Search results for "Macrophages"
showing 10 items of 533 documents
The GRP94 Inhibitor PU-WS13 Decreases M2-like Macrophages in Murine TNBC Tumors: A Pharmaco-Imaging Study with 99mTc-Tilmanocept SPECT
2021
Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancers and is not eligible for hormone and anti-HER2 therapies. Identifying therapeutic targets and associated biomarkers in TNBC is a clinical challenge to improve patients’ outcome and management. High infiltration of CD206+ M2-like macrophages in the tumor microenvironment (TME) indicates poor prognosis and survival in TNBC patients. As we previously showed that membrane expression of GRP94, an endoplasmic reticulum chaperone, was associated with the anti-inflammatory profile of human PBMC-derived M2 macrophages, we hypothesized that intra-tumoral CD206+ M2 macrophages expressing GRP94 may represent innovative…
Human Amnion-Derived Mesenchymal Stromal Cells: A New Potential Treatment for Carbapenem-Resistant Enterobacterales in Decompensated Cirrhosis
2022
Background: Spontaneous bacterial peritonitis (SBP) is a severe and often fatal infection in patients with decompensated cirrhosis and ascites. The only cure for SBP is antibiotic therapy, but the emerging problem of bacterial resistance requires novel therapeutic strategies. Human amniotic mesenchymal stromal cells (hA-MSCs) possess immunomodulatory and anti-inflammatory properties that can be harnessed as a therapy in such a context. Methods: An in vitro applications of hA-MSCs in ascitic fluid (AF) of cirrhotic patients, subsequently infected with carbapenem-resistant Enterobacterales, was performed. We evaluated the effects of hA-MSCs on bacterial load, innate immunity factors, and macr…
Bond-based bilinear indices for computational discovery of novel trypanosomicidal drug-like compounds through virtual screening
2014
Two-dimensional bond-based bilinear indices and linear discriminant analysis are used in this report to perform a quantitative structure-activity relationship study to identify new trypanosomicidal compounds. A data set of 440 organic chemicals, 143 with antitrypanosomal activity and 297 having other clinical uses, is used to develop the theoretical models. Two discriminant models, computed using bond-based bilinear indices, are developed and both show accuracies higher than 86% for training and test sets. The stochastic model correctly indentifies nine out of eleven compounds of a set of organic chemicals obtained from our synthetic collaborators. The in vitro antitrypanosomal activity of …
Evolutionary plasticity of SH3 domain binding by Nef proteins of the HIV-1/SIVcpz lentiviral lineage
2021
The accessory protein Nef of human and simian immunodeficiency viruses (HIV and SIV) is an important pathogenicity factor known to interact with cellular protein kinases and other signaling proteins. A canonical SH3 domain binding motif in Nef is required for most of these interactions. For example, HIV-1 Nef activates the tyrosine kinase Hck by tightly binding to its SH3 domain. An archetypal contact between a negatively charged SH3 residue and a highly conserved arginine in Nef (Arg77) plays a key role here. Combining structural analyses with functional assays, we here show that Nef proteins have also developed a distinct structural strategy—termed the "R-clamp”—that favors the formation …
Proliferative activity in stenotic human aortocoronary bypass grafts
2002
Abstract Background: Aortocoronary bypass graft disease is responsible for long-term failure of autologous vein grafts. The analyses of proliferation and cell type characterisation in human bypass grafts harvested during re-do surgery make it possible to investigate the cellular processes leading to bypass graft failure. Methods: 30 stenotic vein grafts and 25 control veins were explantated during re-do heart surgery procedures. The total area and cell count of the neointima, media and adventitia were calculated computer-assisted. Actively proliferating cells were identified using antibody to Ki-67 and positive cells were determined by double-label immunocytochemistry with SMC α-actin, CD 3…
Preclinical Retinal Neurodegeneration in a Model of Multiple Sclerosis
2012
Neurodegeneration plays a major role in multiple sclerosis (MS), in which it is thought to be the main determinant of permanent disability. However, the relationship between the immune response and the onset of neurodegeneration is still a matter of debate. Moreover, recent findings in MS patients raised the question of whether primary neurodegenerative changes can occur in the retina independent of optic nerve inflammation. Using a rat model of MS that frequently leads to optic neuritis, we have investigated the interconnection between neurodegenerative and inflammatory changes in the retina and the optic nerves with special focus on preclinical disease stages. We report that, before manif…
Bacterial and viral infections and related inflammatory responses in chronic obstructive pulmonary disease
2021
Abstract In chronic obstructive pulmonary disease (COPD) patients, bacterial and viral infections play a relevant role in worsening lung function and, therefore, favour disease progression. The inflammatory response to lung infections may become a specific indication of the bacterial and viral infections. We here review data on the bacterial–viral infections and related airways and lung parenchyma inflammation in stable and exacerbated COPD, focussing our attention on the prevalent molecular pathways in these different clinical conditions. The roles of macrophages, autophagy and NETosis are also briefly discussed in the context of lung infections in COPD. Controlling their combined response…
Genetic regulation of iron homeostasis in sideropenic patients with mild COVID-19 disease under a new oral iron formulation: Lessons from a different…
2022
Background: Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) needs iron to replicate itself. Coronaviruses are able to upregulate Chop/Gadd153 and Arg1 genes, consequently leading to CD8 lymphocytes decrease, degradation of asparagine and decreased nitric oxide (NO), thus impairing immune response and antithrombotic functions. Little is known about regulation of genes involved in iron metabolism in pauci symptomatic patients with COVID-19 disease or in patients with iron deficiency treated with sucrosomial iron. Methods: Whole blood was taken from the COVID-19 patients and from patients with sideropenic anemia, treated or not (control group) with iron supplementations. Enrolled …
Human primary macrophages scavenge AuNPs and eliminate it through exosomes. A natural shuttling for nanomaterials.
2018
Abstract The use of nanomaterials is increasing but the real risk associated with their use in humans has to be defined. In fact, nanomaterials tend to accumulate in organs over a long period of time and are slowly degraded or eliminated by the body. Exosomes are nanovesicles actively shuttle molecules, including chemical products and metals, through the body. Macrophages scavenge the body from both organic and inorganic substances, and they use to release high amounts of exosomes. We hypothesized that macrophages may have a role in eliminating nanomaterials through their exosomes. We treated human primary macrophages with 20 nm gold nanoparticles (AuNPs), analyzing the presence of AuNPs in…
Chronic lymphocytic leukemia nurse-like cells express hepatocyte growth factor receptor (c-MET) and indoleamine 2,3-dioxygenase and display features …
2014
Hepatocyte growth factor, produced by stromal and follicular dendritic cells, and present at high concentrations in the sera of patients with chronic lymphocytic leukemia, prolongs the survival of leukemic B cells by interacting with their receptor, c-MET. It is, however, unknown whether hepatocyte growth factor influences microenvironmental cells, such as nurse-like cells, which deliver survival signals to the leukemic clone. We evaluated the expression of c-MET on nurse-like cells and monocytes from patients with chronic lymphocytic leukemia and searched for phenotypic/functional features supposed to be influenced by the hepatocyte growth factor/c-MET interaction. c-MET is expressed at hi…