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  • 1
    Online Resource
    Online Resource
    Surface TREM2 on circulating M-MDSCs as a novel prognostic factor for adults with treatment-naïve diffuse large B-cell lymphoma
    Springer Science and Business Media LLC ; 2023
    In:  Experimental Hematology & Oncology Vol. 12, No. 1 ( 2023-04-07)
    Details
    In: Experimental Hematology & Oncology, Springer Science and Business Media LLC, Vol. 12, No. 1 ( 2023-04-07)
    Abstract: Circulating monocytic myeloid-derived suppressive cells (M-MDSCs) are implicated as a poor prognostic factor and cause CAR T-cell failure in diffuse large B-cell lymphoma (DLBCL). Triggering receptors expressed on myeloid cells 2 (TREM2) are a transmembrane glycoprotein that polarize macrophages to anti-inflammation phenotype but have never been explored on M-MDSCs. This study aims to elucidate the expression and clinical impact of surface TREM2 on circulating M-MDSCs derived from DLBCL adults. Methods This prospective, observational study enrolled 100 adults with newly diagnosed and treatment-naïve DLBCL from May 2019 to October 2021. Human circulating M-MDSCs were obtained from freshly isolated peripheral blood, and each patient’s surface-TREM2 level on M-MDSCs was normalized via a healthy control at the same performance of flow-cytometry analysis. Murine MDSCs derived from bone marrow (BM-MDSCs) were adopted to assess the link between Trem2 and cytotoxic T lymphocytes. Results More circulating M-MDSCs at diagnosis of DLBCL predicted worse progression-free (PFS) and overall survival (OS). Patients with higher IPI scores, bone marrow involvement, or lower absolute counts of CD4 + or CD8 + T cells in PB had significantly higher normalized TREM2 levels on M-MDSCs. Additionally, normalized TREM2 levels on M-MDSCs could be grouped into low ( 〈  2%), medium (2–44%), or high ( 〉  44%) levels, and a high normalized TREM2 level on M-MDSCs was proven as an independent prognostic factor for both PFS and OS via multivariate Cox regression analysis and associated with worst PFS and OS. Interestingly, normalized levels of surface TREM2 on M-MDSCs were negatively associated with absolute counts of PB CD8 + T cells and positively correlated with levels of intracellular arginase 1 (ARG1) within M-MDSCs. Wild-type BM-MDSCs had significantly higher mRNA levels of Arg1 and showed more prominent ability to suppress the proliferation of co-cultured CD8 + T cells than BM-MDSCs from Trem2 knockout mice, and the suppressive ability could be impaired by adding Arg1 inhibitors (CB1158) or supplementing L-arginine. Conclusion In treatment-naïve DLBCL adults, a high surface-TREM2 level on circulating M-MDSCs is a poor prognostic factor for both PFS and OS and warrants further investigation for its potential as a novel target in immunotherapy.
    Type of Medium: Online Resource
    ISSN: 2162-3619
    URL: Article
    DOI: 10.1186/s40164-023-00399-x
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2023
    detail.hit.zdb_id: 2669066-4
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  • 2
    Online Resource
    Online Resource
    PD-L1 Expression in Monocytes Correlates with Bacterial Burden and Treatment Outcomes in Active Pulmonary Tuberculosis
    MDPI AG ; 2022
    In:  International Journal of Molecular Sciences Vol. 23, No. 3 ( 2022-01-30), p. 1619-
    Details
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 23, No. 3 ( 2022-01-30), p. 1619-
    Abstract: The PD-1/PD-L1 pathway is critical in T cell biology; however, the role of the PD-1/PD-L1 pathway in clinical characteristics and treatment outcomes in pulmonary tuberculosis (PTB) patients is unclear. We prospectively enrolled PTB, latent TB infection (LTBI), and non-TB, non-LTBI subjects. The expression of PD-1/PD-L1 on peripheral blood mononuclear cells (PBMCs) was measured and correlated with clinical characteristics and treatment outcomes in PTB patients. Immunohistochemistry and immunofluorescence were used to visualize PD-1/PD-L1-expressing cells in lung tissues from PTB patients and from murine with heat-killed MTB (HK-MTB) treatment. A total of 76 PTB, 40 LTBI, and 28 non-TB, non-LTBI subjects were enrolled. The expression of PD-1 on CD4+ T cells and PD-L1 on CD14+ monocytes was significantly higher in PTB cases than non-TB subjects. PTB patients with sputum smear/culture unconversion displayed higher PD-L1 expression on monocytes. PD-L1-expressing macrophages were identified in lung tissue from PTB patients, and co-localized with macrophages in murine lung tissues. Mycobacterium tuberculosis (MTB) whole cell lysate/EsxA stimulation of human and mouse macrophages demonstrated increased PD-L1 expression. In conclusion, increased expression of PD-L1 on monocytes in PTB patients correlated with higher bacterial burden and worse treatment outcomes. The findings suggest the involvement of the PD-1/PD-L1 pathway in MTB-related immune responses.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    URL: Article
    DOI: 10.3390/ijms23031619
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2019364-6
    SSG: 12
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  • 3
    Online Resource
    Online Resource
    U‐Shaped Association Between Serum Uric Acid Levels With Cardiovascular and All‐Cause Mortality in the Elderly: The Role of Malnourishment
    Ovid Technologies (Wolters Kluwer Health) ; 2018
    In:  Journal of the American Heart Association Vol. 7, No. 4 ( 2018-02-20)
    Details
    In: Journal of the American Heart Association, Ovid Technologies (Wolters Kluwer Health), Vol. 7, No. 4 ( 2018-02-20)
    Abstract: The link between elevated serum uric acid ( SUA ) levels and cardiovascular disease ( CVD )–related mortality in the elderly population remains inconclusive. Nutritional status influences both SUA and CVD outcomes. Therefore, we investigated whether SUA ‐predicted mortality and the effect‐modifying roles of malnourishment in older people. Methods and Results A longitudinal Taiwanese cohort including 127 771 adults 65 years and older participating in the Taipei City Elderly Health Examination Program from 2001 to 2010 were stratified by 1‐mg/dL increment of SUA . Low SUA ( 〈 4 mg/dL) strata was categorized by malnourishment status defined as Geriatric Nutritional Risk Index 〈 98, serum albumin 〈 38 g/L, or body mass index 〈 22 kg/m 2 . Study outcomes were all‐cause and CVD ‐related mortality. Cox models were used to estimate hazard ratios ( HRs ) of mortality, after adjusting for 20 demographic and comorbid covariates. Over a median follow‐up of 5.8 years, there were 16 439 all‐cause and 3877 CVD ‐related deaths. Compared with the reference SUA strata of 4 to 〈 5 mg/dL, all‐cause mortality was significantly higher at SUA 〈 4 mg/dL ( HR , 1.16; 95% confidence interval, 1.07–1.25) and ≥8 mg/dL ( HR , 1.13; confidence interval, 1.06–1.21), with progressively elevated risks at both extremes. Similarly, increasingly higher CVD ‐related mortality was found at the SUA level 〈 4 mg/dL ( HR , 1.19; confidence interval, 1.00–1.40) and ≥7 mg/dL ( HR , 1.17; confidence interval, 1.04–1.32). Remarkably, among the low SUA ( 〈 4 mg/dL) strata, only malnourished participants had greater all‐cause and CVD ‐related mortality. This modifying effect of malnourishment remained consistent across subgroups. Conclusions SUA ≥8 or 〈 4 mg/dL independently predicts higher all‐cause and CVD ‐related mortality in the elderly, particularly in those with malnourishment.
    Type of Medium: Online Resource
    ISSN: 2047-9980
    URL: Article
    DOI: 10.1161/JAHA.117.007523
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2018
    detail.hit.zdb_id: 2653953-6
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  • 4
    Online Resource
    Online Resource
    Hyperuricemia Predicts an Early Decline in Renal Function among Older People: A Community-Based Cohort Study
    Springer Science and Business Media LLC ; 2019
    In:  Scientific Reports Vol. 9, No. 1 ( 2019-01-30)
    Details
    In: Scientific Reports, Springer Science and Business Media LLC, Vol. 9, No. 1 ( 2019-01-30)
    Abstract: Whether elevated serum uric acid levels (SUA) predict renal dysfunction remains controversial in the elderly. Therefore, we investigated the association between SUA and early renal function decline defined as an estimated glomerular filtration rate (eGFR) reduction ≥30% over 2 years. From 2001 to 2010, we conducted a longitudinal cohort study comprising 44,078 participants aged ≥65 years in the Taipei City Elderly Health Examination Database. Participants were classified by 1-mg/dL increment of SUA. We used multivariable logistic and Cox regression analyses to compare the risk of early renal function decline in different SUA groups. Compared to the reference SUA group of 5.0–5.9 mg/dL, hyperuricemic participants had increased risks of eGFR decline, starting at SUA ≥6.0 mg/dL (adjusted odds ratio [aOR] = 1.21, 95% confidence interval [CI]  = 1.00–1.45). The risk progressively elevated as SUA increased, with the highest in the SUA ≥10.0 mg/dL group (aOR = 3.20, CI = 2.39–4.28). Multivariable Cox regression further confirmed that hyperuricemia was 1.12-fold (CI = 1.03–1.22, SUA ≥6.0 mg/dL) to 1.6-fold (CI = 1.37–1.86, SUA ≥10.0 mg/dL) more likely to develop early eGFR decline. Hyperuricemia-associated increased risks for early eGFR decline were consistent across subgroup and sensitivity analyses. Collectively, SUA ≥6.0 mg/dL independently predicted early renal dysfunction with eGFR decline ≥30% over 2 years in older people.
    Type of Medium: Online Resource
    ISSN: 2045-2322
    URL: Article
    DOI: 10.1038/s41598-018-37529-z
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2019
    detail.hit.zdb_id: 2615211-3
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  • 5
    Online Resource
    Online Resource
    TREM-2 mediates dendritic cell–induced NO to suppress Th17 activation and ameliorate chronic kidney diseases
    Springer Science and Business Media LLC ; 2022
    In:  Journal of Molecular Medicine Vol. 100, No. 6 ( 2022-06), p. 917-931
    Details
    In: Journal of Molecular Medicine, Springer Science and Business Media LLC, Vol. 100, No. 6 ( 2022-06), p. 917-931
    Type of Medium: Online Resource
    ISSN: 0946-2716 , 1432-1440
    URL: Article
    DOI: 10.1007/s00109-022-02201-7
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2022
    detail.hit.zdb_id: 1462132-0
    SSG: 12
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  • 6
    Online Resource
    Online Resource
    Nintedanib Reduces Neutrophil Chemotaxis via Activating GRK2 in Bleomycin-Induced Pulmonary Fibrosis
    MDPI AG ; 2020
    In:  International Journal of Molecular Sciences Vol. 21, No. 13 ( 2020-07-02), p. 4735-
    Details
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 21, No. 13 ( 2020-07-02), p. 4735-
    Abstract: Neutrophils are involved in the alveolitis of idiopathic pulmonary fibrosis (IPF). However, their pathogenic mechanisms are still poorly understood. Nintedanib has antifibrotic and anti-inflammatory activity in IPF. This study aimed to investigate the regulatory mechanism of nintedanib on neutrophil chemotaxis in bleomycin (BLM)-induced pulmonary fibrosis. Nintedanib was administered via oral gavage to male C57BL/6 mice 24 h after a bleomycin intratracheal injection (1.5 U/kg). Lung histopathological findings, the expression of cytokines, and the regulatory signaling pathways of neutrophil chemotaxis were analyzed. The effect of nintedanib was also investigated in a mouse model with adoptive neutrophil transfer in vivo. Nintedanib significantly decreased the histopathological changes and neutrophil recruitment in BLM-induced pulmonary fibrosis. Nintedanib mediated a downregulation of chemokine (C-X-C motif) receptor 2 (CXCR2) and very late antigen 4 (VLA-4) expression, as well as an upregulation of G protein-coupled receptor kinase 2 (GRK2) activity in peripheral blood neutrophils in BLM-induced pulmonary fibrosis. Nintedanib also decreased the activation of endothelial cells by the decreased expression of vascular cell adhesion molecule 1 (VCAM-1). The effect of nintedanib on regulating neutrophil chemotaxis was also confirmed by a mouse model with adoptive neutrophil transfer in vivo. In conclusion, nintedanib reduces neutrophil chemotaxis and endothelial cell activation to regulate the severity of BLM-induced pulmonary fibrosis. These effects are associated with an enhancement of GRK2 activity and a reduction in CXCR2 and VLA-4 expression on neutrophils and a decrease in VCAM-1 expression on endothelial cells.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    URL: Article
    DOI: 10.3390/ijms21134735
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2019364-6
    SSG: 12
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  • 7
    Online Resource
    Online Resource
    A novel TLR 2‐triggered signalling crosstalk synergistically intensifies TNF ‐mediated IL ‐6 induction
    Wiley ; 2014
    In:  Journal of Cellular and Molecular Medicine Vol. 18, No. 7 ( 2014-07), p. 1344-1357
    Details
    In: Journal of Cellular and Molecular Medicine, Wiley, Vol. 18, No. 7 ( 2014-07), p. 1344-1357
    Abstract: Toll‐like receptors ( TLR ) recognize pathogens and trigger the production of vigorous pro‐inflammatory cytokines [such as tumour necrosis factor ( TNF )] that induce systemic damages associated with sepsis and chronic inflammation. Cooperation between signals of TLR and TNF receptor has been demonstrated through the participation of TNF receptor 1 ( TNFR ) adaptors in endotoxin tolerance. Here, we identify a TLR 2‐mediated synergy, through a MyD88‐independent crosstalk, which enhances subsequent TNF ‐mediated nuclear factor‐kappa B activation and interleukin‐6 induction. Membrane‐associated adaptor MAL conduces the link between TNF receptor‐associated factor 6 ( TRAF 6) and TNFR ‐associated death domain, leading to a distinctive K63‐ubiquitinylated TRAF 6 recruitment into TNFR complex. In summary, our results reveal a novel route of TLR signal that synergistically amplifies TNF ‐mediated responses, indicating an innovative target for inflammation manipulation.
    Type of Medium: Online Resource
    ISSN: 1582-1838 , 1582-4934
    URL: Issue
    URL: Article
    DOI: 10.1111/jcmm.2014.18.issue-7
    DOI: 10.1111/jcmm.12294
    Language: English
    Publisher: Wiley
    Publication Date: 2014
    detail.hit.zdb_id: 2076114-4
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  • 8
    Online Resource
    Online Resource
    An oral absorbent, AST-120, restores vascular growth and blood flow in ischemic muscles in diabetic mice via modulation of macrophage transition
    Elsevier BV ; 2021
    In:  Journal of Molecular and Cellular Cardiology Vol. 155 ( 2021-06), p. 99-110
    Details
    In: Journal of Molecular and Cellular Cardiology, Elsevier BV, Vol. 155 ( 2021-06), p. 99-110
    Type of Medium: Online Resource
    ISSN: 0022-2828
    URL: Article
    DOI: 10.1016/j.yjmcc.2021.03.001
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2021
    detail.hit.zdb_id: 1469767-1
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  • 9
    Online Resource
    Online Resource
    TREM-1 Promotes Survival during Klebsiella pneumoniae Liver Abscess in Mice
    American Society for Microbiology ; 2014
    In:  Infection and Immunity Vol. 82, No. 3 ( 2014-03), p. 1335-1342
    Details
    In: Infection and Immunity, American Society for Microbiology, Vol. 82, No. 3 ( 2014-03), p. 1335-1342
    Abstract: Klebsiella pneumoniae liver abscess (KPLA) is prevalent in East Asia. Liver abscess can develop after translocation of K. pneumoniae from a patient's bowel into the liver via the portal circulation. TREM-1 ( t riggering r eceptor e xpressed on m yeloid cells 1 ) amplifies inflammatory signaling during infection, but its role in KPLA is poorly understood. We used an animal study to characterize the role of TREM-1 in KPLA. We compared survival rates, bacterial burdens in tissues, inflammatory cytokine levels, and histology findings between wild-type and Trem-1 knockout (KO) mice after oral inoculation of capsular type K1 K. pneumoniae . Translocation of K. pneumoniae to mesenteric lymph nodes and liver was examined, and intestinal permeability, antimicrobial peptide expression, and the clearance of K. pneumoniae in the small intestine were determined. In the absence of TREM-1, KPLA model mice showed increased K. pneumoniae dissemination, enhanced liver and systemic inflammation, and reduced survival. Impaired bacterial clearance in the small intestine causes enhanced K. pneumoniae translocation, which renders Trem-1 KO mice more susceptible to K. pneumoniae oral infection. In conclusion, TREM-1-mediated bacterial clearance in the small intestine is an important immune response against K. pneumoniae . TREM-1 deficiency enhances K. pneumoniae translocation in the small intestine and increases mortality rates in mice with KPLA.
    Type of Medium: Online Resource
    ISSN: 0019-9567 , 1098-5522
    URL: Article
    DOI: 10.1128/IAI.01347-13
    RVK:
    XA 10000
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2014
    detail.hit.zdb_id: 1483247-1
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  • 10
    Online Resource
    Online Resource
    Vaccine adjuvant activity of a TLR4-activating synthetic glycolipid by promoting autophagy
    Springer Science and Business Media LLC ; 2020
    In:  Scientific Reports Vol. 10, No. 1 ( 2020-05-21)
    Details
    In: Scientific Reports, Springer Science and Business Media LLC, Vol. 10, No. 1 ( 2020-05-21)
    Abstract: Toll-like receptors (TLRs) play crucial roles in host immune defenses. Recently, TLR-mediated autophagy is reported to promote immune responses via increasing antigen processing and presentation in antigen presenting cells. The present study examined whether the synthetic TLR4 activator (CCL-34) could induce autophagy to promote innate and adaptive immunity. In addition, the potential of CCL-34 as an immune adjuvant in vivo was also investigated. Our data using RAW264.7 cells and bone marrow-derived macrophages showed that CCL-34 induced autophagy through a TLR4-NF-κB pathway. The autophagy-related molecules (Nrf2, p62 and Beclin 1) were activated in RAW264.7 cells and bone marrow-derived macrophages under CCL-34 treatment. CCL-34-stimulated macrophages exhibited significant antigen-processing activity and induced the proliferation of antigen-specific CD4+T cells as well as the production of activated T cell-related cytokines, IL-2 and IFN-γ. Furthermore, CCL-34 immunization in mice induced infiltration of monocytes in the peritoneal cavity and elevation of antigen-specific IgG in the serum. CCL-34 treatment in vivo did not cause toxicity based on serum biochemical profiles. Notably, the antigen-specific responses induced by CCL-34 were attenuated by the autophagy inhibitor, 3-methyladenine. In summary, we demonstrated CCL-34 can induce autophagy to promote antigen-specific immune responses and act as an efficient adjuvant.
    Type of Medium: Online Resource
    ISSN: 2045-2322
    URL: Article
    DOI: 10.1038/s41598-020-65422-1
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2020
    detail.hit.zdb_id: 2615211-3
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