Role of CD45 Signaling Pathway in Galactoxylomannan-Induced T Cell Damage

Previously, we reported that Galactoxylomannan (GalXM) activates the extrinsic and intrinsic apoptotic pathways through an interaction with the glycoreceptors on T cells. In this study we establish the role of the glycoreceptor CD45 in GalXM-induced T cell apoptosis, using CD45+/+ and CD45−/− cell lines, derived from BW5147 murine T cell lymphoma. Our results show that whereas CD45 expression is not required for GalXM association by the cells, it is essential for apoptosis induction. In CD45+/+ cells, CD45 triggering by GalXM reduces the activation of Lck, ZAP70 and Erk1/2. Conversely, in CD45−/− cells, Lck was hyperphosphorylated and did not show any modulation after GalXM stimulation. On the whole, our findings provide evidence that the negative regulation of Lck activation occurs via CD45 engagement. This appears to be related to the capacity of GalXM to antagonize T cell activation and induce T cell death. Overall this mechanism may be responsible for the immune paralysis that follows GalXM administration and could explain the powerful immunosuppression that accompanies cryptococcosis

Vestibular (dys)function in children with sensorineural hearing loss: a systematic review

<p><i>Objective</i>: The objective of this study is to provide an overview of the prevalence of vestibular dysfunction in children with SNHL classified according to the applied test and its corresponding sensitivity and specificity. <i>Design</i>: Data were gathered using a systematic search query including reference screening. <i>Study sample</i>: Pubmed, Web of Science and Embase were searched. Strategy and reporting of this review was based on the Meta-analysis of Observational Studies in Epidemiology (MOOSE) guidelines. Methodological quality was assessed with the COnsensus‐based Standards for the selection of health Measurement INstruments (COSMIN) checklist. <i>Results</i>: All studies, regardless the applied vestibular test, showed that vestibular function differs significantly between children with hearing loss and normal hearing (<i>p</i> < 0.05). Compared with caloric testing, the sensitivity of the Rotational Chair Test (RCT) varies between 61 and 80% and specificity between 21 and 80%, whereas this was, respectively, 71–100% and 30–100% for collic Vestibular Evoked Myogenic Potentials (cVEMP). Compared with RCT, the sensitivity was 88–100% and the specificity was 69–100% for the Dynamic Visual Acuity test, respectively, 67–100% and 71–100% for the (video) Head Impulse Test and 83% and 86% for the ocular VEMP. <i>Conclusions</i>: Currently, due to methodological shortcoming, evidence on sensitivity and specificity of vestibular tests is unknown to moderate. Future research should focus on adequate sample sizes (subgroups >30).</p

Synthesis of triazolylmethyl-linked nucleoside analogs via combination of azidofuranoses with propargylated nucleobases and study on their cytotoxicity

KARAYILDIRIM, Tamer/0000-0001-7451-0810; HALAY, Erkan/0000-0002-0084-7709WOS: 000429350900009Copper(I)-catalyzed azide-alkyne 1,3-dipolar cycloaddition reactions (CuAAC) between azidofuranoses and propargyl-nucleobases were carried out in the presence of CuSO4 center dot 5H(2)O and sodium ascorbate as catalytic system to provide the corresponding 1,4-disubstituted-1,2,3-triazole-bridged nucleoside analogs in good yields. Twelve new sugar-based triazolylmethyl-linked nucleoside analogs were synthesized and screened for their cytotoxic activity against MDA-MB-231, Hep3B, PC-3, SH-SY5Y, and HCT-116 cancer cell lines and control cell line (L929). Most of the compounds were moderately effective against all the cancer cell lines assayed. Particularly, among the tested compounds, 1,2,3-triazole-linked 5-fluorouracil-mannofuranose hybrid was found to be the most potent cytotoxic agent against HCT-116, Hep3B, SH-SY5Y cells with IC50 values of 35.6, 71.1, and 75.6 mu M, respectively. None of the triazolylmethyl-linked nucleoside analogs exhibited cytotoxic effect against the control cells L929.TUBITAK-Research Council of Turkey [114Z757]; TUBITAK-BIDEBTurkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK) [2211A]This work was supported by TUBITAK-Research Council of Turkey with the project number 114Z757. Author E. Halay also offers his profound thanks to TUBITAK-BIDEB 2211A for their bursary support