Journal: PLOS Pathogens

Article Title: Single amino acid substitution in RdRp reduces viral recombination frequency of NADC30-like porcine reproductive and respiratory syndrome virus type 2

doi: 10.1371/journal.ppat.1014500

Figure Lengend Snippet: HeB108 and its ribavirin-associated mutants were inoculated into Marc-145 cells that were pre-treated with ribavirin (A) or 5-FU (B) at an MOI of 0.01 for 72 h. HuN4 and its ribavirin-associated mutants were inoculated into Marc-145 cells that were pre-treated with ribavirin (C) or 5-FU (D) . Cells without ribavirin or 5-FU treatment served as a control to evaluate the virus titers. Viral genomic RNA level was determined by RT-qPCR. *, P < 0.05; **, P < 0.01; ***, P < 0.001; ****, P < 0.0001.

Article Snippet: Monolayers of Marc-145 cells were pre-treated with 100, 200, 300, and 350 μM ribavirin, or 400 and 600 μM 5-fluorouracil (5-FU) (MCE, China) for 2 h. The cells were infected with site-directed mutated or parental virus at an MOI of 0.01 for 2 h. The infected cells were washed three times with PBS.

Techniques: Control, Virus, Quantitative RT-PCR

Journal: Asian Journal of Pharmaceutical Sciences

Article Title: Melatonin-inspired hybrid spheroids accelerate intestinal repair via YAP-driven fetal reprogramming

doi: 10.1016/j.ajps.2026.101176

Figure Lengend Snippet: Melatonin enhances regenerative capacity and YAP activation in IOs. (A) GSEA of IOs for a fetal gene signature; (B) t-SNE plots showing cell distribution based on EEC subclusters (left) or treatment groups (right), together with a bar graph indicating the relative proportion of each EEC subpopulation; (C) Dot plot of relative EEC gene expression across subpopulations; (D) t-SNE plots of multicompetent EEC gene expression; (E) Immunofluorescence staining of Arx in IOs. (F, G) Experimental scheme, representative images, and quantification of proliferative capacity in cytomix-exposed IOs following melatonin (F) pre- or (G) post-treatment; (H) Immunofluorescence staining for YAP in IOs demonstrating differential YAP localization after melatonin treatment; (I, J) Time-dependent effects of melatonin on YAP activation: (I) western blots showing total YAP and non-phosphorylated (active) YAP (ac.YAP), with corresponding quantification in IOs, and (J) relative mRNA expression levels of YAP target genes; (K) Experimental design and FC analysis evaluating the induction of Sca1 + cells in IOs. (L) FC analysis of the synergy between PGE 2 and MT1/2 receptor agonists on RSC induction. At least two independent organoid lines were used for all experiments. The number of biological replicates corresponds to the number of data points shown in each graph. Scale bars: 100 µm (E), 200 µm (F), 1000 µm (G), and 20 µm (H). Data are presented as mean ± SEM and were analyzed using an unpaired t -test. * P < 0.05, ** P < 0.01.

Article Snippet: 2-Iodomelatonin (2I), 8-M-PDOT (8M), melatonin, PGE 2 and 5-fluorouracil (5-FU) were purchased from MedChemExpress (NJ, USA).

Techniques: Activation Assay, Gene Expression, Immunofluorescence, Staining, Western Blot, Expressing

Journal: Asian Journal of Pharmaceutical Sciences

Article Title: Melatonin-inspired hybrid spheroids accelerate intestinal repair via YAP-driven fetal reprogramming

doi: 10.1016/j.ajps.2026.101176

Figure Lengend Snippet: In vitro characterization and in vivo retention of 3D-MSCs and Mel-HS. (A) Schematic diagram illustrating the preparation procedure of Mel-MS and (B) a representative SEM image; (C–E) Characterization of Mel-MS, including (C) size distribution, (D) LC and EE, (E) and in vitro release profile of melatonin from Mel-MS in PBS (pH 7.4; n = 3); (F) Schematic diagram depicting formation of Mel-HS; (G) LIVE/DEAD staining of 3D-MSCs and Mel-HS; (H) Cell viability comparison between 3D-MSC and Mel-HS groups; (I) Quantification of PGE 2 secretion; (J, K) Fluorescence images and quantitative analysis of (J) DiR-labeled MSC signals and (K) MS-derived Cy5.5 signals 2 weeks after intraperitoneal injection. Scale bar: 500 µm. Data are presented as mean ± SEM and were analyzed using an unpaired t -test. * P < 0.05, ** P < 0.01.

Article Snippet: 2-Iodomelatonin (2I), 8-M-PDOT (8M), melatonin, PGE 2 and 5-fluorouracil (5-FU) were purchased from MedChemExpress (NJ, USA).

Techniques: In Vitro, In Vivo, Staining, Comparison, Fluorescence, Labeling, Derivative Assay, Injection

Journal: Biomolecules

Article Title: γ-Tocotrienol Sensitises Colorectal Cancer to PD-1 Blockade by Enhancing MHC-I-Associated Tumour Immune Visibility and CD8 + T Cell-Related Antitumour Immunity

doi: 10.3390/biom16070964

Figure Lengend Snippet: γ-T3 suppresses colorectal cancer growth more effectively in immunocompetent than in immunodeficient mice. ( A ) Tumour volume progression over time for each group in MC38 and CT26 syngeneic subcutaneous transplantation tumour models in immunocompetent mice. ( B ) Body weight change curves of each group in MC38 and CT26 models in immunocompetent mice. ( C ) Tumour growth curves of MC38 and CT26 subcutaneous tumours established in NOD-SCID immunodeficient mice and treated with vehicle or γ-T3 at 20 mg/kg. ( D ) Body weight change curves of each group in MC38 and CT26 models in NOD-SCID immunodeficient mice. n = 6, * p < 0.05, ** p < 0.01, *** p < 0.001, **** p < 0.0001.

Article Snippet: γ-T3 was acquired via MedChemExpress (Monmouth Junction, NJ, USA); 5-fluorouracil (5-FU) was obtained from Sigma-Aldrich (St. Louis, MO, USA).

Techniques: Transplantation Assay

Journal: Biomolecules

Article Title: γ-Tocotrienol Sensitises Colorectal Cancer to PD-1 Blockade by Enhancing MHC-I-Associated Tumour Immune Visibility and CD8 + T Cell-Related Antitumour Immunity

doi: 10.3390/biom16070964

Figure Lengend Snippet: γ-T3 enhances the antitumour efficacy of PD-1 blockade in colorectal cancer models. ( A ) Tumour volume trajectories for various treatment arms within MC38 and CT26 subcutaneous tumour models. ( B ) Body weight changes of mice in different treatment groups in MC38 and CT26 subcutaneous tumour models. n = 6, ** p < 0.01, *** p < 0.001, **** p < 0.0001.

Article Snippet: γ-T3 was acquired via MedChemExpress (Monmouth Junction, NJ, USA); 5-fluorouracil (5-FU) was obtained from Sigma-Aldrich (St. Louis, MO, USA).

Techniques:

Journal: Biomolecules

Article Title: γ-Tocotrienol Sensitises Colorectal Cancer to PD-1 Blockade by Enhancing MHC-I-Associated Tumour Immune Visibility and CD8 + T Cell-Related Antitumour Immunity

doi: 10.3390/biom16070964

Figure Lengend Snippet: γ-T3 combined with PD-1 blockade enhances the effector function of tumour-infiltrating T cells. Flow cytometric assessment of cytokine-producing T cell subsets in subcutaneous MC38 and CT26 tumour tissues. ( A ) IFN-γ + CD8 + T cells—representative plots and statistical quantification. ( B ) GZMB + CD8 + T cells—representative plots and statistical quantification. ( C ) IFN-γ + CD4 + T cells—representative plots and statistical quantification. n = 6, * p < 0.05, ** p < 0.01, *** p < 0.001, **** p < 0.0001.

Article Snippet: γ-T3 was acquired via MedChemExpress (Monmouth Junction, NJ, USA); 5-fluorouracil (5-FU) was obtained from Sigma-Aldrich (St. Louis, MO, USA).

Techniques:

Journal: Biomolecules

Article Title: γ-Tocotrienol Sensitises Colorectal Cancer to PD-1 Blockade by Enhancing MHC-I-Associated Tumour Immune Visibility and CD8 + T Cell-Related Antitumour Immunity

doi: 10.3390/biom16070964

Figure Lengend Snippet: The in vivo antitumour activity of γ-T3 is primarily dependent on CD8 + T cells. ( A ) Typical flow cytometry images depicting the depletion efficiency of CD8 + T cells and CD4 + T cells. ( B ) Typical flow cytometry images depicting the depletion efficiency of macrophages. ( C ) Effect of γ-T3 on MC38 subcutaneous tumour growth under CD8 + T cell depletion. ( D ) Effect of γ-T3 on MC38 subcutaneous tumour growth under CD4 + T cell depletion. ( E ) Effect of γ-T3 on MC38 subcutaneous tumour growth under macrophage depletion. n = 6, ns indicates not significant, * p < 0.05, *** p < 0.001.

Article Snippet: γ-T3 was acquired via MedChemExpress (Monmouth Junction, NJ, USA); 5-fluorouracil (5-FU) was obtained from Sigma-Aldrich (St. Louis, MO, USA).

Techniques: In Vivo, Activity Assay, Flow Cytometry

Journal: Biomolecules

Article Title: γ-Tocotrienol Sensitises Colorectal Cancer to PD-1 Blockade by Enhancing MHC-I-Associated Tumour Immune Visibility and CD8 + T Cell-Related Antitumour Immunity

doi: 10.3390/biom16070964

Figure Lengend Snippet: Single-cell transcriptomic analysis of the tumour immune microenvironment after γ-T3 treatment. ( A ) UMAP visualisation of major cell populations in MC38 subcutaneous tumour tissues, including malignant tumour cells and T cells. ( B ) Expression distribution of representative marker genes for major cell populations. ( C ) Relative proportions of major cell populations across different treatment groups. ( D ) UMAP visualisation of T cell subclusters, including CD8_Tcm, CD8_Teff, and CD4_Tem cells. ( E ) Expression distribution of representative marker genes for T cell subclusters. ( F ) Relative proportions of T cell subclusters across different treatment groups. ( G ) UMAP visualisation of malignant tumour cell subclusters. ( H ) Relative proportions of malignant tumour cell subclusters across different treatment groups. ( I ) KEGG-enrichment analysis of differentially expressed genes in malignant tumour cells associated with γ-T3 treatment. The antigen processing and presentation pathway is highlighted by the red box. T3 indicates γ-T3 treatment, PD1 indicates PD-1 blockade, and PT indicates combined γ-T3 and PD-1 blockade.

Article Snippet: γ-T3 was acquired via MedChemExpress (Monmouth Junction, NJ, USA); 5-fluorouracil (5-FU) was obtained from Sigma-Aldrich (St. Louis, MO, USA).

Techniques: Single Cell, Expressing, Marker

Journal: Biomolecules

Article Title: γ-Tocotrienol Sensitises Colorectal Cancer to PD-1 Blockade by Enhancing MHC-I-Associated Tumour Immune Visibility and CD8 + T Cell-Related Antitumour Immunity

doi: 10.3390/biom16070964

Figure Lengend Snippet: LiP-MS screening and validation identify HSPA4 as a potential γ-T3-binding protein. ( A ) Schematic workflow of the LiP-MS analysis. ( B ) Volcano plot showing the screening results of candidate proteins identified by LiP-MS. ( C ) Molecular docking model of γ-T3 with HSPA4. ( D ) SPR analysis of the binding of γ-T3 to wild-type and mutant HSPA4 proteins.

Article Snippet: γ-T3 was acquired via MedChemExpress (Monmouth Junction, NJ, USA); 5-fluorouracil (5-FU) was obtained from Sigma-Aldrich (St. Louis, MO, USA).

Techniques: Biomarker Discovery, Binding Assay, Mutagenesis

Journal: Biomolecules

Article Title: γ-Tocotrienol Sensitises Colorectal Cancer to PD-1 Blockade by Enhancing MHC-I-Associated Tumour Immune Visibility and CD8 + T Cell-Related Antitumour Immunity

doi: 10.3390/biom16070964

Figure Lengend Snippet: γ-T3 enhances MHC-I surface presentation on tumour cells and increases their susceptibility to CD8 + T cell-associated growth inhibition. ( A ) Relative survival of MC38 and CT26 cells following exposure to varying doses of γ-T3, used to evaluate the cytotoxicity of the concentration range applied in subsequent experiments. ( B , C ) Representative histograms and quantification of MHC-I abundance on MC38 and CT26 cells following exposure to γ-T3 treatment, as determined by flow cytometry. ( D , E ) qPCR analysis of the expression changes of the MHC-I heavy-chain genes H2-K1 and H2-D1, as well as the antigen processing- and peptide transport-related genes Psmb8 and Tap2, in MC38 and CT26 cells after γ-T3 treatment. ( F ) qPCR analysis of the effects of γ-T3 on the expression of typical heat-shock response-related genes, Hspa1a and Hspb1. ( G ) Measurement of IFN-γ levels in the culture supernatant after co-culture of MC38 cells with CD8 + T cells. ( H ) Relative viability of tumour cells after co-culture of MC38 cells with CD8 + T cells. n = 3, ns indicates not significant, * p < 0.05, ** p < 0.01, *** p < 0.001, **** p < 0.0001.

Article Snippet: γ-T3 was acquired via MedChemExpress (Monmouth Junction, NJ, USA); 5-fluorouracil (5-FU) was obtained from Sigma-Aldrich (St. Louis, MO, USA).

Techniques: Inhibition, Concentration Assay, Flow Cytometry, Expressing, Co-Culture Assay

Journal: Biomolecules

Article Title: γ-Tocotrienol Sensitises Colorectal Cancer to PD-1 Blockade by Enhancing MHC-I-Associated Tumour Immune Visibility and CD8 + T Cell-Related Antitumour Immunity

doi: 10.3390/biom16070964

Figure Lengend Snippet: Proposed model by which γ-T3 enhances MHC-I-associated tumour immune visibility and CD8 + T cell-related antitumour immunity.

Article Snippet: γ-T3 was acquired via MedChemExpress (Monmouth Junction, NJ, USA); 5-fluorouracil (5-FU) was obtained from Sigma-Aldrich (St. Louis, MO, USA).

Techniques: