determined by RT‐qPCR ( n = 3; 3 bees per time point per treatment). (B) AcSirt2 protein expression levels in bee brains at 24, 48, and 72 h post dsAcSirt2 or dsEGFP treatment, analyzed by Western blot ( n = 3; 3 bees per time point per treatment). (C) Survival curves of worker bees continuously fed dsAcSirt2 or dsEGFP (control) from day 7 after eclosion ( N = 150 per group; 50 bees per cup, 3 biological replicates). (D) Survival curves of worker bees treated with the Sirt2 activator SRT1720 or DMSO (control) from day 7 after eclosion ( N = 150 per group; 50 bees per cup, 3 biological replicates). (E) Senescence‐associated β‐galactosidase (SA‐β‐gal) staining of worker bee brains from different treatment groups. Blue staining indicates SA‐β‐gal‐positive senescent cells ( n = 3). (F, G) Motor function tests of worker bees in different treatment groups and the percentage of bees that reached the top feeding platform within 15 s ( N = 120 per group; 40 bees per cup, 3 biological replicates). (H, I) TEM images of brain cells from worker bees in different treatment groups (scale bar: 500 nm) and quantitative analysis of mitochondrial damage rate and autophagosome number ( n = 3; five fields per bee). Yellow arrows indicate normal mitochondria; red arrows indicate damaged mitochondria; blue arrows indicate autophagosomes. Data in (A, B, H, I) are presented as mean ± SEM. For panels (A, B), two‐way ANOVA (treatment × time) with Tukey's post hoc test: Treatment F (1, 12), time F (2, 12), interaction F (2, 12). For survival curves (C, D): Log‐rank (Mantel‐Cox) test, df = 1 each. For motor function (F, G): Chi‐square test, df = 1 each. For panels (H, I): One‐way ANOVA with Tukey's post hoc test (four groups), F (3, 8). (E) Shows representative images without statistical comparison. * p < 0.05, ** p < 0.01, *** p < 0.001.

Article Snippet: To pharmacologically modulate Sirt2 activity, we prepared stock solutions of the activator SRT1720 (MCE, USA) and the inhibitor AK‐1 (MCE, USA) in dimethyl sulfoxide (DMSO, ≥ 99.9% cell culture grade, Sigma‐Aldrich, USA) at a concentration of 5 mM.

Techniques: In Vivo, Expressing, Control, Quantitative RT-PCR, Western Blot, Staining, Comparison

Journal: Aging Cell

Article Title: Unveiling the AcSirt2 ‐ FOXO ‐Mitophagy Axis: Insights Into Mitochondrial Quality Control and Delayed Aging in Apis cerana

doi: 10.1111/acel.70645

Figure Lengend Snippet: AcSirt2 interacts with FOXO and mediates its deacetylation to regulate mitochondrial function, autophagy, and enzyme activity. (A, B, E) Effects of AcSirt2 knockdown on the activities of antioxidant enzymes and metabolic enzymes in worker bee heads ( n = 3). Enzyme activities include: SOD and CAT (A); α‐KGDH and IDH (B); ATPase (E). (C, D, F) Effects of AcSirt2 activation by SRT1720 on the activities of antioxidant enzymes and metabolic enzymes in worker bee heads ( n = 3). Enzyme activities include: SOD and CAT (C); α‐KGDH and IDH (D); ATPase (F). (G, H) Effects of AcSirt2 knockdown (G) and SRT1720 treatment (H) on ATP levels in worker bee heads ( n = 3). (I, J) Effects of AcSirt2 knockdown (I) and SRT1720 treatment (J) on ROS levels in worker bee heads ( n = 3). (K, L) Protein levels of the mitophagy‐initiating protein PINK1 in worker bee heads upon AcSirt2 knockdown (K) or SRT1720 treatment (L) ( n = 3). (M) Co‐IP assay confirming the in vivo interaction between AcSirt2 and AcFOXO ( n = 3). (N, O) Relative acetylation level of AcFOXO (normalized to total AcFOXO) upon AcSirt2 knockdown (N) or SRT1720 treatment (O), as detected by Co‐IP/Western blot ( n = 3). Data are presented as mean ± SEM. All comparisons were performed using unpaired Student's t ‐test (df = 4 for each comparison). * p < 0.05, ** p < 0.01, *** p < 0.001.

Article Snippet: To pharmacologically modulate Sirt2 activity, we prepared stock solutions of the activator SRT1720 (MCE, USA) and the inhibitor AK‐1 (MCE, USA) in dimethyl sulfoxide (DMSO, ≥ 99.9% cell culture grade, Sigma‐Aldrich, USA) at a concentration of 5 mM.

Techniques: Activity Assay, Knockdown, Activation Assay, Co-Immunoprecipitation Assay, In Vivo, Western Blot, Comparison

Journal: Frontiers in Oncology

Article Title: CFTR functions as a tumor suppressor in adenoid cystic carcinoma and its silencing reveals an associated vulnerability involving the Hsp70 chaperone system

doi: 10.3389/fonc.2026.1836263

Figure Lengend Snippet: Pharmacological modulation of Hsp70 alters cell viability and reveals divergent MAPK1 transcriptional responses in SACC-83 and SACC-LM cells. (A) Cell viability of SACC-83 and SACC-LM cells treated with VER155008 at 0, 10, 20, and 40 μM, as determined by CCK-8 assay. (B) Positive cell ratio of SACC-83 and SACC-LM cells treated with HSF1A at 0, 200, 500, 1000, and 1500 nM, as determined by CCK-8 assay. (C) RT-qPCR analysis of MAPK1 and HSPA1A mRNA expression in SACC-83 cells following VER155008 treatment (left, middle) and HSPA1A expression following HSF1A treatment (right). (D) RT-qPCR analysis of MAPK1 and HSPA1A mRNA expression in SACC-LM cells following VER155008 treatment (left, middle) and HSPA1A expression following HSF1A treatment (right). (E) Representative Western blot images showing Hsp70 protein expression in SACC-83 cells treated with VER155008 or HSF1A, with GAPDH as the loading control. (F) Densitometric quantification of Hsp70 protein levels normalized to GAPDH in SACC-83 cells following VER155008 (left) and HSF1A (right) treatment. (G) Representative Western blot images showing Hsp70 protein expression in SACC-LM cells treated with VER155008 or HSF1A, with GAPDH as the loading control. (H) Densitometric quantification of Hsp70 protein levels normalized to GAPDH in SACC-LM cells following VER155008 (left) and HSF1A (right) treatment. Data are presented as mean ± SD from n = 3 independent biological experiments. *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001.

Article Snippet: The functional impact of Hsp70 modulation was assessed using the inhibitor VER155008 (MedChemExpress, HY10941) and the heat shock response activator HSF1A (MedChemExpress, HY103000 ).

Techniques: CCK-8 Assay, Quantitative RT-PCR, Expressing, Western Blot, Control

Journal: Frontiers in Oncology

Article Title: CFTR functions as a tumor suppressor in adenoid cystic carcinoma and its silencing reveals an associated vulnerability involving the Hsp70 chaperone system

doi: 10.3389/fonc.2026.1836263

Figure Lengend Snippet: Pharmacological modulation of Hsp70 alters the migration and invasion capacities of SACC-83 and SACC-LM cells. (A, B) Wound-healing assays evaluating the migration of SACC-83 (A) and SACC-LM (B) cells following VER155008 treatment. (C, D) Wound-healing assays evaluating the migration of SACC-83 (C) and SACC-LM (D) cells following HSF1A treatment. (E, F) Transwell invasion assays assessing the invasive capacity of SACC-83 (E) and SACC-LM (F) cells treated with VER155008. (G, H) Transwell invasion assays assessing the invasive capacity of SACC-83 (G) and SACC-LM (H) cells treated with HSF1A. Data are presented as mean ± SD from n = 3 independent biological experiments. *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001.

Article Snippet: The functional impact of Hsp70 modulation was assessed using the inhibitor VER155008 (MedChemExpress, HY10941) and the heat shock response activator HSF1A (MedChemExpress, HY103000 ).

Techniques: Migration

Journal: Frontiers in Oncology

Article Title: CFTR functions as a tumor suppressor in adenoid cystic carcinoma and its silencing reveals an associated vulnerability involving the Hsp70 chaperone system

doi: 10.3389/fonc.2026.1836263

Figure Lengend Snippet: Pharmacological and genetic modulation of Hsp70 modulates the proliferation and apoptosis of SACC-83 and SACC-LM cells. (A, B) CCK-8 assays evaluating the proliferation of SACC-83 cells following VER155008 (A) or HSF1A (B) treatment. (C, D) CCK-8 assays evaluating the proliferation of SACC-83 cells with Hsp70 knockdown (C) or overexpression (D) combined with VER155008 treatment. (E, F) CCK-8 assays evaluating the proliferation of SACC-LM cells following VER155008 (E) or HSF1A (F) treatment. (G, H) CCK-8 assays evaluating the proliferation of SACC-LM cells with Hsp70 knockdown (G) or overexpression (H) combined with VER155008 treatment. (I, J) Flow cytometry analysis of apoptosis in SACC-83 cells treated with VER155008 (I) or HSF1A (J) . (K, L) Flow cytometry analysis of apoptosis in SACC-LM cells treated with VER155008 (K) or HSF1A (L) . Data are presented as mean ± SD from n = 3 independent biological experiments. *P < 0.05, ****P < 0.0001.

Article Snippet: The functional impact of Hsp70 modulation was assessed using the inhibitor VER155008 (MedChemExpress, HY10941) and the heat shock response activator HSF1A (MedChemExpress, HY103000 ).

Techniques: CCK-8 Assay, Knockdown, Over Expression, Flow Cytometry

Journal: The Journal of Biological Chemistry

Article Title: Isolinderalactone suppresses the progression of cholangiocarcinoma by modulating the CARMA1-BCL10-MALT1 signalosome

doi: 10.1016/j.jbc.2026.113162

Figure Lengend Snippet: ILL suppresses the NF-κB signaling pathway in CCA cells. A , KEGG pathway enrichment analysis of differentially expressed genes between control and ILL-treated groups. B , GSEA analysis showing enrichment of the NF-κB signaling pathway. C and D , the expressions of p-IκBα (Ser32), IκBα, p-p65 -(Ser468), and p65 in CCA cells treated with different concentrations of ILL were detected by Western blot and quantified (mean ± SD; one-way ANOVA followed by Bonferroni post hoc test; n = 3 biologically independent experiments). E and F , Western blot analysis and quantification of p-IκBα (Ser32), IκBα, p-p65 (Ser468), and p65 in CCA cells treated with ILL, diprovocim, or the combination of ILL and diprovocim (mean ± SD; one-way ANOVA followed by Bonferroni post hoc test; n = 3 biologically independent experiments). G and H , EdU staining and positive rate analysis in CCA cells treated with ILL, diprovocim, or the combination of ILL and diprovocim (mean ± SD; one-way ANOVA followed by Bonferroni post hoc test; n = 3 biologically independent experiments). Scale bars represent 200 μm. I and J , colony formation assays and quantification of colony numbers in CCA cells (mean ± SD; one-way ANOVA followed by Bonferroni post hoc test; n = 3 biologically independent experiments). ∗ p < 0.05, ∗∗ p < 0.01, ∗∗∗ p < 0.001.

Article Snippet: HCCC9810 and RBE cells were pre-exposed to Diprovocim (5 nM, 2 h) and subsequently co-incubated with ILL (20 μm) for 24 h. Additionally, an independent NF-κB activator, PapRIVto (MCE), was applied at 10 μm for 2 h prior to ILL treatment validate the specificity of the rescue effect.

Techniques: Control, Western Blot, Staining

Journal: The Journal of Biological Chemistry

Article Title: Isolinderalactone suppresses the progression of cholangiocarcinoma by modulating the CARMA1-BCL10-MALT1 signalosome

doi: 10.1016/j.jbc.2026.113162

Figure Lengend Snippet: ILL inhibits NF-κB signaling by modulating BCL10 complex formation and inhibiting its ubiquitination. A , co-IP analysis of interactions between BCL10 and CARMA1 or MALT1 in CCA cells expressing WT BCL10. B , co-IP analysis of interactions between BCL10 and CARMA1 or MALT1 in CCA cells expressing WT BCL10 or mutant BCL10 with the effect of ILL. C and D , ubiquitination of BCL10 in BCL10-WT–expressing or BCL10-mut–expressing CCA cells treated with 0 or 20 μm ILL for 24 h.

Article Snippet: HCCC9810 and RBE cells were pre-exposed to Diprovocim (5 nM, 2 h) and subsequently co-incubated with ILL (20 μm) for 24 h. Additionally, an independent NF-κB activator, PapRIVto (MCE), was applied at 10 μm for 2 h prior to ILL treatment validate the specificity of the rescue effect.

Techniques: Ubiquitin Proteomics, Co-Immunoprecipitation Assay, Expressing, Mutagenesis

Journal: The Journal of Biological Chemistry

Article Title: Isolinderalactone suppresses the progression of cholangiocarcinoma by modulating the CARMA1-BCL10-MALT1 signalosome

doi: 10.1016/j.jbc.2026.113162

Figure Lengend Snippet: ILL suppresses tumor growth and NF-κB signaling in vivo . A , schematic diagram of the experimental design for the xenograft mouse model. B , images of excised tumors from each group at the end of the experiment. C , the progression of tumor volume in each group (mean ± SD; one-way ANOVA followed by Bonferroni post hoc test; n = 5 biologically independent experiments). D , the tumor weights at the end of the experiment (mean ± SD; one-way ANOVA followed by Bonferroni post hoc test; n = 5 biologically independent experiments). E , body weight changes of mice during the period (mean ± SD; one-way ANOVA followed by Bonferroni post hoc test; n = 5 biologically independent experiments). F and G , the expressions of p-IκB, IκB, p-p65, and p65 in tumor tissues from each group were detected by Western blot and quantified (mean ± SD; one-way ANOVA followed by Bonferroni post hoc test; n = 3 biologically independent experiments). H , histological analysis of tumor tissues by H&E staining (Scale bars represent 50.8 μm), and IHC staining for Ki-67 and PCNA (Scale bars represent 12.5 μm). I , co-immunoprecipitation analysis of BCL10 interaction with CARMA1 and MALT1 in tumor lysates. ∗ p < 0.05, ∗∗ p < 0.01, ∗∗∗ p < 0.001.

Article Snippet: HCCC9810 and RBE cells were pre-exposed to Diprovocim (5 nM, 2 h) and subsequently co-incubated with ILL (20 μm) for 24 h. Additionally, an independent NF-κB activator, PapRIVto (MCE), was applied at 10 μm for 2 h prior to ILL treatment validate the specificity of the rescue effect.

Techniques: In Vivo, Western Blot, Staining, Immunohistochemistry, Immunoprecipitation