Search results for "pathogen"
showing 10 items of 1657 documents
Gamma-secretase modulation with Abeta42-lowering nonsteroidal anti-inflammatory drugs and derived compounds.
2006
The amyloid-beta (Abeta) peptides and specifically the highly amyloidogenic isoform Abeta42 appear to be key agents in the pathogenesis of familial and sporadic forms of Alzheimer's disease (AD). The final step in the generation of Abeta from the amyloid precursor protein is catalyzed by the multiprotein complex gamma-secretase, which constitutes a prime drug target for prevention and therapy of the disease. However, highly potent gamma-secretase inhibitors that block formation of all Abeta peptides have provoked troubling side effects in preclinical animal models of AD. This toxicity can be readily explained by the promiscuous substrate specificity of gamma-secretase and its essential role…
How Fragile We Are: Influence of Stimulator of Interferon Genes (STING) Variants on Pathogen Recognition and Immune Response Efficiency.
2022
AbstractThe STimulator of INterferon Genes (STING) protein is a cornerstone of the human immune response. Its activation by cGAMP upon the presence of cytosolic DNA stimulates the production of type I interferons and inflammatory cytokines which are crucial for protecting cells from infections. STING signaling pathway can also influence both tumor-suppressive and tumor-promoting mechanisms, rendering it an appealing target for drug design. In the human population, several STING variants exist and exhibit dramatic differences in their activity, impacting the efficiency of the host defense against infections. Understanding the differential molecular mechanisms exhibited by these variants is o…
On the use of carrageenan matrices for the development of antiviral edible coatings of interest in berries
2019
Different film-forming dispersions (FFD) based on κ−, ι− and λ− carrageenans and green tea extract (GTE) have been developed as an innovative strategy to guarantee the food safety of blueberries and raspberries. First, the FFD were characterized (surface tension and viscosity) and the physicochemical properties (water vapour permeability-WVP-, water sorption, contact angle, mechanical properties) of the stand-alone films were evaluated. Then, the FFD were applied to refrigerated-stored raspberries and blueberries, and the antiviral activity against murine norovirus (MNV), a cultivable norovirus surrogate, and hepatitis A virus (HAV) of coated fruits was determined at refrigerated (10 °C) an…
Preemptive CD8 T-Cell Immunotherapy of Acute Cytomegalovirus Infection Prevents Lethal Disease, Limits the Burden of Latent Viral Genomes, and Reduce…
1998
ABSTRACT In the immunocompetent host, primary cytomegalovirus (CMV) infection is resolved by the immune response without causing overt disease. The viral genome, however, is not cleared but is maintained in a latent state that entails a risk of virus recurrence and consequent organ disease. By using murine CMV as a model, we have shown previously that multiple organs harbor latent CMV and that reactivation occurs with an incidence that is determined by the viral DNA load in the respective organ (M. J. Reddehase, M. Balthesen, M. Rapp, S. Jonjic, I. Pavic, and U. H. Koszinowski. J. Exp. Med. 179:185–193, 1994). This predicts that a therapeutic intervention capable of limiting the load of lat…
Gene transfer approaches for the treatment of inflammatory bowel disease.
2003
The pathogenesis of Crohn's disease and ulcerative colitis, the two major forms of inflammatory bowel disease, involves a complex interplay between certain genetic, environmental and immunological factors. Considerable research progress in the last decade defined key inflammatory pathways in the inflamed gut and identified new potential therapeutic targets. Since the current medical treatment with corticosteroids and anti-inflammatory drugs is often associated with undesired side effects and cannot completely cure IBD, these current advances in our understanding of intestinal pathology may now allow the development of new biologic treatment strategies including gene therapy. In this review,…
Cholesterol and Amyloid-β: Evidence for a Cross-Talk between Astrocytes and Neuronal Cells.
2011
Accumulating data supports the concept that alterations of cholesterol metabolism might influence the development of Alzheimer's disease (AD), a neurodegenerative disorder characterized by progressive accumulation of amyloid-β (Aβ) peptides in the brain. Changes in the neuronal production of Aβ have been described as a function of cholesterol levels, thus suggesting a causal link between cholesterol homeostasis dysregulation and AD pathogenesis. Under physiological conditions, cholesterol uptake in the brain is efficiently prevented by the blood-brain barrier, and mature neurons are thought to rely on glial cells for their cholesterol supply. In the present study, we tested the hypothesis t…
Mutated cylindromatosis gene affects the functional state of dendritic cells
2010
Cylindromatosis gene (CYLD) is a ubiquitously expressed deubiquitinating enzyme, which interacts with members of the NF-κB signaling pathway and attenuates NF-κB and JNK signaling. Here, we report that DC derived from transgenic mice, which solely express a naturally occurring CYLD isoform (CYLD(ex7/8)), display a higher content of nuclear RelB and express elevated levels of NF-κB family members as well as of known NF-κB-target genes comprising costimulatory molecules and pro-inflammatory cytokines, as compared with WT DC. Accordingly, unstimulated CYLD(ex7/8) DC exhibited a significantly higher primary allogenic T-cell stimulatory capacity than WT DC and exerted no tolerogenic activity. Tr…
Fatal neuroinvasion and SARS-CoV-2 tropism in K18-hACE2 mice is partially independent on hACE2 expression
2022
ABSTRACTAnimal models recapitulating distinctive features of severe COVID-19 are critical to enhance our understanding of SARS-CoV-2 pathogenesis. Transgenic mice expressing human angiotensin-converting enzyme 2 (hACE2) under the cytokeratin 18 promoter (K18-hACE2) represent a lethal model of SARS-CoV-2 infection. The precise mechanisms of lethality in this mouse model remain unclear. Here, we evaluated the spatiotemporal dynamics of SARS-CoV-2 infection for up to 14 days post-infection. Despite infection and moderate pneumonia, rapid clinical decline or death of mice was invariably associated with viral neuroinvasion and direct neuronal injury (including brain and spinal neurons). Neuroinv…
Immune characterization of the HBHA-specific response in Mycobacterium tuberculosis-infected patients with or without HIV infection.
2017
Introduction RD1-based Interferon-γ Release Assays (IGRAs) cannot distinguish latent from active tuberculosis (TB) disease. Conversely, a positive response to heparin-binding haemagglutinin (HBHA)-based IGRAs, among TB-infected subjects, correlates with Mycobacterium tuberculosis (Mtb) containment and low risk of TB progression. The aim of this study was to characterize HBHA-immune responses in HIV-infected and uninfected subjects with active TB or latent TB infection (LTBI). Methods 49 subjects were prospectively enrolled: 22 HIV-uninfected (13 TB, 9 LTBI) and 27 HIV-infected (12 HIV-TB, 15 HIV-LTBI). Whole blood and peripheral blood mononuclear cells were stimulated with HBHA and RD1 anti…
Sex difference in the interaction of alcohol intake, hepatitis B virus, and hepatitis C virus on the risk of cirrhosis
2017
Background The joint effect of the interaction of alcohol intake, hepatitis B virus (HBV) and hepatitis C virus (HCV) on the risk of cirrhosis is still unexplored because a large sample size is required for this investigation. Objective Evaluation of interaction of HBV, HCV and alcohol abuse on the risk of cirrhosis. Design We analysed 12,262 consecutive patients with chronic liver disease of various aetiologies referring to 95 Italian liver units in 2001 or 2014. To evaluate the interaction between alcohol abuse, HBV infection, and HCV infection, patients unexposed to either factors were used as reference category. Adjustment for BMI and age was done by multiple logistic regression analysi…