Search results for "Extracellular"

Vascular patterns provide therapeutic targets in aggressive neuroblastic tumors

2016

// Irene Tadeo 1 , Gloria Bueno 2 , Ana P. Berbegall 1 , M. Milagro Fernandez-Carrobles 2 , Victoria Castel 3 , Marcial Garcia-Rojo 4 , Samuel Navarro 1 , Rosa Noguera 1 1 Pathology Department, Medical School, University of Valencia, INCLIVA, 46010 Valencia, Spain 2 VISILAB, E.T.S. Ingenieros Industriales, University of Castilla-La Mancha, 13071 Ciudad Real, Spain 3 Pediatric Oncology Unit, University and Polytechnic Hospital La Fe, 46026 Valencia, Spain 4 Department of Pathology, Hospital de Jerez de la Frontera, 11407 Jerez de la Frontera, Cadiz, Spain Correspondence to: Rosa Noguera Salva, e-mail: rnoguera@uv.es Keywords: extracellular matrix, blood vessels, capillaries, sinusoids, neuro…

Optimized Mouse Models for Liver Fibrosis

2017

Fibrosis is the excessive accumulation of extracellular matrix components due to chronic injury, with collagens as predominant structural components. Liver fibrosis can progress to cirrhosis, which is characterized by a severe distortion of the delicate hepatic vascular architecture, the shunting of the blood supply away from hepatocytes and the resultant functional liver failure. Cirrhosis is associated with a highly increased morbidity and mortality and represents the major hard endpoint in clinical studies of chronic liver diseases. Moreover, cirrhosis is a strong cofactor of primary liver cancer. In vivo models are indispensable tools to study the cellular and molecular mechanisms of li…

Introducing the concept of “CSF-shift edema” in traumatic brain injury

2018

Brain edema after severe traumatic brain injury (TBI) plays an important role in the outcome and survival of injured patients. It is also one of the main targets in the therapeutic approach in the current clinical practice. To date, the pathophysiology of traumatic brain swelling is complex and, being that it is thought to be mainly cytotoxic and vasogenic in origin, not yet entirely understood. However, based on new understandings of the hydrodynamic aspects of cerebrospinal fluid (CSF), an additional mechanism of brain swelling can be considered. An increase in pressure into the subarachnoid space, secondary to traumatic subarachnoid hemorrhage, would result in a rapid shift of CSF from t…

A survey of clearing techniques for 3D imaging of tissues with special reference to connective tissue

2016

AbstractFor 3-dimensional (3D) imaging of a tissue, 3 methodological steps are essential and their successful application depends on specific characteristics of the type of tissue. The steps are 1° clearing of the opaque tissue to render it transparent for microscopy, 2° fluorescence labeling of the tissues and 3° 3D imaging. In the past decades, new methodologies were introduced for the clearing steps with their specific advantages and disadvantages. Most clearing techniques have been applied to the central nervous system and other organs that contain relatively low amounts of connective tissue including extracellular matrix. However, tissues that contain large amounts of extracellular mat…

Extracellular vesicles in multiple sclerosis as possible biomarkers: Dream or reality?

2017

Extracellular vesicles are recently described as specialized structures for intercellular communication. Their role in the central nervous system was diffusely studied in both physiological and pathological condition. In particular, an increased extracellular vesicle number was detected in several autoimmune diseases, including multiple sclerosis, a chronic autoimmune, inflammatory, demyelinating and neurodegenerative disease. This chapter summarizes the available information on the involvement of the extracellular vesicles in multiple sclerosis pathogenesis and their possible use as biomarker of therapy efficacy.

Reprint of "EXOSOME LEVELS IN HUMAN BODY FLUIDS: A TUMOR MARKER BY THEMSELVES?"

2017

Despite considerable research efforts, the finding of reliable tumor biomarkers remains challenging and unresolved. In recent years a novel diagnostic biomedical tool with high potential has been identified in extracellular nanovesicles or exosomes. They are released by the majority of the cells and contain detailed molecular information on the cell of origin including tumor hallmarks. Exosomes can be isolated from easy accessible body fluids, and most importantly, they can at once provide with several biomarkers, with different levels of specificity. Recent clinical evidence shows that the levels of exosomes released into body fluids may by themselves represent a predictive/diagnostic of t…

Extracellular Vesicles: Goodies for the Brain?

2015

Evaluating the antifibrotic potency of galunisertib in a human ex vivo model of liver fibrosis

2017

Background and Purpose Liver fibrosis is a major cause of liver-related mortality and, so far, no effective antifibrotic drug is available. Galunisertib, a TGF-β receptor type I kinase inhibitor, is a potential candidate for the treatment of liver fibrosis. Here, we evaluated the potency of galunisertib in a human ex vivo model of liver fibrosis. Experimental Approach Antifibrotic potency and associated mechanisms were studied ex vivo, using both healthy and cirrhotic human precision-cut liver slices. Fibrosis-related parameters, both transcriptional and translational level, were assessed after treatment with galunisertib. Key Results Galunisertib showed a prominent antifibrotic potency. Ph…

Silencing of C3G increases cardiomyocyte survival inhibition and apoptosis via regulation of p-ERK1/2 and Bax.

2018

Experimental studies have shown that overexpression of Rap guanine nucleotide exchange factor 1 (C3G) plays pro-survival and anti-apoptotic roles through molecule phosphorylated extracellular signal-regulated kinase1/2 (p-ERK1/2) in cardiomyocytes. However, it is still unclear if silencing of C3G may increase cell survival inhibition and apoptosis in cardiomyocytes, and whether C3G silence induced injuries are reduced by the overexpression of C3G through regulation of p-ERK1/2 and pro-apoptotic molecule Bax. In this study, the rat-derived H9C2 cardiomyocytes were infected with C3G small hairpin RNA interference recombinant lentiviruses, which silenced the endogenous C3G expression in the ca…

2020

Physical exercise induces acute physiological changes leading to enhanced tissue cross-talk and a liberation of extracellular vesicles (EVs) into the circulation. EVs are cell-derived membranous entities which carry bioactive material, such as proteins and RNA species, and are important mediators of cell-cell-communication. Different types of physical exercise interventions trigger the release of diverse EV subpopulations, which are hypothesized to be involved in physiological adaptation processes leading to health benefits and longevity. Large EVs (“microvesicles” and “microparticles”) are studied frequently in the context of physical exercise using straight forward flow cytometry approach…