Search results for "DISEASES"
showing 10 items of 20537 documents
Plastic and micro-evolutionary responses of a nematode to the host immune environment
2017
9 pages; International audience; Parasitic organisms have to cope with the defences deployed by their hosts and this can be achieved adopting immune evasion strategies or optimal life history traits according to the prevailing pattern of immune-mediated mortality. Parasites often encounter variable immune environments both within and between hosts, promoting the evolution of plastic strategies instead of fixed responses. Here, we explored the plasticity and micro-evolutionary responses of immunomodulatory mechanisms and life history traits to the immune environment provided by the host, using the parasitic nematode Heligmosomoides polygyrus. To test if the parasite responds plastically to t…
Preparing for Winter: The Transcriptomic Response Associated with Different Day Lengths in Drosophila montana
2016
The work has been supported by a Natural Environment Research Council studentship to D.J.P. and an Academy of Finland grant to M.K. (project 268214). At northern latitudes, the most robust cue for assessing the onset of winter is the shortening of day lengths. Many species use day length as a cue to increase their cold tolerance and/or enter into diapause, but little is known about changes in gene expression that occur under different day lengths. We investigate the gene expression changes associated with differences in light/dark cycles in Drosophila montana, a northerly distributed species with a strong adult photoperiodic reproductive diapause. To examine gene expression changes induced …
Palmitoylethanolamide Promotes a Proresolving Macrophage Phenotype and Attenuates Atherosclerotic Plaque Formation
2018
Objective— Palmitoylethanolamide is an endogenous fatty acid mediator that is synthetized from membrane phospholipids by N -acyl phosphatidylethanolamine phospholipase D. Its biological actions are primarily mediated by PPAR-α (peroxisome proliferator-activated receptors α) and the orphan receptor GPR55. Palmitoylethanolamide exerts potent anti-inflammatory actions but its physiological role and promise as a therapeutic agent in chronic arterial inflammation, such as atherosclerosis remain unexplored. Approach and Results— First, the polarization of mouse primary macrophages towards a proinflammatory phenotype was found to reduce N -acyl phosphatidylethanolamine phospholipase D expression …
Ceftazidime-Avibactam Combination Therapy Compared to Ceftazidime-Avibactam Monotherapy for the Treatment of Severe Infections Due to Carbapenem-Resi…
2020
Ceftazidime-avibactam (CZA) is a novel beta-lactam beta-lactamase inhibitor combination approved for the treatment of complicated urinary tract infections, complicated intra-abdominal infections, and for hospital-acquired/ventilator-associated pneumonia. The aim of this systematic review (PROSPERO registration number: CRD42019128927) was to evaluate the effectiveness of CZA combination therapy versus CZA monotherapy in the treatment of severe infections. The databases included in the search, until February 12th, 2020, were MEDLINE by PubMed, EMBASE, and The Cochrane Central Register of Controlled Trials. We included both randomized controlled trials (RCTs) and non-randomized studies publish…
Mimiviruses and the Human Interferon System: Viral Evasion of Classical Antiviral Activities, But Inhibition By a Novel Interferon-β Regulated Immuno…
2017
International audience; In this review we discuss the role of mimiviruses as potential human pathogens focusing on clinical and evolutionary evidence. We also propose a novel antiviral immunomodulatory pathway controlled by interferon-beta (IFN-beta) and mediated by immune-responsive gene 1 (IRG1) and itaconic acid, its product. Acanthamoeba polyphaga Mimivirus (APMV) was isolated from amoebae in a hospital while investigating a pneumonia outbreak. Mimivirus ubiquity and role as protist pathogens are well understood, and its putative status as a human pathogen has been gaining strength as more evidence is being found. The study of APMV and human cells interaction revealed that the virus is …
Mcl-1 targeting could be an intriguing perspective to cure cancer
2018
The Bcl-2 family, which plays important roles in controlling cancer development, is divided into antiapoptotic and proapoptotic members. The change in the balance between these members governs the life and death of the cells. Mcl-1 is an antiapoptotic member of this family and its distribution in normal and cancerous tissues strongly differs from that of Bcl-2. In human cancers, where upregulation of antiapoptotic proteins is common, Mcl-1 expression is regulated independent of Bcl-2 and its inhibition promotes senescence, a major barrier to tumorigenesis. Cancer chemotherapy determines various kinds of responses, such as senescence and autophagy; however, the ideal response to chemotherapy…
Inflammatory Response Mechanisms of the Dentine–Pulp Complex and the Periapical Tissues
2021
The macroscopic and microscopic anatomy of the oral cavity is complex and unique in the human body. Soft-tissue structures are in close interaction with mineralized bone, but also dentine, cementum and enamel of our teeth. These are exposed to intense mechanical and chemical stress as well as to dense microbiologic colonization. Teeth are susceptible to damage, most commonly to caries, where microorganisms from the oral cavity degrade the mineralized tissues of enamel and dentine and invade the soft connective tissue at the core, the dental pulp. However, the pulp is well-equipped to sense and fend off bacteria and their products and mounts various and intricate defense mechanisms. The fron…
Daunorubicin reduces MBNL1 titration by expanded CUG repeat RNA and rescues cardiac dysfunctions in a Drosophila model of myotonic dystrophy
2018
International audience; Myotonic dystrophy (DM) is a dominantly inherited neuromuscular disorder caused by expression of mutant DMPK transcripts containing expanded CUG repeats. Pathogenic RNA sequesters the muscleblind-like (MBNL) proteins, causing alterations of RNA metabolism. Cardiac dysfunction represents the second most common cause of death in DM1 patients. However, the contribution of MBNL titration in DM1 cardiac dysfunction is unclear. We overexpressed Muscleblind (Mbl), Drosophila MBNL orthologue, in cardiomyocytes of DM1 model flies and observed a rescue of heart dysfunctions, which are characteristic of these model flies and resemble cardiac defects observed in patients. We als…
Cardiomyocyte proliferation prevents failure in pressure overload but not volume overload
2017
Induction of the cell cycle is emerging as an intervention to treat heart failure. Here, we tested the hypothesis that enhanced cardiomyocyte renewal in transgenic mice expressing cyclin D2 would be beneficial during hemodynamic overload. We induced pressure overload by transthoracic aortic constriction (TAC) or volume overload by aortocaval shunt in cyclin D2-expressing and WT mice. Although cyclin D2 expression dramatically improved survival following TAC, it did not confer a survival advantage to mice following aortocaval shunt. Cardiac function decreased following TAC in WT mice, but was preserved in cyclin D2-expressing mice. On the other hand, cardiac structure and function were compr…
Homozygous Resistance to Thyroid Hormone β: Can Combined Antithyroid Drug and Triiodothyroacetic Acid Treatment Prevent Cardiac Failure?
2017
Resistance to thyroid hormone β (RTHβ) due to homozygous THRB defects is exceptionally rare, with only five kindreds reported worldwide. Cardiac dysfunction, which can be life-threatening, is recognized in the disorder. Here we describe the clinical, metabolic, ophthalmic, and cardiac findings in a 9-year-old boy harboring a biallelic THRB mutation (R243Q), along with biochemical, physiologic, and cardiac responses to carbimazole and triiodothyroacetic acid (TRIAC) therapy. The patient exhibits recognized features (goiter, nonsuppressed thyroid-stimulating hormone levels, upper respiratory tract infections, hyperactivity, low body mass index) of heterozygous RTHβ, with additional characteri…