Journal: Cell Reports Medicine

Article Title: Rewired type I IFN signaling is linked to age-dependent differences in COVID-19

doi: 10.1016/j.xcrm.2025.102285

Figure Lengend Snippet: Gradual age-dependent change in the phenotype of infection-induced CD4 + T cells and B cells (A) UMAP, showing pre-gated CD4 + T cells from the CyTOF dataset. 19 clusters have been produced using a semi-supervised approach with FlowSOM algorithm. UMAP presents all the patients that were part of the dataset and used for clustering, including follow-up measurements of some patients done approximately 2 weeks and 6 months after the first, acute infection phase measurement (details in ). (B) UMAPs, showing the location of cells belonging to the respective group (colored in, whereas gray identifies cells in other groups). Gray outlines indicate cluster regions enriched in infected children or adults. (C) Boxplots, showing relative abundance of infection-induced clusters resulting from the FlowSOM algorithm, calculated per sample within all CD4 + T cells from the CyTOF data. Kruskal-Wallis + Wilcoxon p value. (D) Scatterplots, showing mean Z score normalized CD38 and CCR6 expression in relationship to patient age for infected patients (linear model fitted to data and Spearman’s rank correlation coefficient in black) within CD4 + T cell CyTOF data. (E) UMAP, showing pre-gated B cells from the CyTOF dataset. 15 clusters have been produced using a semi-supervised approach with FlowSOM algorithm. (F) UMAPs, showing the location of cells belonging to the respective group (colored in, whereas gray identifies cells in other groups). Gray outlines indicate cluster regions enriched in infected children or adults. (G) Boxplots, showing relative abundance of infection-induced clusters resulting from the FlowSOM algorithm, calculated per sample within all B cells from the CyTOF data. Kruskal-Wallis + Wilcoxon p values. (H) Scatterplots, showing mean Z score normalized CXCR5 and CD69 expression in relationship to patient age for infected patients (linear model fitted to data and Spearman’s rank correlation coefficient in black) within B cell CyTOF data. (I) Time-dependent stacked line graphs, displaying the relative mean cluster abundance of all activated CD4 + T cell clusters determined by CyTOF. Activated clusters were defined as clusters having above-average Z -scored expression of activation markers (CD25, HLA-DR, CD38, CD137, CD69, and Ki67) compared to other clusters. Patient group color-coded figurines on the right-hand side point out cluster accumulation patterns. (J) Scatterplot, showing the sum of the relative abundance of all activated CD4 + T cell clusters determined by CyTOF.

Article Snippet: CD38 Inh_78c , Tocris, Biotechne , 6391.

Techniques: Infection, Produced, Expressing, Activation Assay

Journal: Cell Reports Medicine

Article Title: Rewired type I IFN signaling is linked to age-dependent differences in COVID-19

doi: 10.1016/j.xcrm.2025.102285

Figure Lengend Snippet: Consequences for local T cell responses and generated antibody profiles (A) Dotplot, showing scaled average expression of genes in TCRab + T cells, subset from the nasal swab scRNA-seq data. Clusters, increased with infection (0, 4, 5, 6, and 7). A total of 8 clusters have been produced using a graph-based approach as implemented in Seurat package (KNN graph with Louvain community detection). A horizontal line splits the dotplot in two parts; genes above the line were curated based on the presence of clusters with pronounced ISG signature and include other genes useful for annotation; genes below the line were found to be differentially expressed between the clusters (FindMarkers Seurat function). (B) Scatterplots showing CD38 and TNF genes transcription (average scaled expression in clusters 0, 4, 5, 6, and 7, expanded with infection) for each donor, plotted against donor’s age, using TCRab + T cells, subset from nasal swab scRNA-seq data. Linear models fitted to the data points and Spearman’s rank correlation coefficients. (C) Stacked bar chart showing relative expression strength of heavy-chain genes encoding for the different IgG and IgA isotypes in plasmablasts (B cell cluster 12, PBMC scRNA-seq experiment). Plasmablasts, expressing either of the heavy-chain genes, were pre-selected. Expression values for each gene were calculated and normalized to the total expression of all heavy-chain genes. (D) Boxplots of S1-specific IgG (left) and IgA (right) antibody titers for the acute infection phase and follow-up measurements done approximately 2 weeks and 6 months later. Titers for second and third time points are normalized to the first time point for each patient (fold change and ratio). Wilcoxon p values.

Article Snippet: CD38 Inh_78c , Tocris, Biotechne , 6391.

Techniques: Generated, Expressing, Infection, Produced

Journal: Cell Reports Medicine

Article Title: Rewired type I IFN signaling is linked to age-dependent differences in COVID-19

doi: 10.1016/j.xcrm.2025.102285

Figure Lengend Snippet: Mechanistic in vitro studies link age-dependent rewiring of type I IFN responsiveness with in vivo -detected opposite activation profiles (A) Overview of the workflow used to study the responsiveness to type I IFN and IL-1b. PBMCs from uninfected children and adults were stimulated with either SEB or a combination of SEB, ODN CpG2216, B18R, and recombinant IFNa. In a parallel experiment series, different concentrations of IFNa as well as combinations of SEB, ODN CpG2216, IL-1b, and IL-1b inhibitor anakinra were tested. After 4 days of incubation, phenotypic differences in activation marker expression were determined by flow cytometry, while cell culture supernatants were used for cytokine and chemokine quantification. Experiments focused on IL-1b and anakinra influence were only measured in cytokine proteomics. (B) Boxplot of arcsinh-transformed median CD38 fluorescence intensity in proliferating CD4 + T cells, showing influence of CpG2216-mediated activation on CD38 expression. Wilcoxon test p values. Dropout in uninfected children group SEB condition is due to low cell number. (C) Boxplot of arcsinh-transformed median CD38 fluorescence intensity in proliferating CD4 + T cells, showing influence of CpG2216-mediated activation and IFNa (30 ng/mL) on CD38 expression in children. Wilcoxon test p values. Dropouts in SEB and SEB+IFNa perturbations are due to low cell number. (D) Boxplots of CD38 median signal intensity in proliferating CD4 + T cells, separated into CD45RA − (violet filling) memory and CD45RA + naive subpopulations, showing the difference in CD38 upregulation in response to CpG2216-mediated activation and IFNa release between memory and naive CD4 + T cells. Wilcoxon test p values. Dropout in uninfected children, SEB perturbation is due to low cell number. (E) Boxplot of IFNa concentration measured in cell culture supernatant and normalized to values detected in SEB condition for each patient, showing the effectiveness of CpG2216 in provoking IFNa release as well as of B18R in reducing the concentration of soluble IFNa. Dropout in uninfected children is due to low cell number. (F) Heatmap, showing scaled average log concentration of the 18 cytokines measured in co-culturing experiments for different perturbations using PBMC. (G) Line plots, showing the dependence of IFNg, IL-21, and IL-1b concentrations on the IFNa concentration. Wilcoxon p values. (H) Scatterplot, illustrating the correlation between donor age and IL-1b concentration in supernatant when PBMCs are stimulated with SEB and CpG.

Article Snippet: CD38 Inh_78c , Tocris, Biotechne , 6391.

Techniques: In Vitro, In Vivo, Activation Assay, Recombinant, Incubation, Marker, Expressing, Flow Cytometry, Cell Culture, Transformation Assay, Fluorescence, Concentration Assay

Journal: Aging Cell

Article Title: SIRT2 and NAD + Boosting Broadly Suppress Aging‐Associated Inflammation

doi: 10.1111/acel.70162

Figure Lengend Snippet: 78c suppresses aging‐associated inflammation and tissue function decline. Comparison of aged (24 months old) WT mice treated with or without 78c for 2 months. (A–C), Quantitative real‐time PCR analyses for the mRNA levels of the indicated genes in the GA (A, n = 7,6), the liver (B, n = 6) and the hippocampus (C, n = 7). (D–G), Immunostaining for CD68+ cells and quantification of the GA (D, E, n = 7) and the liver (F, G, n = 7,6) sections. Scale bar: 50 μm. 5 images examined from 3 slides/mouse. (H, I), Immunostaining for phosphorylated STING and quantification of the GA sections. Scale bar: 30 μm. n = 7.4 images examined from 3 slides/mouse. (J, K), Western blotting analyses and quantification of TBK1 and phosphorylated TBK1 in the liver. GAPDH was used as a control. n = 3. (L, M), Levels of TNF‐α and IL‐6 in the serum. n = 6. (N), Latency to fall in the grip strength test. n = 10. (O), Time spent in the target quadrant in the Barnes maze test. n = 10, 9. Data are mean ± s.e.m. * p < 0.05. ** p < 0.01. *** p < 0.001. Student's t test.

Article Snippet: 78c (MedChemExpress LLC, #HY‐123999) was administered to mice by intraperitoneal injection (10 mg/kg/dose) twice daily.

Techniques: Comparison, Real-time Polymerase Chain Reaction, Immunostaining, Western Blot, Control

Journal: Translational Oncology

Article Title: CD38 contributes to tumor progression and tumor microenvironment reshaping in epithelial ovarian cancer

doi: 10.1016/j.tranon.2025.102414

Figure Lengend Snippet: Evaluating CD38’s impact on cell infiltration and communication in ovarian cancer by single-cell resolution (A) Cell type annotation for six datasets categorized by major lineage. The heatmap showed the average gene expression of CD38 in different populations of malignant, immune and stromal cells. (B) UMAP dimensionality reduction of cellular landscape of ovarian cancer and CD38 expression across different cell populations. (C) Violin plots illustrated the distribution of CD38 expression levels among various cell populations in normal and ovarian cancer tissues. (D) Violin plots illustrated CD38 expression patterns among cell populations in primary, metastatic, and relapsed ovarian cancer tissues. (E) Heatmap showed the intensity of intercellular communication in the GSE118828 dataset. (F) Comparison of gene expression levels involved in cell-cell interactions between high and low CD38-expressing groups in the GSE9891 dataset (* p < 0.05, ** p < 0.01, **** p < 0.0001). (G) qPCR analysis of relative mRNA expression of cell-cell interaction genes in subcutaneous tumors from C57BL/6 mice treated with Compound 78c, normalized to β-actin ( n = 3 per group, * p < 0.05, ** p < 0.01, *** p < 0.001, **** p < 0.0001).

Article Snippet: Four weeks post-inoculation, the CD38-specific inhibitor Compound 78c (S8906, Selleck Chemicals, TX, USA) was administered to C57BL/6 by intraperitoneal injection (10 mg/kg/dose [ ]) every two days over a period of 3 weeks.

Techniques: Gene Expression, Expressing, Comparison

Journal: Translational Oncology

Article Title: CD38 contributes to tumor progression and tumor microenvironment reshaping in epithelial ovarian cancer

doi: 10.1016/j.tranon.2025.102414

Figure Lengend Snippet: CD38 promotes ovarian cancer proliferation, metastasis and immune cell infiltration in vivo (A) Tumor formation in C57BL/6 mice ubcutaneously injected with ID8 cells stably expressing vector or CD38 (ID8-Vector or ID8-OVE-CD38). After 6 weeks, tumors were excised and photographed. (B) Quantification of tumor volume and total tumor weight in the transplanted tumors ( n = 7 for ID8-Vector, n = 5 for ID8-OVE-CD38, *p<0.05, *** p < 0.001). (C) Flow cytometry detected T cell proportion in the transplanted tumors ( n = 3 per group, * p < 0.05). (D) Abdominal metastases in BALB/c nude mice intraperitoneally injected with SKOV3 cells stably expressing vector or CD38 (SKOV3-Vector or SKOV3-OVE-CD38). After 4 weeks, tumors were excised and photographed. Upper panels: peritoneal metastasis nodules. Lower panels: mesenteric metastasis nodules. (E) Quantification of peritoneal metastasis nodules counts and total tumor weight, n = 7 for SKOV3-Vector, n = 6 for SKOV3-OVE-CD38, * p < 0.05, ** p < 0.01). The proportion of mesenteric metastases nodules was evaluated using Fisher's exact test (* p < 0.05). (F) Tumor formation in C57BL/6 mice subcutaneously injected with ID8 cells. After 4 weeks, Compound 78c were administered intraperitoneally (10 mg/kg/dose) every two days for 3 weeks. Tumors were excised and photographed. (G) Quantification of tumor volume in the transplanted tumors ( n = 5 per group, * p < 0.05, ** p < 0.01). (H) Flow cytometry detected proportion of CD38-positive TCs and TILs, CD4/8 + T cells, macrophages, and PD-L1-positive cells in the transplanted tumors ( n = 3 per group, * p < 0.05, ** p < 0.01).

Article Snippet: Four weeks post-inoculation, the CD38-specific inhibitor Compound 78c (S8906, Selleck Chemicals, TX, USA) was administered to C57BL/6 by intraperitoneal injection (10 mg/kg/dose [ ]) every two days over a period of 3 weeks.

Techniques: In Vivo, Injection, Stable Transfection, Expressing, Plasmid Preparation, Flow Cytometry

Journal: Translational Oncology

Article Title: CD38 contributes to tumor progression and tumor microenvironment reshaping in epithelial ovarian cancer

doi: 10.1016/j.tranon.2025.102414

Figure Lengend Snippet: CD38 promotes ovarian cancer tumorigenesis through PI3K-AKT and IL-6 pathway (A) KEGG enrichment plot of CD38 involvement in JAK-STAT and PI3K-AKT pathways. (B) qPCR analysis of relative core gene mRNA expression in the PI3K-AKT pathway in A2780 cells stably expressing vector or CD38 (Vector or OVE-CD38), normalized to β-actin ( n = 3 per group, *** p < 0.001, **** p < 0.0001). (C) qPCR analysis of relative CD38 and core gene mRNA expression in the PI3K-AKT pathway in subcutaneous tumors from C57BL/6 mice treated with Compound 78c, normalized to β-actin ( n = 3 per group, * p < 0.05, ** p < 0.01, **** p < 0.0001). (D) Western blot analysis of core protein expression levels in the PI3K-AKT pathway in A2780 cells stably expressing vector or CD38 (Vector or OVE-CD38), and CAOV3 cell lines stably expressing shNC or shCD38 (shNC or shCD38). (E) Luminex liquid suspension chip assay for 27 chemokines levels in SKOV3-Vector or SKOV3-OVE-CD38 mouse subcutaneous tumor tissues. (F) qPCR analysis of relative core gene mRNA expression in the IL6 pathway in subcutaneous tumors from C57BL/6 mice treated with Compound 78c, normalized to β-actin ( n = 3 per group, * p < 0.05, ** p < 0.01, **** p < 0.0001). (G) Comparative expression analysis of IL6 pathway core genes between high and low CD38-expressing groups in the GSE9891 dataset (*** p < 0.001, **** p < 0.0001).

Article Snippet: Four weeks post-inoculation, the CD38-specific inhibitor Compound 78c (S8906, Selleck Chemicals, TX, USA) was administered to C57BL/6 by intraperitoneal injection (10 mg/kg/dose [ ]) every two days over a period of 3 weeks.

Techniques: Expressing, Stable Transfection, Plasmid Preparation, Western Blot, Luminex, Suspension

Journal: Cell Reports Medicine

Article Title: Boosting NAD preferentially blunts Th17 inflammation via arginine biosynthesis and redox control in healthy and psoriasis subjects

doi: 10.1016/j.xcrm.2023.101157

Figure Lengend Snippet: The CD4 + T cell immunomodulatory effect of NR is dependent on cellular NAD + levels (A) IL-17 release in response to Compound 78c (78c) to inhibit CD38 or rucaparib (Ruc) to inhibit PARPs (n = 8) in CD4 + T cells. (B and C) Cellular ROS (B) and mitochondrial ROS (C) following 78c or Ruc (n = 4). (D) IL-17 release following 78c or Ruc in Th17 cells (n = 8). (E and F) Cellular ROS (E) and mitochondrial ROS (F) following 78c or Ruc in Th17 cells (n = 4). (G) IL-17 release in cd38 - or sarm1 -KD CD4 + T cells (n = 8). (H and I) ROS (H) and mitochondrial ROS (I) in cd38 - or sarm1 -KD cells (n = 4). (J) IL-17 release in cd38 - or sarm1 -KD Th17 cells (n = 4–8). (K and L) Cellular ROS (K) and mitochondrial ROS (L) in cd38 - or sarm1 -KD Th17 cells (n = 4). (M and N) Protein expression of Nrf2 and Sqstm1 in cd38 -KD CD4 + T cells (N, n = 8) and sarm1 -KD cells (N, n = 4–6). The p values for comparisons of two groups calculated using paired two-tailed Student’s t test, or one-way ANOVA when comparing more than two groups (vehicle vs. treated or NC vs. CD38-KD/SARM1-KD). ∗p < 0.05, ∗∗p < 0.01, ∗∗∗p < 0.001. Histograms represent mean ±SEM.

Article Snippet: PARPs inhibitor Rucaparib camsylate (Sigma) and CD38 inhibitor Compound-78c (Selleckchem) were used in cell culture at 10 μM, 20 μM, or 10 μM for 12 hrs., respectively.

Techniques: Expressing, Two Tailed Test

Journal: Cell Reports Medicine

Article Title: Boosting NAD preferentially blunts Th17 inflammation via arginine biosynthesis and redox control in healthy and psoriasis subjects

doi: 10.1016/j.xcrm.2023.101157

Figure Lengend Snippet:

Article Snippet: PARPs inhibitor Rucaparib camsylate (Sigma) and CD38 inhibitor Compound-78c (Selleckchem) were used in cell culture at 10 μM, 20 μM, or 10 μM for 12 hrs., respectively.

Techniques: Flow Cytometry, Virus, Recombinant, Staining, Cell Stimulation, CyQUANT Assay, Proliferation Assay, Bicinchoninic Acid Protein Assay, In Vitro, Antioxidant Assay, Detection Assay, GSH Assay, Bioassay, Transcription Factor Assay, Extraction, Enzyme-linked Immunosorbent Assay, Control, Software, Cell Isolation, Transfection