Search results for " modulators"
showing 10 items of 97 documents
FMF is not always "fever": from clinical presentation to "treat to target".
2020
AbstractFamilial Mediterranean Fever, a monogenic autoinflammatory disease secondary to MEFV gene mutations in the chromosome 16p13, is characterized by recurrent self-limiting attacks of fever, arthritis, aphthous changes in lips and/or oral mucosa, erythema, serositis. It is caused by dysregulation of the inflammasome, a complex intracellular multiprotein structure, commanding the overproduction of interleukin 1. Familial Mediterranean Fever can be associated with other multifactorial autoinflammatory diseases, as vasculitis and Behçet disease.Symptoms frequently start before 20 years of age and are characterized by a more severe phenotype in patients who begin earlier.Attacks consist of …
Taking the stock of granule cargo: Platelet releasate proteomics.
2016
Human platelets are key players in a multitude of physiological and pathological processes. Upon activation they release cargo from different types of granules as well as microparticles in an apparently well-regulated and orchestrated manner. The resulting specific platelet releasates create microenvironments of biologically active compounds and proteins during platelet aggregation and thrombus formation, allowing efficient delivery of growth factors and immune modulators to their sites of effect and enhancing the coagulative response in a positive feedback loop. Thus, platelet releasates play a central role in the regulation of platelet homeostasis and heterotypic cell interaction. Additio…
[1,2]Oxazolo[5,4-e]isoindoles as promising tubulin polymerization inhibitors
2016
Abstract A series of [1,2]Oxazolo [5,4- e ]isoindoles has been synthesized through a versatile and high yielding sequence. All the new structures showed in the 1 HNMR spectra, the typical signal in the 8.34–8.47 ppm attributable to the H-3 of the [1,2]oxazole moiety. Among all derivatives, methoxy benzyl substituents at positions 3 and 4 or/and 5 were very effective in reducing the growth of different tumor cell lines, including diffuse malignant peritoneal mesothelioma (DMPM), an uncommon and rapidly malignancy poorly responsive to available therapeutic options. The most active compound 6j was found to impair tubulin polymerization, cause cell cycle arrest at G2/M phase and induce apoptosi…
Design, synthesis, and biological evaluation of a new class of benzo[b]furan derivatives as antiproliferative agents, with in silico predicted antitu…
2018
A new series of 3-benzoylamino-5-(1H-imidazol-4-yl)methylaminobenzo[b]furans were synthesized and screened as antitumor agents. As a general trend, tested compounds showed concentration-dependent antiproliferative activity against HeLa and MCF-7 cancer cell lines, exhibiting GI50 values in the low micromolar range. In most cases, insertion of a methyl substituent on the imidazole moiety improved the antiproliferative activity. Therefore, methyl-imidazolyl-benzo[b]furans compounds were tested in cell cycle perturbation experiments, producing cell cycle arrest with proapoptotic effects. Their core similarity to known colchicine binding site binders led us to further study the structure featur…
Structure-Activity Relationships of Cytotoxic Lactones as Inhibitors and Mechanisms of Action.
2020
Background: Some lactones prevent protein Myb-dependent gene expression. Objective: The object is to calculate inhibitors of Myb-brought genetic manifestation. Methods: Linear quantitative structure–potency relations result expanded, among sesquiterpene lactones of a variety of macrocycles (pseudoguaianolides, guaianolides, eudesmanolides and germacranolides), to establish which part of the molecule constitutes their pharmacophore, and predict their inhibitory potency on Myb-reliant genetic manifestation, which may result helpful as leads for antileukaemic therapies with a new mechanism of action. Results: Several count indices are connected with structure–activity. The α-methylene-γ-lacto…
2-methoxyestradiol impacts on amino acids-mediated metabolic reprogramming in osteosarcoma cells by interaction with NMDA receptor
2017
Deregulation of serine and glycine metabolism, have been identified to function as metabolic regulators in supporting tumor cell growth. The role of serine and glycine in regulation of cancer cell proliferation is complicated, dependent on concentrations of amino acids and tissue-specific. D-serine and glycine are coagonists of N-methyl-D-aspartate receptor subunit GRIN1. Importantly, NMDA receptors are widely expressed in cancer cells and play an important role in regulation of cell death, proliferation and metabolism of numerous malignancies. The aim of the present work was to associate the metabolism of glycine and D-serine with the anticancer activity of 2-methoxyestradiol. 2-methoxyest…
An overview on anti-tubulin agents for the treatment of lymphoma patients
2020
Anti-tubulin agents constitute a large class of compounds with broad activity both in solid tumors and hematologic malignancies, due to the interference with microtubule dynamics. Since microtubules play crucial roles in the regulation of the mitotic spindles, the interference with their function usually leads to a block in cell division with arrest at the metaphase/anaphase junction of mitosis, followed to apoptosis. This explains the reason why tubulin-binding agents (TBAs) proved to be extremely active in patients with cancer. Several anti-tubulin agents are indicated in the treatment of patients with lymphomas both alone and in combination chemotherapy regimens. The article reviews the …
Pharmacological activation of CB2 receptors counteracts the deleterious effect of ethanol on cell proliferation in the main neurogenic zones of the a…
2015
Chronic alcohol exposure reduces endocannabinoid activity and disrupts adult neurogenesis in rodents, which results in structural and functional alterations. Cannabinoid receptor agonists promote adult neural progenitor cell (NPC) proliferation. We evaluated the protective effects of the selective CB1 receptor agonist ACEA, the selective CB2 receptor agonist JWH133 and the fatty-acid amide-hydrolase (FAAH) inhibitor URB597, which enhances endocannabinoid receptor activity, on NPC proliferation in rats with forced consumption of ethanol (10%) or sucrose liquid diets for 2 weeks. We performed immunohistochemical and stereological analyses of cells expressing the mitotic phosphorylation of his…
Cannabinoid type 1 receptor modulates intestinal propulsion by an attenuation of intestinal motor responses within the myenteric part of the peristal…
2007
Cannabinoid-1 (CB1) receptor activation affects gastrointestinal propulsion in vivo. It was our aim to further characterize the involved myenteric mechanisms in vivo and in vitro. In CB1(-/-) mice and wild-type littermates we performed in vivo transit experiments by charcoal feeding and in vitro electrophysiological recordings in mouse small intestinal smooth muscle. Ascending neuronal contraction (ANC) following electrical field stimulation was studied in rat ileum in a partitioned organ bath separating the aboral stimulation site from the oral recording site. The knockout animals displayed an accelerated upper gastrointestinal transit compared to control animals. The CB1 receptor antagoni…
Altered benzodiazepine receptor sensitivity in alcoholism: a study with fMRI and acute lorazepam challenge.
2007
Previous studies suggested altered sensitivity of the GABA/benzodiazepine receptor system in alcoholic patients. Expanding on these findings, the present functional magnetic resonance imaging (fMRI) study aimed to assess whether a differential modulation of cognitive brain activation by an acute GABAergic drug challenge could be detected in patients with alcoholism. Eight detoxified male patients meeting DSM-IV criteria for alcohol dependence and nine healthy male control subjects were studied with fMRI while performing a 2-back working memory task. The fMRI scans were performed 1 h after intravenous administration of saline and again 1 h after 0.03 mg/kg lorazepam I.V. After saline, a task…