Search results for "Signal"

71P Exosomes isolated in plasma of non-small cell lung cancer patients contain microRNA related to the EGFR pathway: Proof of concept

2016

JAK2 mediates lung fibrosis, pulmonary vascular remodelling and hypertension in idiopathic pulmonary fibrosis: an experimental study

2018

BackgroundPulmonary hypertension (PH) is a common disorder in patients with idiopathic pulmonary fibrosis (IPF) and portends a poor prognosis. Recent studies using vasodilators approved for PH have failed in improving IPF mainly due to ventilation (V)/perfusion (Q) mismatching and oxygen desaturation. Janus kinase type 2 (JAK2) is a non-receptor tyrosine kinase activated by a broad spectrum of profibrotic and vasoactive mediators, but its role in PH associated to PH is unknown.ObjectiveThe study of JAK2 as potential target to treat PH in IPF.Methods and resultsJAK2 expression was increased in pulmonary arteries (PAs) from IPF (n=10; 1.93-fold; P=0.0011) and IPF+PH (n=9; 2.65-fold; P<0.00…

Mechanical ventilation alters the development of staphylococcus aureus pneumonia in rabbit

2016

Ventilator-associated pneumonia (VAP) is common during mechanical ventilation (MV). Beside obvious deleterious effects on muco-ciliary clearance, MV could adversely shift the host immune response towards a pro-inflammatory pattern through toll-like receptor (TLRs) up-regulation. We tested this hypothesis in a rabbit model of Staphylococcus aureus VAP. Pneumonia was caused by airway challenge with S. aureus, in either spontaneously breathing (SB) or MV rabbits (n = 13 and 17, respectively). Pneumonia assessment regarding pulmonary and systemic bacterial burden, as well as inflammatory response was done 8 and 24 hours after S. aureus challenge. In addition, ex vivo stimulations of whole blood…

Metabolic and inflammatory reprogramming of macrophages by ONC201 translates in a pro-inflammatory environment even in presence of glioblastoma cells

2020

Tumor-associated macrophages facilitate tumor progression and resistance to therapy. Their capacity for metabolic and inflammatory reprogramming represents an attractive therapeutic target. ONC201/TIC10 is an anticancer molecule that antagonizes the dopamine receptor D2 and affects mitochondria integrity in tumor cells. We examined whether ONC201 induces a metabolic and pro-inflammatory switch in primary human monocyte-derived macrophages that reactivates their antitumor activities, thus enhancing the onco-toxicity of ONC201. Contrary to glioblastoma cells, macrophages exhibited a low ratio of dopamine receptors D2/D5 gene expression and were resistant to ONC201 cytotoxicity. Macrophages re…

Small Rab GTPases in Intracellular Vesicle Trafficking: The Case of Rab3A/Raphillin-3A Complex in the Kidney

2021

Small Rab GTPases, the largest group of small monomeric GTPases, regulate vesicle trafficking in cells, which are integral to many cellular processes. Their role in neurological diseases, such as cancer and inflammation have been extensively studied, but their implication in kidney disease has not been researched in depth. Rab3a and its effector Rabphillin-3A (Rph3A) expression have been demonstrated to be present in the podocytes of normal kidneys of mice rats and humans, around vesicles contained in the foot processes, and they are overexpressed in diseases with proteinuria. In addition, the Rab3A knockout mice model induced profound cytoskeletal changes in podocytes of high glucose fed a…

New Approach of Controlling Cardiac Alternans

2018

The alternans of the cardiac action potential duration is a pathological rhythm. It is considered to be relating to the onset of ventricular fibrillation and sudden cardiac death. It is well known that, the predictive control is among the control methods that use the chaos to stabilize the unstable fixed point. Firstly, we show that alternans (or period-2 orbit) can be suppressed temporally by the predictive control of the periodic state of the system. Secondly, we determine an estimation of the size of a restricted attraction's basin of the unstable equilibrium point representing the unstable regular rhythm stabilized by the control. This result allows the application of predictive control…

Noncoding RNAs in Critical Limb Ischemia

2020

Peripheral artery disease, caused by chronic arterial occlusion of the lower extremities, affects over 200 million people worldwide. Peripheral artery disease can progress into critical limb ischemia (CLI), its more severe manifestation, which is associated with higher risk of limb amputation and cardiovascular death. Aiming to improve tissue perfusion, therapeutic angiogenesis held promise to improve ischemic limbs using delivery of growth factors but has not successfully translated into benefits for patients. Moreover, accumulating studies suggest that impaired downstream signaling of these growth factors (or angiogenic resistance) may significantly contribute to CLI, particularly under h…

Hypoxia‐induced non‐coding rnas controlling cell viability in cancer

2021

Hypoxia, a characteristic of the tumour microenvironment, plays a crucial role in cancer progression and therapeutic response. The hypoxia-inducible factors (HIF-1α, HIF-2α, and HIF-3α), are the master regulators in response to low oxygen partial pressure, modulating hypoxic gene expression and signalling transduction pathways. HIFs’ activation is sufficient to change the cell phenotype at multiple levels, by modulating several biological activities from metabolism to the cell cycle and providing the cell with new characteristics that make it more aggressive. In the past few decades, growing numbers of studies have revealed the importance of non-coding RNAs (ncRNAs) as molecular mediators i…

A genome-wide association study of corneal astigmatism: The CREAM Consortium

2018

Contains fulltext : 191261.pdf (Publisher’s version ) (Open Access) Purpose: To identify genes and genetic markers associated with corneal astigmatism. Methods: A meta-analysis of genome-wide association studies (GWASs) of corneal astigmatism undertaken for 14 European ancestry (n=22,250) and 8 Asian ancestry (n=9,120) cohorts was performed by the Consortium for Refractive Error and Myopia. Cases were defined as having >0.75 diopters of corneal astigmatism. Subsequent gene-based and gene-set analyses of the meta-analyzed results of European ancestry cohorts were performed using VEGAS2 and MAGMA software. Additionally, estimates of single nucleotide polymorphism (SNP)-based heritability for …

The actin remodeling protein cofilin is crucial for thymic αβ but not γδ T-cell development

2018

Cofilin is an essential actin remodeling protein promoting depolymerization and severing of actin filaments. To address the relevance of cofilin for the development and function of T cells in vivo, we generated knock-in mice in which T-cell–specific nonfunctional (nf) cofilin was expressed instead of wild-type (WT) cofilin. Nf cofilin mice lacked peripheral αβ T cells and showed a severe thymus atrophy. This was caused by an early developmental arrest of thymocytes at the double negative (DN) stage. Importantly, even though DN thymocytes expressed the TCRβ chain intracellularly, they completely lacked TCRβ surface expression. In contrast, nf cofilin mice possessed normal numbers of γδ T cel…