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  • 1
    Online Resource
    Online Resource
    Taurine Alleviates Schistosoma-Induced Liver Injury by Inhibiting the TXNIP/NLRP3 Inflammasome Signal Pathway and Pyroptosis
    American Society for Microbiology ; 2019
    In:  Infection and Immunity Vol. 87, No. 12 ( 2019-12)
    Details
    In: Infection and Immunity, American Society for Microbiology, Vol. 87, No. 12 ( 2019-12)
    Abstract: Schistosomiasis is a parasitic helminth disease that can cause severe inflammatory pathology, leading to organ damage, in humans. During a schistosomal infection, the eggs are trapped in the host liver, and products derived from eggs induce a polarized Th2 cell response, resulting in granuloma formation and eventually fibrosis. Previous studies indicated that the nucleotide-binding oligomerization domain-, leucine-rich repeat-, and pyrin domain-containing protein 3 (NLRP3) inflammasome is involved in schistosomiasis-associated liver fibrosis and that taurine could ameliorate hepatic granulomas and fibrosis caused by Schistosoma japonicum infection. Nevertheless, the precise role and molecular mechanism of the NLRP3 inflammasome and the protective effects of taurine in S. japonicum infection have not been extensively studied. In this study, we investigated the role of the NLRP3 inflammasome and the hepatoprotective mechanism of taurine in schistosoma-induced liver injury in mice. NLRP3 deficiency ameliorated S. japonicum -infection-induced hepatosplenomegaly, liver dysfunction, and hepatic granulomas and fibrosis; it also reduced NLRP3-dependent liver pyroptosis. Furthermore, taurine suppressed hepatic thioredoxin-interacting protein (TXNIP)/NLRP3 inflammasome activation in mice with S. japonicum infections, thereby inhibiting the activation of downstream inflammatory mediators such as interleukin-1β and subsequent pyroptosis. Our results suggest that the TXNIP/NLRP3 inflammasome pathway and mediating pyroptosis are involved in S. japonicum -induced liver injury and may be a potential therapeutic target for schistosomiasis treatment. In addition, taurine may be useful to alleviate or to prevent the occurrence of schistosomiasis-associated liver fibrosis.
    Type of Medium: Online Resource
    ISSN: 0019-9567 , 1098-5522
    URL: Article
    DOI: 10.1128/IAI.00732-19
    RVK:
    XA 10000
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2019
    detail.hit.zdb_id: 1483247-1
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  • 2
    Online Resource
    Online Resource
    FBXO22 Possesses Both Protumorigenic and Antimetastatic Roles in Breast Cancer Progression
    American Association for Cancer Research (AACR) ; 2018
    In:  Cancer Research Vol. 78, No. 18 ( 2018-09-15), p. 5274-5286
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 78, No. 18 ( 2018-09-15), p. 5274-5286
    Abstract: The molecular underpinnings behind malignant progression of breast cancer from a localized lesion to an invasive and ultimately metastatic disease are incompletely understood. Here, we report that F-box only protein 22 (FBXO22) plays a dual role in mammary tumorigenesis and metastasis. FBXO22 was upregulated in primary breast tumors and promoted cell proliferation and colony formation in vitro and xenograft tumorigenicity in vivo. Surprisingly, FBXO22 suppressed epithelial–mesenchymal transition (EMT), cell motility, and invasiveness in vitro and metastatic lung colonization in vivo. Clinical data showed that expression levels of FBXO22 were associated with favorable clinical outcomes, supporting the notion that metastasis, rather than primary cancer, is the major determinant of the mortality of patients with breast cancer. Mechanistic investigations further revealed that FBXO22 elicits its antimetastatic effects by targeting SNAIL, a master regulator of EMT and breast cancer metastasis, for ubiquitin-mediated proteasomal degradation in a glycogen synthase kinase 3β phosphorylation–dependent manner. Importantly, expression of SNAIL rescued FBXO22-mediated suppression of EMT, cell migration, and invasion. A patient-derived tryptophan-to-arginine mutation at residue 52 (W52R) within the F-box domain impaired FBXO22 binding to the SKP1–Cullin1 complex and blocked FBXO22-mediated SNAIL degradation, thus abrogating the ability of FBXO22 to suppress cell migration, invasion, and metastasis. Collectively, these findings uncover an unexpected dual role for FBXO22 in mammary tumorigenesis and metastatic progression and delineate the mechanism of an oncogenic mutation of FBXO22 in breast cancer progression. Significance: These findings highlight the paradoxical roles of FBXO22 in breast cancer, as it promotes breast tumor cell proliferation but prevents EMT and metastasis. Cancer Res; 78(18); 5274–86. ©2018 AACR.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/0008-5472.CAN-17-3647
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2018
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
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  • 3
    Online Resource
    Online Resource
    Copeptin and NT-proBNP for prediction of all-cause and cardiovascular death in ischemic stroke
    Ovid Technologies (Wolters Kluwer Health) ; 2017
    In:  Neurology Vol. 88, No. 20 ( 2017-05-16), p. 1899-1905
    Details
    In: Neurology, Ovid Technologies (Wolters Kluwer Health), Vol. 88, No. 20 ( 2017-05-16), p. 1899-1905
    Abstract: To evaluate long-term mortality in patients with acute ischemic stroke (AIS) by exploring the correlation between death and plasma concentrations of copeptin and N-terminal pro-B-type natriuretic peptide (NT-proBNP) in a cohort study. Methods: In a prospective, multicenter observational study of 4,215 patients with AIS, copeptin and NT-proBNP levels were measured with a standardized method when patients were admitted to hospital. The primary endpoint was all-cause mortality or cardiovascular disease (CVD) mortality within 1 year. Results: During a follow-up period, 906 patients (20.1%, 95% confidence interval [CI] 18.9–21.2) died, including 589 cases of CVD mortality (13.1%, 95% CI 12.1–14.0). With the use of a multivariate analysis, both markers were found to have prognostic value in the same model (CVD mortality: odds ratio [OR] for fourth quartile of copeptin and NT-proBNP 1.68 and 2.58, 95% CI 1.22–2.49 and 1.76–4.05, respectively; all-cause mortality: OR for fourth quartile of copeptin and NT-proBNP 1.48 and 2.47, 95% CI 1.22–2.03 and 1.68–3.95, respectively). In a receiver operating characteristics analysis of CVD mortality, the area under the curve varied from 0.80 to 0.83 (95% CI 0.79–0.87) when the index of NT-proBNP was added and increased to 0.86 (95% CI 0.83–0.90) when both markers were added. Conclusions: Copeptin and NT-proBNP may be useful independent prognostic markers of all-cause or CVD mortality in Chinese patients with AIS.
    Type of Medium: Online Resource
    ISSN: 0028-3878 , 1526-632X
    URL: Article
    DOI: 10.1212/WNL.0000000000003937
    RVK:
    XA 10000
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2017
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