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121.
IL‐4‐induced gene 1 maintains high Tob1 expression that contributes to TCR unresponsiveness in human T helper 17 cells
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Alessio Mazzoni Manuela Capone Valentina Querci Maria Caterina Rossi Luca Beltrame Duccio Cavalieri Raffaele De Palma Francesco Liotta Lorenzo Cosmi Enrico Maggi Sergio Romagnani Francesco Annunziato 《European journal of immunology》2014,44(3):654-661
Human Th17 cells have a limited proliferative capacity compared to other T‐cell subsets. We have shown that human Th17 cells display impaired IL‐2 production due to IL‐4‐induced gene 1 (IL4I1) upregulation. Here, we show that in human Th17 cells, IL4I1 also maintains high levels of Tob1, a member of the Tob/BTG (B‐cell traslocation gene) antiproliferative protein family, which prevents cell‐cycle progression mediated by TCR stimulation. Indeed, Th17 cells exhibited higher levels of Tob1 than Th1 cells in both resting and TCR‐activated conditions. Accordingly, the expression of positive regulators of the cell cycle (cyclin A, B, C, and E and Cdk2), as well as of Skp2, which promotes Tob1 degradation, was lower in Th17 cells than in Th1 cells. Tob1 expression in human Th17 cells correlated with both RAR (retinoic acid receptor)‐related orphan receptor C (RORC) and IL4I1 levels. However, RORC was not directly involved in the regulation of Tob1 expression, whereas IL4I1 silencing in Th17 cells induced a substantial decrease of Tob1 expression. These data suggest that IL4I1 upregulation in human Th17 cells limits their TCR‐mediated expansion not only by blocking the molecular pathway involved in the activation of the IL‐2 promoter, but also by maintaining high levels of Tob1, which impairs entry into the cell cycle. 相似文献
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Giovanni Di Salvo Fabio D’Aiello Fortuna Del Gaizo Paolo Indolfi Fiorina Casale Maria Teresa di Tullio Diana Iarussi Raffaele Calabrò Maria Giovanna Russo 《Journal of Cardiovascular Echography》2014,24(1):25-28
We investigated the left ventricular (LV) function, using for the first time strain (S) and strain rate (SR) imaging, in long-term survivors affected by acute lymphoblastic leukemia treated with a low cumulative dose of anthracyclines, and in presence of a normal global LV systolic and diastolic function. A total of 21 were enrolled in the study. The mean cumulative dose of anthracylines was 180 mg/m2 (range: 120-210 mg/m2). As control group 21 age-sex matched healthy subjects were included. Radial S (17 ± 3% vs. 55 ± 6%, P < 0.0001) and SR (2.1 ± 0.3 vs. 3.0 ± 0.8 1\s, P < 0.0001), assessed on the midsegment of the posterior wall from the parasternal views were significantly reduced when compared with controls. Conversely, myocardial performance index was not able to discriminate between patients and controls. In this preliminary study, the myocardial deformation indices appear to be a more sensitive noninvasive technique for detecting subclinical LV dysfunction than other echocardiographic measurements. 相似文献
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Giovanni Ribaudo Alberto Ongaro Maira Zorzan Raffaele Pezzani Marco Redaelli Giuseppe Zagotto Maurizio Memo Alessandra Gianoncelli 《Archiv der Pharmazie》2019,352(5)
The design of a multitarget and multifunctional small molecule containing two functional groups reacting through different mechanisms represents an attractive goal for the medicinal chemist. The preparation of two bifunctional oxiranylmethyloxy anthraquinones, previously investigated as anticancer agents, is described here. These compounds combine a planar, DNA‐intercalating and pro‐oxidant anthraquinone scaffold and the alkylating epoxide functions which can covalently react with the nucleic acid. Their multilevel molecular reactivity was studied through a combination of analytical techniques: The DNA‐binding properties were investigated using a mass spectrometry‐based binding assay and by nuclear magnetic resonance, highlighting the formation of a covalent adduct with a nucleobase. Moreover, the contribution of the pro‐oxidant redox cycling was evaluated. 相似文献
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Alfonso Tatasciore Marta Di Nicola Roberto Tommasi Francesco Santarelli Carlo Palombo Gianfranco Parati Raffaele De Caterina 《Journal of clinical hypertension (Greenwich, Conn.)》2020,22(7):1218-1227
Both arterial blood pressure (BP) average levels and short‐term BP variability (BPV) relate to hypertension‐mediated organ damage, in particular increased carotid artery intima‐media thickness (IMT) and carotid‐femoral pulse wave velocity (PWV). Endothelial dysfunction possibly mediates such damage. The authors aimed at further investigating such role in hypertensive patients. In 189 recently diagnosed, untreated hypertensive patients the authors evaluated, in a cross‐sectional design, the relationships of BP average levels and short‐term systolic (S) BPV (standard deviation of awake SBP or of 24‐hour‐weighted SBP) with IMT and PWV, and how much these relationships are explained by endothelial function parameters—brachial artery flow‐mediated dilation (FMD) and digital reactive hyperemia index (RHI). Multivariable models assessed the strength of these relationships to derive a plausible pathogenetic sequence. Both average SBP values and our measures of SBPV were significantly related to IMT (24‐hour mean SBP: r = .156, P = .034; 24‐hour‐weighted SBPV: r = .157, P = .033) and to PWV (24‐hour mean SBP: r = .179, P = .015; 24‐hour‐weighted SBPV: r = .175; P = .018), but only poorly related to FMD or RHI (P > .05 for all). At univariable regression analysis, FMD and RHI were both related to IMT, (P < .001), but not to PWV. When FMD and RHI were added to average SBP and SBPV parameters in a multivariable model, both significantly (P < .005) contributed to predict IMT, but not PWV. Thus, endothelial dysfunction relates to IMT independently of BP parameters, but appears to play a minor role in the association between BP variability‐related variables and arterial stiffening. 相似文献
129.
Giuseppe Limongelli Teo Roselli Giuseppe Pacileo Paolo Calabró Valeria Maddaloni Daniele Masarone Lucia Riegler Rita Gravino Raffaella Scarafile Gemma Salerno Tiziana Miele Antonello D’Andrea Lucio Santangelo Massimo Romano Giovanni Di Salvo Maria Giovanna Russo Raffaele Calabró 《Internal and emergency medicine》2014,9(1):43-50
Cardiotrophin-1 (CT-1) is a member of the interleukin (IL-6) family of cytokines. Plasma CT-1 levels correlate with the left ventricle mass index in patients with dilatated cardiomyopathy and congestive heart failure (CHF). The aim of this paper was to evaluate CT-1 plasma levels, before and after cardiac resynchronization therapy CRT, and to characterizeits prognostic role in patients with CHF. Fifty-two consecutive patients (M/F = 39/13; 56 ± 11 years old) underwent clinical and echocardiographic evaluation, and blood sample collection at baseline. The same evaluation was repeated 6.4 ± 0.79 months after CRT. Patients with a decreased LV end-systolic volume by at least 15% (reverse remodeling) were considered echo responders to CRT. Twenty-nine patients (56%) were responders to CRT. After CRT, only 15 patients (29%) showed increased CT-1 after CRT. They were all non responders to CRT. A multivariate, logistic modelshowed CT-1 as an independent predictor of CRT echo response (p = 0.005; OR 0.97). During follow-up (18 ± 7 months), 21 cardiac events in 18 patients occurred. A Cox multivariable model showed plasma BNP pre-CRT (p = 0.02; CI 1.2–5.6; OR 3.1) and CT1 post-CRT (p = 0.01; CI 1.4–4.3; OR 2.7) as independent predictors of cardiac events. Analysis of CT-1 plasma levels deserves future consideration for larger, longitudinal studies in patients with CHF. 相似文献
130.
Cristiano Spadaccio Federico De Marco Fabio Di Domenico Raffaella Coccia Mario Lusini Raffaele Barbato Elvio Covino Massimo Chello 《Thrombosis research》2014