Search results for "DISCOVERY"

Translation of Basic Research into Clinics: Killer Immunoglobulin-like Receptors Genes in Autoimmune and Infectious Diseases

2018

Killer immunoglobulin-like receptors (KIRs) regulate the activation of natural killer cells through their interaction with human leucocyte antigens (HLA). KIRs and HLA loci are highly polymorphic, and some of their combinations have been found to protect against viral infections or to predispose to autoimmune disorders. In particular, some activating KIRs profiles may be detrimental in autoimmune pathogenesis, and specific KIRs may be particularly aggressive in the clearance of different microorganisms, protecting individuals in the control of a given pathogen. So, considering that in the pathogenesis of many autoimmune disorders and infections innate immunity plays a key role, the recent …

Do urocortins have a role in treating cardiovascular disease?

2018

Corticotropin-releasing factor (CRF) and the three homolog neuropeptides, urocortin (UCN) 1, 2 and 3, are the major neuroendocrine factors implicated in the response of the body to stress. Recent evidence suggests that UCNs have a significant role in the pathogenesis and management of cardiovascular disease, such as congestive heart failure, ischemic heart disease, and hypertension. These data led to the initiation of clinical trials testing a possible role of UCNs in the diagnosis and therapy of cardiovascular disease, with encouraging results. Here, we summarize the available literature concerning the role of UCNs in the cardiovascular system, focusing on the emerging data creating a pote…

Cryptotanshinone deregulates unfolded protein response and eukaryotic initiation factor signaling in acute lymphoblastic leukemia cells.

2015

Abstract Background: Unfolded protein responses (UPR) determine cell fate and are recognized as anticancer targets. In a previous research, we reported that cryptotanshinone (CPT) exerted cytotoxic effects toward acute lymphoblastic leukemia cells through mitochondria-mediated apoptosis. Purpose: In the present study, we further investigated the role of UPR in CPT-induced cytotoxicity on acute lymphoblastic leukemia cells by applying tools of pharmacogenomics and bioinformatics. Methods: Gene expression profiling was performed by mRNA microarray hybridization. Potential transcription factor binding motifs were identified in the promoter regions of the deregulated genes by Cistrome software.…

2019

Glaucoma is an optic neurological disorder and the leading cause of irreversible blindness worldwide, with primary open angle glaucoma (POAG) as its most prevalent form. An early diagnosis of the disease is crucial to prevent loss of vision. Mechanisms behind glaucoma pathogenesis are not completely understood, but disease related alterations in the serological autoantibody profile indicate an immunologic component. These changes in immunoreactivity may serve as potential biomarkers for glaucoma diagnostics. We aimed to identify novel disease related autoantibodies targeting antigens in the trabecular meshwork as biomarkers to support early detection of POAG. We used serological proteome an…

Immunization Status against Measles of Health-Care Workers Operating at Three Sicilian University Hospitals: An Observational Study

2019

Measles is a highly contagious vaccine-preventable disease (VPD) that also commonly affects health-care workers (HCWs). Measles immunization of HCWs was strongly recommended by international health authorities, in order to limit the spreading of the illness to susceptible patients and colleagues. An observational study, evaluating the immunization and vaccination status against measles of HCWs working at three Sicilian university hospitals, was conducted. All subjects not completely immune (vaccinated with only one dose in their lifetime), not immune (not vaccinated or not naturally immunized), and with an unknown immunization status were considered not immunized. Among HCWs operating in th…

MicroRNA and receptor mediated signaling pathways as potential therapeutic targets in heart failure.

2016

Cardiac remodelling is a complex pathogenetic pathway involving genome expression, molecular, cellular, and interstitial changes that cause changes in size, shape and function of the heart after cardiac injury. Areas covered: We will review recent advances in understanding the role of several receptor-mediated signaling pathways and micro-RNAs, in addition to their potential as candidate target pathways in the pathogenesis of heart failure. The myocyte is the main target cell involved in the remodelling process via ischemia, cell necrosis and apoptosis (by means of various receptor pathways), and other mechanisms mediated by micro-RNAs. We will analyze the role of some receptor mediated sig…

mRNA-Based Vaccines

2021

Increases in the world’s population and population density promote the spread of emerging pathogens. Vaccines are the most cost-effective means of preventing this spread. Traditional methods used to identify and produce new vaccines are not adequate, in most instances, to ensure global protection. New technologies are urgently needed to expedite large scale vaccine development. mRNA-based vaccines promise to meet this need. mRNA-based vaccines exhibit a number of potential advantages relative to conventional vaccines, namely they (1) involve neither infectious elements nor a risk of stable integration into the host cell genome; (2) generate humoral and cell-mediated immunity; (3) are well-t…

Everolimus as first line therapy for pancreatic neuroendocrine tumours: current knowledge and future perspectives

2017

urpose Everolimus has been shown to be effective for advanced pancreatic neuroendocrine tumours (pNETs), but its positioning in the therapeutic algorithm for pNETs is matter of debate. Methods With the aim to shed light on this point, we performed an up-to-date critical review taking into account the results of both retrospective and prospective published studies, and the recommendations of international guidelines. In addition, we performed an extensive search on the Clinical Trial Registries databases worldwide, to gather information on the ongoing clinical trials related to this specific topic. Results We identified eight retrospective published studies, two prospective published studies…

The swinholide biosynthesis gene cluster from a terrestrial cyanobacterium, Nostoc sp. strain UHCC 0450

2017

ABSTRACT Swinholides are 42-carbon ring polyketides with a 2-fold axis of symmetry. They are potent cytotoxins that disrupt the actin cytoskeleton. Swinholides were discovered from the marine sponge Theonella sp. and were long suspected to be produced by symbiotic bacteria. Misakinolide, a structural variant of swinholide, was recently demonstrated to be the product of a symbiotic heterotrophic proteobacterium. Here, we report the production of swinholide A by an axenic strain of the terrestrial cyanobacterium Nostoc sp. strain UHCC 0450. We located the 85-kb trans -AT polyketide synthase (PKS) swinholide biosynthesis gene cluster from a draft genome of Nostoc sp. UHCC 0450. The swinholide …

Prospecting for cytotoxic and antiprotozoal 4-aryl-4H-chromenes and 10-aryldihydropyrano[2,3-f]chromenes.

2018

Different studies reported that genetic predisposition or metabolic dysfunction are the risk factors for cancer. Infectious parasitic diseases were listed among factors that predispose to cancer. Because of the resemblance between the life cycle of cancer cells and some parasites, this study aimed to prepare pyran derivatives with cytotoxic and antiprotozoal potencies. Therefore, 7 chromenes, 10 pyranocoumarins, and an unexpected intermediate were obtained from a multi-reagent one-pot reaction. These compounds were evaluated for their cytotoxicity on sensitive and resistant leukemia cancer cells lines and against two protozoan parasites, namely Trypanosoma cruzi and Leishmania amazonensis a…