Exclusive semileptonic BB-meson decays using lattice QCD and unitarity

We present the results of the application of the Dispersion Matrix approach to exclusive semileptonic $B$-meson decays. This method allows to determine the hadronic form factors in a non-perturbative and completely model-independent way. Starting from lattice results available at large values of the momentum transfer, the behaviour of the form factors in their whole kinematical range is obtained without introducing any parameterization of their momentum dependence. We will focus on the determination of the Cabibbo-Kobayashi-Maskawa matrix elements $\vert V_{cb} \vert$ and $\vert V_{ub} \vert$ through the analysis of $B_{(s)} \to D_{(s)}^{(*)} \ell \nu$ and $B_{(s)} \to \pi(K) \ell \nu$ decays. New theoretical determinations of the Lepton Flavour Universality ratios relevant for these transitions will be also presented.Comment: 8 pages, 5 figures, 2 tables; contribution to QCD@Work - International Workshop on QCD - Theory and Experiment, 27 - 30 June 2022, Lecce (Italy). arXiv admin note: substantial text overlap with arXiv:2205.1395

The DM approach to semileptonic heavy-to-heavy and heavy-to-light BB decays

We present the results of the application of the Dispersion Matrix approach to semileptonic heavy-to-heavy and heavy-to-light $B$-meson decays. This method allows to determine the hadronic form factors in a non-perturbative and model-independent way. Starting from the available lattice results at large values of the momentum transfer, we obtain the behaviour of the form factors in their whole kinematical range without introducing any parameterization of their momentum dependence. We will focus on the determination of the Cabibbo-Kobayashi-Maskawa matrix elements $\vert V_{cb} \vert$ and $\vert V_{ub} \vert$ through the analysis of $B \to D^{(*)} \ell \nu$, $B_s \to D_s^{(*)} \ell \nu$, $B \to \pi \ell \nu$ and $B_s \to K \ell \nu$ decays. New theoretical determinations of the Lepton Flavour Universality ratios relevant for these transitions will be also presented, by focusing in particular on the $R(D_{(s)}^{(*)})$ ratios.Comment: 9 pages, 3 figures. Proceedings for the 39th International Symposium on Lattice Field Theory (Lattice 2022). arXiv admin note: substantial text overlap with arXiv:2209.15413, arXiv:2205.13952; text overlap with arXiv:2211.0723

Vanillin prevents doxorubicin-induced apoptosis and oxidative stress in rat H9c2 cardiomyocytes

Doxorubicin (doxo) is an effective anticancer compound in several tumor types. However, as a consequence of oxidative stress induction and ROS overproduction, its high cardiotoxicity demands urgent attention. Vanillin possesses antioxidant, antiproliferative, antidepressant and anti-glycating properties. Therefore, we investigated the potential vanillin protective effects against doxo-induced cardiotoxicity in H9c2 cells. Using multiparametric approach, we demonstrated that vanillin restored both cell viability and damage in response to doxo exposure. Contextually, vanillin decreased sub-G1 appearance and caspase-3 and PARP1 activation, reducing the doxo-related apoptosis induction. From a mechanistic point of view, vanillin hindered doxo-induced ROS accumulation and impaired the ERK phosphorylation. Notably, besides the cardioprotective effects, vanillin did not counteract the doxo effectiveness in osteosarcoma cells. Taken together, our results suggest that vanillin ameliorates doxo-induced toxicity in H9c2 cells, opening new avenues for developing alternative therapeutic approaches to prevent the anthracycline-related cardiotoxicity and to improve the long-term outcome of antineoplastic treatment

Rapid determination of esterified glycerol and glycerides in triglycerides fats and oils by means of periodate method after transesterfication

The paper describes an accurate method to determine esterified glycerol in the glycerides edible fats and oils and in general in all triglycerides fats and oils

Rituximab Unveils Hypogammaglobulinemia and Immunodeficiency in Children with Autoimmune Cytopenia

BACKGROUND: Rituximab (RTX; anti-CD20 mAb) is a treatment option in children with refractory immune thrombocytopenia, autoimmune hemolytic anemia (AHA), and Evans syndrome (ES). Prevalence and clinical course of RTX-induced hypogammaglobulinemia in these patients are poorly known. OBJECTIVE: To evaluate the prevalence and risk factors for persistent hypogammaglobulinemia (PH) after RTX use. METHODS: Clinical and immunologic data from children treated with RTX for immune thrombocytopenia, AHA, and ES were collected from 16 Italian centers and 1 UK center at pre-RTX time point (0), +6 months, and yearly, up to 4 years post-RTX. Patients with previously diagnosed malignancy or primary immune deficiency (PID) were excluded. RESULTS: We analyzed 53 children treated with RTX for immune thrombocytopenia (n = 36), AHA (n = 13), and ES (n = 4). Median follow-up was 30 months (range, 12-48). Thirty-two percent of patients (17 of 53) experienced PH, defined as IgG levels less than 2 SD for age at last follow-up (>12 months after RTX). Significantly delayed B-cell recovery was observed in children experiencing PH (hazard ratio, 0.55; P < .05), and 6 of 17 (35%) patients had unresolved B-cell lymphopenia at last follow-up. PH was associated with IgA and IgM deficiency, younger age at RTX use (51 vs 116 months; P < .01), a diagnosis of AHA/ES, and better response to RTX. Nine patients with PH (9 of 17 [53%]) were eventually diagnosed with a PID. CONCLUSIONS: Post-RTX PH is a frequent condition in children with autoimmune cytopenia; a sizable proportion of patients with post-RTX PH were eventually diagnosed with a PID. In-depth investigation for PID is therefore recommended in these patients

Neutralization of extracellular NAMPT (nicotinamide phosphoribosyltransferase) ameliorates experimental murine colitis

Extracellular nicotinamide phosphoribosyltransferase (eNAMPT) is increased in inflammatory bowel disease (IBD) patients, and its serum levels correlate with a worse prognosis. In the present manuscript, we show that eNAMPT serum levels are increased in IBD patients that fail to respond to anti-TNF\u3b1 therapy (infliximab or adalimumab) and that its levels drop in patients that are responsive to these therapies, with values comparable with healthy subjects. Furthermore, eNAMPT administration in dinitrobenzene sulfonic acid (DNBS)-treated mice exacerbates the symptoms of colitis, suggesting a causative role of this protein in IBD. To determine the druggability of this cytokine, we developed a novel monoclonal antibody (C269) that neutralizes in vitro the cytokine-like action of eNAMPT and that reduces its serum levels in rodents. Of note, this newly generated antibody is able to significantly reduce acute and chronic colitis in both DNBS- and dextran sulfate sodium (DSS)-induced colitis. Importantly, C269 ameliorates the symptoms by reducing pro-inflammatory cytokines. Specifically, in the lamina propria, a reduced number of inflammatory monocytes, neutrophils, Th1, and cytotoxic T lymphocytes are found upon C269 treatment. Our data demonstrate that eNAMPT participates in IBD and, more importantly, that eNAMPT-neutralizing antibodies are endowed with a therapeutic potential in IBD. Key messages: What are the new findings?Higher serum eNAMPT levels in IBD patients might decrease response to anti-TNF therapy.The cytokine-like activity of eNAMPT may be neutralized with a monoclonal antibody.Neutralization of eNAMPT ameliorates acute and chronic experimental colitis.Neutralization of eNAMPT limits the expression of IBD inflammatory signature.Neutralization of eNAMPT impairs immune cell infiltration in lamina propria

Autocrine Prostaglandin E2 Signaling Promotes Tumor Cell Survival and Proliferation in Childhood Neuroblastoma

Background: Prostaglandin E2 (PGE2) is an important mediator in tumor-promoting inflammation. High expression of cyclooxygenase-2 (COX-2) has been detected in the embryonic childhood tumor neuroblastoma, and treatment with COX inhibitors significantly reduces tumor growth. Here, we have investigated the significance of a high COX-2 expression in neuroblastoma by analysis of PGE2 production, the expression pattern and localization of PGE2 receptors and intracellular signal transduction pathways activated by PGE2. Principal Findings: A high expression of the PGE2 receptors, EP1, EP2, EP3 and EP4 in primary neuroblastomas, independent of biological and clinical characteristics, was detected using immunohistochemistry. In addition, mRNA and protein corresponding to each of the receptors were detected in neuroblastoma cell lines. Immunofluorescent staining revealed localization of the receptors to the cellular membrane, in the cytoplasm, and in the nuclear compartment. Neuroblastoma cells produced PGE2 and stimulation of serum-starved neuroblastoma cells with PGE2 increased the intracellular concentration of calcium and cyclic AMP with subsequent phosphorylation of Akt. Addition of 16,16-dimethyl PGE 2 (dmPGE2) increased cell viability in a time, dose- and cell line-dependent manner. Treatment of neuroblastoma cells with a COX-2 inhibitor resulted in a diminished cell growth and viability that was reversed by the addition of dmPGE2. Similarly, PGE 2 receptor antagonists caused a decrease in neuroblastoma cell viability in a dose-dependent manner