Search results for "Rase"
showing 10 items of 4343 documents
New insights into the mechanism of action of pyrazolo[1,2-a]benzo[1,2,3,4]tetrazin-3-one derivatives endowed with anticancer potential
2018
Due to the scarce biological profile, the pyrazolo[1,2-a]benzo[1,2,3,4]tetrazine-3-one scaffold (PBT) has been recently explored as promising core for potential anticancer candidates. Several suitably decorated derivatives (PBTs) exhibited antiproliferative activity in the low-micromolar range associated with apoptosis induction and cell cycle arrest on S phase. Herein, we selected the most active derivatives and submitted them to further biological explorations to deepen the mechanism of action. At first, a DNA targeting is approached by means of flow Linear Dichroism experiments so as to evaluate how small planar molecules might interact with DNA, including the interference with the catal…
Bioenergetic Failure in Rat Oligodendrocyte Progenitor Cells Treated with Cerebrospinal Fluid Derived from Multiple Sclerosis Patients
2017
In relapsing-remitting multiple sclerosis (RRMS) subtype, the patient's brain itself is capable of repairing the damage, remyelinating the axon and recovering the neurological function. Cerebrospinal fluid (CSF) is in close proximity with brain parenchyma and contains a host of proteins and other molecules, which influence the cellular physiology, that may balance damage and repair of neurons and glial cells. The purpose of this study was to determine the pathophysiological mechanisms underpinning myelin repair in distinct clinical forms of MS and neuromyelitis optica (NMO) patients by studying the effect of diseased CSF on glucose metabolism and ATP synthesis. A cellular model with primary…
Tissue factor at the crossroad of coagulation and cell signaling
2018
The tissue factor (TF) pathway plays a central role in hemostasis and thrombo-inflammatory diseases. Although structure-function relationships of the TF initiation complex are elucidated, new facets of the dynamic regulation of TF?s activities on cells continue to emerge. Cellular pathways that render TF non-coagulant participate in signaling of distinct TF complexes with associated proteases through the protease-activated receptor (PAR) family of G-protein coupled receptors. Additional coreceptors, including the endothelial protein C receptor (EPCR) and integrins, confer signaling specificity by directing subcellular localization and trafficking. We here review how TF is switchedbetween it…
Type 5 phosphodiesterase (PDE5) and the vascular tree: from embryogenesis to aging and disease
2020
Highlights • Vascular development depends on the timely differentiation of endothelial and smooth muscle cells, that mutually influence their developmental fate. • Endothelial and vascular smooth muscle cell (VSMC) compartments can mutually influence cell and tissue modifications during vascular aging and in vascular disease. • Keeping in mind that PDE5 is mainly expressed in VSMCs, we surveyed the literature on the role of PDE5 in vascular development, aging and disease. • Although most results have been obtained by PDE5 pharmacological inhibition, no data are available, to date, on vascular development, aging or disease following PDE5 genetic ablation.
Long Term Culture of the A549 Cancer Cell Line Promotes Multilamellar Body Formation and Differentiation towards an Alveolar Type II Pneumocyte Pheno…
2016
Pulmonary research requires models that represent the physiology of alveolar epithelium but concerns with reproducibility, consistency and the technical and ethical challenges of using primary or stem cells has resulted in widespread use of continuous cancer or other immortalized cell lines. The A549 'alveolar' cell line has been available for over four decades but there is an inconsistent view as to its suitability as an appropriate model for primary alveolar type II (ATII) cells. Since most work with A549 cells involves short term culture of proliferating cells, we postulated that culture conditions that reduced proliferation of the cancer cells would promote a more differentiated ATII ce…
Acid sphingomyelinase – a regulator of canonical transient receptor potential channel 6 (TRPC6) activity
2019
Recent investigations propose the acid sphingomyelinase (ASM)/ceramide system as a novel target for antidepressant action. ASM catalyzes the breakdown of the abundant membrane lipid sphingomyelin to the lipid messenger ceramide. This ASM‐induced lipid modification induces a local shift in membrane properties, which influences receptor clustering and downstream signaling. Canonical transient receptor potential channels 6 (TRPC6) are non‐selective cation channels located in the cell membrane that play an important role in dendritic growth, synaptic plasticity and cognition in the brain. They can be activated by hyperforin, an ingredient of the herbal remedy St. John’s wort for treatment of de…
Opposing Effects of CREBBP Mutations Govern the Phenotype of Rubinstein-Taybi Syndrome and Adult SHH Medulloblastoma
2018
Recurrent mutations in chromatin modifiers are specifically prevalent in adolescent or adult patients with Sonic hedgehog-associated medulloblastoma (SHH MB). Here, we report that mutations in the acetyltransferase CREBBP have opposing effects during the development of the cerebellum, the primary site of origin of SHH MB. Our data reveal that loss of Crebbp in cerebellar granule neuron progenitors (GNPs) during embryonic development of mice compromises GNP development, in part by downregulation of brain-derived neurotrophic factor (Bdnf). Interestingly, concomitant cerebellar hypoplasia was also observed in patients with Rubinstein-Taybi syndrome, a congenital disorder caused by germline mu…
Whole-genome sequencing of Neisseria gonorrhoeae in a forensic transmission case.
2019
Abstract Molecular epidemiology and phylogenetic analyses are frequently used in the investigation of viral transmission cases in forensic contexts. Here, we present the methods and results of the analysis of a bacterial transmission episode in an alleged child abuse case using complete genome sequences obtained by high-throughput sequencing (HTS) methods. We obtained genomes of Neisseria gonorrhoeae from the victim, the suspect, and 29 unrelated controls. The analysis of the genomes revealed that the victim and suspect isolates had identical sequences in both the bacterial chromosome and the single plasmid present in them. One of the local controls was very similar (differing in only 2 SNP…
A role for Mog1 in H2Bub1 and H3K4me3 regulation affecting RNAPII transcription and mRNA export.
2018
17 páginas, 12 figuras.
Selective Inhibition of Phosphodiesterases 4A, B, C and D Isoforms in Chronic Respiratory Diseases: Current and Future Evidences
2016
Chronic respiratory diseases affect millions of people every day. According to the World Health Organization estimates, ~235 million people suffer from asthma, ~64 million suffer from chronic obstructive pulmonary disease (COPD), and millions more suffer from allergic rhinitis around the world. In recent last years, the first phosphodiesterase 4 (PDE4) inhibitor, roflumilast, was approved as a treatment to reduce the risk of exacerbations in stable and severe COPD associated with chronic bronchitis and a history of exacerbations. PDE4 exists as four subtypes (A, B, C, and D) each with a capacity to degrade cAMP, a second messenger involved in inflammatory responses. PDE4 inhibitors inhibit …