يعرض 1 - 10 نتائج من 208 نتيجة بحث عن '"Nardone A."', وقت الاستعلام: 0.90s تنقيح النتائج
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    دورية أكاديمية

    الوصف: In arthropods, hemolymph carries immune cells and solubilizes and transports nutrients, hormones, and other molecules that are involved in diverse physiological processes including immunity, metabolism, and reproduction. However, despite such physiological importance, little is known about its composition. We applied mass spectrometry-based label-free quantification approaches to study the proteome of hemolymph perfused from sugar-fed female and male Aedes aegypti mosquitoes. A total of 1403 proteins were identified, out of which 447 of them were predicted to be extracellular. In both sexes, almost half of these extracellular proteins were predicted to be involved in defense/immune response, and their relative abundances (based on their intensity-based absolute quantification, iBAQ) were 37.9 and 33.2%, respectively. Interestingly, among them, 102 serine proteases/serine protease-homologues were identified, with almost half of them containing CLIP regulatory domains. Moreover, proteins belonging to families classically described as chemoreceptors, such as odorant-binding proteins (OBPs) and chemosensory proteins (CSPs), were also highly abundant in the hemolymph of both sexes. Our data provide a comprehensive catalogue of A. aegypti hemolymph basal protein content, revealing numerous unexplored targets for future research on mosquito physiology and disease transmission. It also provides a reference for future studies on the effect of blood meal and infection on hemolymph composition.

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    دورية أكاديمية

    المصدر: Current Allergy and Asthma Reports. 18(5)

    الوصف: Purpose of reviewGiven racial disparities in ambient air pollution (AAP) exposure and asthma risk, this review offers an overview of the literature investigating the ambient air pollution-asthma relationship in children of color between 2013 and 2017.Recent findingsAAP is likely a key contributor to the excess burden of asthma in children of color due to pervasive exposure before birth, at home, and in school. Recent findings suggest that psychosocial stressors may modify the relationship between AAP and asthma. The effect of AAP on asthma in children of color is likely modulated by multiple unique psychosocial stressors and gene-environment interactions. Although children of color are being included in asthma studies, more research is still needed on impacts of specific criteria pollutants throughout the life course. Additionally, future studies should consider historical factors when analyzing current exposure profiles.

    وصف الملف: application/pdf

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    الوصف: Background Consolidative thoracic radiotherapy (TRT) has been commonly used in the management of extensive-stage small cell lung cancer (ES-SCLC). Nevertheless, phase III trials exploring first-line chemoimmunotherapy have excluded this treatment approach. However, there is a strong biological rationale to support the use of radiotherapy (RT) as a boost to sustain anti-tumor immune responses. Currently, the benefit of TRT after chemoimmunotherapy remains unclear. The present report describes the real-world experiences of 120 patients with ES-SCLC treated with different chemoimmunotherapy combinations. Preclinical data supporting the hypothesis of anti-tumor immune responses induced by RT are also presented. Methods A total of 120 ES-SCLC patients treated with chemoimmunotherapy since 2019 in the South of Italy were retrospectively analyzed. None of the patients included in the analysis experienced disease progression after undergoing first-line chemoimmunotherapy. Of these, 59 patients underwent TRT after a multidisciplinary decision by the treatment team. Patient characteristics, chemoimmunotherapy schedule, and timing of TRT onset were assessed. Safety served as the primary endpoint, while efficacy measured in terms of overall survival (OS) and progression-free survival (PFS) was used as the secondary endpoint. Immune pathway activation induced by RT in SCLC cells was explored to investigate the biological rationale for combining RT and immunotherapy. Results Preclinical data supported the activation of innate immune pathways, including the STimulator of INterferon pathway (STING), gamma-interferon-inducible protein (IFI-16), and mitochondrial antiviral-signaling protein (MAVS) related to DNA and RNA release. Clinical data showed that TRT was associated with a good safety profile. Of the 59 patients treated with TRT, only 10% experienced radiation toxicity, while no ≥ G3 radiation-induced adverse events occurred. The median time for TRT onset after cycles of chemoimmunotherapy was 62 days. Total radiation dose ...

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    دورية أكاديمية

    الوصف: Pneumonia is the primary cause of death among HIV-infected children in Africa, with mortality rates as high as 35-40% in infants hospitalized with severe pneumonia. Bacterial pathogens and Pneumocystis jirovecii are well known causes of pneumonia-related death, but other important causes such as cytomegalovirus (CMV) and tuberculosis (TB) remain under-recognized and undertreated. The immune response elicited by CMV may be associated with the risk of developing TB and TB disease progression, and CMV may accelerate disease caused both by HIV and TB. Minimally invasive autopsies confirm that CMV and TB are unrecognized causes of death in children with HIV. CMV and TB may also co-infect the same child. The aim of this study is to compare the impact on 15-day and 1-year mortality of empirical treatment against TB and CMV plus standard of care (SoC) versus SoC in HIV-infected infants with severe pneumonia.This is a Phase II-III, open-label randomized factorial (2 × 2) clinical trial, conducted in six African ... : الالتهاب الرئوي هو السبب الرئيسي للوفاة بين الأطفال المصابين بفيروس نقص المناعة البشرية في أفريقيا، حيث تصل معدلات الوفيات إلى 35-40 ٪ بين الرضع الذين يدخلون المستشفى بالالتهاب الرئوي الحاد. تعد مسببات الأمراض البكتيرية والمكورات الرئوية الجيروفية من الأسباب المعروفة للوفاة المرتبطة بالالتهاب الرئوي، ولكن لا تزال الأسباب المهمة الأخرى مثل الفيروس المضخم للخلايا والسل غير معترف بها ولا يتم علاجها. قد ترتبط الاستجابة المناعية التي أثارها فيروس CMV بخطر تطور مرض السل والسل، وقد يؤدي فيروس CMV إلى تسريع المرض الناجم عن كل من فيروس نقص المناعة البشرية والسل. تؤكد عمليات تشريح الجثث طفيفة التوغل أن الفيروس المضخم للخلايا والسل هي أسباب غير معروفة للوفاة لدى الأطفال المصابين بفيروس نقص المناعة البشرية. قد يصيب فيروس الورم الحليمي البشري والسل نفس الطفل. الهدف من هذه الدراسة هو مقارنة التأثير على وفيات 15 يومًا وسنة واحدة من العلاج التجريبي ضد السل وفيروس CMV بالإضافة إلى معيار الرعاية (SoC) مقابل SoC في الرضع المصابين بفيروس نقص المناعة البشرية المصابين بالالتهاب الرئوي الحاد. هذه هي المرحلة الثانية والثالثة، تجربة ...

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    دورية أكاديمية

    المساهمون: Fondazione Just Italia, Ministero della Salute, Fondation Jérôme Lejeune

    المصدر: Cell Death & Disease ; volume 13, issue 11 ; ISSN 2041-4889

    الوصف: Smith-Magenis syndrome (SMS) is a neurodevelopmental disorder characterized by cognitive and behavioral symptoms, obesity, and sleep disturbance, and no therapy has been developed to alleviate its symptoms or delay disease onset. SMS occurs due to haploinsufficiency of the retinoic acid-induced-1 ( RAI1 ) gene caused by either chromosomal deletion (SMS-del) or RAI1 missense/nonsense mutation. The molecular mechanisms underlying SMS are unknown. Here, we generated and characterized primary cells derived from four SMS patients (two with SMS-del and two carrying RAI1 point mutations) and four control subjects to investigate the pathogenetic processes underlying SMS. By combining transcriptomic and lipidomic analyses, we found altered expression of lipid and lysosomal genes, deregulation of lipid metabolism, accumulation of lipid droplets, and blocked autophagic flux. We also found that SMS cells exhibited increased cell death associated with the mitochondrial pathology and the production of reactive oxygen species. Treatment with N-acetylcysteine reduced cell death and lipid accumulation, which suggests a causative link between metabolic dyshomeostasis and cell viability. Our results highlight the pathological processes in human SMS cells involving lipid metabolism, autophagy defects and mitochondrial dysfunction and suggest new potential therapeutic targets for patient treatment.

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    دورية أكاديمية

    المساهمون: Nardone V., Tini P., Pastina P., Botta C., Reginelli A., Carbone S.F., Giannicola R., Calabrese G., Tebala C., Guida C., Giudice A., Barbieri V., Tassone P., Tagliaferri P., Cappabianca S., Capasso R., Luce A., Caraglia M., Mazzei M.A., Pirtoli L., Correale P.

    الوصف: Immune checkpoint blockade is an emerging anticancer strategy, and Nivolumab is a human mAb to PD-1 that is used in the treatment of a number of different malignancies, including non-small cell lung cancer (NSCLC), kidney cancer, urothelial carcinoma and melanoma. Although the use of Nivolumab prolongs survival in a number of patients, this treatment is hampered by high cost. Therefore, the identification of predictive markers of response to treatment in patients is required. In this context, PD-1/PDL1 blockade antitumor effects occur through the reactivation of a pre-existing immune response, and the efficacy of these effects is strictly associated with the presence of necrosis, hypoxia and inflammation at the tumour sites. It has been indicated that these events can be evaluated by specific assessments using a computed tomography (CT) texture analysis (TA) or radiomics. Therefore, a retrospective study was performed, which aimed to evaluate the potential use of this analysis in the identification of patients with NSCLC who may benefit from Nivolumab treatment. A retrospective analysis was performed of 59 patients with metastatic NSCLC who received Nivolumab treatment between January 2015 and July 2017 at Siena University Hospital (35 patients, training dataset), Catanzaro University Hospital and Reggio Calabria Grand Metropolitan Hospital, Italy (24 patients, validation dataset). Pre- and post-contrast CT sequences were used to contour the gross tumour volume (GTV) of the target lesions prior to Nivolumab treatment. The impact of variations on contouring was analysed using two delineations, which were performed on each patient, and the TA parameters were tested for reliability using the Intraclass Coefficient Correlation method (ICC). All analyses for the current study were performed using LifeX Software©. Imaging, clinical and pathological parameters were correlated with progression free survival and overall survival (OS) using Kaplan Meier analysis. An external validation testing was performed for the TA ...

    العلاقة: info:eu-repo/semantics/altIdentifier/pmid/31966081; info:eu-repo/semantics/altIdentifier/wos/WOS:000508895000055; volume:19; issue:2; firstpage:1559; lastpage:1566; numberofpages:8; journal:ONCOLOGY LETTERS; http://hdl.handle.net/10447/513588Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85077918734

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    المصدر: Frontiers in Immunology. 14

    مصطلحات موضوعية: Immunology, Immunology and Allergy

    الوصف: Autoimmune diseases vary in the magnitude and diversity of autoantibody profiles, and these differences may be a consequence of different types of breaks in tolerance. Here, we compared the disparate autoimmune diseases autoimmune polyendocrinopathy–candidiasis–ecto-dermal dystrophy (APECED), systemic lupus erythematosus (SLE), and Sjogren’s syndrome (SjS) to gain insight into the etiology of breaks in tolerance triggering autoimmunity. APECED was chosen as a prototypical monogenic disease with organ-specific pathology while SjS and SLE represent polygenic autoimmunity with focal or systemic disease. Using protein microarrays for autoantibody profiling, we found that APECED patients develop a focused but highly reactive set of shared mostly anti-cytokine antibodies, while SLE patients develop broad and less expanded autoantibody repertoires against mostly intracellular autoantigens. SjS patients had few autoantibody specificities with the highest shared reactivities observed against Ro-52 and La. RNA-seq B-cell receptor analysis revealed that APECED samples have fewer, but highly expanded, clonotypes compared with SLE samples containing a diverse, but less clonally expanded, B-cell receptor repertoire. Based on these data, we propose a model whereby the presence of autoreactive T-cells in APECED allows T-dependent B-cell responses against autoantigens, while SLE is driven by breaks in peripheral B-cell tolerance and extrafollicular B-cell activation. These results highlight differences in the autoimmunity observed in several monogenic and polygenic disorders and may be generalizable to other autoimmune diseases.

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    دورية أكاديمية