Journal: Signal transduction and targeted therapy

Article Title: Myeloid but not hepatocytic CD38 is a key driver for hepatic ischemia/reperfusion injury.

doi: 10.1038/s41392-025-02233-8

Figure Lengend Snippet: Fig. 1 CD38 deficiency alleviated hepatic ischemia-reperfusion injury (HIRI) in mice. a CD38 expressions were determined by Western blotting and quantitative analysis in liver tissues after ischemia/reperfusion (I/R) injury. b The mRNA expressions of IL1B and IL-6 in liver tissues after I/R injury. c Representative fluorescence images of IL-1β/F4/80 and IL-1β/ASGR1 were taken from CD38KO mice subjected to HIRI, respectively. d, e Serum ALT and AST were measured in CD38KO and CD38MKO mice subjected to HIRI. f, g Representative H&E staining images and the quantitative analysis of liver ischemic necrosis were taken from CD38KO and CD38MKO mice subjected to HIRI, respectively. Data are shown as means ± SEM, *p < 0.05, **p < 0.01 and ***p < 0.001, n = 3–9 per group

Article Snippet: CD38 (R&D), GAPDH (KangChen), SOD2 (CST), NOX2 (Abcam), IL-1β (CST), PPARγ (Santa Cruz Biotechnology), NLRP3 (CST), IL-18 (Abmart), GSDMD-N (Abmart), SIRT3 (Sigma-Aldrich), SIRT1 (Sigma-Aldrich), p53 (Abcam), Acetylp53 (Abcam) antibodies were diluted 1:400/1000, respectively.

Techniques: Western Blot, Staining

Journal: Signal transduction and targeted therapy

Article Title: Myeloid but not hepatocytic CD38 is a key driver for hepatic ischemia/reperfusion injury.

doi: 10.1038/s41392-025-02233-8

Figure Lengend Snippet: Fig. 2 Global CD38 deficiency inhibited oxidative stress and inflammation during HIRI. a Representative DHE staining images were taken from CD38KO and CD38fl/flmice subjected to HIRI, respectively. b MDA contents were quantitatively measured in liver tissues from CD38KO and CD38fl/flmice after I/R injury. c Serum TNF-α and IL-1β were detected by Elisa in CD38KO and CD38fl/flmice after HIRI. d The protein expressions and the quantitative analysis of NOX2 and SOD2 were determined by western blot in liver tissues from CD38KO and CD38fl/flmice after HIRI. e The mRNA expressions of TNF-α, IL1B, TGF-β, CD206, and PPARγ were determined by QPCR in CD38KO and CD38fl/flmice after HIRI, respectively. f, g The expressions and the quantitative analysis of IL-1β and PPARγ were detected by Western blot in liver tissues in CD38KO and CD38fl/flmice after HIRI, respectively. Data are shown as means ± SEM, *p < 0.05, **p < 0.01 and ***p < 0.001, n = 3–8 per group

Article Snippet: CD38 (R&D), GAPDH (KangChen), SOD2 (CST), NOX2 (Abcam), IL-1β (CST), PPARγ (Santa Cruz Biotechnology), NLRP3 (CST), IL-18 (Abmart), GSDMD-N (Abmart), SIRT3 (Sigma-Aldrich), SIRT1 (Sigma-Aldrich), p53 (Abcam), Acetylp53 (Abcam) antibodies were diluted 1:400/1000, respectively.

Techniques: Staining, Enzyme-linked Immunosorbent Assay, Western Blot

Journal: Signal transduction and targeted therapy

Article Title: Myeloid but not hepatocytic CD38 is a key driver for hepatic ischemia/reperfusion injury.

doi: 10.1038/s41392-025-02233-8

Figure Lengend Snippet: Fig. 3 Myeloid CD38 deficiency reduced hepatic ischemia-reperfusion-triggered inflammation. a–c The mRNA expressions of IL1B, TNF-α, iNOS, IL-10, ARG1, TGF-β and PPARγ were analyzed by QPCR in CD38MKO and CD38fl/flmice after HIRI. d The expressions and the quantitative analysis of PPARγ were detected by Western blot in liver tissues of CD38MKO and CD38fl/flmice after HIRI. e MDA contents were measured in liver tissues of CD38LKO and CD38fl/flmice after HIRI. f The mRNA expressions of TNF-α and IL1B were determined by QPCR in liver tissues of CD38LKO and CD38fl/flmice after HIRI. Data are shown as means ± SEM, *p < 0.05, **p < 0.01 and ***p < 0.001, n = 3 ~ 9 per group

Article Snippet: CD38 (R&D), GAPDH (KangChen), SOD2 (CST), NOX2 (Abcam), IL-1β (CST), PPARγ (Santa Cruz Biotechnology), NLRP3 (CST), IL-18 (Abmart), GSDMD-N (Abmart), SIRT3 (Sigma-Aldrich), SIRT1 (Sigma-Aldrich), p53 (Abcam), Acetylp53 (Abcam) antibodies were diluted 1:400/1000, respectively.

Techniques: Western Blot

Journal: Signal transduction and targeted therapy

Article Title: Myeloid but not hepatocytic CD38 is a key driver for hepatic ischemia/reperfusion injury.

doi: 10.1038/s41392-025-02233-8

Figure Lengend Snippet: Fig. 4 Global and myeloid deletion of CD38 ameliorated HIRI-induced pyroptosis in vivo. The protein expressions and the quantitative analysis of NLRP3, IL-18 and GSDMD-N and the mRNA expressions of NLRP3, Caspase-1 and IL-18 were examined by Western blot (a) and QPCR (b) in liver tissues of CD38KO and CD38fl/flmice after HIRI, respectively. The protein expressions and the quantitative analysis of NLRP3, GSDMD-N and IL-18, and the mRNA expressions of NLRP3, Caspase-1 and IL-18 were determined by Western blot (c) and QPCR (d) in liver tissues from CD38MKO and CD38fl/flmice after HIRI. Data are shown as means ± SEM, *p < 0.05, **p < 0.01and ***p < 0.001, n = 3–6 per group

Article Snippet: CD38 (R&D), GAPDH (KangChen), SOD2 (CST), NOX2 (Abcam), IL-1β (CST), PPARγ (Santa Cruz Biotechnology), NLRP3 (CST), IL-18 (Abmart), GSDMD-N (Abmart), SIRT3 (Sigma-Aldrich), SIRT1 (Sigma-Aldrich), p53 (Abcam), Acetylp53 (Abcam) antibodies were diluted 1:400/1000, respectively.

Techniques: In Vivo, Western Blot

Journal: Signal transduction and targeted therapy

Article Title: Myeloid but not hepatocytic CD38 is a key driver for hepatic ischemia/reperfusion injury.

doi: 10.1038/s41392-025-02233-8

Figure Lengend Snippet: Fig. 5 Myeloid CD38 deficiency alleviated hepatocytic hypoxia/reoxygenation injury in a co-culture condition in vitro. a Representative flow cytometry plots of PI staining, along with the quantitative analysis, for hepatocytes from CD38fl/flmice co-cultured with BMDMs from CD38KO

Article Snippet: CD38 (R&D), GAPDH (KangChen), SOD2 (CST), NOX2 (Abcam), IL-1β (CST), PPARγ (Santa Cruz Biotechnology), NLRP3 (CST), IL-18 (Abmart), GSDMD-N (Abmart), SIRT3 (Sigma-Aldrich), SIRT1 (Sigma-Aldrich), p53 (Abcam), Acetylp53 (Abcam) antibodies were diluted 1:400/1000, respectively.

Techniques: Co-Culture Assay, In Vitro, Cytometry, Staining, Cell Culture

Journal: Signal transduction and targeted therapy

Article Title: Myeloid but not hepatocytic CD38 is a key driver for hepatic ischemia/reperfusion injury.

doi: 10.1038/s41392-025-02233-8

Figure Lengend Snippet: Fig. 6 Global and myeloid deletion of CD38 upregulated SIRT1-p53 signaling pathway. The expressions and the quantitative analysis of SIRT1 (a, b), SIRT3 (a, b), p53 (c, d), and AC-p53 (c, d) were determined by Western blot in liver tissues from CD38KO, CD38MKO, and CD38fl/flmice after HIRI. Data are shown as means ± SEM, *p < 0.05, **p < 0.01 and ***p < 0.001, n = 3 per group

Article Snippet: CD38 (R&D), GAPDH (KangChen), SOD2 (CST), NOX2 (Abcam), IL-1β (CST), PPARγ (Santa Cruz Biotechnology), NLRP3 (CST), IL-18 (Abmart), GSDMD-N (Abmart), SIRT3 (Sigma-Aldrich), SIRT1 (Sigma-Aldrich), p53 (Abcam), Acetylp53 (Abcam) antibodies were diluted 1:400/1000, respectively.

Techniques: Western Blot

Journal: Signal transduction and targeted therapy

Article Title: Myeloid but not hepatocytic CD38 is a key driver for hepatic ischemia/reperfusion injury.

doi: 10.1038/s41392-025-02233-8

Figure Lengend Snippet: Fig. 7 Myeloid CD38 deficiency promoted macrophage M2 polarization through activating NAD+/SIRT1 pathway in vitro. The mRNA expressions of IL1B (a), CD206 (a), and the protein expressions and the quantitative analysis of SIRT1 (b) and SIRT3 (b) were determined by QPCR and Western blot in BMDMs from CD38fl/fland CD38KO mice after LPS stimulation, respectively. c The mRNA expressions of IL1B and IL-6 were determined by QPCR in BMDMs from CD38fl/flmice with the stimulation of hepatocytes-derived conditioned media after hypoxia/ reoxygenation injury (HCMHR). The protein expressions and the quantitative analysis of SIRT1/SIRT3 (d), the NAD+ contents (e) and the infiltrations of the type 2 macrophages (CD206/Il-10, f, g), and type 1 macrophages (CD86/iNOS, f, g) were determined in BMDMs from CD38KO and CD38fl/flmice with HCMHR stimulation. Data are shown as means ± SEM, *p < 0.05, **p < 0.01 and ***p < 0.001, n = 3–6 per group

Article Snippet: CD38 (R&D), GAPDH (KangChen), SOD2 (CST), NOX2 (Abcam), IL-1β (CST), PPARγ (Santa Cruz Biotechnology), NLRP3 (CST), IL-18 (Abmart), GSDMD-N (Abmart), SIRT3 (Sigma-Aldrich), SIRT1 (Sigma-Aldrich), p53 (Abcam), Acetylp53 (Abcam) antibodies were diluted 1:400/1000, respectively.

Techniques: In Vitro, Western Blot, Derivative Assay

Journal: Signal transduction and targeted therapy

Article Title: Myeloid but not hepatocytic CD38 is a key driver for hepatic ischemia/reperfusion injury.

doi: 10.1038/s41392-025-02233-8

Figure Lengend Snippet: Fig. 8 Myeloid CD38 deficiency facilitated macrophage M2-type polarization through activating SIRT1-p53 and SIRT1-PPARγ pathway in vitro. The mRNA expressions of TNF-α (a), IL1B (b), IL-10 (c) and CD206 (d) were determined by QPCR in BMDMs from CD38KO and CD38fl/flmice with the stimulation of the hepatocytes-derived conditioned media after hypoxia/reoxygenation injury (HCMHR) in the pretreatment of Compound C (AMPK inhibitor), PFT-α (P53 inhibitor) and T0070907(PPARγ inhibitor), respectively. Data are shown as means ± SEM, *p < 0.05, **p < 0.01 and ***p < 0.001, n = 3 per group. e The mechanism of myeloid-specific deletion of CD38 (CD38MKO) protecting against hepatic ischemia/ reperfusion injury (HIRI): CD38MKO elevates the intracellular NAD+ levels in macrophages, and in turn, alleviates hepatic ischemia/reperfusion injury (HIRI)-induced inflammation and pyroptosis via activating SIRT1 signaling pathways in macrophages. On the one hand, SIRT1 promotes myeloid monocytes toward macrophage type 2 polarization through activating PPARγ signaling pathway in macrophages and inhibits monocytes toward macrophage type 1 polarization via activating p53 signaling, reducing HIRI-induced inflammation. On the other hand, SIRT1 also suppresses the release of pro-inflammatory factors such as IL1-β and IL18 through inactivating the canonical inflammasome- pyroptosis pathway of NLRP3-mediated caspase-1/GSDMD processing in macrophages. Image created with BioRender.com, with permission (agreement number: FG27ZL6X5O; citation to use: https://www.biorender.com/j12e628)

Article Snippet: CD38 (R&D), GAPDH (KangChen), SOD2 (CST), NOX2 (Abcam), IL-1β (CST), PPARγ (Santa Cruz Biotechnology), NLRP3 (CST), IL-18 (Abmart), GSDMD-N (Abmart), SIRT3 (Sigma-Aldrich), SIRT1 (Sigma-Aldrich), p53 (Abcam), Acetylp53 (Abcam) antibodies were diluted 1:400/1000, respectively.

Techniques: In Vitro, Derivative Assay, Protein-Protein interactions

Journal: Journal of translational medicine

Article Title: Proteomic profiling reveals the significance of lipid metabolism in small cell lung cancer recurrence and metastasis.

doi: 10.1186/s12967-024-05926-w

Figure Lengend Snippet: Fig. 7 Validation of PLA2G2A expression and significance in SCLC. A Representative hematoxylin and eosin and immunohistochemical staining images for PLA2G2A on epithelial cancer cells and stromal cells. B Kaplan–Meier curves show disease free survival (DFS) of patients with high expression of PLA2G2A in stroma, with low expression of PLA2G2A in stroma, and lack of stroma, respectively. C Forest plot shows the results of multivariable Cox proportional hazards regression modeling of DFS for limited-stage SCLC patients. D Representative immunofluoresence images for CD38, CD8, CD68, CD15 and PLA2GA

Article Snippet: Then, slides were stained with PLA2G2A antibody (1:50, Abcam, ab23705), CD8 antibody (ready to use antibody, Abcarta, PA577), CD15 antibody (ready to use antibody, Zsbio, ZM-0037), CD38 antibody (ready to use antibody, Zsbio, ZM-0422), CD68 antibody (ready to use antibody, Roche, KP-1), ASCL1 antibody (1:100, Santa Cruz Biotechnology, sc-374104), NEUROD1 antibody (1:300, Abcam, ab60704), POU2F3 antibody (1:100, Cell Signaling Technology, #36,135) and YAP1 antibody (1:80, Abcam, ab52771), respectively.

Techniques: Biomarker Discovery, Expressing, Immunohistochemical staining, Staining

Journal: bioRxiv

Article Title: CD38 biallelic loss is a recurrent mechanism of resistance to anti-CD38 antibodies in multiple myeloma

doi: 10.1101/2024.12.17.628799

Figure Lengend Snippet: Functional validation of CD38 variants. A) Wild-type and mutant CD38 protein expression in K562 cell lines by monoclonal and polyclonal anti-CD38 antibodies. B) CD38 binding assays: K562 cells were incubated with either Dara or Isa followed by secondary anti-IgG staining. C) Left: Repeated binding assay for K562 CD38 R140G (blue) at different drug concentrations with dose-independent decreased affinity for Dara compared to wild-type (grey). Right: Change in mean fluorescence intensity (MFI) recapitulating maintained binding of Isa for the R140G protein at all drug concentrations compared to the dose-independent decreased binding of Dara. D) Co-culture experiment with healthy donor peripheral blood mononuclear cells at Effector:Target ratio of 20:1 for various Dara and Isa concentrations demonstrating impaired antibody dependent cellular cytotoxicity of Dara compared to Isa for K562 CD38 R140G compared to K562 CD38 wild-type . E) Structure of human CD38 (grey) with mapped epitopes for Isa (blue) and Dara (red), and three identified missense SNV (green spheres). Protein structure was visualized using PyMOL (The PyMOL Molecular Graphics System, Version 3.0, Schrödinger, LLC). The effect of R140G is described in text. Cys 275 forms a critical disulfide bond stabilising the protein structure. Mutation to bulky Tyr destabilizes CD38 structural integrity, affecting both epitopes. The aliphatic Leu 153 contributes to CD38 hydrophobic core formation under the Isa epitope. Its mutation to a charged His will destabilize the Isa epitope structural integrity affecting the antibody binding.

Article Snippet: Surface expression of CD38 was confirmed using monoclonal (BioLegend, #356610) and polyclonal (Cell Signaling Technology, #14637S) anti-CD38 antibodies.

Techniques: Functional Assay, Mutagenesis, Expressing, Binding Assay, Incubation, Staining, Fluorescence, Co-Culture Assay

Journal: Neurobiology of disease

Article Title: Decreased plasma nicotinamide and altered NAD + metabolism in glial cells surrounding Aβ plaques in a mouse model of Alzheimer's disease.

doi: 10.1016/j.nbd.2024.106694

Figure Lengend Snippet: Fig. 5. CD38 is expressed in reactive astrocytes and microglia surrounding Aβ plaques in AppNLGF brains. (A) Representative images of the cortex from 24-month-old female WT (left panels) and AppNLGF (right panels) mice immunostained with antibodies against CD38 (green) and MAP2 (magenta). FSB was used for detecting Aβ plaques (blue). (B) Representative images of the cortex from 24-month-old female WT (upper panels) and AppNLGF (lower panels) mice immunostained with antibodies against CD38 (green), CX43 (magenta), and GFAP (orange). FSB was used for detecting Aβ plaques (blue). (C) Higher magnification images of framed regions in the cortex stained with anti-CD38 (green), anti-CX43 (magenta), and anti-GFAP (orange) antibodies (B, lower panels). White arrows indicated the colocalization of CD38 and CX43. (D) Representative images of the cortex from 24-month-old female WT (left panels) and AppNLGF (right panels) mice immunostained with antibodies against CD38 (green) and IBA1 (magenta). FSB was used for detecting Aβ plaques (blue). (E) Higher magnification images of framed regions in the cortex stained with anti-CD38 (green) and anti-IBA1 (magenta) antibodies (D, right panels; AppNLGF). White arrows indicated the localization of CD38 in microglia. Scale bars represent 50 μm in A, B, and D. For higher magnification views (C, E), scale bars represent 20 μm. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)

Article Snippet: The first antibodies used in this study were following; mouse monoclonal anti-NAPRT antibody (SantaCruz, sc-398404; 1/200), rabbit polyclonal anti-PBEF (NAMPT) antibody (Bethyl Laboratories, A300372A; 1/500), rabbit monoclonal anti-CD38 antibody (Cell Signaling, 68336; 1/50), rat monoclonal anti-GFAP antibody (Millipore, 345860; 1/1000), rabbit polyclonal anti-IBA1 antibody (Wako, 019–19741; 1/ 500), goat polyclonal anti-IBA1 antibody (Wako, 011–27991; 1/500), rabbit polyclonal anti-MAP2 antibody (Millipore, AB5622; 1/200), chicken polyclonal anti-MAP2 antibody (Abcam, ab5392; 1/500), and mouse monoclonal anti-connexin 43 antibody (Millipore, MAB3067; 1/ 200).

Techniques: Staining