Journal: Veterinary Research

Article Title: Mechanistic role of lipid metabolism in foot-and-mouth disease virus (FMDV) replication

doi: 10.1186/s13567-026-01762-6

Figure Lengend Snippet: The effect of FASN on FMDV replication. A BHK-21 cells were treated with 30 μM C75, 75 μM palmitic acid, or 30 μM C75 plus 75 μM palmitic acid. After fixation, cells were stained with Nile red. Scale bar, 20 µm. B BHK-21 cells were treated with 5–45 μM C75 for 24 h, and cell viability was not significantly affected. C Cytopathic effect (CPE) following FMDV infection in the presence of increasing concentrations of C75. D RT–qPCR confirmed that C75 treatment inhibits FMDV replication. E Western blot analysis verified that C75 treatment suppresses the expression of FMDV VP1 protein. F Combined treatment with 10 μM C75 and TOFA exerted a stronger inhibitory effect on FMDV replication. G Viral plaque assay demonstrated that C75 treatment significantly inhibits FMDV replication. H BHK-21 cells were treated with 5–75 μM palmitic acid for 24 h, and cell viability was not substantially affected. I RT–qPCR showed that, in the presence of 30 μM C75, supplementation with 0–75 μM palmitic acid partially restored FMDV replication. J Western blot analysis confirmed that, in the presence of 45 μM C75, addition of 75 μM palmitic acid partially rescued FMDV VP1 protein expression. K BHK-21 cells were treated with 5–30 μM 2-bromopalmitate (2‑BP) for 24 h, and cell viability was not significantly affected. L RT–qPCR confirmed that 2‑BP treatment inhibits FMDV replication. M Western blot analysis verified that 2‑BP treatment suppresses the expression of FMDV VP1 protein.

Article Snippet: The hamster kidney fibroblasts (BHK-21) used in the experiments were purchased from Wuhan Punosai Life Science and Technology Co. Acetyl-CoA carboxylase inhibitor TOFA (HY-100568) was purchased from MedChemExpress (MCE); fatty acid synthase inhibitor C75 (HY-12364) was purchased from MCE; malonyl-CoA (HY-115899) was purchased from MCE; palmitic acid (HY-N0830) was purchased from MCE; DGAT-1 inhibitor A922500 (HY-10038) was purchased from MCE; oleic acid (HY-N1446) was purchased from MCE; CPT1A inhibitors Etomoxir (HY-50202) and CP640186 (HY-15259) were purchased from MCE; and rabbit polyclonal antibody against FMDV VP1 protein (type O) (bs-41049R) was purchased from Beijing Biosynthesis Biotechnology Co., Ltd. (bioss).

Techniques: Staining, Infection, Quantitative RT-PCR, Western Blot, Expressing, Viral Plaque Assay

Journal: Veterinary Research

Article Title: Mechanistic role of lipid metabolism in foot-and-mouth disease virus (FMDV) replication

doi: 10.1186/s13567-026-01762-6

Figure Lengend Snippet: Utilization of the lipid metabolism model during FMDV infection. ACC catalyzes the carboxylation of acetyl-CoA to generate malonyl-CoA; malonyl-CoA and acetyl-CoA are catalyzed by FASN to produce fatty acids; fatty acids are catalyzed by DGAT-1 to form triglycerides, which are stored in LDs; the degradation of LDs generates a large amount of FFAs, which are transported into mitochondria under the action of CPT1A to participate in β-oxidation for ATP production.

Article Snippet: The hamster kidney fibroblasts (BHK-21) used in the experiments were purchased from Wuhan Punosai Life Science and Technology Co. Acetyl-CoA carboxylase inhibitor TOFA (HY-100568) was purchased from MedChemExpress (MCE); fatty acid synthase inhibitor C75 (HY-12364) was purchased from MCE; malonyl-CoA (HY-115899) was purchased from MCE; palmitic acid (HY-N0830) was purchased from MCE; DGAT-1 inhibitor A922500 (HY-10038) was purchased from MCE; oleic acid (HY-N1446) was purchased from MCE; CPT1A inhibitors Etomoxir (HY-50202) and CP640186 (HY-15259) were purchased from MCE; and rabbit polyclonal antibody against FMDV VP1 protein (type O) (bs-41049R) was purchased from Beijing Biosynthesis Biotechnology Co., Ltd. (bioss).

Techniques: Infection

Journal: Chirality

Article Title: Differential in radiosensitizing potency of enantiomers of the fatty acid synthase inhibitor C75

doi: 10.1002/chir.22668

Figure Lengend Snippet: Structure of the enantiomers of C75.

Article Snippet: Enantiomers of C75 [(−)‐trans‐C75 and (+)‐trans‐C75] were purchased from Santa Cruz Biotechnology.

Techniques:

Journal: Chirality

Article Title: Differential in radiosensitizing potency of enantiomers of the fatty acid synthase inhibitor C75

doi: 10.1002/chir.22668

Figure Lengend Snippet: Cytotoxicity of different stereoisomers of C75. MTT assay of A , PC3 and B , LNCaP cells in response to racemic mixtures of C75 (+/−) from two commercial sources (Sigma‐Aldrich and Santa Cruz Biotechnology), or (−) and (+) enantiomers of C75 from Santa Cruz Biotechnology.

Article Snippet: Enantiomers of C75 [(−)‐trans‐C75 and (+)‐trans‐C75] were purchased from Santa Cruz Biotechnology.

Techniques: MTT Assay

Journal: Chirality

Article Title: Differential in radiosensitizing potency of enantiomers of the fatty acid synthase inhibitor C75

doi: 10.1002/chir.22668

Figure Lengend Snippet: Clonogenic survival of PC3 prostate cancer cells in response to racemic mixtures and enantiomers of C75.

Article Snippet: Enantiomers of C75 [(−)‐trans‐C75 and (+)‐trans‐C75] were purchased from Santa Cruz Biotechnology.

Techniques:

Journal: Chirality

Article Title: Differential in radiosensitizing potency of enantiomers of the fatty acid synthase inhibitor C75

doi: 10.1002/chir.22668

Figure Lengend Snippet: Enhancement of the clonogenic killing activity of x‐radiation by C75 administered in the form of a racemic mixture (+/−) or (−) and (+) enantiomers (Santa Cruz Biotechnology). PC3 cells were treated simultaneously with x‐radiation (2 Gy) and A , 10 μM or B , 25 μM C75. * P < 0.05, ** P < 0.01 compared with x‐radiation alone.

Article Snippet: Enantiomers of C75 [(−)‐trans‐C75 and (+)‐trans‐C75] were purchased from Santa Cruz Biotechnology.

Techniques: Activity Assay

Journal: Cell death and differentiation

Article Title: Fatty acid synthesis promotes mtDNA release via ETS1-mediated oligomerization of VDAC1 facilitating endothelial dysfunction in sepsis-induced lung injury.

doi: 10.1038/s41418-025-01524-5

Figure Lengend Snippet: Fig. 2 Inhibition of fatty acid synthesis ameliorated endotoxemia-induced lung injury and EC activation in vivo. The C57BL/6N mice were i.p. injected with LPS (10 mg/kg) with or without C75 (10 mg/kg, i.p.) pretreatment for 1 h (n = 5). A–C The levels of TNF-α, IL-6, and TF in mice plasma were measured by ELISA (n = 5). D H&E staining showing the tissue injury in the lung (n = 5). E, F IHC staining showing the levels and distribution of VCAM-1 and E-selectin in the lung tissues (n = 5). G, H Immunofluorescent staining showing the levels of fibrinogen (anti- fibrinogen, Red) in lungs from septic mice pretreated with or without C75 (n = 5). CD31 (anti-CD31, Green) was used to label endothelial cells and nuclei were stained in blue with DAPI. I, J Immunoblot showing the expression levels of VCAM-1, E-selectin, PAI-1, and TF in the lung tissues in mice (n = 3). All data were expressed as the mean ± SD. Comparison among three or more groups was analyzed by one-way ANOVA. ns no significance, *p < 0.05, **p < 0.01, ***p < 0.001, and ****p < 0.0001.

Article Snippet: In the intervention group, the mice were i.p injected with C75 (#S9819, Selleck, Shanghai, China) (10mg/kg body weight) before LPS injection.

Techniques: Inhibition, Activation Assay, In Vivo, Injection, Clinical Proteomics, Enzyme-linked Immunosorbent Assay, Staining, Immunohistochemistry, Western Blot, Expressing, Comparison

Journal: Cell death and differentiation

Article Title: Fatty acid synthesis promotes mtDNA release via ETS1-mediated oligomerization of VDAC1 facilitating endothelial dysfunction in sepsis-induced lung injury.

doi: 10.1038/s41418-025-01524-5

Figure Lengend Snippet: Fig. 3 Inhibition of fatty acid synthesis ameliorated LPS-induced EC dysfunction in vitro. A, B HUVEC were pretreated with FASN inhibitor C75 for 30 min before LPS stimuli for 4 h. Protein levels of VCAM-1, E-selectin, PAI-1 and TF were analyzed by western blot (n = 3). C–I The mRNA levels of E-selectin, VCAM-1, ICAM-1, TF, PAI-1, MCP-1 and IL-8 with C75 treatment were detected by RT-qPCR (n = 3). J, K HUVEC were transfected with siRNA specific to FASN before LPS stimuli for 4 h. Protein levels of FASN, VCAM-1, E-selectin, PAI-1 and TF were analyzed by western blot (n = 3). L, M Immunoblot showing the expression levels of VCAM-1, E-selectin, PAI-1, and TF with PA (10 µM) or PAS (20 µM) (n = 3). All data were expressed as the mean ± SD. Comparison among three or more groups was analyzed by one-way ANOVA. ns no significance, *p < 0.05, **p < 0.01, ***p < 0.001, and ****p < 0.0001.

Article Snippet: In the intervention group, the mice were i.p injected with C75 (#S9819, Selleck, Shanghai, China) (10mg/kg body weight) before LPS injection.

Techniques: Inhibition, In Vitro, Western Blot, Quantitative RT-PCR, Transfection, Expressing, Comparison

Journal: Cell death and differentiation

Article Title: Fatty acid synthesis promotes mtDNA release via ETS1-mediated oligomerization of VDAC1 facilitating endothelial dysfunction in sepsis-induced lung injury.

doi: 10.1038/s41418-025-01524-5

Figure Lengend Snippet: Fig. 5 Fatty acid synthesis promoted mtDNA-related activation of cGAS-STING signaling and pyroptosis in ECs in response to LPS. A Heatmap of DEGs enriched in cytosolic DNA-sensing pathway. B–E HUVEC were pretreated with C75 before LPS stimuli. Protein levels of cGAS, p-STING, and p-p65 were determined by western blot (n = 3). F, G Representative immunoblots of cGAS, p-STING, and p-p65 in the lung tissues of septic mice pretreated with or without C75 (n = 3). H, I Confocal images of p65 nuclear translocation in LPS-challenged HUVEC with or without C75 pretreatment. Quantitative results from 8 cells per group are reported. All data were expressed as the mean ± SD. Comparison among three or more groups was analyzed by one-way ANOVA. ns no significance, *p < 0.05, **p < 0.01, ***p < 0.001, and ****p < 0.0001.

Article Snippet: In the intervention group, the mice were i.p injected with C75 (#S9819, Selleck, Shanghai, China) (10mg/kg body weight) before LPS injection.

Techniques: Activation Assay, Western Blot, Translocation Assay, Comparison

Journal: Cell death and differentiation

Article Title: Fatty acid synthesis promotes mtDNA release via ETS1-mediated oligomerization of VDAC1 facilitating endothelial dysfunction in sepsis-induced lung injury.

doi: 10.1038/s41418-025-01524-5

Figure Lengend Snippet: Fig. 8 ETS1 promoted VDAC1 oligomerization to facilitate mtDNA release and EC activation via limiting VDAC1 ubiquitination. A CoIP-MS image of VDAC1. B Molecular docking showing the interaction between ETS1 and VDAC1. C Immunoblot showing the binding of ETS1 with VDAC1 by GST pull-down (n = 3). D, E HUVEC were transfected with siRNA specific to ETS1 before LPS stimuli. The levels of VDAC1 oligomerization were detected by western blot (n = 3). F KEGG analysis of proteins binding to ETS1. G, H HUVEC were transfected with siRNA specific to ETS1 or pretreated with C75 before LPS stimuli. The ubiquitination levels of VDAC1 were detected by western blot (n = 3). All data were expressed as the mean ± SD. Comparison among three or more groups was analyzed by one-way ANOVA. ns no significance, *p < 0.05, **p < 0.01, ***p < 0.001, and ****p < 0.0001.

Article Snippet: In the intervention group, the mice were i.p injected with C75 (#S9819, Selleck, Shanghai, China) (10mg/kg body weight) before LPS injection.

Techniques: Activation Assay, Ubiquitin Proteomics, Western Blot, Binding Assay, Transfection, Comparison

Journal: bioRxiv

Article Title: Integrated stress response associated with dark microglia promotes microglial lipogenesis and contributes to neurodegeneration

doi: 10.1101/2024.03.04.582965

Figure Lengend Snippet: (a) The schematic shows the basic approach to test the predicted mechanism of microglial toxicity. Created with BioRender.com . (b, c) The bar graphs show the qPCR-based measurement of Atf4 and ATF4 target genes in recipient primary OPCs (b) and primary neurons (c) 6 hours after receiving conditioned media from BV2 cells treated with DMSO (DMSO-CM), SLB (SLB-CM), SLB and C75 (C75-SLB-CM), and conditioned media from BV2 cells treated with SLB that was subjected to lipid removal (Lip-SLB-CM, n=3 wells/condition). (d) The bar graph shows the percentage of cCASP3+ apoptotic OLIG2+ OPCs 24 hours after receiving conditioned media from BV2 cells treated as in (b, c) (n=4 wells/condition). (c) Representative immunofluorescence images (left) and quantification (right) show NeuN+ neuronal cells: green, cCASP3+ apoptotic cells: red, DAPI+ nuclei: blue. The bar graphs show cCASP3+ apoptotic NeuN+ neuronal cells 24 hours after receiving conditioned media (n=4 wells/condition). (e) The bar shows the percentage change in the mean firing rate of primary neurons 1 hour after treatment compared to their baseline before drug treatment in an Axion multi-electrode array plate (n=12 wells/condition). (f) Schematic shows a simplified lipid synthesis pathway highlighting the upregulated genes in iPKR and 5xFAD microglia. Adapted from “Lipids and Proteins Involved in Lipid Uptake and Metabolism in Cardiac Lipotoxicity” by BioRender.com (2023). (g) Heatmap shows log2 (fold change) of lipogenesis genes that are differentially regulated (p value<0.05, baseMean>20 by DESeq2) by microglia-specific TRAP sequencing. (h) The pie chart shows the classification of differentially regulated lipid species in SLB-conditioned media compared to control. (i) Schematic shows the bi-weekly month-long treatment of iPKR mice as the intermittent treatment paradigm. (j) Representative immunofluorescence images (left) and quantification (right) show presynaptic VGLUT2+ puncta: gray. The bar graph shows VGLUT2 density normalized in the layer V cortex of 6-month-old vehicle-treated control (n=5), vehicle-treated 5xFAD (n=5), and C75-treated 5xFAD mice (n=5). One-way ANOVA with multiple comparisons. Bar graphs with individual data points show mean ± s.e.m.

Article Snippet: To prepare CM with C75 (Tocris, 2489), BV2 cells were treated with 25μM C75 24 hours after plating and 1 hour before treatment with DMSO or SLB.

Techniques: Immunofluorescence, Sequencing, Control

Journal: Molecular Oncology

Article Title: Combined spatially resolved metabolomics and spatial transcriptomics reveal the mechanism of RACK1 ‐mediated fatty acid synthesis

doi: 10.1002/1878-0261.13752

Figure Lengend Snippet: RACK1 increased SREBP1 mediated fatty acid synthesis by activating fatty acid synthesis enzymes. (A) Western blot analysis for protein expression levels of SREBP1, ACC1 and FASN in CC cell with SREBP1 overexpression ( n = 3). The Effect of trans‐C75 and PF‐05175157on the shRACK1 cell transfected with OE‐SREBP1 lentivirus. (B) The SREBP1, ACC1 and FASN expression were examined using western blot analysis ( n = 3). (C) Neutral lipid content detection by staining with fluorescence dye BODIPY 493/503 in CC cell ( n = 3). Scale bars, 10 or 30 μm. ACC1, acetyl‐CoA carboxylase 1; CC, cervical cancer; FASN, fatty acid Synthase; RACK1, Receptor for activated C‐kinase 1; SREBP1, sterol regulatory element binding protein 1.

Article Snippet: Reagents trans‐C75 (HY‐12364A) and PF‐05175157 (HY‐12942) were purchased from MedChemExpress.

Techniques: Western Blot, Expressing, Over Expression, Transfection, Staining, Fluorescence, Binding Assay