Search results for "INHIBITOR"
showing 10 items of 3742 documents
On the prospect of serum exosomal miRNA profiling and protein biomarkers for the diagnosis of ascending aortic dilatation in patients with bicuspid a…
2018
Background: To determine the impact of circulating miRNA and protein activity on the severity of ascending aortic dilatation in patients with bicuspid (BAV) and tricuspid aortic valve (TAV). Methods: By reverse transcription polymerase chain reaction, exosomal circulating expression levels (versus healthy aorta) of miRNAs and absolute levels of transforming growth factor β (TGF-β), matrix metalloproteinases (MMP-2, -3 and -9), tissue inhibitors (TIMP-1, -2, -3 and -4), and soluble receptors for advanced glycation end products AGEs (sRAGE) were evaluated in ascending dilated aortas of 71 patients with different valve morphotype. Results: Less-dilated ascending aorta exhibited a specific miRN…
Novel iodoacetamido benzoheterocyclic derivatives with potent antileukemic activity are inhibitors of STAT5 phosphorylation
2016
Signal Transducer and Activator of Transcription 5 (STAT5) protein, a component of the STAT family of signaling proteins, is considered to be an attractive therapeutic target because of its involvement in the progression of acute myeloid leukemia. In an effort to discover potent molecules able to inhibit the phosphorylation-activation of STAT5, twenty-two compounds were synthesized and evaluated on the basis of our knowledge of the activity of 2-(3’,4’,5’-trimethoxybenzoyl)-3-iodoacetamido-6-methoxy benzo[b]furan derivative 1 as a potent STAT5 inhibitor. Most of these molecules, structurally related to compound 1, were characterized by the presence of a common 3’,4’,5’-trimethoxybenzoyl moi…
Marine Actinomycetes-Derived Secondary Metabolites Overcome TRAIL-Resistance via the Intrinsic Pathway through Downregulation of Survivin and XIAP
2020
Resistance of cancer cells to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis represents the major hurdle to the clinical use of TRAIL or its derivatives. The discovery and development of lead compounds able to sensitize tumor cells to TRAIL-induced cell death is thus likely to overcome this limitation. We recently reported that marine actinomycetes&rsquo
Altered gastrointestinal motility in an animal model of Lesch-Nyhan disease.
2018
Mutations in the HGPRT1 gene, which encodes hypoxanthine-guanine phosphoribosyltransferase (HGprt), housekeeping enzyme responsible for recycling purines, lead to Lesch-Nyhan disease (LND). Clinical expression of LND indicates that HGprt deficiency has adverse effects on gastrointestinal motility. Therefore, we aimed to evaluate intestinal motility in HGprt knockout mice (HGprt(−)). Spontaneous and neurally evoked mechanical activity was recorded in vitro as changes in isometric tension in circular muscle strips of distal colon. HGprt(−) tissues showed a lower in amplitude spontaneous activity and atropine-sensitivity neural contraction compared to control mice. The responses to carbachol a…
The cytoprotective protein MANF promotes neuronal survival independently from its role as a GRP78 cofactor
2021
Mesencephalic astrocyte-derived neurotrophic factor (MANF) is an endoplasmic reticulum (ER)-stress-regulated protein exhibiting cytoprotective properties through a poorly understood mechanism in various in vitro and in vivo models of neuronal and non-neuronal damage. Although initially characterized as a secreted neurotrophic factor for midbrain dopamine neurons, MANF has recently gained more interest for its intracellular role in regulating the ER homeostasis, including serving as a cofactor of the chaperone glucose-regulated protein 78 (GRP78). We aimed for a better understanding of the neuroprotective mechanisms of MANF. Here we show for the first time that MANF promotes the survival of …
Biosynthesis of selenium-nanoparticles and -nanorods as a product of selenite bioconversion by the aerobic bacterium Rhodococcus aetherivorans BCP1
2018
The wide anthropogenic use of selenium compounds represents the major source of selenium pollution world- wide, causing environmental issues and health concerns. Microbe-based strategies for metal removal/recovery have received increasing interest thanks to the association of the microbial ability to detoxify toxic metal/ metalloid polluted environments with the production of nanomaterials. This study investigates the tolerance and the bioconversion of selenite (SeO32−) by the aerobically grown Actinomycete Rhodococcus aetherivorans BCP1 in association with its ability to produce selenium nanoparticles and nanorods (SeNPs and SeNRs). The BCP1 strain showed high tolerance towards SeO32− with…
Temporal quantitative phosphoproteomics of ADP stimulation reveals novel central nodes in platelet activation and inhibition
2017
Adenosine diphosphate (ADP) enhances platelet activation by virtually any other stimulant to complete aggregation. It binds specifically to the G-protein-coupled membrane receptors P2Y1 and P2Y12, stimulating intracellular signaling cascades, leading to integrin aIIbb3 activation, a process antagonized by endothelial prostacyclin. P2Y12 inhibitors are among the most successful antiplatelet drugs, however, show remarkable variability in efficacy. We reasoned whether a more detailed molecular understanding of ADP-induced protein phosphorylation could identify (1) critical hubs in platelet signaling toward aggregation and (2) novel molecular targets for antiplatelet treatment strategies. We ap…
The potential of cystatin C as a predictive biomarker in breast cancer
2020
Breast cancer (BCa) is the leading cause of cancer-related deaths among women. Numerous efforts are being directed toward identifying novel tissue and/or circulating molecular markers that may help clinicians in detecting early-stage BCa patients and in providing an accurate estimation of the prognosis and prediction of response to clinical treatments. In this setting, emerging evidence has indicated Cystatin C (Cyst C), as the most potent endogenous inhibitor of cysteine cathepsins, as a possible useful marker in the clinical management of BCa patients.This review analyzes the results of emerging studies underpinning a potential clinical role of Cyst C, as additional marker in BCa.Cyst C e…
The role of tumor-associated macrophages in gastric cancer development and their potential as a therapeutic target.
2020
Gastric cancer (GC) represents the fifth cause of cancer-related death worldwide. Molecular biology has become a central area of research in GC and there are currently at least three major classifications available to elucidate the mechanisms that drive GC oncogenesis. Further, tumor microenvironment seems to play a crucial role, and tumor-associated macrophages (TAMs) are emerging as key players in GC development. TAMs are cells derived from circulating chemokine- receptor-type 2 (CCR2) inflammatory monocytes in blood and can be divided into two main types, M1 and M2 TAMs. M2 TAMs play an important role in tumor progression, promoting a pro-angiogenic and immunosuppressive signal in the tu…
CD36 gene is associated with intraocular pressure elevation after intravitreal application of anti-VEGF agents in patients with age-related macular d…
2017
IF 1.886; International audience; Background: The wet form of age-related macular degeneration (AMD) is characterized by pathological vascularization of the outer retinal layers. The condition responds to treatment with antibodies against vascular endothelial growth factor (VEGF), but the patients receiving such anti-VEGF therapy sometimes show undesirable acute short-term increases in the intraocular pressure (IOP). The cause of this adverse effect is unknown, and here, we are testing a hypothesis that it is related to CD36 gene polymorphisms.Materials and Methods: A group of 134 patients with AMD were given three therapeutic doses of anti-VEGF antibody (ranibizumab) at monthly intervals. …