Manuel Morales-Ruiz

Manuel Morales-Ruiz
Hospital Clínic de Barcelona · Servicio de Bioquímica y Genética Molecular

Doctor of Medicine

About

187
Publications
63,296
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8,751
Citations
Additional affiliations
October 2015 - present
University of Barcelona
Position
  • Professor
January 2002 - present
IDIBAPS August Pi i Sunyer Biomedical Research Institute
Position
  • Principal Investigator

Publications

Publications (187)
Article
Our findings that PlGF is a cancer target and anti-PlGF is useful for anticancer treatment have been challenged by Bais et al. Here we take advantage of carcinogen-induced and transgenic tumor models as well as ocular neovascularization to report further evidence in support of our original findings of PlGF as a promising target for anticancer thera...
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Vascular endothelial growth factor (VEGF) induces endothelial cell proliferation, migration, and actin reorganization, all necessary components of an angiogenic response. However, the distinct signal transduction mechanisms leading to each angiogenic phenotype are not known. In this study, we examined the ability of VEGF to stimulate cell migration...
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Portal hypertension in cirrhosis is secondary to an increase in hepatic resistance that occurs mainly through collagen deposition. However, recent evidence points to a major contribution by other factors, such as an intrahepatic reduction in nitric oxide production. Akt is a major activator of the endothelial nitric oxide synthase (eNOS) enzyme, bu...
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Unlabelled: Liver cirrhosis is a very complex disease in which several pathological processes such as inflammation, fibrosis, and pathological angiogenesis are closely integrated. We hypothesized that treatment with pharmacological agents with multiple mechanisms of action will produce superior results to those achieved by only targeting individua...
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INTRODUCTION Early‐onset Alzheimer's disease (EOAD) shows a higher burden of neuropsychiatric symptoms than late‐onset Alzheimer's disease (LOAD). We aim to determine the differences in the severity of neuropsychiatric symptoms and locus coeruleus (LC) integrity between EOAD and LOAD accounting for disease stage. METHODS One hundred four subjects...
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Aim To evaluate the impact of aldosterone excess on renal function in individuals with primary aldosteronism and to compare its evolution after surgery or mineralocorticoid receptor antagonist (MRA) treatment. Methods A multicentre, retrospective cohort study of primary aldosteronism patients in follow-up in 36 Spanish tertiary hospitals, who unde...
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Introduction: Urine free cortisol measurements are routinely performed to evaluate hypercortisolism. Despite their analytical inaccuracy, immunoassay-based methods are frequently used. Advances in liquid chromatography–high-resolution mass spectrometry (LC-HRMS) facilitate the incorporation of powerful diagnostic tools into clinical laboratories. I...
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RNA helicase DHX15 plays a significant role in vasculature development and lung metastasis in vertebrates. In addition, several studies have demonstrated the overexpression of DHX15 in the context of hepatocellular carcinoma. Therefore, we hypothesized that this helicase may play a significant role in liver regeneration, physiology, and pathology....
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Purpose To compare the clinical and hormonal characteristics of patients with familial hyperaldosteronism (FH) and sporadic primary aldosteronism (PA). Methods A systematic review of the literature was performed for the identification of FH patients. The SPAIN-ALDO registry cohort of patients with no suspicion of FH was chosen as the comparator gr...
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Primary aldosteronism (PA) is associated with several cardiometabolic comorbidities. Specific treatment by mineralocorticoid receptor antagonists (MRA) or adrenalectomy has been reported to reduce the cardiometabolic risk. However, the cardiovascular benefit could depend on plasma renin levels in patients on MRA. To compare the development of cardi...
Preprint
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Background: RNA helicase DHX15 plays a significant role in vasculature development and lung metastasis in vertebrates. In addition, several studies have demonstrated the overexpression of DHX15 in the context of hepatocellular carcinoma. Therefore, we hypothesized that this helicase may play a significant role in liver regeneration, physiology and...
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Purpose To evaluate whether the clinical, biochemical and radiological features of patients with primary aldosteronism (PA) can predict both main subtypes of PA. Methods A retrospective multicenter study of PA patients followed in 27 Spanish tertiary hospitals (SPAIN-ALDO Register). Only patients with confirmed unilateral or bilateral PA based on...
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Acute inflammation can either resolve through immunosuppression or persist, leading to chronic inflammation. These transitions are driven by distinct molecular and metabolic reprogramming of immune cells. The anti-diabetic drug Metformin inhibits acute and chronic inflammation through mechanisms still not fully understood. Here, we report that the...
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Background Patients with decompensated cirrhosis experience high mortality rates. Current prognostic scores, including the model for end-stage liver disease (MELD), may underperform in settings other than in those they were initially developed. Novel biomarkers have been proposed to improve prognostication accuracy and even to predict development o...
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Disclosure: M. Araujo-Castro: None. M. Paja Fano: None. M. González Boillos: None. B. Pla Peris: None. E. Pascual-Corrales: None. A. García Cano: None. P. Parra: None. P. Martín Rojas-Marcos: None. J. Ruiz-Sanchez: None. A. Vicente Delgado: None. E. Gómez Hoyos: None. R. Ferreira: None. I. García Sanz: None. M. Recasens Sala: None. R. Barahona San...
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Resumen Objetivos La enfermedad hepática crónica y sus complicaciones, la cirrosis y el carcinoma hepatocelular, presentan una elevada mortalidad. Los tratamientos curativos, como la hepatectomía parcial o el trasplante hepático, tienen una aplicación limitada en pacientes con cirrosis, por su escasa capacidad de regeneración hepática. Son necesar...
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Objectives Chronic liver disease and related complications, cirrhosis and hepatocellular carcinoma, are associated with high mortality. Curative treatments, partial hepatectomy or liver transplantation, have limited applicability in patients with cirrhosis due to the poor liver regenerative capacity. Thus, we need to find new diagnostic and therape...
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Background: Patients with obesity have an overactivated renin-angiotensin-aldosterone system (RAAS) that is associated with essential hypertension. However, the influence of obesity in primary aldosteronism (PA) is unknown. We analyzed the impact of obesity on the characteristics of PA, and the association between obesity and RAAS components. Met...
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Background & aims: Transcription co-activator factor 20 (TCF20) is a regulator of transcription factors involved in extracellular matrix remodelling. In addition, TCF20 genomic variants in humans have been associated with impaired intellectual disability. Therefore, we hypothesized that TCF20 has several functions beyond those described in neuroge...
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Purpose: To develop a predictive model of hypertension resolution after adrenalectomy in patients with primary aldosteronism (PA), based on their presurgical characteristics. Methods: A retrospective multicenter study of PA patients in follow-up in 20 Spanish tertiary hospitals between 2018 and 2021 was performed (SPAIN-ALDO Register). Clinical...
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Background The diagnosis of hepatitis B virus (HBV) infection requires HBV DNA testing and serologic testing for detection of the surface antigen (HBsAg) and the hepatitis B core antibody (anti-HBc). There is a population of patients with occult HBV infection (OBI), which is not detected by HBsAg or HBV DNA quantification in blood, despite the pres...
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Resumen Introducción El diagnóstico actual del virus de la hepatitis B (VHB) está basado en la detección mediante técnicas moleculares de ADN de VHB y ensayos serológicos, como el antígeno de superficie (HBsAg) y anticuerpos frente al core VHB (anti-HBc). Existe un grupo de pacientes con infección oculta de VHB (OBI) en los que estos ensayos no so...
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Introduction Abnormal liver biochemistry is not a rare finding in the context of SARS-CoV-2 infection, regardless of patients having pre-existing chronic disease or not Content This review examines the current body of knowledge on the relationship between COVID-19 and liver injury, which is frequently found in this setting Summary Although the pa...
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Resumen Introducción En el contexto de la infección por SARS-CoV-2 no es infrecuente encontrar alteraciones hepáticas, tanto en pacientes con enfermedad hepática crónica previa como sin ella. Contenido En esta revisión, se examina el conocimiento actual sobre la relación entre la COVID-19 y el daño hepático, frecuentemente observado en el seno de...
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Impairment of kidney function is common in acute-on-chronic liver failure (ACLF). Patterns of kidney dysfunction and their impact on kidney and patient outcomes are ill-defined. Aims of the current study were to investigate patterns of kidney dysfunction and their impact on kidney and patient outcomes in patients with acute decompensation (AD) of c...
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Circulating levels of 2-hydroxybutyrate (2HB) are highly related to glycemic status in different metabolomic studies. According to recent evidence, 2HB is an early biomarker of the future development of dysglycemia and type 2 diabetes mellitus and may be causally related to the progression of normal subjects to impaired fasting glucose or insulin r...
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Patients with decompensated cirrhosis, particularly those with acute‐on‐chronic liver failure (ACLF), show profound alterations in plasma metabolomics. The aim of this study was to investigate the effect of treatment with simvastatin and rifaximin on plasma metabolites of patients with decompensated cirrhosis, specifically on compounds characterist...
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DHX15 is a downstream substrate for Akt1, which is involved in key cellular processes affecting vascular biology. Here, we explored the vascular regulatory function of DHX15. Homozygous DHX15 gene deficiency was lethal in mouse and zebrafish embryos. DHX15—/— zebrafish also showed downregulation of VEGF-C and reduced formation of lymphatic structur...
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Whether tubular injury develops in patients with acute kidney injury due to hepatorenal syndrome (AKI-HRS) is controversial. We performed repeated measurements of biomarkers of tubular injury during a 14-day period in 60 patients with cirrhosis and AKI (34 with AKI-HRS meeting the classical definition of type 1 HRS and 26 with AKI due to acute tubu...
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Background/Aim Decompensated cirrhosis (DC) is associated with high mortality, mainly due to development of acute-on-chronic liver failure (ACLF). There is need to identify patients with DC with high risk of mortality and ACLF development. Liver fatty acid-binding protein (L-FABP) is expressed in several organs and correlates with liver and systemi...
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Elevated plasma bilirubin levels are a frequent clinical finding. It can be secondary to alterations in any stage of its metabolism: (a) excess bilirubin production (i.e., pathologic hemolysis); (b) impaired liver uptake, with elevation of indirect bilirubin; (c) impaired conjugation, prompted by a defect in the UDP-glucuronosyltransferase; and (d)...
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Resumen Un aumento en los niveles plasmáticos de bilirrubina es una alteración frecuente. Puede deberse a cualquier causa que altere alguna de las fases de su metabolismo: a) producción excesiva de bilirrubina (ej. hemólisis patológica); b) defecto en la captación hepática, con aumento de bilirrubina indirecta); c) defecto de conjugación, por alter...
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Obesity is one of the most important public health problems that is associated with an array of metabolic disorders linked to cardiovascular disease, stroke, type 2 diabetes, and cancer. A sustained therapeutic approach to stop the escalating prevalence of obesity and its associated metabolic comorbidities remains elusive. Herein, we developed a no...
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The metabolic ratios lactate/pyruvate and β-hydroxybutyrate/acetoacetate are considered valuable tools to evaluate the in vivo redox cellular state by estimating the free NAD+/NADH in cytoplasm and mitochondria, respectively. The aim of the current study was to validate a gas-chromatography mass spectrometry method for simultaneous determination of...
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Oxidative stress induced by the overproduction of free radicals or reactive oxygen species (ROS) has been considered as a key pathogenic mechanism contributing to the initiation and progression of injury in liver diseases. Consequently, during the last few years antioxidant substances, such as superoxide dismutase (SOD), resveratrol, colchicine, eu...
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Metabolic-associated fatty liver disease (MAFLD) is defined as fat accumulation in the liver in the presence of metabolic alterations. This disorder is generally asymptomatic and may progress to severe liver disease, which are linked to inflammation and/or fibrosis. MAFLD has a high prevalence (26%) and therefore a considerable number of patients a...
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Liver fibrosis is a major health problem with multiple associated complications, which, to date, has no effective treatment. Hepatic stellate cells are the main responsible cells for fibrosis formation; upon their activation, excess accumulation of extracellular matrix and collagen deposits occurs. The mitogen platelet-derived growth factor (PDGF)...
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Background: COVID-19 causes high mortality and long hospitalization periods. The aim of this study was to search for new early prognostic strategies accessible to most health care centers. Methods: Laboratory results, demographic and clinical data from 500 patients with positive SARS-CoV-2 infection were included in our study. The data set was s...
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Resumen Introducción La enfermedad hepática grasa asociada a la disfunción metabólica (MAFLD) se define por el acúmulo de grasa en el hígado en presencia de alteraciones metabólicas. Suele cursar de forma asintomática y puede progresar a formas graves de enfermedad hepática, ligadas a la aparición de inflamación y/o fibrosis. Su prevalencia es muy...
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Introduction Chronic liver disease is associated with high mortality. Liver transplantation is the definitive treatment for patients with end-stage liver disease, improving their survival and quality of life. However, chronic rejection of the graft and the imbalance between the demand and the availability of organs limit its applicability. Therefor...
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DHX15 is an ATP-dependent RNA helicase involved in pre-mRNA splicing and a downstream substrate for Akt1, which plays a significant role in vascular biology. The aim of this study was to explore the regulatory function of DHX15 over the vasculature and endothelial cell biology. Results: DHX15 -/- was lethal in mouse and zebrafish embryos. DHX15 -/-...
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To investigate the role of classical (CLM, CD14++CD16-), intermediate (INTM, CD14++CD16+), and non-classical (Non-CLM, CD14+CD16++) monocytes in scar formation after ST-elevation myocardial infarction (STEMI), evaluated with cardiac magnetic resonance (CMR). One hundred two patients with a first STEMI had serial blood analyses after 1, 3, and 7 day...
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The benefits of classic antioxidants can be translated to clinical therapies owing to the superior activity of CeO2 nanoparticles as redox buffers. In article number 1907322, Wladimiro Jiménez, Víctor Puntes, Gregori Casals, and co‐workers present a historical background of their development for medicine, and analyze their pharmacokinetics, toxicit...
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Antioxidant nanoparticles have recently gained tremendous attention for their enormous potential in biomedicine. However, discrepant reports of either medical benefits or toxicity, and lack of reproducibility of many studies, generate uncertainties delaying their effective implementation. Herein, the case of cerium oxide is considered, a well‐known...
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Resumen Introducción El estradiol en suero (E2) se emplea para el diagnóstico y/o seguimiento de una amplia variedad de patologías. El objeto del presente estudio es evaluar el ensayo enhanced estradiol (eE2) de Siemens en el sistema Atellica IM 1600 (Siemens Healthineers) y llevar a cabo una comparación de muestras con el analizador Advia Centaur...
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Background & aims: Despite the availability of new generation drugs, hepatocellular carcinoma (HCC) is still the third most frequent cause of cancer-related deaths worldwide. Cerium oxide nanoparticles (CeO2 NPs) have emerged as a novel antioxidant agent in experimental liver disease because of their antioxidant, anti-inflammatory and antisteatoti...
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Background Serum estradiol (E2) levels may be used in the diagnostic and/or monitoring of a broad variety of clinical conditions. The aims of this study were to evaluate the Siemens enhanced estradiol assay (eE2) on Atellica IM 1600 (Siemens Healthineers) and to perform a sample comparison with the Siemens ADVIA Centaur XP (Siemens Healthineers)....
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Cerium oxide nanoparticles (CeO2NPs) possess powerful antioxidant properties, thus emerging as a potential therapeutic tool in non-alcoholic fatty liver disease (NAFLD) progression, which is characterized by a high presence of reactive oxygen species (ROS). The aim of this study was to elucidate whether CeO2NPs can prevent or attenuate oxidant inju...
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Objectives: This study aimed to characterize the long-term scar remodeling process after an acute myocardial infarction (AMI) and the underlying scar-related arrhythmogenic substrate using serial late gadolinium enhancement cardiac magnetic resonance (LGE-CMR). Background: Little is known about the time course needed for completion of the scar h...
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Background and aims: Cerium oxide nanoparticles are effective scavengers of reactive oxygen species and have been proposed as a treatment for oxidative stress-related diseases. Consequently, we aimed to investigate the effect of these nanoparticles on hepatic regeneration after liver injury by partial hepatectomy and acetaminophen overdose. Metho...
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Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease worldwide, ranging from steatosis to non-alcoholic steatohepatitis (NASH). Recently, cerium oxide nanoparticles (CeO2NPs) have emerged as a new antioxidant agent with hepatoprotective properties in experimental liver disease. The aim of the current investiga...
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Nonalcoholic fatty liver disease (NAFLD) is characterized by hepatic accumulation of lipids. Antisteatotic effects of cerium oxide nanoparticles (CeO2NPs) have recently been shown in animal models of liver disease. However, it is unclear whether the activity of CeO2NPs is related solely to the decrease in oxidative stress or, in addition, they dire...
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Induction of specific cellular transitions is of clinical importance, as it allows to revert disease cellular phenotype, or induce cellular reprogramming and differentiation for regenerative medicine. Signalling is a convenient way to accomplish such transitions without transfer of genetic material. Here we present the first general computational m...
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Background and aims The occurrence of endothelial alterations in the liver and in the splanchnic vasculature of cirrhotic patients and experimental models of liver diseases has been demonstrated. However, the pathological role of the portal vein endothelium in this clinical context is scarcely studied and, therefore, deserves attention. In this con...
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Purpose of Review The lymphatic network plays a major role in maintaining tissue fluid homeostasis. Therefore, several pathological conditions associated with edema formation result in deficient lymphatic function. However, traditionally, the lymphatic system has been underestimated until recent years when it has been noticed the importance of this...